Sexes often have differing fitness optima, potentially generating intra-locus sexual conflict, as each sex bears a genetic 'load' of alleles beneficial to the other sex. One strategy to evaluate ...conflict in the genome is to artificially select populations discordantly, against established sexual dimorphism, reintroducing attenuated conflict. We investigate a long-term artificial selection experiment reversing sexual size dimorphism in Drosophila melanogaster during ~350 generations of sexually discordant selection. We explore morphological and genomic changes to identify loci under selection between the sexes in discordantly and concordantly size selected treatments. Despite substantial changes to overall size, concordant selection maintained ancestral sexual dimorphism. However, discordant selection altered size dimorphism in a trait-specific manner. We observe multiple, possible soft selective sweeps in the genome, with size related genes showing signs of selection. Patterns of genomic differentiation between the sexes within lineages identified potential sites maintained by sexual conflict. One discordant selected lineage shows a pattern of elevated genomic differentiation between males and females, on chromosome 3L, consistent with the maintenance of sexual conflict. Our results suggest visible signs of conflict and differentially segregating alleles between the sexes due to discordant selection.
Abstract
Identifying the genetic architecture of complex traits is important to many geneticists, including those interested in human disease, plant and animal breeding, and evolutionary genetics. ...Advances in sequencing technology and statistical methods for genome-wide association studies have allowed for the identification of more variants with smaller effect sizes, however, many of these identified polymorphisms fail to be replicated in subsequent studies. In addition to sampling variation, this failure to replicate reflects the complexities introduced by factors including environmental variation, genetic background, and differences in allele frequencies among populations. Using Drosophila melanogaster wing shape, we ask if we can replicate allelic effects of polymorphisms first identified in a genome-wide association studies in three genes: dachsous, extra-macrochaete, and neuralized, using artificial selection in the lab, and bulk segregant mapping in natural populations. We demonstrate that multivariate wing shape changes associated with these genes are aligned with major axes of phenotypic and genetic variation in natural populations. Following seven generations of artificial selection along the dachsous shape change vector, we observe genetic differentiation of variants in dachsous and genomic regions containing other genes in the hippo signaling pathway. This suggests a shared direction of effects within a developmental network. We also performed artificial selection with the extra-macrochaete shape change vector, which is not a part of the hippo signaling network, but showed a largely shared direction of effects. The response to selection along the emc vector was similar to that of dachsous, suggesting that the available genetic diversity of a population, summarized by the genetic (co)variance matrix (G), influenced alleles captured by selection. Despite the success with artificial selection, bulk segregant analysis using natural populations did not detect these same variants, likely due to the contribution of environmental variation and low minor allele frequencies, coupled with small effect sizes of the contributing variants.
Physical literacy is a multidimensional concept that describes a holistic foundation for physical activity engagement. Understanding the utilization and effectiveness of physical literacy in the ...context of health and the health care setting will support clinical and population health programming. The purpose of this rapid scoping review was to: 1) map the conceptualization of physical literacy as it relates to health; 2) identify and describe the utilization of physical literacy in the context of health and engagement of health care providers; and 3) better understand the relationship between physical literacy, physical activity, and health.
Following established scoping review methods adapted for a rapid review approach, we searched electronic databases Medline OVID, CINAHL Ebsco, PsycInfo Ebsco, Web of Science ISI, and ERIC Ebsco from conception until September 2019. Tabulation coding was used to identify the key themes across included articles and synthesize findings. The review follows an integrated knowledge translation approach based on a partnership between the health system, community organizations, and researchers.
Following removal of duplicates, our search identified 475 articles for title and abstract screening. After full text review, 17 articles were included (12 original research papers and five conceptual or review papers). There was near consensus among included papers with 16 of 17 using the Whiteheadian definition of physical literacy. There was limited involvement of health care providers in the concept of physical literacy. Physical literacy was connected to the following health indicators: BMI and body weight, waist circumference, cardiorespiratory fitness, physical activity, and sedentary behaviour. The primary demographic focus of included studies was children and there was a conceptual focus on the physical domain of physical literacy.
