1,721,035 research outputs found
Developmental Emergence of Cortical Neurogliaform Cell Diversity
Full text linkGABAergic interneurons are key inhibitory regulators of cortical circuit function. Among the dozens of reported transcriptionally distinct types of cortical interneurons, neurogliaform cells (NGCs) are unique: they are the primary source of ‘slow’ cortical inhibition and are recruited by long-range excitatory inputs. Despite their functional importance, the developmental emergence and cellular diversity within this cell type remain unclear. Here, combining single- cell transcriptomics, genetic fate-mapping, electrophysiological characterization and morphological reconstruction, we show that discrete molecular subtypes of NGCs emerge from a common progenitor domain in the embryonic preoptic area (POA). Moreover, using in-utero electroporation, we show that the different NGC subtypes are generated in the POA at E14.5. By reconstructing NGC molecular architecture across development, we demonstrate that newborn NGCs and their postnatal progeny harbor shared molecular features and that the transcription factor Tox2 constitutes an identity hallmark for the different members of the NGC family. Subsequently, using CRISPR-mediated genetic loss-of-function, we reveal that the transcription factor Tox2 is critical for the development of these cells: POA-born cells lacking Tox2 fail to differentiate into NGCs. Together, these results indicate that the different NGC subtypes are born from a spatially restricted pool of POA progenitors, after which subtype signatures are gradually acquired through development via diverging molecular programs and reach a stabilization plateau at early postnatal stages
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
Plasticity in neurogenic competence of cortical progenitors in the developing mouse neocortex
No full textLa diversité de neurones à la base des fonctions corticales est générée au cours du développement embryonnaire par des progéniteurs. Leur capacité à répondre à des changements de signaux environnementaux pendant le développement, ainsi que leur restriction du potentiel reste mal connus. Nous avons examiné le devenir des neurones générés par des progéniteurs apicaux et intermédiaires après transplantations hétérochroniques. A l'inverse des progéniteurs intermédiaires qui perdent leur capacité de générer des neurones précoces, les progéniteurs apicaux conservent leur multipotencialité et restent en mesure d'inverser leur identité afin de produire des types neuronaux précoces. Ainsi, la progression temporelle de l'identité des progéniteurs apicaux qui sous-tend la génération de types neuronaux distincts au cours de temps ne fait pas l'objet de restriction au cours du développement. Ces résultats mettent en évidence les différences de plasticité de chaque type de progéniteurs, ceux-ci pouvant être exploités dans le cadre d'études de pathologies neurodégénératives
Region-specific mechanisms of brain growth during mouse development
No full textMammalian brain development is characterized by disproportionate growth of the forebrain compared to other regions. However, the exact process driving this localized enlargement remains largely unknown. In order to characterize region specific birthdating patterns, we generated an atlas of neuronal birthdate in the mouse brain. We used two complementary birthdating techniques to systematically acquire the time of birth of neurons across a big variety of brain structures during the embryonic neurogenic period. We identified that most brain stem regions are born in a transient manner with the majority of neurogenesis taking place in the early stages of brain development, while the forebrain neurogenesis is sustained along a much longer time window. This sustained neurogenesis coincides with a lengthened cell cycle and a reduction of consumptive division of apical progenitor resulting in their preservation for longer time period. Using single-cell RNA sequencing, we identified functional spatio-temporal molecular programs regulating progenitors cycling properties. We used loss-of-function assay of the forebrain-enriched mitochondrial protein FAM210B to successfully decreased cell cycle length of neocortical progenitors and thus increase their consumptive division rate, creating a “hindbrain-like” scenario. These results reveal a parsimonious mechanism to locally regulate neuronal production, in which the time window during which progenitors generate cells is a critical determinant of region-specific brain expansion.</p
Becoming a new neuron in the cerebral cortex
No full textNeocortical neurons are born from progenitors situated in the ventricular zone (VZ) and migrate to the cortex to form circuits that underlie mammalian high skilled behavior. Genetic programs that broadly specify distinct subtypes of neurons within the neocortex are increasingly understood. But despite the mounting evidence on how different genes regulate different aspects of cortical neurogenesis and neuron differentiation, the genetic program that drives acquisition and maintenance of neuronal identity upon progenitor division is unknown. It is thus important to dissect the proper sequence of molecular events that occurs during acquisition of neuronal identity. A major limitation in studying this has been the inability to specifically identify, access and track specific cohort of neurons from their time of birth in vivo with the requisite temporal resolution. To overcome this obstacle, I have developed and standardized a novel technique “FlashTag” that enables precise in vivo tagging of isochronic cohorts of VZ-born neurons and progenitors from the time of mitosis. By combining this high temporal resolution “FlashTag” technology with single-cell RNA sequencing, we have identified and functionally characterized neuron-specific primordial transcriptional programs as they dynamically unfold in vivo during the first forty-eight hours following mitosis. Our results provide a detailed functional account of early neuronal life, including the discovery of successive “transcriptional waves” that organize the temporal sequence of cellular differentiation events. This high-resolution dynamic blueprint of neuronal specification can identify the transient molecular events that guide a neuron towards its final fate, and contribute to a roadmap for the reverse engineering of specific classes of cortical neurons from undifferentiated cells
Neuro_SCpedia: an interactive tool for single cell sequencing data in neuroscience
No full textNervous tissue is composed of highly heterogeneous types and subtypes of neurons. The advent of single-cell RNA sequencing (scRNA-seq) techniques has provided a way to extensively study the molecular identities and cellular diversity of nervous tissue at the single-cell level. This has led to the generation of large number of scRNA-seq datasets. However, accessing desired scRNA-seq datasets from the main public biodata repository “Gene Expression Omnibus” (GEO) remains challenging due to its complex and nonuniform searching interface.
To promote the re-using and enhance retrieval accessibility of generated scRNA-seq datasets in the field of neuroscience, we developed a comprehensive and user-friendly Shiny App named “Neuro_SCpedia”. Using the NCBI’s web API tool “E-utilites” through R, we automatically compiled metadata of single-cell datasets related to neuroscience available in GEO. We then use “Neuro_SCpedia” (https://cmushiny.unige.ch/zhux/Neuro_SCpedia/) for statistical analysis to reveal trends in the technical development and application of scRNA-seq techniques in neuroscience. Finally, we created automated tools to display the data in Neuro_SCpedia to facilitate the use and analysis of these datas.
We believe that this resource will significantly improve access to single-cell RNA sequencing data in the neuroscience field, promoting the reuse of existing data and facilitating meta-analyses.</p
Dispelling 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
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