Origin and recent expansion of an endogenous gammaretroviral lineage in domestic and wild canids

Abstract Background Vertebrate genomes contain a record of retroviruses that invaded the germlines of ancestral hosts and are passed to offspring as endogenous retroviruses (ERVs). ERVs can impact host function since they contain the necessary sequences for expression within the host. Dogs are an important system for the study of disease and evolution, yet no substantiated reports of infectious retroviruses in dogs exist. Here, we utilized Illumina whole genome sequence data to assess the origin and evolution of a recently active gammaretroviral lineage in domestic and wild canids. Results We identified numerous recently integrated loci of a canid-specific ERV-Fc sublineage within Canis, including 58 insertions that were absent from the reference assembly. Insertions were found throughout the dog genome including within and near gene models. By comparison of orthologous occupied sites, we characterized element prevalence across 332 genomes including all nine extant canid species, revealing evolutionary patterns of ERV-Fc segregation among species as well as subpopulations. Conclusions Sequence analysis revealed common disruptive mutations, suggesting a predominant form of ERV-Fc spread by trans complementation of defective proviruses. ERV-Fc activity included multiple circulating variants that infected canid ancestors from the last 20 million to within 1.6 million years, with recent bursts of germline invasion in the sublineage leading to wolves and dogs.https://deepblue.lib.umich.edu/bitstream/2027.42/148209/1/12977_2019_Article_468.pd

Origin and recent expansion of an endogenous gammaretroviral lineage in domestic and wild canids

Background: Vertebrate genomes contain a record of retroviruses that invaded the germlines of ancestral hosts and are passed to offspring as endogenous retroviruses (ERVs). ERVs can impact host function since they contain the necessary sequences for expression within the host. Dogs are an important system for the study of disease and evolution, yet no substantiated reports of infectious retroviruses in dogs exist. Here, we utilized Illumina whole genome sequence data to assess the origin and evolution of a recently active gammaretroviral lineage in domestic and wild canids. Results: We identified numerous recently integrated loci of a canid-specific ERV-Fc sublineage within Canis, including 58 insertions that were absent from the reference assembly. Insertions were found throughout the dog genome including within and near gene models. By comparison of orthologous occupied sites, we characterized element prevalence across 332 genomes including all nine extant canid species, revealing evolutionary patterns of ERV-Fc segregation among species as well as subpopulations. Conclusions: Sequence analysis revealed common disruptive mutations, suggesting a predominant form of ERV-Fc spread by trans complementation of defective proviruses. ERV-Fc activity included multiple circulating variants that infected canid ancestors from the last 20 million to within 1.6 million years, with recent bursts of germline invasion in the sublineage leading to wolves and dogs

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Health, wellbeing and active citizenship

This paper is based on a current research project at the University of Huddersfield’s Institute for Health Citizenship. The research is exploring the understandings of health, wellbeing and citizenship by analysing the discourse of trainee further education (FE) lecturers. Initially, a literature review of policy documents was undertaken to identify dominant discourses in relation to health, wellbeing and inclusion. Two exploratory focus groups were held: one with a group of pre-service trainees and one with in service trainees. The policy literature suggests that ideas around health and wellbeing are being discursively repositioned. Whilst previously regarded as a fortunate state of being or condition, the dominant discourses now tend to construct health and wellbeing as contingent on individual behaviour – behaviour that is inextricably tied up with a particular model of citizenship and personal accountability. Put another way, the ‘good and active citizen’ must ‘choose’ to be healthy. Despite this individualisation, issues of health and wellbeing appear to be embedded within systems of surveillance, carried out by various state agencies, organisations and charities, including the further education sector. However, this surveillance and intervention is not straightforward. Initial findings from the focus groups suggest that trainee lecturers draw on conflicting discourses of health and wellbeing, and have developed counter discourses that resist or provide alternatives to the dominant model of ‘active citizenship’. This paper begins to disentangle the complexities between active citizenship, health and wellbeing and government public health policy, and how these directives are practised and understood at ground-level

Vascular dysfunction and the age‐related decline in critical power

Abstract Ageing results in lower exercise tolerance, manifested as decreased critical power (CP). We examined whether the age‐related decrease in CP occurs independently of changes in muscle mass and whether it is related to impaired vascular function. Ten older (63.1 ± 2.5 years) and 10 younger (24.4 ± 4.0 years) physically active volunteers participated. Physical activity was measured with accelerometry. Leg muscle mass was quantified with dual X‐ray absorptiometry. The CP and maximum power during a graded exercise test (PGXT) of single‐leg knee‐extension exercise were determined over the course of four visits. During a fifth visit, vascular function of the leg was assessed with passive leg movement (PLM) hyperaemia and leg blood flow and vascular conductance during knee‐extension exercise at 10 W, 20 W, slightly below CP (90% CP) and PGXT. Despite not differing in leg lean mass (P = 0.901) and physical activity (e.g., steps per day, P = 0.735), older subjects had ∼30% lower mass‐specific CP (old = 3.20 ± 0.94 W kg−1 vs. young = 4.60 ± 0.87 W kg−1; P < 0.001). The PLM‐induced hyperaemia and leg blood flow and/or conductance were blunted in the old at 20 W, 90% CP and PGXT (P < 0.05). When normalized for leg muscle mass, CP was strongly correlated with PLM‐induced hyperaemia (R2 = 0.52; P < 0.001) and vascular conductance during knee‐extension exercise at 20 W (R2 = 0.34; P = 0.014) and 90% CP (R2 = 0.39; P = 0.004). In conclusion, the age‐related decline in CP is not only an issue of muscle quantity, but also of impaired muscle quality that corresponds to impaired vascular function

Impact of Interrepetition Rest on Muscle Blood Flow and Exercise Tolerance during Resistance Exercise

Background and Objectives: Muscle blood flow is impeded during resistance exercise contractions, but immediately increases during recovery. The purpose of this study was to determine the impact of brief bouts of rest (2 s) between repetitions of resistance exercise on muscle blood flow and exercise tolerance. Materials and Methods: Ten healthy young adults performed single-leg knee extension resistance exercises with no rest between repetitions (i.e., continuous) and with 2 s of rest between each repetition (i.e., intermittent). Exercise tolerance was measured as the maximal power that could be sustained for 3 min (PSUS) and as the maximum number of repetitions (Reps80%) that could be performed at 80% one-repetition maximum (1RM). The leg blood flow, muscle oxygenation of the vastus lateralis and mean arterial pressure (MAP) were measured during various exercise trials. Alpha was set to p &le; 0.05. Results: Leg blood flow was significantly greater, while vascular resistance and MAP were significantly less during intermittent compared with continuous resistance exercise at the same power outputs (p &lt; 0.01). PSUS was significantly greater during intermittent than continuous resistance exercise (29.5 &plusmn; 2.1 vs. 21.7 &plusmn; 1.2 W, p = 0.01). Reps80% was also significantly greater during intermittent compared with continuous resistance exercise (26.5 &plusmn; 5.3 vs. 16.8 &plusmn; 2.1 repetitions, respectively; p = 0.02), potentially due to increased leg blood flow and muscle oxygen saturation during intermittent resistance exercise (p &lt; 0.05). Conclusions: In conclusion, a brief rest between repetitions of resistance exercise effectively decreased vascular resistance, increased blood flow to the exercising muscle, and increased exercise tolerance to resistance exercise