1,721,007 research outputs found
Maternal Programming Of Behavior
No full textWhile development is fundamentally determined and regulated by genetics, it is also substantially modified by environmental influences, particularly those originating from the mother; a phenomenon known as “maternal programming”. Factors such as nutrition, genetic perturbations, infection, and psychiatric conditions can all contribute to the development of specific, adverse conditions in the offspring. In many cases, the effects of the maternal environment extend beyond the first generation of offspring, to the grand- and even great-grand-offspring. The mechanisms underlying maternal programming are poorly understood, but are believed to involve non-genetic stimuli such as immunological molecules and epigenetic signatures. The central nervous system is particularly sensitive during gestation, and abnormalities during fetal development could contribute to altered brain-behavior circuitry. In this dissertation, two maternally-programmed conditions are dissected into their underlying transmission mechanisms. A partial/complete maternal tumor necrosis factor (TNF) deficiency results in augmented postnatal offspring hippocampal proliferation, and ultimately, atypical adult spatial memory. This occurs via a TNF-dependent “lactocrine” pathway, in which the levels of specific chemokines are reduced in the mother’s milk. Because TNF levels can be regulated by lifestyle, it is possible that this maternal TNF-milk chemokine pathway evolved to promote offspring adaptation to the post-weaning environment. Maternal serotonin 1A receptor (5-HT1AR) deficiency programs a multi-symptom psychiatric-like phenotype in genetically wild-type offspring. The symptoms are not inherited together, but rather propagated to consecutive generations by separate, parallel mechanisms, producing varied offspring emotional phenotypes. Some symptoms are transmitted somatically via a neuro-immune pathway, while others are depend on a gametic mode of transmission. Both maternal programming scenarios in this dissertation describe non-Mendelian inheritance of neurodevelopmental and behavioral phenotypes across generations. Understanding non-genetic inheritance mechanisms is becoming increasingly important, as it is apparent that most complex diseases are the result of a combination of genetic and environmental influences. The development of neurodevelopmental diseases may not be inevitable. In fact, the work presented here suggests it could be possible to anticipate, and even prevent, some disorders through revised diagnostic approaches and more personalized therapeutic applications
Environmentally Malleable Epigenomic Regions In The Mammalian Brain
Get PDFUnderstanding the development of epigenetic patterns that underlie neural development and differentiation is an essential foundation for understanding what occurs in “abnormal” situations. DNA methylation, in concert with other epigenetic regulators, controls the accessibility of transcription factors to DNA and/or their function. While extensively studied in neuronal progenitors in vitro, the role of methylation/demethylation in neuronal lineage/subtype specification in vivo is not known. By profiling two distinct neuronal lineages, and five neuron subtypes in the hippocampus and striatum, we uncovered a set of five principles that govern DNA methylation-dynamics in neurodevelopment. By dividing neurodevelopment to three alternating methylation and demethylation periods and applying the principles to each of these stages, we created a matrix that comprehensively describes the targets, genomic contexts, functional consequences and putative mechanisms of methylation/demethylation events. The overarching theme is that the developmental methylation program is remarkably similar in the hippocampus and striatum, with significant divergence only occurring during subtype specification. Our matrix can be cross-referenced with disease-associated methylation changes to specify possible events and underlying principles compromised in disease. Adverse environmental conditions, particularly during early life, are associated with increased risk for behavioral and/or psychiatric disorders. However, the molecular basis that can potentially link environmental conditions to psychopathologies are unknown, complicating diagnosis and therapeutic measures. We identified differentially methylated regions (DMRs) in mammalian offspring exposed to an adverse maternal environment associated with anxiety in both the mother and offspring. We hypothesized the presence of metastable “hotspots” in the genome that display an inherent sensitivity to environmental cues. These hotspots would enable an adaptive/maladaptive molecular response to multiple environmental conditions by modifying appropriate gene expression patterns and cellular phenotypes. Using several animal models of early life adversities, which result in a common offspring anxiety phenotype, we used genome-wide DNA methylation sequencing to detect common environmentally sensitive DMRs (E-DMRs). E-DMRs displayed several DNA features including: Exonic enrichment, intermediate methylation, and enhancer activity. Interestingly, E-DMRs did not perturb the overall patterning of DNA methylation that takes place during neural development. The experience dependent variations in DNA methylation at E-DMRs may prime the genome for differential transcriptional response to later events. This metaplasticity may be especially important in brain regions responsible for processing environmental input to elicit a behavioral response. Since maternal conditions impact the offspring during gametogenesis and through fetal/early-postnatal life, the resultant phenotype is likely the aggregate of consecutive germline and somatic effects; a concept that hasn’t been previously studied. We dissected a complex maternally-transmitted phenotype, reminiscent of comorbid generalized anxiety/depression, to elementary behaviors/domains and their transmission mechanisms. We show that four anxiety/stress-reactive traits are transmitted via independent iterative-somatic and gametic epigenetic mechanisms across multiple generations. Somatic/gametic transmission alters DNA methylation at enhancers within synaptic genes whose functions can be linked to the behavioral-traits. Traits have generation-dependent penetrance and sex-specificity resulting in pleiotropy, often seen in psychiatry. A transmission-pathway based concept can refine current inheritance models of psychiatric diseases and facilitate the development of better animal models and new therapeutic approaches
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
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