scholarly journals Selection shapes the landscape of functional variation in wild house mice

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Raman Akinyanju Lawal ◽  
Uma P. Arora ◽  
Beth L. Dumont
Keyword(s):  
Positive Selection ◽  
Significant Proportion ◽  
Wild Mouse ◽  
House Mice ◽  
Functional Variation ◽  
Disease Associated Genes ◽  
Functional Alleles ◽  
The Impact ◽  
Mouse Genetic

Abstract Background Through human-aided dispersal over the last ~ 10,000 years, house mice (Mus musculus) have recently colonized diverse habitats across the globe, promoting the emergence of new traits that confer adaptive advantages in distinct environments. Despite their status as the premier mammalian model system, the impact of this demographic and selective history on the global patterning of disease-relevant trait variation in wild mouse populations is poorly understood. Results Here, we leveraged 154 whole-genome sequences from diverse wild house mouse populations to survey the geographic organization of functional variation and systematically identify signals of positive selection. We show that a significant proportion of wild mouse variation is private to single populations, including numerous predicted functional alleles. In addition, we report strong signals of positive selection at many genes associated with both complex and Mendelian diseases in humans. Notably, we detect a significant excess of selection signals at disease-associated genes relative to null expectations, pointing to the important role of adaptation in shaping the landscape of functional variation in wild mouse populations. We also uncover strong signals of selection at multiple genes involved in starch digestion, including Mgam and Amy1. We speculate that the successful emergence of the human-mouse commensalism may have been facilitated, in part, by dietary adaptations at these loci. Finally, our work uncovers multiple cryptic structural variants that manifest as putative signals of positive selection, highlighting an important and under-appreciated source of false-positive signals in genome-wide selection scans. Conclusions Overall, our findings highlight the role of adaptation in shaping wild mouse genetic variation at human disease-associated genes. Our work also highlights the biomedical relevance of wild mouse genetic diversity and underscores the potential for targeted sampling of mice from specific populations as a strategy for developing effective new mouse models of both rare and common human diseases.

scholarly journals Selection shapes the landscape of functional variation in wild house mice

2021 ◽  
Author(s):  
Raman Akinyanju Lawal ◽  
Uma P Arora ◽  
Beth L Dumont
Keyword(s):  
Positive Selection ◽  
Significant Proportion ◽  
Wild Mouse ◽  
House Mice ◽  
Functional Variation ◽  
Disease Associated Genes ◽  
Functional Alleles ◽  
The Impact ◽  
Mouse Genetic

Background Through human-aided dispersal, house mice have recently colonized new and diverse habitats across the globe, promoting the emergence of new traits that confer adaptive advantages in distinct environments. Despite their status as the premiere mammalian model system, the impact of this demographic and selective history on the global patterning of disease-relevant trait variation in wild mouse populations is poorly understood. Results Here, we leveraged 154 whole-genome sequences from diverse wild house mouse populations, subspecies, and species to survey the geographic organization of functional variation and systematically identify signals of positive selection. We show that a significant proportion of wild mouse variation is private to single populations, including numerous predicted functional alleles. In addition, we report strong signals of positive selection at numerous genes associated with both complex and Mendelian diseases in humans. Notably, we detect a significant excess of selection signals at disease-associated genes relative to null expectations, pointing to the important role of adaptation in shaping the landscape of functional variation in wild mouse populations. We also uncover strong signals of selection at multiple genes involved in starch digestion, including Mgam and Amy1. We speculate that the successful emergence of the human-mouse commensalism may have been facilitated, in part, by dietary adaptations at these loci. Finally, our work uncovers multiple cryptic structural variants that manifest as putative signals of positive selection, highlighting an important and under-appreciated source of false-positive signals in genome-wide selection scans. Conclusions Overall, our findings underscore the role of adaptation in shaping wild mouse genetic variation at human disease-associated genes. Our work highlights the biomedical relevance of wild mouse genetic diversity and underscores the potential for targeted sampling of mice from specific populations as a strategy for developing effective new mouse models of both rare and common human diseases.

scholarly journals Prostate cancer and the human papilloma virus: causative association, role of vaccines, and the impact of the COVID-19 pandemic

2021 ◽  
Author(s):  
Naomi Morka ◽  
Joseph M. Norris ◽  
Mark Emberton ◽  
Daniel Kelly
Keyword(s):  
Prostate Cancer ◽  
Human Papilloma Virus ◽  
Hpv Vaccination ◽  
Significant Proportion ◽  
Vaccine Uptake ◽  
Papilloma Virus ◽  
Vaccination Campaigns ◽  
The Impact ◽  
Hpv Vaccine Uptake

