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A functional analysis of the IDDM2 susceptibility locus in type 1 diabetes /
No full textType 1 diabetes is an autoimmune disease characterized by destruction of the insulin-producing pancreatic beta-cells. Genetic predisposition, encoded by a number of loci, plays a large role in the probability of disease development. The IDDM2 susceptibility locus maps to the insulin gene (INS) variable number of tandem repeats (VNTR) minisatellite, which has two main clusters of alleles. As a whole, alleles of the class III cluster reduce the probability of developing type 1 diabetes and those of the class I cluster predispose to type 1 diabetes. To determine the functional basis of this susceptibility and protection, we tested the hypothesis that the IDDM2 effect is mediated through INS VNTR effects on transcription levels of the nearby INS and insulin-like growth factor 2 (IGF2) genes, in tissues known to be of importance in the pathogenesis of the disease. We have found evidence to suggest that protective INS VNTR alleles are associated with different levels of INS expression in the thymus than predisposing alleles, and that these levels correlate with the level of protection conferred by the INS VNTR alleles in population studies. Thus, alleles associated with high expression are protective, while alleles associated with no expression are very predisposing. This suggests that IDDM2-encoded susceptibility is mediated, at least in part, through variable expression of thymic INS which may in turn affect the efficiency of central immune tolerance induction to INS-encoded antigenic epitopes and the probability of an autoimmune response against the beta-cells. Furthermore, we did not detect any significant difference in IGF2 mRNA levels associated with the protective INS VNTR class of alleles as compared to the predisposing class in thymus, pancreas and leukocytes. This argues against IGF2 as a target gene through which INS VNTR alleles mediate susceptibility to type 1 diabetes
Variability of genomic imprinting in human disease
No full textGenomic imprinting is the differential expression of genetic material depending on the parent from which it is transmitted. It is involved in the pathogenesis of many diseases, especially those involved in development, growth abnormalities and cancer. We examined the extent of and the variability of genomic imprinting amongst individuals in three human diseases, Wilms' tumour, Type 1 diabetes and Silver-Russell syndrome.Wilms' tumour (WT) is a renal embryonal cancer associated with overexpression of the insulin-like growth factor 2 (IGF2). IGF2 is directed to the lysosomes for degradation by the mannose-6-phosphate/insulin-like growth factor two receptor (M6P/IGF2R) encoded by the IGF2R gene, a known tumour suppressor gene on 6826. IGF2R is imprinted in the mouse, with exclusive maternal expression. In humans, however, IGF2R imprinting is a polymorphic phenomenon only being found in a small subset of people. We present results suggesting that IGF2R imprinting provides the first "hit" in IGF2R inactivation in WT, and show the presence of a second "hit" in the form of deletions detectable as loss of heterozygosity.Another disease investigated in this report is Type 1 diabetes (TID), an autoimmune, polygenic disease. Of the several T1D loci, IDDM8 on 6q, has been found to be subject to parent-of-origin effects and encompasses IGF2R. M6P/IGF2R is involved in immune system regulation. In this study we show an association between TID and IGF2R that is confined to maternally inherited alleles. Our results strongly suggest that IGF2R is a TID susceptibility gene and may be universally imprinted at some tissue or developmental stage not yet studied.A third disease displaying both tissue-specific and isoform-specific imprinting is Silver-Russell syndrome (SRS), a growth disorder associated with double dose of a maternally expressed gene within 7p11.2--p13, a region in which the imprinted GRB10 gene was a prime candidate. We studied the complex tissue and isoform-dependence of GRB10 imprinting and demonstrated absence of imprinting in growth plate cartilage, the tissue most directly involved in linear growth thus eliminating GRB10 as the gene responsible for SRS.It is evident that genomic imprinting plays a prominent role in various diseases. Imprinted genes can be expressed in a tissue-specific, isoform-specific or a temporally regulated manner. In addition, there is a wide variability of imprinting between individuals
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
Genetic variations at the human growth hormone receptor (GHR) gene locus are associated with idiopathic short stature
No full textGH plays an essential role in the growing child by binding to the growth hormone receptor (GHR) on target cells and regulating multiple growth promoting and metabolic effects. Mutations in the GHR gene coding regions result in GH insensitivity (dwarfism) due to a dysfunctional receptor protein. However, children with idiopathic short stature (ISS) show growth impairment without GH or GHR defects. We hypothesized that decreased expression of the GHR gene may be involved. To test this, we investigated whether common genetic variants (microsatellites, SNPs) in regulatory regions of the GHR gene region were associated with the ISS phenotype. Genotyping of a GT-repeat microsatellite in the GHR 5'UTR in a Montreal ISS cohort (n = 37 ISS, n = 105 controls) revealed that the incidence of the long/short (L/S) genotype was 3.3× higher in ISS children than controls (P = 0.04, OR = 3.85). In an Italian replication cohort (n = 143 ISS, n = 282 controls), the medium/short (M/S) genotype was 1.9× more frequent in the male ISS than controls (P = 0.017, OR = 2.26). In both ISS cohorts, logistic regression analysis of 27 SNPs showed an association of ISS with rs4292454, while haplotype analysis revealed specific risk haplotypes in the 3' haploblocks. In contrast, there were no differences in GT genotype frequencies in a cohort of short stature (SS) adults versus controls (CARTaGENE: n = 168 SS, n = 207 controls) and the risk haplotype in the SS cohort was located in the most 5' haploblock. These data suggest that the variants identified are potentially genetic markers specifically associated with the ISS phenotype
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
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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