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Sample records for activation promotes anti-thrombotic

  1. In vitro Anti-Thrombotic Activity of Extracts from Blacklip Abalone (Haliotis rubra Processing Waste

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    Hafiz Ansar Rasul Suleria

    2016-12-01

    Full Text Available Waste generated from the processing of marine organisms for food represents an underutilized resource that has the potential to provide bioactive molecules with pharmaceutical applications. Some of these molecules have known anti-thrombotic and anti-coagulant activities and are being investigated as alternatives to common anti-thrombotic drugs, like heparin and warfarin that have serious side effects. In the current study, extracts prepared from blacklip abalone (Haliotis rubra processing waste, using food grade enzymes papain and bromelain, were found to contain sulphated polysaccharide with anti-thrombotic activity. Extracts were found to be enriched with sulphated polysaccharides and assessed for anti-thrombotic activity in vitro through heparin cofactor-II (HCII-mediated inhibition of thrombin. More than 60% thrombin inhibition was observed in response to 100 μg/mL sulphated polysaccharides. Anti-thrombotic potential was further assessed as anti-coagulant activity in plasma and blood, using prothrombin time (PT, activated partial thromboplastin time (aPTT, and thromboelastography (TEG. All abalone extracts had significant activity compared with saline control. Anion exchange chromatography was used to separate extracts into fractions with enhanced anti-thrombotic activity, improving HCII-mediated thrombin inhibition, PT and aPTT almost 2-fold. Overall this study identifies an alternative source of anti-thrombotic molecules that can be easily processed offering alternatives to current anti-thrombotic agents like heparin.

  2. A class of 3S-2-aminoacyltetrahydro-beta-carboline-3-carboxylic acids: their facile synthesis, inhibition for platelet activation, and high in vivo anti-thrombotic potency.

    Science.gov (United States)

    Liu, Jiawang; Jiang, Xueyun; Zhao, Ming; Zhang, Xiaoyi; Zheng, Meiqing; Peng, Li; Peng, Shiqi

    2010-04-22

    3S-Tetrahydro-beta-carboline-3-carboxylic acid (TCCA) effectively inhibits ADP-induced platelet activation. This paper used TCCA as a lead, modified its 2-position with amino acids, and provided 20 novel 3S-2-aminoacyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acids (5a-t). With the in vitro assay, it was demonstrated that this modification diminished the IC(50) values from 701 nM of TCCA to 10 nM of 5a-t. With the in vivo assay, it was demonstrated that this modification reduced the efficacious dose from 5.0 micromol/kg of TCCA to 0.1 micromol/kg of 5a-t. Comparing the Cerius based conformation of them with that of their analogues, the 3-position modified TCCA, it was suggested that the comparatively unfolded conformation was one of the important factors of enhancing the in vivo antithrombotic potency.

  3. [Dental treatment and anti-thrombotic therapy. Part II: the era of new anti-thrombotic drugs].

    Science.gov (United States)

    Chackartchi, T; Sachar Helft, S; Findler, M

    2014-01-01

    Surgical intra-oral treatment for patients under antithrombotic therapy presents a challenge for the dental team. Within the last few years evidence based systematic reviews established new clinical guidelines for wide groups of patients which need to use antithrombotic treatment. The expected increase in use of antithrombotic treatment forced the pharmaceutical industry to provide new treatments. The former anticoagulant and anti-platelets aggregation groups of drugs were limited to small variety of medication. The search for the new treatments with ideal properties led to newly invented groups of drugs. In this article we will describe the new advancements in anti-thrombotic treatments. The article will summarize the limited knowledge of surgical management of patients under the new anti-thrombotic medications and the recommended approach for oral surgical procedures.

  4. [Testing system design and analysis for the execution units of anti-thrombotic device].

    Science.gov (United States)

    Li, Zhelong; Cui, Haipo; Shang, Kun; Liao, Yuehua; Zhou, Xun

    2015-02-01

    In an anti-thrombotic pressure circulatory device, relays and solenoid valves serve as core execution units. Thus the therapeutic efficacy and patient safety of the device will directly depend on their performance. A new type of testing system for relays and solenoid valves used in the anti-thrombotic device has been developed, which can test action response time and fatigue performance of relay and solenoid valve. PC, data acquisition card and test platform are used in this testing system based on human-computer interaction testing modules. The testing objectives are realized by using the virtual instrument technology, the high-speed data acquisition technology and reasonable software design. The two sets of the system made by relay and solenoid valve are tested. The results proved the universality and reliability of the testing system so that these relays and solenoid valves could be accurately used in the antithrombotic pressure circulatory equipment. The newly-developed testing system has a bright future in the aspects of promotion and application prospect.

  5. Anti-thrombotic effect of rutin isolated from Dendropanax morbifera Leveille.

    Science.gov (United States)

    Choi, Jun-Hui; Kim, Dae-Won; Park, Se-Eun; Lee, Hyo-Jeong; Kim, Ki-Man; Kim, Kyung-Je; Kim, Myung-Kon; Kim, Sung-Jun; Kim, Seung

    2015-08-01

    Dendropanax morbifera H. Lev. is well known in Korean traditional medicine for improvement of blood circulation. In this study, rutin, a bioflavonoid having anti-thrombotic and anticoagulant activities was isolated from a traditional medicinal plant, D. morbifera H. Lev. The chemical characteristics of rutin was studied to be quercetin 3-O-α-l-rhamnopyranosyl-(1-6)-β-d-glucopyranoside using high performance liquid chromatography mass spectrometry (HPLC-MS), proton nuclear magnetic resonance ((1)H NMR) and carbon-13 nuclear magnetic resonance ((13)C NMR). Turbidity and fibrin clotting studies revealed that rutin reduces fibrin clot in concentration dependent manner. Rutin was found to prolong activated partial thromboplastin time (aPTT), prothrombin time (PT) and closure time (CT). Furthermore, it decreased the activity of pro-coagulant protein, thrombin. In vivo study showed that rutin exerted a significant protective effect against collagen and epinephrine (or thrombin) induced acute thromboembolism in mice. These results suggest that rutin has a potent to be an anti-thrombotic agent for cardiovascular diseases.

  6. Anti-thrombotic effects of selective estrogen receptor modulator tamoxifen.

    Science.gov (United States)

    Nayak, Manasa K; Singh, Sunil K; Roy, Arnab; Prakash, Vivek; Kumar, Anand; Dash, Debabrata

    2011-10-01

    Tamoxifen is a known anti-cancer drug and established estrogen receptor modulator. Few clinical studies have earlier implicated the drug in thrombotic complications attributable to lower anti-thrombin and protein S levels in plasma. However, action of tamoxifen on platelet signalling machinery has not been elucidated in detail. In the present report we show that tamoxifen is endowed with significant inhibitory property against human platelet aggregation. From a series of in vivo and in vitro studies tamoxifen was found to inhibit almost all platelet functions, prolong tail bleeding time in mouse and profoundly prevent thrombus formation at injured arterial wall in mice, as well as on collagen matrix perfused with platelet-rich plasma under arterial shear against the vehicle dimethylsulfoxide (DMSO). These findings strongly suggest that tamoxifen significantly downregulates platelet responses and holds potential as a promising anti-platelet/anti-thrombotic agent.

  7. Preparation and characterization of a novel aspirin derivative with anti-thrombotic and gastric mucosal protection properties.

    Directory of Open Access Journals (Sweden)

    Xi-E Zhen

    Full Text Available The use of acetylsalicylic acid (ASP is limited by its adverse effects, especially the effect on the gastric mucosa. To address this problem, we synthesized a derivative form of ASP, prepared by modification of ASP with nano-hydroxyapatite (a kind of inorganic particle containing Ca(2+. The derivative was named Ca-ASP. Structural study showed that Ca-ASP was a kind of carboxylate containing intramolecular hydrogen bonds. Rats given a high dose of Ca-ASP (5 mmol per kg body weight showed similar anti-thrombotic activity as those given the same dose of ASP, but had much lower gastric mucosal damage than ASP (UI: 2 versus UI: 12.5. These rats also showed reduced expression of COX-2, but their COX-1 expression was similar to that of control rats, but significantly higher than that of ASP-administered rats. Furthermore, the level of prostaglandin E2 (PGE2 was up-regulated in Ca-ASP-administered rats compared to ASP-administered rats. Taken together, the results showed that Ca-ASP possessed similar antithrombotic activity as ASP but without the side effect associated with ASP, and the underlying mechanism may center on inhibiting COX-2 without inhibiting COX-1, and thus favouring the production of PGE2, the prostaglandin that plays a vital role in the suppression of platelet aggregation and thrombosis, as well as in the repair of gastric damage.

  8. Assessment of Novel Anti-thrombotic Fusion Proteins for Inhibition of Stenosis in a Porcine Model of Arteriovenous Graft.

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    Christi M Terry

    Full Text Available Hemodialysis arteriovenous synthetic grafts (AVG provide high volumetric blood flow rates shortly after surgical placement. However, stenosis often develops at the vein-graft anastomosis contributing to thrombosis and early graft failure. Two novel fusion proteins, ANV-6L15 and TAP-ANV, inhibit the tissue factor/factor VIIa coagulation complex and the factor Xa/factor Va complex, respectively. Each inhibitor domain is fused to an annexin V domain that targets the inhibitor activity to sites of vascular injury to locally inhibit thrombosis. This study's objective was to determine if these antithrombotic proteins are safe and effective in inhibiting AVG stenosis.A bolus of either TAP-ANV or ANV-6L15 fusion protein was administered intravenously immediately prior to surgical placement of a synthetic graft between the external jugular vein and common carotid artery in a porcine model. At surgery, the vein and artery were irrigated with the anti-thrombotic fusion protein. Control animals received intravenous heparin. At 4 weeks, MRI was performed to evaluate graft patency, the pigs were then euthanized and grafts and attached vessels were explanted for histomorphometric assessment of neointimal hyperplasia at the vein-graft anastomosis. Blood was collected at surgery, immediately after surgery and at euthanasia for serum metabolic panels and coagulation chemistries.No acute thrombosis occurred in the control group or in either experimental group. No abnormal serum chemistries, activated clotting times or PT, PTT values were observed after treatment in experimental or control animals. However, at the vein-graft anastomosis, there was no difference between the control and experimental groups in cross-sectional lumen areas, as measured on MRI, and no difference in hyperplasia areas as determined by histomorphometry. These results suggest that local irrigation of TAP-ANV or ANV-6L15 intra-operatively was as effective in inhibiting acute graft thrombosis

  9. Neutrophil Protease Cleavage of Von Willebrand Factor in Glomeruli - An Anti-thrombotic Mechanism in the Kidney.

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    Tati, Ramesh; Kristoffersson, Ann-Charlotte; Manea Hedström, Minola; Mörgelin, Matthias; Wieslander, Jörgen; van Kooten, Cees; Karpman, Diana

    2017-02-01

    Adequate cleavage of von Willebrand factor (VWF) prevents formation of thrombi. ADAMTS13 is the main VWF-cleaving protease and its deficiency results in development of thrombotic microangiopathy. Besides ADAMTS13 other proteases may also possess VWF-cleaving activity, but their physiological importance in preventing thrombus formation is unknown. This study investigated if, and which, proteases could cleave VWF in the glomerulus. The content of the glomerular basement membrane (GBM) was studied as a reflection of processes occurring in the subendothelial glomerular space. VWF was incubated with human GBMs and VWF cleavage was assessed by multimer structure analysis, immunoblotting and mass spectrometry. VWF was cleaved into the smallest multimers by the GBM, which contained ADAMTS13 as well as neutrophil proteases, elastase, proteinase 3 (PR3), cathepsin-G and matrix-metalloproteinase 9. The most potent components of the GBM capable of VWF cleavage were in the serine protease or metalloprotease category, but not ADAMTS13. Neutralization of neutrophil serine proteases inhibited GBM-mediated VWF-cleaving activity, demonstrating a marked contribution of elastase and/or PR3. VWF-platelet strings formed on the surface of primary glomerular endothelial cells, in a perfusion system, were cleaved by both elastase and the GBM, a process blocked by elastase inhibitor. Ultramorphological studies of the human kidney demonstrated neutrophils releasing elastase into the GBM. Neutrophil proteases may contribute to VWF cleavage within the subendothelium, adjacent to the GBM, and thus regulate thrombus size. This anti-thrombotic mechanism would protect the normal kidney during inflammation and could also explain why most patients with ADAMTS13 deficiency do not develop severe kidney failure.

  10. Downstream Regulatory Element Antagonist Modulator (DREAM), a target for anti-thrombotic agents.

    Science.gov (United States)

    Cho, Jaehyung

    2017-03-01

    Circulating platelets participate in the process of numerous diseases including thrombosis, inflammation, and cancer. Thus, it is of great importance to understand the underlying mechanisms mediating platelet activation under disease conditions. Emerging evidence indicates that despite the lack of a nucleus, platelets possess molecules that are involved in gene transcription in nucleated cells. This review will summarize downstream regulatory element antagonist modulator (DREAM), a transcriptional repressor, and highlight recent findings suggesting its novel non-transcriptional role in hemostasis and thrombosis.

  11. 黄粉虫纤溶活性蛋白免疫原性与抗血栓作用的研究%The Study of Immuongenicity and Anti-thrombotic Effect of Tenebrio Fibrinolyric Proteins

    Institute of Scientific and Technical Information of China (English)

    张冰; 谭竹钧

    2015-01-01

    为了研究黄粉虫纤溶活性蛋白( Tenebrio Fibrinolytic Proteins,TFP)的免疫原性及其抗血栓作用,本研究将纯化的TFP经皮下注射免疫小鼠,间接ELISA法检测小鼠血清中的抗体含量及抗体效价;小鼠灌胃TFP后,取血浆检测凝血酶时间(thrombin time,TT)、凝血酶原时间(prothrombin time,PT)、活化部分凝血活酶时间(activated partial thromboplastin time ,APTT)、组织型纤溶酶原激活剂( tissue-type plasminogen activator ,t-PA)和其抑制物( plasminogen activator inhibitor ,PAI),角叉菜胶使小鼠尾部形成血栓,测量血栓形成长度。结果显示,TFP免疫小鼠后产生特异性抗体且随着免疫次数的增加,抗体含量逐渐升高,末次免疫后产生的抗体效价为1∶640;TFP可以显著延长TT,增强t-PA的活性,抑制PAI的活性,同时显著抑制由角叉菜胶引起的小鼠尾部血栓的形成。这说明TFP具有良好的免疫原性且具有一定的抗血栓作用。%To study the immuongenicity and anti-thrombotic effect of Tenebrio Fibrinolyric Proteins ( TFP) , mice were immunized with purified TFP by subcutaneous injection , then the antibody content and antibody titer were detected by the optimal ELISA method .Mice were gavaged with purified TFP , then thrombin time ( TT) , prothrombin time ( PT) , activated partial thromboplastin time ( APTT) , tissue-type plasminogen activator ( t-PA) and plasminogen activator inhibitor ( PAI) activity were detected .The results show that the specific antibody is found after TFP immunized mice and the antibody content in -creases when the number of immunization rises .The specific antibody titer is 1∶640 after the last immuni-zation .The TT of mice is remarkably prolonged after using TFP .The t-PA activity increases while the PAI activity decreases .Meanwhile the average thrombosis length of tail is significantly reduced .This shows that the TFP has good

  12. Anti-platelet Aggregation and Anti-thrombotic Effects of Marine Natural Products Sargahydroquinoic Acid and Sargaquinoic Acid

    Energy Technology Data Exchange (ETDEWEB)

    Park, Byonggon; Oh, Sangtae; Kwon, Daeho; Cui, Yuan; Ham, Jungyeob; Shin, Woonseob; Lee, Seokjoon [Kwandong Univ. College of Medicine, Gangneung (Korea, Republic of)

    2013-10-15

    On the basis of the results of the in vitro platelet aggregation inhibition test, we discovered that of SHQA (1) and SQA (2) show a strong inhibitory effect on platelet aggregation. To enable preclinical and clinical studies to be conducted, we synthesized SQA from natural SHQA in high yield. In addition, we confirmed that SHQA (1) and SQA (2) show a fast recovery time from paralysis in the mouse pulmonary thromboembolism model, indicating that they are strong, novel anti-platelet drug candidates. As bleeding is a main side effect of the APDs used clinically, we also plan to conduct a bleeding test with SHQA and SQA and will report these results in a future proper paper. Platelets circulate in blood and their activity is regulated by nitric oxide (NO) and prostaglandin I{sub 2} (PGI{sub 2}) released from endothelial cells in a quiescent state under physiological conditions.

  13. Chebulagic acid inhibits the LPS-induced expression of TNF-α and IL-1β in endothelial cells by suppressing MAPK activation.

    Science.gov (United States)

    Liu, Yueying; Bao, Luer; Xuan, Liying; Song, Baohua; Lin, Lin; Han, Hao

    2015-07-01

    Inflammatory response in the vasculature, including the overexpression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β, has been demonstrated to increase the risk of thrombosis development. Chebulagic acid (CA) is a key chemical component in the traditional Mongolian anti-thrombotic drug Garidi-13, and has been suggested to exert anti-inflammatory and anti-infective effects. The present study aimed to evaluate the regulatory impact of CA on a number of biological processes, including lipopolysaccharide (LPS)-induced inflammation, LPS-promoted mitogen-activated protein kinase (MAPK) activation and the expression of toll-like receptor (TLR)4 in EA.hy926 human endothelial cells. The results indicated that CA significantly inhibited the LPS-induced upregulation of TNF-α and IL-1β in a dose- and time-dependent manner. Furthermore, LPS-activated MAPK signaling was inhibited by CA treatment in the EA.hy926 cells. However, TLR4, which serves a key function in LPS-induced inflammation as the receptor of LPS, was not regulated by the CA treatment. In summary, the results of the present study indicate that CA inhibits the LPS-induced promotion of TNF-α and IL-1β in endothelial cells by suppressing MAPK activation, which may contribute to the anti-thrombotic effect of Garidi-13.

  14. 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.

  15. Promoting Business Education through Student Organization Activities.

    Science.gov (United States)

    Yelverton, Sandra

    1983-01-01

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

  16. 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.

  17. Anti-thrombotic technologies for medical devices.

    Science.gov (United States)

    Lavery, Karen S; Rhodes, Candace; Mcgraw, Adam; Eppihimer, Michael J

    2016-08-03

    Thrombosis associated with medical devices may lead to dramatic increases in morbidity, mortality and increased health care costs. Innovative strategies are being developed to reduce this complication and provide a safe biocompatible interface between device and blood. This article aims to describe the biological phenomena underlying device-associated thrombosis, and surveys the literature describing current and developing technologies designed to overcome this challenge. To reduce thrombosis, biomaterials with varying topographical properties and incorporating anti-thrombogenic substances on their surface have demonstrated potential. Overall, there is extensive literature describing technical solutions to reduce thrombosis associated with medical devices, but clinical results are required to demonstrate significant long-term benefits.

  18. THE PROMOTIONAL ACTIVITY IN THE TOURISTIC SECTOR

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    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.

  19. Activities for Engaging Schools in Health Promotion

    Science.gov (United States)

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

    2014-01-01

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

  20. 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.

  1. 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

  2. Promoting Active Involvement in Classrooms

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    Conderman, Greg; Bresnahan, Val; Hedin, Laura

    2012-01-01

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

  3. 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.

  4. Heavy drinking and health promotion activities.

    Science.gov (United States)

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

    2010-07-01

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

  5. Estudo de segurança e eficácia da enoxaparina sódica na profilaxia e terapêutica antitrombótica Safety and efficacy of sodium enoxaparin in anti-thrombotic prophylaxis and treatment

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    Silvia G Lage

    2007-03-01

    was to evaluate safety and efficacy of test sodium enoxaparin (ENOX-T compared to the reference drug (ENOX-R. METHODS: We conducted a prospective, randomized, comparative, unicentric and open-labeled trial including patients with either prophylactic or therapeutic anti-thrombotic indications. A total of 100 patients were enrolled in two branches: prophylactic (n=50 and therapeutic (n=50 and two groups for each branch (group 1: ENOX-R and group 2: ENOX-T. We analyzed clinical and laboratory data in each segment. Anti-factor Xa was measured in three different moments: baseline (1st evaluation; 1st or 2nd day (2nd evaluation and 5th to 7th day (3rd evaluation. Doppler-sonography of inferior limbs was performed on all patients in prophylactic group on 2nd or 3rd evaluation. RESULTS: The data showed that both branches (prophylactic and therapeutic were homogenous in regard of sex, age, body mass index (BMI, serum creatinine and APACHE II severity score at admission. Anti-factor Xa results, in both prophylactic and therapeutic branches, showed expected efficacy to both drugs, without any clinical or statistical difference between them. Adverse events incurred in both groups in a similar way, without any clinical or statistical difference between them. In prophylactic branch, Doppler-sonography of inferior limbs added useful information on drugs efficacy. CONCLUSIONS: We conclude that test sodium enoxaparin (ENOX-T was effective and safe in our patient's cohort and equivalent to reference drug (ENOX-R.

  6. THE CONTROL AND EVALUATION OF PROMOTIONAL ACTIVITIES

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    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.

  7. 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...

  8. PROMOTION OF ACTIVE MEASURES AND EMPLOYMENT STIMULATION

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    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.

  9. In-vitro anti-atherothrombosis activity of four Bangladeshi plants

    OpenAIRE

    Irin Sultana; Md. Abdun Noor; Joy Barua; Ayesha Mahmood; Mishon Chandra Das; Md. Torequl Islam; Mohammed Ibrahim; M Mohi Uddin Chowdhury

    2012-01-01

    Thrombous formation inside the blood vessels obstructs blood flow through the circulatory system leading hypertension, stroke to the heart, anoxia and so on. The complete deprivation of oxygen and infarction is a mode of cell death. Crude biologicals and their components possessing anti-thrombotic activity have been reported before. This study was aimed to investigate thrombolytic activity of ethanol extracts of four traditionally used medicinal plants. For this an in-vitro thrombolytic study...

  10. Promoter proximal polyadenylation sites reduce transcription activity

    DEFF Research Database (Denmark)

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

    2012-01-01

    on transcription requires promoter proximity, as demonstrated using artificial constructs and supported by a genome-wide data set. Importantly, transcription down-regulation can be recapitulated in a gene context devoid of splice sites by placing a functional bona fide pA site/transcription terminator within ∼500...... base pairs of the promoter. In contrast, promoter-proximal positioning of a pA site-independent histone gene terminator supports high transcription levels. We propose that optimal communication between a pA site-dependent gene terminator and its promoter critically depends on gene length and that short...

  11. 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.

  12. 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.

  13. 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.

  14. 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…

  15. Promoter activities in Vibrio cholerae ctx phi prophage.

    Science.gov (United States)

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

    1997-04-01

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

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

    Science.gov (United States)

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

    2014-08-01

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

  17. 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…

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

    Science.gov (United States)

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

    2016-12-01

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

  19. 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...

  20. 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…

  1. ROLE AND IMPORTANCE OF PROMOTIONAL ACTIVITIES IN RESTAURANT BUSINESS

    Directory of Open Access Journals (Sweden)

    Ivica Batinić

    2014-07-01

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

  2. 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.

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

    Science.gov (United States)

    Welk, Gregory J.

    2008-01-01

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

  4. 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

  5. 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...

  6. 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.

  7. 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.

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

    Science.gov (United States)

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

    2012-11-01

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

  9. Applying Transtheoretical Model to Promote Physical Activities Among Women

    OpenAIRE

    2015-01-01

    Background: Physical activity is one of the most important indicators of health in communities but different studies conducted in the provinces of Iran showed that inactivity is prevalent, especially among women. Objectives: Inadequate regular physical activities among women, the importance of education in promoting the physical activities, and lack of studies on the women using transtheoretical model, persuaded us to conduct this study with the aim of determining the application of transtheo...

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-08-04

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

  12. 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.

  13. 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…

  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...... further co-benefits. Little is known, however, about the interconnections among effects of policies considered, including potential unintended consequences....

  15. 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....

  16. 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…

  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. 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.

  19. 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.

  20. 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.

  1. 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.

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

    Science.gov (United States)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Elizabeth A Perotti

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

  5. 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.

  6. Applying Transtheoretical Model to Promote Physical Activities Among Women

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    2011-09-16

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

  8. 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.

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

    Science.gov (United States)

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

    2015-12-14

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

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

    DEFF Research Database (Denmark)

    Thing, Lone Friis

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

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

    Science.gov (United States)

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

    2005-02-01

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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

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

    Science.gov (United States)

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

    2001-08-01

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

  20. 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.

  1. 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.

  2. Melatonin activates the peroxidase-oxidase reaction and promotes oscillations.

    Science.gov (United States)

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

    2001-06-22

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

  3. 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.

  4. Active aging promotion: results from the vital aging program.

    Science.gov (United States)

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

    2013-01-01

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

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

    DEFF Research Database (Denmark)

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

    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. Paradoxically......, chronic activation of AMPK causes an increase in glycogen accumulation in skeletal and cardiac muscles, which in some cases is associated with cardiac dysfunction. The aim of this study was to elucidate the molecular mechanism by which AMPK activation promotes muscle glycogen accumulation. RESEARCH DESIGN...... AND METHODS We recently generated knock-in mice in which wild-type muscle GS was replaced by a mutant (Arg582Ala) that could not be activated by glucose-6-phosphate (G6P), but possessed full catalytic activity and could still be activated normally by dephosphorylation. Muscles from GS knock-in or transgenic...

  6. 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.

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

    Science.gov (United States)

    Dickinson, Tom

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

  8. 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.

  9. 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.

  10. 7 CFR 981.441 - Credit for market promotion activities, including paid advertising.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Credit for market promotion activities, including paid... promotion activities, including paid advertising. (a) In order for a handler to receive credit for his/her... expenses, or for any promotional activities that result in price discounting. (i) Paid advertising...

  11. 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.

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

    Science.gov (United States)

    Wei, Shi-hui; Zhao, Jia-liang

    2010-12-01

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

  13. 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

  14. 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

    2015-09-01

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

  15. 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.

  16. 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

  17. 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

  18. ADP stimulates human endothelial cell migration via P2Y1 nucleotide receptor-mediated mitogen-activated protein kinase pathways.

    Science.gov (United States)

    Shen, Jianzhong; DiCorleto, Paul E

    2008-02-29

    Extensive research on the role of ADP in platelet activation led to the design of new anti-thrombotic drugs, such as clopidogrel (Plavix; sanofi-aventis); however, very little is known about the ADP-preferring nucleotide receptors (P2Y1, P2Y12, and P2Y13) in endothelium. Here, we show that ADP stimulates migration of cultured human umbilical vein endothelial cells (HUVECs) in both Boyden chamber and in vitro wound repair assays. This promigratory effect was mimicked by 2-MeSADP, but not by AMP, and was inhibited by MRS2179 (P2Y1 receptor antagonist) but not by AR-C69931MX (P2Y12/13 receptor antagonist). RT-PCR revealed abundant P2Y1, barely detectable P2Y12, and absent P2Y13 receptor message in these cells. In addition, both ADP and 2-MeSADP, but not AMP, activated the mitogen-activated protein kinase pathways as evidenced by increased phosphorylation of extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK), and p38 kinase. ADP also stimulated phosphorylation of p90RSK, a downstream substrate of phosphorylated ERK1/2, and induced phosphorylation of such transcription factors downstream of the JNK and p38 pathways as c-Jun and activating transcription factor-2. These signaling events were inhibited by MRS2179 but not by AR-C69931MX. Furthermore, blockade of the ERK or JNK pathways by U0126 and SP600125, respectively, abolished ADP- and 2-MeSADP-stimulated HUVEC migration. However, inhibition of the p38 pathway by SB203580 partially suppressed ADP- and 2-MeSADP-induced HUVEC migration. We conclude that ADP promotes human endothelial cell migration by activating P2Y1 receptor-mediated MAPK pathways, possibly contributing to reendothelialization and angiogenesis after vascular injury.

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

    Science.gov (United States)

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

    2012-11-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2016-10-01

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

  2. 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.

  3. 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.

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

    Science.gov (United States)

    Mor, Y; Halevy, A H

    1980-11-01

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

  5. [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.

  6. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

  8. 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...

  9. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

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

    Science.gov (United States)

    Cale, Lorraine; Harris, Jo; Duncombe, Rebecca

    2016-01-01

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

  12. 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…

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

    OpenAIRE

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

    2009-01-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  15. 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.

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

    OpenAIRE

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

    2015-01-01

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

  17. 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.

  18. 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

  19. 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

  20. 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…

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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…

  7. 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...

  8. 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

  9. 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

  10. 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.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    María Martínez-Solís

    2016-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-07-01

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

  14. Promoting Physical Activity through Hand-Held Computer Technology

    Science.gov (United States)

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

    2009-01-01

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

  15. 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

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

    Science.gov (United States)

    Yan, Zi; Cardinal, Bradley J.

    2013-01-01

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

  17. 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

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  19. 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.

  20. 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.

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

    Science.gov (United States)

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

    2017-02-01

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

  2. 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

  3. Armodafinil promotes wakefulness and activates Fos in rat brain.

    Science.gov (United States)

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

    2009-05-01

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

  4. PKC-δ activation in neutrophils promotes fungal clearance.

    Science.gov (United States)

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

    2016-09-01

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

  5. AKT1 Activation Promotes Development of Melanoma Metastases

    Directory of Open Access Journals (Sweden)

    Joseph H. Cho

    2015-11-01

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

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

    Science.gov (United States)

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

    2006-11-01

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

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

    Science.gov (United States)

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

    2017-03-18

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

  8. Mobile Health Applications to Promote Active and Healthy Ageing

    Science.gov (United States)

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

    2017-01-01

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

  9. Endothelial Notch activity promotes angiogenesis and osteogenesis in bone

    Science.gov (United States)

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

    2014-03-01

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

  10. 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.

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

    Science.gov (United States)

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

    2008-04-01

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

  12. 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.

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

    OpenAIRE

    Everett, R D; Dunlop, M

    1984-01-01

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

  14. 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…

  15. 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…

  16. 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…

  17. 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...

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

    Science.gov (United States)

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

    2017-04-03

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

  19. 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…

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

    Science.gov (United States)

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

    2016-12-01

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

  1. 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.

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

    Science.gov (United States)

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

    2011-06-23

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

  3. 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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Rebecca E. Lee

    2011-01-01

    Full Text Available Physical inactivity, poor dietary habits, and obesity are vexing problems among minorities. SAving Lives, Staying Active (SALSA was an 8-week randomized controlled crossover design, pilot study to promote regular physical activity (PA and fruit and vegetable (FV consumption as a means to preventing weight gain among women of color. Participants completed measures of demographics, PA, and dietary habits. Women (=50;=42 years who participated were overweight (BMI=29.7 kg/m2; bodyfat=38.5% and reported low levels of leisure time PA (=10.7 MET-min/wk and FV consumption (=4.2 servings/day. All were randomized to a four-week (1 semiweekly Latin dance group or (2 internet-based dietary education group. All participants reported a significant increase in weekly leisure time PA from baseline (=10.7 MET-min/wk to follow up (=34.0 MET-min/wk, <.001, and FV consumption increased over time by group (=.02. Data suggest that Latin dance interventions to improve PA and web-based interventions to improve dietary habits show promise for improving health among women of color.

  6. SIRT1 promotes DNA repair activity in response to radiation

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-07-01

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

  7. 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.

  8. 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, ...).

  9. 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.

  10. 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.

  11. 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.

  12. 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.

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

    OpenAIRE

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

    2014-01-01

    Background Low levels of physical activity, musculoskeletal morbidity and weight gain are commonly reported problems in children with cancer. Intensive medical treatment and a decline in physical activity may also result in reduced motor performance. Therefore, simple and inexpensive ways to promote physical activity and exercise are becoming an increasingly important part of children’s cancer treatment. Methods The aim of this study is to evaluate the effect of active video games in promotio...

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

    OpenAIRE

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

    2009-01-01

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

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

    OpenAIRE

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

    2009-01-01

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

  16. 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.

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

    Science.gov (United States)

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

    2011-01-01

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

  18. 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…

  19. 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.

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

    Science.gov (United States)

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

    2009-04-01

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

  1. 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.

  2. 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.

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

    Science.gov (United States)

    Murase, Daisuke; Namekawa, Shoko; Ohkubo, Takeshi

    2016-01-01

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

  4. 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.

  5. 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.

  6. Activated T cell exosomes promote tumor invasion via Fas signaling pathway.

    Science.gov (United States)

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

    2012-06-15

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

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

    OpenAIRE

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

    1985-01-01

    The role of conserved nucleotides in nitrogen-fixation promoter function has been examined using both oligonucleotide and chemical mutagenesis to introduce base changes in the Klebsiella pneumoniae nifL and nifH promoters. Among ten mutations analysed, including six spontaneous mutations, base changes at -12, -13, -14, and -26, located in previously identified conserved sequences, perturbed the activity of the promoters, demonstrating that these sequences are required for transcription. Not a...

  8. 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.

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

    Science.gov (United States)

    Goszczyńska, Eliza

    2010-01-01

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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. HNF1 alpha activates the aminopeptidase N promoter in intestinal (Caco-2) cells

    DEFF Research Database (Denmark)

    Olsen, Jørgen; Laustsen, Lotte; Troelsen, J

    1994-01-01

    The importance of HNF1 binding proteins for intestinal aminopeptidase N expression was investigated using the Caco-2 cell-line. Aminopeptidase N promoter activity in Caco-2 cells depends on the HNF1 element (positions -85 to -58) and co-transfection with an HNF1 alpha expression vector demonstrates...... a direct activation of the promoter by HNF1 alpha through this element. Electrophoretic mobility shift assays using nuclear extracts from Caco-2 cells show the presence of high amounts of HNF1 binding proteins irrespective of their state of differentiation....

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

    Science.gov (United States)

    Rafii, Forough; Seyedfatemi, Naima; Rezaei, Mahboubeh

    2013-01-01

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

  17. Using the tax system to promote physical activity: critical analysis of Canadian initiatives.

    Science.gov (United States)

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

    2011-08-01

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

  18. 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.

  19. Identification of a type 1 diabetes-associated CD4 promoter haplotype with high constitutive activity

    DEFF Research Database (Denmark)

    Kristiansen, O P; Karlsen, A E; Larsen, Z M;

    2004-01-01

    CD4 is a candidate gene in autoimmune diseases, including Type 1 diabetes mellitus (T1DM), because the CD4 receptor is crucial for appropriate antigen responses of CD4(+) T cells. We previously found linkage between a CD4-1188(TTTTC)(5-14) promoter polymorphism and T1DM. In the present study, we...... screened the human CD4 promoter for mutations and identified three frequent single nucleotide polymorphisms (SNPs): CD4-181C/G, CD4-521C/G and CD4-1050T/C. The SNPs are in strong linkage disequilibrium (LD) and association with the CD4-1188(TTTTC)(5-14) alleles, and we observed nine CD4 promoter haplotypes...... promoter activity and (2) the CD4-181G variant encodes higher stimulated promoter activity than the CD4-181C variant. This difference is in part neutralized in the frequently occurring CD4 promoter haplotypes by the more upstream genetic variants. Thus, we report functional impact of a novel CD4-181C/G SNP...

  20. 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.

  1. 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.

  2. Evaluation of physical activity in the health promotion for brazilian teenagers: a systematic review

    Directory of Open Access Journals (Sweden)

    Alvaro Adolfo Duarte Alberto

    2014-05-01

    Full Text Available Objective: To analyze the methodological designs of national studies that assessed the level of physical activity for promoting adolescent health. Methods: a systematic literature review of original researches and publications of MEDLINE, LILACS, SCOPUS and ADOLEC electronic databases. It focused on determinant aspects of physical activity for health promotion using the following keywords: physical activity, physical fitness, physical activity, physical exercise, motor activity, sedentary and sedentariness, adolescent, adolescence, young, youth, teenager, and teenage, Brazil, Brazilian, South America, Low-middle income and country(ies. Data analysis covered the period from 2005 to 2011. First, 449 studies were identified. After analyzing the titles of the manuscripts, 130 articles were eligible for abstract evaluation and subsequent full text analysis. In the end, 31 articles met all inclusion criteria. Results: A total of 93.6% (n=29 of the evaluated studies used cross-sectional design, with samples ranging from 92 to 5028 subjects, and all of them used questionnaires for measuring physical activity. The main analysis of the studies was based on the association between physical activity, biodemographic data (age, gender and socioeconomic data (income, social class and parental education. Conclusion: The national studies assessing the level of physical activity for promoting adolescent health appear with great methodological variability since there is no standardization in the methodological design, instrument and definition of variables, highlighting the need for longitudinal studies in this area. doi:10.5020/18061230.2013.p426

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

    Science.gov (United States)

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

    2013-01-01

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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Gyrase-dependent stabilization of pSC101 plasmid inheritance by transcriptionally active promoters.

    Science.gov (United States)

    Beaucage, S L; Miller, C A; Cohen, S N

    1991-09-01

    The pSC101 plasmid encodes a cis-acting genetic locus termed par that ensures the stable inheritance of plasmids in a population of dividing cells. In the absence of selection, par-defective plasmids are lost rapidly from the bacterial population. We report here that the stability of par-deleted pSC101 derivatives is restored by introducing certain adventitious bacterial promoters onto the plasmid. Stabilization requires active transcription from the inserted promoter and is affected by the site and orientation of the insertion, the length of the nascent transcript and DNA gyrase activity. While a promotor-associated overall increase in negative superhelicity of plasmid DNA was observed, stabilized inheritance appeared to be dependent on localized rather than generalized supercoiling. Our demonstration that promoter-induced DNA supercoiling can mimic the effects of the pSC101 par locus provides evidence that the previously reported superhelicity-generating effects of par are intrinsic to its function.

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

    Science.gov (United States)

    Arendse, Gillian J.

    2009-04-01

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

  10. 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.

  11. hTERT promoter activity and CpG methylation in HPV-induced carcinogenesis

    Directory of Open Access Journals (Sweden)

    Snijders Peter JF

    2010-06-01

    Full Text Available Abstract Background Activation of telomerase resulting from deregulated hTERT expression is a key event during high-risk human papillomavirus (hrHPV-induced cervical carcinogenesis. In the present study we examined hTERT promoter activity and its relation to DNA methylation as one of the potential mechanisms underlying deregulated hTERT transcription in hrHPV-transformed cells. Methods Using luciferase reporter assays we analyzed hTERT promoter activity in primary keratinocytes, HPV16- and HPV18-immortalized keratinocyte cell lines and cervical cancer cell lines. In the same cells as well as cervical specimens we determined hTERT methylation by bisulfite sequencing analysis of the region spanning -442 to +566 (relative to the ATG and quantitative methylation specific PCR (qMSP analysis of two regions flanking the hTERT core promoter. Results We found that in most telomerase positive cells increased hTERT core promoter activity coincided with increased hTERT mRNA expression. On the other hand basal hTERT promoter activity was also detected in telomerase negative cells with no or strongly reduced hTERT mRNA expression levels. In both telomerase positive and negative cells regulatory sequences flanking both ends of the core promoter markedly repressed exogenous promoter activity. By extensive bisulfite sequencing a strong increase in CpG methylation was detected in hTERT positive cells compared to cells with no or strongly reduced hTERT expression. Subsequent qMSP analysis of a larger set of cervical tissue specimens revealed methylation of both regions analyzed in 100% of cervical carcinomas and 38% of the high-grade precursor lesions, compared to 9% of low grade precursor lesions and 5% of normal controls. Conclusions Methylation of transcriptionally repressive sequences in the hTERT promoter and proximal exonic sequences is correlated to deregulated hTERT transcription in HPV-immortalized cells and cervical cancer cells. The detection of DNA

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

    Science.gov (United States)

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

    2008-05-01

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

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

    Science.gov (United States)

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

    1975-11-01

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

  14. 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

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

    Science.gov (United States)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  17. A Highly Active and Selective Manganese Oxide Promoted Cobalt-on-Silica Fischer-Tropsch Catalyst

    NARCIS (Netherlands)

    den Breejen, Johan P.; Frey, Anne M.; Yang, Jia; Holmen, Anders; van Schooneveld, Matti M.; de Groot, Frank M. F.; Stephan, Odile; Bitter, Johannes H.; de Jong, Krijn P.

