1,558 research outputs found

    Cathelicidin suppresses lipid accumulation and hepatic steatosis by inhibition of the CD36 receptor.

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    Background and objectivesObesity is a global epidemic which increases the risk of the metabolic syndrome. Cathelicidin (LL-37 and mCRAMP) is an antimicrobial peptide with an unknown role in obesity. We hypothesize that cathelicidin expression correlates with obesity and modulates fat mass and hepatic steatosis.Materials and methodsMale C57BL/6 J mice were fed a high-fat diet. Streptozotocin was injected into mice to induce diabetes. Experimental groups were injected with cathelicidin and CD36 overexpressing lentiviruses. Human mesenteric fat adipocytes, mouse 3T3-L1 differentiated adipocytes and human HepG2 hepatocytes were used in the in vitro experiments. Cathelicidin levels in non-diabetic, prediabetic and type II diabetic patients were measured by enzyme-linked immunosorbent assay.ResultsLentiviral cathelicidin overexpression reduced hepatic steatosis and decreased the fat mass of high-fat diet-treated diabetic mice. Cathelicidin overexpression reduced mesenteric fat and hepatic fatty acid translocase (CD36) expression that was reversed by lentiviral CD36 overexpression. Exposure of adipocytes and hepatocytes to cathelicidin significantly inhibited CD36 expression and reduced lipid accumulation. Serum cathelicidin protein levels were significantly increased in non-diabetic and prediabetic patients with obesity, compared with non-diabetic patients with normal body mass index (BMI) values. Prediabetic patients had lower serum cathelicidin protein levels than non-diabetic subjects.ConclusionsCathelicidin inhibits the CD36 fat receptor and lipid accumulation in adipocytes and hepatocytes, leading to a reduction of fat mass and hepatic steatosis in vivo. Circulating cathelicidin levels are associated with increased BMI. Our results demonstrate that cathelicidin modulates the development of obesity

    Everyday cosmopolitanism in representations of Europe among young Romanians in Britain

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    The paper presents an analysis of everyday cosmopolitanism in constructions of Europe among young Romanian nationals living in Britain. Adopting a social representations approach, cosmopolitanism is understood as a cultural symbolic resource that is part of everyday knowledge. Through a discursively-oriented analysis of focus group data, we explore the ways in which notions of cosmopolitanism intersect with images of Europeanness in the accounts of participants. We show that, for our participants, representations of Europe are anchored in an Orientalist schema of West-vs.-East, whereby the West is seen as epitomising European values of modernity and progress, while the East is seen as backward and traditional. Our findings further show that representations of cosmopolitanism reinforce this East/West dichotomy, within a discourse of ‘Occidental cosmopolitanism’. The paper concludes with a critical discussion of the diverse and complex ideological foundations of these constructions of European cosmopolitanism and their implications

    Seagrass can mitigate negative ocean acidification effects on calcifying algae

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    The ultimate effect that ocean acidification (OA) and warming will have on the physiology of calcifying algae is still largely uncertain. Responses depend on the complex interactions between seawater chemistry, global/local stressors and species-specific physiologies. There is a significant gap regarding the effect that metabolic interactions between coexisting species may have on local seawater chemistry and the concurrent effect of OA. Here, we manipulated CO2 and temperature to evaluate the physiological responses of two common photoautotrophs from shallow tropical marine coastal ecosystems in Brazil: the calcifying alga Halimeda cuneata, and the seagrass Halodule wrightii. We tested whether or not seagrass presence can influence the calcification rate of a widespread and abundant species of Halimeda under OA and warming. Our results demonstrate that under elevated CO2, the high photosynthetic rates of H. wrightii contribute to raise H. cuneata calcification more than two-fold and thus we suggest that H. cuneata populations coexisting with H. wrightii may have a higher resilience to OA conditions. This conclusion supports the more general hypothesis that, in coastal and shallow reef environments, the metabolic interactions between calcifying and non-calcifying organisms are instrumental in providing refuge against OA effects and increasing the resilience of the more OA-susceptible species.E.B. would like to thank the Coordenação de Aperfeiçoamento de Pessoas de Nível Superior (CAPES) for Masters funding. Funding for this project came from the Synergism grant (CNPq 407365/2013-3). We extend our thanks to the Brazil-based Projeto Coral Vivo and its sponsor PetroBras Ambiental for providing the Marine Mesocosm structure and experimental assistance.info:eu-repo/semantics/publishedVersio

    Noisy Monte Carlo: Convergence of Markov chains with approximate transition kernels

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    Monte Carlo algorithms often aim to draw from a distribution π\pi by simulating a Markov chain with transition kernel PP such that π\pi is invariant under PP. However, there are many situations for which it is impractical or impossible to draw from the transition kernel PP. For instance, this is the case with massive datasets, where is it prohibitively expensive to calculate the likelihood and is also the case for intractable likelihood models arising from, for example, Gibbs random fields, such as those found in spatial statistics and network analysis. A natural approach in these cases is to replace PP by an approximation P^\hat{P}. Using theory from the stability of Markov chains we explore a variety of situations where it is possible to quantify how 'close' the chain given by the transition kernel P^\hat{P} is to the chain given by PP. We apply these results to several examples from spatial statistics and network analysis.Comment: This version: results extended to non-uniformly ergodic Markov chain

    Frontotemporal dementia caused by CHMP2B mutation is characterised by neuronal lysosomal storage pathology

