2,791 research outputs found

    A recommended numbering scheme for influenza A HA subtypes.

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    Comparisons of residues between sub-types of influenza virus is increasingly used to assess the zoonotic potential of a circulating strain and for comparative studies across subtypes. An analysis of N-terminal cleavage sites for thirteen subtypes of influenza A hemagglutinin (HA) sequences, has previously been described by Nobusawa and colleagues. We have expanded this analysis for the eighteen known subtypes of influenza. Due to differences in the length of HA, we have included strains from multiple clades of H1 and H5, as well as strains of H5 and H7 subtypes with both high and low pathogenicity. Analysis of known structures of influenza A HA enables us to define amino acids which are structurally and functionally equivalent across all HA subtypes using a numbering system based on the mature HA sequence. We provide a list of equivalences for amino acids which are known to affect the phenotype of the virus.Funding provided by (DJS) Bill & Melinda Gates Foundation Global Health (http://www.gatesfoundation.org/) Grant # OPPGH5383, (DJS) European Union FP7 program ANTIGONE (http://cordis.europa.eu/programme/rcn/852_en.html) (278976) and (DJS) National Institute of Allergy and Infectious disease (http://www.niaid.nih.gov) Contract HHSN266200700010C. The funders had no role in the study design, data collection, analysis, decision to publish or preparation of the manuscript.This is the final published version. It originally appeared at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0112302

    The evolution of the natural killer complex; a comparison between mammals using new high-quality genome assemblies and targeted annotation.

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    Natural killer (NK) cells are a diverse population of lymphocytes with a range of biological roles including essential immune functions. NK cell diversity is in part created by the differential expression of cell surface receptors which modulate activation and function, including multiple subfamilies of C-type lectin receptors encoded within the NK complex (NKC). Little is known about the gene content of the NKC beyond rodent and primate lineages, other than it appears to be extremely variable between mammalian groups. We compared the NKC structure between mammalian species using new high-quality draft genome assemblies for cattle and goat; re-annotated sheep, pig, and horse genome assemblies; and the published human, rat, and mouse lemur NKC. The major NKC genes are largely in the equivalent positions in all eight species, with significant independent expansions and deletions between species, allowing us to propose a model for NKC evolution during mammalian radiation. The ruminant species, cattle and goats, have independently evolved a second KLRC locus flanked by KLRA and KLRJ, and a novel KLRH-like gene has acquired an activating tail. This novel gene has duplicated several times within cattle, while other activating receptor genes have been selectively disrupted. Targeted genome enrichment in cattle identified varying levels of allelic polymorphism between the NKC genes concentrated in the predicted extracellular ligand-binding domains. This novel recombination and allelic polymorphism is consistent with NKC evolution under balancing selection, suggesting that this diversity influences individual immune responses and may impact on differential outcomes of pathogen infection and vaccination

    Serological responses to IBR viral vaccine and Mannheimia haemolytica bacterin/leukotoxoid administered with needle-free injection technology

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    Yearling steers were randomized to treatment and vaccinated with 5-way modified live viral vaccine and Mannheimia haemolytica bacterin/toxoid by using either needle-free or standard needle injection. Blood samples were collected from all animals at the time of vaccination and 21 days later, and the serum was analyzed for antibody titers to infectious bovine rhinotracheitis (IBR) virus and M. haemolytica leukotoxoid. Serological responses to the IBR viral fraction of the 5-way viral vaccine were significantly greater on day 21 after administration with the needle-free injection system. Serological responses to the M. haemolytica leukotoxoid tended to be greater on day 21 after administration with the needle-free injection system

    Outcomes following oesophagectomy in patients with oesophageal cancer: a secondary analysis of the ICNARC Case Mix Programme Database

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    Introduction: This report describes the case mix and outcomes of patients with oesophageal cancer admitted to adult critical care units following elective oesophageal surgery in England, Wales and Northern Ireland. Methods: Admissions to critical care following elective oesophageal surgery for malignancy were identified using data from the Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme Database. Information on admissions between December 1995 and September 2007 were extracted and the association between in-hospital mortality and patient characteristics on admission to critical care was assessed using multiple logistic regression analysis. The performance of three prognostic models (Simplified Acute Physiology Score (SAPS) II, Acute Physiology and Chronic Health Evaluation (APACHE) II and the ICNARC physiology score) was also evaluated. Results: Between 1995 and 2007, there were 7227 admissions to 181 critical care units following oesophageal surgery for malignancy. Overall mortality in critical care was 4.4% and in-hospital mortality was 11%, although both declined steadily over time. Eight hundred and seventy-three (12.2%) patients were readmitted to critical care, most commonly for respiratory complications (49%) and surgical complications (25%). Readmitted patients had a critical care unit mortality of 24.7% and in-hospital mortality of 33.9%. Overall in-hospital mortality was associated with patient age, and various physiological measurements on admission to critical care (partial pressure of arterial oxygen (PaO2):fraction of inspired oxygen (FiO2) ratio, lowest arterial pH, mechanical ventilation, serum albumin, urea and creatinine). The three prognostic models evaluated performed poorly in measures of discrimination, calibration and goodness of fit. Conclusions: Surgery for oesophageal malignancy continues to be associated with significant morbidity and mortality. Age and organ dysfunction in the early postoperative period are associated with an increased risk of death. Postoperative serum albumin is confirmed as an additional prognostic factor. More work is required to determine how this knowledge may improve clinical management

    Serological evidence for non-lethal exposures of Mongolian wild birds to highly pathogenic avian influenza H5N1 virus.

