1,721,134 research outputs found

    Pathological glial reactions in neurodegenerative disorders: Prospects for future therapeutics

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    Pathological activation of the immune-competent glial cells is an obligatory event in neurodegenerative diseases. The secondary recruitment of astrocytes, resulting from an upgraded microglial activation, represents a critical point. Reactive astrocytes have to give up physiologically important functions (control of extracellular homeostasis and of synaptic transmission) and build a synergistic alliance with microglia in promoting oxidative, excitotoxic and β-amyloid-induced neuronal damage. Growing understanding of the pathogenically relevant molecular signaling pathways opens new possibilities of pharmacological corrections at the second messenger level. Here, the respective know-how of endogenous modulators, such as adenosine, might be used. The aim should be a titration of the glia reaction in order to maintain supposed beneficial functions of reactive microglia and to prevent the dangerous involvement of astrocytes

    Adenosine modulates a voltage-dependent chloride conductance in cultured hippocampal neurons

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    Whole cell currents were recorded in cultured rat hippocampal neurons using the patch-clamp method. When the cells were held near the resting membrane potential (-60 mV) the application of adenosine (1 μM) the adenosine analogues 2CA (100 nM) and R-PIA (40 nM) induced a steady-state inward current. This response was unchanged when extra- and intracellular media were used, in which Na+ and K+ were substituted by impermeable ions in equimolar concentrations. In contrast the current was affected by lowering the extracellular Cl- concentration and thus Cl- was considered to be the ionic carrier. Additionally an almost complete block of the current was observed after application of DIDS (50 μM), a putative Cl- channel blocker. The modulated current was voltage-dependent and was slowly activated by hyperpolarizing voltage steps. The adenosine action was theophylline- and pertussis toxin-sensitive indicating that the modulatory effect is mediated via an A1 receptor coupled to a G protein of the Gi or Go class. © 1990

    Characterization of two voltage-dependent, inwardly rectifying currents in dibutyryl-cyclic AMP treated cortical astrocytes

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    In astrocytes, a simultaneous influx of chloride (Cl-) along with potassium (K+) ions has been postulated for explaining the process of the extracellular K+ buffering via the mechanism of local accumulation. With the patch-clamp technique we have investigated in primary culture (2-4 weeks) of rat cortical astrocytes the presence of K+ and Cl- conductances which are active around the resting membrane potential. Whole-cell currents were recorded in GFAP positive cells after treatment (1-2 weeks) of the cultures with 0.25 mM db-cAMP. In intra- and extracellular physiological solutions the cell currents elicited in response to hyperpolarized step potentials from an holding potential of – 60 mV revealed the existance of two different conductances. The first on had characteristics comparable to a voltage-dependent, invar-rectifying potassium current (K-ir): it displayed a quasi-instantaneous activation kinetic, a voltage- and time-dependent inactivation for potential more negative than -120 mV and was fully and reversibly blocked by 0.1 mM barium (Ba2+). In 4 mM extracellular K+ solution this conductance was already activated at resting potential; by increasing the external K+ from 4 mM to 12 mM the current-voltage relationship showed an increase in slope conductance while replacement of external 100 mM sodium (Na+) with N-methyl-D-glucamine (NMDG+) decreased the rate and the extent of the inactivation. The secondo ne was a voltage-dependent but not inactivating current which developed at membrane potential more negative than -40 mV. It had a slow activation and deactivation kinetics requiring 3-6 sec to reach the peak amplitude and it was insensitive to 0.1 mM Ba2+. Changes in the external monovalent cations content did not modify neither the amplitude nor the current kinetics. With the intra- and extracellular K+ and Na+ substituted by NMDG+ and in symmetrical Cl- the reversal potential was at 0 mV. The findings suggest that this second conductance i san inward-rectifying chloride current (Cl-ir) with different gating properties from the Cl- currents previously described in astrocytes. These data all together demonstrate the existance in cortical astrocytes of conductances which may be involved in the process f K+ extracellular clearing, playing also a crucial role in the mechanism of swelling which occur in physiophatological conditions

    Environmental impact assessment of renewable energy communities: the analysis of an Italian neighbourhood

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    In recent years, research in renewable energy community (REC) schemes, coupling renewable energy sources and building energy efficiency, is gaining momentum. In this context, Urban Building Energy Modelling tools (UBEMs) have proved to comply with the design requirements of such schemes. However, a clear methodology exploiting UBEMs to support the design of RECs is still missing, especially for assessing the greenhouse gas (GHG) emissions associated with their specific technical configuration. Here, the REC is modelled in “urban modeling interface” (umi), one of the main bottom-up physics-based UBEMs. A building archetype approach is exploited to model the scenarios and assess embodied GHG emissions. The proposed methdology gives the possibility to investigate both the embodied and operational emissions for different REC configuration. A residential neighbourhood in Italy is selected as case study. The results demonstrate the importance of considering building characteristics when analysing emissions reductions in energy-sharing schemes, underlining the necessity of coupling the REC design with energy retrofit interventions

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

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    We 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

    Author Index

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