    2011-01-01

    A highly active and selective manganese oxide-promoted silica-supported cobalt catalyst for the Fischer-Tropsch reaction is reported. Co/MnO/SiO2 catalysts were prepared via impregnation of a cobalt nitrate and manganese nitrate precursor, followed by drying and calcination in an NO/He flow. The cat

  18. 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.

  19. 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...

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

    Science.gov (United States)

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

    2013-01-01

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

  1. 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…

  2. Tailored interventions to promote Active Ageing using mobile technology: a feasibility study

    NARCIS (Netherlands)

    Cabrita, M.; Melenk, J.; El Menshawy, N.; Tabak, M.; Vollenbroek-Hutten, M.

    2016-01-01

    Introduction: Mobile technologies facilitate innovative and ubiquitous interventions to promote Active Ageing in daily life. To ensure adoption, such interventions must be designed in co-operation with older adults. This work presents the results of a feasibility study of a system that monitors phys

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

    Science.gov (United States)

    Bush, Paula Louise; García Bengoechea, Enrique

    2015-01-01

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

  4. Neutrophil myeloperoxidase activity and the influence of two single-nucleotide promoter polymorphisms

    NARCIS (Netherlands)

    Rutgers, Abraham; Heeringa, Peter; Giesen, Joyce E H M; Theunissen, Ruud T; Jacobs, Heinz; Tervaert, Jan Willem Cohen

    2003-01-01

    Myeloperoxidase (MPO) catalyses the formation of hypochlorous acid and is involved in many (patho)physiological processes. The present study was designed to determine the effect of two MPO promoter polymorphisms (463G/A and 129G/A) on enzyme activity. In 243 healthy controls, genotypes were determin

  5. 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...

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

    Science.gov (United States)

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

    2014-01-01

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

  7. 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

  8. 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…

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

    Science.gov (United States)

    Kitazono, Ana A.

    2010-01-01

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

  10. 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…

  11. Adding effect sizes to a systematic review on interventions for promoting physical activity among European teenagers

    OpenAIRE

    Crutzen Rik

    2010-01-01

    Abstract This commentary adds effect sizes to the recently published systematic review by De Meester and colleagues and provides a more detailed insight into the effectiveness of interventions to promote physical activity among European teenagers. The main findings based on this evidence were: (1) school-based interventions generally lead to short term improvement in physical activity levels, but there were large differences between interventions with regard to effect sizes; (2) a multi-compo...

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

    Science.gov (United States)

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

    2017-01-11

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

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

    Science.gov (United States)

    Liu, Dan; Liu, Xin; Wu, Ye; Wang, Wen; Ma, Xinliang; Liu, Huirong

    2016-01-16

    HtrA serine peptidase 2 (HtrA2), also named Omi, is a pro-apoptotic protein that exhibits dramatic changes in expression levels in a variety of disorders, including ischemia/reperfusion injury, cancer, and neurodegeneration. In our study, Omi/HtrA2 protein levels were high in the heart, brain, kidney and liver, with elevated heart/brain expression in aging mice. A similar expression pattern was observed at the mRNA level, which suggests that the regulation of Omi/HtrA2 is predominately transcriptional. Promoter binding by transcription factors is the main influencing factor of transcription, and to identify specific promoter elements that contribute to the differential expression of mouse Omi/HtrA2, we constructed truncated Omi/HtrA2 promoter/luciferase reporter vectors and analyzed their relative luciferase activity; it was greatest in the promoter regions at -1205~-838 bp and -146~+93 bp, with the -838~-649 bp region exhibiting negative regulatory activity. Bioinformatics analysis suggested that the Omi/HtrA2 gene promoter contains a CpG island at -709~+37 bp, and eight heat shock transcription factor 1 (HSF1) sites, two Sp1 transcription factor (SP1)sites, one activator protein (AP) site, seven p53 sites, and four YY1 transcription factor(YY1) sites were predicted in the core areas. Furthermore, we found that p53 and HSF1 specifically binds to the Omi/HtrA2 promoter using chromatin immunoprecipitation analysis. These results provide a foundation for understanding Omi/HtrA2 regulatory mechanisms, which could further understanding of HtrA-associated diseases.

  14. 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

    Summary Microorganisms can utilize different sugars as energy and carbon sources and the genes involved in sugar metabolism often exhibit highly regulated expression. To study cis-acting elements controlling arabinose-responsive expression in archaea, the promoter of the Sulfolobus solfataricus a...

  15. 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

    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...

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Catherine Moorwood

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

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

    Directory of Open Access Journals (Sweden)

    Maria Letizia Taddei

    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.

  19. Activation of the Notch signaling pathway promotes neurovascular repair after traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Qi-shan Ran; Yun-hu Yu; Xiao-hong Fu; Yuan-chao Wen

    2015-01-01

    The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after traumatic brain injury. Therefore, in the present study, we controlled the Notch signaling path-way using overexpression and knockdown constructs. Activation of the Notch signaling pathway by Notch1 or Jagged1 overexpression enhanced the migration, invasiveness and angiogenic ability of endothelial progenitor cells. Suppression of the Notch signaling pathway with Notch1 or Jagged1 siRNAs reduced the migratory capacity, invasiveness and angiogenic ability of endo-thelial progenitor cells. Activation of the Notch signaling pathwayin vivo in a rat model of mild traumatic brain injury promoted neurovascular repair. These ifndings suggest that the activation of the Notch signaling pathway promotes blood vessel formation and tissue repair after brain trauma.

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

    Directory of Open Access Journals (Sweden)

    Kimberly Aebli

    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.

  1. 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

    Accumulating evidence shows that there seems to be a relation between the existence of a policy and at least some health behaviours of children. The purpose of this paper is to give a brief account of the value of policy as a tool that can be used at local level to guide action to promote healthy...... lifestyle in kindergartens. A policy can be defi ned as a set of adopted principles that guide the work of an organization and aim to achieve a well defi ned goal, but only policies that rely on the active participation and involvement of concerned actors will be effi cient. A number of studies suggest...... that local level policy on nutrition and on physical activity seems to have the potential to work as a good frame for the organizational efforts that the kindergarten undertakes in order to promote healthy eating and physical activity among children in kindergarten. However, kindergartens need to make...

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

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    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.

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

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

    Science.gov (United States)

    Martin, Robert G; Rosner, Judah L

    2011-01-01

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

  5. 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.

  6. Interventions to promote physical activity in older people with type 2 diabetes mellitus: A systematic review

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    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.

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

    Science.gov (United States)

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

    2013-01-01

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

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

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    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

  9. 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.

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

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    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.

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

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    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.

  12. Diffusing a Research-based Physical Activity Promotion Program for Seniors Into Diverse Communities: CHAMPS III

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    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

  13. 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...

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

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    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.

  15. 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.

  16. TLR4 activation promotes podocyte injury and interstitial fibrosis in diabetic nephropathy.

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    Jin Ma

    Full Text Available Toll like receptor (TLR 4 has been reported to promote inflammation in diabetic nephropathy. However the role of TLR4 in the complicated pathophysiology of diabetic nephropathy is not understood. In this study, we report elevated expression of TLR4, its endogenous ligands and downstream cytokines, chemokines and fibrogenic genes in diabetic nephropathy in WT mice with streptozotocin (STZ diabetes. Subsequently, we demonstrated that TLR4-/- mice were protected against the development of diabetic nephropathy, exhibiting less albuminuria, inflammation, glomerular hypertrophy and hypercellularity, podocyte and tubular injury as compared to diabetic wild-type controls. Marked reductions in interstitial collagen deposition, myofibroblast activation (α-SMA and expression of fibrogenic genes (TGF-β and fibronectin were also evident in TLR4 deficient mice. Consistent with our in vivo results, high glucose directly promoted TLR4 activation in podocytes and tubular epithelial cells in vitro, resulting in NF-κB activation and consequent inflammatory and fibrogenic responses. Our data indicate that TLR4 activation may promote inflammation, podocyte and tubular epithelial cell injury and interstitial fibrosis, suggesting TLR4 is a potential therapeutic target for diabetic nephropathy.

  17. 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.

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

    Science.gov (United States)

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

    2016-04-01

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

  19. 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.

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, Darrion L. [Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064 (United States); DiMario, Joseph X., E-mail: joseph.dimario@rosalindfranklin.edu [Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064 (United States)

    2010-01-15

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

  2. 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

  3. 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

    204) although phosphorylation of b-Raf (Ser445) and c-Raf (Ser 338) remained unchanged. Furthermore, increased activation of the PAK1 activator Rac1 induced the formation of a triple complex of Rac1, PAK1 and Mek1, independent of the kinase activity of PAK1. These data suggest that PAK1 can stimulate...

  4. 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,…

  5. FBI-1 enhances ETS-1 signaling activity and promotes proliferation of human colorectal carcinoma cells.

    Science.gov (United States)

    Zhu, Min; Li, Mingyang; Zhang, Fan; Feng, Fan; Chen, Weihao; Yang, Yutao; Cui, Jiajun; Zhang, Dong; Linghu, Enqiang

    2014-01-01

    In this study, we investigated a potential regulatory role of FBI-1 in transcription factor activity of ETS-1. The protein interaction was identified between ETS-1 and FBI-1 in lovo cells. The accumulating data showed that FBI-1 promoted the recruitment of ETS-1 to endogenous promoter of its target genes and increase ETS-1 accumulation in the nuclear. Our work also indicated that the FBI-1 enhances ETS-1 transcription factor activity via down-regulating p53-mediated inhibition on ETS-1. Further, FBI-1 plays a role in regulation of colorectal carcinoma cells proliferation. These findings supported that FBI-1 might be a potential molecule target for treating colorectal carcinoma.

  6. 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.

  7. 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.

  8. 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…

  9. Pleiotropic β-Agonist–Promoted Receptor Conformations and Signals Independent of Intrinsic Activity

    OpenAIRE

    2006-01-01

    β-Agonists used for treatment of obstructive lung disease have a variety of different structures but are typically classified by their intrinsic activities for stimulation of cAMP, and predictions are made concerning other downstream signals based on such a classification. We generated modified β2-adrenergic receptors with insertions of energy donor and acceptor moieties to monitor agonist-promoted conformational changes of the receptor using intramolecular bioluminescence resonance energy tr...

  10. The effectiveness of an intervention promoting physical activity in elemantary school children

    OpenAIRE

    Verstraete, S

    2006-01-01

    Regular physical activity (PA) is an important component of a healthfully lifestyle in children and adolescents. The main purpose of this dissertation was to evaluate the effectiveness of a comprehensive PA promotion intervention in elementary school children. Furthermore, the effectiveness of some of the intervention components was evaluated. Sixteen elementary schools participated in the intervention study. They were randomly assigned to the intervention (n = 8) and control condition (n = 8...

  11. Canadian Society for Exercise Physiology position stand: Benefit and risk for promoting childhood physical activity.

    Science.gov (United States)

    Longmuir, Patricia E; Colley, Rachel C; Wherley, Valerie A; Tremblay, Mark S

    2014-11-01

    Current guidelines recommend children accumulate 60 min of daily physical activity; however, highly publicized sudden-death events among young athletes raise questions regarding activity safety. An expert group convened (June 2012) to consider the safety of promoting increased physical activity for children, and recommended the publication of an evidence-based statement of current knowledge regarding the benefits and risks of physical activity for children. Recommendations for encouraging physical activity while maximizing the opportunity to identify children who have been prescribed a physical activity restriction include (1) professionals and (or) researchers that encourage children to change the type of physical activity or to increase the frequency, intensity, or duration of their activity should inquire whether a child has primary healthcare provider-prescribed activity limitations before the child's activity participation changes; (2) physical activity researchers should prioritize the development of evidence regarding the benefits and risks of childhood physical activity and inactivity, particularly data on the risks of sedentary lifestyles and physical activity-associated injury risks that accounts for the amount of activity performed, and the effectiveness of current risk-management strategies and screening approaches; (3) professionals and researchers should prioritize the dissemination of information regarding the benefits of physical activity and the risks of sedentary behaviour in children; and (4) parents and professionals should encourage all children to accumulate at least 60 min of physical activity daily. The recommendations are established as a minimum acceptable standard that is applicable to all physical activity opportunities organized for children, whether those opportunities occur in a community, school, or research setting.

  12. 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.

  13. Tumor suppressor protein C53 antagonizes checkpoint kinases to promote cyclin-dependent kinase 1 activation.

    Science.gov (United States)

    Jiang, Hai; Wu, Jianchun; He, Chen; Yang, Wending; Li, Honglin

    2009-04-01

    Cyclin-dependent kinase 1 (Cdk1)/cyclin B1 complex is the driving force for mitotic entry, and its activation is tightly regulated by the G2/M checkpoint. We originally reported that a novel protein C53 (also known as Cdk5rap3 and LZAP) potentiates DNA damage-induced cell death by modulating the G2/M checkpoint. More recently, Wang et al. (2007) found that C53/LZAP may function as a tumor suppressor by way of inhibiting NF-kappaB signaling. We report here the identification of C53 protein as a novel regulator of Cdk1 activation. We found that knockdown of C53 protein causes delayed Cdk1 activation and mitotic entry. During DNA damage response, activation of checkpoint kinase 1 and 2 (Chk1 and Chk2) is partially inhibited by C53 overexpression. Intriguingly, we found that C53 interacts with Chk1 and antagonizes its function. Moreover, a portion of C53 protein is localized at the centrosome, and centrosome-targeting C53 potently promotes local Cdk1 activation. Taken together, our results strongly suggest that C53 is a novel negative regulator of checkpoint response. By counteracting Chk1, C53 promotes Cdk1 activation and mitotic entry in both unperturbed cell-cycle progression and DNA damage response.

  14. 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.

  15. 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.

  16. Promoting Physical Activity With Group Pictures. Affiliation-Based Visual Communication for High-Risk Populations.

    Science.gov (United States)

    Reifegerste, Doreen; Rossmann, Constanze

    2017-02-01

    Past research in social and health psychology has shown that affiliation motivation is associated with health behavior, especially for high-risk populations, suggesting that targeting this motivation could be a promising strategy to promote physical activity. However, the effects that affiliation appeals (e.g., pictures depicting companionship during physical activities) and accompanying slogans have on motivating physical activity have been largely unexplored. Hence, our two studies experimentally tested the effects of exposure to affiliation-based pictures for overweight or less active people, as well as the moderating effect of affiliation motivation. The results of these two studies give some indication that group pictures (with or without an accompanying slogan) can be an effective strategy to improve high-risk populations' attitudes, self-efficacy, and intentions to engage in physical activity. Affiliation motivation as a personality trait did not interact with these effects, but was positively associated with attitudes, independent of the group picture effect.

  17. 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.

  18. Effect of environmental estrogens on IL-1beta promoter activity in a macrophage cell line.

    Science.gov (United States)

    Ruh, M F; Bi, Y; Cox, L; Berk, D; Howlett, A C; Bellone, C J

    1998-10-01

    Environmental estrogens or estrogen disrupters have recently received a great deal of attention because of their potential health impact on reproductive tissues. Few, if any, studies have been made on the impact of these compounds on the immune system. We sought to determine the activities of various environmental estrogens on the modulation of the interleukin-1beta (IL-1beta) gene in a model monocytic cell line, hER + IL-1beta-CAT+. This cell line stably transfected with the human estrogen receptor, and an IL-1beta promoter construct fused to the CAT reporter gene allows us to monitor the effect of estrogenic compounds on IL-1beta promoter activity. 17beta-estradiol (E2) markedly enhanced lipopolysaccharide- (LPS) induced IL-1beta promoter-driven CAT activity in a dose-dependent manner. The mycotoxins alpha-zearalenol and zearalenone both exhibited full agonist activity, but at lower potencies, with EC50 values of 1.8 and 54 nM, respectively, compared with E2 at 0.5 nM. In addition, genistein was a very low-potency agonist, having an EC50 of 1.5 microM. Similar to the E2 response, the slope factors for alpha-zearalenol, zearalenone, and genistein were close to 3.0, suggesting positive cooperativity in the estrogenic response. The activity of the mycotoxins appeared to be mediated through the estrogen receptor, since both the antiestrogens H1285 and ICI 182,780 effectively inhibited their agonist activity in a dose-dependent manner. Representative environmental estrogenic compounds both from plant and industrial sources were also tested. Unlike the mycoestrogens, none of the compounds, with the exception of genistein, synergized with LPS to enhance IL-1beta promoter activity. When tested for antiestrogenic activity, the industrial compound 4-octylphenol was able to antagonize the response to E2; however, the response was three orders of magnitude less potent than H 1285. Naringenin, a plant flavonoid, showed little or no ability to antagonize the response to E2

  19. Identification of a small molecule activator of novel PKCs for promoting glucose-dependent insulin secretion

    Institute of Scientific and Technical Information of China (English)

    Shuai Han; Heling Pan; Jianhua Zhang; Li Tan; Dawei Ma; Junying Yuan; Jia-Rui Wu

    2011-01-01

    Using an image-based screen for small molecules that can affect Golgi morphology, we identify a small molecule,Sioc145, which can enlarge the Golgi compartments and promote protein secretion. More importantly, Siocl45 potentiates insulin secretion in a glucose-dependent manner. We show that Sioc145 selectively activates novel protein kinase Cs (nPKCs; δ and ε) but not conventional PKCs;cPKCs; a, βI and βll) in INS-1E insulinoma cells. In contrast, PMA, a non-selective activator of cPKCs and nPKCs, promotes insulin secretion independent of glucose concentrations. Furthermore, we demonstrate that Sioc145 and PMA show differential abilities in depolarizing the cell membrane, and suggest that Sioc145 promotes insulin secretion in the amplifying pathway downstream of K ATp channels. In pancreatic islets, the treatment with Sioc145 enhances the second phase of insulin secretion. Increased insulin granules close to the plasma membrane are observed after Sioc145 treatment. Finally, the administration of Sioc145 to diabetic GK rats increases their serum insulin levels and improves glucose tolerance. Collectively, our studies identify Sioc145 as a novel glucose-dependent insulinotropic compound via selectively activating nPKCs.

  20. Sevoflurane preconditioning induced endogenous neurogenesis against ischemic brain injury by promoting microglial activation.

    Science.gov (United States)

    Li, Li; Saiyin, Hexige; Xie, Jingmo; Ma, Lixiang; Xue, Lei; Wang, Wei; Liang, Weimin; Yu, Qiong

    2017-02-14

    Brain ischemia causes irreversible damage to functional neurons in cases of infarct. Promoting endogenous neurogenesis to replace necrotic neurons is a promising therapeutic strategy for ischemia patients. The neuroprotective role of sevoflurane preconditioning implies that it might also enhance endogenous neurogenesis and functional restoration in the infarct region. By using a transient middle cerebral artery occlusion (tMCAO) model, we discovered that endogenous neurogenesis was enhanced by sevoflurane preconditioning. This enhancement process is characterized by the promotion of neuroblast proliferation within the subventricular zone (SVZ), migration and differentiation into neurons, and the presence of astrocytes and oligodendrocytes at the site of infarct. The newborn neurons in the sevoflurane preconditioning group showed miniature excitatory postsynaptic currents (mEPSCs), increased synaptophysin and PSD95 staining density, indicating normal neuronal function. Furthermore, long-term behavioral improvement was observed in the sevoflurane preconditioning group consistent with endogenous neurogenesis. Further histological analyses showed that sevoflurane preconditioning accelerated microglial activation, including migration, phagocytosis and secretion of brain-derived neurotrophic factor (BDNF). Intraperitoneal injection of minocycline, a microglial inhibitor, suppressed microglial activation and reversed neurogenesis. Our data showed that sevoflurane preconditioning promoted microglial activities, created a favorable microenvironment for endogenous neurogenesis and accelerated functional reconstruction in the infarct region.

  1. ATPase activity tightly regulates RecA nucleofilaments to promote homologous recombination

    Science.gov (United States)

    Zhao, Bailin; Zhang, Dapeng; Li, Chengmin; Yuan, Zheng; Yu, Fangzhi; Zhong, Shangwei; Jiang, Guibin; Yang, Yun-Gui; Le, X Chris; Weinfeld, Michael; Zhu, Ping; Wang, Hailin

    2017-01-01

    Homologous recombination (HR), catalyzed in an evolutionarily conserved manner by active RecA/Rad51 nucleofilaments, maintains genomic integrity and promotes biological evolution and diversity. The structures of RecA/Rad51 nucleofilaments provide information critical for the entire HR process. By exploiting a unique capillary electrophoresis-laser-induced fluorescence polarization assay, we have discovered an active form of RecA nucleofilament, stimulated by ATP hydrolysis, that contains mainly unbound nucleotide sites. This finding was confirmed by a nuclease protection assay and electron microscopy (EM) imaging. We further found that these RecA-unsaturated filaments promote strand exchange in vitro and HR in vivo. RecA mutants (P67D and P67E), which only form RecA-unsaturated nucleofilaments, were able to mediate HR in vitro and in vivo, but mutants favoring the formation of the saturated nucleofilaments failed to support HR. We thus present a new model for RecA-mediated HR in which RecA utilizes its intrinsic DNA binding-dependent ATPase activity to remodel the nucleofilaments to a less saturated form and thereby promote HR. PMID:28101376

  2. CD147 promotes melanoma progression through hypoxia-induced MMP2 activation.

    Science.gov (United States)

    Zeng, W; Su, J; Wu, L; Yang, D; Long, T; Li, D; Kuang, Y; Li, J; Qi, M; Zhang, J; Chen, X

    2014-01-01

    Hypoxia enhances MMP2 expression and the invasion and metastatic potential of melanoma cells. CD147 has been shown to induce MMP2 in multiple cancers. To investigate the role of CD147 in hypoxiainduced MMP2 activation, we performed immunohistochemistry (IHC) staining in 206 normal and melanoma tissue samples, and analyzed the correlation between HIF1α and CD147. ChIP (chromosome Immunoprecipitation) in melanoma cell lines supports that HIF1α directly binds to CD147 promoter. Moreover, we made a series of deletion mutants of CD147 promoter, and identified a conserved HIF1α binding site. Point mutation in this site significantly decreased CD147 response to hypoxia. Importantly, knocking down CD147 attenuates MMP2 response to hypoxia in melanoma cell lines. MMP2 could not be efficiently activated by hypoxia in CD147 depletion cells. ELISA data showed that MMP2 secretion was reduced in CD147 depletion cells than control under hypoxia condition. To verify the data from cell culture model, we performed in vivo mouse xenograft experiment. IHC staining showed reduced MMP2 level in CD147 depleted xenografts compared to the control group, with the HIF1α level being comparable. Our study demonstrates a novel pathway mediated by CD147 to promote the MMP2 activation induced by hypoxia, and helps to understand the interplay between hypoxia and melanoma progression.

  3. Cardiovascular pharmacogenetics of anti-thrombotic agents and non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    Stitham, J; Vanichakarn, P; Ying, L; Hwa, J

    2014-01-01

    The use of antithrombotic agents, particularly antiplatelet drugs like aspirin and clopidogrel, has been instrumental in decreasing the risk for adverse cardiovascular events across a wide range of patients. However, despite the established benefits, the use of these medications remains suboptimal. There is a high degree of inter-individual variation in response to these treatments, whereby patients experience occlusive thromboembolic events, in spite of maintaining an appropriate treatment regimen. This has lead to the notion of antithrombotic "resistance" or "poor responders", which has been a growing concern amongst clinicians and other healthcare providers. Compounding this matter even further, reports of increased cardiovascular risk associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen, have revealed additional and unforeseen contributors to myocardial infarction and stroke. With all medications, striking a balance between the potential risks and benefits seems more art than science at times. However, given their widespread use and critical cardiovascular implications, further emphasis has been placed on understanding factors influencing antithrombotic and NSAID therapies. A major aim in cardiovascular pharmacogenetics is the discovery of genetic biomarkers that will allow for prospective screening and individualized prediction of drug efficacy and adverse reactions for these medications (both alone and together) within the context of cardiovascular disease.

  4. The Effect of Dietary Glycine on the Hepatic Tumor Promoting Activity of Polychlorinated Biphenyls (PCBs) in Rats

    OpenAIRE

    Bunaciu, Rodica Petruta; Tharappel, Job C.; Lehmler, Hans-Joachim; Korwel, Izabela; Robertson, Larry W.; Srinivasan, Cidambi; Spear, Brett T.; Glauert, Howard P.

    2007-01-01

    Polychlorinated biphenyls (PCBs) are ubiquitious lipophilic environmental pollutants. Some of the PCB congeners and mixtures of congeners have tumor promoting activity in rat liver. The mechanism of their activity is not fully understood and is likely to be multifactorial. The aim of this study was to investigate if the resident liver macrophages, Kupffer cells, are important in the promoting activity of PCBs. The hypothesis of this study was that the inhibition of Kupffer cell activity would...

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

    Directory of Open Access Journals (Sweden)

    Lien Nanna

    2009-12-01

    Full Text Available Abstract Background Although physical activity is considered to yield substantial health benefits, the level of physical activity among European teenagers is not sufficient. Adolescence is characterized by a decline in physical activity level. Many studies investigated the effectiveness of interventions promoting physical activity among young people, but none dealt with the available evidence specific for Europe. This review was conducted to summarize the effectiveness of interventions to promote physical activity among European teenagers. Methods A systematic review was conducted to identify European intervention studies published in the scientific literature since 1995. Four databases were searched, reference lists were scanned and the publication lists of the authors of the retrieved articles were checked. The ANGELO framework was used to categorise the included studies by setting and by intervention components. Results The literature search identified 20 relevant studies. Fifteen interventions were delivered through the school setting, of which three included a family component and another three a family and community component. One intervention was conducted within a community setting, three were delivered in primary care and one was delivered through the internet. Ten interventions included only an individual component, whereas the other ten used a multi-component approach. None of the interventions included only an environmental component. Main findings of the review were: (1 school-based interventions generally lead to short term improvements in physical activity levels; (2 improvements in physical activity levels by school-based interventions were limited to school related physical activity with no conclusive transfer to leisure time physical activity; (3 including parents appeared to enhance school-based interventions; (4 the support of peers and the influence of direct environmental changes increased the physical activity level of

  6. Endogenous activation of adenosine A1 receptors promotes post-ischemic electrocortical burst suppression

    DEFF Research Database (Denmark)

    Ilie, A; Ciocan, D; Constantinescu, A O

    2009-01-01

    . Several lines of evidence suggest that BS reflects an impairment of neocortical connectivity. Here we tested in vivo whether synaptic depression by adenosine A1 receptor (A1R) activation contributes to BS patterns following GCI. Male Wistar rats were subjected to 1, 5 or 10 min of GCI using a "four...... of post-ischemic BS patterns following brief ischemic episodes. It is likely that synaptic depression by post-ischemic A1R activation functionally disrupts the connectivity within the cortical networks to an extent that promotes BS patterns....

  7. Promoting Active Learning in Calculus and General Physics through Interactive and Media-Enhanced Lectures

    Directory of Open Access Journals (Sweden)

    Guoqing Tang

    2004-02-01

    Full Text Available In this paper we present an approach of incorporating interactive and media-enhanced lectures to promote active learning in Calculus and General Physics courses. The pedagogical practice of using interactive techniques in lectures to require "heads-on" and "hands-on" learning, and involve students more as active participants than passive receivers is a part of academic curricular reform efforts undertaken currently by the mathematics, physics and chemistry departments at North Carolina A&T State University under the NSF funded project "Talent-21: Gateway for Advancing Science and Mathematics Talents."

  8. 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

  9. Behaviour change interventions to promote physical activity in rheumatoid arthritis: a systematic review.

    Science.gov (United States)

    Larkin, Louise; Gallagher, Stephen; Cramp, Fiona; Brand, Charles; Fraser, Alexander; Kennedy, Norelee

    2015-10-01

    Research has shown that people who have rheumatoid arthritis (RA) do not usually participate in enough physical activity to obtain the benefits of optimal physical activity levels, including quality of life, aerobic fitness and disease-related characteristics. Behaviour change theory underpins the promotion of physical activity. The aim of this systematic review was to explore behaviour change interventions which targeted physical activity behaviour in people who have RA, focusing on the theory underpinning the interventions and the behaviour change techniques utilised using specific behaviour change taxonomy. An electronic database search was conducted via EBSCOhost, PubMed, Cochrane Central Register of Controlled Trials and Web of Science databases in August 2014, using Medical Subject Headings and keywords. A manual search of reference lists was also conducted. Randomised control trials which used behaviour change techniques and targeted physical activity behaviour in adults who have RA were included. Two reviewers independently screened studies for inclusion. Methodological quality was assessed using the Cochrane risk of bias tool. Five studies with 784 participants were included in the review. Methodological quality of the studies was mixed. The studies consisted of behaviour change interventions or combined practical physical activity and behaviour change interventions and utilised a large variety of behaviour change techniques. Four studies reported increased physical activity behaviour. All studies used subjective methods of assessing physical activity with only one study utilising an objective measure. There has been varied success of behaviour change interventions in promoting physical activity behaviour in people who have RA. Further studies are required to develop and implement the optimal behaviour change intervention in this population.

  10. 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.

  11. 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.

  12. NR2D-containing NMDA receptors mediate tissue plasminogen activator-promoted neuronal excitotoxicity.

    Science.gov (United States)

    Baron, A; Montagne, A; Cassé, F; Launay, S; Maubert, E; Ali, C; Vivien, D

    2010-05-01

    Although the molecular bases of its actions remain debated, tissue-type plasminogen activator (tPA) is a paradoxical brain protease, as it favours some learning/memory processes, but increases excitotoxic neuronal death. Here, we show that, in cultured cortical neurons, tPA selectively promotes NR2D-containing N-methyl-D-aspartate receptor (NMDAR)-dependent activation. We show that tPA-mediated signalling and neurotoxicity through the NMDAR are blocked by co-application of an NR2D antagonist (phenanthrene derivative (2S(*), 3R(*))-1-(phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid, PPDA) or knockdown of neuronal NR2D expression. In sharp contrast with cortical neurons, hippocampal neurons do not exhibit NR2D both in vitro and in vivo and are consequently resistant to tPA-promoted NMDAR-mediated neurotoxicity. Moreover, we have shown that activation of synaptic NMDAR prevents further tPA-dependent NMDAR-mediated neurotoxicity and sensitivity to PPDA. This study shows that the earlier described pro-neurotoxic effect of tPA is mediated by NR2D-containing NMDAR-dependent extracellular signal-regulated kinase activation, a deleterious effect prevented by synaptic pre-activation.

  13. 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.

  14. 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.

  15. Adding effect sizes to a systematic review on interventions for promoting physical activity among European teenagers

    Directory of Open Access Journals (Sweden)

    Crutzen Rik

    2010-04-01

    Full Text Available Abstract This commentary adds effect sizes to the recently published systematic review by De Meester and colleagues and provides a more detailed insight into the effectiveness of interventions to promote physical activity among European teenagers. The main findings based on this evidence were: (1 school-based interventions generally lead to short term improvement in physical activity levels, but there were large differences between interventions with regard to effect sizes; (2 a multi-component approach (including environmental components generally resulted in larger effect sizes, thereby providing evidence for the assumption that a multi-component approach should produce synergistic results; and (3 if an intervention aimed to affect more health behaviours besides physical activity, then the intervention appeared to be less effective in favour of physical activity.

  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 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.

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

    Science.gov (United States)

    Shiota, Kotomi; Hashimoto, Toshihiko

    2016-01-01

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

  19. 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.

  20. Pregnane X receptor activation and silencing promote steatosis of human hepatic cells by distinct lipogenic mechanisms.

    Science.gov (United States)

    Bitter, Andreas; Rümmele, Petra; Klein, Kathrin; Kandel, Benjamin A; Rieger, Jessica K; Nüssler, Andreas K; Zanger, Ulrich M; Trauner, Michael; Schwab, Matthias; Burk, Oliver

    2015-11-01

    In addition to its well-characterized role in the regulation of drug metabolism and transport by xenobiotics, pregnane X receptor (PXR) critically impacts on lipid homeostasis. In mice, both ligand-dependent activation and knockout of PXR were previously shown to promote hepatic steatosis. To elucidate the respective pathways in human liver, we generated clones of human hepatoma HepG2 cells exhibiting different PXR protein levels, and analyzed effects of PXR activation and knockdown on steatosis and expression of lipogenic genes. Ligand-dependent activation as well as knockdown of PXR resulted in increased steatosis in HepG2 cells. Activation of PXR induced the sterol regulatory element-binding protein (SREBP) 1-dependent lipogenic pathway via PXR-dependent induction of SREBP1a, which was confirmed in primary human hepatocytes. Inhibiting SREBP1 activity by blocking the cleavage-dependent maturation of SREBP1 protein impaired the induction of lipogenic SREBP1 target genes and triglyceride accumulation by PXR activation. On the other hand, PXR knockdown resulted in up-regulation of aldo-keto reductase (AKR) 1B10, which enhanced the acetyl-CoA carboxylase (ACC)-catalyzed reaction step of de novo lipogenesis. In a cohort of human liver samples histologically classified for non-alcoholic fatty liver disease, AKR1B10, SREBP1a and SREBP1 lipogenic target genes proved to be up-regulated in steatohepatitis, while PXR protein was reduced. In summary, our data suggest that activation and knockdown of PXR in human hepatic cells promote de novo lipogenesis and steatosis by induction of the SREBP1 pathway and AKR1B10-mediated increase of ACC activity, respectively, thus providing mechanistic explanations for a putative dual role of PXR in the pathogenesis of steatohepatitis.

  1. Harnessing neural activity to promote repair of the damaged corticospinal system after spinal cord injury

    Directory of Open Access Journals (Sweden)

    John H Martin

    2016-01-01

    Full Text Available As most spinal cord injuries (SCIs are incomplete, an important target for promoting neural repair and recovery of lost motor function is to promote the connections of spared descending spinal pathways with spinal motor circuits. Among the pathways, the corticospinal tract (CST is most associated with skilled voluntary functions in humans and many animals. CST loss, whether at its origin in the motor cortex or in the white matter tracts subcortically and in the spinal cord, leads to movement impairments and paralysis. To restore motor function after injury will require repair of the damaged CST. In this review, I discuss how knowledge of activity-dependent development of the CST-which establishes connectional specificity through axon pruning, axon outgrowth, and synaptic competition among CST terminals-informed a novel activity-based therapy for promoting sprouting of spared CST axons after injur in mature animals. This therapy, which comprises motor cortex electrical stimulation with and without concurrent trans-spinal direct current stimulation, leads to an increase in the gray matter axon length of spared CST axons in the rat spinal cord and, after a pyramidal tract lesion, restoration of skilled locomotor movements. I discuss how this approach is now being applied to a C 4 contusion rat model.

  2. 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.

  3. 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...

  4. Harnessing neural activity to promote repair of the damaged corticospinal system after spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    John H. Martin

    2016-01-01

    As most spinal cord injuries (SCIs) are incomplete, an important target for promoting neural repair and recovery of lost motor function is to promote the connections of spared descending spinal pathways with spinal motor circuits. Among the pathways, the corticospinal tract (CST) is most associated with skilled voluntary functions in humans and many animals. CST loss, whether at its origin in the motor cortex or in the white matter tracts subcortically and in the spinal cord, leads to movement impairments and paraly-sis. To restore motor function after injury will require repair of the damaged CST. In this review, I discuss how knowledge of activity-dependent development of the CST—which establishes connectional speci-ifcity through axon pruning, axon outgrowth, and synaptic competition among CST terminals—informed a novel activity-based therapy for promoting sprouting of spared CST axons after injur in mature animals. This therapy, which comprises motor cortex electrical stimulation with and without concurrent trans-spi-nal direct current stimulation, leads to an increase in the gray matter axon length of spared CST axons in the rat spinal cord and, after a pyramidal tract lesion, restoration of skilled locomotor movements. I discuss how this approach is now being applied to a C4 contusion rat model.

  5. A negative element in the downstream region of the Rice tungro bacilliform virus promoter is orientation- and position-independent and is active with heterologous promoters.

    Science.gov (United States)

    Purkayastha, Arunima; Sharma, Shweta; Dasgupta, Indranil

    2010-10-01

    The promoter of an Indian isolate of the pararetrovirus Rice tungro bacilliform virus (RTBV-WB) contains a negative element downstream of the transcription start site (TSS), between nucleotide residues +58 and +195 (Mathur and Dasgupta, 2007). To further characterize the element, we show, by using transient gus reporter gene assays in the cells of onion peel, rice calli and Arabidopsis leaves, that it down-regulates heterologous promoters CaMV35S and Maize ubiquitin. Quantitative measurements of transient GUS activity indicated more than 90% inhibition of reporter gene expression by the negative element. We also show, by reversing the orientation of the element downstream and by placing it in a position upstream to a constitutively expressing RTBV promoter, that the negative element is orientation- and position-independent, pointing towards its activity at the transcriptional and not post-transcriptional level.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. The Phenolics from the Roots of Livistona chinensis Show Antioxidative and Obsteoblast Differentiation Promoting Activity

    Directory of Open Access Journals (Sweden)

    Xiaobin Zeng

    2013-12-01

    Full Text Available This study investigated the antioxidative and obsteoblast differentiation promoting activity of the phenolics isolated from the 70% ethanol extract of the roots of Livistona chinensis. Two new phenolics, (2R,3R-3,5,6,7,3',4'-hexahydroxyflavane (1, and phenanthrene-2,4,9-triol (2, together with six known phenolics 3–8, were isolated and identified on the basis of extensive spectroscopic analysis. The antioxidative and obsteoblast differentiation promoting abilities of the compounds 1–3, 7–8 were tested, the phenolics 1–3, 7 showed effects on proliferation of osteoblastic cells and antioxidative activity of 3.125–50 µg/mL. In addition, the phenolics 1–3 observably increased alkaline phosphatase activity, osteocalcin content and hydroxyproline content in osteoblastic cells. Phenolic 1 at 12.5 µg/mL concentration significantly increased the area of nodules by about 9.35-fold. The antioxidative activity results indicated that the anti-osteoporosis effects of these phenolics may be linked to a reduction of oxidative stress. The observed effects of these phenolics on bone formation by rat osteoblastic cells suggest that these phenolics may have beneficial effects on bone health.

  12. 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.

  13. Terazosin activated Pgk1 and Hsp90 to promote stress resistance

    Science.gov (United States)

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

    2015-01-01

    Drugs that can protect against organ damage are urgently needed, especially for diseases such as sepsis and brain stroke. We have discovered that terazosin (TZ), a widely marketed alpha1-adrenergic receptor agonist, alleviated organ damage and improved survival in rodent models of stroke and sepsis. Through combined studies of enzymology and X-ray crystallography, we have discovered that TZ binds to a novel target, phosphoglycerate kinase 1 (Pgk1) and activates its enzymatic activity, probably through 1,3-diamino-6,7-dimethoxyisoquinoline's ability to promote ATP release from Pgk1. Mechanistically, the ATP generated from Pgk1 may enhance the chaperone activity of Hsp90, an ATPase known to associate with Pgk1. Upon activation, Hsp90 promotes multi-stress resistance. Our studies have demonstrated that TZ has a novel protein target, Pgk1, and has revealed its corresponding biological effect. As a clinical drug, TZ may be quickly translated into treatment of devastating diseases including stroke and sepsis. PMID:25383758

  14. [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.

  15. 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.

  16. 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.

  17. Why and how physical activity promotes experience-induced brain plasticity

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    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.

