1,721,045 research outputs found
Tyrosine kinase activity of insulin receptors from an insulin-resistant patient with leprechaunism
No full textDefects in insulin receptor function can impair the response of target cells to insulin. Previously we have described an insulin resistant patient (leprechaun/Ark-1) with qualitative abnormalities in insulin binding suggestive of a structural defect in her insulin receptors. In the present work, we have studied the tyrosine kinase activity associated with insulin receptors from cultured Epstein-Barr virus-transformed lymphocytes. In studies of insulin receptors from leprechaun/Ark-1, we observed that both the magnitude and the dose-dependency of insulin's effect to stimulate the tyrosine kinase activity were normal. This suggests that the defect causing this patient's insulin resistance is independent of the receptor-associated tyrosine kinase. In the course of these studies, we noted that an anti-receptor antiserum (B-d) had a markedly decreased ability to immunoprecipitate insulin receptors from leprechaun/Ark-1. This observation further supports our previous conclusion that the insulin receptor from leprechaun/Ark-1 is abnormal in structure. Moreover, it emphasizes the importance of choosing anti-receptor antisera which are equally effective at immunoprecipitating receptors from both patients and normal subjects when the anti-receptor antisera are employed as reagents in investigations of receptors from insulin-resistant patient
Postbinding characterization of five naturally occurring mutations in the human insulin receptor gene: impaired insulin-stimulated c-jun expression and thymidine incorporation despite normal receptor autophosphorylation
No full textSome patients with extreme insulin resistance have mutations in their insulin receptor gene. We previously identified five such mutations located in the extracellular domain of the insulin receptor (Asn-->Lys15, His-->Arg209, Phe-->Val382, Lys-->Glu460, and Asn-->Ser462) and studied the effects of these mutations upon posttranslational processing, insulin binding, and tyrosine autophosphorylation. We now characterize the ability of these mutant receptors to mediate biological actions of insulin in transfected NIH-3T3 fibroblasts. All cell lines expressing mutant receptors showed marked impairment in insulin-stimulated c-jun expression and thymidine incorporation when compared with cells expressing wild-type human insulin receptors. The most severe impairment was seen in cells expressing the Val382 mutant (a mutation which causes an intrinsic defect in receptor autophosphorylation). These cells had insulin responses similar to the untransfected cells (used as a negative control). In contrast, cells expressing the Lys15 mutant have the ability to achieve a normal level of maximal autophosphorylation but require an abnormally high concentration of insulin to do so (as the result of decreased insulin binding affinity). These cells show a higher basal rate and much lower insulin stimulation of both c-jun expression and thymidine incorporation when compared with the cells expressing the wild-type human insulin receptors. This pattern is also seen in the cells expressing the other mutants with normal autophosphorylation (Arg209, Glu460, and Ser462). Although the most severe defects in insulin action are seen with the mutation which has an intrinsic defect in receptor autophosphorylation, the ability to undergo normal autophosphorylation does not seem to preclude mutations from impairing the ability of receptors to mediate some of the actions of insulin
Mutations of the human insulin receptor gene
No full textMutations in the insulin receptor gene have been identified in patients with genetic forms of insulin resistance. These mutations provide insight into structure-function relationships of the insulin receptor, and also into the causes of insulin resistance in human diseas
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
Methods for routine diagnosis of genomic rearrangements: multiplex PCR-based methods and future perspectives
No full textGermline and somatic genomic rearrangement play a relevant role in the pathogenesis of genetic disorders, and their identification is a fundamental task in molecular diagnosis. However, screening for structural genomic abnormalities is often not included in routine mutational analyses and consequently the proportion of rearrangements playing a pathogenic role in several genetic disorders is likely to be underestimated. A wide range of molecular techniques for the detection of large genomic rearrangements has been developed: some methods have the power to screen the whole genome, others are designed to analyze one or few loci that are known to be involved in a specific disease; some may detect balanced rearrangements, while others only unbalanced rearrangements; some are suitable for detection of germline abnormalities, yet others also detect somatic abnormalities. This review provides a brief summary of principles, applications and limitations of the methods available for the screening of genomic rearrangements, focusing on multiplex PCR-based protocols that are currently employed in routine detection of extended germline genomic deletions or duplications. Future developments based on microarray platforms and high-throughput sequencing are also 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
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