1,720,969 research outputs found
The Significance of the Late Na+ Current for Arrhythmia Induction and the Therapeutic Antiarrhythmic Potential of Ranolazine
No full textThe purpose of this article is to review the basis of arrhythmogenesis, the functional and clinical role of the late Na current, and its therapeutic inhibition. Under pathological conditions such as ischemia and heart failure this current is abnormally enhanced and influences cellular electrophysiology as a proarrhythmic substrate in myocardial pathology. Ranolazine the only approved late Na current blocker has been demonstrated to produce antiarrhythmic effects in the atria and the ventricle. We summarize recent experimental and clinical studies of ranolazine and other experimental late Na current blockers and discuss the significance of the available data
Through the haze: unveiling the link between smoking and atrial fibrillation
No full textFunder:
Deutsche Forschungsgemeinschaft
http://dx.doi.org/10.13039/501100001659Funder:
German Research Foundation
http://dx.doi.org/10.13039/501100001659Funder:
Deutsches Zentrum für Herz-Kreislaufforschung
http://dx.doi.org/10.13039/10001044
Blebbistatin reduces calcium buffering in cardiomyocytes: Consequences for cellular electrophysiology
No full textAbstract Blebbistatin is an excitation–contraction uncoupling agent commonly used in cardiac optical mapping; however, it has been reported to influence cardiac myofilament Ca 2+ sensitivity. As primary contributors to Ca 2+ buffering within cardiomyocytes, cardiac myofilaments play a critical role, and even minor disruptions in intracellular Ca 2+ buffering significantly alter the free Ca 2+ concentration. In this study, we investigated the effect of blebbistatin, a myosin II ATPase inhibitor, on intracellular Ca 2+ buffering and cellular electrophysiology in induced pluripotent stem cell‐derived atrial cardiomyocytes. Simultaneous whole‐cell ruptured patch‐clamp and fluorescence microscopy techniques were used to assess intracellular Ca 2+ handling, in addition to automated high‐throughput patch‐clamp to investigate ion channel function. Comprehensive analysis of Ca 2+ buffering revealed that blebbistatin (10 µmol/l) causes a significant increase in buffer dissociation constant, suggesting decreased affinity of Ca 2+ buffers. Furthermore, systolic and diastolic Ca 2+ levels, sarcoplasmic reticulum Ca 2+ leak and the incidence of spontaneous Ca 2+ release events were significantly higher upon blebbistatin treatment. Although there was lack of impact on I Na and I Ca,L peak density, Ca 2+ ‐dependent inactivation of I Ca,L was significantly enhanced, and I K1 density was significantly smaller after blebbistatin. Importantly, these effects were reversed after chelation of intracellular Ca 2+ with EGTA. Our observations indicate that blebbistatin reduces Ca 2+ buffering, which, in turn, causes changes in cellular electrophysiology in cardiomyocytes. image Key points Intracellular Ca 2+ buffering plays an important role in determining Ca 2+ dynamics in cardiomyocytes. Blebbistatin, an excitation–contraction uncoupling agent widely used in experimental studies, decreases the affinity of intracellular Ca 2+ buffers, as indicated by an increased buffer dissociation constant. Blebbistatin leads to higher systolic and diastolic Ca 2+ levels and increased sarcoplasmic reticulum Ca 2+ leak. Blebbistatin enhances L‐type Ca 2+ current ( I Ca,L ) Ca 2+ ‐dependent inactivation and reduces inward rectifier potassium current ( I K1 ) density, while I Na and I Ca,L remain unchanged. The effects of blebbistatin are mitigated by chelation of intracellular Ca 2+ with EGTA, showing that they are secondary to altered Ca 2+ buffering
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Increased cytosolic calcium buffering contributes to a cellular arrhythmogenic substrate in iPSC-cardiomyocytes from patients with dilated cardiomyopathy
No full textDilated cardiomyopathy (DCM) is a major risk factor for heart failure and is associated with the development of life-threatening cardiac arrhythmias. Using a patient-specific induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) model harbouring a mutation in cardiac troponin T (R173W), we aim to examine the cellular basis of arrhythmogenesis in DCM patients with this mutation. iPSC from control (Ctrl) and DCM-TnT-R173W donors from the same family were differentiated into iPSC-CM and analysed through optical action potential (AP) recordings, simultaneous measurement of cytosolic calcium concentration ([Ca(2+)](i)) and membrane currents and separately assayed using field stimulation to detect the threshold for AP- and [Ca(2+)](i)-alternans development. AP duration was unaltered in TnT-R173W iPSC-CM. Nevertheless, TnT-R173W iPSC-CM showed a strikingly low stimulation threshold for AP- and [Ca(2+)](i)-alternans. Myofilaments are known to play a role as intracellular Ca(2+) buffers and here we show increased Ca(2+) affinity of intracellular buffers in TnT-R173W cells, indicating increased myofilament sensitivity to Ca(2+). Similarly, EMD57033, a myofilament Ca(2+) sensitiser, replicated the abnormal [Ca(2+)](i) dynamics observed in TnT-R173W samples and lowered the threshold for alternans development. In contrast, application of a Ca(2+) desensitiser (blebbistatin) to TnT-R173W iPSC-CM was able to phenotypically rescue Ca(2+) dynamics, normalising Ca(2+) transient profile and minimising the occurrence of Ca(2+) alternans at physiological frequencies. This finding suggests that increased Ca(2+) buffering likely plays a major arrhythmogenic role in patients with DCM, specifically in those with mutations in cardiac troponin T. In addition, we propose that modulation of myofilament Ca(2+) sensitivity could be an effective anti-arrhythmic target for pharmacological management of this disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00395-022-00912-z
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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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