1,720,974 research outputs found
Removal of the calcium-dependent regulation of ATP binding in Synapsin I has distinct effects at excitatory and inhibitory synapses
No full textSynapsins are the most abundant family of neuro-specific phosphoproteins associated with the cytoplasmic surface of the synaptic vesicle membrane. These proteins actively regulate synaptic transmission at the level of the presynaptic terminal by controlling the storage and mobilization of synaptic vesicles within a reserve pool. However, it is hypothesized that synapsins could be involved in other stages of synaptic vesicle dynamics such as trafficking, docking, fusion with the plasma membrane and consequent recycling. Synapsin I (SynI) in particular is expressed two isoforms (Ia and Ib) at the presynaptic compartment of all neurons in the adult brain. Several studies suggest that SynI is also involved in axon elongation and synaptic vesicle fusion kinetics. In human, nonsense and missense mutations of SYN1 gene are related to several diseases such as epilepsy and autism spectrum disorder; in fact, SynI knockout (KO) mice show an epileptic and autism-like phenotype. To carry out its functions, SynI requires to bind ATP in a Ca2+-dependent manner thanks to the coordination of a glutamate residue (E373). As ATP binding regulates SynI oligomerization and SV clustering, we analyzed the effect of E373K mutation on neurotransmitter release and short-term plasticity in excitatory and inhibitory synapses. We coupled electrophysiology (patch-clamp recordings) with electron microscopy in primary SynI KO hippocampal neurons in which either the human wild type or the E373K mutant SynI were re-introduced by infection with lentiviral vectors. Our data indicate that E373K mutation affects predominantly excitatory synapses. The frequency of miniature excitatory postsynaptic currents (mEPSCs) was enhanced, without changes in the amplitude and in the number of excitatory synapses. The increment of mEPSCs frequency was totally abolished after acute injection of BAPTA-AM (a specific Ca2+ chelator), suggesting a possible alteration of Ca2+ homeostasis at the presynaptic terminal. Excitatory E373K-Syn I neurons showed reduced evoked EPSC amplitude attributable to a reduction of the readily releasable pool (RRP), while, on the contrary, inhibitory E373K-Syn I neurons did not show any difference both in miniature, evoked IPSC amplitude and RRP size. While no effects in the dynamics and steady state of depression were detected, both excitatory and inhibitory E373K-Syn I neurons failed to recover after stimulation with long high-frequency trains. No mutation-induced changes were observed in network firing/bursting activity as determined with multi-electrode extracellular recordings. Our data suggest that the Ca2+-dependent regulation of ATP-binding to SynI plays important roles in spontaneous and evoked neurotransmitter release that differentially affect the strength of excitatory and inhibitory transmission
Modulation of Mechanosensitive Potassium Channels by a Membrane-targeted Nongenetic Photoswitch
Full text linkMechanosensitive ion channels are present in the plasma membranes of all cells. They play a fundamental role in converting mechanical stimuli into biochemical signals and are involved in several physiological processes such as touch sensation, hearing, and blood pressure regulation. This protein family includes TWIK-related arachidonic acid-stimulated K+ channel (TRAAK), which is specifically implicated in the maintenance of the resting membrane potential and in the regulation of a variety of important neurobiological functions. Dysregulation of these channels has been linked to various diseases, including blindness, epilepsy, cardiac arrhythmia, and chronic pain. For these reasons, mechanosensitive channels are targets for the treatment of several diseases. Here, we propose a new approach to investigate TRAAK ion channel modulation that is based on nongenetic photostimulation. We employed an amphiphilic azobenzene, named Ziapin2. In the dark, Ziapin2 preferentially dwells in the plasma membrane, causing a thinning of the membrane. Upon light irradiation, an isomerization occurs, breaking the dimers and inducing membrane relaxation. To study the effect of Ziapin2 on the mechanosensitive channels, we expressed human TRAAK (hTRAAK) channels in HEK293T cells. We observed that Ziapin2 insertion in the membrane is able per se to recruit hTRAAK, permitting the exit of K+ ions outside the cells with a consequent hyperpolarization of the cell membrane. During light stimulation, membrane relaxation induces hTRAAK closure, generating a consistent and compensatory depolarization. These results add information to the Ziapin2 mechanism and suggest that membrane deformation can be a tool for the nonselective modulation of mechanosensitive channels
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
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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