1,720,974 research outputs found
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
Apoptosis and adaptive responses to oxidative stress in human endothelial cells exposed to cyclosporin A correlate with Bcl-2 expression levels
No full textTreatment of transplanted patients with cyclosporin A (CSA) may cause adverse effects such as nephrotoxicity and hypertension. As CSA is known to induce oxidative stress in several tissues, it may cause vascular problems by triggering oxidative stress in endothelial cells (EC). However, oxidative stress has been reported for acute exposure to CSA concentrations exceeding its clinical range, whereas immunosuppression requires life-long treatment with therapeutic concentrations. We therefore compared the effects of 21 h pharmacological (200 μM) vs. 8 days clinical (0.5-2.5 μM) doses of CSA on cultured human EC. Pharmacological doses of CSA cause a decrease in cell density via apoptosis and a down-regulation of the antiapoptotic protein Bcl-2. However, these effects are independent of CSA-induced oxidative stress. In contrast, therapeutic concentrations of CSA cause Bcl-2 up-regulation and modification of EC morphology, both effects blocked by antioxidants. Therefore, a low level of oxidants may act in EC as second messengers that up-regulate Bcl-2, thus promoting survival of impaired EC. Our data suggest that the oxidative stress induced by clinical concentrations of CSA may be involved in the adverse effects of the drug on the vascular system of transplanted patients via an adaptive response involving Bcl-2 up-regulation rather than an apoptotic process
Effect of blocking the Na/K ATPase on Ca extrusion and light adapatation in mammalian retinal rods
No full textMembrane current and light response were recorded from rods of monkey and guinea pig by means of suction electrodes. The correlation between adaptation and the Na+/K+ pump was investigated by measuring light-dependent changes in sensitivity with and without inhibition of Na+/K+ ATPase by strophanthidin. Strophanthidin was found to reduce the dark current, to slow the time course of the photoresponse, and to increase light sensitivity. At concentrations between 20 and 500 nM, the pump inhibitor suppressed in a reversible way the current re-activation occurring during prolonged illumination and modified the light-dependent decrease in sensitivity, which in control conditions approximates to a Weber-Fechner function. The effects of the pump inhibitor on the adaptive properties of rods are associated with an increased time constant of the membrane current attributed to the operation of the Na+:Ca2+,K+ exchanger. The effects of rapid application of the pump inhibitor on the current re-activation are consistent with the idea that significant changes in the internal sodium occur in rods of mammals during background illumination and that they play an important role in the process of light adaptation
Targeted in vivo genetic manipulation of the mouse or rat brain by in utero electroporation with a triple-electrode probe
No full text3,5,3'-Triiodothyronine deprivation affects phenotype and intracellular [Ca2+]i of human cardiomyocytes in culture
No full textOBJECTIVE:
A decrease in plasma T3 concentration is a frequent finding in patients with heart failure. However, the role of this 'low T3 syndrome' on disease evolution has never been clarified. As phenotypic and functional cardiomyocyte impairments are alterations that correlate with the failing myocardium, we studied the long-term effects of T3 deprivation on human cardiomyocyte structure and calcium handling.
METHODS:
Atrial cardiomyocytes and myocardial tissue were cultured with or without 3 nM T3. Microscopical examination of structural features was followed by analysis of alpha-sarcomeric actinin and sarcoplasmic reticulum calcium ATP-ase (SERCA-2) content. Calcium handling was studied by [Ca2+](i) imaging.
RESULTS:
When stimulated with cyclopiazonic acid, a SERCA-2 inhibitor, T3-deprived cardiomyocytes showed significantly faster (P=0.03) and more transient (P=0.04) increases in [Ca(2+)](i) than T3-supplemented cells. Moreover, in the T3-free cultures a significantly lower number of cells (P=0.003) responded to caffeine, a typical activator of sarcoplasmic reticulum Ca(2+)-release channel. T3-deprived cardiomyocytes also presented altered morphology with larger dimensions than T3-supplemented cells (P < 0.0001). Additionally, in T3-deprived samples alpha-sarcomeric actinin and SERCA-2 protein levels were reduced to 65.6 +/- 3% (P < 0.0001) and 74.1 +/- 4% (P=0.005), respectively, when compared with the T3-supplemented group.
CONCLUSIONS:
Our data show that human cardiomyocyte calcium handling and phenotype are strongly influenced by T3 suggesting important implications of the 'low T3 syndrome' on the progression of heart failure
Synthesis, cellular delivery and in vivo application of dendrimer-based pH sensors
No full textThe development of fluorescent indicators represented a revolution for life sciences. Genetically encoded and synthetic fluorophores with sensing abilities allowed the visualization of biologically relevant species with high spatial and temporal resolution. Synthetic dyes are of particular interest thanks to their high tunability and the wide range of measureable analytes. However, these molecules suffer several limitations related to small molecule behavior (poor solubility, difficulties in targeting, often no ratiometric imaging allowed). In this work we introduce the development of dendrimer-based sensors and present a procedure for pH measurement in vitro, in living cells and in vivo. We choose dendrimers as ideal platform for our sensors for their many desirable properties (monodispersity, tunable properties, multivalency) that made them a widely used scaffold for several biomedical devices. The conjugation of fluorescent pH indicators to the dendrimer scaffold led to an enhancement of their sensing performances. In particular dendrimers exhibit reduced cell leakage, improved intracellular targeting and allow ratiometric measurements. These novel sensors were successfully employed to measure pH in living HeLa cells and in vivo in mouse brain
Blockage of voltage dependent sodium channels prevents dendritic competition in the cat retina
No full textVariations 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
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