1,721,031 research outputs found

    Razvoj visoko-propusne optičke metode za određivanje funkcionalne povezanosti mreže živčanih stanica u kulturi

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    Neurons connect into networks via synapses which are plastic and stochastic; however, all under the control of perfectly coordinated molecular machinery which facilitates synaptic coupling and communication. Any change to the presynaptic apparatus jeopardizes vesicle release, thus instantaneously altering neuronal activation. Failed or over- activation of neurons directly changes patterns of functional connectivity in the neural network, whose emergence is still a big neuroscientific mystery. For that reason, studying synaptic activity is essential for understanding functional connectivity. Many optical tools are available for probing networkwide dynamics, but little achieve single-synaptic resolution. I used a novel intensity-based glutamate-sensing fluorescence reporter (iGluSnFR) to explore its potential to report singlesynaptic activity in vitro. iGluSnFR successfully reported evoked and spontaneous synaptic glutamate release. It also detected subtle differences in genetically modified synaptic activity when compared to wild-type. Therefore, it proved equipped to resolve many synapse-related questions. If applied in large-scale network research, iGluSnFR will contribute to better understanding of physiological and pathological changes in neural networks.Neuroni se udružuju u mreže putem sinapsi čija je aktivnost, iako promjenjiva i nepredvidiva, pod kontrolom koordiniranih molekularnih procesa koji olakšavaju sinaptičko povezivanje i komunikaciju. Svaka promjena u djelovanju presinaptičkih molekula ugrožava kontrolirano oslobađanje vezikula, što odmah utječe na daljnju aktivaciju neurona. Neispravna ili pretjerana aktivacija neurona izravno mijenja obrasce funkcionalne povezanosti u neuronskoj mreži. Nastanak tih obrazaca još je uvijek velika nepoznanica u neuroznanosti. Iz tog je razloga proučavanje sinaptičke aktivnosti ključno za razumijevanje funkcionalne povezanosti neurona u mreži. Postoje mnogi optički alati za ispitivanje aktivacije neurona u mreži, ali malo ih postiže rezoluciju pojedinačnih sinapsi. U ovom je radu korišten novi fluorescentni reporter iGluSnFR (eng. intensity-based glutamate-sensing fluorescence reporter) pri čemu je istraživan njegov potencijal za mjerenje aktivnosti pojedinačnih sinapsi in vitro. iGluSnFR je pokazao efikasnost u mjerenju presinaptičkog glutamata oslobođenog nakon stimulacije ili spontane sinaptičke aktivnosti. Također, iGluSnFR je otkrio suptilne razlike u genetski modificiranoj sinaptičkoj aktivnosti u usporedbi s divljim tipom. Stoga se iGluSnFR pokazao učinkovitim za rješavanje mnogih pitanja vezanih uz sinaptičku aktivnost. Primjena iGluSnFR reportera u istraživanju neuronskih mreža pridonijet će boljem razumijevanju njihovih fizioloških i patoloških promjena

    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

    Neuropeptide secretion principles:Vesicle populations, characteristics and fusion mechanisms

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    Our brain consists of a complex network of neurons which communicate by secreting signaling molecules as neurotransmitters and neuromodulators. For fast communication, neurotransmitters are released by synaptic vesicles (SVs) at the contact points between neurons, the synapses. Neuromodulators are secreted by dense-core vesicles (DCVs) to regulate processes such as development, circadian rhythm, metabolism, behavior and emotions. Defects in neuromodulator signaling result in brain disorders as depression, schizophrenia, autism or obesity, but how neuromodulators are released by neurons is largely unknown. The general aim of this thesis was to characterize the mechanism of neuromodulator secretion by DCVs. We have determined the number, location and release characteristics of DCVs in neurons. Furthermore, we show that two proteins, RAB3 and RIM proteins, are essential for DCV fusion. Finally, we identified two new proteins present on DCVs and developed new tools to study DCVs in the future. The fundamental knowledge and new methods provided in this thesis will contribute to new directions for treatments of disorders related to neuromodulator signaling. Mammalian neurons contain a large number of DCVs, ranging from 1,400-18,000 per neuron, which are distributed equally throughout the neuron. DCV fusion, like SV fusion, is triggered by calcium influx but requires more prolonged repetitive stimulation to release only a small fraction. While SV fusion mechanisms have been extensively studied, providing a molecular framework of proteins organizing the release of neurotransmitters, much less is known about proteins that regulate neuromodulator secretion. We now show that RIM proteins are indispensable organizers of DCV fusion by positioning the active zone protein MUNC13 and interacting with DCVs via RAB3. Together, these data identified an essential mechanism that brings DCVs to their release site for fusion. The identification of the essential function of RAB3 in DCV fusion resolved a longstanding question in the field. In 1980, a breakthrough study by Novick and Schekman identified SEC4, the yeast RAB3, as one of the essential proteins required for fusion. Many of the proteins they identified have been shown to be essential for SV fusion in the mammalian brain, but surprisingly, RAB3 proteins are not required for SV fusion. However, removal of all RAB3 proteins is lethal for mice, suggesting RAB3 proteins had an unidentified important function. Our data now shows that RAB3 is an indispensableregulator of DCV fusion. The crucial role of RAB3 in DCV fusion shows the first distinct feature between DCV and SV fusion, and provides new explanations for the multiple, severe problems in mice which lack RAB3. This thesis contributes with fundamental insights into different aspects of neuromodulator secretion, but we currently do not have a consistent overview of what is on and inside a DCV. Therefore, we developed a new approach to isolate intact DCVs from neurons. This approach could be used for future studies to determine the composition of DCVs, which will identify important molecules that function in the DCV pathway, providing new directions to study neuromodulator secretion and new leads for diagnostics and treatments of neuromodulator signaling related disorders

    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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    Geological controlling parameters on seismic imaging of igneous intrusions on Svalbard

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    Imaging and mapping igneous intrusions such a sills and dykes has been one of the challenges in recent years. However, igneous intrusions in seismic data have properties that make them good targets for visualization, such as high amplitude and sophisticated shapes. 3D visualization methods are especially well suited for sill reflections. One of the main limitations of tying offshore seismic data to onshore observations and vice versa is a matter of scale. Igneous sills that are exposed onshore might be too thin to consistently map in seismic data, whereas features that are visible in seismic surveys offshore might be too long to be able to view onshore. Understanding the geometry of these intrusions may provide key insights regarding emplacement processes, geological history, and potential for hydrocarbon exploration. The research is based on photogrammetric research, analysis of intrusions and their host rocks, and building 3-D models to use for synthetic seismic generation. Well analysis is also required in order to estimate the properties used for these synthetic seismics. Five different geometries have been tested using different lithologies for the host rocks. Sandstone/shale, organic rich shale, clean sandstone and Paleozoic carbonates. The test cases using organic shale show a high impedance contrast, where the cases using carbonates show a very low contrast, due to the similarities of the Vp and Vs with the doleritic intrusions. The sandstone/shale and shale lithologies have more contrast than the carbonates, but less than the organic rich shale. Most shapes show up fairly well on the synthetic data, however sub-vertical geometries have low visibility regardless of the lithology. There are some seismic properties that are hard to simulate using synthetic seismic, such as seismic attenuation, variance of properties within a lithology, and the presence of other geological features. Regardless, the use of synthetic seismic data may help bridge the data integration gap between onshore and offshore data

    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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