1,721,108 research outputs found
The effect of statin treatment on developmental angiogenesis in zebrafish
No full text2024Atherosclerosis is the leading cause of cardiovascular disease globally and is characterized by the accumulation of low density lipoprotein cholesterol (LDL-C) in the sub-endothelial space of arteries. Statins have proven effective at lowering LDL-C and protecting against atherogenic risk. However, the effect of statin on early vascular development, including intussusceptive and sprouting angiogenesis, proves inconclusive suggesting both pro- and anti-angiogenic effects. In this study, we treated wild type (wt) and low-density lipoprotein receptor (ldlr) knockout (Tg:flk:GFP) zebrafish with atorvastatin and simvastatin at 1-day post fertilization (1dpf) and 24 hours later at 2-days post-fertilization (2dpf) we quantified survival (%), intracranial hemorrhage (ICH) (%), and developmental angiogenesis in the dorsal aorta (DA), caudal venous plexus (CVP) and intersegmental vessels (ISV). Our findings demonstrate ldlr mutant zebrafish treated with lethal doses of 50 nM atorvastatin and 100 nM simvastatin demonstrated a significant reduction in intersegmental vessels compared to wt. Furthermore, ldlr mutant zebrafish had significantly greater number of intussusceptive pillars in both untreated and sublethal statin treatment (10 nM atorvastatin and 1 nM simvastatin) compared to wt zebrafish. Additionally, there was a dose-dependent effect on survival and ICH for both atorvastatin and simvastatin treated wt and ldlr mutant genotypes. Moreover, ldlr homozygous mutants treated with atorvastatin but not with simvastatin demonstrated a protective effect on statin-induced lethality compared to wt zebrafish. Despite the enhanced survival of ldlr mutant zebrafish with doses of statin lethal in wild-type fish, our findings suggest an exaggerated anti-angiogenic effect for both sprouting angiogenesis and intussusceptive angiogenesis in ldlr knockout. The results presented in this work sets the foundation for mechanistic studies and further exploration of distinguishing pro-angiogenic and anti-angiogenic effects, such as looking at endothelial cell turnover and cytoskeletal structure in the characterized vascular phenotypes presented in this study
Avaliação da toxicidade causada pela exposição a IONPS utilizando zebrafish como organismo modelo
Get PDFGoing Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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Novel Regulators of Liver Development and Metabolism
Get PDFChronic liver diseases such as non-alcoholic fatty liver disease and alcoholic liver disease are significant health concerns worldwide. Despite knowledge of disease features and environmental causes, we lack understanding of the genetic factors and molecular mechanisms that can be targeted for liver disease therapeutics. Many of these factors are also essential during embryonic development and organogenesis. Here, we use liver development in zebrafish as a model and paradigm for the discovery of regulators impacting liver disease pathogenesis. A chemical screen in zebrafish identified the endocannabinoid (EC) signaling pathway as a regulator of liver development. This pathway was previously implicated in animal models of chronic liver disease, but little was known about its role in development. We generated cannabinoid receptor mutant zebrafish using genome editing and show that EC signaling is required for hepatic maturation and outgrowth, but not earlier milestones such as hepatic specification. Mutant zebrafish also exhibited defects in lipid processing, and we found that methionine metabolism, involving sterol regulatory element binding proteins (SREBPs), is an integral mediator in this process. In a separate study, we used zebrafish to functionally annotate a panel of candidate genes identified by a genome-wide association study (GWAS) for elevated liver plasma enzymes, which are used as a clinical liver disease marker. We prioritized GWAS candidates for morpholino knockdown in zebrafish and discovered effects on hepatic progenitor and hepatocyte development as well as differences in susceptibility to metabolic and toxic injury. Our approach can be applied to other GWAS data sets to rapidly assess additional characteristics during zebrafish development. The work presented here gives valuable insight into how regulators of hepatogenesis also have roles in metabolism and disease. Medical SciencesMedical Sciencesliver; development; zebrafish; cannabinoid recepto
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Human amyloidogenic light chain proteins result in cardiac dysfunction, cell death, and early mortality in zebrafish
No full textDispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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