The complete genome sequence and comparative genome analysis of the high pathogenicity Yersinia enterocolitica strain 8081

The human enteropathogen, Yersinia enterocolitica, is a significant link in the range of Yersinia pathologies extending from mild gastroenteritis to bubonic plague. Comparison at the genomic level is a key step in our understanding of the genetic basis for this pathogenicity spectrum. Here we report the genome of Y. enterocolitica strain 8081 (serotype 0:8; biotype 1B) and extensive microarray data relating to the genetic diversity of the Y. enterocolitica species. Our analysis reveals that the genome of Y. enterocolitica strain 8081 is a patchwork of horizontally acquired genetic loci, including a plasticity zone of 199 kb containing an extraordinarily high density of virulence genes. Microarray analysis has provided insights into species-specific Y. enterocolitica gene functions and the intraspecies differences between the high, low, and nonpathogenic Y. enterocolitica biotypes. Through comparative genome sequence analysis we provide new information on the evolution of the Yersinia. We identify numerous loci that represent ancestral clusters of genes potentially important in enteric survival and pathogenesis, which have been lost or are in the process of being lost, in the other sequenced Yersinia lineages. Our analysis also highlights large metabolic operons in Y. enterocolitica that are absent in the related enteropathogen, Yersinia pseudotuberculosis, indicating major differences in niche and nutrients used within the mammalian gut. These include clusters directing, the production of hydrogenases, tetrathionate respiration, cobalamin synthesis, and propanediol utilisation. Along with ancestral gene clusters, the genome of Y. enterocolitica has revealed species-specific and enteropathogen-specific loci. This has provided important insights into the pathology of this bacterium and, more broadly, into the evolution of the genus. Moreover, wider investigations looking at the patterns of gene loss and gain in the Yersinia have highlighted common themes in the genome evolution of other human enteropathogens

A study of prisms and therapy in attention loss after stroke (SPATIAL): A feasibility randomised controlled trial running title: SPATIAL feasibility trial

Objective: Investigate feasibility and acceptability of prism adaptation training (PAT) for people with inattention, early after stroke, in a usual care setting.Design: Phase II feasibility randomised controlled trial with 3:1 stratified allocation to standard occupational therapy with or without PAT, and nested process evaluation (qualitative interviews with stakeholders).Setting: Ten NHS sites providing in-patient stroke services.Participants: Screened positive for inattention >one-week post-stroke; informal carers. Occupational therapists participated in qualitative interviews. Intervention: Adjunctive PAT at the start of standard occupational therapy sessions for three weeks.Main measures: Feasibility measures included recruitment and retention rates, intervention fidelity and attrition. Outcomes collected at baseline, three weeks and 12 weeks tested candidate measures including Nottingham Extended Activities of Daily Living Scale (NEADL). Acceptability was explored through qualitative interviews and structured questions.Results: Eighty (31%) patients were eligible, 57 (71%) consented, 54 randomised (40:13, +1 exclusion) and 39 (74%) completed 12-week outcomes. Treatment fidelity was good: participants received median eight PAT sessions (IQR: 5, 12) lasting 4.7 minutes (IQR: 4.1, 5.0). All six serious adverse events were unrelated. There was no signal that patients allocated to PAT did better than without. Twenty five of 35 recruited carers provided outcomes with excellent data completeness. Therapists, patients and carers found PAT acceptable. Conclusions: It is feasible and acceptable to conduct a high-quality definitive trial of PAT within occupational therapy early after stroke in usual care setting, but difficult to justify given no sign of benefit over standard occupational therapy.Clinical trial registration: https://www.isrctn.com/ Ref ISRCTN8839526

Complete genome of acute rheumatic fever-associated serotype M5 Streptococcus pyogenes strain Manfredo

Comparisons of the 1.84-Mb genome of serotype M5 Streptococcus pyogenes strain Manfredo with previously sequenced genomes emphasized the role of prophages in diversification of S. pyogenes and the close relationship between strain Manfredo and MGAS8232, another acute rheumatic fever-associated strain

Intra- and Interhost Evolutionary Dynamics of Equine Influenza Virus▿ §

Determining the evolutionary basis of cross-species transmission and immune evasion is key to understanding the mechanisms that control the emergence of either new viruses or novel antigenic variants with pandemic potential. The hemagglutinin glycoprotein of influenza A viruses is a critical host range determinant and a major target of neutralizing antibodies. Equine influenza virus (EIV) is a significant pathogen of the horse that causes periodical outbreaks of disease even in populations with high vaccination coverage. EIV has also jumped the species barrier and emerged as a novel respiratory pathogen in dogs, canine influenza virus. We studied the dynamics of equine influenza virus evolution in horses at the intrahost level and how this evolutionary process is affected by interhost transmission in a natural setting. To this end, we performed clonal sequencing of the hemagglutinin 1 gene derived from individual animals at different times postinfection. Our results show that despite the population consensus sequence remaining invariant, genetically distinct subpopulations persist during the course of infection and are also transmitted, with some variants likely to change antigenicity. We also detected a natural case of mixed infection in an animal infected during an outbreak of equine influenza, raising the possibility of reassortment between different strains of virus. In sum, our data suggest that transmission bottlenecks may not be as narrow as originally perceived and that the genetic diversity required to adapt to new host species may be partially present in the donor host and potentially transmitted to the recipient host