Despite growing popularity, the empirical evidence base linking physical literacy and health outcomes is limited and the relationship remains theoretical. Physical literacy may present a novel and holistic framework for health-enhancing physical activity interventions that consider factors vital to sustained participation in physical activity across the life course. Future work should continue to explore the nature and direction of the relationship between physical activity and physical literacy to identify appropriate focused approaches for health promotion.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Children's independent mobility (CIM) is the freedom of children to move around their neighbourhood without adult supervision and is closely related to overall physical activity participation. The ...COVID-19 pandemic has impacted movement behaviours for children, with evidence indicating a decrease in physical activity. The aim of this study was to explore experiences of CIM and physical activity during the COVID-19 pandemic from the perspectives of children and their parents. We completed 21 family (at least one parent and one child aged 7-12) semi-structured interviews with 45 participants living in small urban and rural areas of British Columbia, Canada. Three themes were identified through a reflexive thematic analysis: (1) keeping everyone safe from COVID-19; (2) change in pattern and types of activity; (3) social impacts with family, friends, and community. Participants expressed a perceived increase in unstructured activity and a decrease in structured physical activity during the pandemic, which many parents viewed as a positive change. Parents and children indicated negative feelings due to spending less time with peers and reflected positively about spending more time with family. Parents and children expressed fear and anxiety in trying to keep their families safe from virus spread and creativity in adapting play behaviours. Findings highlight the impact of the pandemic on social friendship networks for families and a shift in activity patterns for children toward unstructured play.
Children's independent mobility (CIM) is the freedom of children to move around their neighbourhood or community without adult supervision. The aim of this study was to explore experiences with CIM ...from the perspectives of children and their parents living in rural and remote areas of British Columbia, Canada. Semi-structured interviews were conducted with 21 parent-child dyads or triads (45 participants). Child participants aged 7-12 were invited to create and describe drawings, maps, or take images of their independent mobility. Artwork and interview transcripts were analysed following an inductive thematic approach and mapped to the social-ecological model. We developed four themes to describe rural and remote family perspectives on CIM: (1) natural places, spaces, and forces; (2) embracing informal and unstructured play destinations; (3) decision-making and knowing when they are ready; (4) neighbourhood and community environments. Children identified several environmental characteristics impacting their independent mobility including wildlife, seasonal weather patterns, and lack of destinations. Parents reported the environment of rural communities, including neighbourhood cohesiveness and people looking out for each other, as being supportive of CIM. To promote CIM in rural and remote areas, efforts should focus on providing education on wildlife encounters, creating safe and interesting destinations for play, and consider children's safety and connectivity in road design.
Due to accelerating wildland fire activity, there is mounting urgency to understand, prevent, and mitigate the occupational health impacts associated with wildland fire suppression. The objectives of ...this review of academic and grey literature were to: 1. Identify the impact of occupational exposure to wildland fires on physical, mental, and emotional health; and 2. Examine the characteristics and effectiveness of prevention, mitigation, or management strategies studied to reduce negative health outcomes associated with occupational exposure to wildland fire.
Following established scoping review methods, academic literature as well as government and industry reports were identified by searching seven academic databases and through a targeted grey literature search. 4679 articles were screened using pre-determined eligibility criteria. Data on study characteristics, health outcomes assessed, prevention or mitigation strategies studied, and main findings were extracted from each included document. The results of this scoping review are presented using descriptive tables and a narrative summary to organize key findings.
