1,720,962 research outputs found
STUDY OF THE ROLE OF THE SEROTONINERGIC SYSTEM IN THE BRAIN FUNCTIONALITY AND IN THE VULNERABILITY TO PSYCHOPATHOLOGIES:A GENETIC APPROACH
Get PDFPsychiatric pathologies are the second leading cause of disability worldwide with about 10% of the general population that manifest at least one symptom during their lifetime. This, together with the only partial effectiveness of the treatments adopted to date, make these illnesses an important burden for the society as well as for families and patients.
The first theory elaborated to explain the onset of psychiatric pathologies is the monoaminergic hypothesis that postulated how low levels of monoamines such as serotonin in the brain could be at the basis of depressive episodes and of other mood disorders. In line, human studies highlighted how alterations in different genes coding for different players involved in the serotoninergic system can be related to an increased susceptibility for psychopathologies.
Despite this linkage seems striking, different aspects of these pathologies cannot be explained with a direct causal relationship, making this hypothesis part of a bigger picture that also involves the environmental factors as well as other mechanisms.
On these bases, understanding the complexity of the systems that are modulated by serotoninergic alterations could give novel insights in understanding these such heterogeneous diseases.
To better clarify this aspect, during my PhD I took advantage of different genetically modified animal models characterized by alterations in the serotoninergic system. In particular, we evaluated the effect of low functionality of the serotonin transporter (SERT) on brain functions and we confirmed the pathological-like behavior of SERT-/- rats, characterized by a massive presence of serotonin in the extracellular compartments of the whole body. Moreover, we perform molecular analyses that confirmed alterations in different systems such as the neuroplastic mechanisms, the GABAergic system, and the dendritic spine functionality. Furthermore, we evaluated if a positive environment could ameliorate the behavior and the molecular abnormalities of SERT-/- rats finding a restorative effect of one month of enriched environment both on the anhedonic and anxiety-like behavior and on the molecular abnormalities.
Moreover, by altering the expression of the isoforms 1 or 2 of the tryptophan hydroxylase (TPH) enzyme, responsible for the production of serotonin in the periphery or in the brain respectively, we took into consideration TPH1-/- and TPH2-/- rats. More specifically, we worked on TPH2-/- rats, which do not have serotonin in the central nervous system and are characterized by an aggressive behavior and low anxiety levels at adulthood. Interestingly, we found that the lack of brain-serotonin was counteracted by an upregulation in the neurotrophin Brain-derived neurotrophic factor (Bdnf) expression. Moreover, we found that this compensatory mechanism was present also at early adolescence, while at post-natal day 10, when the blood-brain-barrier is not completely formed and we cannot distinguish between central and peripheral serotonin, Bdnf expression was lowered. Interestingly, this increased neuroplasticity at adulthood was not enough to cope with an acute stress such as one hour of restraint stress. Indeed, while wild-type rats showed an activation of the Bdnf machinery and of the transcription of the immediate early genes, this effect was reduced in TPH2-/- rats. Accordingly, we found that the hypothalamic pituitary adrenal (HPA) axis and specifically its genomic pathway activation was much more consistent in TPH2+/+ than in TPH2-/- rats.
Interestingly, we observed similar results also in TPH1-/- rats that showed a dramatic reduction in serotonin levels in different peripheral organs. Indeed, the lack of peripheral serotonin was able to reduce the anxiety-like behavior in these rats suggesting that also the peripheral pool of this molecule can alter brain functionality. Moreover, this positive effect on their behavior was sustained, at central level, by an increased expression of Bdnf. Nevertheless, also in this case, we found deficits in the reaction to the acute stress. Indeed, we found that the increased transcription of Bdnf and of the immediate early gene Arc happened specifically in wild-type while not in TPH1-/- rats. Similarly, the upregulation in the glucocorticorticoid responsive gene transcription was lower in a condition of absence of peripheral serotonin.
All the molecular analyses were conducted in the prefrontal cortex, a brain region highly innervated by serotoninergic fibers and involved in environmental changes response and in behavioral adaptations.
These results highlighted how these genetically modified animal models can be useful to study the role of serotonin in the modulation of brain functionality and the mechanisms involved in this process. Moreover, these findings supported the serotonin involvement in brain development and functionality. Ultimately, the data collected in this thesis give novel insights on the brain pathways affected by serotonin and on the role of this system in shaping the reaction to environmental stimuli in the field of psychiatric disorders
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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