185 research outputs found

    Neutral Evolution as Diffusion in phenotype space: reproduction with mutation but without selection

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    The process of `Evolutionary Diffusion', i.e. reproduction with local mutation but without selection in a biological population, resembles standard Diffusion in many ways. However, Evolutionary Diffusion allows the formation of local peaks with a characteristic width that undergo drift, even in the infinite population limit. We analytically calculate the mean peak width and the effective random walk step size, and obtain the distribution of the peak width which has a power law tail. We find that independent local mutations act as a diffusion of interacting particles with increased stepsize.Comment: 4 pages, 2 figures. Paper now representative of published articl

    Calcium Regulates the Nuclear Localization of Protein Arginine Deiminase 2

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    Protein arginine deiminases (PADs) are calcium-dependent enzymes that mediate the post-translational conversion of arginine into citrulline. Dysregulated PAD activity is associated with numerous autoimmune disorders and cancers. In breast cancer, PAD2 citrullinates histone H3R26 and activates the transcription of estrogen receptor target genes. However, PAD2 lacks a canonical nuclear localization sequence, and it is unclear how this enzyme is transported into the nucleus. Here, we show for the first time that PAD2 translocates into the nucleus in response to calcium signaling. Using BioID2, a proximity-dependent biotinylation method for identifying interacting proteins, we found that PAD2 preferentially associates with ANXA5 in the cytoplasm. Binding of calcium to PAD2 weakens this cytoplasmic interaction, which generates a pool of calcium-bound PAD2 that can interact with Ran. We hypothesize that this latter interaction promotes the translocation of PAD2 into the nucleus. These findings highlight a critical role for ANXA5 in regulating PAD2 and identify an unusual mechanism whereby proteins translocate between the cytosol and nucleus

    Genetic Reporter System for Positioning of Proteins at the Bacterial Pole

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    Spatial organization within bacteria is fundamental to many cellular processes, although the basic mechanisms underlying localization of proteins to specific sites within bacteria are poorly understood. The study of protein positioning has been limited by a paucity of methods that allow rapid large-scale screening for mutants in which protein positioning is altered. We developed a genetic reporter system for protein localization to the pole within the bacterial cytoplasm that allows saturation screening for mutants in Escherichia coli in which protein localization is altered. Utilizing this system, we identify proteins required for proper positioning of the Shigella autotransporter IcsA. Autotransporters, widely distributed bacterial virulence proteins, are secreted at the bacterial pole. We show that the conserved cell division protein FtsQ is required for localization of IcsA and other autotransporters to the pole. We demonstrate further that this system can be applied to the study of proteins other than autotransporters that display polar positioning within bacterial cells.Molecular and Cellular Biolog

    Perfectionism and achievement goals revisited: The 3 × 2 achievement goal framework

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    Objectives: Perfectionistic strivings (PS) and perfectionistic concerns (PC) have shown different profiles with the 2 × 2 achievement goals in sport. Whether PS and PC also show comparable profiles with the achievement goals of the expanded 3 × 2 framework, however, is unclear. Design: Cross-sectional. Method: We examined self-reported perfectionistic strivings, perfectionistic concerns, and the 3 × 2 achievement goals in 136 junior athletes (mean age 17.0 years). Results: The results of structural equation modeling showed that PS were positively associated with task-, self-, and other-approach goals and negatively with task- and self-avoidance goals. In contrast, PC were positively associated with task-, self-, and other-avoidance goals and negatively with task- and self-approach goals. Conclusions: The findings suggest that PS and PC show different profiles also with the 3 × 2 achievement goals which may help explain why the two perfectionism dimensions show differential relations with achievement-related outcomes in sport

    Sequence composition underlying centromeric and heterochromatic genome compartments of the Pacific oyster Crassostrea gigas

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    Segments of the genome enriched in repetitive sequences still present a challenge and are omitted in genome assemblies. For that reason, the exact composition of DNA sequences underlying the heterochromatic regions and the active centromeres are still unexplored for many organisms. The centromere is a crucial region of eukaryotic chromosomes responsible for the accurate segregation of genetic material. The typical landmark of centromere chromatin is the rapidly-evolving variant of the histone H3, CenH3, while DNA sequences packed in constitutive heterochromatin are associated with H3K9me3-modified histones. In the Pacific oyster Crassostrea gigas we identified its centromere histone variant, Cg-CenH3, that shows stage-specific distribution in gonadal cells. In order to investigate the DNA composition of genomic regions associated with the two specific chromatin types, we employed chromatin immunoprecipitation followed by high-throughput next-generation sequencing of the Cg-CenH3- and H3K9me3-associated sequences. CenH3-associated sequences were assigned to six groups of repetitive elements, while H3K9me3-associated-ones were assigned only to three. Those associated with CenH3 indicate the lack of uniformity in the chromosomal distribution of sequences building the centromeres, being also in the same time dispersed throughout the genome. The heterochromatin of C. gigas exhibited general paucity and limited chromosomal localization as predicted, with H3K9me3-associated sequences being predominantly constituted of DNA transposons

