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HIF-1 Regulated Variant Splicing of CaMKIIγ in the Hypoxic Heart
No full textHypoxia-inducible factor 1 (HIF-1) is an oxygen-labile transcription factor that plays a crucial role in the regulation of cellular processes associated with hypoxia in the heart. In this study, we evaluated the effects of HIF-1 on variant RNA splicing of calcium/calmodulindependent protein kinase II gamma (CaMKIIγ). CaMKIIγ is known to play an important role in calcium signaling and heart function. Previously collected data indicated that expression of an oxygen-stable HIF-1 altered the relative abundance of three CaMKIIγ splicing variants in the hearts of transgenic mice. Expression of the full-length variant appeared to be down-regulated whereas variants 2 and 3 increased in abundance following HIF-1 induction. Based on this preliminary data, we chose to examine the mechanism of HIF-mediated splicing using two different models of physiological hypoxia: cell culture and a mouse MI surgical model. My hypothesis was that the altered splicing pattern seen in the HIF transgenic mice would be recapitulated in the physiological settings. We have found that in cells, expression levels of all three transcript variants initially decreased when exposed to hypoxia but that the expression levels of variant 3 returned to normoxic levels, and thus greater relative abundance relative to the other isoforms by 24 hours. In our in vivo model of infarction, CaMKIIγ variant 1 expression decreased 3 days after surgery, as was seen in the transgenic model. These results support the hypothesis that HIF-1 is involved in the alternative splicing of CaMKIIγ and could contribute to the loss of cardiac contractility observed after hypoxic injury.Department of Molecular and Cell Biolog
Going 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
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
Protein Kinase C Binding Protein 1 Modulates Hypoxia Inducible Factor 1 Activity
No full textDuring ischemia, the heart elicits robust physiological and molecular changes in response to oxygen deprivation (i.e. hypoxia). Hypoxia-inducible factor 1 (HIF-1) is a conserved transcription factor that directs the cellular response to hypoxia by regulating genes important in glycolysis, angiogenesis, and contractility. Recently, our lab observed that overexpression of the chromatin factor, PRKCBP1, inhibits HIF-1 activity and that Prkcbp1 is upregulated in the hypoxic heart. Previous studies have shown PRKCBP1 recruits histone demethylases to specific enhancer elements, leading to gene repression. The function of PRKCBP1 in the heart is unknown. During ischemia, PRKCBP1 may act in a negative-feedback loop to reduce HIF-1- target gene expression. We hypothesized that decreasing PRKCBP1 would lead to upregulation of HIF-1 target genes. To explore this, we simultaneously induced HIF-1 activity by expressing the active form of HIF-1a and depleted Prkcbp1 mRNA using siRNA in mouse embryonic fibroblasts. Using semi-quantitative PCR, co-transfection of siPRKCBP1 and the HIF-1a construct showed increased expression of two HIF-1 target genes, Ldha and Pfkp, relative to treatment with the HIF-1a construct alone. To determine endogenous PRKCBP1 levels in neonatal hearts, we performed western blotting using a PRKCBP1-specific antibody and detected a faint band at the predicted molecular weight of PRKCBP1. We also tested if ischemia causes upregulation of PRKCBP1 levels in adult heart tissue and found an increased abundance of PRKCBP1 in ischemic regions relative to unaffected regions. Taken together, our results support a potential HIF-1/PRKCBP1 regulatory circuit in the heart and suggests that PRKCBP1 regulates HIF-1 activity through chromatin remodeling
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
Dispelling 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
Regulation of Cardiac Metabolism and Inflammation by Pyruvate Kinase Muscle Isoform 2
No full textPh.D
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