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Therapeutic potential of immature neuroblasts from adult mouse subventricular zone
No full textChez les mammifères, la production de nouveaux neurones continue à l'âge adulte grâce à la persistance de cellules souches neurales (CSN) dans des niches neurogéniques, qui sont capables de produire les trois types cellulaires du lignage neural : astrocytes, oligodendrocytes et neurones. Physiologiquement, les CSN de la zone sous-ventriculaire (ZSV) peuvent proliférer pour produire des neuroblastes qui migrent vers le bulbe olfactif où ils formeront de nouveaux neurones fonctionnels. Dans cette thèse, un modèle génétique de souris permettant de suivre les neuroblastes et leur progénie a permis de caractériser une nouvelle sous-population abondante de progéniteurs neuronaux, les neuroblastes immatures (NBi), qui présentent des marqueurs de la différentiation neuronale, mais conservent leurs capacités prolifératives et leur plasticité, contrairement aux neuroblastes matures. Puis, la combinaison d'une analyse du transcriptome des populations neurogéniques avec le séquençage ARN des cellules individuelles de la ZSV a permis de mettre en lumière l'identité et l'hétérogénéité des différentes populations neurogéniques, fournissant des marqueurs spécifiques à chacune d'entre elles. Il en ressort un modèle alternatif de la neurogenèse précisant les étapes de l'engagement vers un destin neuronal. Dans l'ensemble, ces travaux mettent en lumière donc une population de NBi multipotente et abondante, dont la plasticité pourrait être exploitée en contexte thérapeutique dans le cadre d'atteintes neurodégénératives. Par la suite, un un micro-ARN régulateur de l'engagement vers le lignage neuronal, le miR-342-3p, a été identifié. In vitro, le miR-342-p a un effet de levier promouvant la différenciation neuronale et inhibant la différenciation oligodendrocytaire. A l'inverse, son inhibition inhibe la différenciation neuronale et favorise la différenciation oligodendrocytaire. Sa modulation dans un cadre thérapeutique pourrait donc orienter le destin des progéniteurs neuraux pour stimuler la régénération des tissus dans le cadre de pathologies neurodégénératives ou démyélinisantes.In mammals, the production of new neurons throughout adulthood continues through the persistence of neural stem cells (NSC) in neurogenic niches that are able to produce the three cell types of the neural lineage: astrocytes, oligodendrocytes, and neurons. Physiologically, NSC from the mouse subventricular zone (SVZ) can proliferate and produce neuroblasts that migrate towards the olfactory bulb and produce new, functional neurons. In this thesis, a genetic murine model allowing the tracking of neuroblasts and their progeny was used to characterize a new abundant sub-population of neural progenitors, the immature neuroblasts (iNB), that exhibit markers of cells committed to a neuronal fate, but retain proliferative abilities and multipotence, conversely to mature neuroblasts. Then, a combination of bulk-transcriptomic analysis of the progenitor populations with large-scale RNA-seq of individual SVZ cells highlighted the identity and heterogeneity of the neurogenic populations, and provided markers specific to each. This offers an alternative model of neurogenesis detailing the steps of neuronal fate commitment. Overall, this research highlights a population of abundant, multipotent iNB and offers an alternative model for the dynamics of neurogenic populations and their commitment to a neuronal fate whose plasticity could be harnessed in a therapeutic context for the treatment of neurodegenerative diseases. Subsequent experiments identified a micro-RNA regulating the commitment to the neuronal lineage, miR-342-3p. It acted as a switch in vitro, promoting neuronal differentiation and inhibiting oligodendroglial differentiation were shown. Conversely, inhibition of miR-342-3p resulted in inhibited neuronal differentiation and favored oligodendroglial differentiation. Its modulation in a therapeutic context might therefore orient neural progenitors to stimulate tissue regeneration in neurodegenerative or demyelinating diseases
Potentiel thérapeutique des neuroblastes immatures de la zone sous-ventriculaire murine adulte
No full textIn mammals, the production of new neurons throughout adulthood continues through the persistence of neural stem cells (NSC) in neurogenic niches that are able to produce the three cell types of the neural lineage: astrocytes, oligodendrocytes, and neurons. Physiologically, NSC from the mouse subventricular zone (SVZ) can proliferate and produce neuroblasts that migrate towards the olfactory bulb and produce new, functional neurons. In this thesis, a genetic murine model allowing the tracking of neuroblasts and their progeny was used to characterize a new abundant sub-population of neural progenitors, the immature neuroblasts (iNB), that exhibit markers of cells committed to a neuronal fate, but retain proliferative abilities and multipotence, conversely to mature neuroblasts. Then, a combination of bulk-transcriptomic analysis of the progenitor populations with large-scale RNA-seq of individual SVZ cells highlighted the identity and heterogeneity of the neurogenic populations, and provided markers specific to each. This offers an alternative model of neurogenesis detailing the steps of neuronal fate commitment. Overall, this research highlights a population of abundant, multipotent iNB and offers an alternative model for the dynamics of neurogenic populations and their commitment to a neuronal fate whose plasticity could be harnessed in a therapeutic context for the treatment of neurodegenerative diseases. Subsequent experiments identified a micro-RNA regulating the commitment to the neuronal lineage, miR-342-3p. It acted as a switch in vitro, promoting neuronal differentiation and inhibiting oligodendroglial differentiation were shown. Conversely, inhibition of miR-342-3p resulted in inhibited neuronal differentiation and favored oligodendroglial differentiation. Its modulation in a therapeutic context might therefore orient neural progenitors to stimulate tissue regeneration in neurodegenerative or demyelinating diseases.Chez les mammifères, la production de nouveaux