1,721,367 research outputs found
The emerging role of TRIB3 as a gene affecting human insulin resistance and related clinical outcomes
No full textType 2 diabetes is becoming epidemic. The personal and social burden imposed by diabetes will increase in the close future as its prevalence is expected to double in the next 15-20 years. Type 2 diabetes is caused by the combination of resistance to insulin action and inadequate insulin secretion. Despite the role of profound changes in individual environmental exposure is incontrovertible, several findings clearly indicate that type 2 diabetes and insulin resistance are also heritable. Among the several inhibitors of insulin signalling, which have been recently proposed as determinants of insulin resistance, is TRIB3, a mammalian tribbles homolog which affects insulin signalling at the level of Akt-2, a key modulator of insulin action in target cells. We here report data on a prevalent Q84R TRIB3 missense single nucleotide polymorphism (rs2295490) we first described few years ago. Several lines of evidences indicate that this amino-acid change is, in fact, a gain of function mutation with the potential to affect insulin signalling and thus, to increase the risk of insulin resistance and related clinical outcomes. © 2009 Springer-Verlag
Disentangling the heterogeneity of adulthood-onset non-autoimmune diabetes: a little closer but lot more to do
No full textDiabetes diagnosed in adults is a highly heterogeneous disorder. It mostly consists of what is referred to as type 2 diabetes but also comprises other entities (i.e different diseases), including latent autoimmune diabetes, late onset forms of monogenic diabetes and familial diabetes of the adulthood, which has recently been the source of new diabetogenes discovery. Notably, type 2 diabetes is itself heterogeneous as it includes subtypes with onset at the extremes of age and/or weight distributions characterized by different degree of hyperglycemia and cardiovascular risk as compared to common forms of type 2 diabetes occurring in middle-aged, overweight/obese individuals. Understanding whether these are different presentations of one, highly heterogeneous disease or separate nosological entities with different clinical trajectories and requiring different treatments is essential to effectively pursue the path of precision medicine
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
Chromosomal sensitivity to clastogenic agents and cell cycle perturbations in Nijmegen breakage syndrome lymphoblastoid cell lines
No full text: The relationship between chromosomal breakage and perturbations of cell cycle progression was investigated in lymphoblastoid cell lines established from a healthy donor, two subjects affected by Nijmegen Breakage Syndrome (NBS) and an ataxia-telangiectasia (AT) patient. The cytogenetic analysis revealed a similar chromosomal hypersensitivity in both NBS and AT cells exposed in the G1 phase to 200 cGy X-rays or in G2 to 15-30 cGy. Similarly, no differences were observed in the frequency of chromatid-type aberrations induced in G2 by 1-2 pg/ml calicheamicin gamma 1I, a DNA double-strand break inducer. In addition, as observed in AT cells, the rate of G2 radiation-induced chromosomal damage was less enhanced in NBS than in control cells following 3-h incubation with inhibitors of DNA synthesis/repair (cytosine arabinoside, aphidicolin, DMSO, hydroxyurea, caffeine). This is suggestive of an altered DNA lesion-processing pathway common to both syndromes. Despite the close resemblance of cellular phenotypes in the two syndromes, the analysis of mitotic indices carried out at 2 and 4 h postirradiation indicated that NBS sustained a G2-delay greater than that observed in AT cells, Furthermore, the flow cytometric analysis of 50-300 cGy irradiated cells at 10 and 20 h before harvesting showed that NBS cells sustained a G2/M phase arrest markedly lower than AT cells. Our data indicate that NBS and AT gene products are involved in a common pathway of radiation-induced chromosomal damage, but in a different one for cell cycle control after irradiation
Chromosomal sensitivity to clastogens and cell cycle perturbations in Nijmegen breakage syndrome lymphoblastoid cell lines
No full textVariations 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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