  18. “I am active”: effects of a program to promote active aging

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    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

  19. Acanthamoeba protease activity promotes allergic airway inflammation via protease-activated receptor 2.

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    Park, Mi Kyung; Cho, Min Kyoung; Kang, Shin Ae; Park, Hye-Kyung; Kim, Dong-Hee; Yu, Hak Sun

    2014-01-01

    Acanthamoeba is a free-living amoeba commonly present in the environment and often found in human airway cavities. Acanthamoeba possesses strong proteases that can elicit allergic airway inflammation. To our knowledge, the aeroallergenicity of Acanthamoeba has not been reported. We repeatedly inoculated mice with Acanthamoeba trophozoites or excretory-secretory (ES) proteins intra-nasally and evaluated symptoms and airway immune responses. Acanthamoeba trophozoites or ES proteins elicited immune responses in mice that resembled allergic airway inflammation. ES proteins had strong protease activity and activated the expression of several chemokine genes (CCL11, CCL17, CCL22, TSLP, and IL-25) in mouse lung epithelial cells. The serine protease inhibitor phenyl-methane-sulfonyl fluoride (PMSF) inhibited ES protein activity. ES proteins also stimulated dendritic cells and enhanced the differentiation of naive T cells into IL-4-secreting T cells. After repeated inoculation of the protease-activated receptor 2 knockout mouse with ES proteins, airway inflammation and Th2 immune responses were markedly reduced, but not to basal levels. Furthermore, asthma patients had higher Acanthamoeba-specific IgE titers than healthy controls and we found Acanthamoeba specific antigen from house dust in typical living room. Our findings suggest that Acanthamoeba elicits allergic airway symptoms in mice via a protease allergen. In addition, it is possible that Acanthamoeba may be one of the triggers human airway allergic disease.

  20. Acanthamoeba protease activity promotes allergic airway inflammation via protease-activated receptor 2.

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    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.

  1. Promoting Children's Physical Activity in Physical Education: The Role of Active Video Gaming

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    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…

  2. Identification of a single-nucleotide insertion in the promoter region affecting the sodC promoter activity in Brucella neotomae.

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    Dina A Moustafa

    Full Text Available Brucella neotomae is not known to be associated with clinical disease in any host species. Previous research suggested that B. neotomae might not express detectable levels of Cu/Zn superoxide dismutase (SOD, a periplasmic enzyme known to be involved in protecting Brucella from oxidative bactericidal effects of host phagocytes. This study was undertaken to investigate the genetic basis for the disparity in SOD expression in B. neotomae. Our Western blot and SOD enzyme assay analyses indicated that B. neotomae does express SOD, but at a substantially reduced level. Nucleotide sequence analysis of region upstream to the sodC gene identified a single-nucleotide insertion in the potential promoter region. The same single-nucleotide insertion was also detected in the sodC promoter of B. suis strain Thomsen, belonging to biovar 2 in which SOD expression was undetectable previously. Examination of the sodC promoter activities using translational fusion constructs with E. coli β-galactosidase demonstrated that the B. neotomae and B. suis biovar 2 promoters were very weak in driving gene expression. Site-directed mutation studies indicated that the insertion of A in the B. neotomae sodC promoter reduced the promoter activity. Increasing the level of SOD expression in B. neotomae through complementation with B. abortus sodC gene did not alter the bacterial survival in J774A.1 macrophage-like cells and in tissues of BALB/c and C57BL/6 mice. These results for the first time demonstrate the occurrence of a single-nucleotide polymorphism affecting promoter function and gene expression in Brucella.

  3. High-throughput identification of promoters and screening of highly active promoter-5'-UTR DNA region with different characteristics from Bacillus thuringiensis.

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    Jieping Wang

    Full Text Available In bacteria, both promoters and 5'-untranslated regions (5'-UTRs of mRNAs play vital regulatory roles in gene expression. In this study, we identified 1203 active promoter candidates in Bacillus thuringiensis through analysis of the genome-wide TSSs based on the transcriptome data. There were 11 types of σ-factor and 34 types of transcription factor binding sites found in 723 and 1097 active promoter candidates, respectively. Moreover, within the 1203 transcriptional units (TUs, most (52% of the 5'-UTRs were 10-50 nucleotides in length, 12.8% of the TUs had a long 5'-UTR greater than 100 nucleotides in length, and 16.3% of the TUs were leaderless. We then selected 20 active promoter candidates combined with the corresponding 5'-UTR DNA regions to screen the highly active promoter-5'-UTR DNA region complexes with different characteristics. Our results demonstrate that among the 20 selected complexes, six were able to exert their functions throughout the life cycle, six were specifically induced during the early-stationary phase, and four were specifically activated during the mid-stationary phase. We found a direct corresponding relationship between σ-factor-recognized consensus sequences and complex activity features: the great majority of complexes acting throughout the life cycle possess σ(A-like consensus sequences; the maximum activities of the σ(F-, σ(E-, σ(G-, and σ(K-dependent complexes appeared at 10, 14, 16, and 22 h under our experimental conditions, respectively. In particular, complex Phj3 exhibited the strongest activity. Several lines of evidence showed that complex Phj3 possessed three independent promoter regions located at -251∼-98, -113∼-31, and -54∼+14, and that the 5'-UTR +1∼+118 DNA region might be particularly beneficial to both the stability and translation of its downstream mRNA. Moreover, Phj3 successfully overexpressed the active β-galactosidase and turbo-RFP, indicating that Phj3 could be a proper

  4. Reduced graphene oxide is not a universal promoter for photocatalytic activities of TiO2

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    Hui Ling Tan

    2017-03-01

    Full Text Available Addition of reduced graphene oxide (RGO to P25 TiO2 was made and its impacts on photocatalytic oxidation of various organic substances were studied. Although the presence of RGO in TiO2 can enhance certain TiO2-based photocatalytic reactions, it is not a universal observation that can be expected in all types of organic substances. The factor of photocatalytic activity enhancement is strongly affected by the various functional groups appeared in the organic substances. In this work, it is realised that the length of alkyl chain in alcohols and carboxylic acids have the minimum influence on the overall activity while the number of hydroxyl groups can promote the further activity enhancement in the presence of RGO.

  5. Physical Activity Promotion in the Preschool Years: A Critical Period to Intervene

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    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.

  6. Line active molecules promote inhomogeneous structures in membranes: theory, simulations and experiments.

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    Palmieri, Benoit; Yamamoto, Tetsuya; Brewster, Robert C; Safran, Samuel A

    2014-06-01

    We review recent theoretical efforts that predict how line-active molecules can promote lateral heterogeneities (or domains) in model membranes. This fundamental understanding may be relevant to membrane composition in living cells, where it is thought that small domains, called lipid rafts, are necessary for the cells to be functional. The theoretical work reviewed here ranges in scale from coarse grained continuum models to nearly atomistic models. The effect of line active molecules on domain sizes and shapes in the phase separated regime or on fluctuation length scales and lifetimes in the single phase, mixed regime, of the membrane is discussed. Recent experimental studies on model membranes that include line active molecules are also presented together with some comparisons with the theoretical predictions.

  7. Notch2 signaling promotes osteoclast resorption via activation of PYK2.

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    Jin, Won Jong; Kim, Bongjun; Kim, Jung-Wook; Kim, Hong-Hee; Ha, Hyunil; Lee, Zang Hee

    2016-05-01

    Notch signaling plays a central role in various cell fate decisions, including skeletal development. Recently, Notch signaling was implicated in osteoclast differentiation and maturation, including the resorption activity of osteoclasts. However, the specific involvement of notch signaling in resorption activity was not fully investigated. Here, we investigated the roles of Notch signaling in the resorption activity of osteoclasts by use of the gamma-secretase inhibitor dibenzazepine (DBZ). Attenuating Notch signaling by DBZ suppressed the expression of NFATc1, a master transcription factor for osteoclast differentiation. However, overexpression of a constitutively active form of NFATc1 did not fully rescue the effects of DBZ. DBZ suppressed the autophosphorylation of PYK2, which is essential for the formation of the podosome belt and sealing zone, with reduced c-Src/PYK2 interaction. We found that RANKL increases PYK2 activation accompanied by increased NICD2 production in osteoclasts. Overexpression of NICD2 in osteoclasts rescued DBZ-mediated suppression of resorption activity with promotion of PYK2 autophosphorylation and microtubule acetylation. Consistent with the in vitro results, DBZ strongly suppressed bone destruction in an interleukin-1-induced bone loss model. Collectively, these results demonstrate that Notch2 in osteoclasts plays a role in the control of resorption activity via the PYK2-c-Src-microtubule signaling pathway.

  8. Vacancy associates promoting solar-driven photocatalytic activity of ultrathin bismuth oxychloride nanosheets.

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    Guan, Meili; Xiao, Chong; Zhang, Jie; Fan, Shaojuan; An, Ran; Cheng, Qingmei; Xie, Junfeng; Zhou, Min; Ye, Bangjiao; Xie, Yi

    2013-07-17

    Crystal facet engineering of semiconductors is of growing interest and an important strategy for fine-tuning solar-driven photocatalytic activity. However, the primary factor in the exposed active facets that determines the photocatalytic property is still elusive. Herein, we have experimentally achieved high solar photocatalytic activity in ultrathin BiOCl nanosheets with almost fully exposed active {001} facets and provide some new and deep-seated insights into how the defects in the exposed active facets affect the solar-driven photocatalytic property. As the thickness of the nanosheets reduces to atomic scale, the predominant defects change from isolated defects V(Bi)‴ to triple vacancy associates V(Bi)‴V(O)••V(Bi)‴, which is unambiguously confirmed by the positron annihilation spectra. By virtue of the synergic advantages of enhanced adsorption capability, effective separation of electron–hole pairs and more reductive photoexcited electrons benefited from the V(Bi)‴V(O)••V(Bi)‴ vacancy associates, the ultrathin BiOCl nanosheets show significantly promoted solar-driven photocatalytic activity, even with extremely low photocatalyst loading. The finding of the existence of distinct defects (different from those in bulks) in ultrathin nanosheets undoubtedly leads to new possibilities for photocatalyst design using quasi-two-dimensional materials with high solar-driven photocatalytic activity.

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

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    Niloofar Peykari

    2015-01-01

    Full Text Available Background: Physical activity is a complex behavior. To designing the effective intervention, qualitative researches may be allowed for greater understanding of the reasons behind the adolescences′ physical activity-related behaviors′. Methods: Using the grounded theory approach, including semi-structured focus group discussions (FGDs and in-depth interviews, we conducted a quantitative study to elicit the adolescents and key informants′ opinion regarding the satiation, needs, social and environmental barriers of adolescents′ physical activity. For FGDs, participants were selected from volunteered adolescent (aged 10-19 years of the populated western part of Tehran, which was selected as a research field. Key informants were invited from the health professionals and experts in the field of adolescents′ health. Results: According to findings, although the majority of participants agreed on the important role of physical activity, the lack of essential motivation and the pressure of educational assignments remove it from the daily program priorities. Lack of a safe environment for girls′ physical activity and high cost of professional sports were two first mentioned barriers. It was also suggested that future interventions should focus on improving more parents′ engagement and their direct participation in physical activities with their adolescents. Conclusions: We proposed the participatory strategies for adolescent′s physical activity promotion. Through which target groups participation during the designing, development, and implementation of health programs led to more effective interventions.

  10. Critical narrative review to identify educational strategies promoting physical activity in preschool.

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    Kreichauf, S; Wildgruber, A; Krombholz, H; Gibson, E L; Vögele, C; Nixon, C A; Douthwaite, W; Moore, H J; Manios, Y; Summerbell, C D

    2012-03-01

    The aim of this narrative review is critically to evaluate educational strategies promoting physical activity that are used in the preschool setting in the context of obesity prevention programmes. Literature search was conducted between April and August 2010 in English and German databases (PubMED, PsychINFO, PSYNDEX, ERIC, FIS Bildung). Outcomes considered were time and intensity of physical activity, motor skills or measures of body composition. A total of 19 studies were included. Ten studies added physical activity lessons into their curriculum, one study provided more time for free play, eight studies focused on the social and play environment. Studies reporting positive outcomes implemented physical activity sessions that lasted at least 30 min d(-1). Several studies showed that children are most active in the first 10-15 min. The existence or installation of playground markings or fixed play equipment had no effect, whereas the presence or addition of portable play equipment was positively correlated with moderate-to-vigorous physical activity. Teacher training may be a key element for successful interventions. To overcome time constraints, a suggested solution is to integrate physical activity into daily routines and other areas of the preschool curriculum.

  11. Yeast homologous recombination-based promoter engineering for the activation of silent natural product biosynthetic gene clusters.

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    Montiel, Daniel; Kang, Hahk-Soo; Chang, Fang-Yuan; Charlop-Powers, Zachary; Brady, Sean F

    2015-07-21

    Large-scale sequencing of prokaryotic (meta)genomic DNA suggests that most bacterial natural product gene clusters are not expressed under common laboratory culture conditions. Silent gene clusters represent a promising resource for natural product discovery and the development of a new generation of therapeutics. Unfortunately, the characterization of molecules encoded by these clusters is hampered owing to our inability to express these gene clusters in the laboratory. To address this bottleneck, we have developed a promoter-engineering platform to transcriptionally activate silent gene clusters in a model heterologous host. Our approach uses yeast homologous recombination, an auxotrophy complementation-based yeast selection system and sequence orthogonal promoter cassettes to exchange all native promoters in silent gene clusters with constitutively active promoters. As part of this platform, we constructed and validated a set of bidirectional promoter cassettes consisting of orthogonal promoter sequences, Streptomyces ribosome binding sites, and yeast selectable marker genes. Using these tools we demonstrate the ability to simultaneously insert multiple promoter cassettes into a gene cluster, thereby expediting the reengineering process. We apply this method to model active and silent gene clusters (rebeccamycin and tetarimycin) and to the silent, cryptic pseudogene-containing, environmental DNA-derived Lzr gene cluster. Complete promoter refactoring and targeted gene exchange in this "dead" cluster led to the discovery of potent indolotryptoline antiproliferative agents, lazarimides A and B. This potentially scalable and cost-effective promoter reengineering platform should streamline the discovery of natural products from silent natural product biosynthetic gene clusters.

  12. Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis.

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    Jose L Nieto-Torres

    2014-05-01

    Full Text Available Deletion of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV envelope (E gene attenuates the virus. E gene encodes a small multifunctional protein that possesses ion channel (IC activity, an important function in virus-host interaction. To test the contribution of E protein IC activity in virus pathogenesis, two recombinant mouse-adapted SARS-CoVs, each containing one single amino acid mutation that suppressed ion conductivity, were engineered. After serial infections, mutant viruses, in general, incorporated compensatory mutations within E gene that rendered active ion channels. Furthermore, IC activity conferred better fitness in competition assays, suggesting that ion conductivity represents an advantage for the virus. Interestingly, mice infected with viruses displaying E protein IC activity, either with the wild-type E protein sequence or with the revertants that restored ion transport, rapidly lost weight and died. In contrast, mice infected with mutants lacking IC activity, which did not incorporate mutations within E gene during the experiment, recovered from disease and most survived. Knocking down E protein IC activity did not significantly affect virus growth in infected mice but decreased edema accumulation, the major determinant of acute respiratory distress syndrome (ARDS leading to death. Reduced edema correlated with lung epithelia integrity and proper localization of Na+/K+ ATPase, which participates in edema resolution. Levels of inflammasome-activated IL-1β were reduced in the lung airways of the animals infected with viruses lacking E protein IC activity, indicating that E protein IC function is required for inflammasome activation. Reduction of IL-1β was accompanied by diminished amounts of TNF and IL-6 in the absence of E protein ion conductivity. All these key cytokines promote the progression of lung damage and ARDS pathology. In conclusion, E protein IC activity represents a new determinant for SARS

  13. Feasibility of a mobile phone application to promote physical activity in cancer survivors

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    Anna Roberts

    2016-01-01

    Full Text Available Background: Regular participation in physical activity is associated with improved physical and psychosocial outcomes in cancer survivors. However, physical activity levels are low during and after cancer treatment. Interventions to promote physical activity in this population are needed. Mobile technology has potential, but currently, there is no mobile phone application designed to promote physical activity in cancer survivors. Objectives: The first aim is to assess feasibility and acceptability of an existing physical activity mobile application (‘app’ designed for the general population, in a sample of breast, colorectal and prostate cancer survivors. A further aim is to understand how the application could be adapted to overcome barriers to physical activity participation in this population. Methods: A feasibility study was carried out that investigated acceptability of and participants’ opinions on the application. A total of 11 cancer survivors tested the application for 6 weeks. Physical activity (Godin Leisure Time Exercise Questionnaire, wellbeing (FACT-G, fatigue (FACIT-Fatigue scale, quality of life (EQ5D, sleep quality (Pittsburgh Sleep Quality Index, anxiety and depression (Hospital Anxiety and Depression Scale were self-reported at baseline and at 6-week follow-up. Participants completed qualitative telephone interviews about their experiences of using the app, and these were coded using thematic analysis. Results: The application was acceptable among the participants; 73% of people who responded to the study advertisement agreed to participate, and 100% of participants who started the study completed. There was a significant increase in participants’ mean strenuous physical activity of 51.91 minutes per week from baseline to 6-week follow-up (P=0.005. There was also a significant reduction in reported sleep problems from baseline (mean=9.27, SD=6.72 to 6-week follow-up (mean=6.72, SD=5.50; P=0.01. There were no other

  14. Therapeutic intraspinal stimulation to generate activity and promote long-term recovery

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    Sarah E. Mondello

    2014-02-01

    Full Text Available Neuroprosthetic approaches have tremendous potential for the treatment of injuries to the brain and spinal cord by inducing appropriate neural activity in otherwise disordered circuits. Substantial work has demonstrated that stimulation applied to both the central and peripheral nervous system leads to immediate and in some cases sustained benefits after injury. Here we focus on cervical intraspinal microstimulation (ISMS as a promising method of activating the spinal cord distal to an injury site, either to directly produce movements or more intriguingly to improve subsequent volitional control of the paretic extremities. Incomplete injuries to the spinal cord are the most commonly observed in human patients, and these injuries spare neural tissue bypassing the lesion that could be influenced by neural devices to promote recovery of function. In fact, recent results have demonstrated that therapeutic ISMS leads to modest but sustained improvements in forelimb function after an incomplete spinal cord injury. This therapeutic spinal stimulation may promote long-term recovery of function by providing the necessary electrical activity needed for neuron survival, axon growth, and synaptic stability.

  15. Nuclease activity of Legionella pneumophila Cas2 promotes intracellular infection of amoebal host cells.

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    Gunderson, Felizza F; Mallama, Celeste A; Fairbairn, Stephanie G; Cianciotto, Nicholas P

    2015-03-01

    Legionella pneumophila, the primary agent of Legionnaires' disease, flourishes in both natural and man-made environments by growing in a wide variety of aquatic amoebae. Recently, we determined that the Cas2 protein of L. pneumophila promotes intracellular infection of Acanthamoeba castellanii and Hartmannella vermiformis, the two amoebae most commonly linked to cases of disease. The Cas2 family of proteins is best known for its role in the bacterial and archeal clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein (Cas) system that constitutes a form of adaptive immunity against phage and plasmid. However, the infection event mediated by L. pneumophila Cas2 appeared to be distinct from this function, because cas2 mutants exhibited infectivity defects in the absence of added phage or plasmid and since mutants lacking the CRISPR array or any one of the other cas genes were not impaired in infection ability. We now report that the Cas2 protein of L. pneumophila has both RNase and DNase activities, with the RNase activity being more pronounced. By characterizing a catalytically deficient version of Cas2, we determined that nuclease activity is critical for promoting infection of amoebae. Also, introduction of Cas2, but not its catalytic mutant form, into a strain of L. pneumophila that naturally lacks a CRISPR-Cas locus caused that strain to be 40- to 80-fold more infective for amoebae, unequivocally demonstrating that Cas2 facilitates the infection process independently of any other component encoded within the CRISPR-Cas locus. Finally, a cas2 mutant was impaired for infection of Willaertia magna but not Naegleria lovaniensis, suggesting that Cas2 promotes infection of most but not all amoebal hosts.

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

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    shahla pashapour

    2016-03-01

    Full Text Available 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 rhizosphere and root nodules grown around Zanjan. Materials and methods: These bacteria were isolated from alfalfa roots grown around Zinc industries in Zanjan province. After bacterial isolation and purification from root and soil samples, isolates were screened in vitro for plant growth promoting traits such as IAA (Indole Acetic Acid, ACC- deaminase (Amino Cyclopropan Carboxylate, HCN (Hydrogen Cyanide, siderophore, chitinase production and mineral and organic phosphate solubilization activities. Results: The results indicated that 43 bacterial isolates produced IAA (4.04- 4.95 μg/ml and 15 isolates produced ACC- deaminase (0.23- 1.05 μg/ml. Only one isolate (Rm66 produced high amount of HCN. Qualitative siderophore production was observed in 9 isolates. None of the isolates produced chitinase. Solubilization of mineral phosphate was commonly detected in 19 isolates (4.33- 5.86 μg/ml, and 15 isolates solubilized organic phosphate (1.66- 144.28 μg/ml. Discussion and conclusion: This study shows that most of the bacterial strains which isolated from alfalfa cultivated lands had PGP activities and also a good potential to increase plant growth after inoculation with to seeds as eco- friendly fertilizers.

  17. Mechanism for the catastrophe-promoting activity of the microtubule destabilizer Op18/stathmin.

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    Gupta, Kamlesh K; Li, Chunlei; Duan, Aranda; Alberico, Emily O; Kim, Oleg V; Alber, Mark S; Goodson, Holly V

    2013-12-17

    Regulation of microtubule dynamic instability is crucial for cellular processes, ranging from mitosis to membrane transport. Stathmin (also known as oncoprotein 18/Op18) is a prominent microtubule destabilizer that acts preferentially on microtubule minus ends. Stathmin has been studied intensively because of its association with multiple types of cancer, but its mechanism of action remains controversial. Two models have been proposed. One model is that stathmin promotes microtubule catastrophe indirectly, and does so by sequestering tubulin; the other holds that stathmin alters microtubule dynamics by directly destabilizing growing microtubules. Stathmin's sequestration activity is well established, but the mechanism of any direct action is mysterious because stathmin binds to microtubules very weakly. To address these issues, we have studied interactions between stathmin and varied tubulin polymers. We show that stathmin binds tightly to Dolastatin-10 tubulin rings, which mimic curved tubulin protofilaments, and that stathmin depolymerizes stabilized protofilament-rich polymers. These observations lead us to propose that stathmin promotes catastrophe by binding to and acting upon protofilaments exposed at the tips of growing microtubules. Moreover, we suggest that stathmin's minus-end preference results from interactions between stathmin's N terminus and the surface of α-tubulin that is exposed only at the minus end. Using computational modeling of microtubule dynamics, we show that these mechanisms could account for stathmin's observed activities in vitro, but that both the direct and sequestering activities are likely to be relevant in a cellular context. Taken together, our results suggest that stathmin can promote catastrophe by direct action on protofilament structure and interactions.

  18. Activities for the Promotion of Gender Equality in Japan—Japan Society of Applied Physics

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    Kodate, Kashiko; Tanaka, Kazuo

    2005-10-01

    Since 1946, the Japan Society of Applied Physics (JSAP) has strived to promote research and development in applied physics for benefits beyond national boundaries. Activities of JSAP involve multidisciplinary fields, from physics and engineering to life sciences. Of its 23,000 members, 48% are from industry, 29% from academia, and about 7% from semi-autonomous national research laboratories. Its large industrial membership is one of the distinctive features of JSAP. In preparation for the First IUPAP International Conference on Women in Physics (Paris, 2002), JSAP members took the first step under the strong leadership of then-JSAP President Toshio Goto, setting up the Committee for the Promotion Equal Participation of Men and Women in Science and Technology. Equality rather than women's advancement is highlighted to further development in science and technology. Attention is also paid to balancing the number of researchers from different age groups and affiliations. The committee has 22 members: 12 female and 10 male; 7 from corporations, 12 from universities, and 3 from semi-autonomous national research institutes. Its main activities are to organize symposia and meetings, conduct surveys among JSAP members, and provide child-care facilities at meetings and conferences. In 2002 the Japan Physics Society and the Chemical Society of Japan jointly created the Japan Inter-Society Liaison Association for the Promotion of Equal Participation of Men and Women in Science and Engineering. Membership has grown to 44 societies (of which 19 are observers) ranging from mathematics, information, and life sciences to civil engineering. Joint activities across sectors and empower the whole. The Gender Equality Bureau in the Cabinet Office recently launched a large-scale project called "Challenge Campaign" to encourage girls to major in natural science and engineering, which JSAP is co-sponsoring.

  19. Activation of dopamine receptors in the nucleus accumbens promotes sucrose-reinforced cued approach behavior

    Directory of Open Access Journals (Sweden)

    Saleem M. Nicola

    2016-07-01

    Full Text Available 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.

  20. ADD1/SREBP1c activates the PGC1-alpha promoter in brown adipocytes

    DEFF Research Database (Denmark)

    Hao, Qin; Hansen, Jacob B; Petersen, Rasmus K

    2010-01-01

    regulatory element-binding protein-1c (SREBP1c) and peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC1alpha) in brown and inguinal white adipose tissues, but not in epididymal white adipose tissue. Using in vitro models of white and brown adipocytes we demonstrate that beta......-adrenergic stimulation induced expression of LXRalpha, ADD1/SREBP1c and PGC1alpha in cells with a brown-like adipose phenotype. We demonstrate that ADD1/SREBP1c is a powerful inducer of PGC1alpha expression via a conserved E box in the proximal promoter and that beta-adrenergic stimulation led to recruitment of ADD1...

  1. Transformational teaching and physical activity: a new paradigm for adolescent health promotion?

    Science.gov (United States)

    Morton, K L; Keith, S E; Beauchamp, M R

    2010-03-01

    Drawing from transformational leadership theory, this research examined adolescent perceptions of transformational teaching within school-based physical education. In Study 1, focus groups with 62 adolescents examined perceptions of physical education teachers' behaviors. In Study 2, follow-up semi-structured interviews were conducted with 18 purposively sampled students. Findings revealed that behaviors within physical education settings can be understood within a conceptual framework that includes transformational teaching. In addition, students who perceived their teachers to utilize transformational behaviors described more adaptive responses. Issues concerning theory development and the application of transformational teaching to physical activity and health promotion settings are considered.

  2. 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.

  3. The artificial zinc finger coding gene 'Jazz' binds the utrophin promoter and activates transcription.

    Science.gov (United States)

    Corbi, N; Libri, V; Fanciulli, M; Tinsley, J M; Davies, K E; Passananti, C

    2000-06-01

    Up-regulation of utrophin gene expression is recognized as a plausible therapeutic approach in the treatment of Duchenne muscular dystrophy (DMD). We have designed and engineered new zinc finger-based transcription factors capable of binding and activating transcription from the promoter of the dystrophin-related gene, utrophin. Using the recognition 'code' that proposes specific rules between zinc finger primary structure and potential DNA binding sites, we engineered a new gene named 'Jazz' that encodes for a three-zinc finger peptide. Jazz belongs to the Cys2-His2 zinc finger type and was engineered to target the nine base pair DNA sequence: 5'-GCT-GCT-GCG-3', present in the promoter region of both the human and mouse utrophin gene. The entire zinc finger alpha-helix region, containing the amino acid positions that are crucial for DNA binding, was specifically chosen on the basis of the contacts more frequently represented in the available list of the 'code'. Here we demonstrate that Jazz protein binds specifically to the double-stranded DNA target, with a dissociation constant of about 32 nM. Band shift and super-shift experiments confirmed the high affinity and specificity of Jazz protein for its DNA target. Moreover, we show that chimeric proteins, named Gal4-Jazz and Sp1-Jazz, are able to drive the transcription of a test gene from the human utrophin promoter.

  4. Promoting Physical Activity among Children: The “Great Live and Move Challenge”

    Science.gov (United States)

    Mourgues, Marion; Gourlan, Mathieu; Coste, Olivier; Fregeac, Bruno; Mora, Lucile; Cousson-Gélie, Florence

    2016-06-08

    Objective: The “Great Live and Move Challenge” (GLMC) is an intervention designed to promote physical activity (PA) in schools and the community among 6- to 11-year-old schoolchildren and their families.Method: This project, implemented in the Montpellier and Pays Coeur d’Hérault regions since 2013, encourages children to quantify their daily PA level by illustrating each 15 minutes of exercise by an “energy cube”. Based on collaboration between pilots, teachers and policymakers, this project is implemented over a 6-week period in schools, municipalities and recreation centres. “Great Challenge” events are organized to promote PA. The GLMC is also a theory-based intervention based on the tenets of the planned behaviour theory.Results: Since the 2014-2015 edition, 2,243 children have taken part in the GLMC and have accumulated 391,102 “energy cubes”. In addition, more than 30 “Great Challenge” events have been organized. Since its launch during the 2012-2013 school year, the numbers of children who have taken part in the GLMC have been multiplied by 5.58. The mean number of daily “energy cubes” accumulated by children has increased from 4.04 in the first year to 6.22 in 2014-2015.Conclusion: The “energy cube” can provide a measure of the commitment of children and their surrounding community in a comprehensive approach to PA promotion.

  5. Coactivator CBP/p300 increased the activity of C/EBP-mediated human interleukin-5 gene promoter

    Institute of Scientific and Technical Information of China (English)

    LIU Chunyan; LU Jun; LI Lin; TAN Jiang; SHAO Yangguang; HUANG Baiqu

    2004-01-01

    Interleukin-5 (IL-5), expressed primarily by type-2 T helper (Th2) cells, plays an essential role in the development of allergic diseases, such as allergic asthma. Histone acetyltransferase CBP/p300 remodels chromatin by acetylating histones, resulting in open structure of chromatin and active transcription. Adenovirus protein E1A inhibits the activity of CBP/p300. In this study, we analyzed the effects of E1A on IL-5 gene promoter/luciferase reporter activity. The results showed that E1A protein inhibited the activity of PMA/ionomycin-stimulated IL-5 gene promoter/luciferase reporter construct. In contrast, overexpression of the CBP/p300-binding defective E1A A2-36 protein did not inhibit IL-5 gene promoter activity. These data demonstrated for the first time that transcriptional coactivator CBP/p300was involved in the activation of IL-5 gene promoter. E1A protein can modulate CBP/p300 function to activate the transcription of IL-5 gene promoter/luciferase reporter plasmid. Furthermore, in collaboration with transcription factor C/EBP, CBP/p300 activated IL-5 gene promoter/luciferase reporter expression. This study provides further insight into the mechanisms of transcriptional regulation of IL-5 gene.

  6. Glutamate transporter activity promotes enhanced Na+/K+-ATPase-mediated extracellular K+ management during neuronal activity

    DEFF Research Database (Denmark)

    Larsen, Brian Roland; Holm, Rikke; Vilsen, Bente;

    2016-01-01

    , in addition, Na+/K+-ATPase-mediated K+ clearance could be governed by astrocytic [Na+]i. During most neuronal activity, glutamate is released in the synaptic cleft and is re-absorbed by astrocytic Na+-coupled glutamate transporters, thereby elevating [Na+]i. It thus remains unresolved whether the different Na...... constellations in Xenopus oocytes and determined their apparent Na+ affinity in intact oocytes and isolated membranes. The Na+/K+-ATPase was not fully saturated at basal astrocytic [Na+]i, irrespective of isoform constellation, although the β1 subunit conferred lower apparent Na+ affinity to the α1 and α2...

  7. A CYCLIC-AMP RESPONSE ELEMENT IS INVOLVED IN RETINOIC ACID-DEPENDENT RAR-BETA-2 PROMOTER ACTIVATION

    NARCIS (Netherlands)

    KRUYT, FAE; FOLKERS, G; VANDENBRINK, CE; VANDERSAAG, PT; Kruyt, Frank

    1992-01-01

    Activation of the retinoic acid receptor (RAR) beta2 promoter is known to be mediated by a RA response element located in the proximity of the TATA-box. By deletion studies in P19 embryonal carcinoma cells we have analyzed the RARbeta2 promoter for the presence of additional regulatory elements. We

  8. The promoter competition assay (PCA): a new approach to identify motifs involved in the transcriptional activity of reporter genes.

    Science.gov (United States)

    Hube, Florent; Myal, Yvonne; Leygue, Etienne

    2006-05-01

    Identifying particular motifs responsible for promoter activity is a crucial step toward the development of new gene-based preventive and therapeutic strategies. However, to date, experimental methods to study promoter activity remain limited. We present in this report a promoter competition assay designed to identify, within a given promoter region, motifs critical for its activity. This assay consists in co-transfecting the promoter to be analyzed and double-stranded oligonucleotides which will compete for the binding of transcription factors. Using the recently characterized SBEM promoter as model, we first delineated the feasibility of the method and optimized the experimental conditions. We then identified, within an 87-bp region responsible for a strong expression of the reporter gene, an octamer-binding site essential for its transcriptional regulation. The importance of this motif has been confirmed by site-directed mutagenesis. The promoter competition assay appears to be a fast and efficient approach to identify, within a given promoter sequence, sites critical for its activity.

  9. Differentiation-dependent activation of the human intestinal alkaline phosphatase promoter by HNF-4 in intestinal cells

    DEFF Research Database (Denmark)

    Olsen, Line; Bressendorff, Simon; Troelsen, Jesper T;

    2005-01-01

    of HNF-4alpha to stimulate the expression from the ALPI promoter was investigated in the nonintestinal Hela cell line. Cotransfection with an HNF-4alpha expression vector demonstrated a direct activation of the ALPI promoter through this -94 to -82 element. EMSA showed that HNF-4alpha from nuclear...

  10. Active form Notch4 promotes the proliferation and differentiation of 3T3-L1 preadipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Peng-Yeh [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China); Tsai, Chong-Bin [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China); Department of Ophthalmology, Chiayi Christian Hospital, Chiayi 600, Taiwan, ROC (China); Tseng, Min-Jen, E-mail: biomjt@ccu.edu.tw [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China)

    2013-01-18

    Highlights: ► Notch4IC modulates the ERK pathway and cell cycle to promote 3T3-L1 proliferation. ► Notch4IC facilitates 3T3-L1 differentiation by up-regulating proadipogenic genes. ► Notch4IC promotes proliferation during the early stage of 3T3-L1 adipogenesis. ► Notch4IC enhances differentiation during subsequent stages of 3T3-L1 adipogenesis. -- Abstract: Adipose tissue is composed of adipocytes, which differentiate from precursor cells in a process called adipogenesis. Many signal molecules are involved in the transcriptional control of adipogenesis, including the Notch pathway. Previous adipogenic studies of Notch have focused on Notch1 and HES1; however, the role of other Notch receptors in adipogenesis remains unclear. Q-RT-PCR analyses showed that the augmentation of Notch4 expression during the differentiation of 3T3-L1 preadipocytes was comparable to that of Notch1. To elucidate the role of Notch4 in adipogenesis, the human active form Notch4 (N4IC) was transiently transfected into 3T3-L1 cells. The expression of HES1, Hey1, C/EBPδ and PPARγ was up-regulated, and the expression of Pref-1, an adipogenic inhibitor, was down-regulated. To further characterize the effect of N4IC in adipogenesis, stable cells expressing human N4IC were established. The expression of N4IC promoted proliferation and enhanced differentiation of 3T3-L1 cells compared with those of control cells. These data suggest that N4IC promoted proliferation through modulating the ERK pathway and the cell cycle during the early stage of 3T3-L1 adipogenesis and facilitated differentiation through up-regulating adipogenic genes such as C/EBPα, PPARγ, aP2, LPL and HSL during the middle and late stages of 3T3-L1 adipogenesis.

  11. Optically-Induced Neuronal Activity Is Sufficient to Promote Functional Motor Axon Regeneration In Vivo.

    Directory of Open Access Journals (Sweden)

    Patricia J Ward

    Full Text Available Peripheral nerve injuries are common, and functional recovery is very poor. Beyond surgical repair of the nerve, there are currently no treatment options for these patients. In experimental models of nerve injury, interventions (such as exercise and electrical stimulation that increase neuronal activity of the injured neurons effectively enhance axon regeneration. Here, we utilized optogenetics to determine whether increased activity alone is sufficient to promote motor axon regeneration. In thy-1-ChR2/YFP transgenic mice in which a subset of motoneurons express the light-sensitive cation channel, channelrhodopsin (ChR2, we activated axons in the sciatic nerve using blue light immediately prior to transection and surgical repair of the sciatic nerve. At four weeks post-injury, direct muscle EMG responses evoked with both optical and electrical stimuli as well as the ratio of these optical/electrical evoked EMG responses were significantly greater in mice that received optical treatment. Thus, significantly more ChR2+ axons successfully re-innervated the gastrocnemius muscle in mice that received optical treatment. Sections of the gastrocnemius muscles were reacted with antibodies to Synaptic Vesicle Protein 2 (SV2 to quantify the number of re-occupied motor endplates. The number of SV2+ endplates was greater in mice that received optical treatment. The number of retrogradely-labeled motoneurons following intramuscular injection of cholera toxin subunit B (conjugated to Alexa Fluor 555 was greater in mice that received optical treatment. Thus, the acute (1 hour, one-time optical treatment resulted in robust, long-lasting effects compared to untreated animals as well as untreated axons (ChR2-. We conclude that neuronal activation is sufficient to promote motor axon regeneration, and this regenerative effect is specific to the activated neurons.

  12. Gβγ interacts with mTOR and promotes its activation

    Energy Technology Data Exchange (ETDEWEB)

    Robles-Molina, Evelyn [Department of Pharmacology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Apartado postal 14-740, México, D.F. 07360 (Mexico); Dionisio-Vicuña, Misael [Department of Cell Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Apartado postal 14-740, México, D.F. 07360 (Mexico); Guzmán-Hernández, María Luisa [Department of Pharmacology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Apartado postal 14-740, México, D.F. 07360 (Mexico); Reyes-Cruz, Guadalupe [Department of Cell Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Apartado postal 14-740, México, D.F. 07360 (Mexico); Vázquez-Prado, José, E-mail: jvazquez@cinvestav.mx [Department of Pharmacology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Apartado postal 14-740, México, D.F. 07360 (Mexico)

    2014-02-07

    Highlights: • Gβγ interacts with mTOR kinase domain via a mechanism sensitive to chronic treatment with rapamycin. • Gβγ interacts with mTORC1 and mTORC2 which correlates with its ability to promote mTORC1 and mTORC2 signaling. • Gβγ heterodimers containing different Gβ subunits, except Gβ{sub 4}, interact with mTOR. - Abstract: Diverse G protein-coupled receptors depend on Gβγ heterodimers to promote cell polarization and survival via direct activation of PI3Kγ and potentially other effectors. These events involve full activation of AKT via its phosphorylation at Ser473, suggesting that mTORC2, the kinase that phosphorylates AKT at Ser473, is activated downstream of Gβγ. Thus, we tested the hypothesis that Gβγ directly contributes to mTOR signaling. Here, we demonstrate that endogenous mTOR interacts with Gβγ. Cell stimulation with serum modulates Gβγ interaction with mTOR. The carboxyl terminal region of mTOR, expressed as a GST-fusion protein, including the serine/threonine kinase domain, binds Gβγ heterodimers containing different Gβ subunits, except Gβ{sub 4}. Both, mTORC1 and mTORC2 complexes interact with Gβ{sub 1}γ{sub 2} which promotes phosphorylation of their respective substrates, p70S6K and AKT. In addition, chronic treatment with rapamycin, a condition known to interfere with assembly of mTORC2, reduces the interaction between Gβγ and mTOR and the phosphorylation of AKT; whereas overexpression of Gαi interfered with the effect of Gβγ as promoter of p70S6K and AKT phosphorylation. Altogether, our results suggest that Gβγ positively regulates mTOR signaling via direct interactions and provide further support to emerging strategies based on the therapeutical potential of inhibiting different Gβγ signaling interfaces.

