8,754 research outputs found

    Brain-derived neurotrophic factor enhances GABA release probability and nonuniform distribution of N- and P/Q-type channels on release sites of hippocampal inhibitory synapses.

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    Long-lasting exposures to brain-derived neurotrophic factor (BDNF) accelerate the functional maturation of GABAergic transmission in embryonic hippocampal neurons, but the molecular bases of this phenomenon are still debated. Evidence in favor of a postsynaptic site of action has been accumulated, but most of the data support a presynaptic site effect. A crucial issue is whether the enhancement of evoked IPSCs (eIPSCs) induced by BDNF is attributable to an increase in any of the elementary parameters controlling neurosecretion, namely the probability of release, the number of release sites, the readily releasable pool (RRP), and the quantal size. Here, using peak-scaled variance analysis of miniature IPSCs, multiple probability fluctuation analysis, and cumulative amplitude analysis of action potential-evoked postsynaptic currents, we show that BDNF increases release probability and vesicle replenishment with little or no effect on the quantal size, the number of release sites, the RRP, and the Ca2 dependence of eIPSCs. BDNF treatment changes markedly the distribution of Ca2 channels controlling neurotransmitter release. It enhances markedly the contribution of Nand P/Q-type channels, which summed to100% (“supra-additivity”), and deletes the contribution of R-type channels. BDNF accelerates the switch of presynaptic Ca2 channel distribution from “segregated” to “nonuniform” distribution. This maturation effect was accompanied by an uncovered increased control of N-type channels on paired-pulse depression, otherwise dominated by P/Q-type channels in untreated neurons. Nevertheless, BDNF preserved the fast recovery from depression associated with N-type channels. These novel presynaptic BDNF actions derive mostly from an enhanced overlapping and better colocalization of N- and P/Q-type channels to vesicle release sites. Key words: neurotrophin

    The long pentraxin 3 and its role in autoimmunity

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    Objectives: To review the physiological and physiopathological roles of pentraxin 3 (PTX3), focusing on autoimmunity and vascular pathology. Methods: A systematic literature review using the keywords 'pentraxin 3,' 'innate immunity,' 'apoptosis,' 'autoimmunity,' and 'endothelial dysfunction' from 1990 to 2007 was performed. All relevant articles and pertinent secondary references in English were reviewed. Results: PTX3 has a large number of multiple functions in different contexts. PTX3 plays an important role in innate immunity, inflammation, vascular integrity, fertility, pregnancy, and also in the central nervous system. In innate immunity, its normal function is to increase the immune response to selected pathogens while also exerting control over potential autoimmune reactions. It maintains a tightly homeostatic equilibrium in the local immune microenvironment by avoiding an exaggerated immune response and controlling peripheral tolerance to self-antigens. In contrast, in some autoimmune diseases, PTX3 appears to be involved in the development of autoimmune phenomena. A possible explanation for these apparent paradoxical functions may be related to the highly polymorphic PTX3 gene. Conclusion: PTX3 is physiologically a protective molecule. However, in several autoimmune diseases PTX3 appears to facilitate the development of autoimmunity. The PTX3 gene could influence the development of autoimmune reactions and vascular involvement in human pathology. © 2008 Elsevier Inc. All rights reserved

    The SSC of the Generalised Jahangir’s Graph Jm,k and its Algebraic Characterizations

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    In this article, we present important combinatorial and algebraicproperties of spanning simplicial complex (SSC) of the generalised Jahangir’sgraph Jm,k. We describe the relation to find f−vectors associatedto Δs(Jm,k) and determine the Hilbert series for the SR-ring KΔs(Jm,k).In the end, we present the associated primes of the facet ideal IF(Δs(Jm,k))and the Cohen-Macaulay characterization of the SR-ring of Δs(Jm,k).AMS (MOS) Subject Classification Codes: Primary 13-P10, Secondary 13-F20, 13-C14, 13-H10.Corresponding Author: Agha KashifKey Words: Simplicial Complexes, f-vectors, Spanning Trees, Face Ring, Hilbert Series, CohenMacaulay

