478 research outputs found

    Synaptic vesicle dynamics in mouse rod bipolar cells.

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    To better understand synaptic signaling at the mammalian rod bipolar cell terminal and pave the way for applying genetic approaches to the study of visual information processing in the mammalian retina, synaptic vesicle dynamics and intraterminal calcium were monitored in terminals of acutely isolated mouse rod bipolar cells and the number of ribbon-style active zones quantified. We identified a releasable pool, corresponding to a maximum of 7 s. The presence of a smaller, rapidly releasing pool and a small, fast component of refilling was also suggested. Following calcium channel closure, membrane surface area was restored to baseline with a time constant that ranged from 2 to 21 s depending on the magnitude of the preceding Ca2+ transient. In addition, a brief, calcium-dependent delay often preceded the start of onset of membrane recovery. Thus, several aspects of synaptic vesicle dynamics appear to be conserved between rod-dominant bipolar cells of fish and mammalian rod bipolar cells. A major difference is that the number of vesicles available for release is significantly smaller in the mouse rod bipolar cell, both as a function of the total number per neuron and on a per active zone basis

    Protein Kinase Activation Increases Insulin Secretion by Sensitizing the Secretory Machinery to Ca2+

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    Glucose and other secretagogues are thought to activate a variety of protein kinases. This study was designed to unravel the sites of action of protein kinase A (PKA) and protein kinase C (PKC) in modulating insulin secretion. By using high time resolution measurements of membrane capacitance and flash photolysis of caged Ca2+, we characterize three kinetically different pools of vesicles in rat pancreatic β-cells, namely, a highly calcium-sensitive pool (HCSP), a readily releasable pool (RRP), and a reserve pool. The size of the HCSP is ∼20 fF under resting conditions, but is dramatically increased by application of either phorbol esters or forskolin. Phorbol esters and forskolin also increase the size of RRP to a lesser extent. The augmenting effect of phorbol esters or forskolin is blocked by various PKC or PKA inhibitors, indicating the involvement of these kinases. The effects of PKC and PKA on the size of the HCSP are not additive, suggesting a convergent mechanism. Using a protocol where membrane depolarization is combined with photorelease of Ca2+, we find that the HCSP is a distinct population of vesicles from those colocalized with Ca2+ channels. We propose that PKA and PKC promote insulin secretion by increasing the number of vesicles that are highly sensitive to Ca2+

    Association between NR5A2 and the risk of pancreatic cancer, especially among Caucasians: a meta-analysis of case-control studies

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    Background: Previous studies have reported that nuclear receptor subfamily 5, group A, member 2 (NR5A2) polymorphisms (rs3790843 G>A, rs3790844 T>C, rs12029406 C>T) are associated with the risk of pancreatic cancer. However, the results of epidemiological investigations are still controversial. In order to explore its potential attributing factors, we pooled the updated literatures to evaluate the association between NR5A2 polymorphism and the risk of pancreatic cancer in this meta-analysis. Materials and methods: Databases such as PubMed, Google Scholar and China National Knowledge Infrastructure were searched for eligible articles following strict inclusion and exclusion criteria (updated to November 18, 2017). Odds ratios (ORs) and 95% C Is were computed to assess the intensity of association. In addition, heterogeneity, sensitivity analysis and publication bias were explored. All statistical analyses were conducted by STATA 14.0. Results: Our results showed that the rs3790843 (GA vs GG: OR=0.86, CI=0.76-0.98, P=0.992;GA+AA vs GG: OR=0.83, CI=0.73-0.94, P=0.950;A vs G: OR=0.85, CI=0.78-0.93, P=0.802), rs3790844 (CC vs TT: OR=0.65, CI=0.54-0.78, P=0.617;CC vs TT+CT: OR=0.73, CI=0.62-0.85, P=0.742;C vs T: OR=0.78, CI=0.73-0.84, P=0.555) and rs12029406 (TT vs CC: OR=0.73, CI=0.61-0.89, P=0.483;TT vs CC+CT: OR=0.78, CI=0.66-0.92, P=0.648;T vs C: OR=0.87, CI=0.79-0.95, P=0.837) polymorphisms were associated statistically with the risk of pancreatic cancer. Furthermore, the results of subgroup analysis showed that rs3790843 and rs3790844 polymorphisms were especially related to the risk of pancreatic cancer in Caucasian population. Conclusion: Our results revealed that NR5A2 may have a protective effect on pancreatic cancer. However, more well-designed researches are needed to verify the relationship between NR5A2 polymorphisms and the risk of pancreatic cancer

