1,720,974 research outputs found
Complement system as glutamate modulator and synaptic organizer in EAE animal model.
No full textIn recent years, there has been a growing interest in the interaction between the central nervous system (CNS) and the immune system. This has led to the finding that the CNS is an immune-privileged environment. A principal component of the innate immune system is the complement system, which is essential for the primary defense of the human body against pathogens.
The complement system is frequently described as a "double-edged sword" in the context of the CNS. On one hand, it facilitates the physiological maturation of neural networks and plays a crucial role in promoting synaptic pruning during brain development. On the other hand, a dysregulation of this system can lead to excessive synaptic loss, which could contribute to the progression of neurodegenerative diseases. Additionally, research conducted over the past two decades has revealed a "non-canonical" role for the complement system in modulating neurotransmission at chemical synapses.
This thesis aims to examine the function of the complement system in pathological conditions, in both aberrant synaptic elimination and glutamate modulation, as promoter of neurodegenerative processes. In particular, the study employed an experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis (MS).
To evaluate the first aim regarding the role of the complement system as a synaptic modulator of neurotransmission, three specific objectives were pursued: first, to assess complement-induced glutamate release from both synapses and astrocytes in healthy mice, second to evaluate complement system alterations and glutamate release in EAE mice at various disease stages, and third to explore the role of excitatory amino acid transporters in these processes.
To elucidate the second aim regarding the involvement of excessive synaptic pruning in neurodegeneration, I focused on developing appropriate methods to highlight microglial phagocytosis of cortical nerve terminals (synaptosomes). Next, the objective was to quantify pruning differences between EAE and healthy mice, and to explore the impact of complement proteins (C3) on synaptic vulnerability.
In the initial phase of the study, an investigation was conducted into structural synapse impairments within the cortex and hippocampus of EAE mice. It was observed that while inflammatory markers GFAP and CD11b were elevated, only the cortical region exhibited changes in the postsynaptic marker PSD95, that resulted overexpressed. This may be a compensatory mechanism for reduced glutamate release efficiency. In addition to astrocytosis and microgliosis an overexpression in the protein density of C1q and C3 complement components was detected in EAE mice.
Building on these findings, I analysed the role of the complement system in modulating glutamate transmission. The results showed that complement-induced glutamate release varies depending on the particle type, specifically whether it is synaptosomes or gliosomes. Astrocytic gliosomes exhibit higher release activity, which is mediated by glutamate transporters working in reverse mode. In EAE mice, this modulation becomes imbalanced, with reduced release in synaptosomes and increased release in gliosomes. This imbalance, supported by proteomic changes in glutamate transporters EAAT1 and EAAT2, suggests that complement activity can be involved in a maladaptation of the astrocyte-neuron communication, indicating a potential excitotoxic imbalance.
The second phase of the study examines complement-mediated synaptic pruning, employing new techniques to measure microglial phagocytosis of synaptosomes. The results demonstrate that EAE synaptosomes have an increase susceptibility to pruning, which may be driven by the interaction between C3 and its receptor, resulting in the phagocytosis of synapses by microglia.
These findings collectively highlight the complex role of the complement system in synaptic dysfunction, providing insights into potential therapeutic targets for MS and other neurodegenerative diseases
Non-canonical Roles of Complement in the CNS: From Synaptic Organizer to Presynaptic Modulator of Glutamate Transmission
No full textThe central nervous system (CNS) is not an immune-privileged compartment, but it is intimately intertwined with the immune system. Among the components shared by the two compartments is the complement, a main constituent of innate immunity, which is also produced centrally and controls the development and organization of synaptic connections. Complement is considered a doubled-faced system that, besides controlling the physiological development of the central network, also subserves synaptic engulfment pivotal to the progression of neurodegenerative diseases. Quite interestingly, besides these “canonical” roles, evidence in the last two decades highlighted other “non-canonical” role(s), thereby complementing modulates chemical transmission at central synapsis. It emerged that glutamate is the preferential target of these “non-canonical” complement-induced effects, which include i) the control of the release of glutamate from neurons and astrocytes and ii) the control of the number and the functions of central glutamatergic receptor subtypes (i.e., the NMDA receptors, the AMPA/kainate receptors, and the metabotropic glutamate receptors) in plasma membranes. This review summarizes some of the available results supporting the role of complement as a “modulator” of central glutamate transmission, paying particular attention to those events that occur presynaptically. Taking into consideration the enormous progress in complement pharmacology and the increasing number of therapeutics in clinical trials, deepening our knowledge of these” non-canonical” role(s) could pave the road to new therapeutic approaches for the management of central neurological diseases
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
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
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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