2,825 research outputs found

    miR-34a-/- mice are susceptible to diet-induced obesity

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    Objective: MicroRNA (miR)−34a regulates inflammatory pathways, and increased transcripts have been observed in serum and subcutaneous adipose of subjects who have obesity and type 2 diabetes. Therefore, the role of miR-34a in adipose tissue inflammation and lipid metabolism in murine diet-induced obesity was investigated. Methods: Wild-type (WT) and miR-34a−/− mice were fed chow or high-fat diet (HFD) for 24 weeks. WT and miR-34a−/− bone marrow-derived macrophages were cultured in vitro with macrophage colony-stimulating factor (M-CSF). Brown and white preadipocytes were cultured from the stromal vascular fraction (SVF) of intrascapular brown and epididymal white adipose tissue (eWAT), with rosiglitazone. Results: HFD-fed miR-34a−/− mice were significantly heavier with a greater increase in eWAT weight than WT. miR-34a−/− eWAT had a smaller adipocyte area, which significantly increased with HFD. miR-34a−/− eWAT showed basal increases in Cd36, Hmgcr, Lxrα, Pgc1α, and Fasn. miR-34a−/− intrascapular brown adipose tissue had basal reductions in c/ebpα and c/ebpβ, with in vitro miR-34a−/− white adipocytes showing increased lipid content. An F4/80high macrophage population was present in HFD miR-34a−/− eWAT, with increased IL-10 transcripts and serum IL-5 protein. Finally, miR-34a−/− bone marrow-derived macrophages showed an ablated CXCL1 response to tumor necrosis factor-α. Conclusions: These findings suggest a multifactorial role of miR-34a in controlling susceptibility to obesity, by regulating inflammatory and metabolic pathways

    Atlantic Ocean Heat Transport Enabled by Indo-Pacific Heat Uptake and Mixing

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    The ocean transports vast amounts of heat around the planet, helping to regulate regional climate. One important component of this heat transport is the movement of warm water from equatorial regions toward the poles, with colder water flowing in return. Here, we introduce a framework relating meridional heat transport to the diabatic processes of surface forcing and turbulent mixing that move heat across temperature classes. Applied to a (1/4)° global ocean model the framework highlights the role of the tropical Indo‐Pacific in the global ocean heat transport. A large fraction of the northward heat transport in the Atlantic is ultimately sourced from heat uptake in the eastern tropical Pacific. Turbulent mixing moves heat from the warm, shallow Indo‐Pacific circulation to the cold deeper‐reaching Atlantic circulation. Our results underscore a renewed focus on the tropical oceans and their role in global circulation pathways

    Avian oncogenesis induced by lymphoproliferative disease virus: a neglected or emerging retroviral pathogen?

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    Lymphoproliferative disease virus (LPDV) is an exogenous oncogenic retrovirus that induces lymphoid tumors in some galliform species of birds. Historically, outbreaks of LPDV have been reported from Europe and Israel. Although the virus has previously never been detected in North America, herein we describe the widespread distribution, genetic diversity, pathogenesis, and evolution of LPDV in the United States. Characterization of the provirus genome of the index LPDV case from North America demonstrated an 88% nucleotide identity to the Israeli prototype strain. Although phylogenetic analysis indicated that the majority of viruses fell into a single North American lineage, a small subset of viruses from South Carolina were most closely related to the Israeli prototype. These results suggest that LPDV was transferred between continents to initiate outbreaks of disease. However, the direction (New World to Old World or vice versa), mechanism, and time frame of the transcontinental spread currently remain unknown

    Evolutionary History and Attenuation of Myxoma Virus on Two Continents

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    The attenuation of myxoma virus (MYXV) following its introduction as a biological control into the European rabbit populations of Australia and Europe is the canonical study of the evolution of virulence. However, the evolutionary genetics of this profound change in host-pathogen relationship is unknown. We describe the genome-scale evolution of MYXV covering a range of virulence grades sampled over 49 years from the parallel Australian and European epidemics, including the high-virulence progenitor strains released in the early 1950s. MYXV evolved rapidly over the sampling period, exhibiting one of the highest nucleotide substitution rates ever reported for a double-stranded DNA virus, and indicative of a relatively high mutation rate and/or a continually changing selective environment. Our comparative sequence data reveal that changes in virulence involved multiple genes, likely losses of gene function due to insertion-deletion events, and no mutations common to specific virulence grades. Hence, despite the similarity in selection pressures there are multiple genetic routes to attain either highly virulent or attenuated phenotypes in MYXV, resulting in convergence for phenotype but not genotype. © 2012 Kerr et al

    Effects of Subchronic Phencyclidine (PCP) Treatment on Social Behaviors, and Operant Discrimination and Reversal Learning in C57BL/6J Mice