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    Mutations in the charged multivesicular body protein 2B (CHMP2B) cause frontotemporal dementia (FTD). We report that mice which express FTD-causative mutant CHMP2B at physiological levels develop a novel lysosomal storage pathology characterised by large neuronal autofluorescent aggregates. The aggregates are an early and progressive pathology that occur at 3 months of age and increase in both size and number over time. These autofluorescent aggregates are not observed in mice expressing wild-type CHMP2B, or in non-transgenic controls, indicating that they are a specific pathology caused by mutant CHMP2B. Ultrastructural analysis and immuno- gold labelling confirmed that they are derived from the endolysosomal system. Consistent with these findings, CHMP2B mutation patient brains contain morphologically similar autofluorescent aggregates. These aggregates occur significantly more frequently in human CHMP2B mutation brain than in neurodegenerative disease or age-matched control brains. These data suggest that lysosomal storage pathology is the major neuronal pathology in FTD caused by CHMP2B mutation. Recent evidence suggests that two other genes associated with FTD, GRN and TMEM106B are important for lysosomal function. Our identification of lysosomal storage pathology in FTD caused by CHMP2B mutation now provides evidence that endolysosomal dysfunction is a major degenerative pathway in FTD

    The holistic phase model of early adult crisis

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    The objective of the current study was to explore the structural, temporal and experiential manifestations of crisis episodes in early adulthood, using a holistic-systemic theoretical framework. Based on an analysis of 50 interviews with individuals about a crisis episode between the ages of 25 and 35, a holistic model was developed. The model comprises four phases: (1) Locked-in, (2) Separation/Time-out, (3) Exploration and (4) Rebuilding, which in turn have characteristic features at four levels—person-in-environment, identity, motivation and affect-cognition. A crisis starts out with a commitment at work or home that has been made but is no longer desired, and this is followed by an emotionally volatile period of change as that commitment is terminated. The positive trajectory of crisis involves movement through an exploratory period towards active rebuilding of a new commitment, but ‘fast-forward’ and ‘relapse’ loops can interrupt Phases 3 and 4 and make a positive resolution of the episode less likely. The model shows conceptual links with life stage theories of emerging adulthood and early adulthood, and it extends current understandings of the transitional developmental challenges that young adults encounter

    Identifying juvenile and sub-adult movements to inform recovery strategies for a high value fishery—European bass (Dicentrarchus labrax)

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    Abstract The European bass (Dicentrarchus labrax) support high value commercial and recreational fisheries, however the Spawning Stock Biomass (SSB) of the northern Atlantic stock (ICES divisions 4.b–c, 7.a, and 7.d–h) has rapidly declined to an unsustainable level. The decline in SSB has been attributed to high fishing pressure combined with poor recruitment. By tracking juvenile fish their spatial ecology can be identified, and appropriate fisheries management policies designed to boost recruitment can be implemented. Using acoustic telemetry 146 sub-adult European bass (25.2–60 cm fork length) were tracked for up to 370 d across three sites in the southwest of the UK. Tagged fish were detected 2 724 548 times (Range: 166–106 393 detections per fish). Linear modelling estimated tagged fish were resident within 2.4–20.1 km of the site where they were first caught for 42.9–75.5% of the year. Some fish were however resident throughout summer and winter. Individual fish were also tracked moving up to 317 km to other coastal sites, 81% of which returned to their original capture site. Fisheries management should account for the high site fidelity displayed by juveniles and sub-adults of this species and coastal nursery sites should be considered essential habitat.</jats:p

    Actinomycosis of the parotid masquerading as malignant neoplasm.

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    BACKGROUND: Primary actinomycosis of the parotid gland is of rare occurrence and can mimic a malignant neoplasm both clinically as well as radiologically. CASE PRESENTATION: We present here a case of primary actinomycosis of the parotid gland presenting with a parotid mass lesion with erosion of skull bones. CONCLUSIONS: Clinical presentation of cervico-facial actinomycosis is characterized by the presence of a suppurative or indurative mass with discharging sinuses. The lesion demonstrates characteristic features on fine needle aspiration cytology and histology, however at times the findings are equivocal

    Psychometric properties of the CDC Symptom Inventory for assessment of Chronic Fatigue Syndrome

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    OBJECTIVES: Validated or standardized self-report questionnaires used in research studies and clinical evaluation of chronic fatigue syndrome (CFS) generally focus on the assessment of fatigue. There are relatively few published questionnaires that evaluate case defining and other accompanying symptoms in CFS. This paper introduces the self-report CDC CFS Symptom Inventory and analyzes its psychometric properties. METHODS: One hundred sixty-four subjects (with CFS, other fatiguing illnesses and non fatigued controls) identified from the general population of Wichita, Kansas were enrolled. Evaluation included a physical examination, a standardized psychiatric interview, three previously validated self-report questionnaires measuring fatigue and illness impact (Medical Outcomes Survey Short-Form-36 [MOS SF-36], Multidimensional Fatigue Inventory [MFI], Chalder Fatigue Scale), and the CDC CFS Symptom Inventory. Based on theoretical assumptions and statistical analyses, we developed several different Symptom Inventory scores and evaluated them on their ability to differentiate between participants with CFS and non-fatigued controls. RESULTS: The Symptom Inventory had good internal consistency and excellent convergent validity. A Total score (all symptoms), Case Definition score (CFS case defining symptoms) and Short Form score (6 symptoms with minimal correlation) differentiated CFS cases from controls. Furthermore, both the Case Definition and Short Form scores distinguished people with CFS from fatigued subjects who did not meet criteria for CFS. CONCLUSION: The Symptom Inventory appears to be a reliable and valid instrument to assess symptoms that accompany CFS. It is a positive addition to existing instruments measuring fatigue because it allows other dimensions of the illness to be assessed. Further research is needed to confirm and replicate the current findings in a normative population
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