1,720,956 research outputs found

    Microtubules as a signal hub for axon growth in response to mechanical force

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    Microtubules are highly polar structures and are characterized by high anisotropy and stiffness. In neurons, they play a key role in the directional transport of vesicles and organelles. In the neuronal projections called axons, they form parallel bundles, mostly oriented with the plus-end towards the axonal termination. Their physico-chemical properties have recently attracted attention as a potential candidate in sensing, processing and transducing physical signals generated by mechanical forces. Here, we discuss the main evidence supporting the role of microtubules as a signal hub for axon growth in response to a traction force. Applying a tension to the axon appears to stabilize the microtubules, which, in turn, coordinate a modulation of axonal transport, local translation and their cross-talk. We speculate on the possible mechanisms modulating microtubule dynamics under tension, based on evidence collected in neuronal and non-neuronal cell types. However, the fundamental question of the causal relationship between these mechanisms is still elusive because the mechano-sensitive element in this chain has not yet been identified

    Effects of Zika virus infection on FOXG1 transcription factor in human neural progenitors

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    The brain is the most complex and enigmatic organ of our body, its formation and development need extended time and a fine regulation. These aspects make the brain susceptible to many insults that might disrupt the normal development. In particular, the neocortex is structured and organized by a complex mechanism defined “inside out”, during which different cellular types are generated from neural stem cells (NSCs). Many neurological and psychiatric disorders occur because of alterations in these processes for environmental or genetic causes. Among the latter, are the congenital infections of central nervous system, for example pathologies caused by viruses belonging to the TORCH group, neurotropic and teratogenic agents. Following the 2015 outbreak in Brazil, Zika virus (ZIKV) has been added to this group. ZIKV is a viral agent able to cause severe neurodevelopmental impairments, including microcephaly, defined “Congenital Zika Syndrome” (CZS). Among the congenital causes of microcephaly, particularly interesting are the mutations of the transcriptional factor Forkhead box g1 (FOXG1). This protein is required for proper telencephalon and cortical development and many mutations are responsible for the “FOXG1-related disorders”, a spectrum of neurodevelopmental disorders, including microcephaly, intellectual disability, and cerebral malformation. In this thesis we investigated a possible functional alteration of FOXG1, with subsequent neurodevelopmental dis-regulation, as a consequence of ZIKV infection. Previous studies demonstrated that ZIKV infects mainly NSCs, therefore for our work we chose an in vitro model based on human neural precursors cells derived from induced pluripotent cells (hiPS-NPCs), by using a protocol of neural induction based on “Dual SMAD inhibition”. Generated hiPS-NPCs were infected with ZIKV and analysed by immunofluorescence to observe a possible impact on FOXG1 after infection. Our observations suggest that, while in the control FOXG1 is localized mainly in nucleus, after infection it dislocates to the cytoplasm. hiPS-NPCs use provided us an alternative model to the study of ZIKV and its effect on neurodevelopment, this has let us to highlight how an exogenous insult can affect function and localization of an endogenous transcriptional factor, fundamental for the cortical development

    Structural and functional axonal plasticity following mechanical stimulation

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    Organs and cells of our body are constantly subjected to mechanical forces. Neurons experience mechanical stimuli during neurodevelopment, aging, pathologic conditions and in everyday functions such as homeostatic processes and movement. Recent literature highlights microtubules (MTs) as crucial mediators in mechanotransduction. While the effects of transient and acute forces on neurons have been explored, the impact of repetitive mechanical stresses throughout the lifespan remain mostly unknown. Recently, in vitro studies have unveiled that repetitive mechanical motion can damage MTs. How do cells, which are subjected to mechanical stress daily, withstand this stimulation and keep working throughout our long lives? Using a device that applies compressive strains, I simulated the mechanical stress neurons experience daily. My findings show that mechanical stress intensity is key to neuronal fate. I found that low stress (2.5%) activates protective mechanisms, such as increased MT acetylation, preserving axon integrity. Moderate stress (5%) temporarily disrupts MT organization and reduces axon length, but neurons gradually recover structure and function, likely through repair mechanisms. However, high stress (10%) induces irreversible damage and cell death, revealing a critical threshold beyond which repair fails. These findings provide new insights into neuronal resilience and lay the groundwork for identifying how cellular functions can be restored

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

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    We 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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We 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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