555 research outputs found

    St. John\u27s Wort inhibits adipocyte differentiation and induces insulin resistance in adipocytes

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    Adipocytes are insulin sensitive cells that play a major role in energy homeostasis. Obesity is the primary disease of fat cells and a major risk factor for the development of Type II diabetes, cardiovascular disease, and metabolic syndrome. Obesity and its related disorders result in dysregulation of the mechanisms that control adipocyte gene expression and function. To identify potential novel therapeutic modulators of adipocytes, we screened 425 botanical extracts for their ability to modulate adipogenesis and insulin sensitivity. We observed that less than 2% of the extracts had substantial effects on adipocyte differentiation of 3T3-L1 cells. Two of the botanical extracts that inhibited adipogenesis were extracts from St. John\u27s Wort (SJW). Our studies revealed that leaf and flower, but not root, extracts isolated from SJW inhibited adipogenesis as judged by examining PPARγ and adiponectin levels. We also examined the effects of these SJW extracts on insulin sensitivity in mature 3T3-L1 adipocytes. Both leaf and flower extracts isolated from SJW substantially inhibited insulin sensitive glucose uptake. The specificity of the observed effects was demonstrated by showing that treatment with SJW flower extract resulted in a time and dose dependent inhibition of insulin stimulated glucose uptake. SJW is commonly used in the treatment of depression. However, our studies have revealed that SJW may have a negative impact on adipocyte related diseases by limiting differentiation of preadipocytes and significantly inducing insulin resistance in mature fat cells. © 2009 Elsevier Inc. All rights reserved

    The Influence of Setting on Care Coordination for Childhood Asthma

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    Asthma affects 7.1 million children in the United States, disproportionately burdening African American and Latino children. Barriers to asthma control include insufficient patient education and fragmented care. Care coordination represents a compelling approach to improve quality of care and address disparities in asthma. The sites of The Merck Childhood Asthma Network Care Coordination Programs implemented different models of care coordination to suit specific settings—school district, clinic or health care system, and community—and organizational structures. A variety of qualitative data sources were analyzed to determine the role setting played in the manifestation of care coordination at each site. There were inherent strengths and challenges of implementing care coordination in each of the settings, and each site used unique strategies to deliver their programs. The relationship between the lead implementing unit and entities that provided (1) access to the priority population and (2) clinical services to program participants played a critical role in the structure of the programs. The level of support and infrastructure provided by these entities to the lead implementing unit influenced how participants were identified and how asthma care coordinators were integrated into the clinical care team.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113262/1/MCAN_Settings_Manuscript_20150708.docxhttp://deepblue.lib.umich.edu/bitstream/2027.42/113262/3/MCAN_Settings_Manuscript_20150708.pdfDescription of MCAN_Settings_Manuscript_20150708.docx : Main ArticleDescription of MCAN_Settings_Manuscript_20150708.pdf : Main Article with Title Page and Abstrac

    Density-dependent, central-place foraging in a grazing herbivore: competition and tradeoffs in time allocation near water

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    Optimal foraging theory addresses one of the core challenges of ecology: predicting the distribution and abundance of species. Tests of hypotheses of optimal foraging, however, often focus on a single conceptual model rather than drawing upon the collective body of theory, precluding generalization. Here we demonstrate links between two established theoretical frameworks predicting animal movements and resource use: central-place foraging and density-dependent habitat selection. Our goal is to better understand how the nature of critical, centrally placed resources like water (or minerals, breathing holes, breeding sites, etc.) might govern selection for food (energy) resources obtained elsewhere - a common situation for animals living in natural conditions. We empirically test our predictions using movement data from a large herbivore distributed along a gradient of water availability (feral horses, Sable Island, Canada, 2008–2013). Horses occupying western Sable Island obtain freshwater at ponds while in the east horses must drink at self-excavated wells (holes). We studied the implications of differential access to water (time needed for a horse to obtain water) on selection for vegetation associations. Consistent with predictions of density-dependent habitat selection, horses were reduced to using poorer-quality habitat (heathland) more than expected close to water (where densities were relatively high), but were free to select for higher-quality grasslands farther from water. Importantly, central-place foraging was clearly influenced by the type of water-source used (ponds vs. holes, the latter with greater time constraints on access). Horses with more freedom to travel (those using ponds) selected for grasslands at greater distances and continued to select grasslands at higher densities, whereas horses using water holes showed very strong density-dependence in how habitat could be selected. Knowledge of more than one theoretical framework may be required to explain observed variation in foraging behavior of animals where multiple constraints simultaneously influence resource selection