AbstractProstate cancer affects a significant proportion of men worldwide. Evidence from genetic and clinical studies suggests that there may be a causal association between prostate cancer and the human papilloma virus (HPV). As HPV is a vaccine-preventable pathogen, the possibility of a role in prostate cancer causation may reinforce the importance of effective HPV vaccination campaigns. This is of particular relevance in light of the COVID-19 pandemic, which may have considerable effects on HPV vaccine uptake and distribution.

scholarly journals 178 Continuing to enhance efficiency in swine

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 183-183
Author(s):  
Graham Plastow
Keyword(s):  
New Technologies ◽  
Significant Proportion ◽  
Swine Production ◽  
Live Animal ◽  
Enhance Efficiency ◽  
Market Needs ◽  
The Impact ◽  
Near Future ◽  
Made In

Abstract Efficiency in swine production is made up of a number of traits including reproduction, health, and the conversion of feed into pork. Due to the large proportion of cost associated with feed (>70% of overall costs) there has been a focus on this aspect of efficiency. Indeed, significant progress has been made in reducing the amount of feed required to reach market weight. This has been achieved at the same time as increasing growth rate (and therefore decreasing age at slaughter) whilst maintaining carcass quality to meet market needs. A significant proportion of this improvement was delivered through genetics and the application of new measurement technologies. Examples, include the use of ultrasound to measure fat content on the live animal and individual feed intake recording. At a time when sustainable production is increasingly demanded then efficiency will continue to be important through its impact on the economics of farming – productivity and profit. However, sustainability takes into account other aspects such as the impact on the environment as well as social aspects such as animal welfare. Many of these components support each other, for example, more prolific sows producing more efficient full market value pigs contribute to a smaller environmental footprint (more product and less waste). Likewise pigs that stay healthy even when responding to infection continue to eat and require less medication. When antagonisms exist they can be addressed in a balanced selection program that addresses all aspects. We are now at a point where new technologies will make it feasible to address these additional factors providing the opportunity for even greater progress in these key traits in the near future. This presentation will provide examples of the progress made and the role of genomics in utilizing “big data” to continue to improve the efficiency of swine production.

scholarly journals The Influence of the Internet on the Socialization of Students

2021 ◽  
Vol 16 (4) ◽  
pp. 6-10
Author(s):  
Bazarova Tatyana S. ◽  
◽  
Fomitskaya Galina N. ◽  
Keyword(s):  
Social Networks ◽  
Young People ◽  
Information Search ◽  
Significant Proportion ◽  
Value Orientations ◽  
The Internet ◽  
Young Generation ◽  
Dependent Behavior ◽  
The Impact

The article is devoted to an urgent pedagogical problem – the influence of the Internet on the socialization of student youth in modern conditions, which determined the purpose and objectives of the article: to characterize the role of the Internet in the formation of values and attitudes of student youth, the development of Internet-dependent behavior. To achieve the goal, the following research methods were used: literature analysis on the problem under study, express survey and testing, comparative analysis of the results. This problem is considered taking into account the increasing importance of electronic resources in the context of digitalization of modern society. The characteristics of the main concepts of the problem under study are given: socialization, student youth, the Internet, etc. The approaches to defining the place of the Internet as the main means of communication and information for young people are reflected. The authors present the results of a comprehensive monitoring study conducted in recent years among the students of the Dorzhi Banzarov Buryat State University. On the basis of the primary data of the study the actual characteristics of the problem under study are highlighted: the goals and reasons for visiting the Internet (communication in social networks, information search, entertainment, studies), the respondents’ evaluation of the impact of the Internet as more positive than negative. The study of the value orientations of modern student youth showed that the respondents choose the main traditional values: family, health, love, self-development. Thus, the peculiarities of the influence of the Internet on the socialization of student youth are presented as follows: the main purpose of visiting the Internet is to communicate in social networks; young people are quite aware of the role of Internet influence; the main life values of the young generation retain a traditional character; a significant proportion of respondents have formed and stable Internet addictive behavior. The analysis of the results obtained shows that the use of the Internet as the main means of communication and information does not, in general, have a negative impact on the formation of values and attitudes of student youth, but contributes to the development of Internet-dependent behavior. Keywords: socialization, student youth, the Internet, value orientations, Internet-dependent behavior

scholarly journals A network modelling approach to assess non-pharmaceutical disease controls in a worker population: An application to SARS-CoV-2

