1,176 research outputs found

    Political candidates can successfully use targeted appeals to increase support from female voters

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    Recent presidential and congressional elections have featured growing appeals to specific groups, including women. But are these marketing techniques actually effective at persuading women voters? In new research using experiments which test how voters respond to such appeals, Mirya R Holman, Monica C Schneider and Kristin Pondel find that such identity-based targeting makes it more likely that both men and women will vote for a certain candidate. Appeals by women candidates, they write, are also more likely to be effective with women voters, as they activate group identity among women

    Weight gain prevention in the school worksite setting: Results of a multi-level cluster randomized trial

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    OBJECTIVE: To describe the effectiveness, reach and implementation of a weight gain prevention intervention among public school employees. METHOD: A multi-level intervention was tested in a cluster randomized trial among 782 employees in 12 central Massachusetts public high schools from 2009 to 2012. The intervention targeted the nutrition and physical activity environment and policies, the social environment and individual knowledge, attitudes and skills. The intervention was compared to a materials only condition. The primary outcome measures were change in weight and body mass index (BMI) at 24-month follow-up. Implementation of physical environment, policy and social environment strategies at the school and interpersonal levels, and intervention participation at the individual level were assessed. RESULTS: At 24-month follow-up, there was a net change (difference of the difference) of -3.03 pounds (p=.04) and of -.48 BMI units (p=.05) between intervention and comparison conditions. The majority of intervention strategies were successfully implemented by all intervention schools, although establishing formal policies was challenging. Employee participation in programs targeting the physical and social environment was maintained over time. CONCLUSION: This study supports that a multi-level intervention integrated within the organizational culture can be successfully implemented and prevent weight gain in public high school employees

    Altering Murine Leukemia Virus Integration Through Disruption of the Integrase and BET Protein Family Interaction

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    We report alterations to the murine leukemia virus (MLV) integrase (IN) protein that successfully result in decreasing its integration frequency at transcription start sites and CpG islands, thereby reducing the potential for insertional activation. The host bromo and extraterminal (BET) proteins Brd2, 3 and 4 interact with the MLV IN protein primarily through the BET protein ET domain. Using solution NMR, protein interaction studies, and next generation sequencing, we showthat the C-terminal tail peptide region ofMLV IN is important for the interaction with BET proteins and that disruption of this interaction through truncation mutations affects the global targeting profile of MLV vectors. The use of the unstructured tails of gammaretroviral INs to direct association with complexes at active promoters parallels that used by histones and RNA polymerase II. Viruses bearingMLV IN C-terminal truncations can provide new avenues to improve the safety profile of gammaretroviral vectors for human gene therapy

    ÁCIDO LINOLEICO CONJUGADO: UMA BREVE REVISÃO

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    O ácido linoleico conjugado (CLA) é um ácido graxo poli-insaturado natural, encontrado principalmente na gordura do leite e na carne de animais ruminantes. Seus isômeros geométricos e de posição c9t11 e t10c12 vêm despertando interesse, uma vez que o primeiro é considerado um agente anticarcinogênico natural e o segundo, um repartidor de nutrientes efetivo. Pesquisas relacionam o CLA a outros efeitos positivos à saúde como a redução de aterosclerose, prevenção e tratamento do diabetes mellitus, estimulação do sistema imunológico, redução da pressão arterial e da gordura corporal com aumento da massa magra. Apresenta propriedade hipocolesteronica além de atuar como poderoso antioxidante. Assim, este trabalho de revisão tem por objetivo o enfoque na produção de CLA, seus benefícios à saúde, bem como os métodos analíticos de quantificação do mesmo em alimentos

    EpiDiP/NanoDiP: a versatile unsupervised machine learning edge computing platform for epigenomic tumour diagnostics.