  13. Improving health through policies that promote active travel: A review of evidence to support integrated health impact assessment

    NARCIS (Netherlands)

    Nazelle, A. de; Nieuwenhuijsen, M.J.; Antó, J.M.; Brauer, M.; Briggs, D.; Braun-Fahrlander, C.; Cavill, N.; Cooper, A.R.; Desqueyroux, H.; Fruin, S.; Hoek, G.; Panis, L.I.; Janssen, N.; Jerrett, M.; Joffe, M.; Andersen, Z.J.; Kempen, E. van; Kingham, S.; Kubesch, N.; Leyden, K.M.; Marshall, J.D.; Matamala, J.; Mellios, G.; Mendez, M.; Nassif, H.; Ogilvie, D.; Peiró, R.; Pérez, K.; Rabl, A.; Ragettli, M.; Rodríguez, D.; Rojas, D.; Ruiz, P.; Sallis, J.F.; Terwoert, J.; Toussaint, J.-F.; Tuomisto, J.; Zuurbier, M.; Lebret, E.

    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 fur

  14. ACTIVE MARKETING STRATEGY IN THE EDUCATION MARKET:BREAKTHROUGH POSITIONING STRATEGY IN PROMOTING UNIVERSITY’S INNOVATIONS

    OpenAIRE

    Pashkus N. A.; Pashkus V.

    2013-01-01

    The article discusses the possibility of using active marketing strategies for promoting the results of university’s innovations. Benefits, that can be obtained by university through its strategy of breakthrough positioning explored

  15. Improvement of complex of integrated marketing communications to promote speciality «Management of Innovative Activity» of SSU

    Directory of Open Access Journals (Sweden)

    Ya.O. Timokhina

    2012-09-01

    Full Text Available In this article target audience analysis of speciality Management of Innovative Activity of SSU by geographical principle is carried out, complex of integrated marketing communications for its promotion is proposed and media plan is offered.

  16. Behavioral Counseling to Promote a Healthful Diet and Physical Activity for CVD Prevention in Adults with Risk Factors

    Science.gov (United States)

    Understanding Task Force Recommendations Behavioral Counseling to Promote a Healthful Diet and Physical Activity for Cardiovascular Disease Prevention in Adults with Cardiovascular Risk Factors The U.S. Preventive ...

  17. The CXCL12/CXCR4 axis promotes ligand-independent activation of the androgen receptor.

    Science.gov (United States)

    Kasina, Sathish; Macoska, Jill A

    2012-04-01

    The molecular mechanisms responsible for the transition of some prostate cancers from androgen ligand-dependent to androgen ligand-independent are incompletely established. Molecules that are ligands for G protein coupled receptors (GPCRs) have been implicated in ligand-independent androgen receptor (AR) activation. The purpose of this study was to examine whether CXCL12, the ligand for the GPCR, CXCR4, might mediate prostate cancer cell proliferation through AR-dependent mechanisms involving functional transactivation of the AR in the absence of androgen. The results of these studies showed that activation of the CXCL12/CXCR4 axis promoted: The nuclear accumulation of both wild-type and mutant AR in several prostate epithelial cell lines; AR-dependent proliferative responses; nuclear accumulation of the AR co-regulator SRC-1 protein; SRC-1:AR protein:protein association; co-localization of AR and SRC-1 on the promoters of AR-regulated genes; AR- and SRC-1 dependent transcription of AR-regulated genes; AR-dependent secretion of the AR-regulated PSA protein; P13K-dependent phosphorylation of AR; MAPK-dependent phosphorylation of SRC-1, and both MAPK- and P13K-dependent secretion of the PSA protein, in the absence of androgen. Taken together, these studies identify CXCL12 as a novel, non-steroidal growth factor that promotes the growth of prostate epithelial cells through AR-dependent mechanisms in the absence of steroid hormones. These findings support the development of novel therapeutics targeting the CXCL12/CXCR4 axis as an ancillary to those targeting the androgen/AR axis to effectively treat castration resistant/recurrent prostate tumors.

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

    Science.gov (United States)

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

    2016-01-01

    Topoisomerase I-DNA-cleavage complexes (Top1cc) stabilized by camptothecin (CPT) have specific effects at transcriptional levels. We recently reported that Top1cc increase antisense transcript (aRNAs) levels at divergent CpG-island promoters and, transiently, DNA/RNA hybrids (R-loop) in nuclear and mitochondrial genomes of colon cancer HCT116 cells. However, the relationship between R-loops and aRNAs was not established. Here, we show that aRNAs can form R-loops in N-TERA-2 cells under physiological conditions, and that promoter-associated R-loops are somewhat increased and extended in length immediately upon cell exposure to CPT. In contrast, persistent Top1ccs reduce the majority of R-loops suggesting that CPT-accumulated aRNAs are not commonly involved in R-loops. The enhancement of aRNAs by Top1ccs is present both in human colon cancer HCT116 cells and WI38 fibroblasts suggesting a common response of cancer and normal cells. Although Top1ccs lead to DSB and DDR kinases activation, we do not detect a dependence of aRNA accumulation on ATM or DNA-PK activation. However, we showed that the cell response to persistent Top1ccs can involve an impairment of aRNA turnover rather than a higher synthesis rate. Finally, a genome-wide analysis shows that persistent Top1ccs also determine an accumulation of sense transcripts at 5'-end gene regions suggesting an increased occurrence of truncated transcripts. Taken together, the results indicate that Top1 may regulate transcription initiation by modulating RNA polymerase-generated negative supercoils, which can in turn favor R-loop formation at promoters, and that transcript accumulation at TSS is a response to persistent transcriptional stress by Top1 poisoning.

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

    Directory of Open Access Journals (Sweden)

    Jessica Marinello

    Full Text Available Topoisomerase I-DNA-cleavage complexes (Top1cc stabilized by camptothecin (CPT have specific effects at transcriptional levels. We recently reported that Top1cc increase antisense transcript (aRNAs levels at divergent CpG-island promoters and, transiently, DNA/RNA hybrids (R-loop in nuclear and mitochondrial genomes of colon cancer HCT116 cells. However, the relationship between R-loops and aRNAs was not established. Here, we show that aRNAs can form R-loops in N-TERA-2 cells under physiological conditions, and that promoter-associated R-loops are somewhat increased and extended in length immediately upon cell exposure to CPT. In contrast, persistent Top1ccs reduce the majority of R-loops suggesting that CPT-accumulated aRNAs are not commonly involved in R-loops. The enhancement of aRNAs by Top1ccs is present both in human colon cancer HCT116 cells and WI38 fibroblasts suggesting a common response of cancer and normal cells. Although Top1ccs lead to DSB and DDR kinases activation, we do not detect a dependence of aRNA accumulation on ATM or DNA-PK activation. However, we showed that the cell response to persistent Top1ccs can involve an impairment of aRNA turnover rather than a higher synthesis rate. Finally, a genome-wide analysis shows that persistent Top1ccs also determine an accumulation of sense transcripts at 5'-end gene regions suggesting an increased occurrence of truncated transcripts. Taken together, the results indicate that Top1 may regulate transcription initiation by modulating RNA polymerase-generated negative supercoils, which can in turn favor R-loop formation at promoters, and that transcript accumulation at TSS is a response to persistent transcriptional stress by Top1 poisoning.

  20. Growth-promoting activity of Hominis Placenta extract on regenerating sciatic nerve

    Institute of Scientific and Technical Information of China (English)

    Tae-beom SEO; Dong-hee KIM; Seung-kiel PARK; Deok-chun YANG; Uk NAMGUNG; In-sun HAN; Jin-hwan YOON; In-chan SEOL; Yun-sik KIM; Hyun-kyung JO; Joung-jo AN; Kwon-eui HONG; Young-bae SEO

    2006-01-01

    Aim: Extract of Hominis Placenta (HP) has been used in oriental medicine as an agent for improving physiological function. The present study was conducted to investigate whether HP treatment in an experimental sciatic nerve injury animal model produces growth-promoting effects on regenerating peripheral nerve fibers after injury. Methods: After HP was injected into a sciatic nerve injury site, changes in protein levels were analyzed in the regenerating nerve area by Western blotting and immunofluorescence staining analyses. For quantitative assessment of axonal regeneration, a retrograde tracing technique was used to identify the neuronal cell bodies corresponding to regenerating axons, and the extent of neurite outgrowth in cultured dorsal root ganglia (DRG) sensory neurons prepared from animals that had experienced a sciatic nerve crush injury 7 d before neuron collection was analyzed. Results: Induction levels of axonal growth-associated protein (GAP-43) in the injured sciatic nerves were elevated by HP treatment. HP treatment also upregulated cell division cycle 2 (Cdc2) protein levels in the distal stump of the injured sciatic nerve. Induced Cdc2 protein was detected in Schwann cells, suggesting that Cdc2 kinase activity may be involved in the growth-promoting activity of regenerating axons via Schwann cell proliferation. Cell body measurement by retrograde tracing indicated that HP treatment produced significant increases in regenerating motor axons. Finally, HP treatment of cultured DRG sensory neurons significantly increased neurite arborization and elongation.Conclusion: HP promotes the regeneration of injured sciatic axons by upregulating the synthesis of regeneration-related protein factors such as GAP-43 and Cdc2.

  1. The metastasis-promoting phosphatase PRL-3 shows activity toward phosphoinositides.

    Science.gov (United States)

    McParland, Victoria; Varsano, Giulia; Li, Xun; Thornton, Janet; Baby, Jancy; Aravind, Ajay; Meyer, Christoph; Pavic, Karolina; Rios, Pablo; Köhn, Maja

    2011-09-06

    Phosphatase of regenerating liver 3 (PRL-3) is suggested as a biomarker and therapeutic target in several cancers. It has a well-established causative role in cancer metastasis. However, little is known about its natural substrates, pathways, and biological functions, and only a few protein substrates have been suggested so far. To improve our understanding of the substrate specificity and molecular determinants of PRL-3 activity, the wild-type (WT) protein, two supposedly catalytically inactive mutants D72A and C104S, and the reported hyperactive mutant A111S were tested in vitro for substrate specificity and activity toward phosphopeptides and phosphoinositides (PIPs), their structural stability, and their ability to promote cell migration using stable HEK293 cell lines. We discovered that WT PRL-3 does not dephosphorylate the tested phosphopeptides in vitro. However, as shown by two complementary biochemical assays, PRL-3 is active toward the phosphoinositide PI(4,5)P(2). Our experimental results substantiated by molecular docking studies suggest that PRL-3 is a phosphatidylinositol 5-phosphatase. The C104S variant was shown to be not only catalytically inactive but also structurally destabilized and unable to promote cell migration, whereas WT PRL-3 promotes cell migration. The D72A mutant is structurally stable and does not dephosphorylate the unnatural substrate 3-O-methylfluorescein phosphate (OMFP). However, we observed residual in vitro activity of D72A against PI(4,5)P(2), and in accordance with this, it exhibits the same cellular phenotype as WT PRL-3. Our analysis of the A111S variant shows that the hyperactivity toward the unnatural OMFP substrate is not apparent in dephosphorylation assays with phosphoinositides: the mutant is completely inactive against PIPs. We observed significant structural destabilization of this variant. The cellular phenotype of this mutant equals that of the catalytically inactive C104S mutant. These results provide a possible

  2. Terpenoids with neurite outgrowth-promoting activity from the branches and leaves of Illicium merrillianum.

    Science.gov (United States)

    Tian, Xin-Hui; Yue, Rong-Cai; Fang, Xin; Zhang, Jian-Ping; Wang, Guo-Wei; Shan, Lei; Zhang, Wei-Dong; Shen, Yun-Heng

    2016-05-01

    Eighteen terpenoids (1-18) were isolated from Illicium merrillianum. Compound 1 was identified as new compound, and its structure was established by comprehensive spectroscopic analysis and single-crystal X-ray diffraction. All compounds were evaluated for nerve growth factor (NGF)-mediated neurite outgrowth activity using rat pheochromocytoma (PC12) cells as a model system of neuronal differentiation. Compounds 1, 3, 18 showed significant neurite outgrowth-promoting activity in the presence of 20 ng/ml NGF in a dose-dependent manner at concentrations of 1-100 μM after 24-h treatment. Subtle difference of functional groups at C-2 position in hopane-type triterpene resulted in enormous bioactivity difference, compound 1 was neurotrophic but 2 was cytotoxic.

  3. Nanoparticle-induced unfolding of fibrinogen promotes Mac-1 receptor activation and inflammation

    Science.gov (United States)

    Deng, Zhou J.; Liang, Mingtao; Monteiro, Michael; Toth, Istvan; Minchin, Rodney F.

    2011-01-01

    The chemical composition, size, shape and surface characteristics of nanoparticles affect the way proteins bind to these particles, and this in turn influences the way in which nanoparticles interact with cells and tissues. Nanomaterials bound with proteins can result in physiological and pathological changes, including macrophage uptake, blood coagulation, protein aggregation and complement activation, but the mechanisms that lead to these changes remain poorly understood. Here, we show that negatively charged poly(acrylic acid)-conjugated gold nanoparticles bind to and induce unfolding of fibrinogen, which promotes interaction with the integrin receptor, Mac-1. Activation of this receptor increases the NF-κB signalling pathway, resulting in the release of inflammatory cytokines. However, not all nanoparticles that bind to fibrinogen demonstrated this effect. Our results show that the binding of certain nanoparticles to fibrinogen in plasma offers an alternative mechanism to the more commonly described role of oxidative stress in the inflammatory response to nanomaterials.

  4. Strong and coverage-independent promotion of catalytic activity of a noble metal by subsurface vanadium

    Science.gov (United States)

    Reichl, Wolfgang; Hayek, Konrad

    2003-07-01

    While common bimetallic surfaces have a variable composition, the stable subsurface alloys of V/Rh and V/Pd are characterised by a purely noble metal-terminated surface and the second metal positioned in near-surface layers. The uniform composition of the topmost surface layer excludes conventional ensemble effects in catalysis, and the activity of the surface can be controlled by the metal loading and by the temperature of annealing. For example, the activity of a polycrystalline Rh surface in CO hydrogenation is significantly increased by promotion with subsurface vanadium. The modification of the subsurface layer with a different metal must be considered a promising approach to improve the catalytic properties of a metal surface.

  5. Active Achilles tendon kinesitherapy accelerates Achilles tendon repair by promoting neurite regeneration

    Institute of Scientific and Technical Information of China (English)

    Jiasharete Jielile; Beicen Hunapia; Ayidaer Jialihasi; Jingping Bai; Murat Kizaibek; Minawa Aibai; Gulnur Sabirhazi; Nuerai Shawutali; Wulanbai Tangkejie; Aynaz Badelhan; Yeermike Nuerduola; Turde Satewalede; Darehan Buranbai

    2012-01-01

    Active Achilles tendon kinesitherapy facilitates the functional recovery of a ruptured Achilles tendon. However, protein expression during the healing process remains a controversial issue. New Zealand rabbits, aged 14 weeks, underwent tenotomy followed immediately by Achilles tendon microsurgery to repair the Achilles tendon rupture. The tendon was then immobilized or subjected to postoperative early motion treatment (kinesitherapy). Mass spectrography results showed that after 14 days of motion treatment, 18 protein spots were differentially expressed, among which, 12 were up-regulated, consisting of gelsolin isoform b and neurite growth-related protein collapsing response mediator protein 2. Western blot analysis showed that gelsolin isoform b was up-regulated at days 7–21 of motion treatment. These findings suggest that active Achilles tendon kinesitherapy promotes the neurite regeneration of a ruptured Achilles tendon and gelsolin isoform b can be used as a biomarker for Achilles tendon healing after kinesitherapy.

  6. The Vibrio cholerae cytolysin (VCC) promotes activation of mast cell (T helper 2) cytokine production

    Science.gov (United States)

    Arcidiacono, Diletta; Odom, Sandra; Frossi, Barbara; Rivera, Juan; Paccani, Silvia Rossi; Baldari, Cosima T.; Pucillo, Carlo; Montecucco, Cesare; de Bernard, Marina

    2008-01-01

    Summary Many strains of Vibrio cholerae produce a cytolysin (VCC) that forms oligomeric transmembrane pores responsible for vacuolization of several cell types in culture. Here we report that VCC is a TLR2 agonist able to stimulate mast cells to produce several cytokines (IL-4 included) which could contribute to the Th2 response seen in the natural infection. Moreover, VCC-induced cytokine production was dependent on increased cytosolic Ca2+ and on the presence of the two Src family kinases Lyn and Fyn, known to be required for FcεRI-dependent activation of mast cells. These findings strongly suggest that VCC is endowed with pro-inflammatory activity that promotes a Th2-type immune profile. PMID:18005391

  7. Acetylation of malate dehydrogenase 1 promotes adipogenic differentiation via activating its enzymatic activity.

    Science.gov (United States)

    Kim, Eun Young; Kim, Won Kon; Kang, Hyo Jin; Kim, Jeong-Hoon; Chung, Sang J; Seo, Yeon Soo; Park, Sung Goo; Lee, Sang Chul; Bae, Kwang-Hee

    2012-09-01

    Acetylation is one of the most crucial post-translational modifications that affect protein function. Protein lysine acetylation is catalyzed by acetyltransferases, and acetyl-CoA functions as the source of the acetyl group. Additionally, acetyl-CoA plays critical roles in maintaining the balance between carbohydrate metabolism and fatty acid synthesis. Here, we sought to determine whether lysine acetylation is an important process for adipocyte differentiation. Based on an analysis of the acetylome during adipogenesis, various proteins displaying significant quantitative changes were identified by LC-MS/MS. Of these identified proteins, we focused on malate dehydrogenase 1 (MDH1). The acetylation level of MDH1 was increased up to 6-fold at the late stage of adipogenesis. Moreover, overexpression of MDH1 in 3T3-L1 preadipocytes induced a significant increase in the number of cells undergoing adipogenesis. The introduction of mutations to putative lysine acetylation sites showed a significant loss of the ability of cells to undergo adipogenic differentiation. Furthermore, the acetylation of MDH1 dramatically enhanced its enzymatic activity and subsequently increased the intracellular levels of NADPH. These results clearly suggest that adipogenic differentiation may be regulated by the acetylation of MDH1 and that the acetylation of MDH1 is one of the cross-talk mechanisms between adipogenesis and the intracellular energy level.

  8. Connective tissue growth factor promoter activity in normal and wounded skin

    Directory of Open Access Journals (Sweden)

    Kapoor Mohit

    2008-10-01

    Full Text Available Abstract In skin, connective tissue growth factor (CTGF/CCN2 is induced during tissue repair. However, what the exact cell types are that express CTGF in normal and wounded skin remain controversial. In this report, we use transgenic knock-in mice in which the Pacific jellyfish Aequorea victoria enhanced green fluorescent protein (E-GFP gene has been inserted between the endogenous CTGF promoter and gene. Unwounded (day 0 and wounded (days 3 and 7 skin was examined for GFP to detect cells in which the CTGF promoter was active, α-smooth muscle actin (α-SMA to detect myofibroblasts, and NG2 expression to detect pericytes. In unwounded mice, CTGF expression was absent in epidermis and was present in a few cells in the dermis. Upon wounding, CTGF expression was induced in the dermis. Double immunolabeling revealed that CTGF-expressing cells also expressed α-SMA, indicating the CTGF was expressed in myofibroblasts. A subset (~30% of myofibroblasts were also NG2 positive, indicating that pericytes significantly contributed to the number of myofibroblasts in the wound. Pericytes also expressed CTGF. Collectively, these results indicate that CTGF expression in skin correlates with myofibroblast induction, and that CTGF-expressing pericytes are significant contributors to myofibroblast activity during cutaneous tissue repair.

  9. Activation of GLP-1 Receptor Promotes Bone Marrow Stromal Cell Osteogenic Differentiation through β-Catenin

    Directory of Open Access Journals (Sweden)

    Jingru Meng

    2016-04-01

    Full Text Available Glucagon-like peptide 1 (GLP-1 plays an important role in regulating bone remodeling, and GLP-1 receptor agonist shows a positive relationship with osteoblast activity. However, GLP-1 receptor is not found in osteoblast, and the mechanism of GLP-1 receptor agonist on regulating bone remodeling is unclear. Here, we show that the GLP-1 receptor agonist exendin-4 (Ex-4 promoted bone formation and increased bone mass and quality in a rat unloading-induced bone loss model. These functions were accompanied by an increase in osteoblast number and serum bone formation markers, while the adipocyte number was decreased. Furthermore, GLP-1 receptor was detected in bone marrow stromal cells (BMSCs, but not in osteoblast. Activation of GLP-1 receptor by Ex-4 promoted the osteogenic differentiation and inhibited BMSC adipogenic differentiation through regulating PKA/β-catenin and PKA/PI3K/AKT/GSK3β signaling. These findings reveal that GLP-1 receptor regulates BMSC osteogenic differentiation and provide a molecular basis for therapeutic potential of GLP-1 against osteoporosis.

  10. 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

  11. Applied neuroanatomy elective to reinforce and promote engagement with neurosensory pathways using interactive and artistic activities.

    Science.gov (United States)

    Dao, Vinh; Yeh, Pon-Hsiu; Vogel, Kristine S; Moore, Charleen M

    2015-01-01

    One in six Americans is currently affected by neurologic disease. As the United States population ages, the number of neurologic complaints is expected to increase. Thus, there is a pressing need for more neurologists as well as more neurology training in other specialties. Often interest in neurology begins during medical school, so improving education in medical neural courses is a critical step toward producing more neurologists and better neurology training in other specialists. To this end, a novel applied neuroanatomy elective was designed at the University of Texas Health Science Center at San Antonio (UTHSCSA) to complement the traditional first-year medical neuroscience course and promote engagement and deep learning of the material with a focus on neurosensory pathways. The elective covered four neurosensory modalities (proprioception/balance, vision, auditory, and taste/olfaction) over four sessions, each with a short classroom component and a much longer activity component. At each session, students reviewed the neurosensory pathways through structured presentations and then applied them to preplanned interactive activities, many of which allowed students to utilize their artistic talents. Students were required to complete subjective pre-course and post-course surveys and reflections. The survey results and positive student comments suggest that the elective was a valuable tool when used in parallel with the traditional medical neuroscience course in promoting engagement and reinforcement of the neurosensory material.

  12. Characterization of the highly active fragment of glyceraldehyde-3-phosphate dehydrogenase gene promoter for recombinant protein expression in Pleurotus ostreatus.

    Science.gov (United States)

    Yin, Chaomin; Zheng, Liesheng; Zhu, Jihong; Chen, Liguo; Ma, Aimin

    2015-03-01

    Developing efficient native promoters is important for improving recombinant protein expression by fungal genetic engineering. The promoter region of glyceraldehyde-3-phosphate dehydrogenase gene in Pleurotus ostreatus (Pogpd) was isolated and optimized by upstream truncation. The activities of these promoters with different lengths were further confirmed by fluorescence, quantitative real-time PCR and Western blot analysis. A truncated Pogpd-P2 fragment (795 bp) drove enhanced green fluorescence protein (egfp) gene expression in P. ostreatus much more efficiently than full-length Pogpd-P1. Further truncating Pogpd-P2 to 603, 403 and 231 bp reduced the eGFP expression significantly. However, the 403-bp fragment between -356 bp and the start codon was the minimal but sufficient promoter element for eGFP expression. Compact native promoters for genetic engineering of P. ostreatus were successfully developed and validated in this study. This will broaden the preexisting repertoire of fungal promoters for biotechnology application.

  13. Perceptions and Attitudes of Egyptian Health Professionals and Policy-Makers towards Pharmaceutical Sales Representatives and Other Promotional Activities.

    Directory of Open Access Journals (Sweden)

    Susan Kamal

    Full Text Available Pharmaceutical promotion activities in low and middle-income countries are often neither regulated nor monitored. While Egypt has the highest population and per capita use of medicines in the Arab world, we know very little about pharmaceutical companies promotional activities in the country.To explore and analyze the perceptions of physicians towards promotional and marketing activities of pharmaceutical companies among physicians and pharmacists in Egypt.Perspectives of different healthcare system stakeholders were explored through semi-structured, in-depth interviews conducted in 2014 in Cairo, Egypt. Interviewees were chosen via purposive sampling and snowball technique. Each interview was recorded and transcribed. Then qualitative, thematic analysis was conducted with the help of NVIVO software.The majority of physicians and pharmacists acknowledged exposure to pharmaceutical promotion. It was commonly believed that interaction with the pharmaceutical industry is necessary and both associated risks and benefits were acknowledged. The interviewed physicians considered themselves competent enough to minimize risks and maximize benefits to their prescribing habits. Views diverged on the extent and magnitude of the risks and benefits of pharmaceutical promotion, especially in regard to the influence on patients' health.Pharmaceutical promotion in Egypt is intensely directed at prescribers and dispensers. Physicians, pharmacists and policymakers expressed little skepticism to the influence of promotion towards their individual prescribing. Raising awareness of the pitfalls of pharmaceutical promotion is necessary, especially among the less experienced physicians.

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

    Directory of Open Access Journals (Sweden)

    Janet M Young

    2013-11-01

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

  15. Comparative Assessment of DFT Performances in Ru- and Rh-Promoted σ-Bond Activations.

    Science.gov (United States)

    Sun, Yuanyuan; Hu, Lianrui; Chen, Hui

    2015-04-14

    In this work, the performances of 19 density functional theory (DFT) methods are calibrated comparatively on Ru- and Rh-promoted σ-bond (C-H, O-H, and H-H) activations. DFT calibration reference is generated from explicitly correlated coupled cluster CCSD(T)-F12 calculations, and the 4s4p core-valence correlation effect of the two 4d platinum group transition metals is also included. Generally, the errors of DFT methods for calculating energetics of Ru-/Rh-mediated reactions appear to correlate more with the magnitude of energetics itself than other factors such as metal identity. For activation energy calculations, the best performing functionals for both Ru and Rh systems are MN12SX DFT empirical dispersion correction on the performance of the DFT methods is beneficial for most density functionals tested in this work, reducing their MUDs to different extents. After including empirical dispersion correction, ωB97XD, B3LYP-D3, and CAM-B3LYP-D3 (PBE0-D3, B3LYP-D3, and ωB97XD) are the three best performing DFs for activation energy (reaction energy) calculations, from which B3LYP-D3 and ωB97XD can notably be recommended uniformly for both the reaction energy and reaction barrier calculations. The good performance of B3LYP-D3 in quantitative description of the energetic trends further adds value to B3LYP-D3 and singles this functional out as a reasonable choice in the Ru/Rh-promoted σ-bond activation processes.

  16. Assessing the Physical Activity of Health Volunteers Based on the Pender’s Health Promotion Model

    Directory of Open Access Journals (Sweden)

    Rahimian M.* MSc,

    2015-12-01

    Full Text Available Aims Physical inactivity has been identified as the 4th leading risk factor for global mortality causing an estimated of 3.2million deaths per year. This study aimed to assess the physical activity of health volunteers with Pender’s Health Promotion Model. Instrument & Methods This cross-sectional analytical study was performed on 80 health volunteers in Torbat-e-Jam City, Iran, in 2015. A researcher-made questionnaire with the following sections was used to gather data; perceived benefits, perceived barriers, selfefficacy, interpersonal influences, positive emotion, commitment, modeling and competing preferences. SPSS 16 sofware was used to analyze data by independent T, Pearson’s correlation coefficient and linear regression tests. Findings There was no significant difference between the scores according to educational levels, age groups, BMI score, marital status, habitat and experience as a health volunteer duration. Physical activity had positive correlation with perceived benefits, self-efficacy, commitment, positive emotion and situational influences and a negative correlation with perceived barriers. Situational influences, as the strongest predictor of the physical activity, predicted 35.1% of it and then positive emotions predicted 34.7% and self-efficacy predicted 23.4% of physical activity. Conclusion The level of physical activity in health volunteers of Torbat-e-Jam City, Iran, is not appropriate and is less than moderate.

  17. Physical Activity Promotion in Schools: Which Strategies Do Schools (Not) Implement and Which Socioecological Factors Are Associated with Implementation?

    Science.gov (United States)

    Cardon, Greet M.; Van Acker, Ragnar; Seghers, Jan; De Martelaer, Kristine; Haerens, Leen L.; De Bourdeaudhuij, Ilse M. M.

    2012-01-01

    We studied the implementation and associated factors of strategies (e.g. sports after school and during lunch break, active schoolyards, active school commuting) and organizational principles (e.g. safe bike racks, pupil involvement) that facilitate the physical activity (PA)-promoting role of schools. Key representatives of 111 elementary and 125…

  18. Promoting physical activity participation among people with profound intellectual and multiple disabilities : An overview of practice-based knowledge

    NARCIS (Netherlands)

    van Alphen, Leentje; Waninge, Aly; van der Putten, Annette

    2016-01-01

    Aim: Promoting physical activity participation as part of the support of people with profound intellectual and multiple disabilities (PIMD) is important for the functioning of people with PIMD and their participation in daily activities. However, people with PIMD hardly participate in physical activ

  19. The oncoprotein HBXIP upregulates PDGFB via activating transcription factor Sp1 to promote the proliferation of breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yingyi; Zhao, Yu; Li, Leilei; Shen, Yu; Cai, Xiaoli [Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071 (China); Zhang, Xiaodong, E-mail: zhangxd@nankai.edu.cn [Department of Cancer Research, Institute for Molecular Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China); Ye, Lihong, E-mail: yelihong@nankai.edu.cn [Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071 (China)

    2013-05-03

    Highlights: •HBXIP is able to upregulate the expression of PDGFB in breast cancer cells. •HBXIP serves as a coactivator of activating transcription factor Sp1. •HBXIP stimulates the PDGFB promoter via activating transcription factor Sp1. •HBXIP promotes the proliferation of breast cancer cell via upregulating PDGFB. -- Abstract: We have reported that the oncoprotein hepatitis B virus X-interacting protein (HBXIP) acts as a novel transcriptional coactivator to promote proliferation and migration of breast cancer cells. Previously, we showed that HBXIP was able to activate nuclear factor-κB (NF-κB) in breast cancer cells. As an oncogene, the platelet-derived growth factor beta polypeptide (PDGFB) plays crucial roles in carcinogenesis. In the present study, we found that both HBXIP and PDGFB were highly expressed in breast cancer cell lines. Interestingly, HBXIP was able to increase transcriptional activity of NF-κB through PDGFB, suggesting that HBXIP is associated with PDGFB in the cells. Moreover, HBXIP was able to upregulate PDGFB at the levels of mRNA, protein and promoter in the cells. Then, we identified that HBXIP stimulated the promoter of PDGFB through activating transcription factor Sp1. In function, HBXIP enhanced the proliferation of breast cancer cells through PDGFB in vitro. Thus, we conclude that HBXIP upregulates PDGFB via activating transcription factor Sp1 to promote proliferation of breast cancer cells.

  20. EFFECTS OF SP1 SITE TO hTERT PROMOTER ACTIVITY AND ITS RESPONSE TO RETINOID ACID

    Institute of Scientific and Technical Information of China (English)

    应磊; 戴冰冰; 王楚; 卢健; 钱关祥

    2005-01-01

    Objective To investigate the function of Sp1 consensus sites to human telomerase reverse transcriptase (hTERT) promoter in different cell lines and in TRA-treated Held cell. Methods Different length of hTERT promoter was cloned and inserted into pGL3/basic reporter plasmid. The last four Sp1 sites were deleted by PCR and pGL3 B/TRTP413 A reporter plasmid was constructed. All reporter plasmids were transiently transfected into 293, A549, Hela and HepG2 cell lines. 48 h after transfection, luciferase activity was analyzed. hTERT promoter activity of Held cell which was treated with trans-retinoid acid (TRA) was tested too. Total RNA of these cells were extracted and reverse transcript. hTERT mRNA level was analyzed in all tested cells. c-Myc and Sp1 expression were examined in Hela cell before and after TRA treatment. U937 was used as a positive control in TRA treatment.Results hTERT was expressed at different level in all tested cell lines. 207bp promoter upstream of transcription start site maintained complete activity. Deletion of last 4 Sp1 sites greatly decreased activity of hTERT promoter, and almost eliminated its activity in HepG2. TRA increased the activity of different length hTERT promoters in Hela cell,but the activity of Sp1 site-deleted promoter decreased by 3 times. Unlike U937 cell, hTERT expression of Held cell increased after TRA treatment, and c-Myc and Sp1 mRNA level were relatively stable. Conclusion Sp1 site was required for transactivation of hTERT promoter and played an important role during TRA treatment.

  1. Genetic and cytological evidence that heterocyst patterning is regulated by inhibitor gradients that promote activator decay.

    Science.gov (United States)

    Risser, Douglas D; Callahan, Sean M

    2009-11-24

    The formation of a pattern of differentiated cells from a group of seemingly equivalent, undifferentiated cells is a central paradigm of developmental biology. Several species of filamentous cyanobacteria differentiate nitrogen-fixing heterocysts at regular intervals along unbranched filaments to form a periodic pattern of two distinct cell types. This patterning has been used to exemplify application of the activator-inhibitor model to periodic patterns in biology. The activator-inhibitor model proposes that activators and inhibitors of differentiation diffuse from source cells to form concentration gradients that in turn mediate patterning, but direct visualization of concentration gradients of activators and inhibitors has been difficult. Here we show that the periodic pattern of heterocysts produced by cyanobacteria relies on two inhibitors of heterocyst differentiation, PatS and HetN, in a manner consistent with the predictions of the activator-inhibitor model. Concentration gradients of the activator, HetR, were observed adjacent to heterocysts, the natural source of PatS and HetN, as well as adjacent to vegetative cells that were manipulated to overexpress a gene encoding either of the inhibitors. Gradients of HetR relied on posttranslational decay of HetR. Deletion of both patS and hetN genes prevented the formation of gradients of HetR, and a derivative of the inhibitors was shown to promote decay of HetR in a concentration-dependent manner. Our results provide strong support for application of the activator-inhibitor model to heterocyst patterning and, more generally, the formation of periodic patterns in biological systems.

  2. An evaluation of a model for the systematic documentation of hospital based health promotion activities: results from a multicentre study

    DEFF Research Database (Denmark)

    Tønnesen, Hanne; Christensen, Mette E; Groene, Oliver;

    2007-01-01

    The first step of handling health promotion (HP) in Diagnosis Related Groups (DRGs) is a systematic documentation and registration of the activities in the medical records. So far the possibility and tradition for systematic registration of clinical HP activities in the medical records and in pat......The first step of handling health promotion (HP) in Diagnosis Related Groups (DRGs) is a systematic documentation and registration of the activities in the medical records. So far the possibility and tradition for systematic registration of clinical HP activities in the medical records...

  3. Prostaglandin E2 promotes endothelial differentiation from bone marrow-derived cells through AMPK activation.

    Directory of Open Access Journals (Sweden)

    Zhenjiu Zhu

    Full Text Available Prostaglandin E2 (PGE2 has been reported to modulate angiogenesis, the process of new blood vessel formation, by promoting proliferation, migration and tube formation of endothelial cells. Endothelial progenitor cells are known as a subset of circulating bone marrow mononuclear cells that have the capacity to differentiate into endothelial cells. However, the mechanism underlying the stimulatory effects of PGE2 and its specific receptors on bone marrow-derived cells (BMCs in angiogenesis has not been fully characterized. Treatment with PGE2 significantly increased the differentiation and migration of BMCs. Also, the markers of differentiation to endothelial cells, CD31 and von Willebrand factor, and the genes associated with migration, matrix metalloproteinases 2 and 9, were significantly upregulated. This upregulation was abolished by dominant-negative AMP-activated protein kinase (AMPK and AMPK inhibitor but not protein kinase, a inhibitor. As a functional consequence of differentiation and migration, the tube formation of BMCs was reinforced. Along with altered BMCs functions, phosphorylation and activation of AMPK and endothelial nitric oxide synthase, the target of activated AMPK, were both increased which could be blocked by EP4 blocking peptide and simulated by the agonist of EP4 but not EP1, EP2 or EP3. The pro-angiogenic role of PGE2 could be repressed by EP4 blocking peptide and retarded in EP4(+/- mice. Therefore, by promoting the differentiation and migration of BMCs, PGE2 reinforced their neovascularization by binding to the receptor of EP4 in an AMPK-dependent manner. PGE2 may have clinical value in ischemic heart disease.

  4. Mast cell histamine promotes the immunoregulatory activity of myeloid-derived suppressor cells.

    Science.gov (United States)

    Martin, Rebecca K; Saleem, Sheinei J; Folgosa, Lauren; Zellner, Hannah B; Damle, Sheela R; Nguyen, Giang-Kim T; Ryan, John J; Bear, Harry D; Irani, Anne-Marie; Conrad, Daniel H

    2014-07-01

    It has been shown recently that MCs are required for differential regulation of the immune response by granulocytic versus monocytic MDSCs. Granulocytic MDSCs promoted parasite clearance, whereas monocytic MDSCs enhanced tumor progression; both activities were abrogated in MC-deficient mice. Herein, we demonstrate that the lack of MCs also influences MDSC trafficking. Preferential trafficking to the liver was not seen in MC-deficient mice. In addition, evidence that the MC mediator histamine was important in MDSC trafficking and activation is also shown. MDSCs express HR1-3. Blockade of these receptors by HR1 or HR2 antagonists reversed the histamine enhancement of MDSC survival and proliferation observed in cell culture. In addition, histamine differentially influenced Arg1 and iNOS gene expression in MDSCs and greatly enhanced IL-4 and IL-13 message, especially in granulocytic MDSCs. Evidence that histamine influenced activity seen in vitro translated to in vivo when HR1 and HR2 antagonists blocked the effect of MDSCs on parasite expulsion and tumor metastasis. All of these data support the MDSC-mediated promotion of Th2 immunity, leading to the suggestion that allergic-prone individuals would have elevated MDSC levels. This was directly demonstrated by looking at the relative MDSC levels in allergic versus control patients. Monocytic MDSCs trended higher, whereas granulocytic MDSCs were increased significantly in allergic patients. Taken together, our studies indicate that MCs and MC-released histamine are critical for MDSC-mediated immune regulation, and this interaction should be taken into consideration for therapeutic interventions that target MDSCs.

  5. Histone H4 Lys 20 methyltransferase SET8 promotes androgen receptor-mediated transcription activation in prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Lushuai [Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Li, Yanyan; Du, Fengxia [Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); Han, Xiao [Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Li, Xiaohua [Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); Niu, Yuanjie [Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, Tianjin Medical University, Tianjin 300070 (China); Ren, Shancheng, E-mail: renshancheng@gmail.com [Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Sun, Yingli, E-mail: sunyl@big.ac.cn [Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China)

    2014-07-18

    Highlights: • Dihydrotestosterone stimulates H4K20me1 enrichment at the PSA promoter. • SET8 promotes AR-mediated transcription activation. • SET8 interacts with AR and promotes cell proliferation. - Abstract: Histone methylation status in different lysine residues has an important role in transcription regulation. The effect of H4K20 monomethylation (H4K20me1) on androgen receptor (AR)-mediated gene transcription remains unclear. Here we show that AR agonist stimulates the enrichment of H4K20me1 and SET8 at the promoter of AR target gene PSA in an AR dependent manner. Furthermore, SET8 is crucial for the transcription activation of PSA. Co-immunoprecipitation analyses demonstrate that SET8 interacts with AR. Therefore, we conclude that SET8 is involved in AR-mediated transcription activation, possibly through its interaction with AR and H4K20me1 modification.