2021 ◽  
Vol 17 (6) ◽  
pp. e1009058
Author(s):  
Edward M. Hill ◽  
Benjamin D. Atkins ◽  
Matt J. Keeling ◽  
Louise Dyson ◽  
Michael J. Tildesley
Keyword(s):  
Network Model ◽  
Significant Proportion ◽  
Disease Spread ◽  
Contact Tracing ◽  
Work Patterns ◽  
General Role ◽  
Work From Home ◽  
Working Practices ◽  
The Impact

As part of a concerted pandemic response to protect public health, businesses can enact non-pharmaceutical controls to minimise exposure to pathogens in workplaces and premises open to the public. Amendments to working practices can lead to the amount, duration and/or proximity of interactions being changed, ultimately altering the dynamics of disease spread. These modifications could be specific to the type of business being operated. We use a data-driven approach to parameterise an individual-based network model for transmission of SARS-CoV-2 amongst the working population, stratified into work sectors. The network is comprised of layered contacts to consider the risk of spread in multiple encounter settings (workplaces, households, social and other). We analyse several interventions targeted towards working practices: mandating a fraction of the population to work from home; using temporally asynchronous work patterns; and introducing measures to create ‘COVID-secure’ workplaces. We also assess the general role of adherence to (or effectiveness of) isolation and test and trace measures and demonstrate the impact of all these interventions across a variety of relevant metrics. The progress of the epidemic can be significantly hindered by instructing a significant proportion of the workforce to work from home. Furthermore, if required to be present at the workplace, asynchronous work patterns can help to reduce infections when compared with scenarios where all workers work on the same days, particularly for longer working weeks. When assessing COVID-secure workplace measures, we found that smaller work teams and a greater reduction in transmission risk reduced the probability of large, prolonged outbreaks. Finally, following isolation guidance and engaging with contact tracing without other measures is an effective tool to curb transmission, but is highly sensitive to adherence levels. In the absence of sufficient adherence to non-pharmaceutical interventions, our results indicate a high likelihood of SARS-CoV-2 spreading widely throughout a worker population. Given the heterogeneity of demographic attributes across worker roles, in addition to the individual nature of controls such as contact tracing, we demonstrate the utility of a network model approach to investigate workplace-targeted intervention strategies and the role of test, trace and isolation in tackling disease spread.

Effect of Adjuvant Chemotherapy in Stage III Cervical Cancer Patients Treated With Concurrent Chemoradiation: A Multicenter Study

2022 ◽  
Author(s):  
Muhammed Mustafa Atci ◽  
Baran Akagunduz ◽  
Metin Demir ◽  
Binnur Dönmez Yılmaz ◽  
Tugba Akin Telli ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Significant Proportion ◽  
Progression Free Survival ◽  
Figo Stage ◽  
Stage Iii ◽  
Free Survival ◽  
The Impact

Introduction: A significant proportion of cervical cancer (CC) patients are diagnosed at a locally advanced stage. Concurrent chemoradiotherapy (CCRT) is the cornerstone of treatment for patients with locally advanced CC. However, the role of adjuvant chemotherapy (AC) after CCRT is controversial. In this study, we analyzed the efficacy of AC after CCRT in stage III CC patients. Methods: We performed a multicenter, retrospective analysis of 139 FIGO stage III CC patients treated with CCRT of whom 45.3% received AC. Our goal was to determine the impact of AC on survival in these patients. Results: Five-year progression-free survival was 37.5% and 16% in patients receiving CCRT with and without AC, respectively (p=0.008). Median PFS was 30.9 months (CI 95 %14.8-46.9) and 16.6 months (CI 95% 9.3-23.9) in patients receiving CCRT with and without AC, respectively. Five-year overall survival was 78.2% and 28.4% in patients receiving CCRT with and without AC, respectively (p<0.001). Median OS was 132.2 months (CI 95, %66.5-197.8) and 34.9 months (CI 95% 23.1-46.7) in patients receiving CCRT with and in without AC, respectively. Conclusion: Our study suggests that AC provides OS and PFS benefit in stage III CC patients. Larger studies are needed to identify subgroups of patients who would benefit from AC.

scholarly journals A network modelling approach to assess non-pharmaceutical disease controls in a worker population: An application to SARS-CoV-2

2020 ◽  
Author(s):  
Edward M Hill ◽  
Benjamin D Atkins ◽  
Matt J Keeling ◽  
Louise Dyson ◽  
Michael J Tildesley
Keyword(s):  
Network Model ◽  
Significant Proportion ◽  
Disease Spread ◽  
Contact Tracing ◽  
Work Patterns ◽  
General Role ◽  
Work From Home ◽  
Working Practices ◽  
The Impact

