1,721,141 research outputs found
Genetic Manipulation of the Murine Choline Transporter
No full textNeuroscience
Dissertation under the direction of Professor Randy D. Blakely
This dissertation is focused on the function and regulation of the choline transporter (CHT). I used CHT heterozygous and homozygous mice, and combined biochemical, pharmacological, and behavioral approaches to test the hypothesis that CHT is essential for acetylcholine (ACh) turnover and behaviors dependent on cholinergic signaling in vivo. My work demonstrates that CHT homozygous knockout mice are born with wild type levels of ACh, but are unable to sustain ACh synthesis and release under high demand for ACh turnover. CHT heterozygosity, on the other hand, results in diminished pools of ACh. Consequenly, focused behavioral and pharmacological challenges reveal that CHT heterozygous mice are vulnerable to sustained demands on cholinergically-supported behaviors. In summary, my thesis work provides new insights into the role of CHT in the maintenance of ACh turnover and cholinergic neurotransmission. The CHT heterozygous mice constitute a new animal model of cholinergic dysfunction, and offer opportunities for further studies of CHT function and regulation, with the eventual goal of manipulating CHT in disorders of cholinergic origin.
Approved: Professor Randy D. Blakely, May 200
Food-dependent swimming-induced paralysis in C. elegans: a novel serotonin transporter dependent phenotype
No full textThe monoamine neurotransmitter serotonin (5-HT) is an essential component of vertebrate cognitive function and the autonomous nervous system, regulating body temperature, sleep, appetite, and mood. Abnormal 5-HT signaling is implicated in a variety of disorders such as depression, anxiety, alcoholism, and obsessive-compulsive disorder. Synaptic serotonergic activity is primarily regulated by the recycling of 5-HT from the synaptic cleft by the presynaptic 5-HT transporter (SERT), a target for many psychostimulants and anti-depressants such as MDMA (“Ecstasy”) and Fluoxetine (Prozac). In the model system Caenorhabditis elegans (C. elegans), 5-HT is an active participant in a variety of motor, autonomic, and behavioral functions including egg-laying, pharyngeal pumping, locomotion, male mating, aging, and enhanced slowing. The goal of this work is to use the C. elegans model system to manipulate the SERT homolog (MOD-5) and examine regulatory genes controlling MOD-5 trafficking, localization, and activity. We characterized the behavioral phenotypes of endogenous 5-HT activity in C. elegans and in 5-HT transporter deletion mutants, especially those pertaining to locomotor function. We also describe a novel, food dependent immobilization phenotype and use genetic and pharmacological approaches to establish the role of 5-HT and MOD-5 within this phenotype. These techniques provide the necessary tools for use of this phenotype as the basis for a forward genetic screen which will provide unbiased assessments of transporter regulatory molecules. This work provides the foundation for elucidation of proteins that regulate determinants of serotonin transporter function and support normal serotonin transporter activity
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
Impact of dopamine transporter-mediated, non-vesicular DA release on ADHD traits as studied in the DAT Val559 mouse model
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