1,720,973 research outputs found
Cortical grey matter demyelination can be induced by elevated pro-inflammatory cytokines in the subarachnoid space of MOG-immunized rats
No full textA substantial proportion of cases with secondary progressive multiple sclerosis have extensive inflammation in the leptomeninges that is associated with increased subpial demyelination, neuronal loss and an exacerbated disease course. However, the mechanisms underlying this extensive subpial pathology are poorly understood. We hypothesize that pro-inflammatory cytokine production within the meninges may be a key to this process. Post-mortem cerebrospinal fluid and dissected cerebral leptomeningeal tissue from patients with multiple sclerosis were used to study the presence of tumour necrosis factor and interferon gamma protein and messenger RNA levels. A novel model of subpial cortical grey matter demyelination was set up in Dark Agouti rats and analysed using quantitative immunohistochemistry. Increased expression of the pro-inflammatory cytokines tumour necrosis factor and interferon gamma was found in the meninges of cases with secondary progressive multiple sclerosis exhibiting tertiary lymphoid-like structures. Injection of tumour necrosis factor and interferon gamma into the subarachnoid space of female Dark Agouti rats pre-immunized with a subclinical dose of myelin oligodendrocyte glycoprotein mimicked the pathology seen in multiple sclerosis, including infiltration of lymphocytes (CD4+ and CD8+ T cells and CD79+ B cells) into the meninges and extensive subpial demyelination. Extensive microglial/macrophage activation was present in a gradient from the pial surface to deeper cortical layers. Demyelination did not occur in control animals immunized with incomplete Freund's adjuvant and injected with cytokines. These results support the hypothesis that pro-inflammatory molecules produced in the meninges play a major role in cortical demyelination in multiple sclerosis, but also emphasize the involvement of an anti-myelin immune response
Altered Expression of Brain Proteinase-Activated Receptor-2, Trypsin-2 and Serpin Proteinase Inhibitors in Parkinson's Disease
Full text linkNeuroinflammation is thought to contribute to cell
death in neurodegenerative disorders, but the factors involved
in the inflammatory process are not completely understood.
Proteinase-activated receptor-2 (PAR2) expression in brain is
increased in Alzheimer’s disease and multiple sclerosis, but
the status of PAR2 in Parkinson’s disease is unknown. This
study examined expression of PAR2 and endogenous proteinase
activators (trypsin-2, mast cell tryptase) and proteinase
inhibitors (serpin-A5, serpin-A13) in areas vulnerable and resistant
to neurodegeneration in Parkinson’s disease at different
Braak α-synuclein stages of the disease in post-mortem brain.
In normal aged brain, expression of PAR-2, trypsin-2, and
serpin-A5 and serpin-A13 was found in neurons and microglia,
and alterations in the amount of immunoreactivity for these
proteins were found in some brain regions. Namely, there
was a decrease in neurons positive for serpin-A5 in the dorsal
motor nucleus, and serpin-A13 expression was reduced in the
locus coeruleus and primary motor cortex, while expression of
PAR2, trypsin-2 and both serpins was reduced in neurons
within the substantia nigra. There was an increased number
of microglia that expressed serpin-A5 in the dorsal motor nucleus
of vagus and elevated numbers of microglia that
expressed serpin-A13 in the substantia nigra of late
Parkinson’s disease cases. The number of microglia that
expressed trypsin-2 increased in primary motor cortex of incidental
Lewy body disease cases. Analysis of Parkinson’s
disease cases alone indicated that serpin-A5 and serpin-A13,
and trypsin-2 expression in midbrain and cerebral cortex was
different in cases with a high incidence of L-DOPA-induced
dyskinesia and psychosis compared to those with low levels of
these treatment-induced side effects. This study showed that
there was altered expression in brain of PAR2 and some proteins
that can control its function in Parkinson’s disease. Given
the role of PAR2 in neuroinflammation, drugs that mitigate
these changes may be neuroprotective when administered to
patients with Parkinson’s diseas
DIFFERENTIAL EXPRESSION OF STRUCTURAL SYNAPTIC ELEMENTS IN THE LEFT SUPERIOR TEMPORAL CORTEX OF SCHIZOPHRENIA PATIENTS
No full textDIFFERENTIAL EXPRESSION OF STRUCTURAL SYNAPTIC ELEMENTS IN THE LEFT SUPERIOR TEMPORAL CORTEX OF SCHIZOPHRENIA PATIENTS
No full text
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
Peripheral and central mechanisms in chronic human inflammatory and neuropathic pain and associated animal models
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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
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