431 research outputs found

    Make it Simple

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    [Excerpt] All citizens of the European Union have a democratic right to participate in the social and economic life of the society in which they live. Access to information about their society’s culture, literature, laws, local and national policies and ethos is fundamental in order to take part in mainstream life. Only informed citizens can influence or monitor the decisions that affect their lives and the lives of their families. This applies also to information about the policies and work of the European Union which are increasingly influencing the lives of its citizens. Furthermore, the new Information Society” makes it vital to be able to use and to understand the information systems being developed today

    Structures of falcipain-2 and falcipain-3 bound to small molecule inhibitors: implications for substrate specificity.

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    Falcipain-2 and falcipain-3 are critical hemoglobinases of Plasmodium falciparum, the most virulent human malaria parasite. We have determined the 2.9 A crystal structure of falcipain-2 in complex with the epoxysuccinate E64 and the 2.5 A crystal structure of falcipain-3 in complex with the aldehyde leupeptin. These complexes represent the first crystal structures of plasmodial cysteine proteases with small molecule inhibitors and the first reported crystal structure of falcipain-3. Our structural analyses indicate that the relative shape and flexibility of the S2 pocket are affected by a number of discrete amino acid substitutions. The cumulative effect of subtle differences, including those at "gatekeeper" positions, may explain the observed kinetic differences between these two closely related enzymes

    In vitro and in vivo studies of the trypanocidal properties of WRR-483 against Trypanosoma cruzi.

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    BackgroundCruzain, the major cysteine protease of Trypanosoma cruzi, is an essential enzyme for the parasite life cycle and has been validated as a viable target to treat Chagas' disease. As a proof-of-concept, K11777, a potent inhibitor of cruzain, was found to effectively eliminate T. cruzi infection and is currently a clinical candidate for treatment of Chagas' disease.Methodology/principal findingsWRR-483, an analog of K11777, was synthesized and evaluated as an inhibitor of cruzain and against T. cruzi proliferation in cell culture. This compound demonstrates good potency against cruzain with sensitivity to pH conditions and high efficacy in the cell culture assay. Furthermore, WRR-483 also eradicates parasite infection in a mouse model of acute Chagas' disease. To determine the atomic-level details of the inhibitor interacting with cruzain, a 1.5 A crystal structure of the protease in complex with WRR-483 was solved. The structure illustrates that WRR-483 binds covalently to the active site cysteine of the protease in a similar manner as other vinyl sulfone-based inhibitors. Details of the critical interactions within the specificity binding pocket are also reported.ConclusionsWe demonstrate that WRR-483 is an effective cysteine protease inhibitor with trypanocidal activity in cell culture and animal model with comparable efficacy to K11777. Crystallographic evidence confirms that the mode of action is by targeting the active site of cruzain. Taken together, these results suggest that WRR-483 has potential to be developed as a treatment for Chagas' disease

    Reclaiming public space:Sound and mobile media use by teenagers

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    This article explores the relationship between teenagers, mobile media, and public spaces in the city. We use a range of qualitative methods, including interviews, sound walks, sound maps, and photography, to explore how teenagers use mobile media to respond to the visual and sonic landscape of a public space in Dublin, Ireland. This space was a “nonplace” for our contemporary participants from which they felt economically, socially, visually, and aurally excluded. They responded by using mobile media to create safe, centripetal, and meaningful spaces. Our findings underline the role that local soundscapes play in understanding the audio and mobile media practices of teenagers in public spaces

    Effectiveness of a Home-Based Postal and Telephone Physical Activity and Nutrition Pilot Program for Seniors

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    Objective. To evaluate the effectiveness of a 12-week home-based postal and telephone physical activity and nutrition pilot program for seniors. Methods. The program was delivered by mailed material and telephone calls. The main intervention consisted of a booklet tailored for seniors containing information on dietary guidelines, recommended physical activity levels, and goal setting. Dietary and walking activity outcomes were collected via a self-administered postal questionnaire pre- and postintervention and analysed using linear mixed regressions. Of the 270 seniors recruited, half were randomly selected for the program while others served as the control group. Results. The program elicited favourable responses. Postintervention walking for exercise/recreation showed an average gain of 27 minutes per week for the participants in contrast to an average drop of 5 minutes for the controls (P<.01). Little change was evident in errand walking for both groups. The intervention group (n=114) demonstrated a significant increase in fibre intake (P<.01) but no reduction in fat intake (P>.05) compared to controls (n=134). Conclusions. The participants became more aware of their health and wellbeing after the pilot program, which was successful in increasing time spent walking for recreation and improving fibre intake

    Effects of a physical activity and nutrition program for seniors on body mass index and waist-to-hip ratio: A randomised controlled trial

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    Objective: To investigate whether a home-based program, physical activity and nutrition for seniors (PANS), made positive changes to central obesity, measured by body mass index (BMI) and waist-to-hip ratio (WHR). Methods: A 6-month randomised controlled trial was conducted targeting overweight and sedentary older adults aged 60 to 70 years residing in low to medium socio-economic suburbs within metropolitan Perth. Intervention participants (n = 248) received mailed materials and telephone/email support to improve nutrition and physical activity levels. Controls (n = 230) received small incentives to complete baseline and post-intervention questionnaires. Both groups reported anthropometric measures following specific written instructions. Generalised estimating equation models were used to assess repeated outcomes of BMI and WHR over both time points. Results: 176 intervention and 199 controls (response rate 78.5%) with complete data were available for analysis. After controlling for demographic and other confounding factors, the intervention group demonstrated a small (0.02) but significant reduction in WHR (p = 0.03) compared to controls, no apparent change in BMI was evident for both groups. The 0.02 reduction in mean WHR corresponded to a 2.11 cm decrease in waist circumference for a typical hip circumference. Conclusion: PANS appears to improve the WHR of participants. Changes in BMI might require a longer term intervention to take effect, and/or a follow-up study to confirm its sustainability

    Development of a nutrition and physical activity booklet to engage seniors

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    <p>Abstract</p> <p>Background</p> <p>This paper describes the development and process evaluation of an interactive booklet aimed at motivating older adults to improve their nutrition and physical activity.</p> <p>Findings</p> <p>The booklet was developed in consultation with seniors via focus groups, individual interviews and self administered questionnaires. The booklet was disseminated to a group of 114 seniors as the main component of a 12-week intervention program. Process evaluation was conducted during and at the end of the intervention period.</p> <p>A large proportion of participants (86%) were engaged in the program in that they had, as a minimum, read the booklet. The majority of the participants found the booklet provided them with useful and interesting advice in an easy-to-read and informative manner. Three quarters (76%) reported the materials to be motivating and increased their awareness of nutrition and physical activity, while 79% intended to continue with changes to their physical activity and diet after the program concluded.</p

    Research & Action Report, Spring/Summer 2015

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    In this issue: Black History Month in Germany Commentary with Layli Maparyan, Ph.D. Commentary with Linda Charmaraman, Ph.D. Depression Prevention and Obstetric Fistula New Connections New Findings & Publications Prevention of Child & Adolescent Depression in Latin America Q&A with Sari Pekkala Kerr, Ph.D. Spotlight on New Funding & Projects Women’s Studies and Women in Academiahttps://repository.wellesley.edu/researchandactionreport/1026/thumbnail.jp
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