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

    Directory of Open Access Journals (Sweden)

    Yaiza del Pozo Martin

    2015-12-01

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

  7. Oxidized CaMKII promotes asthma through the activation of mast cells

    Science.gov (United States)

    Qu, Jingjing; Do, Danh C.; Luczak, Elizabeth; Mitzner, Wayne; Anderson, Mark E.; Gao, Peisong

    2017-01-01

    Oxidation of calmodulin-dependent protein kinase II (ox-CaMKII) by ROS has been associated with asthma. However, the contribution of ox-CaMKII to the development of asthma remains to be fully characterized. Here, we tested the effect of ox-CaMKII on IgE-mediated mast cell activation in an allergen-induced mouse model of asthma using oxidant-resistant CaMKII MMVVδ knockin (MMVVδ) mice. Compared with WT mice, the allergen-challenged MMVVδ mice displayed less airway hyperresponsiveness (AHR) and inflammation. These MMVVδ mice exhibited reduced levels of ROS and diminished recruitment of mast cells to the lungs. OVA-activated bone marrow–derived mast cells (BMMCs) from MMVVδ mice showed a significant inhibition of ROS and ox-CaMKII expression. ROS generation was dependent on intracellular Ca2+ concentration in BMMCs. Importantly, OVA-activated MMVVδ BMMCs had suppressed degranulation, histamine release, leukotriene C4, and IL-13 expression. Adoptive transfer of WT, but not MMVVδ, BMMCs, reversed the alleviated AHR and inflammation in allergen-challenged MMVVδ mice. The CaMKII inhibitor KN-93 significantly suppressed IgE-mediated mast cell activation and asthma. These studies support a critical but previously unrecognized role of ox-CaMKII in mast cells that promotes asthma and suggest that therapies to reduce ox-CaMKII may be a novel approach for asthma. PMID:28097237

  8. Gas6/Axl pathway promotes tumor invasion through the transcriptional activation of Slug in hepatocellular carcinoma.

    Science.gov (United States)

    Lee, Hsin-Jung; Jeng, Yung-Ming; Chen, Yu-Ling; Chung, Ling; Yuan, Ray-Hwang

    2014-04-01

    Hepatocellular carcinoma (HCC) is one of the most common fatal cancers worldwide. Other than the sorafenib treatment, no effective systemic therapy has been available thus far. Most targets in molecularly targeted therapy for cancer are receptor tyrosine kinases (RTKs). Therefore, identifying activated RTKs in HCC is critical for developing new molecularly targeted therapies. Using a phospho-RTK array, we found that Axl is one of the most frequently activated RTKs in liver cancer cell lines. The knockdown of Axl by RNA interference significantly reduced cell migration and invasion in the HCC cell lines HA22T and Mahlavu. Stimulation of HCC cell lines by Axl ligand growth arrest-specific 6 (Gas6) enhanced cell migration and invasion. The Gas6/Axl pathway enhanced the expression of the epithelial-mesenchymal transition-inducing transcription factor Slug, which is essential for the invasion-promoting activity of Axl. Treating HCC cells with the Axl inhibitor bosutinib suppressed Slug expression and decreased the invasiveness of HCC cell lines. These findings indicate that Gas6/Axl regulates tumor invasion through the transcriptional activation of Slug.

  9. Staphylococcal lipoteichoic acid promotes osteogenic differentiation of mouse mesenchymal stem cells by increasing autophagic activity.

    Science.gov (United States)

    Liu, Xin; Wang, Yuan; Cao, Zhen; Dou, Ce; Bai, Yun; Liu, Chuan; Dong, Shiwu; Fei, Jun

    2017-02-16

    This study sought to explore the effect of staphylococcal lipoteichoic acid (LTA) on autophagy in mouse mesenchymal stem cells (MSCs), and then influence osteogenesis through the change of autophagy. C3H10T1/2 cells were induced by osteogenic medium with the treatment of LTA at different concentrations (1, 5, 10 μg/mL); 3-methyladenine (3-MA) were used as the autophagy inhibitor, and rapamycin (rapamycin, Rap) were used to activate autophagy; the effects on osteogenesis were detected by alkaline phosphatase staining, alizarin red staining, real-time quantitative PCR, and western blotting; autophagic activity was investigated by the expression of LC3-Ⅱand p62 proteins. Compared with control group, the expression of osteogenesis markers was significantly up-regulated with the LTA treatment on the mRNA and protein level; the positive rate of alkaline phosphatase was enhanced in the LTA groups; and the formation of calcium nodules was increased simultaneously. The expression of LC3-Ⅱ protein was increased in LTA groups, while the expression of p62 protein was decreased. Inhibition of autophagy significantly reduced the effect of LTA on osteogenesis of MSCs; the promotion of LTA on osteogenic differentiation was further enhanced when adding rapamycin to activate autophagic activity. It provides new insight of prevention and treatment for bone infection.

  10. Activation of brain endothelium by pneumococcal neuraminidase NanA promotes bacterial internalization.

    Science.gov (United States)

    Banerjee, Anirban; Van Sorge, Nina M; Sheen, Tamsin R; Uchiyama, Satoshi; Mitchell, Tim J; Doran, Kelly S

    2010-11-01

    Streptococcus pneumoniae (SPN), the leading cause of meningitis in children and adults worldwide, is associated with an overwhelming host inflammatory response and subsequent brain injury. Here we examine the global response of the blood-brain barrier to SPN infection and the role of neuraminidase A (NanA), an SPN surface anchored protein recently described to promote central nervous system tropism. Microarray analysis of human brain microvascular endothelial cells (hBMEC) during infection with SPN or an isogenic NanA-deficient (ΔnanA) mutant revealed differentially activated genes, including neutrophil chemoattractants IL-8, CXCL-1, CXCL-2. Studies using bacterial mutants, purified recombinant NanA proteins and in vivo neutrophil chemotaxis assays indicated that pneumococcal NanA is necessary and sufficient to activate host chemokine expression and neutrophil recruitment during infection. Chemokine induction was mapped to the NanA N-terminal lectin-binding domain with a limited contribution of the sialidase catalytic activity, and was not dependent on the invasive capability of the organism. Furthermore, pretreatment of hBMEC with recombinant NanA protein significantly increased bacterial invasion, suggesting that NanA-mediated activation of hBMEC is a prerequisite for efficient SPN invasion. These findings were corroborated in an acute murine infection model where we observed less inflammatory infiltrate and decreased chemokine expression following infection with the ΔnanA mutant.

  11. SIRT2 activates G6PD to enhance NADPH production and promote leukaemia cell proliferation

    Science.gov (United States)

    Xu, Shuang-Nian; Wang, Tian-Shi; Li, Xi; Wang, Yi-Ping

    2016-01-01

    Like most other types of cancer cells, leukaemia cells undergo metabolic reprogramming to support rapid proliferation through enhancing biosynthetic processes. Pentose phosphate pathway (PPP) plays a pivotal role in meeting the anabolic demands for cancer cells. However, the molecular mechanism by which PPP contributes to leukaemia remains elusive. Here, we report that leukaemia cell proliferation is dependent on the oxidative branch of PPP, in particular the first and rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD). Knockdown of G6PD reduces NADPH level in acute myeloid leukaemia (AML) cell lines. Exogenous lipid supplements partially restore the proliferation of G6PD-depleted cells. Deacetylase SIRT2 promotes NADPH production through deacetylating G6PD at lysine 403 (K403). Activation of G6PD by SIRT2 supports the proliferation and clonogenic activity of leukaemia cells. Chemical inhibitors against SIRT2 suppress G6PD activity, leading to reduced cell proliferation of leukaemia cells, but not normal hematopoietic stem and progenitor cells. Importantly, SIRT2 is overexpressed in clinical AML samples, while K403 acetylation is downregulated and G6PD catalytic activity is increased comparing to that of normal control. Together, our study reveals that acetylation regulation of G6PD is involved in the metabolic reprogramming of AML, and SIRT2 serves as a promising target for further therapeutic investigations. PMID:27586085

  12. Promoting fit bodies, healthy eating and physical activity among Indigenous Australian men: a study protocol

    Directory of Open Access Journals (Sweden)

    Ricciardelli Lina A

    2012-01-01

    Full Text Available Abstract Background Overall the physical health of Indigenous men is among the worst in Australia. Research has indicated that modifiable lifestyle factors, such as poor nutrition and physical inactivity, appear to contribute strongly to these poor health conditions. To effectively develop and implement strategies to improve the health of Australia's Indigenous peoples, a greater understanding is needed of how Indigenous men perceive health, and how they view and care for their bodies. Further, a more systematic understanding of how sociocultural factors affect their health attitudes and behaviours is needed. This article presents the study protocol of a community-based investigation into the factors surrounding the health and body image of Indigenous Australian men. Methods and design The study will be conducted in a collaborative manner with Indigenous Australian men using a participatory action research framework. Men will be recruited from three locations around Australia (metropolitan, regional, and rural and interviewed to understand their experiences and perspectives on a number of issues related to health and health behaviour. The information that is collected will be analysed using modified grounded theory and thematic analysis. The results will then be used to develop and implement community events in each location to provide feedback on the findings to the community, promote health enhancing strategies, and determine future action and collaboration. Discussion This study will explore both risk and protective factors that affect the health of Indigenous Australian men. This knowledge will be disseminated to the wider Indigenous community and can be used to inform future health promotion strategies. The expected outcome of this study is therefore an increased understanding of health and health change in Indigenous Australian men, the development of strategies that promote healthy eating and positive patterns of physical activity and, in

  13. Minimizing the cancer-promotional activity of cox-2 as a central strategy in cancer prevention.

    Science.gov (United States)

    McCarty, Mark F

    2012-01-01

    A recent meta-analysis examining long-term mortality in subjects who participated in controlled studies evaluating the impact of daily aspirin on vascular risk, has concluded that aspirin confers substantial protection from cancer mortality. Remarkably, low-dose aspirin was as effective as higher-dose regimens; hence this protection may be achievable with minimal risk. There is reason to believe that this protection stems primarily from inhibition of cox-2 in pre-neoplastic lesions. Since safe aspirin regimens can only achieve a partial and transitory inhibition of cox-2, it may be feasible to complement the cancer-protective benefit of aspirin with other measures which decrease cox-2 expression or which limit the bioactivity of cox-2-derived PGE2. Oxidative stress boosts cox-2 expression by up-regulating activation of NF-kappaB and MAP kinases; NADPH oxidase activation may thus promote carcinogenesis by increasing cox-2 expression while also amplifying oxidant-mediated mutagenesis. A prospective cohort study has observed that relatively elevated serum bilirubin levels are associated with a marked reduction in subsequent cancer mortality; this may reflect bilirubin's physiological role as a potent inhibitor of NADPH oxidase. It may be feasible to mimic this protective effect by supplementing with spirulina, a rich source of a phycobilin which shares bilirubin's ability to inhibit NADPH oxidase. Ancillary antioxidant measures - phase 2 inducing phytochemicals, melatonin, N-acetylcysteine, and astaxanthin - may also aid cox-2 down-regulation. The cancer protection often associated with high-normal vitamin D status may be attributable, in part, to the ability of the activated vitamin D receptor to decrease cox-2 expression while promoting PGE2 catabolism and suppressing the expression of PGE2 receptors. Diets with a relatively low ratio of omega-6 to long-chain omega-3 fats may achieve cancer protection by antagonizing the production and bioactivity of PGE2. Growth

  14. Amino acid 1-209 is essential for PDX-1-mediated repression of human CMV IE promoter activity

    Institute of Scientific and Technical Information of China (English)

    Jing CHEN; Lei CHEN; Ge LI; Lu CHENG; Yin HUANG; Jia-xin ZHANG; Wei-wei FAN; Da-ru LU

    2006-01-01

    Aim: To explore the different roles of pancreatic duodenal homeobox factors-1 (PDX-1) domains in PDX-1 mediated repression of human cytomegalovirus immediately early (CMV IE) promoter. Methods: A series of truncated PDX-1 mutants were constructed. The binding of PDX-1 and CMV IE promoter was identified by electrophoretic mobility shift assay (EMSA). The dual-reporter assay was applied to examine the repression activities of PDX-1 mutants on CMV IE promoter. In addition, RNAi technology was used to specifically knock down the endogenous PDX-1 expression. Results: The reporter assay indicated that compared to the mock controls (pEGFP-N2), overexpression of PDX-1 resulted in a 41% decrease of CMV IE promoter activity in the 293 cells (P<0.05) and 43% decrease in HeLa cells (P<0.05), and the repression levels of various truncated mutants played on CMV IE promoter were different. Specific knock down of the endogenous PDX-1 expression significantly restored the activity of CMV IE promoter. EMS A demonstrated that domain 3 is necessary for nuclear localization and DNA binding activity of PDX-1. However, binding of PDX-1 alone to CMV IE promoter was not sufficient to inhibit its transcriptional activity, and other domains of PDX-1 presented were also required. Conclusion: Our data suggested that the DNA binding activity of PDX-1 domain 3 and the cooperative binding of PDX-1 domain 1/2 with other proteins were required for PDX-1 mediated repression of CMV IE promoter.

  15. Cysteine dioxygenase type 1 promotes adipogenesis via interaction with peroxisome proliferator-activated receptor gamma

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Peng; Chen, Yi; Ji, Ning; Lin, Yunfeng; Yuan, Quan; Ye, Ling; Chen, Qianming, E-mail: qmchen@scu.edu.cn

    2015-02-27

    Mammalian cysteine dioxygenase type 1 (CDO1) is an essential enzyme for taurine biosynthesis and the biodegradation of toxic cysteine. As previously suggested, Cdo1 may be a marker of liposarcoma progression and adipogenic differentiation, but the role of Cdo1 in adipogenesis has yet been reported. In this study, we found that the expression of Cdo1 is dramatically elevated during adipogenic differentiation of 3T3-L1 pre-adipocytes and mouse bone marrow-derived mesenchymal stem cells (mBMSCs). Conversely, knockdown of Cdo1 inhibited expression of adipogenic specific genes and lipid droplet formation in 3T3-L1 cells and mBMSCs. Mechanistically, we found Cdo1 interacted with Pparγ in response to adipogenic stimulus. Further, depletion of Cdo1 reduced the recruitment of Pparγ to the promoters of C/EBPα and Fabp4. Collectively, our finding indicates that Cdo1 may be a co-activator of Pparγ in adipogenesis, and may contribute to the development of disease associated with excessive adipose tissue. - Highlights: • Cdo1expression is highly up-regulated during adipogenic differentiation of 3T3-L1 and mBMSCs. • Depletion of Cdo1 inhibited expression of adipogenic specific genes and lipid droplet formation. • Cdo1interacts with Pparγ during adipogenesis. • Knockdown of Cdo1 inhibited Pparγ binding to the promoters of C/EBPα and Fabp4.

  16. Isolation, cDNA cloning, and growth promoting activity of rabbitfish (Siganus guttatus) growth hormone.

    Science.gov (United States)

    Ayson, F G; de Jesus, E G; Amemiya, Y; Moriyama, S; Hirano, T; Kawauchi, H

    2000-02-01

    We report the isolation, cDNA cloning, and growth promoting activity of rabbitfish (Siganus guttatus; Teleostei; Perciformes; Siganidae) growth hormone (GH). Rabbitfish GH was extracted from pituitary glands under alkaline conditions, fractionated by gel filtration chromatography on Sephadex G-100, and purified by high-performance liquid chromatography. The fractions containing GH were identified by immunoblotting with bonito GH antiserum. Under nonreducing conditions, the molecular weight of rabbitfish GH is about 19 kDa as estimated by SDS-PAGE. The purified hormone was potent in promoting growth in rabbitfish fry. Weekly intraperitoneal injections of the hormone significantly accelerated growth. This was evident 3 weeks after the start of the treatment, and its effect was still significant 2 weeks after the treatment was terminated. Rabbitfish GH cDNA was cloned to determine its nucleotide sequence. Excluding the poly (A) tail, rabbitfish GH cDNA is 860 base pairs (bp) long. It contained untranslated regions of 94 and 175 bp in the 5' and 3' ends, respectively. It has an open reading frame of 588 bp coding for a signal peptide of 18 amino acids and a mature protein of 178 amino acid residues. Rabbitfish GH has 4 cysteine residues. On the amino acid level, rabbitfish GH shows high identity (71-74%) with GHs of other perciforms, such as tuna, sea bass, yellow tail, bonito, and tilapia, and less (47-49%) identity with salmonid and carp GHs.

  17. Activation of the ATM-Snail pathway promotes breast cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    Mianen Sun; David A. Engler; Ming Zhan; Stephen T.C. Wong; Li Fu; Bo Xu; Xiaojing Guo; Xiaolong Qian; Haibo Wang; Chunying Yang; Kathryn L. Brinkman; Monica Serrano-Gonzalez; Richard S. Jope; Binhua Zhou

    2012-01-01

    The DNA damage response (DDR) is critical for the maintenance of genetic stability and serves as an anti-cancer barrier during early tumorigenesis.However,the role of the DDR in tumor progression and metastasis is less known.Here,we demonstrate that the ATM kinase,one of the critical DDR elements,is hyperactive in late stage breast tumor tissues with lymph-node metastasis and this hyperactivity correlates with elevated expression of the epitheliai-mesenchymal transition marker,Snail.At the molecular level,we demonstrate that ATM regulates Snail stabilization by phosphorylation on Serine-100.Using mass spectrometry,we identified HSP90 as a critical binding protein of Snail in response to DNA damage.HsP9o binds to and stabilizes phosphorylated Snail.We further provide in vitro and in vivo evidence that activation of ATM-mediated Snail phosphorylation promotes tumor invasion and metastasis.Finally,we demonstrate that Snail Serine-100 phosphorylation is elevated in breast cancer tissues with lymph-node metastasis,indicating clinical significance of the ATM-Snail pathway.Together,our findings provide strong evidence that the ATM-Snail pathway promotes tumor metastasis,highlighting a previously undescribed role of the DDR in tumor invasion and metastasis.

  18. Activated iNKT cells promote memory CD8+ T cell differentiation during viral infection.

    Directory of Open Access Journals (Sweden)

    Emma C Reilly

    Full Text Available α-Galactosylceramide (α-GalCer is the prototypical lipid ligand for invariant NKT cells. Recent studies have proposed that α-GalCer is an effective adjuvant in vaccination against a range of immune challenges, however its mechanism of action has not been completely elucidated. A variety of delivery methods have been examined including pulsing dendritic cells with α-GalCer to optimize the potential of α-GalCer. These methods are currently being used in a variety of clinical trials in patients with advanced cancer but cannot be used in the context of vaccine development against pathogens due to their complexity. Using a simple delivery method, we evaluated α-GalCer adjuvant properties, using the mouse model for cytomegalovirus (MCMV. We measured several key parameters of the immune response to MCMV, including inflammation, effector, and central memory CD8(+ T cell responses. We found that α-GalCer injection at the time of the infection decreases viral titers, alters the kinetics of the inflammatory response, and promotes both increased frequencies and numbers of virus-specific memory CD8(+ T cells. Overall, our data suggest that iNKT cell activation by α-GalCer promotes the development of long-term protective immunity through increased fitness of central memory CD8(+ T cells, as a consequence of reduced inflammation.

  19. Salicylic acid promotes seed germination under high salinity by modulating antioxidant activity in Arabidopsis.

    Science.gov (United States)

    Lee, Sangmin; Kim, Sang-Gyu; Park, Chung-Mo

    2010-10-01

    • Findings regarding the role of salicylic acid (SA) in seed germination are somewhat variable, depending on the plant genotypes and experimental conditions used, and thus the molecular mechanisms underlying SA regulation of germination are still unclear. Here, we report that physiological concentrations of SA promote germination under high salinity by modulating antioxidant activity in Arabidopsis. • Germination of SA induction deficient 2 (sid2) seeds was hypersensitive to high salinity. While the inhibitory effect of high salinity was exaggerated in the presence of higher concentrations of SA (> 100 μM), it was significantly reduced in the presence of lower concentrations of SA (salinity, the endogenous contents of H(2) O(2) were elevated in wild-type and sid2 seeds but reduced to original concentrations after treatment with 1 μM SA. • Germination of NahG transgenic plants was influenced to a lesser degree by high salinity (NahG is a bacterial gene encoding salicylate hydroxylase that converts salicylic acid to catechol). We found that catechol, an SA degradation product accumulated in the transgenic plants, acts as an antioxidant that compromises the inhibitory effects of high salinity. • Our observations indicate that, although SA is not essential for germination under normal growth conditions, it plays a promotive role in seed germination under high salinity by reducing oxidative damage.

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

    Institute of Scientific and Technical Information of China (English)

    LI Yongmei; LI Wenshu; GU Guowei

    2007-01-01

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

  1. Differential effects of Sp cellular transcription factors on viral promoter activation by varicella-zoster virus (VZV) IE62 protein.

    Science.gov (United States)

    Khalil, Mohamed I; Ruyechan, William T; Hay, John; Arvin, Ann

    2015-11-01

    The immediate early (IE) 62 protein is the major varicella-zoster virus (VZV) regulatory factor. Analysis of the VZV genome revealed 40 predicted GC-rich boxes within 36 promoters. We examined effects of ectopic expression of Sp1-Sp4 on IE62- mediated transactivation of three viral promoters. Ectopic expression of Sp3 and Sp4 enhanced IE62 activation of ORF3 and gI promoters while Sp3 reduced IE62 activation of ORF28/29 promoter and VZV DNA replication. Sp2 reduced IE62 transactivation of gI while Sp1 had no significant influence on IE62 activation with any of these viral promoters. Electrophoretic mobility shift assays (EMSA) confirmed binding of Sp1 and Sp3 but not Sp2 and Sp4 to the gI promoter. Sp1-4 bound to IE62 and amino acids 238-258 of IE62 were important for the interaction with Sp3 and Sp4 as well as Sp1. This work shows that Sp family members have differential effects on IE62-mediated transactivation in a promoter-dependent manner.

  2. Proteomic identification of an embryo-specific 1Cys-Prx promoter and analysis of its activity in transgenic rice.

    Science.gov (United States)

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

    2011-04-29

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

  3. 20S proteasome activation promotes life span extension and resistance to proteotoxicity in Caenorhabditis elegans.

    Science.gov (United States)

    Chondrogianni, Niki; Georgila, Konstantina; Kourtis, Nikos; Tavernarakis, Nektarios; Gonos, Efstathios S

    2015-02-01

    Protein homeostasis (proteostasis) is one of the nodal points that need to be preserved to retain physiologic cellular/organismal balance. The ubiquitin-proteasome system (UPS) is responsible for the removal of both normal and damaged proteins, with the proteasome being the downstream effector. The proteasome is the major cellular protease with progressive impairment of function during aging and senescence. Despite the documented age-retarding properties of proteasome activation in various cellular models, simultaneous enhancement of the 20S core proteasome content, assembly, and function have never been reported in any multicellular organism. Consequently, the possible effects of the core proteasome modulation on organismal life span are elusive. In this study, we have achieved activation of the 20S proteasome at organismal level. We demonstrate enhancement of proteasome levels, assembly, and activity in the nematode Caenorhabditis elegans, resulting in life span extension and increased resistance to stress. We also provide evidence that the observed life span extension is dependent on the transcriptional activity of Dauer formation abnormal/Forkhead box class O (DAF-16/FOXO), skinhead-1 (SKN-1), and heat shock factor-1 (HSF-1) factors through regulation of downstream longevity genes. We further show that the reported beneficial effects are not ubiquitous but they are dependent on the genetic context. Finally, we provide evidence that proteasome core activation might be a potential strategy to minimize protein homeostasis deficiencies underlying aggregation-related diseases, such as Alzheimer's disease (AD) or Huntington's disease (HD). In summary, this is the first report demonstrating that 20S core proteasome up-regulation in terms of both content and activity is feasible in a multicellular eukaryotic organism and that in turn this modulation promotes extension of organismal health span and life span.

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

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    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.

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

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    Orlov, Sergey V., E-mail: serge@iem.sp.ru [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation); Mogilenko, Denis A. [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation); Shavva, Vladimir S. [Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation); Dizhe, Ella B.; Ignatovich, Irina A. [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Perevozchikov, Andrej P., E-mail: app@iem.sp.ru [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation)

    2010-07-23

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

  6. A 5A's communication intervention to promote physical activity in underserved populations

    Directory of Open Access Journals (Sweden)

    Carroll Jennifer K

    2012-10-01

    Full Text Available Abstract Background The present study protocol describes the trial design of a clinician training intervention to improve physical activity counseling in underserved primary care settings using the 5As. The 5As (Ask, Advise, Agree, Assist, Arrange are a clinical tool recommended for health behavior counseling in primary care. Methods/Design The study is a two-arm randomized pilot pragmatic trial to examine a primary care clinician communication intervention on use of the 5As in discussion of physical activity in audio-recorded office visits in an ethnically diverse, low-income patient population. The study setting consists of two federally qualified community health centers in Rochester, NY. Eligible clinicians (n=15 are recruited and randomized into two groups. Group 1 clinicians participate in the training intervention first; Group 2 clinicians receive the intervention six months later. The intervention and its outcomes are informed by self-determination theory and principles of patient-centered communication. Assessment of outcomes is blinded. The primary outcome will be the frequency and quality of 5As discussions as judged by evaluating 375 audio-recorded patient visits distributed over baseline and in the post-intervention period (immediately post and at six months. Secondary outcomes will be changes in patients’ perceived competence to increase physical activity (Aim 2 and patients and clinicians beliefs regarding whether pertinent barriers to promoting exercise have been reduced. (Aim 3. Exploratory outcomes (Aim 4 are potential mediators of the intervention’s effect and whether the intervention affects actual enrollment in the community program recommended for exercise. The analysis will use repeated measures (in the form of recorded office visits from each clinician at each time point and aggregate measures of Groups 1 and 2 over time. Discussion Results will help elucidate the role of 5As communication training for clinicians on

  7. Promotion of physical activity in a developing country: the Agita São Paulo experience.

    Science.gov (United States)

    Matsudo, Victor; Matsudo, Sandra; Andrade, Douglas; Araujo, Timoteo; Andrade, Erinaldo; de Oliveira, Luis Carlos; Braggion, Glaucia

    2002-02-01

    The purpose of this paper is to present key points of an intervention programme (Agita São Paulo Program) to promote physical activity in a developing country. Agita is a multi-level, community-wide intervention designed to increase knowledge about the benefits and the level of physical activity in a mega-population of 34 million inhabitants of São Paulo State, Brazil. The main message was taken from the Centers for Disease Control/American College of Sports Medicine (CDC/ACSM) recommendation that: 'everyone should accumulate at least 30 minutes of physical activity, on most days of the weeks, of moderate intensity, in one single or in multiple sessions'. Activities were encouraged in three settings: home, transport and leisure time. Focus groups were students from elementary schools through to college, white and blue collar workers, and elderly people. Innovative aspects included: (1) a research centre leading the process, (2) scientific and institutional partnerships (over 160 groups), (3) a feasible approach--the 'one-step-ahead' model, (4) empowerment, (5) inclusion, (6) non-paid media, (7) social marketing, and (8) culture-linked. Data were obtained from 645 random, home-based questionnaires over four years--stratified by sex, age, education and socio-economic level. These data show that the Agita message reached 55.7% of the population, and among these, 23.1% knew the main message. Recall of Agita and knowledge of its purpose were well distributed among different socioeconomic levels, being known by 67% of the most educated. The prevalence of people reaching the recommendation was 54.8% (men 48.7%, women 61%); and risk of being sedentary was quite smaller among those who knew the Agita message (7.1%) compared with those who did not know (13.1%). In conclusion, based upon the Agita São Paulo experience, it appears that a multi-level, community-wide intervention to promote physical activity may obtain good results if the model contains the items listed above.

  8. Nickel-doped ceria nanoparticles for promoting catalytic activity of Pt/C for ethanol electrooxidation

    Science.gov (United States)

    Tan, Qiang; Du, Chunyu; Sun, Yongrong; Du, Lei; Yin, Geping; Gao, Yunzhi

    2014-10-01

    This paper reports the facile synthesis of monodispersed nickel-doped ceria nanoparticles by a thermal decomposition method, which is used to promote catalytic properties of Pt/C. The Pt/Ni-doped CeO2/C catalyst obtained exhibits remarkably high activity and stability towards the ethanol electrooxidation in acidic media. This is attributed to higher oxygen releasing capacity and stronger interaction of Ni-doped CeO2 with Pt than pure CeO2 nanoparticles that contribute positively to the removal of poisoning intermediates. We believe that the design concept and synthetic strategy of metal doped oxides used for fuel cell catalysts can be potentially extended to other catalytic fields.

  9. 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.

  10. Maggot debridement therapy promotes diabetic foot wound healing by up-regulating endothelial cell activity.

    Science.gov (United States)

    Sun, Xinjuan; Chen, Jin'an; Zhang, Jie; Wang, Wei; Sun, Jinshan; Wang, Aiping

    2016-03-01

    To determine the role of maggot debridement therapy (MDT) on diabetic foot wound healing, we compared growth related factors in wounds before and after treatment. Furthermore, we utilized human umbilical vein endothelial cells (HUVECs) to explore responses to maggot excretions/secretions on markers of angiogenesis and proliferation. The results showed that there was neo-granulation and angiogenesis in diabetic foot wounds after MDT. Moreover, significant elevation in CD34 and CD68 levels was also observed in treated wounds. In vitro, ES increased HUVEC proliferation, improved tube formation, and increased expression of vascular endothelial growth factor receptor 2 in a dose dependent manner. These results demonstrate that MDT and maggot ES can promote diabetic foot wound healing by up-regulating endothelial cell activity.

  11. CHIP promotes thyroid cancer proliferation via activation of the MAPK and AKT pathways.

    Science.gov (United States)

    Zhang, Li; Liu, Lianyong; He, Xiaohua; Shen, Yunling; Liu, Xuerong; Wei, Jing; Yu, Fang; Tian, Jianqing

    2016-08-26

    The carboxyl terminus of Hsp70-interacting protein (CHIP) is a U box-type ubiquitin ligase that plays crucial roles in various biological processes, including tumor progression. To date, the functional mechanism of CHIP in thyroid cancer remains unknown. Here, we obtained evidence of upregulation of CHIP in thyroid cancer tissues and cell lines. CHIP overexpression markedly enhanced thyroid cancer cell viability and colony formation in vitro and accelerated tumor growth in vivo. Conversely, CHIP knockdown impaired cell proliferation and tumor growth. Notably, CHIP promoted cell growth through activation of MAPK and AKT pathways, subsequently decreasing p27 and increasing cyclin D1 and p-FOXO3a expression. Our findings collectively indicate that CHIP functions as an oncogene in thyroid cancer, and is therefore a potential therapeutic target for this disease.

  12. Promotion of protein crystal growth by actively switching crystal growth mode via femtosecond laser ablation

    Science.gov (United States)

    Tominaga, Yusuke; Maruyama, Mihoko; Yoshimura, Masashi; Koizumi, Haruhiko; Tachibana, Masaru; Sugiyama, Shigeru; Adachi, Hiroaki; Tsukamoto, Katsuo; Matsumura, Hiroyoshi; Takano, Kazufumi; Murakami, Satoshi; Inoue, Tsuyoshi; Yoshikawa, Hiroshi Y.; Mori, Yusuke

    2016-11-01

    Large single crystals with desirable shapes are essential for various scientific and industrial fields, such as X-ray/neutron crystallography and crystalline devices. However, in the case of proteins the production of such crystals is particularly challenging, despite the efforts devoted to optimization of the environmental, chemical and physical parameters. Here we report an innovative approach for promoting the growth of protein crystals by directly modifying the local crystal structure via femtosecond laser ablation. We demonstrate that protein crystals with surfaces that are locally etched (several micrometers in diameter) by femtosecond laser ablation show enhanced growth rates without losing crystal quality. Optical phase-sensitive microscopy and X-ray topography imaging techniques reveal that the local etching induces spiral growth, which is energetically advantageous compared with the spontaneous two-dimensional nucleation growth mode. These findings prove that femtosecond laser ablation can actively switch the crystal growth mode, offering flexible control over the size and shape of protein crystals.

  13. Promoting active learning of graduate student by deep reading in biochemistry and microbiology pharmacy curriculum.

    Science.gov (United States)

    Peng, Ren

    2017-01-06

    To promote graduate students' active learning, deep reading of high quality papers was done by graduate students enrolled in biochemistry and microbiology pharmacy curriculum offered by college of life science, Jiangxi Normal University from 2013 to 2015. The number of graduate students, who participated in the course in 2013, 2014, and 2015 were eleven, thirteen and fifteen, respectively. Through deep reading of papers, presentation, and group discussion in the lecture, these graduate students have improved their academic performances effectively, such as literature search, PPT document production, presentation management, specialty document reading, academic inquiry, and analytical and comprehensive ability. The graduate students also have increased their understanding level of frontier research, scientific research methods, and experimental methods. © 2017 by The International Union of Biochemistry and Molecular Biology, 2017.

  14. Activities for the Promotion of Gender Equality in Japan—Physical Society of Japan

    Science.gov (United States)

    Agui, Akane; Tanida, Kiyoshi; Torikai, Eiko

    2005-10-01

    The Gender Equality Promotion Committee of the Physical Society of Japan (JPS) was established as a result of the First International IUPAP Conference on Women in Physics (Paris, 2002). It is a gender-balanced team of 12 full members and a group of net-commentators. The former chairperson of the committee, Masako Bando, was selected to be the president of JPS between September 2006 and August 2007. Based on the survey on the present status of the gender equality and the research environment of the JPS members in 2001, JPS advanced two recommendations to the governmental authorities, academic institutes, and organizations: for flexible childcare supports and for improved research granting systems for post-doctoral fellows and part-time researchers in August 2003. Now these activities have become nationwide with the establishment in October 2002 of the Japan Inter-Society Liaison Association Committee for Promoting Equal Participation of Men and Women in Science and Engineering (EPMEWSE). It has 44 member societies, including 19 observers, from various academic fields. An extended survey was carried out by EPMEWSE in November 2003; 20,000 respondents revealed diverse visions of scientists and engineers. These activities effectively help foster public understanding and awareness of the state of women in physics, especially among policy-making authorities. In 2005 the Cabinet is drawing up two Basic Plans for 2006-2010: the Science and Technology Basic Plan for the third term and the Basic Plan for the Gender-Equal Society for the second term. To attract girls into science and engineering, JPS is organizing the Girls Science Summer School to be held in August 2005 in collaboration with the National Women Education Center and EPMEWSE.

  15. Activating chronic kidney disease patients and family members through the Internet to promote integration of care

    Directory of Open Access Journals (Sweden)

    Michael Trisolini

    2004-10-01

    Full Text Available Purpose: To describe the potential role of the Internet as a vehicle for improving integration of care through activating chronic kidney disease patients and their family members. Also, to describe how that potential is being developed through a website sponsored by the Medicare program in the United States. Background: The Internet is expanding at a rapid rate, and health-related websites are one of its most popular features. Efforts to promote integration of care have focused mainly on providers up to now, and more emphasis is needed on the potential roles of patients. Chronically ill patients have particular needs for improved education about their conditions and enhanced involvement in care planning and treatment decisions. Medicare developed the Dialysis Facility Compare website to serve those goals for people with chronic kidney disease. Methods: We conducted qualitative research with 140 chronic kidney disease patients and family members, and 130 renal care professionals to evaluate and improve the Dialysis Facility Compare website. A series of 19 focus groups, 13 triads (small focus groups, and 56 individual interviews were conducted in four regions of the United States and by telephone. Results: We found that the Dialysis Facility Compare website has the potential to improve integration of care for people with chronic kidney disease in at least three ways. First: by expanding the roles of patients as members of the multi-disciplinary team of caregivers treating their disease. Second: through better integration of the informal care provided in the home and community with the formal care provided by health professionals. Third: by improving coordination of between care provided in the pre-dialysis and dialysis phases of the disease. Discussion: We developed recommendations for revising and enhancing the Dialysis Facility Compare website in a number of ways to better promote patient activation and integration of care. The unique features

  16. Drosophila pico and its mammalian ortholog lamellipodin activate serum response factor and promote cell proliferation.

    Science.gov (United States)

    Lyulcheva, Ekaterina; Taylor, Eleanor; Michael, Magdalene; Vehlow, Anne; Tan, Shengjiang; Fletcher, Adam; Krause, Matthias; Bennett, Daimark

    2008-11-01

    MIG-10/RIAM/lamellipodin (MRL) proteins link activated Ras-GTPases with actin regulatory Ena/VASP proteins to induce local changes in cytoskeletal dynamics and cell motility. MRL proteins alter monomeric (G):filamentous (F) actin ratios, but the impact of these changes had not been fully appreciated. We report here that the Drosophila MRL ortholog, pico, is required for tissue and organismal growth. Reduction in pico levels resulted in reduced cell division rates, growth retardation, increased G:F actin ratios and lethality. Conversely, pico overexpression reduced G:F actin ratios and promoted tissue overgrowth in an epidermal growth factor (EGF) receptor (EGFR)-dependent manner. Consistently, in HeLa cells, lamellipodin was required for EGF-induced proliferation. We show that pico and lamellipodin share the ability to activate serum response factor (SRF), a transcription factor that responds to reduced G:F-actin ratios via its co-factor Mal. Genetics data indicate that mal/SRF levels are important for pico-mediated tissue growth. We propose that MRL proteins link EGFR activation to mitogenic SRF signaling via changes in actin dynamics.

  17. Inhibition of Nischarin Expression Promotes Neurite Outgrowth through Regulation of PAK Activity.

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    Yuemin Ding

    Full Text Available Nischarin is a cytoplasmic protein expressed in various organs that plays an inhibitory role in cell migration and invasion and the carcinogenesis of breast cancer cells. We previously reported that Nischarin is highly expressed in neuronal cell lines and is differentially expressed in the brain tissue of adult rats. However, the physiological function of Nischarin in neural cells remains unknown. Here, we show that Nischarin is expressed in rat primary cortical neurons but not in astrocytes. Nischarin is localized around the nucleus and dendrites. Using shRNA to knockdown the expression of endogenous Nischarin significantly increases the percentage of neurite-bearing cells, remarkably increases neurite length, and accelerates neurite extension in neuronal cells. Silencing Nischarin expression also promotes dendrite elongation in rat cortical neurons where Nischarin interacts with p21-activated kinase 1/2 (PAK1/2 and negatively regulates phosphorylation of both PAK1 and PAK2. The stimulation of neurite growth observed in cells with decreased levels of Nischarin is partially abolished by IPA3-mediated inhibition of PAK1 activity. Our findings indicate that endogenous Nischarin inhibits neurite outgrowth by blocking PAK1 activation in neurons.

  18. Drosophila Pico and Its Mammalian Ortholog Lamellipodin Activate Serum Response Factor and Promote Cell Proliferation

    Science.gov (United States)

    Lyulcheva, Ekaterina; Taylor, Eleanor; Michael, Magdalene; Vehlow, Anne; Tan, Shengjiang; Fletcher, Adam; Krause, Matthias; Bennett, Daimark

    2008-01-01

    Summary MIG-10/RIAM/lamellipodin (MRL) proteins link activated Ras-GTPases with actin regulatory Ena/VASP proteins to induce local changes in cytoskeletal dynamics and cell motility. MRL proteins alter monomeric (G):filamentous (F) actin ratios, but the impact of these changes had not been fully appreciated. We report here that the Drosophila MRL ortholog, pico, is required for tissue and organismal growth. Reduction in pico levels resulted in reduced cell division rates, growth retardation, increased G:F actin ratios and lethality. Conversely, pico overexpression reduced G:F actin ratios and promoted tissue overgrowth in an epidermal growth factor (EGF) receptor (EGFR)-dependent manner. Consistently, in HeLa cells, lamellipodin was required for EGF-induced proliferation. We show that pico and lamellipodin share the ability to activate serum response factor (SRF), a transcription factor that responds to reduced G:F-actin ratios via its co-factor Mal. Genetics data indicate that mal/SRF levels are important for pico-mediated tissue growth. We propose that MRL proteins link EGFR activation to mitogenic SRF signaling via changes in actin dynamics. PMID:19000833

  19. IL-15 promotes activation and expansion of CD8+ T cells in HIV-1 infection

    Science.gov (United States)

    Younes, Souheil-Antoine; Freeman, Michael L.; Mudd, Joseph C.; Shive, Carey L.; Reynaldi, Arnold; Estes, Jacob D.; Deleage, Claire; Lucero, Carissa; Anderson, Jodi; Schacker, Timothy W.; Davenport, Miles P.; McCune, Joseph M.; Hunt, Peter W.; Lee, Sulggi A.; Debernardo, Robert L.; Jacobson, Jeffrey M.; Canaday, David H.; Sekaly, Rafick-Pierre; Sieg, Scott F.; Lederman, Michael M.

