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The monoselective sphingosine-1-phosphate receptor-1 modulator ponesimod enhances remyelination in the cuprizone model of demyelination
No full textThe Monoselective Sphingosine-1-Phosphate Receptor-1 Modulator Ponesimod Enhances Remyelination in the Cuprizone Model of Demyelination
No full textBackground: Sphingosine-1-phosphate (S1P1) receptor modulators are used clinically to treat relapsing forms of multiple sclerosis (MS). Selective functional antagonism of the S1PR1 subtype by ponesimod prevents lymphocyte egression from lymph nodes, hence hampering neuroinflammation in MS. Recent findings suggest a potential additional role for ponesimod in the Central Nervous System (CNS) in the differentiation of oligodendrocyte precursor cells (OPC) into mature myelinating oligodendrocytes, and therefore potentially having some effects on remyelination
The Monoselective Sphingosine-1-Phosphate Receptor-1 Modulator Ponesimod Enhances Remyelination in the Cuprizone Model of Demyelination
No full textBackground: Sphingosine-1-phosphate (S1P1) receptor modulators are used clinically to treat relapsing forms of multiple sclerosis (MS). Selective functional antagonism of the S1PR1 subtype by ponesimod prevents lymphocyte egression from lymph nodes, hence hampering neuroinflammation in MS. Recent findings suggest a potential additional role for ponesimod in the Central Nervous System (CNS) in the differentiation of oligodendrocyte precursor cells (OPC) into mature myelinating oligodendrocytes, and therefore potentially having some effects on remyelination
The monoselective sphingosine-1-phosphate receptor-1 modulator ponesimod enhances remyelination in the cuprizone model of demyelination
No full textPonesimod, mono-selective sphingosine-1-phosphate receptor 1 modulator enhances oligodendrocyte precursor cell differentiation
No full textMS, EW ad TV report no competing interest. MAT is an employee of Janssen and may own stock or stock options in Johnson & Johnson
The sphingosine-1-phosphate receptor 1 modulator ponesimod repairs cuprizone-induced demyelination and induces oligodendrocyte differentiation
No full textSphingosine-1-phosphate receptor (S1PR) modulators are clinically used to treat relapse-remitting multiple sclerosis (MS) and the early phase of progressive MS when inflammation still prevails. In the periphery, S1PR modulators prevent lymphocyte egress from lymph nodes, hence hampering neuroinflammation. Recent findings suggest a role for S1PR modulation in remyelination. As the Gi alpha-coupled S1P1 subtype is the most prominently expressed S1PR in oligodendrocyte precursor cells (OPCs), selective modulation (functional antagonism) of S1P1 may have direct effects on OPC functionality. We hypothesized that functional antagonism of S1P1 by ponesimod induces remyelination by boosting OPC differentiation. In the cuprizone mouse model of demyelination, we found ponesimod to decrease the latency time of visual evoked potentials compared to vehicle conditions, which is indicative of functional remyelination. In addition, the Y maze spontaneous alternations test revealed that ponesimod reversed cuprizone-induced working memory deficits. Myelin basic protein (MBP) immunohistochemistry and transmission electron microscopy of the corpus callosum revealed an increase in myelination upon ponesimod treatment. Moreover, treatment with ponesimod alone or in combination with A971432, an S1P5 monoselective modulator, significantly increased primary mouse OPC differentiation based on O4 immunocytochemistry. In conclusion, S1P1 functional antagonism by ponesimod increases remyelination in the cuprizone model of demyelination and significantly increases OPC differentiation in vitro.Ponesimod reverses a cuprizone-induced working memory deficit, restores the cuprizone-induced delay in latency time of the optic pathway, and enhances remyelination after cuprizone intoxication in vivo. Furthermore, ponesimod enhances differentiation of oligodendrocyte precursor cells into mature oligodendrocytes in vitro.imag
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
Seas of Clarity: the role of European brown seaweed extracts in combination with rehabilitation exercise in enhancing cognitive function in progressive MS
No full textVariations 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
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