    To <i>JM</i> on Its 75th Anniversary

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    This article discusses how Journal of Marketing ( JM) has influenced marketing science and practice by publishing articles on substantive topics relevant to customers, managers, organizations, markets, and society. The journal's 75th anniversary coincides with the 50th anniversary of the Marketing Science Institute (MSI). Frequently, JM and MSI have collaborated to address important substantive marketing issues identified in MSI's Research Priorities. The author highlights seminal articles on brand equity; business-to-business marketing (including sales force management); connecting marketing information, metrics, and strategy; consumer behavior; innovation, new product development. and product management; marketing orientation and capabilities; and market research, methodology and services. She also draws attention to articles that have won the Sheth Foundation/ JM Award and the H. Paul Root Award. The article describes how JM‘s knowledge dissemination is amplified by powerful social network effects. Ideas in JM articles diffuse through the business community, influencing the mind-set of managers worldwide. </jats:p

    JM-20, a Benzodiazepine-Dihydropyridine Hybrid Molecule, Inhibits the Formation of Alpha-Synuclein-Aggregated Species

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    \ua9 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Studies showed that JM-20, a benzodiazepine-dihydropyridine hybrid molecule, protects against rotenone and 6-hydroxydopamine neurotoxicity. However, its protective effects against cytotoxicity induced by endogenous neurotoxins involved in Parkinson’s disease (PD) pathogenesis have never been investigated. In this study, we evaluated the ability of JM-20 to inhibit alpha-synuclein (aSyn) aggregation. We also evaluated the interactions of JM-20 with aSyn by molecular docking and molecular dynamics and assessed the protective effect of JM-20 against aminochrome cytotoxicity. We demonstrated that JM-20 induced the formation of heterogeneous amyloid fibrils, which were innocuous to primary cultures of mesencephalic cells. Moreover, JM-20 reduced the average size of aSyn positive inclusions in H4 cells transfected with SynT wild-type and synphilin-1-V5, but not in HEK cells transfected with synphilin-1-GFP. In silico studies showed the interaction between JM-20 and the aSyn-binding site. Additionally, we showed that JM-20 protects SH-SY5Y cells against aminochrome cytotoxicity. These results reinforce the potential of JM-20 as a neuroprotective compound for PD and suggest aSyn as a molecular target for JM-20

    Uterine transplantation: a promising surrogate to surrogacy?

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    Uterine transplantation: a promising surrogate to surrogacy? Grynberg M1, Ayoubi JM, Bulletti C, Frydman R, Fanchin R. Author information Abstract Infertility due to the inability of the uterus to carry a pregnancy ranks among the most unresolved issues in reproductive medicine. It affects millions of women worldwide who have congenital or acquired uterine affections, often requiring hysterectomy, and potentially represents a considerable fraction of the general infertile population. Patients suffering from severe uterine infertility are currently compelled to go through gestational surrogacy or adoption; both approaches, unfortunately, deprive them of the maternal experience of pregnancy and birth. Uterine transplantation represents an outstanding, yet complex, perspective to alleviating definitive uterine infertility. In the past decades, a number of scientific experiments conducted both in animals and women, focusing on uterine transplantation, have led to promising results. Collectively, these findings undoubtedly constitute a sound basis to clinically apply uterine transplantation in the near future. This paper is, however, an overview not only of the extent and limitations of accumulated scientific knowledge on uterine transplantation, but also its ethical implications, in an effort to define the actual place of such an approach among the therapeutic arsenal for alleviating infertility. © 2011 New York Academy of Sciences

    Translation and interpretation: Translation redundancy reconsidered

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    Interpretation is an integral part of the process of translating. This article raises the question of whether interpretation fo a literary work by a translator should be guided by extratextual factors or not. The discussion is illustrated with examples taken from David Hawkes&apos; translation of a Chinese classic, A Dream of Red Mansions. As the work of a scholar-translator, Hawkes&apos; version is richly supplemented with disclosures concerning the characters and explanations of the cultural environment embodied in the novel. In many cases, however, this translation procedure is redundant and explanatory, enlightening the readers but at the same time robbing them of the pleasure of literary interpretation and cultural exploration. By means of this illustration of translation redundancy, the author points out that there is difference between a scholar who helps the interpretation fo a work and a translator who presents a work close to its original version. It is particularly important to pay attention tot his difference in literary translations in a cross-cultural situation involving two enormously different cultures.Language &amp; LinguisticsA&HCI0ARTICLE1,SI115-12
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