1,721,037 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
Development of mass spectrometry approaches to characterize intrinsically disordered proteins \u3b1-synuclein : a key protein in Parkinson\u2019s disease
No full textAbstract: Over the last years the use of mass spectrometry (MS) in the structural biology field has significantly increased. Native MS approaches, structure-sensitive digestion and fragmentation, crosslinking and labeling techniques coupled to MS gained their position in the structural MS field. The information obtained includes the protein mass, subunit stoichiometry of protein complexes, which protein regions are solvent exposed or buried inside the structure, ligands that interact with the protein, ligand stoichiometry, ligand binding sites, general shape and conformational changes of the protein, protein-protein interaction sites and of course the protein sequence with eventual mutations or post translational modifications (PTMs). An important class of proteins are intrinsically disordered proteins (IDPs), that account for over 30% of all eukaryotic proteins. With a (partial) natively disordered structure these proteins are very challenging to characterize, due to their dynamic and heterogeneous conformational ensemble. Development and use of structural MS is important to further elucidate IDP structure since MS methods can cope with their flexible and dynamic nature. In this thesis the IDP alpha synuclein (\u3b1-syn) is investigated using various MS approaches, to further characterize this protein and show the possibilities of MS as a structural technique in the challenging field of IDP characterisation. \u3b1-syn consists of 140 amino acids, is mainly expressed in presynaptic nerve terminals and plays a major role in the development of Parkinson\u2019s disease (PD). \u3b1-syn monomers can aggregate and form intermediate structures such as oligomers, which then further aggregate and form mature \u3b1-syn fibrils. Various factors, e.g. mutations, PTMs, ligands, pH and the presence of biological membranes, can affect this aggregation pathway. It is important to know how these changes occur at the molecular level to gain more understanding about aggregate formation and how this might be tackled. Using native and ion mobility (IM) MS it was investigated how far we can characterize interactions and conformational changes of \u3b1-syn monomers, and we show how instrumental advances in MS contribute to the structural IDP field. Native IM-MS was also used to determine possible structural effects of disease related mutations and relevant PTMs of \u3b1-syn. Finally we show that MS-based techniques can bridge the gap between molecular events that determine monomer conformations and the resulting aggregate structures. In general the value, relevance and importance of using MS-based techniques in the structural biology field to study challenging systems such as IDPs to characterize their full conformational ensemble and aggregation pathway is highlighted
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
The regulation and dysregulation of small heat shock proteins and an associated co-chaperone in health and disease
No full textAbstract: Small heat shock proteins are molecular chaperones which prevent misfolded proteins from aggregating. Many aspects regarding the molecular mechanisms of small heat shock proteins, both in health and disease, remain to be unraveled. In this thesis we found that mammalian small heat shock proteins are targeted to the mitochondrial intermembrane space. While small heat shock proteins of plants are targeted to virtually every membrane-enclosed compartment, this is the first example of mammalian small heat shock proteins to have an organelle-localization. This previously unknown mitochondrial function of HSPB1 is disturbed by CMT disease-causing mutations. One of the most severe HSPB1 mutations is located in a conserved IxI/V motif in the C-terminal domain. This mutation is known to cause the formation of extremely large oligomers, which we found to prevent HSPB1 from being imported into mitochondria. The underlying structural changes, associated to the formation of these large mutant oligomers, were so far poorly characterized. In this thesis we identified an unexpected mechanism underlying the structural changes. The substitution of Pro182 with Leu allows the IxI/V peptide to sample a larger conformational space and the peptide therefore finds itself less frequently in the required conformation to bind the hydrophobic cleft. As a consequence, other IxI/V containing proteins can bind more to HSPB1, explaining the altered protein-protein interactions. Finally, the co-chaperone BAG3 forms a protein scaffold which binds both small heat proteins and Hsp70. As such, it brings both arms of protein surveillance together. In this thesis we studied three different mutations in the IPV-motif of BAG3, which is where small heat shock proteins bind BAG3, and found that they induce aggresome formation. As a result of that, mutant BAG3 traps the small heat shock proteins and Hsp70 at the aggresome which leads to a general collapse in the chaperone-network
The investigation of the GIT2-RXFP3 synergistic system and its potential role in aging and age-related disorders
No full textAbstract: Most treatments for age-related disorders have been symptomatic, or target one aspect at a time, we hypothesize however that to combat these disorders at a global early level, we need to prevent these pathologies at a network level. This could be facilitated via the identification of a network-regulating master controller proteins whose modulation would thus possess multidimensional effects, termed \u2018keystone\u2019. One such aging keystone has recently been discovered, G protein-coupled receptor (GPCR) kinase interacting protein 2 (GIT2), a scaffolding protein and thus unfortunately not a canonical drug target. Our recent work however has demonstrated that G protein-coupled receptors (GPCRs) can have transcriptional control of protein expression. As such, a GPCR-based control of GIT2 expression/functionality may be an important mechanism to therapeutically control the aging process. In this dissertation, we will discuss the discovery of one such a receptor, Relaxin family peptide 3 receptor (RXFP3). We have discovered that these two proteins activate different aspects of DNA damage response and repair. In addition, they have the ability to function together and facilitate these processes. DNA damage has been classified as one of the most important hallmarks of aging, as such suggesting that if we can compel RXFP3 to engage a GIT2-dependent signaling pathway, we could potentially ameliorate multiple pathologies associated with diverse age-related disorders. Through the combined use of proteomics, interactomics and bioinformatic analysis, we were able to establish the role of the GIT2-RXFP3 system and already identify a potential GIT2-biased ligand
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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