    2016-01-01

    In HIV-1–infected patients, increased numbers of circulating CD8+ T cells are linked to increased risk of morbidity and mortality. Here, we identified a bystander mechanism that promotes CD8 T cell activation and expansion in untreated HIV-1–infected patients. Compared with healthy controls, untreated HIV-1–infected patients have an increased population of proliferating, granzyme B+, CD8+ T cells in circulation. Vβ expression and deep sequencing of CDR3 revealed that in untreated HIV-1 infection, cycling memory CD8 T cells possess a broad T cell repertoire that reflects the repertoire of the resting population. This suggests that cycling is driven by bystander activation, rather than specific antigen exposure. Treatment of peripheral blood mononuclear cells with IL-15 induced a cycling, granzyme B+ phenotype in CD8+ T cells. Moreover, elevated IL-15 expression in the lymph nodes of untreated HIV-1–infected patients correlated with circulating CD8+ T cell counts and was normalized in these patients following antiretroviral therapy. Together, these results suggest that IL-15 drives bystander activation of CD8+ T cells, which predicts disease progression in untreated HIV-1–infected patients and suggests that elevated IL-15 may also drive CD8+ T cell expansion that is linked to increased morbidity and mortality in treated patients. PMID:27322062

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

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    He Zhang

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

  1. Strategy to combat obesity and to promote physical activity in Arab countries

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    Abdulrahman O Musaiger

    2011-03-01

    Full Text Available Abdulrahman O Musaiger1, Hazzaa M Al Hazzaa2, Aayed Al-Qahtani3, Jalila Elati4, Jasem Ramadan5, Nebal A AboulElla6, Najat Mokhtar7, Hashem A Kilani81Arab Center for Nutrition, Bahrain; 2,3King Saud University, Saudi Arabia, 4National Institute of Nutrition, Tunisia; 5University of Kuwait, Kuwait; 6National Nutrition Institute, Egypt; 7Ibn Tofail University, Morocco; 8Sultan Qaboos University, OmanAbstract: Obesity has become a major public health problem in the Arab countries, creating a health and economic burden on these countries’ government services. There is an urgent need to develop a strategy for prevention and control of obesity. The third Arab Conference on Obesity and Physical Activity was held in Bahrain in January 2010, and proposed the Strategy to Combat Obesity and Promote Physical Activity in Arab Countries. This strategy provides useful guidelines for each Arab country to prepare its own strategy or plan of action to prevent and control obesity. The strategy focused on expected outcomes, objectives, indicators to measure the objectives, and action needs for 9 target areas: child-care centers for preschool children, schools, primary health care, secondary care, food companies, food preparation institutes, media, public benefit organizations, and the workplace. Follow-up and future developments of this strategy were also included.Keywords: obesity, physical activity, strategy, Arab countries

  2. Lamin A Is an Endogenous SIRT6 Activator and Promotes SIRT6-Mediated DNA Repair

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    Shrestha Ghosh

    2015-11-01

    Full Text Available The nuclear lamins are essential for various molecular events in the nucleus, such as chromatin organization, DNA replication, and provision of mechanical support. A specific point mutation in the LMNA gene creates a truncated prelamin A termed progerin, causing Hutchinson-Gilford progeria syndrome (HGPS. SIRT6 deficiency leads to defective genomic maintenance and accelerated aging similar to HGPS, suggesting a potential link between lamin A and SIRT6. Here, we report that lamin A is an endogenous activator of SIRT6 and facilitates chromatin localization of SIRT6 upon DNA damage. Lamin A promotes SIRT6-dependent DNA-PKcs (DNA-PK catalytic subunit recruitment to chromatin, CtIP deacetylation, and PARP1 mono-ADP ribosylation in response to DNA damage. The presence of progerin jeopardizes SIRT6 activation and compromises SIRT6-mediated molecular events in response to DNA damage. These data reveal a critical role for lamin A in regulating SIRT6 activities, suggesting that defects in SIRT6 functions contribute to impaired DNA repair and accelerated aging in HGPS.

  3. Expressing activity of promoter elements of large intergenic region from cotton leaf curl virus in host plant*

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Cotton leaf curl virus (CLCuV) is a type of single-stranded DNAvirus, belonging to geminivirus of subgroup III. In order to determine the function of CLCuV large intergenic region (LIR), total DNA of CLCuV-infected cotton leaves was used as template, and fragment of LIR was obtained by PCR and inserted into clone vector. The fragment of LIR was fused with gus reporter gene and nos terminator in the orientation of transcription of virion sense and complementary sense respectively, and the plant expression vectors were constructed. GUS activity of Agrobacterium-mediated transgenic tobacco was measured. The result indicated that LIR showed strong promoter activity in complementary sense gene orientation. Average GUS activity of the complementary sense promoter was 5-6 times that of CaMV 35S promoter, and the highest GUS activity of individual plant was ten times of that of CaMV 35S promoter. Histochemical localization confirmed its activity in both mesophyll and vascular tissues. Activity of virion sense of LIR was rather low. Thus LIR isolated from CLCuV could be used as a novel strong promoter in plant genetic manipulation.

  4. SWI/SNF enzymes promote SOX10- mediated activation of myelin gene expression.

    Science.gov (United States)

    Marathe, Himangi G; Mehta, Gaurav; Zhang, Xiaolu; Datar, Ila; Mehrotra, Aanchal; Yeung, Kam C; de la Serna, Ivana L

    2013-01-01

    SOX10 is a Sry-related high mobility (HMG)-box transcriptional regulator that promotes differentiation of neural crest precursors into Schwann cells, oligodendrocytes, and melanocytes. Myelin, formed by Schwann cells in the peripheral nervous system, is essential for propagation of nerve impulses. SWI/SNF complexes are ATP dependent chromatin remodeling enzymes that are critical for cellular differentiation. It was recently demonstrated that the BRG1 subunit of SWI/SNF complexes activates SOX10 expression and also interacts with SOX10 to activate expression of OCT6 and KROX20, two transcriptional regulators of Schwann cell differentiation. To determine the requirement for SWI/SNF enzymes in the regulation of genes that encode components of myelin, which are downstream of these transcriptional regulators, we introduced SOX10 into fibroblasts that inducibly express dominant negative versions of the SWI/SNF ATPases, BRM or BRG1. Dominant negative BRM and BRG1 have mutations in the ATP binding site and inhibit gene activation events that require SWI/SNF function. Ectopic expression of SOX10 in cells derived from NIH 3T3 fibroblasts led to the activation of the endogenous Schwann cell specific gene, myelin protein zero (MPZ) and the gene that encodes myelin basic protein (MBP). Thus, SOX10 reprogrammed these cells into myelin gene expressing cells. Ectopic expression of KROX20 was not sufficient for activation of these myelin genes. However, KROX20 together with SOX10 synergistically activated MPZ and MBP expression. Dominant negative BRM and BRG1 abrogated SOX10 mediated activation of MPZ and MBP and synergistic activation of these genes by SOX10 and KROX20. SOX10 was required to recruit BRG1 to the MPZ locus. Similarly, in immortalized Schwann cells, BRG1 recruitment to SOX10 binding sites at the MPZ locus was dependent on SOX10 and expression of dominant negative BRG1 inhibited expression of MPZ and MBP in these cells. Thus, SWI/SNF enzymes cooperate with SOX10 to

  5. SWI/SNF enzymes promote SOX10- mediated activation of myelin gene expression.

    Directory of Open Access Journals (Sweden)

    Himangi G Marathe

    Full Text Available SOX10 is a Sry-related high mobility (HMG-box transcriptional regulator that promotes differentiation of neural crest precursors into Schwann cells, oligodendrocytes, and melanocytes. Myelin, formed by Schwann cells in the peripheral nervous system, is essential for propagation of nerve impulses. SWI/SNF complexes are ATP dependent chromatin remodeling enzymes that are critical for cellular differentiation. It was recently demonstrated that the BRG1 subunit of SWI/SNF complexes activates SOX10 expression and also interacts with SOX10 to activate expression of OCT6 and KROX20, two transcriptional regulators of Schwann cell differentiation. To determine the requirement for SWI/SNF enzymes in the regulation of genes that encode components of myelin, which are downstream of these transcriptional regulators, we introduced SOX10 into fibroblasts that inducibly express dominant negative versions of the SWI/SNF ATPases, BRM or BRG1. Dominant negative BRM and BRG1 have mutations in the ATP binding site and inhibit gene activation events that require SWI/SNF function. Ectopic expression of SOX10 in cells derived from NIH 3T3 fibroblasts led to the activation of the endogenous Schwann cell specific gene, myelin protein zero (MPZ and the gene that encodes myelin basic protein (MBP. Thus, SOX10 reprogrammed these cells into myelin gene expressing cells. Ectopic expression of KROX20 was not sufficient for activation of these myelin genes. However, KROX20 together with SOX10 synergistically activated MPZ and MBP expression. Dominant negative BRM and BRG1 abrogated SOX10 mediated activation of MPZ and MBP and synergistic activation of these genes by SOX10 and KROX20. SOX10 was required to recruit BRG1 to the MPZ locus. Similarly, in immortalized Schwann cells, BRG1 recruitment to SOX10 binding sites at the MPZ locus was dependent on SOX10 and expression of dominant negative BRG1 inhibited expression of MPZ and MBP in these cells. Thus, SWI/SNF enzymes cooperate

  6. Flavonoid Compound Icariin Activates Hypoxia Inducible Factor-1α in Chondrocytes and Promotes Articular Cartilage Repair.

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    Pengzhen Wang

    Full Text Available Articular cartilage has poor capability for repair following trauma or degenerative pathology due to avascular property, low cell density and migratory ability. Discovery of novel therapeutic approaches for articular cartilage repair remains a significant clinical need. Hypoxia is a hallmark for cartilage development and pathology. Hypoxia inducible factor-1alpha (HIF-1α has been identified as a key mediator for chondrocytes to response to fluctuations of oxygen availability during cartilage development or repair. This suggests that HIF-1α may serve as a target for modulating chondrocyte functions. In this study, using phenotypic cellular screen assays, we identify that Icariin, an active flavonoid component from Herba Epimedii, activates HIF-1α expression in chondrocytes. We performed systemic in vitro and in vivo analysis to determine the roles of Icariin in regulation of chondrogenesis. Our results show that Icariin significantly increases hypoxia responsive element luciferase reporter activity, which is accompanied by increased accumulation and nuclear translocation of HIF-1α in murine chondrocytes. The phenotype is associated with inhibiting PHD activity through interaction between Icariin and iron ions. The upregulation of HIF-1α mRNA levels in chondrocytes persists during chondrogenic differentiation for 7 and 14 days. Icariin (10-6 M increases the proliferation of chondrocytes or chondroprogenitors examined by MTT, BrdU incorporation or colony formation assays. Icariin enhances chondrogenic marker expression in a micromass culture including Sox9, collagen type 2 (Col2α1 and aggrecan as determined by real-time PCR and promotes extracellular matrix (ECM synthesis indicated by Alcian blue staining. ELISA assays show dramatically increased production of aggrecan and hydroxyproline in Icariin-treated cultures at day 14 of chondrogenic differentiation as compared with the controls. Meanwhile, the expression of chondrocyte catabolic

  7. Methylation of DACT2 promotes papillary thyroid cancer metastasis by activating Wnt signaling.

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    Zhiyan Zhao

    Full Text Available Thyroid cancer is the most common endocrine malignant disease and the incidence is increasing. DACT2 was found frequently methylated in human lung cancer and hepatocellular carcinoma. To explore the epigenetic change and the role of DACT2 in thyroid cancer, 7 thyroid cancer cell lines, 10 cases of non-cancerous thyroid tissue samples and 99 cases of primary thyroid cancer samples were involved in this study. DACT2 was expressed and unmethylated in K1, SW579, FTC-133, TT, W3 and 8505C cell lines. Loss of expression and complete methylation was found in TPC-1 cells. Restoration of DACT2 expression was induced by 5-aza-2'deoxycytidine treatment. It demonstrates that the expression of DACT2 was regulated by promoter region methylation. In human primary papillary thyroid cancer, 64.6% (64/99 was methylated and methylation of DACT2 was related to lymph node metastasis (p<0.01. Re-expression of DACT2 suppresses cell proliferation, invasion and migration in TPC-1 cells. The activity of TCF/LEF was inhibited by DACT2 in wild-type or mutant β-catenin cells. The activity of TCF/LEF was increased by co-transfecting DACT2 and Dvl2 in wild-type or mutant β-catenin cells. Overexpression of wild-type β-catenin promotes cell migration and invasion in DACT2 stably expressed cells. The expression of β-catenin, c-myc, cyclinD1 and MMP-9 were decreased and the level of phosphorylated β-catenin (p-β-catenin was increased after restoration of DACT2 expression in TPC-1 cells. The expression of β-catenin, c-myc, cyclinD1 and MMP-9 were increased and the level of p-β-catenin was reduced after knockdown of DACT2 in W3 and SW579 cells. These results suggest that DACT2 suppresses human papillary thyroid cancer growth and metastasis by inhibiting Wnt signaling. In conclusion, DACT2 is frequently methylated in papillary thyroid cancer. DACT2 expression was regulated by promoter region methylation. DACT2 suppresses papillary thyroid cancer proliferation and metastasis

  8. Incorporation of RANKL promotes osteoclast formation and osteoclast activity on β-TCP ceramics.

    Science.gov (United States)

    Choy, John; Albers, Christoph E; Siebenrock, Klaus A; Dolder, Silvia; Hofstetter, Wilhelm; Klenke, Frank M

    2014-12-01

    β-Tricalcium phosphate (β-TCP) ceramics are approved for the repair of osseous defects. In large defects, however, the substitution of the material by authentic bone is inadequate to provide sufficient long-term mechanical stability. We aimed to develop composites of β-TCP ceramics and receptor activator of nuclear factor κ-B ligand (RANKL) to enhance the formation of osteoclasts and promote cell mediated calcium phosphate resorption. RANKL was adsorbed superficially onto β-TCP ceramics or incorporated into a crystalline layer of calcium phosphate by the use of a co-precipitation technique. Murine osteoclast precursors were seeded onto the ceramics. After 15 days, the formation of osteoclasts was quantified cytologically and colorimetrically with tartrate-resistant acidic phosphatase (TRAP) staining and TRAP activity measurements, respectively. Additionally, the expression of transcripts encoding the osteoclast gene products cathepsin K, calcitonin receptor, and of the sodium/hydrogen exchanger NHA2 were quantified by real-time PCR. The activity of newly formed osteoclasts was evaluated by means of a calcium phosphate resorption assay. Superficially adsorbed RANKL did not induce the formation of osteoclasts on β-TCP ceramics. When co-precipitated onto β-TCP ceramics RANKL supported the formation of mature osteoclasts. The development of osteoclast lineage cells was further confirmed by the increased expression of cathepsin K, calcitonin receptor, and NHA2. Incorporated RANKL stimulated the cells to resorb crystalline calcium phosphate. Our in vitro study shows that RANKL incorporated into β-TCP ceramics induces the formation of active, resorbing osteoclasts on the material surface. Once formed, osteoclasts mediate the release of RANKL thereby perpetuating their differentiation and activation. In vivo, the stimulation of osteoclast-mediated resorption may contribute to a coordinated sequence of material resorption and bone formation. Further in vivo studies

  9. Social transfer of pathogenic fungus promotes active immunisation in ant colonies.

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    Matthias Konrad

    Full Text Available Due to the omnipresent risk of epidemics, insect societies have evolved sophisticated disease defences at the individual and colony level. An intriguing yet little understood phenomenon is that social contact to pathogen-exposed individuals reduces susceptibility of previously naive nestmates to this pathogen. We tested whether such social immunisation in Lasius ants against the entomopathogenic fungus Metarhizium anisopliae is based on active upregulation of the immune system of nestmates following contact to an infectious individual or passive protection via transfer of immune effectors among group members--that is, active versus passive immunisation. We found no evidence for involvement of passive immunisation via transfer of antimicrobials among colony members. Instead, intensive allogrooming behaviour between naive and pathogen-exposed ants before fungal conidia firmly attached to their cuticle suggested passage of the pathogen from the exposed individuals to their nestmates. By tracing fluorescence-labelled conidia we indeed detected frequent pathogen transfer to the nestmates, where they caused low-level infections as revealed by growth of small numbers of fungal colony forming units from their dissected body content. These infections rarely led to death, but instead promoted an enhanced ability to inhibit fungal growth and an active upregulation of immune genes involved in antifungal defences (defensin and prophenoloxidase, PPO. Contrarily, there was no upregulation of the gene cathepsin L, which is associated with antibacterial and antiviral defences, and we found no increased antibacterial activity of nestmates of fungus-exposed ants. This indicates that social immunisation after fungal exposure is specific, similar to recent findings for individual-level immune priming in invertebrates. Epidemiological modeling further suggests that active social immunisation is adaptive, as it leads to faster elimination of the disease and lower

  10. Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity.

    Science.gov (United States)

    McCarty, M F

    1999-12-01

    Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets

  11. TERT promoter mutations lead to high transcriptional activity under hypoxia and temozolomide treatment and predict poor prognosis in gliomas.

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    Chen Chen

    Full Text Available This study explored the effects of telomerase reverse transcriptase (TERT promoter mutations on transcriptional activity of the TERT gene under hypoxic and temozolomide (TMZ treatment conditions, and investigated the status and prognostic value of these mutations in gliomas.The effect of TERT promoter mutations on the transcriptional activity of the TERT gene under hypoxic and TMZ treatment conditions was investigated in glioma cells using the luciferase assay. TERT promoter mutations were detected in 101 glioma samples (grades I-IV and 49 other brain tumors by sequencing. TERT mRNA expression in gliomas was examined by real-time PCR. Hazard ratios from survival analysis of glioma patients were determined relative to the presence of TERT promoter mutations.Mutations in the TERT promoter enhanced gene transcription even under hypoxic and TMZ treatment conditions, inducing upregulation of TERT mRNA expression. Mutations were detected in gliomas, but not in meningiomas, pituitary adenomas, cavernomas, intracranial metastases, normal brain tissues, or peripheral blood of glioma patients. Patients with TERT promoter mutations had lower survival rates, even after adjusting for other known or potential risk factors, and the incidence of mutation was correlated with patient age.TERT promoter mutations were specific to gliomas. TERT promoter mutations maintained its ability of inducing high transcriptional activity even under hypoxic and TMZ treatment conditions, and the presence of mutations was associated with poor prognosis in glioma patients. These findings demonstrate that TERT promoter mutations are novel prognostic markers for gliomas that can inform prospective therapeutic strategies.

  12. Bioinformatics based structural characterization of glucose dehydrogenase (gdh) gene and growth promoting activity of Leclercia sp. QAU-66.

    Science.gov (United States)

    Naveed, Muhammad; Ahmed, Iftikhar; Khalid, Nauman; Mumtaz, Abdul Samad

    2014-01-01

    Glucose dehydrogenase (GDH; EC 1.1. 5.2) is the member of quinoproteins group that use the redox cofactor pyrroloquinoline quinoine, calcium ions and glucose as substrate for its activity. In present study, Leclercia sp. QAU-66, isolated from rhizosphere of Vigna mungo, was characterized for phosphate solubilization and the role of GDH in plant growth promotion of Phaseolus vulgaris. The strain QAU-66 had ability to solubilize phosphorus and significantly (p ≤ 0.05) promoted the shoot and root lengths of Phaseolus vulgaris. The structural determination of GDH protein was carried out using bioinformatics tools like Pfam, InterProScan, I-TASSER and COFACTOR. These tools predicted the structural based functional homology of pyrroloquinoline quinone domains in GDH. GDH of Leclercia sp. QAU-66 is one of the main factor that involved in plant growth promotion and provides a solid background for further research in plant growth promoting activities.

  13. Health Promotion Efforts as Predictors of Physical Activity in Schools: An Application of the Diffusion of Innovations Model

    Science.gov (United States)

    Glowacki, Elizabeth M.; Centeio, Erin E.; Van Dongen, Daniel J.; Carson, Russell L.; Castelli, Darla M.

    2016-01-01

    Background: Implementing a comprehensive school physical activity program (CSPAP) effectively addresses public health issues by providing opportunities for physical activity (PA). Grounded in the Diffusion of Innovations model, the purpose of this study was to identify how health promotion efforts facilitate opportunities for PA. Methods: Physical…

  14. Perspectives of Constraining and Enabling Factors for Health-Promoting Physical Activity by Adults with Intellectual Disability

    Science.gov (United States)

    Temple, Viviene A.; Walkley, Jeff W.

    2007-01-01

    Background: Physical activity influences health in individuals and within populations. This study explored factors perceived as enabling or inhibiting participation in physical activity by adults with intellectual disability from a health promotion perspective. Method: Six focus group interviews were conducted: adults with intellectual disability…

  15. Evaluation of a web-based program promoting healthy eating and physical activity for adolescents: Teen Choice: Food and Fitness

    Science.gov (United States)

    This randomized clinical trial tested the impact of a website promoting nutrition and physical activity for adolescents (Teen Choice: Food and Fitness). Participants, 408 12- to 17-year-old adolescents in the Houston area, completed online surveys measuring diet, physical activity, sedentary behavio...

  16. Promoting Leisure Physical Activity Participation among Adults with Intellectual Disabilities: Validation of Self-Efficacy and Social Support Scales

    Science.gov (United States)

    Peterson, Jana J.; Peterson, N. Andrew; Lowe, John B.; Nothwehr, Faryle K.

    2009-01-01

    Background: Many individuals with intellectual disabilities are not sufficiently active for availing health benefits. Little is known about correlates of physical activity among this population on which to build health promotion interventions. Materials and Methods: We developed scales for measurement of self-efficacy and social support for…

  17. Health-Related Messages about Physical Activity Promotion: An Analysis of Photographs on Social Networking Sites of Universities

    Science.gov (United States)

    Martínez-Bello, Vladimir E.; Martínez-Rojas, Ángela; Molina-García, Javier

    2017-01-01

    The main aim of this study was to examine how different physical activity domains are represented on the official social media sites of Spanish universities, through a content analysis of the photographs. Our results show that the representation of different physical activity domains is not balanced. While the analysed images do promote a message…

  18. The TAF9 C-terminal conserved region domain is required for SAGA and TFIID promoter occupancy to promote transcriptional activation.

    Science.gov (United States)

    Saint, Malika; Sawhney, Sonal; Sinha, Ishani; Singh, Rana Pratap; Dahiya, Rashmi; Thakur, Anushikha; Siddharthan, Rahul; Natarajan, Krishnamurthy

    2014-05-01

    A common function of the TFIID and SAGA complexes, which are recruited by transcriptional activators, is to deliver TBP to promoters to stimulate transcription. Neither the relative contributions of the five shared TBP-associated factor (TAF) subunits in TFIID and SAGA nor the requirement for different domains in shared TAFs for transcriptional activation is well understood. In this study, we uncovered the essential requirement for the highly conserved C-terminal region (CRD) of Taf9, a shared TAF, for transcriptional activation in yeast. Transcriptome profiling performed under Gcn4-activating conditions showed that the Taf9 CRD is required for induced expression of ∼9% of the yeast genome. The CRD was not essential for the Taf9-Taf6 interaction, TFIID or SAGA integrity, or Gcn4 interaction with SAGA in cell extracts. Microarray profiling of a SAGA mutant (spt20Δ) yielded a common set of genes induced by Spt20 and the Taf9 CRD. Chromatin immunoprecipitation (ChIP) assays showed that, although the Taf9 CRD mutation did not impair Gcn4 occupancy, the occupancies of TFIID, SAGA, and the preinitiation complex were severely impaired at several promoters. These results suggest a crucial role for the Taf9 CRD in genome-wide transcription and highlight the importance of conserved domains, other than histone fold domains, as a common determinant for TFIID and SAGA functions.

  19. Cloning of rainbow trout (Oncorhynchus mykiss ) histone H3 promoter and the activity analysis in rare minnow (Gobiocypris rarus)

    Institute of Scientific and Technical Information of China (English)

    MAO Weifeng; SUN Yonghua; WANG Yaping; WU Gang; CHEN Shangping; ZHU Zuoyan

    2004-01-01

    Rainbow trout histone H3(RH3)promoter was cloned via high fidelity PCR.The cloned RH3 promoter was inserted into a promoter-lacked vector pEGFP-1,resulting in an expression vector pRH3EGFP-1.The linearized pRH3EGFP-1 was microinjected into fertilized eggs of rare minnows and the sequential embryogenetic processes were monitored under a fluorescent microscope.Strong green fluorescence was ubiquitously observed at as early as the gastrula stage and then in various tissues at the fry stage.The results indi cate that RH3 promoter,as a piscine promoter,could serve in producing transgenic Cyprinoid such as rare minnow.Promoter activity of RH3,CMV and common carp β-actin(CA)were compared in rare minnow by the expression of respective recombinant EGFP vectors.The expression of pCMVEGFP occurred earlier than the following one,pRH3EGFP-1,and then pCAEGFP during the embryogenesis of the transgenics.Their expression activities demonstrated that the CMV promoter is the strongest one,followed by the CA and then the RH3.

  20. Does School-Based Health Promotion Affect Physical Activity on Weekends? And, Does It Reach Those Students Most in Need of Health Promotion?

    Directory of Open Access Journals (Sweden)

    Kerry A Bastian

    Full Text Available To determine whether a school-based health promotion program affects children's weekend physical activity and whether this effect varies according to socioeconomic-status.This was a quasi-experimental trial of school-based programs on physical activity levels implemented in disadvantaged neighborhoods in Alberta, Canada. In 2009 and 2011, 7 full days of pedometer data were collected from cross-sectional samples of grade 5 students (age 10-11 years from 10 intervention schools in low-socioeconomic neighbourhoods and 20 comparison schools in middle-socioeconomic neighbourhoods. Multilevel models assessed differences in step-counts between intervention and comparison groups over-time by weight (objectively measured and socioeconomic status subgroups.In 2009, children from intervention schools were less active on weekends relative to comparison schools (9212 vs. 11186 steps/day p<0.01. Two years later, daily step-counts on weekend days among children in low socioeconomic intervention schools increased such that they approximated those of children from middle socioeconomic comparison schools (12148 vs. 12121 steps/day p = 0.96. The relative difference in steps between intervention and comparison schools on weekends reduced from -21.4% to 0.2% following the intervention. The normalization of weekend step counts was similar for normal weight (-21.4% to +2.0% and overweight (-19.1 to +3.9% children, and was balanced across socioeconomic subgroups.These data suggest that school-based health promotion is effective for reducing inequities in physical activity levels outside school hours. Investments in school-based health promotion lead to behavior modification beyond the school environment.ClinicalTrials.gov NCT01914185.

  1. The Impact of Promotion Activities on Touristic Area Selection: A Case Study of Japanese Tourists Visiting Cappadocia

    Directory of Open Access Journals (Sweden)

    R. Pars Şahbaz

    2012-09-01

    Full Text Available The purpose of this research is to examine the impact of promotion activities on destination selection and to determine the level of the impact of promotion activities on Japanese tourists visiting Cappadocia region. The target population of the study is all Japanese tourists visiting Nevsehir province of Turkey. The sample of the study is composed of tourists visiting the city center and some districts of Nevsehir. After getting the required permissions, the questionnaires were distributed to Japanese tourists while they were staying at the hotels in Cappadocia. The software SPSS (Statistical Package for Social Sciences was used to analyze the data. The findings of the study indicate that the Japanese tourists visiting Cappadocia were influenced at a certain level from the promotion activities. As a result, it was determined that the promotion activities have a significant impact on destinations. It was also determined that as the importance given to the promotion activities increase, both the familiarity of the destinations and the tourist arrivals could increase.

  2. Mitogen-activated protein kinase kinase 4 (MAP2K4 promotes human prostate cancer metastasis.

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    Janet M Pavese

    Full Text Available Prostate cancer (PCa is the second leading cause of cancer death in the US. Death from PCa primarily results from metastasis. Mitogen-activated protein kinase kinase 4 (MAP2K4 is overexpressed in invasive PCa lesions in humans, and can be inhibited by small molecule therapeutics that demonstrate favorable activity in phase II studies. However, MAP2K4's role in regulating metastatic behavior is controversial and unknown. To investigate, we engineered human PCa cell lines which overexpress either wild type or constitutive active MAP2K4. Orthotopic implantation into mice demonstrated MAP2K4 increases formation of distant metastasis. Constitutive active MAP2K4, though not wild type, increases tumor size and circulating tumor cells in the blood and bone marrow. Complementary in vitro studies establish stable MAP2K4 overexpression promotes cell invasion, but does not affect cell growth or migration. MAP2K4 overexpression increases the expression of heat shock protein 27 (HSP27 protein and protease production, with the largest effect upon matrix metalloproteinase 2 (MMP-2, both in vitro and in mouse tumor samples. Further, MAP2K4-mediated increases in cell invasion are dependent upon heat shock protein 27 (HSP27 and MMP-2, but not upon MAP2K4's immediate downstream targets, p38 MAPK or JNK. We demonstrate that MAP2K4 increases human PCa metastasis, and prolonged over expression induces long term changes in cell signaling pathways leading to independence from p38 MAPK and JNK. These findings provide a mechanistic explanation for human studies linking increases in HSP27 and MMP-2 to progression to metastatic disease. MAP2K4 is validated as an important therapeutic target for inhibiting human PCa metastasis.

  3. Activation of PPARγ in myeloid cells promotes lung cancer progression and metastasis.

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    Howard Li

    Full Text Available Activation of peroxisome proliferator-activated receptor-γ (PPARγ inhibits growth of cancer cells including non-small cell lung cancer (NSCLC. Clinically, use of thiazolidinediones, which are pharmacological activators of PPARγ is associated with a lower risk of developing lung cancer. However, the role of this pathway in lung cancer metastasis has not been examined well. The systemic effect of pioglitazone was examined in two models of lung cancer metastasis in immune-competent mice. In an orthotopic model, murine lung cancer cells implanted into the lungs of syngeneic mice metastasized to the liver and brain. As a second model, cancer cells injected subcutaneously metastasized to the lung. In both models systemic administration of pioglitazone increased the rate of metastasis. Examination of tissues from the orthotopic model demonstrated increased numbers of arginase I-positive macrophages in tumors from pioglitazone-treated animals. In co-culture experiments of cancer cells with bone marrow-derived macrophages, pioglitazone promoted arginase I expression in macrophages and this was dependent on the expression of PPARγ in the macrophages. To assess the contribution of PPARγ in macrophages to cancer progression, experiments were performed in bone marrow-transplanted animals receiving bone marrow from Lys-M-Cre+/PPARγ(flox/flox mice, in which PPARγ is deleted specifically in myeloid cells (PPARγ-Mac(neg, or control PPARγ(flox/flox mice. In both models, mice receiving PPARγ-Mac(neg bone marrow had a marked decrease in secondary tumors which was not significantly altered by treatment with pioglitazone. This was associated with decreased numbers of arginase I-positive cells in the lung. These data support a model in which activation of PPARγ may have opposing effects on tumor progression, with anti-tumorigenic effects on cancer cells, but pro-tumorigenic effects on cells of the microenvironment, specifically myeloid cells.

  4. Hypoxia promotes Rab5 activation, leading to tumor cell migration, invasion and metastasis.

    Science.gov (United States)

    Silva, Patricio; Mendoza, Pablo; Rivas, Solange; Díaz, Jorge; Moraga, Carolina; Quest, Andrew F G; Torres, Vicente A

    2016-05-17

    Hypoxia, a common condition of the tumor microenvironment, is associated with poor patient prognosis, tumor cell migration, invasion and metastasis. Recent evidence suggests that hypoxia alters endosome dynamics in tumor cells, leading to augmented cell proliferation and migration and this is particularly relevant, because endosomal components have been shown to be deregulated in cancer. The early endosome protein Rab5 is a small GTPase that promotes integrin trafficking, focal adhesion turnover, Rac1 activation, tumor cell migration and invasion. However, the role of Rab5 and downstream events in hypoxia remain unknown. Here, we identify Rab5 as a critical player in hypoxia-driven tumor cell migration, invasion and metastasis. Exposure of A549 human lung carcinoma, ZR-75, MDA-MB-231 and MCF-7 human breast cancer and B16-F10 mouse melanoma cells to hypoxia increased Rab5 activation, followed by its re-localization to the leading edge and association with focal adhesions. Importantly, Rab5 was required for hypoxia-driven cell migration, FAK phosphorylation and Rac1 activation, as shown by shRNA-targeting and transfection assays with Rab5 mutants. Intriguingly, the effect of hypoxia on both Rab5 activity and migration was substantially higher in metastatic B16-F10 cells than in poorly invasive B16-F0 cells. Furthermore, exogenous expression of Rab5 in B16-F0 cells predisposed to hypoxia-induced migration, whereas expression of the inactive mutant Rab5/S34N prevented the migration of B16-F10 cells induced by hypoxia. Finally, using an in vivo syngenic C57BL/6 mouse model, Rab5 expression was shown to be required for hypoxia-induced metastasis. In summary, these findings identify Rab5 as a key mediator of hypoxia-induced tumor cell migration, invasion and metastasis.

  5. Using Web-Based Activities to Promote Reading: An Exploratory Study with Teenagers

    Directory of Open Access Journals (Sweden)

    Rátiva Velandia Marlén

    2012-10-01

    Full Text Available

    It is considered valuable to take advantage of web activities to improve and qualify the English teaching and learning processes, especially in the promotion of reading comprehension. In this article we share the process and results of a study that focused on some activities based on web materials that were designed and used with 10th grade students, with the purpose of promoting reading. Data was gathered through the use of questionnaires, surveys and web activities. The results showed that most of the
    students agree on the fact that reading more information concerning a specific topic or about different subjects makes them work with enthusiasm; they also had new possibilities to access knowledge in a different way and to improve reading comprehension.


    Se considera valioso tomar ventaja de las actividades basadas en materiales web para mejorar y cualificar los procesos de la enseñanza y aprendizaje del idioma inglés, especialmente en la promoción de la comprensión lectora. En este artículo compartimos los procesos y resultados de un estudio que se centró en algunas actividades basadas en materiales web que fueron diseñadas y empleadas por
    estudiantes de décimo grado con el propósito de promover la lectura. La información se recogió mediante cuestionarios, encuestas y materiales web. Los resultados mostraron que la mayoría de los estudiantes están de acuerdo con que leer información concerniente a un tema específico o de diferentes materias los puede motivar a trabajar con entusiasmo y que también tienen nuevas posibilidades para
    acceder al conocimiento de una manera diferente y mejorar su comprensión lectora

  6. Persuasive Technology in Mobile Applications Promoting Physical Activity: a Systematic Review.

    Science.gov (United States)

    Matthews, John; Win, Khin Than; Oinas-Kukkonen, Harri; Freeman, Mark

    2016-03-01

    Persuasive technology in mobile applications can be used to influence the behaviour of users. A framework known as the Persuasive Systems Design model has been developed for designing and evaluating systems that influence the attitudes or behaviours of users. This paper reviews the current state of mobile applications for health behavioural change with an emphasis on applications that promote physical activity. The inbuilt persuasive features of mobile applications were evaluated using the Persuasive Systems Design model. A database search was conducted to identify relevant articles. Articles were then reviewed using the Persuasive Systems Design model as a framework for analysis. Primary task support, dialogue support, and social support were found to be moderately represented in the selected articles. However, system credibility support was found to have only low levels of representation as a persuasive systems design feature in mobile applications for supporting physical activity. To ensure that available mobile technology resources are best used to improve the wellbeing of people, it is important that the design principles that influence the effectiveness of persuasive technology be understood.

  7. Aurora kinase A induces papillary thyroid cancer lymph node metastasis by promoting cofilin-1 activity.

    Science.gov (United States)

    Maimaiti, Yusufu; Jie, Tan; Jing, Zhou; Changwen, Wang; Pan, Yu; Chen, Chen; Tao, Huang

    2016-04-22

    Aurora-A (Aur-A), a member of the serine/threonine Aurora kinase family, plays an important role in ensuring genetic stability during cell division. Previous studies indicated that Aur-A possesses oncogenic activity and may be a valuable therapeutic target in cancer therapy. However, the role of Aur-A in the most common thyroid cancer, papillary thyroid cancer (PTC), remains largely unknown. In patients with PTC, cancer cell migration and invasion account for most of the metastasis, recurrence, and cancer-related deaths. Cofilin-1 (CFL-1) is the most important effector of actin polymerization and depolymerization, determining the direction of cell migration. Here, we assessed the correlation between Aur-A and CFL-1 in PTC with lymph node metastasis. Tissue microarray data showed that simultaneous overexpression of Aur-A and CFL-1 correlated with lymph node metastasis in thyroid cancer tissue. Inhibition of Aur-A suppressed thyroid cancer cell migration in vitro and decreased lymph node metastasis in nude mice. Importantly, Aur-A increased the non-phosphorylated, active form of CFL-1 in TPC-1 cells, thus promoting cancer cell migration and thyroid cancer lymph node metastasis. Our findings indicate that the combination of Aur-A and CFL-1 may be useful as a molecular prediction model for lymph node metastasis in thyroid cancer and raise the possibility of targeting Aur-A and CFL-1 for more effective treatment of thyroid cancer.

  8. Perilipin1 promotes unilocular lipid droplet formation through the activation of Fsp27 in adipocytes.

    Science.gov (United States)

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

    2013-01-01

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

  9. ACTH Modulates PTP-PEST Activity and Promotes Its Interaction With Paxillin.

    Science.gov (United States)

    Gorostizaga, Alejandra Beatriz; Mori Sequeiros Garcia, M Mercedes; Acquier, Andrea B; Lopez-Costa, Juan J; Mendez, Carlos F; Maloberti, Paula M; Paz, Cristina

    2016-09-01

    Adrenocorticotropic hormone (ACTH) treatment has been proven to promote paxillin dephosphorylation and increase soluble protein tyrosine phosphatase (PTP) activity in rat adrenal zona fasciculata (ZF). Also, in-gel PTP assays have shown the activation of a 115-kDa PTP (PTP115) by ACTH. In this context, the current work presents evidence that PTP115 is PTP-PEST, a PTP that recognizes paxillin as substrate. PTP115 was partially purified from rat adrenal ZF and PTP-PEST was detected through Western blot in bioactive samples taken in each purification step. Immunohistochemical and RT-PCR studies revealed PTP-PEST expression in rat ZF and Y1 adrenocortical cells. Moreover, a PTP-PEST siRNA decreased the expression of this phosphatase. PKA phosphorylation of purified PTP115 isolated from non-ACTH-treated rats increased KM and VM . Finally, in-gel PTP assays of immunoprecipitated paxillin from control and ACTH-treated rats suggested a hormone-mediated increase in paxillin-PTP115 interaction, while PTP-PEST and paxillin co-localize in Y1 cells. Taken together, these data demonstrate PTP-PEST expression in adrenal ZF and its regulation by ACTH/PKA and also suggest an ACTH-induced PTP-PEST-paxillin interaction. J. Cell. Biochem. 117: 2170-2181, 2016. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.

  10. Repressor and activator protein accelerates hepatic ischemia reperfusion injury by promoting neutrophil inflammatory response.

