Lipids of the Spirochaetales: Comparison of the Lipids of Several Members of the Genera Spirochaeta, Treponema, and Leptospira

The lipid compositions of 17 spirochetes belonging to the genera Spirochaeta and Treponema were investigated and compared with data previously derived from 11 strains of Leptospira. The lipid compositions and lipid metabolism of any of these genera is sufficiently different to be characteristic of that genus and to differentiate it from the other two genera. Members of the genus Leptospira are characterized by their ability to beta-oxidize long chain fatty acids as their major carbon and energy source. With few exceptions, they are incapable of synthesizing fatty acids de novo. The major phospholipid found was phosphatidyl ethanolamine. No glycolipid or phosphatidyl choline was found in these organisms. Members of the genus Treponema studied were incapable of beta-oxidation as well as de novo synthesis of fatty acids. Phosphatidyl choline is the major phospholipid of this genus. The glycolipid, monogalactosyl diglyceride, is a major component of the Treponema. Members of the Spirochaeta did synthesize fatty acids de novo. Although these spirochetes contain a monoglycosyl diglyceride, the hexose content of the glycolipid varied from species to species. Neither phosphatidyl ethanolamine nor phosphatidyl choline was found in the Spirochaeta.     

Evidence of dimerisation among class D beta-lactamases: kinetics of OXA-14 beta-lactamase

OXA-14 enzyme, a class D beta-lactamase, gave biphasic kinetics with all penicillin and cephalosporin substrates tested, such that the catalytic rate declined more swiftly than was explicable by substrate depletion. This biphasic behaviour was independent of temperature or extraneous protein but was lost if the enzyme was diluted to occupy almost the total assay volume before addition of a small amount of concentrated substrate. The presence of substrate could partially protect the enzyme against conversion to the less active form, with protection greatest at substrate concentration above the K(m). These observations are compatible with the hypothesis that the biphasic kinetics depended on the enzyme existing as a highly active dimer at high concentration and as a less active monomer at low concentration. Direct evidence supporting this hypothesis came from the observation that gel exclusion chromatography indicated a higher molecular weight for concentrated enzyme than for dilute. Biphasic kinetics are not so universal for different substrates amongst beta-lactamases (OXA-10, -11, -13, -16 and -17) that differ from OXA-14 by only one to two amino acid substitutions. It may be that the monomer:dimer equilibrium is more rapidly achieved with these enzymes than with OXA-14, or that the kinetic properties of the dimers and monomers of these enzymes are similar, masking any biphasic trait.     

The influence of training on chemosensory event-related potentials and interactions between the olfactory and trigeminal systems

It is not possible to accurately predict the perceptual response to odorants and odorant mixtures without understanding patterns of suppression and facilitation that result from interactions between the olfactory and trigeminal systems. The current study extends previous findings by exploring the effect of intensive training on the interaction between these systems and also by using a different mixed chemosensory stimulus to examine whether the principles established in earlier studies generalize to different odorants. Stimuli were chosen so as to selectively activate the olfactory (H2S) and trigeminal (CO2) nerves. In addition, linalool was included as a stimulus that activated both systems. Thirty-five participants (19 men, 16 women) rated the intensity of each stimulus when presented both alone and in binary mixtures (linalool + H2S, and linalool + CO2). Chemosensory event-related potentials were obtained from three recording positions. Analysis of intensity ratings showed that linalool was significantly less intense than the other stimuli when presented alone. In binary mixtures, H2S was strongly suppressed by linalool. One week of intensive odor training produced significant and specific reductions in the intensity of linalool and H2S, both alone and in their mixture. Training with a different odor (champignol) had no effect. Chemosensory event-related potential data confirmed previous findings showing changes in topographical distribution that reflected the degree of trigeminal activity. Binary mixtures generally produced larger amplitudes than single stimuli. Latencies clearly differentiated between the three single stimuli and the binary mixtures. Changes were observed in event-related potentials that reflected those obtained for intensity ratings in that they were observed for linalool and H2S in the linalool trained group only. The amplitude of the late 'endogenous' component (P3) was significantly decreased for these odors at frontal recording sites. In summary, strong and specific training effects were observed in intensity ratings for participants trained with the test odor (linalool), but not for those trained with a different odor. This was supported by a significant decrease of amplitudes of the event-related potentials at frontal recording sites following training with the test odor only     