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    DNA methylation analysis based on supervised machine learning algorithms with static reference data, allowing diagnostic tumour typing with unprecedented precision, has quickly become a new standard of care. Whereas genome-wide diagnostic methylation profiling is mostly performed on microarrays, an increasing number of institutions additionally employ nanopore sequencing as a faster alternative. In addition, methylation-specific parallel sequencing can generate methylation and genomic copy number data. Given these diverse approaches to methylation profiling, to date, there is no single tool that allows (1) classification and interpretation of microarray, nanopore and parallel sequencing data, (2) direct control of nanopore sequencers, and (3) the integration of microarray-based methylation reference data. Furthermore, no software capable of entirely running in routine diagnostic laboratory environments lacking high-performance computing and network infrastructure exists. To overcome these shortcomings, we present EpiDiP/NanoDiP as an open-source DNA methylation and copy number profiling suite, which has been benchmarked against an established supervised machine learning approach using in-house routine diagnostics data obtained between 2019 and 2021. Running locally on portable, cost- and energy-saving system-on-chip as well as gpGPU-augmented edge computing devices, NanoDiP works in offline mode, ensuring data privacy. It does not require the rigid training data annotation of supervised approaches. Furthermore, NanoDiP is the core of our public, free-of-charge EpiDiP web service which enables comparative methylation data analysis against an extensive reference data collection. We envision this versatile platform as a useful resource not only for neuropathologists and surgical pathologists but also for the tumour epigenetics research community. In daily diagnostic routine, analysis of native, unfixed biopsies by NanoDiP delivers molecular tumour classification in an intraoperative time frame

    Efficacy of Memantine for Agitation in Alzheimer’s Dementia: A Randomised Double-Blind Placebo Controlled Trial

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    Agitation in Alzheimer's disease (AD) is common and associated with poor patient life-quality and carer distress. The best evidence-based pharmacological treatments are antipsychotics which have limited benefits with increased morbidity and mortality. There are no memantine trials in clinically significant agitation but post-hoc analyses in other populations found reduced agitation. We tested the primary hypothesis, memantine is superior to placebo for clinically significant agitation, in patients with moderate-to-severe AD

    Contribution of S6K1/MAPK signaling pathways in the response to oxidative stress: activation of RSK and MSK by hydrogen peroxide

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    Trobareu correccions de l'article a: http://dx.doi.org/10.1371/annotation/0b485bd9-b1b2-4c60-ab22-3ac5d271dc59Cells respond to different kind of stress through the coordinated activation of signaling pathways such as MAPK or p53. To find which molecular mechanisms are involved, we need to understand their cell adaptation. The ribosomal protein, S6 kinase 1 (S6K1), is a common downstream target of signaling by hormonal or nutritional stress. Here, we investigated the initial contribution of S6K1/MAPK signaling pathways in the cell response to oxidative stress produced by hydrogen peroxide (H2O2). To analyze S6K1 activation, we used the commercial anti-phospho-Thr389-S6K1 antibody most frequently mentioned in the bibliography. We found that this antibody detected an 80-90 kDa protein that was rapidly phosphorylated in response to H2O2 in several human cells. Unexpectedly, this phosphorylation was insensitive to both mTOR and PI3K inhibitors, and knock-down experiments showed that this protein was not S6K1. RSK and MSK proteins were candidate targets of this phosphorylation. We demonstrated that H2O2 stimulated phosphorylation of RSK and MSK kinases at residues that are homologous to Thr389 in S6K1. This phosphorylation required the activity of either p38 or ERK MAP kinases. Kinase assays showed activation of RSK and MSK by H2O2. Experiments with mouse embryonic fibroblasts from p38 animals" knockout confirmed these observations. Altogether, these findings show that the S6K1 signaling pathway is not activated under these conditions, clarify previous observations probably misinterpreted by non-specific detection of proteins RSK and MSK by the anti-phospho-Thr389-S6K1 antibody, and demonstrate the specific activation of MAPK signaling pathways through ERK/p38/RSK/MSK by H2O2
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