1,720,958 research outputs found
Impact of ERK2 missense variants found in cancer: structural, function and stability experimental analysis
Get PDFProteins are the most versatile macromolecules in biosystems and serve crucial functions in essentially all biological processes. A reversible process important for the regulation in biological process is protein phosphorylation. Phosphorylation or dephosphorylation can affect the function of a protein in every conceivable way, increasing or suppressing activity, labelling a protein accessible for degradation, allowing it to move from one subcellular compartment to another, or enabling it to interact with or dissociate from other proteins. The abnormal phosphorylation of proteins is known to be a cause of major diseases, such as tumors.
The progression of the neoplastic disease is generally driven by the accumulation of random genetic changes in cells and tissues, which can then develop independence from normal physiological controls due to randomly accumulating mutations. The most common genetic differences in the human genome are single nucleotide polymorphisms (SNPs), which are defined as single nucleotide variations (SNVs) occurring with a frequency of more than 1% in the population. These differences occur on average once every 300–400 base pairs, either in coding or in non-coding regions. SNVs may affect exon splicing or transcription, and are found more frequently than other types of genetic variations, such as differences in copy number, insertions, deletions, duplications, and rearrangements. SNVs in protein-coding regions have received the most attention, in spite of the fact that those regions account for only about 2% of the total human genome. SNVs in the coding region can be synonymous(sSNVs) if no amino acid change is produced, or non-synonymous(nsSNVs) if the substitution leads to a change in the protein sequence. The nsSNVs can be further divided into two categories: missense mutations, which lead to single amino acid changes, or nonsense mutations, which produce truncated or longer proteins. Missense mutations, that generate protein variants with a single amino acid variation (SAV), are of particular interest in biomedicine, since even just a single amino acid substitution may induce drastic structural alterations, which compromise the protein stability, or may induce crucial structural alterations able to perturb binding interfaces, to the point of impairing the protein function. In particular, this kind of approach seems to be relevant in cancer research considering that several somatic variants resulting from alterations at the amino acid level have been detected in cancer genome for several proteins.
The single amino acid variations detected in the protein kinases and phosphatases, give rise to several of disorders and exert their effects by altering the phosphorylation states of intracellular proteins. The differences between protein kinase variants are at the basis of distinctive traits associated with the susceptibility to specific disease and/or drug response. Many compounds are now marked as ‘specific’ inhibitors of protein kinases, some of which have been used in literally hundreds of papers to study how a protein kinase is implicated in the regulation of a particular cellular event. Nevertheless, very few of these compounds are specific for the protein variants. The information resulting from the analysis of somatic mutations found in cancer tissues can improve the available therapies and create new and more specific ones, the personalized medicine
A glimpse into the structural properties of the intermediate and transition state in the folding of bromodomain 2 d2 by Φ value analysis
Get PDFBromodomains (BRDs) are small protein interaction modules of about 110 amino acids
that selectively recognize acetylated lysine in histones and other proteins. These domains have been
identified in a variety of multi‐domain proteins involved in transcriptional regulation or chromatin
remodeling in eukaryotic cells. BRD inhibition is considered an attractive therapeutic approach in
epigenetic disorders, particularly in oncology. Here, we present a Φ value analysis to investigate
the folding pathway of the second domain of BRD2 (BRD2(2)). Using an extensive mutational analysis
based on 25 site‐directed mutants, we provide structural information on both the intermediate
and late transition state of BRD2(2). The data reveal that the C‐terminal region represents part of
the initial folding nucleus, while the N‐terminal region of the domain consolidates its structure only
later in the folding process. Furthermore, only a small number of native‐like interactions have been
identified, suggesting the presence of a non‐compact, partially folded state with scarce native‐like
characteristics. Taken together, these results indicate that, in BRD2(2), a hierarchical mechanism of
protein folding can be described with non‐native interactions that play a significant role in folding
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
- …
