1,721,143 research outputs found
Behavioural, immunological and transcriptomic consequences of post-weaning social isolation and chronic celecoxib administration in mouse.
No full textEarly life stress (ELS) and chronic low-grade inflammation are associated with psychiatric disease risk, but their neurobiological consequences are poorly understood. Here, we aim to investigate the behavioural, immunological and molecular consequences of ELS in mice. C57Bl6 mice were subjected to post-weaning social isolation (SI - PD21-40) with or without chronic celecoxib (CEL) (PD21-61). ELS-induced behavioural changes were assessed using the open field test (OFT) and three-chambered test (3CT). The anti-inflammatory effects of celecoxib were assessed by enzyme-linked immunosorbent assay (ELISA) of IL-6, TNF-α and IL-10 cytokines released by stimulated splenocytes. Gene expression changes in the hippocampus and amygdala were assessed using RNA-sequencing. Neither SI nor CEL affected OFT time in centre or 3CT discrimination ratio. However, SI induced locomotor changes in both tests. CEL significantly reduced IL-6, TNF-α and IL-10 release from splenocytes. SI induced significant gene expression changes in both hippocampus and amygdala, while CEL only induced gene expression changes in the hippocampus. Differentially expressed genes (DEGs) induced by SI were enriched for ontologies relating to gamma-aminobutyric acid activity and insulin binding in the hippocampus and neurogenesis in the amygdala. CEL-induced DEGs in the hippocampus were enriched for neurogenesis. Cell type enrichment implicated choroid plexus and vascular leptomeningeal cells in SI DEGs and medium spiny neurons (MSNs) in CEL DEGs. CEL-induced DEGs were enriched for heritability for psychiatric disorders and cognitive ability. In conclusion, gene expression changes show convergence with human psychiatric disorders through both enrichments in common genetic heritability and enrichment of previously implicated cell populations
Investigating the effect of environmental risk factors for neuropsychiatric and neurodevelopmental disorders on gene expression in brain tissue from mouse models
No full textExposure to certain environmental stressors before birth or in early life increases risk for neuropsychiatric and neurodevelopmental disorders. These stressors include the prenatal factor of maternal immune activation (MIA) and the early life factor of social isolation (SI). The underlying molecular biology of these factors cannot be actively studied in humans and thus, animals models such as the mouse provide a crucial alternative. Here, using previously published data for MIA (Chapter 2) and newly generated RNA-seq data for SI (Chapter 3), I use mouse models to investigate how gene expression in the brain is impacted by these environmental risk factors. Furthermore, I assess the effects of a non-steroidal anti-inflammatory drug, Celecoxib (CEL) on SI-induced gene expression changes (Chapter 4). The neurobiological relevance of gene expression changes and possible links to established genetic risk for human neuropsychiatric and neurodevelopmental disorders are also investigated. Based on reanalysis of published data, MIA induces highly variable gene expression changes in the mouse brain. The most consistently dysregulated genes however, based on ranking by individuals p-values, had functions related to neural tube folding, regulation of cellular stress, neuronal/glial cell differentiation and some genes were directly associated with neuropsychiatric disorders such as Fgf10 and Cck. Furthermore, cell type enrichment analysis linked genes consistently dysregulated by MIA and common genetic risk for schizophrenia (SCZ) and cognitive ability (IQ). The SI factor, investigated initially in Chapter 3, induced differentially-expressed genes (DEGs) in male and female mouse hippocampus. These DEGS are shown to impact the structure and function of synapse biology, show enrichment for common SNP heritability for SCZ and bipolar disorder (BPD) in males and females as well as for cognitive ability in females. Likewise, DEGs in males are enriched for genes harbouring rare de novo mutations contributing to autism spectrum disorder. Finally, marker genes for hippocampal astrocytes were enriched in females DEGs. The final study (Chapter 4) reinvestigated the SI factor in females, however with the addition of a new region (amygdala) and new factor (CEL). A number of commonalities persisted in the nominally-significant SI-induced DEGs, most notably the implication of cell types with roles in the blood-brain barrier (BBB). When investigated alone, CEL administration had a strong effect on gene expression in the hippocampus, but not amygdala. Consequently, when investigating nominally-significant gene expression changes induced by CEL and SI in combination, CEL appeared to reduce the proportion of DEGs relating to synapse biology in the hippocampus compared to SI alone. This was not found to be the case in the amygdala. The results from this thesis provide an insight into how environmental stressors affect gene expression in the mouse brain. Gene expression changes related to both synapse and glial cell biology. Regions encapsulating genes dysregulated by these factors often overrepresent human genetic variation contributing to neuropsychiatric disorders and cognition. These data generally support the molecular validity of environmental animal models of neuropsychiatric and neurodevelopmental disorder, while also highlighting challenges and limitations associated with their use.1. This work is primarily funded by the Irish Research Council (IRC) Government of Ireland
Postgraduate Scholarship Programme (GOIPG/2019/1932) to Aodán Laighneach.
2. The Immune Response and Social Cognition in Schizophrenia (iRELATE) project on which much
of this work is based, was funded through the European Research Council (ERC-2015-STG 677467; PI = Prof Gary Donohoe).
3. Chapter 4 was partially funded through a Thomas Crawford Hayes Research award to Aodán
Laighneach
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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