Revised COGNOSAG guidelines for gene nomenclature in ruminants 1998

International audienc

Rhesus macaques vaccinated with consensus envelopes elicit partially protective immune responses against SHIV SF162p4 challenge

The development of a preventative HIV/AIDS vaccine is challenging due to the diversity of viral genome sequences, especially in the viral envelope (Env160). Since it is not possible to directly match the vaccine strain to the vast number of circulating HIV-1 strains, it is necessary to develop an HIV-1 vaccine that can protect against a heterologous viral challenge. Previous studies from our group demonstrated that a mixture of wild type clade B Envgp160s were able to protect against a heterologous clade B challenge more effectively than a consensus clade B Envgp160 vaccine. In order to broaden the immune response to other clades of HIV, in this study rhesus macaques were vaccinated with a polyvalent mixture of purified HIV-1 trimerized consensus Envgp140 proteins representing clades A, B, C, and E. The elicited immune responses were compared to a single consensus Envgp140 representing all isolates in group M (Con M). Both vaccines elicited anti- Envgp140 IgG antibodies that bound an equal number of HIV-1 Envgp160 proteins representing clades A, B and C. In addition, both vaccines elicited antibodies that neutralized the HIV-1SF162 isolate. However, the vaccinated monkeys were not protected against SHIV SF162p4 challenge. These results indicate that consensus Env gp160 vaccines, administered as purified Envgp140 trimers, elicit antibodies that bind to Envgp160s from strains representing multiple clades of HIV-1, but these vaccines did not protect against heterologous SHIV challenge. © 2013 Eugene et al.; licensee BioMed Central Ltd

Adverse prognostic and predictive significance of low DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in early-stage breast cancers

Background: DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a serine threonine kinase belonging to the PIKK family (phosphoinositide 3-kinase-like-family of protein kinase), is a critical component of the non-homologous end joining (NHEJ) pathway required for the repair of DNA double strand breaks. DNA-PKcs may be involved in breast cancer pathogenesis. Methods: We evaluated clinicopathological significance of DNA-PKcs protein expression in 1161 tumours and DNA-PKcs mRNA expression in 1950 tumours. We correlated DNA-PKcs to other markers of aggressive phenotypes, DNA repair, apoptosis and cell cycle regulation. Results: Low DNA-PKcs protein expression was associated with higher tumour grade, higher mitotic index, tumour de-differentiation and tumour type (ps<0.05). Absence of BRCA1, low XRCC1/SMUG1/APE1/Polβ were also more likely in low DNA-PKcs expressing tumours (ps<0.05). Low DNA-PKcs protein expression was significantly associated with worse breast cancer specific survival (BCCS) in univariate and multivariate analysis (ps<0.01). At the mRNA level, low DNA-PKcs was associated with PAM50.Her2 and PAM50.LumA molecular phenotypes (ps<0.01) and poor BCSS. In patients with ER positive tumours who received endocrine therapy, low DNA-PKcs (protein and mRNA) was associated with poor survival. In ER negative patients, low DNA-PKcs mRNA remains significantly associated with adverse outcome. Conclusions: Our study suggests that low DNA-PKcs expression may have prognostic and predictive significance in breast cancers

What is the real impact of acute kidney injury?

Background: Acute kidney injury (AKI) is a common clinical problem. Studies have documented the incidence of AKI in a variety of populations but to date we do not believe the real incidence of AKI has been accurately documented in a district general hospital setting. The aim here was to describe the detected incidence of AKI in a typical general hospital setting in an unselected population, and describe associated short and long-term outcomes. Methods: A retrospective observational database study from secondary care in East Kent (adult catchment population of 582,300). All adult patients (18 years or over) admitted between 1st February 2009 and 31st July 2009, were included. Patients receiving chronic renal replacement therapy (RRT), maternity and day case admissions were excluded. AKI was defined by the acute kidney injury network (AKIN) criteria. A time dependent risk analysis with logistic regression and Cox regression was used for the analysis of in-hospital mortality and survival. Results: The incidence of AKI in the 6 month period was 15,325 pmp/yr (adults) (69% AKIN1, 18% AKIN2 and 13% AKIN3). In-hospital mortality, length of stay and ITU utilisation all increased with severity of AKI. Patients with AKI had an increase in care on discharge and an increase in hospital readmission within 30 days. Conclusions: This data comes closer to the real incidence and outcomes of AKI managed in-hospital than any study published in the literature to date. Fifteen percent of all admissions sustained an episode of AKI with increased subsequent short and long term morbidity and mortality, even in those with AKIN1. This confers an increased burden and cost to the healthcare economy, which can now be quantified. These results will furnish a baseline for quality improvement projects aimed at early identification, improved management, and where possible prevention, of AKI

Isolated hepatic actinomycosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Actinomyces are slow growing, non-spore forming, gram-positive, branching bacilli that thrive in anaerobic and microareophilic conditions. Actinomyces are more commonly associated with oral and cervicofacial infections. Hepatic involvement in infections of the abdomen (known as isolated hepatic actinomycosis) is rare, accounting for only 5% of all cases of actinomycosis.</p> <p>Case presentation</p> <p>We present the case of a 75-year-old Caucasian woman with a 3-month history of night sweats, fever, chills, abdominal bloating, anorexia, weight-loss, and early satiety. The patient was found to have isolated hepatic actinomycosis infection after undergoing a laparotomy with a biopsy of the liver. The patient has now recovered.</p> <p>Conclusion</p> <p>Isolated hepatic actinomycosis is a rare and often overlooked etiology for a liver mass. Given its subacute presentation and nondescript symptomatology, physicians should be aware of this differential and the potential pitfalls in diagnosis and management.</p

