1,720,995 research outputs found
Cadherins as regulators of neuronal polarity
No full textA compelling amount of data is accumulating about the polyphonic role of neuronal cadherins during brain development throughout all developmental stages, starting from the involvement of cadherins in the organization of neurulation up to synapse development and plasticity. Recent work has confirmed that specifically N-cadherins play an important role in asymmetrical cellular processes in developing neurons that are at the basis of polarity. In this review we will summarize recent data, which demonstrate how N-cadherin orchestrates distinct processes of polarity establishment in neurons
Distinct temporal hierarchies in membrane and cytoskeleton dynamics precede the morphological polarization of developing neurons
Get PDFFinal morphological polarization of neurons, with the development of a distinct axon and of several dendrites, is preceded by phases of non-polarized architecture. The earliest of these phases is that of the round neuron arising from the last mitosis. A second non polarized stage corresponds to the bipolar neuron, with two morphologically identical neurites. Both phases have their distinctive relevance in the establishment of neuronal polarity. During the round cell stage a decision is made as to where from the cell periphery a first neurite will form, thus creating the first sign of asymmetry. At the bipolar stage a decision is made as to which of the two neurites becomes the axon in neurons polarizing in vitro and the leading edge in neurons in situ. In this study we analysed cytoskeletal and membrane dynamics in cells at these two "pre-polarity" stages. By mean of time lapse imaging in dissociated hippocampal neurons and ex vivo cortical slices we show that both stages are characterized by polarized intracellular arrangements, however with distinct temporal hierarchies: polarized actin dynamics marks the site of first polarization in round cells, whereas polarized membrane dynamics precedes asymmetric growth in the bipolar stage.sponsorship: This work was partially supported by the Flanders Fund for Scientific Research [grant number FWO G 0.666.10N], NEUROBRAINNET grant from the Belgian Government [grant number IAP 7/16]; a Flemish Government Methusalem Grant; the Spanish Ministry of Science [grant number SAF2010-14906]; and Innovation Ingenio-Consolider [grant number CSD2010-00045] to A.G. and C.G.D. The support of the MIUR-PRIN Program to F.V. and E.F.F. is also acknowledged. E.F.F. has been in part supported by an EMBO fellowship [grant number ASTF: 369.00-2007]. The Nikon confocal microscope was acquired through a Hercules Type 1 grant [grant number: AKUL/09/037]. (Flanders Fund for Scientific Research|FWO G 0.666.10N, Belgian Governmen|IAP 7/16, Flemish Government Methusalem Grant, Spanish Ministry of Science|SAF2010-14906, Innovation Ingenio-Consolider|CSD2010-00045, MIUR-PRIN Program, EMBO fellowship|369.00-2007, Hercules Type 1 grant|AKUL/09/037)status: Publishe
Cyp46-mediated cholesterol loss promotes survival in stressed hippocampal neurons
No full textAged neurons constitute an outstanding example of survival robustness, outliving the accumulation of reactive oxygen species (ROS) derived from various physiological activities. Since during aging hippocampal neurons experience a progressive loss of membrane cholesterol and, by virtue of this, a gradual and sustained increase in the activity of the survival receptor tyrosine kinase TrkB, we have tested in this study if cholesterol loss is functionally associated to survival robustness during aging. We show that old neurons that did not undergo the cholesterol drop, upon knockdown of the cholesterol hydroxylating enzyme Cyp46, presented lowTrkB activity and increased apoptotic levels. In further agreement, inducing cholesterol loss in young neurons led to the early appearance of TrkB activity. In vivo, Cyp46 knockdown led to the appearance of damaged hippocampal neurons in old mice exposed to exogenous stressful stimuli. Cholesterol loss seems therefore to contribute to neuronal survival in conditions of prominent stress, either acute or chronic. The relevance of this pathway in health and disease is discussed
Biochemical and functional characterisation of αPIX, a specific regulator of axonal and dendritic branching in hippocampal neurons
No full textCholesterol loss enhances TrkB signaling in hippocampal neurons aging in vitro
Get PDFBinding of the neurotrophin brain-derived neurotrophic factor (BDNF) to the TrkB receptor is a major survival mechanism during embryonic development. In the aged brain, however, BDNF levels are low, suggesting that if TrkB is to play a role in survival at this stage additional mechanisms must have developed. We here show that TrkB activity is most robust in the hippocampus of 21-d-old BDNF-knockout mice as well as in old, wild-type, and BDNF heterozygous animals. Moreover, robust TrkB activity is evident in old but not young hippocampal neurons differentiating in vitro in the absence of any exogenous neurotrophin and also in neurons from BDNF -/- embryos. Age-associated increase in TrkB activity correlated with a mild yet progressive loss of cholesterol. This, in turn, correlated with increased expression of the cholesterol catabolic enzyme cholesterol 24-hydroxylase. Direct cause-effect, cholesterol loss-high TrkB activity was demonstrated by pharmacological means and by manipulating the levels of cholesterol 24-hydroxylase. Because reduced levels of cholesterol and increased expression of choleseterol-24-hydroxylase were also observed in the hippocampus of aged mice, changes in cellular cholesterol content may be used to modulate receptor activity strength in vivo, autonomously or as a way to complement the natural decay of neurotrophin production
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
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