421 research outputs found

    Eukaryotic genome size databases

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    Three independent databases of eukaryotic genome size information have been launched or re-released in updated form since 2005: the Plant DNA C-values Database (), the Animal Genome Size Database () and the Fungal Genome Size Database (). In total, these databases provide freely accessible genome size data for >10 000 species of eukaryotes assembled from more than 50 years' worth of literature. Such data are of significant importance to the genomics and broader scientific community as fundamental features of genome structure, for genomics-based comparative biodiversity studies, and as direct estimators of the cost of complete sequencing programs

    The evolution of farnesoid X, vitamin D, and pregnane X receptors: insights from the green-spotted pufferfish (Tetraodon nigriviridis) and other non-mammalian species

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    <p>Abstract</p> <p>Background</p> <p>The farnesoid X receptor (FXR), pregnane X receptor (PXR), and vitamin D receptor (VDR) are three closely related nuclear hormone receptors in the NR1H and 1I subfamilies that share the property of being activated by bile salts. Bile salts vary significantly in structure across vertebrate species, suggesting that receptors binding these molecules may show adaptive evolutionary changes in response. We have previously shown that FXRs from the sea lamprey (<it>Petromyzon marinus</it>) and zebrafish (<it>Danio rerio</it>) are activated by planar bile alcohols found in these two species. In this report, we characterize FXR, PXR, and VDR from the green-spotted pufferfish (<it>Tetraodon nigriviridis</it>), an actinopterygian fish that unlike the zebrafish has a bile salt profile similar to humans. We utilize homology modelling, docking, and pharmacophore studies to understand the structural features of the <it>Tetraodon </it>receptors.</p> <p>Results</p> <p><it>Tetraodon </it>FXR has a ligand selectivity profile very similar to human FXR, with strong activation by the synthetic ligand GW4064 and by the primary bile acid chenodeoxycholic acid. Homology modelling and docking studies suggest a ligand-binding pocket architecture more similar to human and rat FXRs than to lamprey or zebrafish FXRs. <it>Tetraodon </it>PXR was activated by a variety of bile acids and steroids, although not by the larger synthetic ligands that activate human PXR such as rifampicin. Homology modelling predicts a larger ligand-binding cavity than zebrafish PXR. We also demonstrate that VDRs from the pufferfish and Japanese medaka were activated by small secondary bile acids such as lithocholic acid, whereas the African clawed frog VDR was not.</p> <p>Conclusions</p> <p>Our studies provide further evidence of the relationship between both FXR, PXR, and VDR ligand selectivity and cross-species variation in bile salt profiles. Zebrafish and green-spotted pufferfish provide a clear contrast in having markedly different primary bile salt profiles (planar bile alcohols for zebrafish and sterically bent bile acids for the pufferfish) and receptor selectivity that matches these differences in endogenous ligands. Our observations to date present an integrated picture of the co-evolution of bile salt structure and changes in the binding pockets of three nuclear hormone receptors across the species studied.</p

    Anchoring Hepatic Gene Expression with Development of Fibrosis and Neoplasia in a Toxicant-induced Fish Model of Liver Injury

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    ABSTRACT Fish have been used as laboratory models to study hepatic development and carcinogenesis but not for pathogenesis of hepatic fibrosis. In this study, a dimethylnitrosamine-induced fish model of hepatic injury was developed in Japanese medaka (Oryzias latipes) and gene expression was anchored with the development of hepatic fibrosis and neoplasia. Exposed livers exhibited mild hepatocellular degenerative changes 2 weeks&apos; postexposure. Within 6 weeks, hepatic fibrosis/cirrhosis was evident with development of neoplasia by 10 weeks. Stellate cell activation and development of fibrosis was associated with upregulation of transforming growth factor beta 1 (tgfb1), tgfb receptor 2, mothers against decapentaplegic homolog 3 (smad3a), smad3b, beta-catenin (ctnnb1), myc, matrix metalloproteinase (mmp2), mmp14a, mmp14b, tissue inhibitors of metalloproteinase (timp) 2a, timp2b, timp3, collagen type I alpha 1a (col1a1a), and col1a1b and a less pronounced increase in mmp13 and col4a1 expression. Tgfb receptor I expression was unchanged. Immunohistochemistry suggested that biliary epithelial cells and stellate cells were the main producers of TGF-b1. This study identified a group of candidate genes likely to be involved in the development of hepatic fibrosis and demonstrated that the TGF-b pathway likely plays a major role in the pathogenesis. These results support the medaka as a viable fish model of hepatic fibrosis

    Filmic geographies: audio-visual, embodied-material

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    Although conventionally described as a ‘visual’ method, film-making is also increasingly used within research on embodiment. However, much remains to be said about the ability of filmic methods to enhance researchers’ capacity to think and research through the body. Drawing on my experience of making four research films, in this paper, I attempt to advance this agenda in three steps. First, I introduce anthropological work on the filming body to shed light on the technologically-mediated encounters that enfold around a camera and discuss how they might inform geographical thinking. Second, I describe the corporeally-mediated object ecologies that take shape within the filming setting and highlight how a camera might make objects ‘speak’. Finally, I discuss the affective dimension of screening research films to research participants and the contribution of such intense events to the articulation of collective matters of concerns. Through these three themes, I make the case for understanding knowledge production as located not merely in encounters with filmed audio-visual content, but also in the embodied-material encounters of bodies and objects around the filming and screening apparatus. I finally discuss the implications of these reflections for conceptualising the ‘body’ within embodied methods in social and cultural geography

    Improving Care in Eosinophil-Associated Diseases: A Charter.

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    Eosinophil-associated diseases (EADs) are a range of heterogeneous conditions in which eosinophils are believed to play a critical pathological role. EADs include common illnesses such as eosinophilic asthma and chronic rhinosinusitis and rare conditions such as hypereosinophilic syndromes (HES) and eosinophilic gastrointestinal disorders (EGIDs). EADs are associated with substantial burdens for the patient, including chronic, debilitating symptoms, increased financial burden, decreased health-related quality of life, and the need for repeated visits to multiple different healthcare professionals (HCPs), emergency departments, and/or hospitals. Poor EAD recognition by HCPs often contributes to delayed diagnoses, which further delays patient access to appropriate care and effective treatments, contributing to poor health outcomes. The objective of this charter is to outline key patient rights and expectations with respect to the management of their condition(s) and to set forth an ambitious action plan to improve health outcomes for patients with EADs: (1) people with EADs, their caretakers, HCPs, and the public must have greater awareness and education about EADs; (2) people with EADs must receive a timely, accurate diagnosis; (3) all people with EADs must have access to an appropriate multidisciplinary team, when necessary; and (4) people with EADs must have access to safe and effective treatment options without unnecessary regulatory delays. The principles described in this charter demonstrate the core elements of quality care that people with EADs must receive, and they represent clear steps by which to reduce patient and caregiver burden and improve patient outcomes. We urge HCPs, healthcare systems, and policymakers worldwide to swiftly adopt these principles to ensure patients with EADs have an accurate diagnosis in a timely manner and access to high-level care and treatment in an appropriate setting
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