Successful treatment of Mycobacterium ulcerans osteomyelitis with minor surgical debridement and prolonged rifampicin and ciprofloxacin therapy: a case report

ABSTRACT: INTRODUCTION: Treatment for osteomyelitis-complicating Mycobacterium ulcerans infection typically requires extensive surgery and even amputation, with no reported benefit from adjunctive antibiotics. CASE PRESENTATION: We report a case of an 87-year-old woman with M. ulcerans osteomyelitis that resolved following limited surgical debridement and 6 months of therapy with rifampicin and ciprofloxacin. CONCLUSION: M. ulcerans osteomyelitis can be successfully treated with limited surgical debridement and adjunctive oral antibiotics

Patient-physician interaction in general practice and health inequalities in a multidisciplinary study: design, methods and feasibility in the French INTERMEDE study

<p>Abstract</p> <p>Background</p> <p>The way in which patients and their doctors interact is a potentially important factor in optimal communication during consultations as well as treatment, compliance and follow-up care. The aim of this multidisciplinary study is to use both qualitative and quantitative methods to explore the 'black box' that is the interaction between the two parties during a general practice consultation, and to identify factors therein that may contribute to producing health inequalities. This paper outlines the original multidisciplinary methodology used, and the feasibility of this type of study.</p> <p>Methods and design</p> <p>The study design combines methodologies on two separate samples in two phases. Firstly, a qualitative phase collected ethnographical and sociological data during consultation, followed by in-depth interviews with both patients and doctors independently. Secondly, a quantitative phase on a different sample of patients and physicians collected data via several questionnaires given to patients and doctors consisting of specific 'mirrored' questions asked post-consultation, as well as collecting information on patient and physician characteristics.</p> <p>Discussion</p> <p>The design and methodology used in this study were both successfully implemented, and readily accepted by doctors and patients alike. This type of multidisciplinary study shows great potential in providing further knowledge into the role of patient/physician interaction and its influence on maintaining or producing health inequalities. The next challenge in this study will be implementing the multidisciplinary approach during the data analysis.</p

Selection for Replicases in Protocells

PMCID: PMC3649988This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

3-D Ultrastructure of O. tauri: Electron Cryotomography of an Entire Eukaryotic Cell

The hallmark of eukaryotic cells is their segregation of key biological functions into discrete, membrane-bound organelles. Creating accurate models of their ultrastructural complexity has been difficult in part because of the limited resolution of light microscopy and the artifact-prone nature of conventional electron microscopy. Here we explored the potential of the emerging technology electron cryotomography to produce three-dimensional images of an entire eukaryotic cell in a near-native state. Ostreococcus tauri was chosen as the specimen because as a unicellular picoplankton with just one copy of each organelle, it is the smallest known eukaryote and was therefore likely to yield the highest resolution images. Whole cells were imaged at various stages of the cell cycle, yielding 3-D reconstructions of complete chloroplasts, mitochondria, endoplasmic reticula, Golgi bodies, peroxisomes, microtubules, and putative ribosome distributions in-situ. Surprisingly, the nucleus was seen to open long before mitosis, and while one microtubule (or two in some predivisional cells) was consistently present, no mitotic spindle was ever observed, prompting speculation that a single microtubule might be sufficient to segregate multiple chromosomes

The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes

Many cases of non-standard genetic codes are known in mitochondrial genomes. We carry out analysis of phylogeny and codon usage of organisms for which the complete mitochondrial genome is available, and we determine the most likely mechanism for codon reassignment in each case. Reassignment events can be classified according to the gain-loss framework. The gain represents the appearance of a new tRNA for the reassigned codon or the change of an existing tRNA such that it gains the ability to pair with the codon. The loss represents the deletion of a tRNA or the change in a tRNA so that it no longer translates the codon. One possible mechanism is Codon Disappearance, where the codon disappears from the genome prior to the gain and loss events. In the alternative mechanisms the codon does not disappear. In the Unassigned Codon mechanism, the loss occurs first, whereas in the Ambiguous Intermediate mechanism, the gain occurs first. Codon usage analysis gives clear evidence of cases where the codon disappeared at the point of the reassignment and also cases where it did not disappear. Codon disappearance is the probable explanation for stop to sense reassignments and a small number of reassignments of sense codons. However, the majority of sense to sense reassignments cannot be explained by codon disappearance. In the latter cases, by analysis of the presence or absence of tRNAs in the genome and of the changes in tRNA sequences, it is sometimes possible to distinguish between the Unassigned Codon and Ambiguous Intermediate mechanisms. We emphasize that not all reassignments follow the same scenario and that it is necessary to consider the details of each case carefully.Comment: 53 pages (45 pages, including 4 figures + 8 pages of supplementary information). To appear in J.Mol.Evo