Protective effect of antibiotics against serious complications of common respiratory tract infections: retrospective cohort study with the UK General Practice Research Database

Objective To determine the extent to which antibiotics reduce the risk of serious complications after common respiratory tract infections.Design Retrospective cohort study.Setting UK primary care practices contributing to the general practice research database.Data source 3.36 million episodes of respiratory tract infection.Main outcome measures Risk of serious complications in treated and untreated patients in the month after diagnosis: mastoiditis after otitis media, quinsy after sore throat, and pneumonia after upper respiratory tract infection and chest infection. Number of patients needed to treat to prevent one complication.Results Serious complications were rare after upper respiratory tract infections, sore throat, and otitis media, and the number needed to treat was over 4000. The risk of pneumonia after chest infection was high, particularly in elderly people, and was substantially reduced by antibiotic use, with a number needed to treat of 39 for those aged ≥65 and 96-119 in younger age groups. Conclusion Antibiotics are not justified to reduce the risk of serious complications for upper respiratory tract infection, sore throat, or otitis media. Antibiotics substantially reduce the risk of pneumonia after chest infection, particularly in elderly people in whom the risk is highest.     

Scratchpads 2.0: a Virtual Research Environment supporting scholarly collaboration, communication and data publication in biodiversity science

The Scratchpad Virtual Research Environment (http://scratchpads.eu/) is a flexible system for people to create their own research networks supporting natural history science. Here we describe Version 2 of the system characterised by the move to Drupal 7 as the Scratchpad core development framework and timed to coincide with the fifth year of the project's operation in late January 2012. The development of Scratchpad 2 reflects a combination of technical enhancements that make the project more sustainable, combined with new features intended to make the system more functional and easier to use. A roadmap outlining strategic plans for development of the Scratchpad project over the next two years concludes this article.     

2,5-Diketopiperazines as potent and selective oxytocin antagonists 1: Identification, stereochemistry and initial SAR

This paper covers efforts to discover orally active potent and selective oxytocin antagonists. Screening pooled libraries identified a novel series of 2,5-diketopiperazine derivatives with antagonist activity at the human oxytocin receptor. We report the initial structure-activity relationship investigations and the determination of the stereochemistry of the most potent compounds.     

Multiresistant Gram-negative bacteria: the role of high-risk clones in the dissemination of antibiotic resistance

Multilocus sequence typing reveals that many bacterial species have a clonal structure and that some clones are widespread. This underlying phylogeny was not revealed by pulsed-field gel electrophoresis, a method better suited to short-term outbreak investigation. Some global clones are multiresistant and it is easy to assume that these have disseminated from single foci. Such conclusions need caution, however, unless there is a clear epidemiological trail, as with KPC carbapenemase-positive Klebsiella pneumoniae ST258 from Greece to northwest Europe. Elsewhere, established clones may have repeatedly and independently acquired resistance. Thus, the global ST131 Escherichia coli clone most often has CTX-M-15 extended-spectrum β-lactamase (ESBL), but also occurs without ESBLs and as a host of many other ESBL types. We explore this interaction of clone and resistance for E. coli, K. pneumoniae, Acinetobacter baumannii- a species where three global lineages dominate--and Pseudomonas aeruginosa, which shows clonal diversity, but includes the relatively 'tight' serotype O12/Burst Group 4 cluster that has proved adept at acquiring resistances--from PSE-1 to VIM-1 β-lactamases--for over 20 years. In summary, 'high-risk clones' play a major role in the spread of resistance, with the risk lying in their tenacity--deriving from poorly understood survival traits--and a flexible ability to accumulate and switch resistance, rather than to constant resistance batteries.