    The Set of Measures on the Reduction of Agrarian Risks in the Conditions of Interstate Integration

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    Выполнен сравнительный анализ уровня самообеспеченности основными продуктами питания государств-участников ЕАЭС. Выявлены рискообразующие факторы в аграрной сфере и потенциальные угрозы продовольственной безопасности. Обоснована значимость производственных и финансовых аграрных рисков для целей производства необходимого количества сельскохозяйственного сырья и продовольствия в Республике Беларусь. Предложен комплекс мероприятий по снижению уровня аграрных рисков, реализация которых будет способствовать обеспечению необходимых параметров продовольственной безопасности.A comparative analysis of the level of self-provision with essential foods of the countries of Eurasian Economic Union is carried. Risk factors in the agrarian sphere and potential threats for the food security are revealed. The significance of production and financial agrarian risks for the purposes of producing necessary quantity of agricultural raw materials and food in the Republic of Belarus is justified. The set of measures for reducing the level of agrarian risks is proposed, the implementation of which will facilitate providing necessary parameters of food security

    Climate fluctuations and the spring invasion of the North Sea by Calanus finmarchicus

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    The population of Calanus finmarchicus in the North Sea is replenished each spring by invasion from an overwintering stock located beyond the shelf edge. A combincation of field observations, statistical analysis of Continuous Plankton Recorder (CPR) data, and particle tracking model simulations, was used to investigate the processes involved in the cross-shelf invasion. The results showed that the main source of overwintering animals entering the North Sea in the spring is at depths of greater than 600m in the Faroe Shetland Channel, where concentrations of up to 620m -3 are found in association with the overflow of Norwegian Sea Deep Water (NSDW) across the Iceland Scotland Ridge. The input of this water mass to the Faroe Shetland Channel, and hence the supply of overwintering C. finmarchicus, has declined since the late 1960s due to changes in convective processes in the Greenland Sea. Beginning in February, animals start to emerge from the overwintering state and migrate to the surface waters, where their transport into the North Sea is mainly determined by the incidence of north-westerly winds that have declined since the 1960s. Together, these two factors explain a high proportion of the 30-year trends in spring abundance in the North Sea as measured by the CPR survey. Both the regional winds and the NSDW overflow are connected to the North Atlantic Oscillation Index (NAO), which is an atmospheric climate index, but with different time scales of response. Thus, interannual fluctuations in the NAO can cause immediate changes in the incidence of north-westerly winds without leading to corresponding changes in C. finmarchicus abundance in the North Sea, because the NSDW overflow responds over longer (decadal) time scales

    Stakeholder engagement in eight comparative effectiveness trials in African Americans and Latinos with asthma

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    BACKGROUND: The effects of stakeholder engagement, particularly in comparative effectiveness trials, have not been widely reported. In 2014, eight comparative effectiveness studies targeting African Americans and Hispanics/Latinos with uncontrolled asthma were funded by the Patient-Centered Outcomes Research Institute (PCORI) as part of its Addressing Disparities Program. Awardees were required to meaningfully involve patients and other stakeholders. Using specific examples, we describe how these stakeholders substantially changed the research protocols and in other ways participated meaningfully as full partners in the development and conduct of the eight studies. METHODS: Using the method content analysis of cases, we identified themes regarding the types of stakeholders, methods of engagement, input from the stakeholders, changes made to the research protocols and processes, and perceived benefits and challenges of the engagement process. We used summaries from meetings of the eight teams, results from an engagement survey, and the final research reports as our data source to obtain detailed information. The descriptive data were assessed by multiple reviewers using inductive and deductive qualitative methods and discussed in the context of engagement literature. RESULTS: Stakeholders participated in the planning, conduct, and dissemination phases of all eight asthma studies. All the studies included clinicians and community representatives as stakeholders. Other stakeholders included patients with asthma, their caregivers, advocacy organizations, and health-system representatives. Engagement was primarily by participation in advisory boards, although six of the eight studies (75%) also utilized focus groups and one-on-one interviews. Difficulty finding a time and location to meet was the most reported challenge to engagement, noted by four of the eight teams (50%). Other reported challenges and barriers to engagement included recruitment of stakeholders, varying levels of enthusiasm among stakeholders, controlling power dynamics, and ensuring that stakeholder involvement was reflected and had true influence on the project. CONCLUSION: Engagement-driven modifications led to specific changes in study design and conduct that were felt to have increased enrollment and the general level of trust and support of the targeted communities. The level of interaction described, between investigators and stakeholders in each study and between investigator-stakeholder groups, is-we believe-unprecedented and may provide useful guidance for other studies seeking to improve the effectiveness of community-driven research

