1,720,978 research outputs found
GENOME WIDE ANALYSIS IN A COHORT OF 46,XX PATIENTS AFFECTED BY AN EXTREME PHENOTYPE OF PRIMARY OVARIAN INSUFFICIENCY: AN EFFICIENT TOOL TO IDENTIFY NEW GENES INVOLVED IN OOCYTE MATURATION AND DIFFERENTIATION
Get PDFPrimary Ovarian Insufficiency (POI) is a heterogeneous group of disorders with an incidence of 1:10,000 women by age 20, 1:1,000 by age 30, 1:100 by age 40. POI describes the progression toward the cessation of ovarian function and can occur in the most serious form as primary amenorrhea (PA), with absent pubertal development and/or ovarian dysgenesis (OD), or in milder phenotype with post-pubertal onset and secondary amenorrhea (SA). Several are the etiological causes that may induce ovarian dysfunction, among which the genetic component is considered prevalent (as supported by the occurrence of families with more than one affected women and the existence of several idiopathic cases) but highly heterogeneous.
46,XX non-syndromic women showing the most severe phenotype, characterized by the absence of pubertal development with PA and OD, are very rare but the search for genetic variations in this extreme phenotype may be more effective in identifying novel pathogenic mechanisms. Hence, using high resolution array-CGH we searched for rare high-penetrant CNVs involving genes essential for ovarian function in a cohort of 67 46,XX non-syndromic patients affected by PA, namely 53 sporadic (79.1%) and 14 familial (20.9%) cases. 28 out of 67 women resulted positive to array-CGH analysis because having at least one rare “ovarian” CNV: a total number of 32 CNVs involving 37 ovarian genes was selected.
Population from Database of Genomic Variants (DGV) was used to evaluate the rarity of POI CNVs, but it does not match to the ideal set of controls for POI disease (neither age nor gender of DGV controls are known). Thus, to better understand the CNVs contribution in disease onset, the rare “ovarian” CNVs found in patients according to DGV were searched in an ad hoc control cohort, previously screened by array-CGH, consisting in 140 healthy women with normal reproductive life and physiological menopause. 28 out of 32 rare “ovarian” CNVs detected in patients were not found in the control group thus supporting their role in the POI’s pathogenesis. Moreover, to evaluate the presence of a significant enrichment in ovarian genes in the POI group, array-CGH of the ad hoc control cohort were analyzed with the same approach adopted for patients cohort and 49 CNVs involving 54 ovarian genes were selected. Several statistical analyses were performed comparing patients’ to controls’ data and revealed no significant differences. Nevertheless, the CNVs found in the POI cohort containing ovarian genes are more harmful respect to the CNVs identified in the controls cohort.
The 37 genes perturbed or possibly perturbed by POI CNVs are implicated in several ovarian processes (e.g., regulation of cytoskeleton dynamics for oocytes asymmetric division, maintenance of oocytes genomic integrity, ovarian differentiation, follicular development, and meiotic resumption), thus supporting their involvement in POI etiology. Validation and characterization of selected CNVs, as well as the study of a possible gene perturbation at mRNA level, was also crucial in order to perform a correct genotype-phenotype correlation and to propose new candidate genes for POI disease (e.g. TP63, VLDLR).
39 out of 67 women resulted negative for rare “ovarian” CNVs (58.2%) suggesting to combine different genomic approaches in order to increase the detection rate of the disorder. Hence, 17 out of 67 collected patients, were submitted to a preliminary WES analysis searching for rare SNVs in a total of 191 genes selected from array-CGH data, and literature regarding POI and ovary. The WES preliminary analysis allowed to confirm the importance of some array CGH new candidate genes in POI onset (e.g. VLDLR) and the complex heterogeneity of POI.
The combination of these molecular evidences, with major or minor contribution, might have been at the basis of POI supporting the existence of a disease genetic model characterized by oligogenic heterozygosity (i.e., the simultaneous presence in a single patient of multiple heterozygous quantitative variants/rare mutations, both de novo and/or inherited, affecting multiple genes).
The present approach using both array-CGH and WES techniques, resulted an efficient tool to identify rare variants (CNVs and SNVs) involving both genes already reported in POI, and new candidate genes with a role in oocyte maturation and differentiation. The results of this study are promising to expand the knowledge about the molecular pathways involved in POI pathogenesis and probably provide the basis for a more accurate genetic diagnosis of POI patients
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
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Microdeletion in two unrelated patients with intellectual disability
No full textHere we describe two unrelated patients, a 5 years old male and a 7 years old female referred as Smith-Magenis syndrome-like phenotype. Indeed, they are characterized by craniofacial dysmorphisms, intellectual disability, language impairment, behavioural problems, and sleep disturbance.
As RAI1 mutational study was negative, high resolution array-CGH analysis was performed revealing in both patients a similar deletion at 6p25.1 yet unreported in Database of Genomic Variants. In detail, the male and female patients have respectively a 141 kb and a 304 kb microdeletion spanning 5’ of LYRM4 (encoding a protein required for nuclear and mitochondrial iron-sulfur protein biosynthesis) and 5’ of FARS2 (encoding a phenylalanyl-tRNA synthetase 2 precursor). Both rare CNVs are inherited by the healthy mothers.
Consistent with a putative pathogenic role of the two probands CNVs, a similar deletion was reported in dizygotic twins with clinical features partially overlapping those of the patients herein described. Even twins CNV was inherited by their mother, who had however a borderline phenotype.
Attempting to explain the lack of clinical signs in the mothers of our probands, we carried out RT-qPCR and Sanger sequencing on both genes. These analyses revealed the same expected transcript reduction in patients and mothers as compared to controls and no mutations in the coding regions. Thus, to unveil a second hit contributing to the patients’ phenotype, we sequenced the promoter regions of FARS2 and LYRM4 to search for variants dysregulating the unaffected alleles. The analysis did not evidence any variant that might concur to the patients’ phenotype. Up to now our cases are the second report on CNVs spanning the 5’ of FARS2 and LYRM4 genes. Overall two unrelated patients with the same genomic defect and an overlapping phenotype, according to a previous report, support a pathogenic role for the current 6p25.1 deletions. The identification of second hit is still elusive and further studies are needed to clarify the genotype-phenotype correlation
- …