    The association between delusional-like experiences, and tobacco, alcohol or cannabis use: a nationwide population-based survey

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    <p>Abstract</p> <p>Background</p> <p>Previous population-based studies have found that delusional-like experiences (DLE) are prevalent in the community, and are associated with a wide range of mental health disorders including substance use. The aim of the study was to explore the association between DLE and three commonly used substances - tobacco, alcohol and cannabis.</p> <p>Methods</p> <p>Subjects were drawn from the Australian National Survey of Mental Health and Wellbeing 2007. The Composite International Diagnostic Interview was used to identify DLE, common psychiatric disorders, and substance use. We examined the relationship between the variables of interest using logistic regression, adjusting for potential confounding factors.</p> <p>Results</p> <p>Of 8 773 participants, 8.4% (n = 776) subjects endorsed one or more DLE. With respect to tobacco use, compared to nonusers, DLE were more common in those who (a) had daily use, (b) commenced usage aged 15 years or less, and (c) those who smoked heavily (23 or more cigarettes per day). Participants with cannabis use disorders were more likely to endorse DLE; this association was most prominent in those with an onset of 16 years or younger. In contrast, the pattern of association between DLE versus alcohol use or dependence was less consistent, however those with early onset alcohol use disorders were more likely to endorse DLE probe items.</p> <p>Conclusions</p> <p>While cannabis use disorders have been previously linked with DLE, our findings linking alcohol and tobacco use and DLE suggest that the influence of these substances on psychosis-related outcomes warrants closer scrutiny in longitudinal prospective studies.</p

    ‘Sell[ing] what hasn’t got a name’: An exploration of the different understandings and definitions of ‘community engagement’ work in the performing arts

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    Widely known to promote broader involvement in the processes which define the arts and culture (Webster, 1997), community engagement work in the performing arts — despite employing a set of commonly recognised norms — has tended to be conceptualised differently both historically and contemporarily. Drawing on ethnographic research — particularly semi-structured qualitative interview accounts of numerous British practitioners with a track record of work in the sector, the article explores these different conceptualisations. The article finds that it is the actual ‘work that matters’ and not what it is named, and that the diversity of understandings and definitions among sectoral practitioners is reflective of evolving thinking, values and practice, something that may be destabilising for better or worse

    Shifting the paradigm of prison suicide prevention through enhanced multi-agency integration and cultural change

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    This study examines an unusually sustained reduction in suicide rates in a local London prison during the three year period 2008-2011. The likelihood of this reduction taking place by chance was < 2:100,000, and its perceived success was such that the prison service recommended an evaluation of its characteristics. This study arose from that recommendation, and it used a retrospective case study multi-method approach (including factor identification, qualitative interviews, and triangulation with official documentation) to identify factors which had been associated with the reduced suicide rates. The results endorsed a number of factors which have already been internationally identified as best practice (WHO, 2007), along with some local innovation factors. Two further pivotal factors emerged through analysis, and they are key to service improvements. These factors - senior management support for cultural change and cross-professional collaborative working - indicate that positive leadership and multi-agency integration are vital ingredients

    A Framework to Support Interdisciplinary Engagement with Learning Analytics

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    Learning analytics can provide an excellent opportunity for instructors to get an in-depth understanding of students’ learning experiences in a course. However, certain technological challenges, namely limited availability of learning analytics data because of learning management system restrictions, can make accessing this data seem impossible at some institutions. Furthermore, even in cases where instructors have access to a range of student data, there may not be organized efforts to support students across various courses and university experiences. In the current chapter, the authors discuss the issue of learning analytics access and ways to leverage learning analytics data between instructors, and in some cases administrators, to create interdisciplinary opportunities for comprehensive student support. The authors consider the implications of these interactions for students, instructors, and administrators. Additionally, the authors focus on some of the technological infrastructure issues involved with accessing learning analytics and discuss the opportunities available for faculty and staff to take a multi-pronged approach to addressing overall student success.https://scholarworks.wm.edu/educationbookchapters/1045/thumbnail.jp

    Australia\u27s health 1992 : the third biennial report of the Australian Institute of Health and Welfare

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    Australia\u27s Health is the most comprehensive and authoritative source of national information on health in Australia. Australia\u27s Health is published mid-year in even-numbered years and provides national statistics and related information that form a record of health status, service provision and expenditure in Australia
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