    Science.gov (United States)

    Li, Chang Xian; Lo, Chung Mau; Lian, Qizhou; Ng, Kevin Tak-Pan; Liu, Xiao Bing; Ma, Yuen Yuen; Qi, Xiang; Yeung, Oscar Wai Ho; Tergaonkar, Vinay; Yang, Xin Xiang; Liu, Hui; Liu, Jiang; Shao, Yan; Man, Kwan

    2016-05-10

    Repressor and activator protein (Rap1) directly regulates nuclear factor-κB (NF-κB) dependent signaling, which contributes to hepatic IRI. We here intended to investigate the effect of Rap1 in hepatic ischemia reperfusion injury (IRI) and to explore the underlying mechanisms. The association of Rap1 expression with hepatic inflammatory response were investigated in both human and rat liver transplantation. The effect of Rap1 in hepatic IRI was studied in Rap1 knockout mice IRI model in vivo and primary cells in vitro. Our results showed that over expression of Rap1 was associated with severe liver graft inflammatory response, especially in living donor liver transplantation. The results were also validated in rat liver transplantation model. In mice hepatic IRI model, the knockout of Rap1 reduced hepatic damage and hepatic inflammatory response. In primary cells, the knockout of Rap1 suppressed neutrophils migration activity and adhesion in response to liver sinusoidal endothelial cells through down-regulating neutrophils F-Actin expression and CXCL2/CXCR2 pathway. In addition, the knockout of Rap1 also decreased production of pro-inflammatory cytokines/chemokines in primary neutrophils and neutrophils-induced hepatocyte damage. In conclusion, Rap1 may induce hepatic IRI through promoting neutrophils inflammatory response. Rap1 may be the potential therapeutic target of attenuating hepatic IRI.

  11. The impact of group activities as a strategy for health promotion in the senescence

    Directory of Open Access Journals (Sweden)

    Cléria Bittar

    2012-06-01

    Full Text Available The objective of this study was to investigate the perception of two groups of elderly about the impact of the participation/ non participation in some activities, had in their health and quality of life. Twenty interviews were conducted with two groups of elderly. In the first group, called Participant Group (PG 10 elderly men and women participated in the third age group, a project called "Healthy Aging", which are held in various physical and socialization activities; and with other 10 subjects the Non-Participant Group (NPG, which did not join the project. We compared the two groups’ answers and concluded that the elderly from PG reported better quality of life, health and willingness to form social bonds. Also according to the elderly of NPG, we seek to know their justifications and reasons for non-adherence to the project. They also reported perceiving significant changes in those who participated, understanding that the group was able to improve self-esteem, health and quality of life. We conclude that the group actions, aiming the principles that guide the assumptions of health promotion can create a space for exchanges and experiences, restoring the necessary conditions so that the elderly may have a fuller life, with quality of life and welfare.

  12. Neurogenesis-Promoting Natural Product α-Asarone Modulates Morphological Dynamics of Activated Microglia

    Science.gov (United States)

    Cai, Qing; Li, Yuanyuan; Mao, Jianxin; Pei, Gang

    2016-01-01

    α-Asarone is an active constituent of Acori Tatarinowii, one of the widely used traditional Chinese Medicine to treat cognitive defect, and recently is shown to promote neurogenesis. Here, we demonstrated that low level (3 μM) of α-asarone attenuated LPS-induced BV2 cell bipolar elongated morphological change, with no significant effect on the LPS-induced pro-inflammatory cytokine expressions. In addition, time-lapse analysis also revealed that α-asarone modulated LPS-induced BV2 morphological dynamics. Consistently a significant reduction in the LPS-induced Monocyte Chemoattractant Protein (MCP-1) mRNA and protein levels was also detected along with the morphological change. Mechanistic study showed that the attenuation effect to the LPS-resulted morphological modulation was also detected in the presence of MCP-1 antibodies or a CCR2 antagonist. This result has also been confirmed in primary cultured microglia. The in vivo investigation provided further evidence that α-asarone reduced the proportion of activated microglia, and reduced microglial tip number and maintained the velocity. Our study thus reveals α-asarone effectively modulates microglial morphological dynamics, and implies this effect of α-asarone may functionally relate to its influence on neurogenesis. PMID:28018174

  13. Suppression of Sin3A activity promotes differentiation of pluripotent cells into functional neurons

    Science.gov (United States)

    Halder, Debasish; Lee, Chang-Hee; Hyun, Ji Young; Chang, Gyeong-Eon; Cheong, Eunji; Shin, Injae

    2017-01-01

    Sin3 is a transcriptional corepressor for REST silencing machinery that represses multiple neuronal genes in non-neuronal cells. However, functions of Sin3 (Sin3A and Sin3B) in suppression of neuronal phenotypes are not well characterized. Herein we show that Sin3A knockdown impedes the repressive activity of REST and enhances differentiation of pluripotent P19 cells into electrophysiologically active neurons without inducing astrogenesis. It is also found that silencing Sin3B induces neurogenesis of P19 cells with a lower efficiency than Sin3A knockdown. The results suggest that Sin3A has a more profound effect on REST repressive machinery for silencing neuronal genes in P19 cells than Sin3B. Furthermore, we show that a peptide inhibitor of Sin3A-REST interactions promotes differentiation of P19 cells into functional neurons. Observations made in studies using genetic deletion and a synthetic inhibitor suggests that Sin3A plays an important role in the repression of neuronal genes by the REST regulatory mechanism. PMID:28303954

  14. VAMP-associated protein B (VAPB) promotes breast tumor growth by modulation of Akt activity.

    Science.gov (United States)

    Rao, Meghana; Song, Wenqiang; Jiang, Aixiang; Shyr, Yu; Lev, Sima; Greenstein, David; Brantley-Sieders, Dana; Chen, Jin

    2012-01-01

    VAPB (VAMP- associated protein B) is an ER protein that regulates multiple biological functions. Although aberrant expression of VAPB is associated with breast cancer, its function in tumor cells is poorly understood. In this report, we provide evidence that VAPB regulates breast tumor cell proliferation and AKT activation. VAPB protein expression is elevated in primary and metastatic tumor specimens, and VAPB mRNA expression levels correlated negatively with patient survival in two large breast tumor datasets. Overexpression of VAPB in mammary epithelial cells increased cell growth, whereas VAPB knockdown in tumor cells inhibited cell proliferation in vitro and suppressed tumor growth in orthotopic mammary gland allografts. The growth regulation of mammary tumor cells controlled by VAPB appears to be mediated, at least in part, by modulation of AKT activity. Overexpression of VAPB in MCF10A-HER2 cells enhances phosphorylation of AKT. In contrast, knockdown of VAPB in MMTV-Neu tumor cells inhibited pAKT levels. Pharmacological inhibition of AKT significantly reduced three-dimensional spheroid growth induced by VAPB. Collectively, the genetic, functional and mechanistic analyses suggest a role of VAPB in tumor promotion in human breast cancer.

  15. VAMP-associated protein B (VAPB promotes breast tumor growth by modulation of Akt activity.

    Directory of Open Access Journals (Sweden)

    Meghana Rao

    Full Text Available VAPB (VAMP- associated protein B is an ER protein that regulates multiple biological functions. Although aberrant expression of VAPB is associated with breast cancer, its function in tumor cells is poorly understood. In this report, we provide evidence that VAPB regulates breast tumor cell proliferation and AKT activation. VAPB protein expression is elevated in primary and metastatic tumor specimens, and VAPB mRNA expression levels correlated negatively with patient survival in two large breast tumor datasets. Overexpression of VAPB in mammary epithelial cells increased cell growth, whereas VAPB knockdown in tumor cells inhibited cell proliferation in vitro and suppressed tumor growth in orthotopic mammary gland allografts. The growth regulation of mammary tumor cells controlled by VAPB appears to be mediated, at least in part, by modulation of AKT activity. Overexpression of VAPB in MCF10A-HER2 cells enhances phosphorylation of AKT. In contrast, knockdown of VAPB in MMTV-Neu tumor cells inhibited pAKT levels. Pharmacological inhibition of AKT significantly reduced three-dimensional spheroid growth induced by VAPB. Collectively, the genetic, functional and mechanistic analyses suggest a role of VAPB in tumor promotion in human breast cancer.

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

    Institute of Scientific and Technical Information of China (English)

    WANGHONG-BING; ZHUHUI-GANG

    1996-01-01

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

  17. Dynamic myosin activation promotes collective morphology and migration by locally balancing oppositional forces from surrounding tissue.

    Science.gov (United States)

    Aranjuez, George; Burtscher, Ashley; Sawant, Ketki; Majumder, Pralay; McDonald, Jocelyn A

    2016-06-15

    Migrating cells need to overcome physical constraints from the local microenvironment to navigate their way through tissues. Cells that move collectively have the additional challenge of negotiating complex environments in vivo while maintaining cohesion of the group as a whole. The mechanisms by which collectives maintain a migratory morphology while resisting physical constraints from the surrounding tissue are poorly understood. Drosophila border cells represent a genetic model of collective migration within a cell-dense tissue. Border cells move as a cohesive group of 6-10 cells, traversing a network of large germ line-derived nurse cells within the ovary. Here we show that the border cell cluster is compact and round throughout their entire migration, a shape that is maintained despite the mechanical pressure imposed by the surrounding nurse cells. Nonmuscle myosin II (Myo-II) activity at the cluster periphery becomes elevated in response to increased constriction by nurse cells. Furthermore, the distinctive border cell collective morphology requires highly dynamic and localized enrichment of Myo-II. Thus, activated Myo-II promotes cortical tension at the outer edge of the migrating border cell cluster to resist compressive forces from nurse cells. We propose that dynamic actomyosin tension at the periphery of collectives facilitates their movement through restrictive tissues.

  18. Enhanced Promoter Activity by Replenishment of Sigma Factor rpoE in Klebsiella pneumoniae.

    Science.gov (United States)

    Chen, Liuni; Li, Ying; Tian, Pingfang

    2016-06-01

    Plasmid-dependent overexpression of enzyme(s) aims to divert carbon flux toward a desired compound. One drawback of this strategy is compromise of growth due to massive consumption of host resources. Here we show that replenishment of sigma factor rpoE improves the growth of Klebsiella pneumoniae. The gene rpoE was expressed alone or coexpressed with Ald4 (an aldehyde dehydrogenase from Saccharomyces cerevisiae) in K. pneumoniae. We found that the Ald4 activity was higher in the strain coexpressing Ald4 and rpoE (32.3 U/mg) than that expressing Ald4 alone (29.9 U/mg). Additionally, under shake-flask conditions, the strain coexpressing Ald4 and rpoE produced 0.5 g 3-hydroxypropionic acid (3-HP) and 9.8 g 1,3-propanediol (1,3-PD) per liter in 24 h, which were 1.6- and 0.85-fold enhancement, respectively, compared to those expressing Ald4 alone. Notably, under non-optimized bioreactor conditions, the strain coexpressing Ald4 and rpoE produced 13.5 g 3-HP and 37.8 g 1,3-PD per liter with glycerol conversion ratio of 0.45 mol/mol. These results indicate that replenishment of rpoE enhanced promoter activity and stimulated glycerol consumption.

  19. Methylglyoxal-Mediated Stress Correlates with High Metabolic Activity and Promotes Tumor Growth in Colorectal Cancer

    Science.gov (United States)

    Chiavarina, Barbara; Nokin, Marie-Julie; Bellier, Justine; Durieux, Florence; Bletard, Noëlla; Sherer, Félicie; Lovinfosse, Pierre; Peulen, Olivier; Verset, Laurine; Dehon, Romain; Demetter, Pieter; Turtoi, Andrei; Uchida, Koji; Goldman, Serge; Hustinx, Roland; Delvenne, Philippe; Castronovo, Vincent; Bellahcène, Akeila

    2017-01-01

    Cancer cells generally rely on aerobic glycolysis as a major source of energy. Methylglyoxal (MG), a dicarbonyl compound that is produced as a side product during glycolysis, is highly reactive and induces the formation of advanced glycation end-products that are implicated in several pathologies including cancer. All mammalian cells have an enzymatic defense against MG composed by glyoxalases GLO1 and GLO2 that converts MG to d-lactate. Colorectal cancer (CRC) is one of the most frequently occurring cancers with high morbidity and mortality. In this study, we used immunohistochemistry to examine the level of MG protein adducts, in a series of 102 CRC human tumors divided into four clinical stages. We consistently detected a high level of MG adducts and low GLO1 activity in high stage tumors compared to low stage ones suggesting a pro-tumor role for dicarbonyl stress. Accordingly, GLO1 depletion in CRC cells promoted tumor growth in vivo that was efficiently reversed using carnosine, a potent MG scavenger. Our study represents the first demonstration that MG adducts accumulation is a consistent feature of high stage CRC tumors. Our data point to MG production and detoxification levels as an important molecular link between exacerbated glycolytic activity and CRC progression. PMID:28117708

  20. Neuropeptides stimulate human osteoblast activity and promote gap junctional intercellular communication.

    Science.gov (United States)

    Ma, Wenhui; Zhang, Xuemin; Shi, Shushan; Zhang, Yingze

    2013-06-01

    Neuropeptides released from the skeletal nerve fibers have neurotransmitter and immunoregulatory roles; they exert paracrine biological effects on bone cells present close to the nerve endings expressing these signaling molecules. The aims of this study were a systematic investigation of the effects of the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), Neuropeptide Y (NPY) and tyrosine hydroxylase (TH) on the cell viability and function of the human osteoblasts, and comparing their difference in the role of regulating bone formation. Cultures of normal human osteoblasts were treated with SP, CGRP, VIP, NPY or TH at three concentrations. We found that each of the five neuropeptides induced increases in cell viability of human osteoblasts. The stimulatory action of NPY was the highest, followed by VIP, SP and TH, while CGRP had the lowest stimulatory effect. The viability index of osteoblasts was inversely associated with the concentration of neuropeptides, and positively with the time of exposure. Moreover, the five neuropeptides increased the ALP activity and osteocalcin to different extents in a dose-dependent manner. The GJIC of osteoblasts was significantly promoted by neuropeptides. The results demonstrated that neuropeptides released from skeletal nerve endings after a stimulus appeared to be able to induce the proliferation and activity of osteoblasts via enhancing GJIC between cells, and further influence the bone formation. These findings may contribute toward a better understanding of the neural influence on bone remodeling and improving treatments related to bone diseases.

  1. CLONING PROMOTER OF HUMAN SATB1 GENE AND EFFECT OF ATRA AND CoCl2 ON ITS ACTIVITY

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To explore the structure and activity of SATB1 promoter in different cells, ATRA and CoCl2 effect on its activity. Methods Using luciferase system to assay the promoter activity of human SATB1 gene, three luciferase reporter vectors were constructed which driven by different regions of 5' untranslated sequence from human SATB1 gene, called pGL3-SP2946-luc, pGL3-SP1718-luc and pGL3-SP751-luc, and transfected into Jurkat T, K562, U937 and Hela cells transiently using lipofectinamine, the expression activity was detected at different dosage of ATRA and CoCl2 treatment for different time course. Results The reporter gene expression from SATB1 promoter were high activity in U937 cell, moderate in Jurkat T cell, low activity in K562 cell and showed no obvious activity in Hela cell, the reporter gene expression from pGL3-SP751-luc kept on the higher lever in Jurkat T, K562 and U937 cells than the other two vectors. We also found that the repressive effect of CoCl2 on SATB1 's mRNA expression and the relative luciferase expression from pGL3-SP751-luc in U937 cell was down-regulated obviously by ATRA and CoCl2 in the concentration- and time-dependent manners. Conclusion SATB1 promoter drives gene expression with cell-specificity and its core promoter region maybe exist in the - 751 ~ - 9bp of 5' untranslated region of human SATB1 gene. Combined with the experiment result we found before that SATB1 was down-regulated by ATRA in U937, the results imply that STAB1 maybe is down-regulated by ATRA and CoCl2 through its promoter in the differentiation of myeloid cell line-U937.

  2. Global epigenomic analysis indicates protocadherin-7 activates osteoclastogenesis by promoting cell–cell fusion

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Haruhiko [Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan); Department of Cell Signaling, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549 (Japan); Nakashima, Tomoki [Department of Cell Signaling, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549 (Japan); Japan Science and Technology Agency, PRESTO, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549 (Japan); Hayashi, Mikihito [Department of Cell Signaling, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549 (Japan); Japan Science and Technology Agency, ERATO, Takayanagi Osteonetwork Project, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Izawa, Naohiro; Yasui, Tetsuro [Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan); Aburatani, Hiroyuki [Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1, Komaba, Meguro-ku, Tokyo 153-8904 (Japan); Tanaka, Sakae [Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan); Takayanagi, Hiroshi, E-mail: takayana@m.u-tokyo.ac.jp [Japan Science and Technology Agency, ERATO, Takayanagi Osteonetwork Project, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

    2014-12-12

    Highlights: • Identification of epigenetically regulated genes during osteoclastogenesis. • Pcdh7 is regulated by H3K4me3 and H3K27me3 during osteoclastogenesis. • Pcdh7 expression is increased by RANKL during osteoclastogenesis. • Establishment of novel cell fusion analysis for osteoclasts by imaging cytometer. • Pcdh7 regulates osteoclastogenesis by promoting cell fusion related gene expressions. - Abstract: Gene expression is dependent not only on genomic sequences, but also epigenetic control, in which the regulation of chromatin by histone modification plays a crucial role. Histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 trimethylation (H3K27me3) are related to transcriptionally activated and silenced sequences, respectively. Osteoclasts, the multinucleated cells that resorb bone, are generated by the fusion of precursor cells of monocyte/macrophage lineage. To elucidate the molecular and epigenetic regulation of osteoclast differentiation, we performed a chromatin immunoprecipitation sequencing (ChIP-seq) analysis for H3K4me3 and H3K27me3 in combination with RNA sequencing. We focused on the histone modification change from H3K4me3(+)H3K27me3(+) to H3K4me3(+)H3K27me3(–) and identified the protocadherin-7 gene (Pcdh7) to be among the genes epigenetically regulated during osteoclastogenesis. Pcdh7 was induced by RANKL stimulation in an NFAT-dependent manner. The knockdown of Pcdh7 inhibited RANKL-induced osteoclast differentiation due to the impairment of cell–cell fusion, accompanied by a decreased expression of the fusion-related genes Dcstamp, Ocstamp and Atp6v0d2. This study demonstrates that Pcdh7 plays a key role in osteoclastogenesis by promoting cell–cell fusion.

  3. Hsp20 functions as a novel cardiokine in promoting angiogenesis via activation of VEGFR2.

    Directory of Open Access Journals (Sweden)

    Xiaowei Zhang

    Full Text Available Heat shock proteins (Hsps are well appreciated as intrinsic protectors of cardiomyocytes against numerous stresses. Recent studies have indicated that Hsp20 (HspB6, a small heat shock protein, was increased in blood from cardiomyopathic hamsters. However, the exact source of the increased circulating Hsp20 and its potential role remain obscure. In this study, we observed that the circulating Hsp20 was increased in a transgenic mouse model with cardiac-specific overexpression of Hsp20, compared with wild-type mice, suggesting its origin from cardiomyocytes. Consistently, culture media harvested from Hsp20-overexpressing cardiomyocytes by Ad.Hsp20 infection contained an increased amount of Hsp20, compared to control media. Furthermore, we identified that Hsp20 was secreted through exosomes, independent of the endoplasmic reticulum-Golgi pathway. To investigate whether extracellular Hsp20 promotes angiogenesis, we treated human umbilical vein endothelial cells (HUVECs with recombinant human Hsp20 protein, and observed that Hsp20 dose-dependently promoted HUVEC proliferation, migration and tube formation. Moreover, a protein binding assay and immunostaining revealed an interaction between Hsp20 and VEGFR2. Accordingly, stimulatory effects of Hsp20 on HUVECs were blocked by a VEGFR2 neutralizing antibody and CBO-P11 (a VEGFR inhibitor. These in vitro data are consistent with the in vivo findings that capillary density was significantly enhanced in Hsp20-overexpressing hearts, compared to non-transgenic hearts. Collectively, our findings demonstrate that Hsp20 serves as a novel cardiokine in regulating myocardial angiogenesis through activation of the VEGFR signaling cascade.

  4. Hypoxia promotes uveal melanoma invasion through enhanced Notch and MAPK activation.

    Directory of Open Access Journals (Sweden)

    Laura Asnaghi

    Full Text Available The transcriptional response promoted by hypoxia-inducible factors has been associated with metastatic spread of uveal melanoma. We found expression of hypoxia-inducible factor 1α (HIF-1α protein in well-vascularized tumor regions as well as in four cell lines grown in normoxia, thus this pathway may be important even in well-oxygenated uveal melanoma cells. HIF-1α protein accumulation in normoxia was inhibited by rapamycin. As expected, hypoxia (1% pO2 further induced HIF-1α protein levels along with its target genes VEGF and LOX. Growth in hypoxia significantly increased cellular invasion of all 5 uveal melanoma lines tested, as did the introduction of an oxygen-insensitive HIF-1α mutant into Mel285 cells with low HIF-1α baseline levels. In contrast, HIF-1α knockdown using shRNA significantly decreased growth in hypoxia, and reduced by more than 50% tumor invasion in four lines with high HIF-1α baseline levels. Pharmacologic blockade of HIF-1α protein expression using digoxin dramatically suppressed cellular invasion both in normoxia and in hypoxia. We found that Notch pathway components, including Jag1-2 ligands, Hes1-Hey1 targets and the intracellular domain of Notch1, were increased in hypoxia, as well as the phosphorylation levels of Erk1-2 and Akt. Pharmacologic and genetic inhibition of Notch largely blocked the hypoxic induction of invasion as did the pharmacologic suppression of Erk1-2 activity. In addition, the increase in Erk1-2 and Akt phosphorylation by hypoxia was partially reduced by inhibiting Notch signaling. Our findings support the functional importance of HIF-1α signaling in promoting the invasive capacity of uveal melanoma cells in both hypoxia and normoxia, and suggest that pharmacologically targeting HIF-1α pathway directly or through blockade of Notch or Erk1-2 pathways can slow tumor spread.

  5. Subcutaneous adipocytes promote melanoma cell growth by activating the Akt signaling pathway: role of palmitic acid.

    Science.gov (United States)

    Kwan, Hiu Yee; Fu, Xiuqiong; Liu, Bin; Chao, Xiaojuan; Chan, Chi Leung; Cao, Huihui; Su, Tao; Tse, Anfernee Kai Wing; Fong, Wang Fun; Yu, Zhi-Ling

    2014-10-31

    Tumorigenesis involves constant communication between tumor cells and neighboring normal cells such as adipocytes. The canonical function of adipocytes is to store triglyceride and release fatty acids for other tissues. This study was aimed to find out if adipocytes promoted melanoma cell growth and to investigate the underlying mechanism. Here we isolated adipocytes from inguinal adipose tissue in mice and co-cultured with melanoma cells. We found that the co-cultured melanoma had higher lipid accumulation compared with mono-cultured melanoma. In addition, fluorescently labeled fatty acid BODIPY® FLC16 signal was detected in melanoma co-cultured with the adipocytes that had been loaded with the fluorescent dye, suggesting that the adipocytes provide fatty acids to melanoma cells. Compared with mono-cultured melanoma, co-cultured melanoma cells had a higher proliferation and phospho-Akt (Ser-473 and Thr-450) expression. Overexpression of Akt mutants in melanoma cells reduced the co-culture-enhanced proliferation. A lipidomic study showed that the co-cultured melanoma had an elevated palmitic acid level. Interestingly, we found that palmitic acid stimulated melanoma cell proliferation, changed the cell cycle distribution, and increased phospho-Akt (Ser-473 and Thr-450) and PI3K but not phospho-PTEN (phosphophosphatase and tensin homolog) expressions. More importantly, the palmitic acid-stimulated proliferation was further enhanced in the Akt-overexpressed melanoma cells and was reduced by LY294002 or knockdown of endogenous Akt or overexpression of Akt mutants. We also found that palmitic acid-pretreated B16F10 cells were grown to a significantly larger tumor in mice compared with control cells. Taken together, we suggest that adipocytes may serve as an exogenous source of palmitic acid that promotes melanoma cell growth by activating Akt.

  6. Notch1 Activation or Loss Promotes HPV-Induced Oral Tumorigenesis.

    Science.gov (United States)

    Zhong, Rong; Bao, Riyue; Faber, Pieter W; Bindokas, Vytautas P; Bechill, John; Lingen, Mark W; Spiotto, Michael T

    2015-09-15

    Viral oncogene expression is insufficient for neoplastic transformation of human cells, so human papillomavirus (HPV)-associated cancers will also rely upon mutations in cellular oncogenes and tumor suppressors. However, it has been difficult so far to distinguish incidental mutations without phenotypic impact from causal mutations that drive the development of HPV-associated cancers. In this study, we addressed this issue by conducting a functional screen for genes that facilitate the formation of HPV E6/E7-induced squamous cell cancers in mice using a transposon-mediated insertional mutagenesis protocol. Overall, we identified 39 candidate driver genes, including Notch1, which unexpectedly was scored by gain- or loss-of-function mutations that were capable of promoting squamous cell carcinogenesis. Autochthonous HPV-positive oral tumors possessing an activated Notch1 allele exhibited high rates of cell proliferation and tumor growth. Conversely, Notch1 loss could accelerate the growth of invasive tumors in a manner associated with increased expression of matrix metalloproteinases and other proinvasive genes. HPV oncogenes clearly cooperated with loss of Notch1, insofar as its haploinsufficiency accelerated tumor growth only in HPV-positive tumors. In clinical specimens of various human cancers, there was a consistent pattern of NOTCH1 expression that correlated with invasive character, in support of our observations in mice. Although Notch1 acts as a tumor suppressor in mouse skin, we found that oncogenes enabling any perturbation in Notch1 expression promoted tumor growth, albeit via distinct pathways. Our findings suggest caution in interpreting the meaning of putative driver gene mutations in cancer, and therefore therapeutic efforts to target them, given the significant contextual differences in which such mutations may arise, including in virus-associated tumors.

  7. Control of intestinal promoter activity of the cellular migratory regulator gene ELMO3 by CDX2 and SP1

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Boyd, Mette; Olsen, Jørgen;

    2010-01-01

    An important aspect of the cellular differentiation in the intestine is the migration of epithelial cells from the crypt to the villus tip. As homeodomaine transcription factor CDX2 has been suggested to influence cell migration, we performed a genome-wide promoter analysis for CDX2 binding...... migration. However, no information is available about the transcriptional regulation of the ELMO3 gene. The aim of this study was to investigate the potential role of CDX2 in the regulation of the ELMO3 promoter activity. Electrophoretic mobility shift assays showed that CDX2 bound to conserved CDX2...... sequences and mutations of the CDX2-binding sites, significantly reduced the promoter activity. Reporter gene assays demonstrated that the region mediating ELMO3 basal transcriptional activity to be located between -270 and -31 bp. Sequence analysis revealed no typical TATA-box, but four GC-rich sequences...

  8. The university library reading promotion activities%高校图书馆阅读推广活动研究

    Institute of Scientific and Technical Information of China (English)

    李秋奇

    2015-01-01

    The article proposed the university library reading promotion activities for the importance of the cultivation of talents. And sums up the common problems in the reading promotion activities in coleges and universities, that is: does not pay enough attention to reading promotion activities, and events without fit age characteristics of students, at the same time hold the activities of the continuity is not strong, etc. Thus puts forward the countermeasures of strengthening the reading promotion activities in coleges and universities, namely on the understanding to the reading promotion activities as an important part for the task of personnel training in coleges and universities, to set up dedicated reading promotion department; To take the student as activity, based on the reading promotion activities to conform to the age characteristics of students, so as to better attract students; To enrich the form and content of innovation reading promotion activities.%本文提出了高校图书馆阅读推广活动对高校人才培养的重要性。并总结了目前高校阅读推广活动普遍存在的问题,即在认识上不够重视阅读推广活动,并且举办的活动没有契合学生的年龄特点,同时举办的活动持续性不强等。从而提出了加强高校阅读推广活动的对策,即在认识上要把阅读推广活动作高校为人才培养任务的重要一环,设立专门的阅读推广部门;要以学生为活动的基础,举办的阅读推广活动要符合学生的年龄特点,从而更好的吸引学生;要丰富创新阅读推广活动的形式和内容。

  9. Moderation of calpain activity promotes neovascular integration and lumen formation during VEGF-induced pathological angiogenesis.

    Directory of Open Access Journals (Sweden)

    Mien V Hoang

    Full Text Available BACKGROUND: Successful neovascularization requires that sprouting endothelial cells (ECs integrate to form new vascular networks. However, architecturally defective, poorly integrated vessels with blind ends are typical of pathological angiogenesis induced by vascular endothelial growth factor-A (VEGF, thereby limiting the utility of VEGF for therapeutic angiogenesis and aggravating ischemia-related pathologies. Here we investigated the possibility that over-exuberant calpain activity is responsible for aberrant VEGF neovessel architecture and integration. Calpains are a family of intracellular calcium-dependent, non-lysosomal cysteine proteases that regulate cellular functions through proteolysis of numerous substrates. METHODOLOGY/PRINCIPAL FINDINGS: In a mouse skin model of VEGF-driven angiogenesis, retroviral transduction with dominant-negative (DN calpain-I promoted neovessel integration and lumen formation, reduced blind ends, and improved vascular perfusion. Moderate doses of calpain inhibitor-I improved VEGF-driven angiogenesis similarly to DN calpain-I. Conversely, retroviral transduction with wild-type (WT calpain-I abolished neovessel integration and lumen formation. In vitro, moderate suppression of calpain activity with DN calpain-I or calpain inhibitor-I increased the microtubule-stabilizing protein tau in endothelial cells (ECs, increased the average length of microtubules, increased actin cable length, and increased the interconnectivity of vascular cords. Conversely, WT calpain-I diminished tau, collapsed microtubules, disrupted actin cables, and inhibited integration of cord networks. Consistent with the critical importance of microtubules for vascular network integration, the microtubule-stabilizing agent taxol supported vascular cord integration whereas microtubule dissolution with nocodazole collapsed cord networks. CONCLUSIONS/SIGNIFICANCE: These findings implicate VEGF-induction of calpain activity and impairment of

  10. Ena/VASP proteins regulate activated T-cell trafficking by promoting diapedesis during transendothelial migration.

    Science.gov (United States)

    Estin, Miriam L; Thompson, Scott B; Traxinger, Brianna; Fisher, Marlie H; Friedman, Rachel S; Jacobelli, Jordan

    2017-04-04

    Vasodilator-stimulated phosphoprotein (VASP) and Ena-VASP-like (EVL) are cytoskeletal effector proteins implicated in regulating cell morphology, adhesion, and migration in various cell types. However, the role of these proteins in T-cell motility, adhesion, and in vivo trafficking remains poorly understood. This study identifies a specific role for EVL and VASP in T-cell diapedesis and trafficking. We demonstrate that EVL and VASP are selectively required for activated T-cell trafficking but are not required for normal T-cell development or for naïve T-cell trafficking to lymph nodes and spleen. Using a model of multiple sclerosis, we show an impairment in trafficking of EVL/VASP-deficient activated T cells to the inflamed central nervous system of mice with experimental autoimmune encephalomyelitis. Additionally, we found a defect in trafficking of EVL/VASP double-knockout (dKO) T cells to the inflamed skin and secondary lymphoid organs. Deletion of EVL and VASP resulted in the impairment in α4 integrin (CD49d) expression and function. Unexpectedly, EVL/VASP dKO T cells did not exhibit alterations in shear-resistant adhesion to, or in crawling on, primary endothelial cells under physiologic shear forces. Instead, deletion of EVL and VASP impaired T-cell diapedesis. Furthermore, T-cell diapedesis became equivalent between control and EVL/VASP dKO T cells upon α4 integrin blockade. Overall, EVL and VASP selectively mediate activated T-cell trafficking by promoting the diapedesis step of transendothelial migration in a α4 integrin-dependent manner.

  11. Mast cell activation and neutrophil recruitment promotes early and robust inflammation in the meninges in EAE.

    Science.gov (United States)

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

    2013-05-01

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

  12. Promoter-dependent activity on androgen receptor N-terminal domain mutations in androgen insensitivity syndrome.

    Science.gov (United States)

    Tadokoro-Cuccaro, Rieko; Davies, John; Mongan, Nigel P; Bunch, Trevor; Brown, Rosalind S; Audi, Laura; Watt, Kate; McEwan, Iain J; Hughes, Ieuan A

    2014-01-01

    Androgen receptor (AR) mutations are associated with androgen insensitivity syndrome (AIS). Missense mutations identified in the AR-N-terminal domain (AR-NTD) are rare, and clinical phenotypes are typically mild. We investigated 7 missense mutations and 2 insertion/deletions located in the AR-NTD. This study aimed to elucidate the pathogenic role of AR-NTD mutants in AIS and to use this knowledge to further define AR-NTD function. AR-NTD mutations (Q120E, A159T, G216R, N235K, G248V, L272F, and P380R) were introduced into AR-expression plasmids. Stably expressing cell lines were established for del57L and ins58L. Transactivation was measured using luciferase reporter constructs under the control of GRE and Pem promoters. Intrinsic fluorescence spectroscopy and partial proteolysis studies were performed for mutations which showed reduced activities by using a purified AR-AF1 protein. Pem-luciferase reporter activation was reduced for A159T, N235K, and G248V but not the GRE-luciferase reporter. Protein structure analysis detected no significant change in the AR-AF1 region for these mutations. Reduced cellular expression and transactivation activity were observed for ins58L. The mutations Q120E, G216R, L272F, P380R, and del57L showed small or no detectable changes in function. Thus, clinical and experimental analyses have identified novel AR-signalling defects associated with mutations in the structurally disordered AR-NTD domain in patients with AIS.

  13. Activation of MTOR in pulmonary epithelium promotes LPS-induced acute lung injury.

    Science.gov (United States)

    Hu, Yue; Lou, Jian; Mao, Yuan-Yuan; Lai, Tian-Wen; Liu, Li-Yao; Zhu, Chen; Zhang, Chao; Liu, Juan; Li, Yu-Yan; Zhang, Fan; Li, Wen; Ying, Song-Min; Chen, Zhi-Hua; Shen, Hua-Hao

    2016-12-01

    MTOR (mechanistic target of rapamycin [serine/threonine kinase]) plays a crucial role in many major cellular processes including metabolism, proliferation and macroautophagy/autophagy induction, and is also implicated in a growing number of proliferative and metabolic diseases. Both MTOR and autophagy have been suggested to be involved in lung disorders, however, little is known about the role of MTOR and autophagy in pulmonary epithelium in the context of acute lung injury (ALI). In the present study, we observed that lipopolysaccharide (LPS) stimulation induced MTOR phosphorylation and decreased the expression of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β)-II, a hallmark of autophagy, in mouse lung epithelium and in human bronchial epithelial (HBE) cells. The activation of MTOR in HBE cells was mediated by TLR4 (toll-like receptor 4) signaling. Genetic knockdown of MTOR or overexpression of autophagy-related proteins significantly attenuated, whereas inhibition of autophagy further augmented, LPS-induced expression of IL6 (interleukin 6) and IL8, through NFKB signaling in HBE cells. Mice with specific knockdown of Mtor in bronchial or alveolar epithelial cells exhibited significantly attenuated airway inflammation, barrier disruption, and lung edema, and displayed prolonged survival in response to LPS exposure. Taken together, our results demonstrate that activation of MTOR in the epithelium promotes LPS-induced ALI, likely through downregulation of autophagy and the subsequent activation of NFKB. Thus, inhibition of MTOR in pulmonary epithelial cells may represent a novel therapeutic strategy for preventing ALI induced by certain bacteria.

  14. Two essential regulatory elements in the human interferon gamma promoter confer activation specific expression in T cells.

    Science.gov (United States)

    Penix, L; Weaver, W M; Pang, Y; Young, H A; Wilson, C B

    1993-11-01

    Like interleukin 2 (IL-2), interferon gamma (IFN-gamma) is an early response gene in T cells and both are prototypical T helper cell type 1 (Th-1) lymphokines. Yet IL-2 and IFN-gamma production are independently regulated, as demonstrated by their differential expression in certain T cell subsets, suggesting that the regulatory elements in these two genes must differ. To explore this possibility, the 5' flank of the human IFN-gamma gene was analyzed. Expression of IFN-gamma promoter-driven beta-galactosidase reporter constructs containing 538 bp of 5' flank was similar to that by constructs driven by the IL-2 promoter in activated Jurkat T cells; expression nearly as great was observed with the construct containing only 108 bp of IFN-gamma 5' flank. These IFN-gamma promoter constructs faithfully mirrored expression of the endogenous gene, in that expression required activation both with ionomycin and PMA, was inhibited by cyclosporin A, and was not observed in U937 or THP-1 cells. The region between -108 and -40 bp in the IFN-gamma promoter was required for promoter function and contained two elements that are conserved across species. Deletion of 10 bp within either element reduced promoter function by 70%, whereas deletions in nonconserved portions of this region had little effect on promoter function. The distal conserved element (-96 to -80 bp) contained a consensus GATA motif and a potential regulatory motif found in the promoter regions of the GM-CSF and macrophage inflammatory protein (MIP) genes. Factors binding to this element, including GATA-3, were found in Jurkat nuclear extracts by electromobility shift assays and two of the three complexes observed were altered in response to activation. One or both of these motifs are present in the 5' flank of multiple, other lymphokine genes, including IL-3, IL-4, IL-5, and GM-CSF, but neither is present in the promoter of the IL-2 gene. The proximal conserved element (-73 to -48 bp) shares homology with the NFIL-2

  15. Pancreatic endoplasmic reticulum kinase activation promotes medulloblastoma cell migration and invasion through induction of vascular endothelial growth factor A.

    Directory of Open Access Journals (Sweden)

    Stephanie Jamison

    Full Text Available Evidence is accumulating that activation of the pancreatic endoplasmic reticulum kinase (PERK in response to endoplasmic reticulum (ER stress adapts tumor cells to the tumor microenvironment and enhances tumor angiogenesis by inducing vascular endothelial growth factor A (VEGF-A. Recent studies suggest that VEGF-A can act directly on certain tumor cell types in an autocrine manner, via binding to VEGF receptor 2 (VEGFR2, to promote tumor cell migration and invasion. Although several reports show that PERK activation increases VEGF-A expression in medulloblastoma, the most common solid malignancy of childhood, the role that either PERK or VEGF-A plays in medulloblastoma remains elusive. In this study, we mimicked the moderate enhancement of PERK activity observed in tumor patients using a genetic approach and a pharmacologic approach, and found that moderate activation of PERK signaling facilitated medulloblastoma cell migration and invasion and increased the production of VEGF-A. Moreover, using the VEGFR2 inhibitor SU5416 and the VEGF-A neutralizing antibody to block VEGF-A/VEGFR2 signaling, our results suggested that tumor cell-derived VEGF-A promoted medulloblastoma cell migration and invasion through VEGFR2 signaling, and that both VEGF-A and VEGFR2 were required for the promoting effects of PERK activation on medulloblastoma cell migration and invasion. Thus, these findings suggest that moderate PERK activation promotes medulloblastoma cell migration and invasion through enhancement of VEGF-A/VEGFR2 signaling.

  16. Discovering anti-platelet drug combinations with an integrated model of activator-inhibitor relationships, activator-activator synergies and inhibitor-inhibitor synergies.

