John Radcliffe Hospital

About: John Radcliffe Hospital is a healthcare organization based out in Oxford, Oxfordshire, United Kingdom. It is known for research contribution in the topics: Population & Antigen. The organization has 14491 authors who have published 23670 publications receiving 1459015 citations.

The oligopeptide transport system of Bacillus subtilis plays a role in the initiation of sporulation.

Abstract: Bacillus subtilis spo0K mutants are blocked at the first step in sporulation. The spo0K strain was found to contain two mutations: one was linked to the trpS locus, and the other was elsewhere on the chromosome. The mutation linked to trpS was responsible for the sporulation defect (spo-). The unlinked mutation enhanced this sporulation deficiency but had no phenotype on its own. The spo- mutation was located in an operon of five genes highly homologous to the oligopeptide transport (Opp) system of Gram-negative species. Studies with toxic peptide analogues showed that this operon does indeed encode a peptide-transport system. However, unlike the Opp system of Salmonella typhimurium, one of the two ATP-binding proteins, OppF, was not required for peptide transport or for sporulation. The OppA peptide-binding protein, which is periplasmically located in Gram-negative species, has a signal sequence characteristic of lipoproteins with an amino-terminal lipo-amino acid anchor. Cellular location studies revealed that OppA was associated with the cell during exponential growth, but was released into the medium in stationary phase. A major role of the Opp system in Gram-negative bacteria is the recycling of cell-wall peptides as they are released from the growing peptidoglycan. We postulate that the accumulation of such peptides may play a signalling role in the initiation of sporulation, and that the sporulation defect in opp mutants results from an inability to transport these peptides.

Sleep and circadian rhythm disruption in schizophrenia

Abstract: Sleep disturbances comparable with insomnia occur in up to 80% of people with schizophrenia, but very little is known about the contribution of circadian coordination to these prevalent disruptions.

Inflammatory processes in cardiovascular disease: a route to targeted therapies

Abstract: Inflammatory processes are firmly established as central to the development and complications of cardiovascular diseases. Elevated levels of inflammatory markers have been shown to be predictive of future cardiovascular events. The specific targeting of these processes in experimental models has been shown to attenuate myocardial and arterial injury, reduce disease progression, and promote healing. However, the translation of these observations and the demonstration of clear efficacy in clinical practice have been disappointing. A major limitation might be that tools currently used to measure 'inflammation' are insufficiently precise and do not provide information about disease site and activity, or discriminate between functionally important activation pathways. The challenge, therefore, is to make measures of inflammation that are more meaningful, and which can guide specific targeted therapies. In this Review, we consider the roles of inflammatory processes in the related pathologies of atherosclerosis and acute myocardial infarction, by providing an evaluation of the known and emerging inflammatory pathways. We highlight contemporary techniques to characterize and quantify inflammation, and consider how they might be used to guide specific treatments. Finally, we discuss emerging opportunities in the field, including their current limitations and challenges that are the focus of ongoing study.

Microarrays Reveal that Each of the Ten Dominant Lineages of Staphylococcus aureus Has a Unique Combination of Surface-Associated and Regulatory Genes

Abstract: Staphylococcus aureus is a persistent resident of the human nose in 20% of the population and intermittently carried by another 60% (16). Most carriers harbor a single strain (2). S. aureus is a common cause of minor skin and wound infections, but only rarely causes severe community-acquired invasive infections such as bacteremia, endocarditis, and osteomyelitis. In contrast, S. aureus is the most common cause of hospital-acquired infection, which often occurs in association with breaches of the skin and mucous membranes in the immunocompromised host (14). Hundreds of S. aureus virulence factors and putative virulence genes have been described, including those involved in adherence to human tissue, evasion of the immune response, toxin secretion, and regulation of virulence gene expression (29). Specific toxins have also been described that play a pivotal role in toxin-mediated disease such as toxic shock syndrome (toxic shock syndrome toxin-1, encoded by tst; enterotoxins B and C, encoded by seb, sec) (5), scalded skin syndrome (exfoliative toxins A and B, encoded by eta, etb) (19), food poisoning (enterotoxin A, encoded by sea) (5), and more recently hemolytic pneumonia and skin and soft tissue infection (Panton Valentine leukocidin [PVL], encoded by the lukS-PV and lukF-PV genes) (20). Many of these genes are variably present as a result of being carried on mobile genetic elements (MGE) (22). However, critical to the development of targeted or preventive strategies is the elucidation of which if any of these genes are important in invasive infection. An important isolate collection associated with community-acquired invasive disease or carriage by healthy donors in the Oxford, United Kingdom, region (7) has been examined using multilocus sequence typing (MLST) (6), in which fragments of seven housekeeping genes were amplified and sequenced. Unique alleles at the seven loci were given an allelic number, and the allelic profile (string of seven integers) was used to define sequence type (ST) for each isolate. Isolates with an identical profile were considered to be clonal, and those with at least five of seven matching genes were considered to belong to the same clonal cluster (CC). Isolates clustered into 10 major CCs, none of which were associated with invasive disease (7). This argued against the presence of virulent genotypes but did not exclude the possibility that one or more variable genes were overrepresented in the invasive-isolate group. This possibility was examined during a study that defined the presence or absence of 33 putative virulence genes in this isolate collection using PCR (27). Seven genes were found to be present more commonly in invasive isolates, including eta and those encoding fibronectin binding protein A (fnbA), collagen binding protein (cna), serine-aspartate repeat containing protein E (sdrE), staphylococcal enterotoxin J (sej), gamma-hemolysin (hlg), and intracellular adhesin (ica). This suggested there were differences between isolates that did not correlate with lineage. It also suggested that some isolates are potentially more virulent than others. Each S. aureus isolate is thought to carry hundreds of variable genes including many putative virulence determinants. The first S. aureus comparative-genomics studies using a microarray (covering 92% of the genes found in the S. aureus COL genome) estimated that 22% of the S. aureus genome was variable (8). Many of the variable genes are known or putative virulence and resistance genes carried on MGE, and these elements are likely to transfer horizontally among staphylococci (see reference 22 for a review). The accumulation of such MGE may result in the emergence of “superbugs” that are increasingly resistant and virulent (22). The whole-genome sequencing of seven isolates of S. aureus (1, 10, 12, 18; www.genome.ou.edu/staph.html) has allowed us to design, print, and validate a multistrain PCR product S. aureus microarray carrying PCR products for every gene identified from these projects, probably the most comprehensive microarray of its kind (33). Here we describe the use of the seven-strain S. aureus microarray to investigate the Oxford collection of community-acquired S. aureus isolates. The aims were to identify which regions of the S. aureus genome vary, investigate gene distribution in a typical S. aureus population, and perform a comprehensive search for differences between invasive and carriage isolates.