traT gene sequences, serum resistance and pathogenicity-related factors in clinical isolates of Escherichia coli and other gram-negative bacteria

The R6-5 plasmid-specified outer membrane protein, TraT protein, has previously been shown to mediate resistance to bacterial killing by serum. Colony hybridization with a 700 bp DNA fragment carrying most of the traT gene was used to examine the prevalence of traT in Gram-negative bacteria, particularly strains of Escherichia coli, isolated from clinical specimens. traT was found in isolates of E. coli, Salmonella, Shigella and Klebsiella, but not in Pseudomonas, Aeromonas or Plesiomonas, nor in the few isolates of Enterobacter, Proteus, Acinetobacter, Citrobacter, Serratia or Yersinia that were examined. It was detected in a significantly higher proportion of the E. coli strains isolated from the blood of patients with bacteraemia/septicaemia or from faeces of patients with enteric infections (50-70%) than in that of strains isolated from normal faeces (20-40%). The incidence of traT in strains isolated from cases of urinary tract infections was variable. traT was found to be frequently associated with production of the K1 capsule and with the carriage of ColV plasmids, but not with the carriage of R plasmids, nor with serum resistance or the production of haemolysin

Type and timing of heralding in ST-elevation and non-ST-elevation myocardial infarction: an analysis of prospectively collected electronic healthcare records linked to the national registry of acute coronary syndromes.

AIMS: It is widely thought that ST-elevation myocardial infarction (STEMI) is more likely to occur without warning (i.e. an unanticipated event in a previously healthy person) than non-ST-elevation myocardial infarction (NSTEMI), but no large study has evaluated this using prospectively collected data. The aim of this study was to compare the evolution of atherosclerotic disease and cardiovascular risk between people going on to experience STEMI and NSTEMI. METHODS: We identified patients experiencing STEMI and NSTEMI in the national registry of myocardial infarction for England and Wales (Myocardial Ischaemia National Audit Project), for whom linked primary care records were available in the General Practice Research Database (as part of the CALIBER collaboration). We compared the prevalence and timing of atherosclerotic disease and major cardiovascular risk factors including smoking, hypertension, diabetes, and dyslipidaemia, between patients later experiencing STEMI to those experiencing NSTEMI. RESULTS: A total of 8174 myocardial infarction patients were included (3780 STEMI, 4394 NSTEMI). Myocardial infarction without heralding by previously diagnosed atherosclerotic disease occurred in 71% STEMI (95% CI 69-72%) and 50% NSTEMI patients (95% CI 48-51%). The proportions of myocardial infarctions with no prior atherosclerotic disease, major risk factors, or chest pain was 14% (95% CI 13-16%) in STEMI and 9% (95% CI 9-10%) in NSTEMI. The rate of heralding coronary diagnoses was particularly high in the 12 months before infarct; 4.1-times higher (95% CI 3.3-5.0) in STEMI and 3.6-times higher (95% CI 3.1-4.2) in NSTEMI compared to the rate in earlier years. CONCLUSIONS: Acute myocardial infarction occurring without prior diagnosed coronary, cerebrovascular, or peripheral arterial disease was common, especially for STEMI. However, there was a high prevalence of risk factors or symptoms in patients without previously diagnosed disease. Better understanding of the antecedents in the year before myocardial infarction is required

Characterization of the Basic Replicon of pCM1, a Narrow- Host-Range Plasmid from the Moderate Halophile Chromohalobacter marismortui

The moderately halophilic bacterium Chromohalobacter marismortui contains a 17.5-kb narrow-host-range plasmid, pCM1, which shows interesting properties for the development of cloning vectors for the genetic manipulation of this important group of extremophiles. Plasmid pCM1 can stably replicate and is maintained in most gram-negative moderate halophiles tested. The replication origin has been identified and sequenced, and the minimal pCM1 replicon has been localized to a 1,600-bp region which includes two functionally discrete regions, the oriV region and the repA gene. oriV, located on a 700-bp fragment, contains four iterons 20 bp in length adjacent to a DnaA box that is dispensable but required for efficient replication of pCM1, and it requires trans-acting functions. The repA gene, which encodes a replication protein of 289 residues, is similar to the replication proteins of other gram-negative bacteria

