1,720,954 research outputs found
Neurodevelopment under the prism of environmental challenges
Get PDFPrenatal development affects adult health. Exposures to a variety of prenatal environ-mental factors have important effects on fetal development and, in turn, are extensively associated with neurobehavioral, structural and functional phenotypes after birth. Developmental processes are in part promoted by orchestrated levels of glucocorticoids, which are steroid hormones involved in fetal organ maturation. Glucocorticoids also mediate the hormonal stress response of the organism as part of the hypothalamic-pituitary-adrenal axis. During pregnancy levels of glucocorticoids outside of the normal range, either due to maternal pathology including stress-related psychiatric disorders or to antenatal synthetic glucocorticoid treatments, have been associated with altered brain structural and neurobehavioral phenotypes after birth. Interestingly, developmental time-windows seem to interplay with the exposure to influence the direction of post-natal phenotypes. Exposures later in gestation are mainly associated with adverse out-comes while exposures earlier in gestation are additionally associated with potentially beneficial outcomes. While many studies have investigated the effects of glucocorticoids on late developmental time-windows, so far little evidence is available on their effects on early human cortical development and especially during the neurogenic period, which is when neurons are produced. Thus, the potential cellular and molecular underpinnings of the timing dependent divergent effects of glucocorticoids on postnatal phenotypes are not known.
To investigate these processes in a complex model of early human neurodevelopment that is reactive to environmental stimuli, I used induced Pluripotent Stem Cells-derived 3-dimensional cerebral organoids and combined them with in vivo mouse neurodevelopment. I found that application of glucocorticoids during neurogenesis increases neurogenic processes that are enriched in species with a gyrified brain, like humans, while are rare in species with a smooth brain, like rodents. These processes contribute to the increased neuronal production and cortical expansion seen in gyrencephalic species. More specifically, at the molecular level this effect is mediated by the glucocorticoid receptor, a transcription factor, which in turn activates ZBTB16 by altering its methylation landscape in specific DNA regulatory elements. Subsequently ZBTB16, a transcription factor itself, increases the expression of PAX6, a key driver of neurogenesis, by activating its promoter. This results in increased numbers of progenitor cells expressing PAX6 and EOMES (a marker of more mature progenitors) in the basal regions of the germinal zones in both organoids and mice. PAX6- and EOMES- positive progenitors are enriched in gyrified species while they are rare in species with smooth brains. The increased numbers of these highly proliferative and neurogenic progenitors lead to an extended neurogenic period and ultimately to increased production of deep layer neurons (BCL11B- positive). Finally, the altered cellular architecture due to glucocorticoids and ZBTB16 potentially mediates beneficial postnatal outcomes as indicated by causal associations with higher educational attainment and increased postnatal cortical thick-ness.
This work highlights the importance of early neurodevelopment and specifically of the neurogenic period as a sensitive time-window for glucocorticoid effects. In addition, the molecular and cellular mechanisms as well as the pathways identified could have pro-found implications for our understanding of glucocorticoid effects during early brain development that potentially mediate postnatal outcomes
Hmgb2 improves astrocyte to neuron conversion by increasing the chromatin accessibility of genes associated with neuronal maturation in a proneuronal factor-dependent manner
Get PDFBackground: Direct conversion of reactive glial cells to neurons is a promising avenue for neuronal replacement therapies after brain injury or neurodegeneration. The overexpression of neurogenic fate determinants in glial cells results in conversion to neurons. For repair purposes, the conversion should ideally be induced in the pathology-induced neuroinflammatory environment. However, very little is known regarding the influence of the injury-induced neuroinflammatory environment and released growth factors on the direct conversion process.
Results: We establish a new in vitro culture system of postnatal astrocytes without epidermal growth factor that reflects the direct conversion rate in the injured, neuroinflammatory environment in vivo. We demonstrate that the growth factor combination corresponding to the injured environment defines the ability of glia to be directly converted to neurons. Using this culture system, we show that chromatin structural protein high mobility group box 2 (HMGB2) regulates the direct conversion rate downstream of the growth factor combination. We further demonstrate that Hmgb2 cooperates with neurogenic fate determinants, such as Neurog2, in opening chromatin at the loci of genes regulating neuronal maturation and synapse formation. Consequently, early chromatin rearrangements occur during direct fate conversion and are necessary for full fate conversion.
Conclusions: Our data demonstrate novel growth factor-controlled regulation of gene expression during direct fate conversion. This regulation is crucial for proper maturation of induced neurons and could be targeted to improve the repair process
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
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