Inferring the distribution of fitness effects of spontaneous mutations in Chlamydomonas reinhardtii

Spontaneous mutations are the source of new genetic variation and are thus central to the evolutionary process. In molecular evolution and quantitative genetics, the nature of genetic variation depends critically on the distribution of effects of mutations on fitness and other quantitative traits. Spontaneous mutation accumulation (MA) experiments have been the principal approach for investigating the overall rate of occurrence and cumulative effect of mutations but have not allowed the phenotypic effects of individual mutations to be studied directly. Here, we crossed MA lines of the green alga Chlamydomonas reinhardtii with its unmutated ancestral strain to create haploid recombinant lines, each carrying an average of 50% of the accumulated mutations in a large number of combinations. With the aid of the genome sequences of the MA lines, we inferred the genotypes of the mutations, assayed their growth rate as a measure of fitness, and inferred the distribution of fitness effects (DFE) using a Bayesian mixture model. We infer that the DFE is highly leptokurtic (L-shaped). Of mutations with absolute fitness effects exceeding 1%, about one-sixth increase fitness in the laboratory environment. The inferred distribution of effects for deleterious mutations is consistent with a strong role for nearly neutral evolution. Specifically, such a distribution predicts that nucleotide variation and genetic variation for quantitative traits will be insensitive to change in the effective population size

Population genomics of <i>Escherichia coli</i> in livestock-keeping households across a rapidly developing urban landscape

Quantitative evidence for the risk of zoonoses and the spread of antimicrobial resistance remains lacking. Here, as part of the UrbanZoo project, we sampled Escherichia coli from humans, livestock and peri-domestic wildlife in 99 households across Nairobi, Kenya, to investigate its distribution among host species in this rapidly developing urban landscape. We performed whole-genome sequencing of 1,338 E. coli isolates and found that the diversity and sharing patterns of E. coli were heavily structured by household and strongly shaped by host type. We also found evidence for inter-household and inter-host sharing and, importantly, between humans and animals, although this occurs much less frequently. Resistome similarity was differently distributed across host and household, consistent with being driven by shared exposure to antimicrobials. Our results indicate that a large, epidemiologically structured sampling framework combined with WGS is needed to uncover strain-sharing events among different host populations in complex environments and the major contributing pathways that could ultimately drive the emergence of zoonoses and the spread of antimicrobial resistance

Ireland’s Climate Change Assessment 2023. Volume 1: Climate Science-Ireland in a changing World. Summary of Policymakers

Ireland’s Climate Change Assessment (ICCA) delivers a comprehensive, Ireland-focused, state of scientific knowledge report on our understanding of climate change, its impacts on Ireland, the options to respond to the challenges it poses,and the opportunities from transitions and transformations to a climate-neutral, climate-resilient and sustainable economyand society. This serves to complement and localise the global assessments undertaken by the Intergovernmental Panel on Climate Change (IPCC) reports (see www.ipcc.ch). The findings presented build upon these global assessments and add important local and national context. Volume 1 focuses on the state of knowledge of the physical science basis of climate change, both globally and nationally. The volume contains information published from the IPCC AR6 WGI report, as well as material from the relevant Special Reports from the IPCC and various state agencies including EPA Ireland, Met Éireann and the Marine Institute. The volume updates and extends the analysis provided in the National State of Knowledge Reports on climate change (2012, 2017), and consolidates the current and ongoing research into climate change in Ireland, the observed changes in the climate system as well as future climate projections for Ireland

Healthcare transition in pediatric liver transplantation: The perspectives of pediatric and adult healthcare professionals.

INTRODUCTION Transition from pediatric to adult services of young people with a liver transplant is an important priority due to increasing numbers of young people surviving into adulthood. There is increased incidence of graft loss and non-adherence following transfer to adult services. Although studies have considered the views and perceptions of young people who have undergone liver transplantation and their parents about transition, there is currently no qualitative research with healthcare professionals working in the field of liver transplantation. The aim of this study was to elicit the views of this group of stakeholders about barriers and facilitators of an effective transition process. METHODS Semi-structured interviews were carried out with 11 HCPs from pediatric and adult liver transplant programs and from a range of professional backgrounds. Interviews were transcribed verbatim and analyzed using thematic analysis. RESULTS Four themes were identified: "non-adherence and psychosocial issues," "need for better psychological support," "the role of parents," and "the emotional impact of transition on healthcare professionals." Within these themes, professionals described factors which hindered or promoted an effective transition process. CONCLUSIONS Screening tools which address psychological and social aspects of the lives of young people should be used in routine practice to identify patients requiring psychosocial support and to identify those at risk of non-adherence. All staff involved with transition should be trained in the use of psychosocial screening strategies. The development of a formal referral pathway so that young people can access psychological support in adult services is recommended