neurones continue à l'âge adulte grâce à la persistance de cellules souches neurales (CSN) dans des niches neurogéniques, qui sont capables de produire les trois types cellulaires du lignage neural : astrocytes, oligodendrocytes et neurones. Physiologiquement, les CSN de la zone sous-ventriculaire (ZSV) peuvent proliférer pour produire des neuroblastes qui migrent vers le bulbe olfactif où ils formeront de nouveaux neurones fonctionnels. Dans cette thèse, un modèle génétique de souris permettant de suivre les neuroblastes et leur progénie a permis de caractériser une nouvelle sous-population abondante de progéniteurs neuronaux, les neuroblastes immatures (NBi), qui présentent des marqueurs de la différentiation neuronale, mais conservent leurs capacités prolifératives et leur plasticité, contrairement aux neuroblastes matures. Puis, la combinaison d'une analyse du transcriptome des populations neurogéniques avec le séquençage ARN des cellules individuelles de la ZSV a permis de mettre en lumière l'identité et l'hétérogénéité des différentes populations neurogéniques, fournissant des marqueurs spécifiques à chacune d'entre elles. Il en ressort un modèle alternatif de la neurogenèse précisant les étapes de l'engagement vers un destin neuronal. Dans l'ensemble, ces travaux mettent en lumière donc une population de NBi multipotente et abondante, dont la plasticité pourrait être exploitée en contexte thérapeutique dans le cadre d'atteintes neurodégénératives. Par la suite, un un micro-ARN régulateur de l'engagement vers le lignage neuronal, le miR-342-3p, a été identifié. In vitro, le miR-342-p a un effet de levier promouvant la différenciation neuronale et inhibant la différenciation oligodendrocytaire. A l'inverse, son inhibition inhibe la différenciation neuronale et favorise la différenciation oligodendrocytaire. Sa modulation dans un cadre thérapeutique pourrait donc orienter le destin des progéniteurs neuraux pour stimuler la régénération des tissus dans le cadre de pathologies neurodégénératives ou démyélinisantes
Potentiel thérapeutique des neuroblastes immatures de la zone sous-ventriculaire murine adulte
No full textIn mammals, the production of new neurons throughout adulthood continues through the persistence of neural stem cells (NSC) in neurogenic niches that are able to produce the three cell types of the neural lineage: astrocytes, oligodendrocytes, and neurons. Physiologically, NSC from the mouse subventricular zone (SVZ) can proliferate and produce neuroblasts that migrate towards the olfactory bulb and produce new, functional neurons. In this thesis, a genetic murine model allowing the tracking of neuroblasts and their progeny was used to characterize a new abundant sub-population of neural progenitors, the immature neuroblasts (iNB), that exhibit markers of cells committed to a neuronal fate, but retain proliferative abilities and multipotence, conversely to mature neuroblasts. Then, a combination of bulk-transcriptomic analysis of the progenitor populations with large-scale RNA-seq of individual SVZ cells highlighted the identity and heterogeneity of the neurogenic populations, and provided markers specific to each. This offers an alternative model of neurogenesis detailing the steps of neuronal fate commitment. Overall, this research highlights a population of abundant, multipotent iNB and offers an alternative model for the dynamics of neurogenic populations and their commitment to a neuronal fate whose plasticity could be harnessed in a therapeutic context for the treatment of neurodegenerative diseases. Subsequent experiments identified a micro-RNA regulating the commitment to the neuronal lineage, miR-342-3p. It acted as a switch in vitro, promoting neuronal differentiation and inhibiting oligodendroglial differentiation were shown. Conversely, inhibition of miR-342-3p resulted in inhibited neuronal differentiation and favored oligodendroglial differentiation. Its modulation in a therapeutic context might therefore orient neural progenitors to stimulate tissue regeneration in neurodegenerative or demyelinating diseases.Chez les mammifères, la production de nouveaux neurones continue à l'âge adulte grâce à la persistance de cellules souches neurales (CSN) dans des niches neurogéniques, qui sont capables de produire les trois types cellulaires du lignage neural : astrocytes, oligodendrocytes et neurones. Physiologiquement, les CSN de la zone sous-ventriculaire (ZSV) peuvent proliférer pour produire des neuroblastes qui migrent vers le bulbe olfactif où ils formeront de nouveaux neurones fonctionnels. Dans cette thèse, un modèle génétique de souris permettant de suivre les neuroblastes et leur progénie a permis de caractériser une nouvelle sous-population abondante de progéniteurs neuronaux, les neuroblastes immatures (NBi), qui présentent des marqueurs de la différentiation neuronale, mais conservent leurs capacités prolifératives et leur plasticité, contrairement aux neuroblastes matures. Puis, la combinaison d'une analyse du transcriptome des populations neurogéniques avec le séquençage ARN des cellules individuelles de la ZSV a permis de mettre en lumière l'identité et l'hétérogénéité des différentes populations neurogéniques, fournissant des marqueurs spécifiques à chacune d'entre elles. Il en ressort un modèle alternatif de la neurogenèse précisant les étapes de l'engagement vers un destin neuronal. Dans l'ensemble, ces travaux mettent en lumière donc une population de NBi multipotente et abondante, dont la plasticité pourrait être exploitée en contexte thérapeutique dans le cadre d'atteintes neurodégénératives. Par la suite, un un micro-ARN régulateur de l'engagement vers le lignage neuronal, le miR-342-3p, a été identifié. In vitro, le miR-342-p a un effet de levier promouvant la différenciation neuronale et inhibant la différenciation oligodendrocytaire. A l'inverse, son inhibition inhibe la différenciation neuronale et favorise la différenciation oligodendrocytaire. Sa modulation dans un cadre thérapeutique pourrait donc orienter le destin des progéniteurs neuraux pour stimuler la régénération des tissus dans le cadre de pathologies neurodégénératives ou démyélinisantes
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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