1,720,961 research outputs found
Defective Thyroglobulin: Cell Biology of Disease
Full text linkThe primary functional units of the thyroid gland are follicles of various sizes comprised of a monolayer of epithelial cells (thyrocytes) surrounding an apical extracellular cavity known as the follicle lumen. In the normal thyroid gland, the follicle lumen is filled with secreted protein (referred to as colloid), comprised nearly exclusively of thyroglobulin with a half-life ranging from days to weeks. At the cellular boundary of the follicle lumen, secreted thyroglobulin becomes iodinated, resulting from the coordinated activities of enzymes localized to the thyrocyte apical plasma membrane. Thyroglobulin appearance in evolution is essentially synchronous with the appearance of the follicular architecture of the vertebrate thyroid gland. Thyroglobulin is the most highly expressed thyroid gene and represents the most abundantly expressed thyroid protein. Wildtype thyroglobulin protein is a large and complex glycoprotein that folds in the endoplasmic reticulum, leading to homodimerization and export via the classical secretory pathway to the follicle lumen. However, of the hundreds of human thyroglobulin genetic variants, most exhibit increased susceptibility to misfolding with defective export from the endoplasmic reticulum, triggering hypothyroidism as well as thyroidal endoplasmic reticulum stress. The human disease of hypothyroidism with defective thyroglobulin (either homozygous, or compound heterozygous) can be experimentally modeled in thyrocyte cell culture, or in whole animals, such as mice that are readily amenable to genetic manipulation. From a combination of approaches, it can be demonstrated that in the setting of thyroglobulin misfolding, thyrocytes under chronic continuous ER stress exhibit increased susceptibility to cell death, with interesting cell biological and pathophysiological consequences
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
Structural and spectroscopic characterization of human cystathionine β-synthase
No full textHuman cystathionine β-synthase (CBS), a pyridoxal 5′ -phosphate (PLP)-dependent hemeprotein, catalyzes the condensation of homocysteine and seine to give cystathionine. The CBS catalyzed reaction is the first committed step in the catabolic removal of the toxic metabolite, homocysteine, via the transsulfuration pathway. The latter also represents a pathway for the conversion of homocysteine to cysteine and ultimately to glutathione (GSH). The reaction catalyzed by CBS is of clinical importance. Mutations in CBS result in high levels of homocysteine and is the most common cause of hereditary homocystinuria. High homocysteine levels are an independent risk factor for cardiovascular diseases, neural tube defects and Alzheimer\u27s disease. Human CBS is a homotetramer of 63 kDa subunits and contains 1 mol of heme and 1 mol of PLP per subunit. While the dependence of CBS activity on PLP can be explained by the chemical similarity of the reaction it catalyses to β-replacement reactions catalyzed by other PLP enzymes, the role of the heme and its location relative to the active site was not known when this study was initiated. In this study, we have used a combination of spectroscopic methods to provide the first structural evidence for a regulatory role for the heme. The two cofactors, heme and PLP, were estimated to be grater than 10 Å apart indicating that a catalytic role for the heme is unlikely. However, changes in the heme oxidation state were found to be transmitted to PLP in the active site consistent with a regulatory role for this cofactor. We also purified and characterized a pathogenic CBS mutant, V168M, associated with a B6-responsive phenotype in patients and showed that the cofactor content of the enzyme is regulated by interactions between the C-terminal regulatory and the N-terminal catalytic domains. The defect introduced by the V168M substitution resulted in a 7-fold lower PLP and 2-fold lower heme content with a 13-fold decrease in enzyme activity and was completely alleviated by deletion of 143 amino acids from the C-terminal. Since some CBS mutations described in patients with high levels of homocysteine due to the CBS deficiency appear to result in normal enzyme activity, we hypothesized that CBS interacts with other proteins and that these interactions are disrupted in this subclass of pathogenic mutants. In order to address this question, we have used the yeast two-hybrid system and probed a human brain library with the CBS bait. These studies identified Ubc9 and PIAS1 which represents the E2 and E3 enzymes involved in the sumoylation pathway. CBS contains three consensus ΨKXE sequences that represent targets for sumoylation. All three sequences are surface exposed in the structure of the dimeric enzyme. In fact, K102 in one of the consensus sequences, LKCE, is mutated to a glutamine in a patient and raises the question as to whether sumoylation of the protein may be impaired. Although these studies are still in progress, our efforts to observe sumoylation of CBS is discussed
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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