1,720,958 research outputs found
Charged residues distribution modulates selectivity of the open state of human isoforms of the voltage dependent anion-selective channel
No full textVoltage Dependent Anion-selective Channels (VDACs) are pore-forming proteins located in the outer mitochondrial membrane. They are responsible for the access of ions and energetic metabolites into the inner membrane transport systems. Three VDAC isoforms exist in mammalian, but their specific role is unknown. In this work we have performed extensive (overall ,5 ms) Molecular Dynamics (MD) simulations of the human VDAC isoforms to detect structural and conformational variations among them, possibly related to specific functional roles of these proteins. Secondary structure analysis of the N-terminal domain shows a high similarity among the three human isoforms of VDAC but with a different plasticity. In particular, the N-terminal domain of the hVDAC1 is characterized by a higher plasticity, with a ,20% occurrence for the ‘unstructured’ conformation throughout the folded segment, while hVDAC2, containing a peculiar extension of 11 amino acids at the N-terminal end, presents an additional 310-helical folded portion comprising residues 109 to 3, adhering to the barrel wall. The N-terminal sequences of hVDAC isoforms are predicted to have a low flexibility, with possible consequences in the dynamics of the human VDACs. Clear differences were found between hVDAC1 and hVDAC3 against hVDAC2: a significantly modified dynamics with possible important consequence on the voltage-gating mechanism. Charge distribution inside and at the mouth of the pore is responsible for a different preferential localization of ions with opposite charge and provide a valuable rationale for hVDAC1 and hVDAC3 having a Cl2/K+ selectivity ratio of 1.8, whereas hVDAC2 of 1.4. Our conclusion is that hVDAC isoforms, despite sharing a similar scaffold, have modified working features and a biological work is now requested to give evidence to the described dissimilarities
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
Structural and functional analysis of human voltage-dependent anion channel isoforms (hVDACs): Combining in-vitro and in-silico approaches
No full textThe most abundant porins occurring in the OMM are the voltage dependent anion selective channels (VDACs). Even if they had been previously studied they were not very well characterized until they were isolated from rat liver by Colombini in 1983. VDACs are a small family of conserved proteins located in the outer mitochondrial membrane. They conduct ions, metabolites and small molecules, among which the energetic nucleotides ATP, ADP and NADH. Three different VDAC isoforms have been characterized in higher eukaryotes, encoded by three separate nuclear genes. VDAC1 is the most abundant isoform in most cells, being ten and hundred times more prevalent than VDAC2 and VDAC3, respectively. It is thus not surprising that VDAC1 is the isoform most extensively characterized. Functionally, VDAC1 is anion selective and exhibits a single-channel conductance of ~3.5-4.0 nS in 1 M KCl at an applied voltage between -20 mV and +10 mV. The aim of the PhD project was to perform a comparative study on the human VDAC isoforms focusing on both the whole channels and the individuals N-terminal domains. In this sense, both experimental and computational techniques have been used pointing out their complementarity and contribute to the completeness of the study
Structural and functional analysis of human voltage-dependent anion channel isoforms (hVDACs): Combining in-vitro and in-silico approaches
Full text linkVDACs are a small family of conserved proteins located in the outer mitochondrial membrane.
They conduct ions, metabolites and small molecules, among which the energetic nucleotides ATP,
ADP and NADH.
Three different VDAC isoforms have been characterized in higher eukaryotes, encoded by three
separate nuclear genes. VDAC1 is the most abundant isoform in most cells, being ten and hundred
times more prevalent than VDAC2 and VDAC3, respectively. It is thus not surprising that VDAC1
is the isoform most extensively characterized. Functionally, VDAC1 is anion selective and exhibits
a single-channel conductance of ~3.5-4.0 nS in 1 M KCl at an applied voltage between -20 mV and
10 mV. Raising the applied voltage results in the channel switching to the so-called “closed state”,
with a lower conductance and a channel selectivity reversed to cations. In addition to the poreforming
function, VDAC1 has been involved in various interactions and cross-talk with other
cellular proteins like hexokinase, tubulin, the Ca2+ gate into mitochondria and the Bcl-2 family
members that can impact on the activity of the pore itself and vice versa, testimony to the
involvement of VDAC to crucial cell fates like in pathways leading to apoptosis, cancer and
degeneration
The aim of the PhD project was to perform a comparative study on the human VDAC isoforms
focusing on both the whole channels and the individuals N-terminal domains. In this sense, both
experimental and computational techniques have been used pointing out their complementarity and
contribute to the completeness of the study.
After a brief introduction, the methods used during the PhD will be presented. In the third chapter,
the results together with the discussion will be described. Firstly, focusing on the structural
characterization of the N-termini of the three isoforms. Secondly, the results and the discussion will
concern the comparative study of the entire channels. Both of these characterization have been
performed with either experimental and computational techniques.
Finally, in the 4th chapter a brief conclusion and an outlook on a future perspective will be given
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
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