Background: As part of a concerted pandemic response to protect public health, businesses can enact non-pharmaceutical controls to minimise exposure to pathogens in workplaces and premises open to the public. Amendments to working practices can lead to the amount, duration and/or proximity of interactions being changed, ultimately altering the dynamics of disease spread. These modifications could be specific to the type of business being operated. Methods: We use a data-driven approach to parameterise an individual-based network model for transmission of SARS-CoV-2 amongst the working population, stratified into work sectors. The network is comprised of layered contacts to consider risk of spread in multiple encounter settings (workplaces, households, social and other). We analyse several interventions targeted towards working practices: mandating a fraction of the population to work from home, using temporally asynchronous work patterns and introducing measures to create `COVID-secure' workplaces. We also assess the general role of adherence to (or effectiveness of) isolation and test and trace measures and demonstrate the impact of all these interventions across a variety of relevant metrics. Results: The progress of the epidemic can be significantly hindered by instructing a significant proportion of the workforce to work from home. Furthermore, if required to be present at the workplace, asynchronous work patterns can help to reduce infections when compared with scenarios where all workers work on the same days, particularly for longer working weeks. When assessing COVID-secure workplace measures, we found that smaller work teams and a greater reduction in transmission risk led to a flatter temporal profile for both infections and the number of people isolating, and reduced the probability of large, long outbreaks. Finally, following isolation guidance and engaging with contact tracing alone is an effective tool to curb transmission, but is highly sensitive to adherence levels. Conclusions: In the absence of sufficient adherence to non-pharmaceutical interventions, our results indicate a high likelihood of SARS-CoV-2 spreading widely throughout a worker population. Given the heterogeneity of demographic attributes across worker roles, in addition to the individual nature of controls such as contact tracing, we demonstrate the utility of a network model approach to investigate workplace-targeted intervention strategies and the role of test, trace and isolation in tackling disease spread.

Getting a foot in the door: can expanding the role of podiatry assistant improve access to public podiatry services?

2009 ◽  
Vol 15 (1) ◽  
pp. 45 ◽  
Author(s):  
Shan Bergin
Keyword(s):  
Adverse Events ◽  
Waiting Times ◽  
Significant Proportion ◽  
Practical Training ◽  
Community Based ◽  
The Impact ◽  
Community Based Services ◽  
Improve Access

The aim of this pilot was to evaluate the impact delegation of identified tasks to a qualified podiatry assistant (PA) had on accessibility to footcare services for targeted client groups. The role of PA was defined for the purposes of the pilot. The PA underwent theoretical and practical training and the role was implemented within a community based podiatry unit. Outcome measures included: total number of clients seen, change in available (qualified) podiatry hours through delegation of tasks to the assistant, changes to waiting times for initial and follow-up appointments, adverse events and patient satisfaction. The PA provided footcare to 41 clients during the evaluation period (December 2005 to January 2006 inclusive). Available (qualified) podiatry hours increased by 10 h per week for the same period and waiting times for an initial appointment were reduced from 12 to 2 weeks for the target group and from an ‘indefinite’ waiting period to 12 weeks for follow-up appointments. No adverse events were reported during the pilot. The findings of this pilot have implications for improving affordability and accessibility of footcare services to a significant proportion of the community and reducing the burden on current community based services.

Intergroup Threat and Outgroup Attitudes

2013 ◽  
Vol 44 (5) ◽  
pp. 311-319 ◽  
Author(s):  
Marco Brambilla ◽  
David A. Butz
Keyword(s):  
Gay Men ◽  
Social Group ◽  
Welfare Recipients ◽  
Intergroup Attitudes ◽  
Social Policies ◽  
Intergroup Threat ◽  
Economic Threat ◽  
The Impact ◽  
General Climate

Two studies examined the impact of macrolevel symbolic threat on intergroup attitudes. In Study 1 (N = 71), participants exposed to a macrosymbolic threat (vs. nonsymbolic threat and neutral topic) reported less support toward social policies concerning gay men, an outgroup whose stereotypes implies a threat to values, but not toward welfare recipients, a social group whose stereotypes do not imply a threat to values. Study 2 (N = 78) showed that, whereas macrolevel symbolic threat led to less favorable attitudes toward gay men, macroeconomic threat led to less favorable attitudes toward Asians, an outgroup whose stereotypes imply an economic threat. These findings are discussed in terms of their implications for understanding the role of a general climate of threat in shaping intergroup attitudes.

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