1,720,958 research outputs found
Prader Willi locus Snord116 RNA regulates hypothalamic functions: sleep and temperature
No full textSleep is a complex behavior and it is hierarchically regulated involving several brain regions, neurotransmitters, and genes that co-operate in building modulatory mechanisms aimed at controlling and maintaining sleep. Specifically, this thesis attempts to address/understand how genomic imprinting, which affect a subset of genes in mammals resulting in a monoallelic expression, may regulate sleep. One of the main brain regions involved in sleep regulation is the hypothalamus. Within the hypothalamic region imprinted genes are highly expressed. Interestingly, it has been described that hypothalamic insufficiency caused by lack of paternal expression of chromosome 15q11- q13, leads to Prader-Willi syndrome (PWS). Specifically, the microdeletion of the small nuclear ribonucleic acid (RNA)-116 (SNORD116) cluster within the PWS locus plays a major role in developing the main endophenotypes that characterize this syndrome (i.e. REM sleep dysfunction, hyperphagia and temperature instability). However, what could be the role of the paternally imprinted gene Snord116 in the hypothalamic function is unknown. Additionally, is still unclear the specific contribution of the Snord116 gene in developing the PWS symptoms. Since these unresolved points my research has been split into three parts: In the first part of this research, it has been shown that the paternally imprinted gene Snord116 plays a crucial role in the formation and organization of the orexin (OX) and melanin concentrating hormone (MCH) systems, the two main neuro-modulatory systems within the lateral hypothalamus (LH). Moreover, a compromised neuronal dynamic in the LH and a sleep- wake regulation of mice with paternal deletion of Snord116 (PWScrm+/p-) is observed. This abnormal neuronal dynamic is accompanied by a significant reduction in OX neurons in the LH of mutant mice. For this reason, it is proposed that the dysregulation of rapid eye movement (REM) sleep, food intake and temperature control observed in PWS mice are potentially due to this imbalance between OX- and MCH-expressing neurons in the LH as observed in mutant mice. In the second part of this research, it has been investigated the microstructural electrophysiological components of sleep, such as REM sleep features and sleep spindles during non-REM sleep. Indeed, REM sleep is thought to contribute to neuronal network formation early in brain development, while spindles are markers of thalamocortical processes. In neurodevelopmental disorders both sleep structures (REM and sleep spindles) are often compromised and this influence functional properties of cortical neurons. These results indicate 1 that REM sleep properties and its occurrence (REM sleep episodes classified as short-and long REM sleep episode) throughout the sleep-wake cycles are selectively influenced by the Snord116 gene in mice. Moreover, the specific abnormalities in sleep spindles in PWS model systems, indicate that these sleep features may be translated as potential biomarkers in human PWS sufferers. In the third part of this research, it has been proposed a new therapeutic approach for PWS patients aiming to ameliorate the sleep phenotypes that significantly compromise the quality of life of these patients. Pitolisant (a wake-promoting drug) was orally administrated in mice carrying the paternal deletion of the Snord116 gene that are affected by REM sleep alteration coupled with a reduction of the OX neurons. Overall the results of this research show that Pitolisant ameliorates the REM sleep alteration in these mice, although other studies are needed to clarify whether this drug may be easily translated/used in clinics. In conclusion, this thesis provides support for the important role of Snord116 in the regulation of REM sleep and its propensity and its regulatory mechanisms in the hypothalamus. Finally, a new pharmacological approach for PWS by using Pitolisant has been proposed to ameliorate the sleep alteration that significantly affects the PWS patients
PRELIMINAR ANALYSIS OF ENGINEERED FUNCTIONALLY ACTIVE HUMAN DERIVED CORTICAL NEUROSPHEROIDS FOR DRUG SCREENING AND PRECISION MEDICINE
No full textThe continue development of differentiation protocols to generate human neural cells in vitro, allows more accurate investigations of the functional mechanisms arising in such complex networks, and generates great expectations for new treatments in neurodegenerative diseases for which effective therapies are not yet available. The use of 3D aggregates for neuropharmacological in vitro studies has shown great potentials and the advent of human patient specific in vitro models opens new avenues in the field of drug screening and precision medicine. Moreover, Neuronal Stem Cell (NSC) transplantation has the potential to revolutionize brain disease research, but still presents limitations that hamper the use in therapeutics. It has been shown how the injection of NSCs directly into the host, leads to a random integration into the tissue, while a targeted transplant is needed in the specific area affected by degeneration. An alternative approach would be to produce an already differentiated healthy 3D tissue, that shows all the functional and morphological features suitable for transplant into the degenerated area. To this end, we optimized a fast differentiation protocol to engineer excitatory cortical neurospheres with 1:1 ratio between neurons and astrocytes. We first evaluated its morphology by imaging and then we evaluated its functionality (i.e. electrophysiological activity) with glassbased 60 and CMOS-based 4096 micro-electrode arrays (MEAs). Our preliminary results show how the generated structures are viable and functionally active throughout their development. Furthermore, CMOS-MEAs revealed network properties that did not emerge from standard MEAs. Although the obtained results are preliminary, all neurospheroids adhered to substrates and developed functionally active neuritic arborizations, suggesting their efficient use for functional drugs screening applications and for future in vivo transplantation
Loss of Snord116 alters cortical neuronal activity in mice: a preclinical investigation of Prader-Willi syndrome.
Full text linkPrader-Willi syndrome (PWS) is a neurodevelopmental disorder that is characterized by metabolic alteration and sleep abnormalities mostly related to rapid eye movement (REM) sleep disturbances. The disease is caused by genomic imprinting defects that are inherited through the paternal line. Among the genes located in the PWS region on chromosome 15 (15q11-q13), small nucleolar RNA 116 (Snord116) has been previously associated with intrusions of REM sleep into wakefulness in humans and mice. Here, we further explore sleep regulation of PWS by reporting a study with PWScrm+/p- mouse line, which carries a paternal deletion of Snord116. We focused our study on both macrostructural electrophysiological components of sleep, distributed among REMs and nonrapid eye movements. Of note, here, we study a novel electroencephalography (EEG) graphoelements of sleep for mouse studies, the well-known spindles. EEG biomarkers are often linked to the functional properties of cortical neurons and can be instrumental in translational studies. Thus, to better understand specific properties, we isolated and characterized the intrinsic activity of cortical neurons using in vitro microelectrode array. Our results confirm that the loss of Snord116 gene in mice influences specific properties of REM sleep, such as theta rhythms and, for the first time, the organization of REM episodes throughout sleep-wake cycles. Moreover, the analysis of sleep spindles present novel specific phenotype in PWS mice, indicating that a new catalog of sleep biomarkers can be informative in preclinical studies of PWS
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
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