    Mapping the distribution of Anthrax in Mainland China, 2005-2013

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    Anthrax in China was characterized by significant seasonality and spatial clustering. The spatial distribution of human anthrax was largely driven by livestock husbandry, human density, land cover, elevation, topsoil features and climate. Enhanced surveillance and intervention for livestock and human anthrax in the high-risk regions, particularly on the Qinghai-Tibetan Plateau, is the key to the prevention of human infections

    Emerging tick-borne infections in mainland China: an increasing public health threat

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    Since the beginning of the 1980s, 33 emerging tick-borne agents have been identified in mainland China, including eight species of spotted fever group rickettsiae, seven species in the family Anaplasmataceae, six genospecies in the complex Borrelia burgdorferi sensu lato, 11 species of Babesia, and the virus causing severe fever with thrombocytopenia syndrome. In this Review we have mapped the geographical distributions of human cases of infection. 15 of the 33 emerging tick-borne agents have been reported to cause human disease, and their clinical characteristics have been described. The non-specific clinical manifestations caused by tick-borne pathogens present a major diagnostic challenge and most physicians are unfamiliar with the many tick-borne diseases that present with non-specific symptoms in the early stages of the illness. Advances in and application of modern molecular techniques should help with identification of emerging tick-borne pathogens and improve laboratory diagnosis of human infections. We expect that more novel tick-borne infections in ticks and animals will be identified and additional emerging tick-borne diseases in human beings will be discovered

    MEI Kodierung der frühesten Notation in linienlosen Neumen

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    Das Optical Neume Recognition Project (ONRP) hat die digitale Kodierung von musikalischen Notationszeichen aus dem Jahr um 1000 zum Ziel – ein ambitioniertes Vorhaben, das die Projektmitglieder veranlasste, verschiedenste methodische Ansätze zu evaluieren. Die Optical Music Recognition-Software soll eine linienlose Notation aus einem der ältesten erhaltenen Quellen mit Notationszeichen, dem Antiphonar Hartker aus der Benediktinerabtei St. Gallen (Schweiz), welches heute in zwei Bänden in der Stiftsbibliothek in St. Gallen aufbewahrt wird, erfassen. Aufgrund der handgeschriebenen, linienlosen Notation stellt dieser Gregorianische Gesang den Forscher vor viele Herausforderungen. Das Werk umfasst über 300 verschiedene Neumenzeichen und ihre Notation, die mit Hilfe der Music Encoding Initiative (MEI) erfasst und beschrieben werden sollen. Der folgende Artikel beschreibt den Prozess der Adaptierung, um die MEI auf die Notation von Neumen ohne Notenlinien anzuwenden. Beschrieben werden Eigenschaften der Neumennotation, um zu verdeutlichen, wo die Herausforderungen dieser Arbeit liegen sowie die Funktionsweise des Classifiers, einer Art digitalen Neumenwörterbuchs

    Increasing discrimination of DEA evaluation by utilizing distances to anti-efficient frontiers

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    This paper develops three DEA performance indicators for the purpose of performance ranking by using the distances to both the efficient frontier and the anti-efficient frontier to enhance discrimination power of DEA analysis. The standard DEA models and the Inverted DEA models are used to identify the efficient and anti-efficient frontiers respectively. Important issues like possible intersections of the two frontiers are discussed. Empirical studies show that these indicators indeed have much more discrimination power than that of standard DEA models, and produce consistent ranks. Furthermore, three types of simulation experiments under general conditions are carried out in order to test the performance and characterization of the indicators. The simulation results show that the averages of both the Pearson and Spearman correlation coefficients between true efficiency and indicators are higher than those of true efficiency and efficiency scores estimated by the BCC model when sample size is smal
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