1,721,048 research outputs found
Low-Density Lipoprotein receptor: its structure, function, and mutations
No full textUptake of cholesterol, mediated by the low-density lipoprotein (LDL)-receptor, plays a crucial role in lipoprotein metabolism. The LDL-receptor is responsible for the binding and subsequent cellular uptake of apolipoprotein B- and E-containing lipoproteins. To accomplish this, the receptor has to be transported from the site of synthesis, the membranes of the rough endoplasmatic reticulum (ER), through the Golgi apparatus, to its position on the surface of the cellular membrane. The translation of LDL-receptor messenger RNA into the polypeptide chain for the receptor protein takes place on the surface-bound ribosomes of the rough ER. Immature O-linked carbohydrate chains are attached to this integral precursor membrane protein. The molecular weight of the receptor at this stage is 120.000 d. The precursor-protein is transported from the rough ER to the Golgi apparatus, where the O-linked sugar chains are elongated until their final size is reached. The molecular weight has then increased to 160.000 d. The mature LDL-receptor is subsequently guided to the "coated pits" on the cell surface. These specialized areas of the cell membrane are rich in clathrin and interact with the LDL-receptor protein. Only here can the LDL-receptor bind LDL-particles. Within 3 to 5 minutes of its formation, the LDL-particle-receptor complex is internalized through endocytosis and is further metabolized through the receptor-mediated endocytosis pathway. Mutations in the gene coding for the LDL-receptor can interfere to a varying extent with all the different stages of the posttranslational processing, binding, uptake, and subsequent dissociation of the LDL-particle-LDL-receptor complex, but invariably the mutations lead to familial hypercholesterolemia. Thus, mutations in the LDL-receptor gene give rise to a substantially varying clinical expression of familial hypercholesterolemi
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
Lysosomal acid lipase A and the hypercholesterolaemic phenotype
No full textMutations in lysosomal acid lipase A (LIPA) result in two phenotypes depending on the extent of lysosomal acid lipase (LAL) deficiency: the severe, early-onset Wolman disease or the less severe cholesteryl ester storage disease (CESD). In CESD, the severity of the symptoms, hepatomegaly and hypercholesterolaemia, can be highly variable, presenting in childhood or adulthood. Therefore, it is likely that many patients are undiagnosed or misdiagnosed. Nevertheless, LAL deficiency has been recognized for more than 25 years, but adequate therapeutic strategies are limited. CESD has an estimated prevalence of one in 90,000 to 170,000 individuals in the general population, confirming the likelihood that this disease is currently underdiagnosed. A number of studies have shown that in LIPA deficient patients the hypercholesterolaemic phenotype can be attenuated using statin therapy, and favourable effects on reduction of lipid accumulation in lysosomes have been reported. Targeting lysosomal exocytosis with LAL replacement therapy was shown to be successful in animal models and recently a phase I/II study demonstrated its safety and its potential metabolic efficacy on transaminase levels. The hypercholesterolaemic phenotype in CESD can be difficult to distinguish from other known hypercholesterolaemic disorders. In the majority of CESD cases with hypercholesterolaemia favourable responses on statin treatment are observed, but the effect on reduction of lipid accumulation in lysosomes needs to be further evaluated. Combining statins with LAL replacement therapy may provide a promising approach for optimal treatment of LIPA deficiencies in the futur
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
Defining the challenges of FH screening for familial hypercholesterolemia
No full textThe purpose of this article is to briefly review but also to highlight the rationale, motivation, and methods in the process of identifying patients of all ages with familial hypercholesterolemia (FH), an often hidden but very important genetic disorder. Since the initiation of population screening for FH in 1994 in the Netherlands, a vast amount of experience has been gathered, addressing almost all issues that are encountered in population screenin
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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