Weaponising microbes for peace

There is much human disadvantage and unmet need in the world, including deficits in basic resources and services considered to be human rights, such as drinking water, sanitation and hygiene, healthy nutrition, access to basic healthcare, and a clean environment. Furthermore, there are substantive asymmetries in the distribution of key resources among peoples. These deficits and asymmetries can lead to local and regional crises among peoples competing for limited resources, which, in turn, can become sources of discontent and conflict. Such conflicts have the potential to escalate into regional wars and even lead to global instability. Ergo: in addition to moral and ethical imperatives to level up, to ensure that all peoples have basic resources and services essential for healthy living and to reduce inequalities, all nations have a self-interest to pursue with determination all available avenues to promote peace through reducing sources of conflicts in the world. Microorganisms and pertinent microbial technologies have unique and exceptional abilities to provide, or contribute to the provision of, basic resources and services that are lacking in many parts of the world, and thereby address key deficits that might constitute sources of conflict. However, the deployment of such technologies to this end is seriously underexploited. Here, we highlight some of the key available and emerging technologies that demand greater consideration and exploitation in endeavours to eliminate unnecessary deprivations, enable healthy lives of all and remove preventable grounds for competition over limited resources that can escalate into conflicts in the world. We exhort central actors: microbiologists, funding agencies and philanthropic organisations, politicians worldwide and international governmental and non-governmental organisations, to engage – in full partnership – with all relevant stakeholders, to ‘weaponise’ microbes and microbial technologies to fight resource deficits and asymmetries, in particular among the most vulnerable populations, and thereby create humanitarian conditions more conducive to harmony and peace.Natural History Museum; Indian National Science Academ

Methodologies for quantitative systems pharmacology (QSP) models:Design and Estimation

With the increased interest in the application of quantitative systems pharmacology (QSP) models within medicine research and development, there is an increasing need to formalize model development and verification aspects. In February 2016, a workshop was held at Roche Pharma Research and Early Development to focus discussions on two critical methodological aspects of QSP model development: optimal structural granularity and parameter estimation. We here report in a perspective article a summary of presentations and discussions.</p

PTCHD1 Binds Cholesterol but Not Sonic Hedgehog, Suggesting a Distinct Cellular Function

Deleterious mutations in the X-linked Patched domain-containing 1 (PTCHD1) gene may account for up to 1% of autism cases. Despite this, the PTCHD1 protein remains poorly understood. Structural similarities to Patched family proteins point to a role in sterol transport, but this hypothesis has not been verified experimentally. Additionally, PTCHD1 has been suggested to be involved in Hedgehog signalling, but thus far, the experimental results have been conflicting. To enable a variety of biochemical and structural experiments, we developed a method for expressing PTCHD1 in Spodoptera frugiperda cells, solubilising it in glycol-diosgenin, and purifying it to homogeneity. In vitro and in silico experiments show that PTCHD1 function is not interchangeable with Patched 1 (PTCH1) in canonical Hedgehog signalling, since it does not repress Smoothened in Ptch1−/− mouse embryonic fibroblasts and does not bind Sonic Hedgehog. However, we found that PTCHD1 binds cholesterol similarly to PTCH1. Furthermore, we identified 13 PTCHD1-specific protein interactors through co-immunoprecipitation and demonstrated a link to cell stress responses and RNA stress granule formation. Thus, our results support the notion that despite structural similarities to other Patched family proteins, PTCHD1 may have a distinct cellular function

Visual search behaviour in young cyclists: A naturalistic experiment

Description to be added.Cannot be left empt

Assessing the cost effectiveness of using prognostic biomarkers with decision models: case study in prioritising patients waiting for coronary artery surgery

Objective To determine the effectiveness and cost effectiveness of using information from circulating biomarkers to inform the prioritisation process of patients with stable angina awaiting coronary artery bypass graft surgery

Complete chloroplast genome sequence of Holoparasite Cistanche Deserticola (Orobanchaceae) reveals gene loss and horizontal gene transfer from Its host Haloxylon Ammodendron (Chenopodiaceae)

The central function of chloroplasts is to carry out photosynthesis, and its gene content and structure are highly conserved across land plants. Parasitic plants, which have reduced photosynthetic ability, suffer gene losses from the chloroplast (cp) genome accompanied by the relaxation of selective constraints. Compared with the rapid rise in the number of cp genome sequences of photosynthetic organisms, there are limited data sets from parasitic plants. The authors report the complete sequence of the cp genome of Cistanche deserticola, a holoparasitic desert species belonging to the family Orobanchaceae