1,720,974 research outputs found
Beta-cell hyperplasia and direct acinar-beta-cell trans-differentiation in insulin-resistant partially eNOS-deficient mice.
No full texteNOS-defi cient mice were shown to develop hypertension and insulin
resistance either in basal conditions (eNOS null) or upon high fat diet,
HFD (eNOS +/- heterozygotes). In the model of HFD-fed eNOS +/- mice,
we investigated putative pancreatic morphological changes to fi nd out
clues of the cellular mechanisms responsible for their compensatory
hyperinsulinemic response. C57BL6 wild type (WT) and eNOS +/- mice were
fed with either chow or HFD for 16 weeks. A group of chow-fed eNOS null
mice was also studied. Basal blood glucose and insulin were monitored and
glucose and insulin tolerance tests performed. Then mice were sacrifi ced
and fragments of pancreas were routinely processed for histological,
immunohistochemical and ultrastructural observation (with suitable image
analysis). Both WT and eNOS +/- mice fed with HFD developed insulin
resistance, as assessed by fasting hyperglycemia with hyperinsulinemia,
glucose intolerance and reduced response to exogenous insulin. In HFDfed
groups, evidence of compensatory adaptation of -cells was provided
by increased total pancreatic insulin content, larger -cell fractional area
and enhanced number of extra-islet -cell clusters (2-5 cells) as compared
to chow-fed groups. At ultrastructural level, in the HFD-fed eNOS +/- group
only, besides single -cells surrounded by exocrine cells, a number of cells
simultaneously containing zymogen and insulin granules were surprisingly
observed in most pancreases examined. Such cells, usually retaining the
extended and thick endoplasmic reticulum typical of acinar cells, represent
an interesting example of direct exocrine/-cell trans-differentiation, likely
triggered by strong insulin-demanding metabolic stress, yet independent on
damaging stimuli, such as duct ligation as reported in literature. The reason
why such trans-differentiation process was only detected in the eNOS +/-
mice fed with HFD remains an interesting matter of future investigation
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
Geneticsand epigenetics of congenital heart disease
No full textThe genetic architecture behind the development of congenital heart disease (CHD) still remains unclear, although CHD represents the most common type of birth defect affecting nearly 1% of live births. CHD occurs through heterogeneous and complex processes where common variants and/or (low/intermediate penetrance) mutations in genes critical for cardiac morphogenesis as well as dysregulation of post-transcriptional control play a crucial role.
The purpose of this thesis was to expand the knowledge about the etiology of CHDs through 3 main objectives:
1. to investigate the presence of gene mutations in key cardiac transcription factors in both germline and somatic cells;
2. to analyze the association between SNPs and haplotypes in the 3’UTR of candidate genes and CHD risk as well as their influence on the post-transcriptional control through the binding with specific miRNAs;
3. to investigate the presence of novel rare mutations in 17 genes related to CHD by using a next generation sequencing (NGS) approach.
We performed a Sanger sequencing of GATA4 and NKX2.5 genes in cardiac tissues of 15 sporadic (7 males; 12.4±7.5 years) and in blood samples of 15 familial (6 males; 14.1±9.0 years) patients with non-syndromic CHD. For each SNP in the 3’UTR, computational analysis was used to detect putative miRNAs and to assess the sum of all the Differences of Minimum Free Energy of hybridization (|ΔMFEtot| = Σ|ΔMFE|) in order to predict the biological importance of a SNP binding more miRNAs. Subsequently, we performed a validation reporter gene assay based on the luminescence generated by the luciferase protein, to validate the SNP whit the highest |ΔMFEtot| as a direct target of selected miRNAs. A case-control study and haplotype analysis were completed in order to define the association between the four common variants with the highest |ΔMFEtot| in the GATA4 3’UTR and the CHD risk.
A total of 12 DNA samples of CHD patients was sequenced in a NGS study by using the MiSeq® sequencing platform. The Design Studio included 17 genes related to CHD: NODAL, ZIC3, ELN, NKX2.5, JAG1, CFC1, LEFTY2, ACVR2B, GATA4, GATA6, GDF1, MYH6, TFAP2A, NOTCH1, TBX1, TBX20, and ZFPM2.
No evidence of novel GATA4 and NKX2.5 mutations was found in both sporadic and familial patients. However, we found several SNPs in the 3’UTR of GATA4 gene. Computational analysis revealed 27 putative miRNAs binding to GATA4 3'UTR variants. The most relevant |ΔMFEtot| (21.66 kcal/mol) was found for the miR-583, specifically targeting the +1521C>G SNP. A validation reporter gene assay based on the luminescence generated by the luciferase protein indicated that miR-583 was dose-dependently effective in regulating +1521 C allele compared with +1521 G allele.
The case-control study revealed that the +1158 C>T and +1521 C>G SNPs were significantly associated with the CHD risk (both, p=0.01). The haplotype analysis showed that the C-A-A-C haplotype (more common in CHD than controls) 4-fold increased the risk of CHD (p=0.04). Conversely, the T-T-G-C haplotype (more uncommon in CHDs) was associated with a significantly decreased CHD risk (p=0.035).
As regarded NGS, each single variant resulted from the targeted resequencing analysis has been annotated using the web application wANNOVAR (http://wannovar.usc.edu/) and the Ingenuity Variant Analysis software tool (Ingenuity Systems, QIAGEN), following specific parameters, as quality, frequency and pathogenicity. After filtering, the NGS analysis revealed 8 novel pathogenetic mutations, likely involved in the pathogenesis of CHD. Specifically, the mutations were identified mainly in genes (NOTCH1, MYH6, CFC1, GDF1, LEFTY2) that are related to left and/or right isomerism, involving transposition of the great arteries, tetralogy of Fallot and common atrioventricular canal anomalies.
These results provided important insights into the genetics of isolated, non-syndromic CHDs, underlining the need to investigate both the impact of SNPs on posttranscriptional mechanisms and the effects of novel, rare mutations with a low penetrance
- …