    High-Throughput GoMiner, an 'industrial-strength' integrative gene ontology tool for interpretation of multiple-microarray experiments, with application to studies of Common Variable Immune Deficiency (CVID)

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    BACKGROUND: We previously developed GoMiner, an application that organizes lists of 'interesting' genes (for example, under-and overexpressed genes from a microarray experiment) for biological interpretation in the context of the Gene Ontology. The original version of GoMiner was oriented toward visualization and interpretation of the results from a single microarray (or other high-throughput experimental platform), using a graphical user interface. Although that version can be used to examine the results from a number of microarrays one at a time, that is a rather tedious task, and original GoMiner includes no apparatus for obtaining a global picture of results from an experiment that consists of multiple microarrays. We wanted to provide a computational resource that automates the analysis of multiple microarrays and then integrates the results across all of them in useful exportable output files and visualizations. RESULTS: We now introduce a new tool, High-Throughput GoMiner, that has those capabilities and a number of others: It (i) efficiently performs the computationally-intensive task of automated batch processing of an arbitrary number of microarrays, (ii) produces a human-or computer-readable report that rank-orders the multiple microarray results according to the number of significant GO categories, (iii) integrates the multiple microarray results by providing organized, global clustered image map visualizations of the relationships of significant GO categories, (iv) provides a fast form of 'false discovery rate' multiple comparisons calculation, and (v) provides annotations and visualizations for relating transcription factor binding sites to genes and GO categories. CONCLUSION: High-Throughput GoMiner achieves the desired goal of providing a computational resource that automates the analysis of multiple microarrays and integrates results across all of the microarrays. For illustration, we show an application of this new tool to the interpretation of altered gene expression patterns in Common Variable Immune Deficiency (CVID). High-Throughput GoMiner will be useful in a wide range of applications, including the study of time-courses, evaluation of multiple drug treatments, comparison of multiple gene knock-outs or knock-downs, and screening of large numbers of chemical derivatives generated from a promising lead compound

    Making Sense of Making Meat: Key Moments in the First 20 Years of Tissue Engineering Muscle to Make Food

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    Cultured/clean/cell-based meat (CM) now has a near two decade history of laboratory research, commencing with the early NASA-funded work at Touro College and the bioarts practice of the Tissue Culture and Art project. Across this period the field, or as it is now more commonly termed, the “space,” has developed significantly while promoting different visions for what CM is and can do, and the best mechanisms for delivery. Here we both analyse and critically engage with this near-twenty year period as a productive provocation to those engaged with CM, or considering becoming so. This paper is not a history of the field, and does not offer a comprehensive timeline. Instead it identifies significant activities, transitions, and moments in which key meanings and practices have taken form or exerted influence. We do this through analyzing two related themes: the CM “institutional context” and the CM “interpretative package.” The former, the institutional context, refers to events and infrastructures that have come into being to support and shape the CM field, including university activities, conferences, third sector groups, various potential funding mechanisms, and the establishment of a start-up sector. The latter, the interpretative package, refers to the constellation of factors that shape or assert how CM should be understood, including the various names used to describe it, accounts of what it will achieve, and most recently, the emergent regulatory discussions that frame its legal standing. Across the paper we argue it is productive to think of the CM community in terms of a first and second wave. The first wave was more university-based and broadly covers the period from the millennium until around the 2013 cultured burger event. The second wave saw the increasing prevalence of a start-up culture and the circuits of venture capital interest that support it. Through this analysis we seek to provoke further reflection upon how the CM community has come to be as it is, and how this could develop in the future.Economic and Social Research Council; The Seventh Framework Programme; Wellcome Trust; Centre for Society and Genomics Visiting Scholarship; King's College London; KCL Mary Clark Travel Bursary; Our Planet Our Health (Livestock, Environment and People–LEAP); The Netherlands Organization for Scientific Research; Ministry of Economic Affair
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