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Clinical, Genetic, and Protein Structural Aspects of Familial Dysalbuminemic Hyperthyroxinemia and Hypertriiodothyroninemia
Full text linkFamilial dysalbuminemic hyperthyroxinemia (FDH-T4) and hypertriiodothyroninemia (FDH-T3) are dominantly inherited syndromes characterized by a high concentration of thyroid hormone in the blood stream. The syndromes do not cause disease, because the concentration of free hormone is normal, but affected individuals are at risk of erroneous treatment. FDH-T4 is the most common cause of euthyroid hyperthyroxinemia in Caucasian populations in which its prevalence is about 1 in 10,000 individuals, but the prevalence can be much higher in some ethnic groups. The condition is caused by a genetic variant of human serum albumin (HSA); Arg218 is mutated to histidine, proline, or serine or Arg222 is changed to isoleucine. The disorder is characterized by greater elevation in serum l-thyroxine (T4) than in serum triiodothyronine (T3); T4 can be increased by a factor 8–15. The high serum concentration of T4 is due to modification of a binding site located in the N-terminal half of HSA (in subdomain IIA). Thus, mutating Arg218 or Arg222 for a smaller amino acid reduces the steric restrictions in the site and creates a high-affinity binding site. The mutations can also affect binding of other ligands and can perhaps cause modified pharmacokinetics of albumin-binding drugs. In normal HSA, the high-affinity site has another location (in subdomain IIIB). Different locations of these sites imply that persons with and without FDH-T4 can have different types of interactions, and thereby complications, when given albumin-binding drugs. FDH-T3 is caused by a leucine to proline mutation in position 66 of HSA, which results in a large increment of the binding affinity for T3 but not for T4. For avoiding unwanted treatment of euthyroid persons with hyperthyroxinemia or hypertriiodothyroninemia, protein sequencing and/or sequencing of the albumin gene should be performed
Mutations and polymorphisms of the gene of the major human blood protein, serum albumin
No full textWe have tabulated the 77 currently known mutations of the familiar human blood protein, serum albumin
(ALB). A total of 65 mutations result in bisalbuminemia. Physiological and structural effects of these mutations
are included where observed. Most of the changes are benign. The majority of them were detected upon clinical
electrophoretic studies, as a result of a point mutation of a charged amino acid residue. Three were discovered
by their strong binding of thyroxine or triiodothyronine. A total of 12 of the tabulated mutations result in
analbuminemia, defined as a serum albumin concentration of <1 g/L. These were generally detected upon
finding a low albumin concentration in patients with mild edema, and involve either splicing errors negating
translation or premature stop codons producing truncated albumin molecules. A total of nine mutations, five of
those with analbuminemia and four resulting in variants modified near the C-terminal end, cause frameshifts.
Allotypes from three of the point mutations become N-glycosylated and one C-terminal frameshift mutation
shows O-glycosylation
Molecular Genetics of Analbuminemia
No full textCongenitalanalbuminaemia (CAA) is a very rare condition
manifested by the near complete absence of albumin, the
major blood protein, because of defects in the albumin
(ALB) gene. It is generally regarded as relatively benign in
adults, but analbuminaemic individuals may be at risk
during the perinatal and childhood period. Twenty-one
different molecular lesions in the ALB are now known as
cause of the trait. These include one mutation in the start
codon, one frameshift/insertion, five frameshift/deletions,
seven nonsense mutations and seven mutations
affecting splicing. Thus, nonsense mutations, mutations
affecting splicing and frameshift/deletions seem to be
the most common causes of CAA. These results indicate
that the trait is an allelic heterogeneous disorder caused
by homozygous or, in a single case, compound heterozygous
inheritance of defects. Most mutations are unique,
but one, named Kayseri, is responsible for about half of
the known cases
Mutants and molecular dockings reveal that the primary L-thyroxine binding site in human serum albumin is not the one which can cause familial dysalbuminemic hyperthyroxinemia
No full text
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
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
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