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COPY NUMBER VARIATION AND EXPRESSION OF HTERT AND HTERC GENES IN AMNIOCYTE CULTURED SAMPLES WITH NORMAL AND ABNORMAL KARYOTYPE
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Increased frequency rate and alteration of If current in iPSC-derived atrial fibrillation human cardiomyocytes.
No full textAtrial fibrillation (AF) is the most common sustained arrhythmia worldwide. The mechanisms underlying AF are not fully understood, but multiple pathophysiological pathways have been suggested. On the contrary, the well-established AF risk factors include male sex, advancing age, diabetes, hypertension, heart failure, myocardial infarction, and valvular heart disease. Nevertheless, much of the AF risk variability remains unexplained, leading investigators to look for novel and genetic risk factors. Since 1940, a number of reports have described rare inherited AF disorders mainly associated with cardiac channel mutations. Recently several GWAS studies have shown the association of AF with peculiar chromosomal loci, and, nowadays, parental AF is considered as one of the main risk factor in offspring.
We started characterizing a family where three siblings suffered a common persistent AF. The consanguinity, the variability in risk factors, and the young age of onset of AF in these patients (from 44 to 52 years old) strongly suggested a genetic basis for this form of arrhythmia. Since an extensive single candidate gene analysis, comprising several known AF-associated genes, did not reveal any mutation, we approached the entire exome analysis to identify other sequence abnormalities. Preliminary results show that the three siblings are carrying two different single nucleotide mutations in cellular filaments. These mutations, further confirmed by Sanger sequence analysis, are absent in the rest of the family and have not been described in human exome sequence databases.
In parallel, we built the cellular-based human in vitro AF model, starting from patients-derived primary cultures of dermal fibroblasts. These cells were transduced with Yamanaka’s factors OCT4, KLF4, SOX2 and c-MYC, using two different systems: either a mix of retroviruses each of them carrying a single gene, or a single lentiviral particle carrying an omni-comprehensive polycistronic RNA. Colonies of pluripotent stem cells (iPSC) were generated using both systems, but the lentiviral infection showed a higher reprogramming efficiency. Nevertheless, karyotype analysis of five independent clones showed a common chromosomal translocation (t17;19) that was absent in fibroblast primary culture, as well as in retroviral infected iPS clones.
Following the assessment of pluripotency, we have differentiated AF-derived iPSC into cardiomyocytes (CMs) by a standard differentiation protocol through embryoid bodies formation. The presence of beating cells allowed us to identify and to isolate clusters of CMs whose electrophysiological properties have been analyzed. Cellular spontaneous action potentials were recorded revealing different traces and frequencies in AF-derived CMs versus the normal counterpart. Moreover, after single CM isolation, we measured funny current (If), strongly related to pacemaker activity. We found that the activation of HCN channels in AF-derived CMs is reached before the normal counterpart, thus suggesting a higher cellular excitability.
In conclusion we obtained iPSC-derived human CMs that, as shown, represent a valuable and reliable model of AF. We are presently using our model to understand the link between the identified mutations and the recorded functional alterations. Using this tool we will ultimately be able to identify novel therapeutic targets for this form of cardiac arrhythmia
Evidences of Tert gene and protein in Wharton jelly mesenchymal stem cells and amniotic fluid cultured cells
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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
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