1,720,960 research outputs found
Unravelling region-specific responses to embryonic DNA damage in the developing brain
No full textDNA damage during early neurogenesis, e.g. resulting from DNA repair deficiencies or exposure to moderate and high doses of ionizing radiation, can lead to neurodevelopmental disorders such as microcephaly. The DNA damage response in dorsal neural progenitor cells (NPCs), which are responsible for generating excitatory neurons, has been well-studied, with outcomes including p53-mediated apoptosis and premature neuronal differentiation. However, little is known about the response of ventral NPCs, which give rise to inhibitory interneurons. Given the critical role of the balance between excitation and inhibition in maintaining proper brain function, disruptions in the development of these neuron types are linked to various neurodevelopmental disorders. This thesis aims to fill the knowledge gap regarding the effects of DNA damage on both ventral and dorsal NPC populations. For this, we used ionizing radiation as a mean to induce acute DNA damage in a controlled way. Our study focused on the effects of prenatal ionizing radiation on both ventral and dorsal NPCs, specifically from the medial ganglionic eminence (MGE) and neocortex (NCX), important regions involved in the generation of inhibitory and excitatory neurons, respectively. We exposed mouse fetuses to ionizing radiation during an early stage of forebrain neurogenesis to compare the DNA damage response in the NCX and MGE. Both regions exhibited a p53-mediated DNA damage response, involving cell cycle arrest, DNA repair, and apoptosis. However, the response differed between both regions: NCX cells experienced prolonged cell cycle arrest, while MGE cells exhibited more sustained apoptosis. Furthermore, MGE cells displayed reduced interneuron migration speed in acute living brain slices and MGE explants, the latter indicating a potential cell-intrinsic defect resulting from irradiation. This defect was not seen in explants from p53-deficient mice, indicating it is independent from the canonical DNA damage response. RNA sequencing and protein analyses revealed that disruptions in cytoskeletal-related machinery, particularly involving actin and microtubules, were more prominent in MGE cells. Despite these acute defects, irradiated mice did not show an increased susceptibility to pentylenetetrazole-induced seizures and the overall number of cortical interneurons in the young adult brain was unaffected. These findings suggest a remarkable plasticity of the developing brain in response to acute embryonic DNA damage. Overall, this study highlights region-specific responses to DNA damage in the embryonic forebrain and enhances our understanding of how early developmental insults impact brain development and may contribute to or mitigate the risk of neurodevelopmental disorders
Unravelling region-specific responses to embryonic DNA damage in the developing brain
No full textDNA damage during early neurogenesis, e.g. resulting from DNA repair deficiencies or exposure to moderate and high doses of ionizing radiation, can lead to neurodevelopmental disorders such as microcephaly. The DNA damage response in dorsal neural progenitor cells (NPCs), which are responsible for generating excitatory neurons, has been well-studied, with outcomes including p53-mediated apoptosis and premature neuronal differentiation. However, little is known about the response of ventral NPCs, which give rise to inhibitory interneurons. Given the critical role of the balance between excitation and inhibition in maintaining proper brain function, disruptions in the development of these neuron types are linked to various neurodevelopmental disorders. This thesis aims to fill the knowledge gap regarding the effects of DNA damage on both ventral and dorsal NPC populations. For this, we used ionizing radiation as a mean to induce acute DNA damage in a controlled way. Our study focused on the effects of prenatal ionizing radiation on both ventral and dorsal NPCs, specifically from the medial ganglionic eminence (MGE) and neocortex (NCX), important regions involved in the generation of inhibitory and excitatory neurons, respectively. We exposed mouse fetuses to ionizing radiation during an early stage of forebrain neurogenesis to compare the DNA damage response in the NCX and MGE. Both regions exhibited a p53-mediated DNA damage response, involving cell cycle arrest, DNA repair, and apoptosis. However, the response differed between both regions: NCX cells experienced prolonged cell cycle arrest, while MGE cells exhibited more sustained apoptosis. Furthermore, MGE cells displayed reduced interneuron migration speed in acute living brain slices and MGE explants, the latter indicating a potential cell-intrinsic defect resulting from irradiation. This defect was not seen in explants from p53-deficient mice, indicating it is independent from the canonical DNA damage response. RNA sequencing and protein analyses revealed that disruptions in cytoskeletal-related machinery, particularly involving actin and microtubules, were more prominent in MGE cells. Despite these acute defects, irradiated mice did not show an increased susceptibility to pentylenetetrazole-induced seizures and the overall number of cortical interneurons in the young adult brain was unaffected. These findings suggest a remarkable plasticity of the developing brain in response to acute embryonic DNA damage. Overall, this study highlights region-specific responses to DNA damage in the embryonic forebrain and enhances our understanding of how early developmental insults impact brain development and may contribute to or mitigate the risk of neurodevelopmental disorders
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
No full text“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
No full textWe 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
No full textWe 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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