1,720,955 research outputs found
Late Control of Cortical Histogenesis by Transcription Factors Patterning the Early Pallial Field
No full textA number of transcription factor genes implicated in primary regional patterning of the pallial primordium continue to be active or are specifically reactivated upon completion of such patterning. This late expression may be required for proper tuning of advanced cerebro- cortical histogenesis. It may account for key neurological aberrancies associated to mutations affecting such transcription factor genes.
We have previously shown that a transcription factor implicated in primary tangential patterning of the pallial primordium, Foxg1, shapes the temporal progression of the rates at which pallial stem cells give rise to astrogenic committed progenitors and the latter progress to astrocytes. Inspired by these findings, we hypothesized that these two rates might be also differentially regulated in space, in distinctive regions of the murine developing pallium, and that factors patterning pallium might be implicated in such regulation. This prediction turned out to be correct. We found that, compared to their age-matched rostro-lateral counterparts, early caudo-medial pallial stem cells are more biased to astrogenesis, and generate astroblasts less prone to proliferation and more keen to early differentiation. We got evidence that Emx2, a transcription factor gene mastering caudo-medial cortical specification, drives regionally patterned articulation of astrogliogenesis. Moreover, we demonstrated that three established pro-astrogenic factors, Sox9, Nfia and Couptf1, mediate Emx2 impact on neural stem cells commitment to astrogenesis.
On the other hand, the two mutant FOXG1 alleles FOXG1G224S and FOXG1W308X have been found in children affected by severe varieties of the FOXG1 Syndrome. Previous functional characterization of these alleles in murine wild type cells showed that they act as gain- and loss-of-function variants of their healthy counterpart, respectively. Before any possible therapeutic exploitation, results of this study require a stringent validation in human neural cells, harboring gene configurations matching the patients' ones. To this aim, we obtained human pluripotent stem cells heterozygous for these mutations and their co-isogenic healthy controls, and we set up a protocol suitable to reproducibly generate dorsal telencephalic tissue starting from healthy human pluripotent stem cells. We discovered that, applying such protocol to heterozygous FOXG1W308X mutants, the generation of pallial neuroepithelium is defective. To allow robust interrogation of more advanced derivatives of FOXG1W308X/+ neuroepithelium, we are now managing to mitigate this issue
Assessing Neuronogenic Versus Astrogenic Bias of Neural Stem Cells Via In Vitro Clonal Assay
No full textWithin the developing cerebral cortex, neural stem cells (NSCs) give rise to neurons and glial cells, according to complex spatio-temporal trajectories. In this respect, a key issue is how NSCs are committed to different neural lineages in time and space. Clonal assays are a powerful tool to address this issue. Here we describe an easy clonal assay protocol employable to dissect NSCs lineage commitment and molecular mechanisms underlying it. NSCs of distinctive spatio-temporal origin, and/or having undergone different molecular manipulations, are plated at low density and allowed to differentiate for a few days. Then, systematic immunoprofiling of the resulting clones allows to quantify commitment of their NSC ancestors to neuronal and astroglial fates
Spatial control of astrogenesis progression by cortical arealization genes
No full textSizes of neuronal, astroglial and oligodendroglial complements forming the neonatal cerebral cortex largely depend on rates at which pallial stem cells give rise to lineage-committed progenitors and the latter ones progress to mature cell types. Here, we investigated the spatial articulation of pallial stem cells' (SCs) commitment to astrogenesis as well as the progression of committed astroglial progenitors (APs) to differentiated astrocytes, by clonal and kinetic profiling of pallial precursors. We found that caudal-medial (CM) SCs are more prone to astrogenesis than rostro-lateral (RL) ones, while RL-committed APs are more keen to proliferate than CM ones. Next, we assessed the control of these phenomena by 2 key transcription factor genes mastering regionalization of the early cortical primordium, Emx2 and Foxg1, via lentiviral somatic transgenesis, epistasis assays, and ad hoc rescue assays. We demonstrated that preferential CM SCs progression to astrogenesis is promoted by Emx2, mainly via Couptfl, Nfia, and Sox9 upregulation, while Foxg1 antagonizes such progression to some extent, likely via repression of Zbtb20. Finally, we showed that Foxg1 and Emx2 may be implicated-asymmetrically and antithetically-in shaping distinctive proliferative/differentiative behaviors displayed by APs in hippocampus and neocortex
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
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