The final sample was comprised of 100 articles: 76 research articles and 24 grey literature reports. Grey literature focused on acute injuries and fatalities. Health outcomes reported in academic studies focused on respiratory health (n = 14), mental health (n = 16), and inflammation and oxidative stress (n = 12). The identified studies evaluated short-term outcomes measuring changes across a single shift or wildland fire season. Most research was conducted with wildland firefighters and excluded personnel such as aviation crews, contract crews, and incident management teams. Five articles reported direct study of mitigation strategies, focusing on the potential usage of masks, advanced hygiene protocols to reduce exposure, fluid intake to manage hydration and core temperature, and glutamine supplementation to reduce fatigue.
While broad in scope, the evidence base linking wildland fire exposure to any one health outcome is limited. The lack of long-term evidence on changes in health status or morbidity is a clear evidence gap and there is a need to prioritize research on the mental and physical health impact of occupational exposure to wildland fire.
Mouse models that reflect human disorders provide invaluable tools for the translation of basic science discoveries to clinical therapies. However, many of these in vivo therapeutic studies are short ...term and do not accurately mimic patient conditions. In this study, we used a fully immunocompetent, transgenic mouse model, TGS, in which the spontaneous development of metastatic melanoma is driven by the ectopic expression of a normal neuronal receptor, mGluR1, as a model to assess longitudinal treatment response (up to 8 months) with an inhibitor of glutamatergic signaling, troriluzole, which is a prodrug of riluzole, plus an antibody against PD-1, an immune checkpoint inhibitor. Our results reveal a sex-biased treatment response that led to improved survival in troriluzole and/or anti−PD-1−treated male mice that correlated with differential CD8+ T cells and CD11b+ myeloid cell populations in the tumor−stromal interface, supporting the notion that this model is a responsive and tractable system for evaluating therapeutic regimens for melanoma in an immunocompetent setting.
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Invasive fungal infections have become an important healthcare issue due in large part to high mortality rates under standard of care (SOC) therapies creating an urgent need for new ...and effective anti-fungal agents. We have developed a series of non-peptide, structurally-constrained analogs of host defence proteins that have distinct advantages over peptides for pharmaceutical uses. Here we report the chemical optimization of bis-guanidine analogs focused on alterations of the central aryl core and the connection of it to the terminal guanidines. This effort resulted in the production of highly potent, broadly active compounds with low mammalian cell cytotoxicity that have comparable or improved antifungal activities over SOC agents. One optimal compound was also found to possess favourable in vitro pharmaceutical and off-target properties suitable for further development.
ObjectivesThe increase in global wildland fire activity has accelerated the urgency to understand health risks associated with wildland fire suppression. The aim of this project was to identify ...occupational health research priorities for wildland firefighters and related personnel.DesignIn order to identify, rank and rate health research priorities, we followed a modified Delphi approach. Data collection involved a two-stage online survey followed by semi-structured interviews.SettingBritish Columbia, Canada.ParticipantsParticipants included any current or past wildland firefighter or individuals engaged in related roles. There were 132 respondents to the first survey. Responses to the first survey were analysed to produce 10 research topics which were ranked by 75 participants in the second survey (response rate: 84%).Primary and secondary outcome measuresThe primary outcome was the identification, ranking and level of agreement of research priorities through a two-round online survey. We contextualised these findings through deductive and inductive qualitative content analysis of semi-structured interviews.ResultsThe most important research priorities identified were (% consensus): effects of smoke inhalation on respiratory health (89%), fatigue and sleep (80%), mental health (78%), stress (76%) and long-term risk of disease (67%). Interviews were completed with 14 individuals. Two main themes were developed from an inductive content analysis of interview transcripts: (1) understanding the dynamic risk environment; and (2) organisational fit of mitigation strategies.ConclusionsParticipants expressed a general concern with the unknown mental and physical health impacts of their jobs, including the long-term risk of morbidity and mortality. Future research must address knowledge gaps in our understanding of the health impacts of wildland fire and work to develop appropriate mitigation strategies while considering the needs of workers and unpredictable workplace environment.Trial registration numberOpen Science Framework, https://osf.io/ugz4s/
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