    Directory of Open Access Journals (Sweden)

    Federica Lombardi

    2015-04-01

    Full Text Available Identifying effective therapeutic drug combinations that modulate complex signaling pathways in platelets is central to the advancement of effective anti-thrombotic therapies. However, there is no systems model of the platelet that predicts responses to different inhibitor combinations. We developed an approach which goes beyond current inhibitor-inhibitor combination screening to efficiently consider other signaling aspects that may give insights into the behaviour of the platelet as a system. We investigated combinations of platelet inhibitors and activators. We evaluated three distinct strands of information, namely: activator-inhibitor combination screens (testing a panel of inhibitors against a panel of activators; inhibitor-inhibitor synergy screens; and activator-activator synergy screens. We demonstrated how these analyses may be efficiently performed, both experimentally and computationally, to identify particular combinations of most interest. Robust tests of activator-activator synergy and of inhibitor-inhibitor synergy required combinations to show significant excesses over the double doses of each component. Modeling identified multiple effects of an inhibitor of the P2Y12 ADP receptor, and complementarity between inhibitor-inhibitor synergy effects and activator-inhibitor combination effects. This approach accelerates the mapping of combination effects of compounds to develop combinations that may be therapeutically beneficial. We integrated the three information sources into a unified model that predicted the benefits of a triple drug combination targeting ADP, thromboxane and thrombin signaling.

  17. Application of the dual-luciferase reporter assay to the analysis of promoter activity in Zebrafish embryos

    Directory of Open Access Journals (Sweden)

    Mulero Victoriano

    2008-10-01

    Full Text Available Abstract Background The dual-luciferase assay has been widely used in cell lines to determine rapidly but accurately the activity of a given promoter. Although this strategy has proved very useful, it does not allow the promoter and gene function to be analyzed in the context of the whole organism. Results Here, we present a rapid and sensitive assay based on the classical dual-luciferase reporter technique which can be used as a new tool to characterize the minimum promoter region of a gene as well as the in vivo response of inducible promoters to different stimuli. We illustrate the usefulness of this system for studying both constitutive (telomerase and inducible (NF-κB-dependent promoters. The flexibility of this assay is demonstrated by induction of the NF-κB-dependent promoters using simultaneous microinjection of different pathogen-associated molecular patterns as well as with the use of morpholino-gene mediated knockdown. Conclusion This assay has several advantages compared with the classical in vitro (cell lines and in vivo (transgenic mice approaches. Among others, the assay allows a rapid and quantitative measurement of the effects of particular genes or drugs in a given promoter in the context of a whole organism and it can also be used in high throughput screening experiments.

  18. Single-nucleotide polymorphisms and activity analysis of the promoter and enhancer of the pig lactase gene.

    Science.gov (United States)

    Du, Hai-Ting; Zhu, Hong-Yan; Wang, Jia-Mei; Zhao, Wei; Tao, Xiao-Li; Ba, Cai-Feng; Tian, Yu-Min; Su, Yu-Hong

    2014-07-15

    Lactose intolerance in northern Europeans is strongly associated with a single-nucleotide polymorphism (SNP) located 14 kb upstream of the human lactase gene: -13,910 C/T. We examined whether SNPs in the 5' flanking region of the pig lactase gene are similar to those in the human gene and whether these polymorphisms play a functional role in regulating pig lactase gene expression. The 5' flanking region of the lactase gene from several different breeds of pigs was cloned and analyzed for gene regulatory activity of a luciferase reporter gene. One SNP was found in the enhancer region (-797 G/A) and two were found in the promoter region (-308G/C and -301 A/G). The promoter C-308,G-301(Pro-CG) strongly promotes the expression of the lactase gene, but the promoter G-308,A-301(Pro-GA) does not. The enhancer A-797(Enh-A) genotype for Pro-GA can significantly enhance promoter activity, but has an inhibitory effect on Pro-CG. The Enhancer G-797(Enh-G) has a significant inhibitory effect on both promoters. In conclusion, the order of effectiveness on the pig lactase gene is Enh-A+Pro-GA>Enh-A/G+Pro-CG>Enh-G+Pro-GA.

  19. Characterization of a putative cis-regulatory element that controls transcriptional activity of the pig uroplakin II gene promoter.

    Science.gov (United States)

    Kwon, Deug-Nam; Park, Mi-Ryung; Park, Jong-Yi; Cho, Ssang-Goo; Park, Chankyu; Oh, Jae-Wook; Song, Hyuk; Kim, Jae-Hwan; Kim, Jin-Hoi

    2011-07-01

    Uroplakin II (UPII) is a one of the integral membrane proteins synthesized as a major differentiation product of mammalian urothelium. UPII gene expression is bladder specific and differentiation dependent, but little is known about its transcription response elements and molecular mechanism. To identify the cis-regulatory elements in the pig UPII (pUPII) gene promoter region, we constructed pUPII 5' upstream region deletion mutants and demonstrated that each of the deletion mutants participates in controlling the expression of the pUPII gene in human bladder carcinoma RT4 cells. We also identified a new core promoter region and putative negative cis-regulatory element within a minimal promoter region. In addition, we showed that hepatocyte nuclear factor 4 (HNF4) can directly bind in the pUPII core promoter (5F-1) region, which plays a critical role in controlling promoter activity. Transient cotransfection experiments showed that HNF4 positively regulates pUPII gene promoter activity. Thus, the binding element and its binding protein, HNF4 transcription factor, may be involved in the mechanism that specifically regulates pUPII gene transcription.

  20. PLCz functional haplotypes modulating promoter transcriptional activity are associated with semen quality traits in Chinese Holstein bulls.

    Directory of Open Access Journals (Sweden)

    Qing Pan

    Full Text Available The sperm-specific phospholipase C zeta (PLCz is a candidate sperm-borne oocyte-activating factor that triggers a characteristic series of physiological stimuli via cytoplasmic Ca(2+ oscillations during fertilization. The molecular mechanisms involved in the regulation of PLCz gene expression remain largely unknown. To explore the genetic variations in the 5'-flanking region of the PLCz gene and their common haplotypes in Chinese Holstein bulls, as well as to determine whether these variations affect bovine semen quality traits and transcriptional activity, DNA samples were collected from Chinese Holstein bulls and sequenced for the identification of genetic variants in the 5'-flanking region of PLCz. Two genetic variants were identified, and their haplotypic profiles were constructed. The two novel genetic variations (g. -456 G>A and g. +65 T>C were genotyped in 424 normal Chinese Holstein bulls. Bioinformatics analysis revealed that both loci are in transcription factor binding sites of the core promoter region. The association studies revealed that the two genetic variations and their haplotype combinations significantly affected semen quality traits. Using serially truncated constructs of the bovine PLCz promoters and the luciferase reporter, we found that a 726 bp (-641 nt to +112 nt fragment constitutes the core promoter region. Furthermore, four haplotypes, H1H1 (GTGT, H2H2 (GCGC, H3H3 (ATAT, and H4H4 (ACAC, were significantly associated with semen quality traits and successfully transfected into MLTC-1 cell lines. The luciferase reporter assay showed that the different haplotypes exhibited distinct promoter activities. Maximal promoter activity was demonstrated by the H2H2 haplotypes, as compared with the other haplotypes. To the best of our knowledge, this study is the first report on genetic variants and their respective haplotypes in the 5'-flanking region of PLCz gene that can influence the semen quality of Chinese Holstein bulls as

  1. TGF-β promotes glioma cell growth via activating Nodal expression through Smad and ERK1/2 pathways

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jing [Department of Neurology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang (China); Liu, Su-zhi [Department of Neurology, The Affiliated Taizhou Hospital, Wenzhou Medical University, Taizhou 317000, Zhejiang (China); Lin, Yan; Cao, Xiao-pan [Department of Neurology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang (China); Liu, Jia-ming, E-mail: wzljm@126.com [School of Environmental Science and Public Health, Wenzhou Medical University, Wenzhou 325035, Zhejiang (China)

    2014-01-17

    Highlights: •TGF-β promoted Nodal expression in glioma cells. •TGF-β promoted Nodal expression via activating Smad and ERK1/2 pathways. •TGF-β promotes glioma cell growth via activating Nodal expression. -- Abstract: While there were certain studies focusing on the mechanism of TGF-β promoting the growth of glioma cells, the present work revealed another novel mechanism that TGF-β may promote glioma cell growth via enhancing Nodal expression. Our results showed that Nodal expression was significantly upregulated in glioma cells when TGF-β was added, whereas the TGF-β-induced Nodal expression was evidently inhibited by transfection Smad2 or Smad3 siRNAs, and the suppression was especially significant when the Smad3 was downregulated. Another, the attenuation of TGF-β-induced Nodal expression was observed with blockade of the ERK1/2 pathway also. Further detection of the proliferation, apoptosis, and invasion of glioma cells indicated that Nodal overexpression promoted the proliferation and invasion of tumor cells and inhibited their apoptosis, resembling the effect of TGF-β addition. Downregulation of Nodal expression via transfection Nodal-specific siRNA in the presence of TGF-β weakened the promoting effect of the latter on glioma cells growth, and transfecting Nodal siRNA alone in the absence of exogenous TGF-β more profoundly inhibited the growth of glioma cells. These results demonstrated that while both TGF-β and Nodal promoted glioma cells growth, the former might exert such effect by enhancing Nodal expression, which may form a new target for glioma therapy.

  2. Genetic Variants in the STMN1 Transcriptional Regulatory Region Affect Promoter Activity and Fear Behavior in English Springer Spaniels.

    Directory of Open Access Journals (Sweden)

    Xiaolin Ding

    Full Text Available Stathmin 1 (STMN1 is a neuronal growth-associated protein that is involved in microtubule dynamics and plays an important role in synaptic outgrowth and plasticity. Given that STMN1 affects fear behavior, we hypothesized that genetic variations in the STMN1 transcriptional regulatory region affect gene transcription activity and control fear behavior. In this study, two single nucleotide polymorphisms (SNPs, g. -327 A>G and g. -125 C>T, were identified in 317 English Springer Spaniels. A bioinformatics analysis revealed that both were loci located in the canine STMN1 putative promoter region and affected transcription factor binding. A statistical analysis revealed that the TT genotype at g.-125 C>T produced a significantly greater fear level than that of the CC genotype (P < 0.05. Furthermore, the H4H4 (GTGT haplotype combination was significantly associated with canine fear behavior (P < 0.01. Using serially truncated constructs of the STMN1 promoters and the luciferase reporter, we found that a 395 bp (-312 nt to +83 nt fragment constituted the core promoter region. The luciferase assay also revealed that the H4 (GT haplotype promoter had higher activity than that of other haplotypes. Overall, our results suggest that the two SNPs in the canine STMN1 promoter region could affect canine fear behavior by altering STMN1 transcriptional activity.

  3. Ceruloplasmin Oxidation, a Feature of Parkinson's Disease CSF, Inhibits Ferroxidase Activity and Promotes Cellular Iron Retention

    KAUST Repository

    Olivieri, S.

    2011-12-14

    Parkinson\\'s disease is a neurodegenerative disorder characterized by oxidative stress and CNS iron deposition. Ceruloplasmin is an extracellular ferroxidase that regulates cellular iron loading and export, and hence protects tissues from oxidative damage. Using two-dimensional electrophoresis, we investigated ceruloplasmin patterns in the CSF of human Parkinson\\'s disease patients. Parkinson\\'s disease ceruloplasmin profiles proved more acidic than those found in healthy controls and in other human neurological diseases (peripheral neuropathies, amyotrophic lateral sclerosis, and Alzheimer\\'s disease); degrees of acidity correlated with patients\\' pathological grading. Applying an unsupervised pattern recognition procedure to the two-dimensional electrophoresis images, we identified representative pathological clusters. In vitro oxidation of CSF in two-dimensional electrophoresis generated a ceruloplasmin shift resembling that observed in Parkinson\\'s disease and co-occurred with an increase in protein carbonylation. Likewise, increased protein carbonylation was observed in Parkinson\\'s disease CSF, and the same modification was directly identified in these samples on ceruloplasmin. These results indicate that ceruloplasmin oxidation contributes to pattern modification in Parkinson\\'s disease. From the functional point of view, ceruloplasmin oxidation caused a decrease in ferroxidase activity, which in turn promotes intracellular iron retention in neuronal cell lines as well as in primary neurons, which are more sensitive to iron accumulation. Accordingly, the presence of oxidized ceruloplasmin in Parkinson\\'s disease CSF might be used as a marker for oxidative damage and might provide new insights into the underlying pathological mechanisms.

  4. TLR-induced activation of neutrophils promotes histamine production via a PI3 kinase dependent mechanism.

    Science.gov (United States)

    Smuda, Craig; Wechsler, Joshua B; Bryce, Paul J

    2011-12-30

    Histamine is a bioactive amine that exerts immunomodulatory functions, including many allergic symptoms. It is preformed and stored in mast cells and basophils but recent evidence suggests that other cell types produce histamine in an inducible fashion. During infection, it has been suggested that neutrophils may produce histamine. We also observed that histamine is released in a neutrophil-mediated LPS-induced model of acute lung injury. Therefore, we sought to examine whether innate signals promote histamine production by neutrophils. Bone marrow-derived neutrophils stimulated with a range of TLR agonists secreted histamine in response to LPS or R837, suggesting TLR4 or TLR7 are important. LPS-driven histamine was enhanced by coculture with GM-CSF and led to a transient release of histamine that peaked at 8h post stimulation. This was dependent upon de novo synthesis of histamine, since cells derived from histidine decarboxylase (HDC) deficient mice were unable to produce histamine but did generate reactive oxygen species upon stimulation. Using pharmacological inhibitors, we show that histamine production requires PI3 kinase, which has been shown to regulate other neutrophil functions, including activation and selective granule release. However, unlike mast cells, HDC deficiency did not alter the granule structure of neutrophils, suggesting that histamine does not participate in granule integrity in these cells. Consequently, our findings establish that neutrophils generate histamine in response to a select panel of innate immune triggers and that this might contribute to acute lung injury responses.

  5. Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesis.

    Science.gov (United States)

    Wassef, Michel; Rodilla, Veronica; Teissandier, Aurélie; Zeitouni, Bruno; Gruel, Nadege; Sadacca, Benjamin; Irondelle, Marie; Charruel, Margaux; Ducos, Bertrand; Michaud, Audrey; Caron, Matthieu; Marangoni, Elisabetta; Chavrier, Philippe; Le Tourneau, Christophe; Kamal, Maud; Pasmant, Eric; Vidaud, Michel; Servant, Nicolas; Reyal, Fabien; Meseure, Dider; Vincent-Salomon, Anne; Fre, Silvia; Margueron, Raphaël

    2015-12-15

    Alterations of chromatin modifiers are frequent in cancer, but their functional consequences often remain unclear. Focusing on the Polycomb protein EZH2 that deposits the H3K27me3 (trimethylation of Lys27 of histone H3) mark, we showed that its high expression in solid tumors is a consequence, not a cause, of tumorigenesis. In mouse and human models, EZH2 is dispensable for prostate cancer development and restrains breast tumorigenesis. High EZH2 expression in tumors results from a tight coupling to proliferation to ensure H3K27me3 homeostasis. However, this process malfunctions in breast cancer. Low EZH2 expression relative to proliferation and mutations in Polycomb genes actually indicate poor prognosis and occur in metastases. We show that while altered EZH2 activity consistently modulates a subset of its target genes, it promotes a wider transcriptional instability. Importantly, transcriptional changes that are consequences of EZH2 loss are predominantly irreversible. Our study provides an unexpected understanding of EZH2's contribution to solid tumors with important therapeutic implications.

  6. IL-23 activates innate lymphoid cells to promote neonatal intestinal pathology.

    Science.gov (United States)

    Chen, L; He, Z; Slinger, E; Bongers, G; Lapenda, T Ls; Pacer, M E; Jiao, J; Beltrao, M F; Soto, A J; Harpaz, N; Gordon, R E; Ochando, J C; Oukka, M; Iuga, A C; Chensue, S W; Blander, J M; Furtado, G C; Lira, S A

    2015-03-01

    Interleukin-23 (IL-23) responsive group 3 innate lymphoid cells (ILC3s) have been implicated in immune homeostasis and pathogenesis in the adult, but little is known about their roles in the newborn. Here we show that IL-23 promotes conversion of embryonic intestinal Lin(-)IL-23R(+)Thy1(+) cells into IL-22-producing Thy1(+)Sca-1(hi) ILC3s in vitro. Gut-specific expression of IL-23 also activated and expanded Thy1(+)Sca-1(hi) ILC3s, which produced IL-22, IL-17, interferon gamma (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) and were distinct from canonical CD4(+) lymphoid tissue inducer (LTi) cells. These ILC3s accumulated under the epithelium in intercellular adhesion molecule (ICAM)-1-positive cell aggregates together with neutrophils that disrupted the epithelium, leading to the formation of discrete intestinal erosions, bleeding, and neonatal death. Genetic and antibody depletion of ILC3s rescued the mice from neonatal death. Antibiotic treatment of pregnant mothers and offspring prolonged survival of IL-23 transgenic mice, suggesting a role for the commensal flora on ILC3-induced pathogenesis. Our results reveal a novel role for the IL-23-ILC3s axis in the pathogenesis of neonatal intestinal inflammation.

  7. The Rab2A GTPase Promotes Breast Cancer Stem Cells and Tumorigenesis via Erk Signaling Activation

    Directory of Open Access Journals (Sweden)

    Man-Li Luo

    2015-04-01

    Full Text Available Proline-directed phosphorylation is regulated by the prolyl isomerase Pin1, which plays a fundamental role in driving breast cancer stem-like cells (BCSCs. Rab2A is a small GTPase critical for vesicle trafficking. Here, we show that Pin1 increases Rab2A transcription to promote BCSC expansion and tumorigenesis in vitro and in vivo. Mechanistically, Rab2A directly interacts with and prevents dephosphorylation/inactivation of Erk1/2 by the MKP3 phosphatase, resulting in Zeb1 upregulation and β-catenin nuclear translocation. In cancer cells, Rab2A is activated via gene amplification, mutation or Pin1 overexpression. Rab2A overexpression or mutation endows BCSC traits to primary normal human breast epithelial cells, whereas silencing Rab2A potently inhibits the expansion and tumorigenesis of freshly isolated BCSCs. Finally, Rab2A overexpression correlates with poor clinical outcome in breast cancer patients. Thus, Pin1/Rab2A/Erk drives BCSC expansion and tumorigenicity, suggesting potential drug targets.

  8. Promotion of Sink Activity of Developing Rose Shoots by Light 1

    Science.gov (United States)

    Mor, Yoram; Halevy, Abraham H.

    1980-01-01

    Holding young rose shoots (Rosa hybrida cv. Marimba) in darkness while the rest of the plant was in light reduced the amount of 14C assimilates recovered from the darkened shoot by half. Relative specific activity of the shoot tip grown in light was 13.5 times greater than that of the darkened one. The flower bud at the shoot tip degenerated in darkness and died. Shoots 2 to 3 centimeters long, after flower initiation, were most sensitive to the dark treatment. The degeneration is a gradual and reversible process in the first 8 days of darkness, followed by irreversible damage and atrophy. Darkening enhanced the ability of the young leaves to compete for the available assimilates over that of the darkened shoot tip. The enhancement of the mobilizing ability of the shoot tip by light is independent of photosynthesis since spraying with 3-(3,4-dichlorophenyl)-1,1-dimethylurea or holding shoots in a CO2-free atmosphere did not diminish the promoting effect of light on flower bud development or assimilate import. The possibility that light exerts its effect by photoproduction of ATP was also excluded inasmuch as no differences were found in ATP levels of shoot tips held in darkness and those held in light. PMID:16661566

  9. A-FABP mediates adaptive thermogenesis by promoting intracellular activation of thyroid hormones in brown adipocytes

    Science.gov (United States)

    Shu, Lingling; Hoo, Ruby L. C.; Wu, Xiaoping; Pan, Yong; Lee, Ida P. C.; Cheong, Lai Yee; Bornstein, Stefan R; Rong, Xianglu; Guo, Jiao; Xu, Aimin

    2017-01-01

    The adipokine adipocyte fatty acid-binding protein (A-FABP) has been implicated in obesity-related cardio-metabolic complications. Here we show that A-FABP increases thermogenesis by promoting the conversion of T4 to T3 in brown adipocytes. We find that A-FABP levels are increased in both white (WAT) and brown (BAT) adipose tissues and the bloodstream in response to thermogenic stimuli. A-FABP knockout mice have reduced thermogenesis and whole-body energy expenditure after cold stress or after feeding a high-fat diet, which can be reversed by infusion of recombinant A-FABP. Mechanistically, A-FABP induces the expression of type-II iodothyronine deiodinase in BAT via inhibition of the nuclear receptor liver X receptor α, thereby leading to the conversion of thyroid hormone from its inactive form T4 to active T3. The thermogenic responses to T4 are abrogated in A-FABP KO mice, but enhanced by A-FABP. Thus, A-FABP acts as a physiological stimulator of BAT-mediated adaptive thermogenesis. PMID:28128199

  10. Altered promoter recycling rates contribute to dominant-negative activity of human peroxisome proliferator-activated receptor-gamma mutations associated with diabetes.

    Science.gov (United States)

    Li, Gang; Leff, Todd

    2007-04-01

    The transcription factor peroxisome proliferator-activated receptor-gamma (PPARgamma) plays an important role in regulating lipid and glucose metabolism and improves insulin sensitivity in diabetic patients when activated by thiazolidinedione drugs. Several loss-of-function mutations in PPARgamma have been identified that cause lipodystrophy and diabetes in humans. Because affected individuals are heterozygotes and have one normal PPARgamma allele, it is of interest to know whether these mutations act in a dominant-negative fashion to inhibit the activity of the wild-type (WT) receptor. Here we compare the molecular phenotypes of two previously identified PPARgamma mutations: P467L, reported to be dominant negative; and F388L, reported to be devoid of dominant-negative activity. We developed a competitive chromatin immunoprecipitation assay to measure the relative ability of mutant PPARgamma to compete with WT receptor for binding to a PPAR regulatory element (PPRE)-containing promoter. By determining the ratio of mutant and WT receptors bound to a PPRE over time, we estimated the relative promoter turnover rate of each receptor. This assay demonstrated that PPARgamma bearing the P467L had a reduced promoter turnover rate compared with the F388L receptor, and over time out-competed the WT receptor for promoter binding sites. We propose that the P467L receptor is dominant negative because in a cell containing both WT and mutant receptors, the majority of the PPAR-regulated promoters will be occupied by the transcriptionally defective mutant receptor. In contrast, the F388L mutation lacks dominant-negative activity because its more rapid promoter turnover rate prevented it from out-competing the WT receptor for promoter binding sites.

  11. Orbital fluid shear stress promotes osteoblast metabolism, proliferation and alkaline phosphates activity in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Aisha, M.D. [Institute of Medical Molecular Biotechnology and Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor (Malaysia); Nor-Ashikin, M.N.K. [Institute of Medical Molecular Biotechnology and Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor (Malaysia); DDH, Universiti Teknologi MARA, ShahAlam 40450, Selangor (Malaysia); Sharaniza, A.B.R. [DDH, Universiti Teknologi MARA, ShahAlam 40450, Selangor (Malaysia); Nawawi, H. [Center for Pathology Diagnostic and Research Laboratories, Clinical Training Center, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor (Malaysia); I-PPerForM, Universiti Teknologi MARA, Selayang 47000 Selangor (Malaysia); Froemming, G.R.A., E-mail: gabriele@salam.uitm.edu.my [Institute of Medical Molecular Biotechnology and Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor (Malaysia); I-PPerForM, Universiti Teknologi MARA, Selayang 47000 Selangor (Malaysia)

    2015-09-10

    Prolonged disuse of the musculoskeletal system is associated with reduced mechanical loading and lack of anabolic stimulus. As a form of mechanical signal, the multidirectional orbital fluid shear stress transmits anabolic signal to bone forming cells in promoting cell differentiation, metabolism and proliferation. Signals are channeled through the cytoskeleton framework, directly modifying gene and protein expression. For that reason, we aimed to study the organization of Normal Human Osteoblast (NHOst) cytoskeleton with regards to orbital fluid shear (OFS) stress. Of special interest were the consequences of cytoskeletal reorganization on NHOst metabolism, proliferation, and osteogenic functional markers. Cells stimulated at 250 RPM in a shaking incubator resulted in the rearrangement of actin and tubulin fibers after 72 h. Orbital shear stress increased NHOst mitochondrial metabolism and proliferation, simultaneously preventing apoptosis. The ratio of RANKL/OPG was reduced, suggesting that orbital shear stress has the potential to inhibit osteoclastogenesis and osteoclast activity. Increase in ALP activity and OCN protein production suggests that stimulation retained osteoblast function. Shear stress possibly generated through actin seemed to hold an anabolic response as osteoblast metabolism and functional markers were enhanced. We hypothesize that by applying orbital shear stress with suitable magnitude and duration as a non-drug anabolic treatment can help improve bone regeneration in prolonged disuse cases. - Highlights: • OFS stress transmits anabolic signals to osteoblasts. • Actin and tubulin fibers are rearranged under OFS stress. • OFS stress increases mitochondrial metabolism and proliferation. • Reduced RANKL/OPG ratio in response to OFS inhibits osteoclastogenesis. • OFS stress prevents apoptosis and stimulates ALP and OCN.

  12. Mangiferin decreases plasma free fatty acids through promoting its catabolism in liver by activation of AMPK.

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    Yucun Niu

    Full Text Available Mangiferin has been shown to have the effect of improving dyslipidemia. Plasma free fatty acids (FFA are closely associated with blood lipid metabolism as well as many diseases including metabolic syndrome. This study is to investigate whether mangiferin has effects on FFA metabolism in hyperlipidemic rats. Wistar rats were fed a high-fat diet and administered mangiferin simultaneously for 6 weeks. Mangiferin (50, 100, 150 mg/kg BW decreased dose-dependently FFA and triglycerides (TG levels in plasma, and their accumulations in liver, but increased the β-hydroxybutyrate levels in both plasma and liver of hyperlipidemic rats. HepG2 cells were treated with oleic acid (OA, 0.2 mmol/L to simulate the condition of high level of plasma FFA in vitro, and were treated with different concentrations of mangiferin simultaneously for 24 h. We found that mangiferin significantly increased FFA uptake, significantly decreased intracellular FFA and TG accumulations in HepG2 cells. Mangiferin significantly increased AMP-activated protein kinase (AMPK phosphorylation and its downstream proteins involved in fatty acid translocase (CD36 and carnitine palmitoyltransferase 1 (CPT1, but significantly decreased acyl-CoA: diacylgycerol acyltransferase 2 (DGAT2 expression and acetyl-CoA carboxylase (ACC activity by increasing its phosphorylation level in both in vivo and in vitro studies. Furthermore, these effects were reversed by Compound C, an AMPK inhibitor in HepG2 cells. For upstream of AMPK, mangiferin increased AMP/ATP ratio, but had no effect on LKB1 phosphorylation. In conclusion, mangiferin decreased plasma FFA levels through promoting FFA uptake and oxidation, inhibiting FFA and TG accumulations by regulating the key enzymes expression in liver through AMPK pathway. Therefore, mangiferin is a possible beneficial natural compound for metabolic syndrome by improving FFA metabolism.

  13. Mangiferin Decreases Plasma Free Fatty Acids through Promoting Its Catabolism in Liver by Activation of AMPK

    Science.gov (United States)

    Niu, Yucun; Li, Songtao; Na, Lixin; Feng, Rennan; Liu, Liyan; Li, Ying; Sun, Changhao

    2012-01-01

    Mangiferin has been shown to have the effect of improving dyslipidemia. Plasma free fatty acids (FFA) are closely associated with blood lipid metabolism as well as many diseases including metabolic syndrome. This study is to investigate whether mangiferin has effects on FFA metabolism in hyperlipidemic rats. Wistar rats were fed a high-fat diet and administered mangiferin simultaneously for 6 weeks. Mangiferin (50, 100, 150 mg/kg BW) decreased dose-dependently FFA and triglycerides (TG) levels in plasma, and their accumulations in liver, but increased the β-hydroxybutyrate levels in both plasma and liver of hyperlipidemic rats. HepG2 cells were treated with oleic acid (OA, 0.2 mmol/L) to simulate the condition of high level of plasma FFA in vitro, and were treated with different concentrations of mangiferin simultaneously for 24 h. We found that mangiferin significantly increased FFA uptake, significantly decreased intracellular FFA and TG accumulations in HepG2 cells. Mangiferin significantly increased AMP-activated protein kinase (AMPK) phosphorylation and its downstream proteins involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1), but significantly decreased acyl-CoA: diacylgycerol acyltransferase 2 (DGAT2) expression and acetyl-CoA carboxylase (ACC) activity by increasing its phosphorylation level in both in vivo and in vitro studies. Furthermore, these effects were reversed by Compound C, an AMPK inhibitor in HepG2 cells. For upstream of AMPK, mangiferin increased AMP/ATP ratio, but had no effect on LKB1 phosphorylation. In conclusion, mangiferin decreased plasma FFA levels through promoting FFA uptake and oxidation, inhibiting FFA and TG accumulations by regulating the key enzymes expression in liver through AMPK pathway. Therefore, mangiferin is a possible beneficial natural compound for metabolic syndrome by improving FFA metabolism. PMID:22292039

  14. Flurbiprofen axetil promotes neuroprotection by activation of cerebral peroxisome proliferator-activated receptor gamma after focal cerebral ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    LIU Jun-le; JIN Jian-wen; PEI Shu-jun; WANG Chen

    2012-01-01

    Background Our previous papers indicate that flurbiprofen axetil (FA),a cyclooxygenase inhibitor,is a promising therapeutic strategy for cerebral ischemia in rats.This study aimed to investigate whether FA could promote a neuroprotective effect by activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) after focal cerebral ischemia in rats.Methods Totally 48 male Sprague-Dawley (SD) rats were randomly assigned into six groups (n=8 in each group):animals in group ischemia/reperfusion (I/R) only received 120-minute transient middle cerebral artery occlusion (tMCAO);animals in group I/R +FA were administered FA (10 mg/kg) by caudal vein just after 120-minute tMCAO; animals in group I/R +FA+GW9662 were administered GW9662 (a PPAR-γ inhibitor,1 mg/kg) intraperitoneally 30 minutes before cerebral ischemia onset and FA (10 mg/kg) by caudal vein just after 120-minute tMCAO; animals in group I/R +GW9662 were administered GW9662 (1 mg/kg) intraperitoneally 30 minutes before cerebral ischemia onset; animals in group I/R +DMSO were administered 3% DMSO (vehicle of GW9662,1 ml/kg) intraperitoneally 30 minutes before cerebral ischemia onset; animals in sham group experienced the identical surgery apart from the insertion of the nylon filament.The neurologic deficit score (NDS) were performed at 72 hours after reperfusion,and then mean brain infarct volume percentage (MBIVP) was determined with 2,3,5-triphenyltetrazolium chloride (TTC) 10(g)/L staining.Results NDS was significantly increased in group I/R+FA (12.0 (10.0-15.0)),group I/R+FA+GW9662 (10.0 (8.0-12.0)),and in group I/R+FA+DMSO (12.0 (9.0-14.0)) at 72 hours after reperfusion compared with those in group I/R (7.5(6.0-10.0)) NDS was conspicuously different between group I/R+FA (12.0 (10.0-15.0)) and group I/R+FA+GW9662 (10.0 (8.0-12.0)).MBIVP in group I/R ((45.82±8.83)%) was significantly greater than that in group I/R+FA((23.52±9.90)%),group I/R+FA+GW9662 ((33.17±7.15)%); MBIVP in group

  15. Zinc promotes proliferation and activation of myogenic cells via the PI3K/Akt and ERK signaling cascade

    Energy Technology Data Exchange (ETDEWEB)

    Ohashi, Kazuya, E-mail: asuno10k@yahoo.co.jp [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo (Japan); Nagata, Yosuke, E-mail: cynagata@mail.ecc.u-tokyo.ac.jp [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo (Japan); Wada, Eiji, E-mail: gacchu1@yahoo.co.jp [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo (Japan); Zammit, Peter S., E-mail: peter.zammit@kcl.ac.uk [Randall Division of Cell and Molecular Biophysics, King' s College London, London SE1 1UL (United Kingdom); Shiozuka, Masataka, E-mail: cmuscle@mail.ecc.u-tokyo.ac.jp [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo (Japan); Matsuda, Ryoichi, E-mail: cmatsuda@mail.ecc.u-tokyo.ac.jp [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo (Japan)

    2015-05-01

    Skeletal muscle stem cells named muscle satellite cells are normally quiescent but are activated in response to various stimuli, such as injury and overload. Activated satellite cells enter the cell cycle and proliferate to produce a large number of myogenic progenitor cells, and these cells then differentiate and fuse to form myofibers. Zinc is one of the essential elements in the human body, and has multiple roles, including cell growth and DNA synthesis. However, the role of zinc in myogenic cells is not well understood, and is the focus of this study. We first examined the effects of zinc on differentiation of murine C2C12 myoblasts and found that zinc promoted proliferation, with an increased number of cells incorporating EdU, but inhibited differentiation with reduced myogenin expression and myotube formation. Furthermore, we used the C2C12 reserve cell model of myogenic quiescence to investigate the role of zinc on activation of myogenic cells. The number of reserve cells incorporating BrdU was increased by zinc in a dose dependent manner, with the number dramatically further increased using a combination of zinc and insulin. Akt and extracellular signal-regulated kinase (ERK) are downstream of insulin signaling, and both were phosphorylated after zinc treatment. The zinc/insulin combination-induced activation involved the phosphoinositide 3-kinase (PI3K)/Akt and ERK cascade. We conclude that zinc promotes activation and proliferation of myogenic cells, and this activation requires phosphorylation of PI3K/Akt and ERK as part of the signaling cascade. - Highlights: • Zinc has roles for promoting proliferation and inhibition differentiation of C2C12. • Zinc promotes activation of reserve cells. • Insulin and zinc synergize activation of reserve cells. • PI3K/Akt and ERK cascade affect zinc/insulin-mediated activation of reserve cells.

  16. Epidermal growth factor activates telomerase activity by direct binding of Ets-2 to hTERT promoter in lung cancer cells.

    Science.gov (United States)

    Hsu, Chung-Ping; Lee, Li-Wen; Tang, Sheau-Chung; Hsin, I-Lun; Lin, Yu-Wen; Ko, Jiunn-Liang

    2015-07-01

    Growth signals are directly or indirectly involved in telomerase regulation. In this study, we investigated molecular mechanisms of the effect of EGF (epidermal growth factor) on regulating hTERT (human telomerase reverse transcriptase) expression. To elucidate specific transcription factors involved in EGF-stimulated hTERT transcription in A549 and H1299 lung cancer cells, transcription factors drives hTERT promoter activity, such as Myc, Mad, and Ets-2, was evaluated on luciferase reporter assay. The upregulation of hTERT promoter by Ets-2 and Myc were abolished by Mad. Using DAPA (DNA affinity precipitation assay), Ets-2 binding to SNP (T) was stronger than Ets-2 binding to SNP (C) at -245 bp upstream of the transcription start site within the core promoter of hTERT. Ets-2 silence by siRNA decreased hTERT expression at mRNA and protein levels. The regulation of hTERT promoter by EGF/Ets-2 was diminished via the EGFR kinase signal pathway-specific inhibitors AG1478 and Iressa. Inhibitors of Erk and Akt inhibited Ets-2-activated hTERT promoter activity. These data suggested that Ets-2, a genuine cancer-specific transcription factor, is actively involved in EGFR kinase-induced hTERT overexpression pathway in lung cancer cells. Blockage of this pathway may contribute to targeted gene therapy in lung cancer.

  17. Degradation of Jatropha curcas phorbol esters derived from Jatropha oil cake and their tumor-promoting activity.

    Science.gov (United States)

    Nakao, Motoyuki; Hasegawa, Go; Yasuhara, Tadashi; Ishihara, Yoko

    2015-04-01

    Large amount of oil cake is generated during biodiesel production from Jatropha seeds. Although Jatropha oil cake is rich in plant nutrients, presence of toxic phorbol esters restricts the usage of oil cake as a fertilizer. The objective of this study is to evaluate the components and tumor promoting activity of phorbol esters in Jatropha oil cake-supplemented soil and plants grown in the treated soil. Contents and their biological activity of Jatropha phorbol esters in soil and plants were sequentially analyzed by high-performance liquid chromatography (HPLC) and in vitro cell transformation assay, respectively. Disappearance of Jatropha phorbol-ester-specific peaks were followed with HPLC during incubation of Jatropha oil cake with soil for five weeks. Along with the degradation of Jatropha phorbol ester in soil, tumor-promoting activity in the sample was also attenuated and ultimately disappeared. Jatropha phorbol esters and tumor promoting activity were not detected from mustard spinach grown in the Jatropha oil cake-supplemented soil. In addition, the esterase KM109 degrades DHPB (see definition below; Jatropha phorbol ester) and reduced its tumor-promoting activity. From these data, we conclude: (1) components and tumor promoting activity of Jatropha phorbol esters in the oil cake disappeared completely by incubation with soil for five-week, (2) Jatropha phorbol esters did not transfer into plants grown in the Jatropha oil cake-supplemented soil, and (3) DHPB can be degraded by esterase from soil bacterium. These observations are useful for utilization of Jatropha oil cake as a fertilizer.

  18. An evaluation of a model for the systematic documentation of hospital based health promotion activities: results from a multicentre study

    DEFF Research Database (Denmark)

    Tønnesen, Hanne; Christensen, Mette E; Groene, Oliver;

    2007-01-01

    The first step of handling health promotion (HP) in Diagnosis Related Groups (DRGs) is a systematic documentation and registration of the activities in the medical records. So far the possibility and tradition for systematic registration of clinical HP activities in the medical records and in pat......The first step of handling health promotion (HP) in Diagnosis Related Groups (DRGs) is a systematic documentation and registration of the activities in the medical records. So far the possibility and tradition for systematic registration of clinical HP activities in the medical records...... of two parts; first part includes motivational counselling (7 codes) and the second part comprehends intervention, rehabilitation and after treatment (8 codes).The objective was to evaluate in an international study the usefulness, applicability and sufficiency of a simple model for the systematic...

  19. The human IL-2 gene promoter can assemble a positioned nucleosome that becomes remodeled upon T cell activation.

    Science.gov (United States)

    Attema, Joanne L; Reeves, Raymond; Murray, Vincent; Levichkin, Ilya; Temple, Mark D; Tremethick, David J; Shannon, M Frances

    2002-09-01

    Controlled production of the cytokine IL-2 plays a key role in the mammalian immune system. Expression from the gene is tightly regulated with no detectable expression in resting T cells and a strong induction following T cell activation. The IL-2 proximal promoter (+1 to -300) contains many well-defined transcriptional activation elements that respond to T cell stimulation. To determine the role of chromatin structure in the regulation of interleukin-2 gene transcription, nucleosome assembly across the IL-2 promoter region was examined using in vitro chromatin reconstitution assays. The IL-2 promoter assembles a nucleosome that is both translationally and rotationally positioned, spanning some of the major functional control elements. The binding of transcription factors to these elements, with the exception of the architectural protein HMGA1, was occluded by the presence of the nucleosome. Analysis of the chromatin architecture of the IL-2 gene in Jurkat T cells provided evidence for the presence of a similarly positioned nucleosome in vivo. The region encompassed by this nucleosome becomes remodeled following activation of Jurkat T cells. These observations suggest that the presence of a positioned nucleosome across the IL-2 proximal promoter may play an important role in maintaining an inactive gene in resting T cells and that remodeling of this nucleosome is important for gene activation.

  20. What Might Work? Exploring the Perceived Feasibility of Strategies to Promote Physical Activity among Women Living in Socioeconomically Disadvantaged Neighbourhoods

    Science.gov (United States)

    Cleland, Verity; Ball, Kylie

    2013-01-01

    This study aimed to investigate preferences for, perceived feasibility of and barriers to uptake of hypothetical physical activity promotion strategies among women from socioeconomically disadvantaged neighbourhoods. Semi-structured interviews were conducted with 20 purposively recruited women (18-45 years) living in socioeconomically…