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    Surveillance for highly pathogenic avian influenza viruses (HPAIV) in wild birds is logistically demanding due to the very low rates of virus detection. Serological approaches may be more cost effective as they require smaller sample sizes to identify exposed populations. We hypothesized that antigenic differences between classical Eurasian H5 subtype viruses (which have low pathogenicity in chickens) and H5N1 viruses of the Goose/Guangdong/96 H5 lineage (which are HPAIV) may be used to differentiate populations where HPAIVs have been circulating, from those where they have not. To test this we performed hemagglutination inhibition assays to compare the reactivity of serum samples from wild birds in Mongolia (where HPAIV has been circulating, n = 1,832) and Europe (where HPAIV has been rare or absent, n = 497) to a panel of reference viruses including classical Eurasian H5 (of low pathogenicity), and five HPAIV H5N1 antigens of the Asian lineage A/Goose/Guangdong/1/96. Antibody titres were detected against at least one of the test antigens for 182 Mongolian serum samples (total seroprevalence of 0.10, n = 1,832, 95% adjusted Wald confidence limits of 0.09-0.11) and 25 of the European sera tested (total seroprevalence of 0.05, n = 497, 95% adjusted Wald confidence limits of 0.03-0.07). A bias in antibody titres to HPAIV antigens was found in the Mongolian sample set (22/182) that was absent in the European sera (0/25). Although the interpretation of serological data from wild birds is complicated by the possibility of exposure to multiple strains, and variability in the timing of exposure, these findings suggest that a proportion of the Mongolian population had survived exposure to HPAIV, and that serological assays may enhance the targeting of traditional HPAIV surveillance toward populations where isolation of HPAIV is more likely.Funding for this work was provided by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), and the Department of Health and Human Services under contracts HHSN266200700007C and HHSN266200700010C. Further support was provided through a doctoral training grant to MG by the Biotechnology and Biological Sciences Research Council (BB/F016786/1).This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/ 10.1371/journal.pone.011356

    Organisational Trust: A Case Application in the Air Transport Sector.

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    From a management perspective, it is important to know what the likely feedback effects of efficiency drives might be on levels of employee trust. This paper looks to apply this important question to a case application in the air transport sector by testing the use of recent efficiency measures in a case sample of air transport companies using a modified aggregate trust model. The findings of this study suggest efficiency creating tactics do not lead to resentment and conditions of mistrust in themselves. Rather, occupational group (flight crew/non-flight crew), airline type (FSA,LCC, Charter), and level of seniority (management/non-management level) all have a more important bearing on the employee-employer relationship. Pre-existing labour agreements and legacy arrangements with senior and certain occupational groups were found to have a more damaging effect on the trust relationship than anything else. An underlying level of resentment and defensiveness has developed due to historical agreements being changed and have been observed most notably among FSAs, flight-crew and middle-management staff. The mediating role of the unions in the employee-employer trust relationship was found to be insignificant among the sampled air transport organisations

    Organisational Trust: a case Application In The Air Transport Sector

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    In management, it is important to know what the likely feedback effects of employee-employer relationship outcomes might be on levels of ongoing employee trust. This paper looks to apply this important question to a case application of the air transport sector by testing the impact of recent changes in a case sample of air transport companies using a modified aggregate trust model. The findings of this study suggest that occupational group (flight crew/non-flight crew), airline type (FSA, LCC, Charter), and level of seniority (management/non-management level) all have an important bearing on levels of trust in the employee-employer relationship. Pre-existing labour agreements and legacy arrangements with senior and certain occupational groups were found to have a more damaging effect on the trust relationship than anything else. An underlying level of resentment and defensiveness has developed due to historical labour agreements being changed and have been observed most notably among FSAs, flight-crew and middle-management staff. The mediating role of the unions in the employee-employer trust relationship was found to be insignificant among the sampled air transport organisations mainly due to the perceived weakness among the sampled employees of unions to make any meaningful interventions

    Acclimatization to high-variance habitats does not enhance physiological tolerance of two key Caribbean corals to future temperature and pH

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    Corals are acclimatized to populate dynamic habitats that neighbour coral reefs. Habitats such as seagrass beds exhibit broad diel changes in temperature and pH that routinely expose corals to conditions predicted for reefs over the next 50–100 years. However, whether such acclimatization effectively enhances physiological tolerance to, and hence provides refuge against, future climate scenarios remains unknown. Also, whether corals living in low-variance habitats can tolerate present-day high-variance conditions remains untested. We experimentally examined how pH and temperature predicted for the year 2100 affects the growth and physiology of two dominant Caribbean corals (Acropora palmata and Porites astreoides) native to habitats with intrinsically low (outer-reef terrace, LV) and/or high (neighbouring seagrass, HV) environmental variance. Under present-day temperature and pH, growth and metabolic rates (calcification, respiration and photosynthesis) were unchanged for HV versus LV populations. Superimposing future climate scenarios onto the HV and LV conditions did not result in any enhanced tolerance to colonies native to HV. Calcification rates were always lower for elevated temperature and/or reduced pH. Together, these results suggest that seagrass habitats may not serve as refugia against climate change if the magnitude of future temperature and pH changes is equivalent to neighbouring reef habitats

    Epistatic interactions can moderate the antigenic effect of substitutions in haemagglutinin of influenza H3N2 virus.

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    We previously showed that single amino acid substitutions at seven positions in haemagglutinin determined major antigenic change of influenza H3N2 virus. Here, the impact of two such substitutions was tested in 11 representative H3 haemagglutinins to investigate context-dependence effects. The antigenic effect of substitutions introduced at haemagglutinin position 145 was fully independent of the amino acid context of the representative haemagglutinins. Antigenic change caused by substitutions introduced at haemagglutinin position 155 was variable and context-dependent. Our results suggest that epistatic interactions with contextual amino acids in the haemagglutinin can moderate the magnitude of antigenic change
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