1,720,972 research outputs found
ROLE OF THE NOTCH LIGAND JAGGED1 IN ZEBRAFISH THYROID DEVELOPMENT
No full textNotch signaling is the result of the complex interaction of various Delta and Jagged ligands and their Notch receptors. This signal is known to have a relevant and expanding role in cell fate determination, survival and proliferation during embryonic development. Though Notch pathway is known to have a fundamental role in different endocrine systems (i.e. anterior pituitary and pancreatic cell specification), its possible involvement in thyroid development has never been studied. Our previous gene expression analysis in a thyroid cell line revealed the presence of several transcripts belonging to the Jagged1-Notch pathway, thus suggesting its potential role in thyroid development. Then, we designed a series of experiments aimed at confirming these preliminary data in vitro and understand the role of Notch signaling in thyroid development. For this purpose, we took advantage of zebrafish, a versatile experimental model that has been shown to largely recapitulate the early events of mammalian thyroid gland organogenesis.
Gene expression analysis and experimental manipulations of zebrafish embryos were performed to identify the possible contribution of Jagged1 ligands to the thyroid development. Loss of Notch receptors activation in mind bomb (mib) mutants or DAPT-treated embryos led to an increased number of thyroid primordium cells. Conversely, Notch gain of function resulted in an impaired expression of the early thyroid marker genes (nkx2.1a; tg) in vivo.
Given that the entire pharyngeal architecture was seriously affected by these genetic conditions, the observed thyroid phenotypes could come from either cell-autonomous or non cell-autonomous activities of Notch signaling. In order to understand if Notch signaling plays a direct role in thyroid development, we then analyzed the co-expression pattern of the zebrafish jag1a and jag1b, orthologues of the mammalian Jagged1 ligand, and thyroid markers by double whole-mount in situ hybridization. These experiments show the co-expression of these ligands in the thyroid region, at different times. Next, to understand the biological role of these ligands, we took advantage of both morpholino knock-down strategy and specific zebrafish mutants. Thyroid development was impaired in several of these conditions, as shown by the altered expression of thyroid differentiation markers tg and slc5a5 and T4 production at different time points. As a consequence, a defective function of Jagged1 ligand might constitute a novel mechanism involved in the pathogenesis of congenital hypothyroidism
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
PKA II mediates cAMP-dependent phosphorylation of CREB and activation of gene transcription in differentiated rat thyroid cells
No full textThyroid stimulating hormone (TSH) is the key modulator of thyroid cell function. Binding of TSH to its receptor (TSHR) results in an increase of cAMP intracellular concentration, which activates protein kinase A (PKA) to phosphorylate CREB and other substrates. Eventually, this leads to gene transcription modification associated with both proliferation and differentiation. Two major types of PKA (PKA I and II) exist in mammal cells, but their specific role in TSH signaling is poorly understudy so far. Therefore, the aim of this study was to dissect PKA I/II effects on gene transcription in thyroid cells. In order to selectively activate PKA I or II, pairs of cAMP analogs with different affinities for sites A and B of PKA regulatory subunits were used. The effect of PKA I or II activation on the transcription of early genes, genes involved in cell replication and genes associated with thyroid differentiated function was evaluated in FRTL5 cells by quantitative real-time PCR. The results indicate that PKA II, but not PKA I, stimulation can mimic the effect of TSH treatment on these genes. In addition, pre-treatment with a PKA II inhibitor was able to abolish the effect of TSH. Since CREB is the major transcriptional mediator of cAMP signal, we also evaluated the effect of PKA I or II activation on CREB phosphorylation. Also in this case, only PKA II activation lead to efficient CREB phosphorylation, and TSH-dependent activation was abolished by pre-incubation with the PKA II inhibitor. Finally, silencing of PKA regulatory subunit 2B (Prkar2b) by RNA interference resulted in down-regulation of proliferative genes. These results indicate that PKA II is the principal mediator of cAMP transcriptional effects in thyroid cells. Further studies are needed to evaluate the role of PKA I, which could play a role in post-transcriptional modifications rather than directly affecting gene transcription
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
Zebrafish Ortholog of Human DOT1L Regulates Primitive and Transient Definitive Hematopoiesis and Controls hoxa9 and meis1 Expression
No full textDispelling 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
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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