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    Subchronic treatment with the psychotomimetic phencyclidine (PCP) has been proposed as a rodent model of the negative and cognitive/executive symptoms of schizophrenia. There has, however, been a paucity of studies on this model in mice, despite the growing use of the mouse as a subject in genetic and molecular studies of schizophrenia. In the present study, we evaluated the effects of subchronic PCP treatment (5 mg/kg twice daily × 7 days, followed by 7 days withdrawal) in C57BL/6J mice on (1) social behaviors using a sociability/social novelty-preference paradigm, and (2) pairwise visual discrimination and reversal learning using a touchscreen-based operant system. Results showed that mice subchronically treated with PCP made more visits to (but did not spend more time with) a social stimulus relative to an inanimate one, and made more visits and spent more time investigating a novel social stimulus over a familiar one. Subchronic PCP treatment did not significantly affect behavior in either the discrimination or reversal learning tasks. These data encourage further analysis of the potential utility of mouse subchronic PCP treatment for modeling the social withdrawal component of schizophrenia. They also indicate that the treatment regimen employed was insufficient to impair our measures of discrimination and reversal learning in the C57BL/6J strain. Further work will be needed to identify alternative methods (e.g., repeated cycles of subchronic PCP treatment, use of different mouse strains) that reliably produce discrimination and/or reversal impairment, as well as other cognitive/executive measures that are sensitive to chronic PCP treatment in mice

    Toward a Mixed-Methods Research Approach to Content Analysis in The Digital Age: The Combined Content-Analysis Model and its Applications to Health Care Twitter Feeds

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    BACKGROUND: Twitter’s 140-character microblog posts are increasingly used to access information and facilitate discussions among health care professionals and between patients with chronic conditions and their caregivers. Recently, efforts have emerged to investigate the content of health care-related posts on Twitter. This marks a new area for researchers to investigate and apply content analysis (CA). In current infodemiology, infoveillance and digital disease detection research initiatives, quantitative and qualitative Twitter data are often combined, and there are no clear guidelines for researchers to follow when collecting and evaluating Twitter-driven content. OBJECTIVE: The aim of this study was to identify studies on health care and social media that used Twitter feeds as a primary data source and CA as an analysis technique. We evaluated the resulting 18 studies based on a narrative review of previous methodological studies and textbooks to determine the criteria and main features of quantitative and qualitative CA. We then used the key features of CA and mixed-methods research designs to propose the combined content-analysis (CCA) model as a solid research framework for designing, conducting, and evaluating investigations of Twitter-driven content. METHODS: We conducted a PubMed search to collect studies published between 2010 and 2014 that used CA to analyze health care-related tweets. The PubMed search and reference list checks of selected papers identified 21 papers. We excluded 3 papers and further analyzed 18. RESULTS: Results suggest that the methods used in these studies were not purely quantitative or qualitative, and the mixed-methods design was not explicitly chosen for data collection and analysis. A solid research framework is needed for researchers who intend to analyze Twitter data through the use of CA. CONCLUSIONS: We propose the CCA model as a useful framework that provides a straightforward approach to guide Twitter-driven studies and that adds rigor to health care social media investigations. We provide suggestions for the use of the CCA model in elder care-related contexts

    A simplified, Langendorff-free method for concomitant isolation of viable cardiac myocytes and non-myocytes from the adult mouse heart

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    Rationale: Cardiovascular disease represents a global pandemic. The advent of and recent advances in mouse genomics, epigenomics, and transgenics offer ever-greater potential for powerful avenues of research. However, progress is often constrained by unique complexities associated with the isolation of viable myocytes from the adult mouse heart. Current protocols rely on retrograde aortic perfusion using specialized Langendorff apparatus, which poses considerable logistical and technical barriers to researchers and demands extensive training investment. Objective: To identify and optimize a convenient, alternative approach, allowing the robust isolation and culture of adult mouse cardiac myocytes using only common surgical and laboratory equipment. Methods and Results: Cardiac myocytes were isolated with yields comparable to those in published Langendorff-based methods, using direct needle perfusion of the LV ex vivo and without requirement for heparin injection. Isolated myocytes can be cultured antibiotic free, with retained organized contractile and mitochondrial morphology, transcriptional signatures, calcium handling, responses to hypoxia, neurohormonal stimulation, and electric pacing, and are amenable to patch clamp and adenoviral gene transfer techniques. Furthermore, the methodology permits concurrent isolation, separation, and coculture of myocyte and nonmyocyte cardiac populations. Conclusions: We present a novel, simplified method, demonstrating concomitant isolation of viable cardiac myocytes and nonmyocytes from the same adult mouse heart. We anticipate that this new approach will expand and accelerate innovative research in the field of cardiac biology. </jats:sec

    An evaluation of heart rate variability in female youth soccer players following soccer heading: A pilot study

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    Most head impacts in soccer occur from purposeful heading; however, the link between heading and neurological impairment is unknown. Previous work suggests concussion may result in an uncoupling between the autonomic nervous system and cardiovascular system. Accordingly, heart rate variability (HRV) may be a sensitive measure to provide meaningful information regarding repetitive heading in soccer. The purpose of this pilot study assesses the feasibility of measuring HRV to evaluate autonomic function following soccer heading. Sixteen youth female participants underwent heart rate monitoring during a heading and footing condition. Participants completed a five minute resting supine trial at the start and end of each testing session. Standard 450 g soccer balls were projected at 6 m/s towards participants. Participants performed five headers, for the header condition, and five footers for the footer condition. The HRV for resting supine trials, pre-and post-header and footer conditions were assessed for both time and frequency domains. HRV effect sizes were small when comparing conditions, except absolute low frequency (d = 0.61) and standard deviation of the normal-normal (NN) intervals (d = 0.63). Participant retention and adherence were high, without adverse events. Findings suggest HRV is a feasible measure for evaluating the effects of heading on autonomic function
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