1,720,974 research outputs found
Role of endogenous TRPV1 in the onset of optical-induced Ca2+ signals in endothelial colony forming cells (ECFCs)
Targeting endothelial ion signalling to rescue cerebral blood flow in cerebral disorders
The mechanism whereby an increase in neuronal activity (NA) leads to a local elevation in cerebral blood flow to supply the active neurons with oxygen and nutrients and remove the catabolic waste has been termed neurovascular coupling (NVC). Although it has long been thought that the vasoactive mediators involved in NVC are generated by neurons and astrocytes, recent evidence unveiled the crucial role of cerebrovascular endothelial cells in NVC. Brain capillary endothelial cells express a complement of ion channels, including inward-rectifier K+ (Kir2.1) channels, Transient Receptor Potential Ankyrin 1 channels and N-methyl-d-aspartate receptors that enable them to sense NA and thereby initiate the retrograde transmission of both electrical (via endothelium-dependent hyperpolarization) and chemical (via intercellular Ca2+ waves also sustained by TRP Vanilloid 4 channels and inositol-1,4,5-trisphosphate receptors) signals that induce vasodilation in upstream pial arteries and parenchymal arteries. Notably, a defect in the endothelial ion channel machinery (particularly, Kir2.1 channels) contributes to vascular cognitive impairment and dementia that features many cerebral disorders, including Alzheimer's disease, cerebral small vessel diseases, and traumatic brain injury. Targeting endothelial ion channels through appropriate pharmacological approaches might represent a hitherto unappreciated strategy to rescue CBF and prevent cognitive impairment and dementia in patients affected by cerebral disorders
Optical excitation of organic semiconductors as a highly selective strategy to induce vascular regeneration and tissue repair
Therapeutic neovascularization represents a promising strategy to rescue the vascular network and restore organ function in cardiovascular disorders (CVDs), including acute myocardial infarction, heart failure, peripheral artery disease, and brain stroke. Endothelial colony forming cells (ECFCs), which are mobilized in circulation upon an ischemic insult, are commonly regarded as the most suitable cellular tool to achieve therapeutic neovascularization. ECFCs can be genetically or pharmacologically manipulated to enhance their vasoreparative potential by boosting specific pro-angiogenic signalling pathways. However, optical stimulation represents the most reliable approach to control cellular activity because of its high selectivity and unprecedented spatio-temporal resolution. Herein, we discuss a novel strategy to drive ECFC angiogenic activity in ischemic tissues by combining geneless optical excitation with photosensitive organic semiconductors. We describe how photoexcitation of the conducting polymer poly(3-hexylthiophene-2,5-diyl), also known as P3HT, stimulates extracellular Ca2+ entry through Transient Receptor Potential Vanilloid 1 (TRPV1) channels upon the production of hydrogen peroxide (H2O2) in the cleft between the nanomaterial and the cell membrane. H2O2-induced TRPV1-dependent Ca2+ entry stimulates ECFC proliferation and tube formation, thereby providing the proof-of-concept that photoexcitation of organic semiconductors may offer a reliable strategy to stimulate ECFCs-dependent neovascularization in CVDs
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
We 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
Targeting the endothelial Ca 2+ tool kit to rescue endothelial dysfunction in obesity associated-hypertension
Obesity is a major cardiovascular risk factor which dramatically impairs endothelium-dependent vasodilation and leads to hypertension and vascular damage. The impairment of the vasomotor response to extracellular autacoids, e.g. acetylcholine, mainly depends on the reduced nitric oxide (NO) bioavailability, which hampers vasorelaxation in large conduit arteries. In addition, obesity may affect endothelium-dependent hyperpolarization (EDH), which drives vasorelaxation in small resistance arteries and arterioles. Of note, endothelial Ca 2+ signals drive NO release and trigger EDH
TRPV1 mediates redox-sensitive intracellular Ca2+ release and store-operated Ca2+ entry activation in circulating endothelial colony forming cells
An automated planar patch-clamp approach to measure the membrane potential and resting membrane currents in a human cerebrovascular endothelial cell line
Background: The conventional “whole-cell patch-clamp” recording technique is widely used to measure the resting membrane potential (VM) and to dissect the underlying membrane ionic conductances in isolated vascular endothelial cells. New method: Herein, we assessed whether the automated patch-clamp (APC) technology, which replaces the traditional patch-pipette with a planar substrate to permit researchers lacking formal training in electrophysiology to generate large amounts of data in a relatively short time, can be used to characterize the bioelectrical activity of vascular endothelial cells. We assessed whether the Port-a-Patch planar patch-clamp system, which is regarded as the smallest electrophysiological rig available on the market, can be used to measure the VM and resting membrane currents in the human cerebrovascular endothelial cell line, hCMEC/D3. Comparison with existing methods: We demonstrated that the Port-a-Patch planar patch-clamp system provides the same values of the resting VM as those provided by the conventional patch-clamp technique. Furthermore, the APC technology provides preliminary data demonstrating that the resting VM of hCMEC/D3 cells is primarily contributed by Cl- and Na+, as demonstrated with the patch-clamp technique for many other endothelial cell types. Conclusions: The Port-a-Patch planar patch-clamp system can be successfully used to measure the resting VM and the underlying membrane ionic conductances in hCMEC/D3 cells. We envisage that this easy-to-use APC system could also be extremely useful for the investigation of the membrane currents that can be activated by chemical, thermal, optical, and mechanical stimuli in this cell line as well as in other types of isolated vascular endothelial cells
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