A stomatin dimer modulates the activity of acid-sensing ion channels.

Stomatin proteins oligomerize at membranes and have been implicated in ion channel regulation and membrane trafficking. To obtain mechanistic insights into their function, we determined three crystal structures of the conserved stomatin domain of mouse stomatin that assembles into a banana-shaped dimer. We show that dimerization is crucial for the repression of acid-sensing ion channel 3 (ASIC3) activity.

Reduced expression of the rplU-rpmA ribosomal protein operon in mexXY-expressing pan-aminoglycoside-resistant mutants of pseudomonas aeruginosa.

Pan-aminoglycoside-resistant Pseudomonas aeruginosa mutants expressing the mexXY components of the aminoglycoside-accommodating MexXY-OprM multidrug efflux system but lacking mutations in the mexZ gene encoding a repressor of this efflux system and in the mexXY promoter have been reported (S. Fraud and K. Poole, Antimicrob.

Regulation of ASIC channels by a stomatin/STOML3 complex located in a mobile vesicle pool in sensory neurons.

A complex of stomatin-family proteins and acid-sensing (proton-gated) ion channel (ASIC) family members participate in sensory transduction in invertebrates and vertebrates. Here, we have examined the role of the stomatin-family protein stomatin-like protein-3 (STOML3) in this process. We demonstrate that STOML3 interacts with stomatin and ASIC subunits and that this occurs in a highly mobile vesicle pool in dorsal root ganglia (DRG) neurons and Chinese hamster ovary cells.

Cortical thickness mapping to identify focal osteoporosis in patients with hip fracture.

Background: Individuals with osteoporosis are predisposed to hip fracture during trips, stumbles or falls, but half of all hip fractures occur in those without generalised osteoporosis. By analysing ordinary clinical CT scans using a novel cortical thickness mapping technique, we discovered patches of markedly thinner bone at fracture-prone regions in the femurs of women with acute hip fracture compared with controls.

Methods: We analysed CT scans from 75 female volunteers with acute fracture and 75 age- and sex-matched controls.

Bacterial stress responses as determinants of antimicrobial resistance.

Bacteria encounter a myriad of stresses in their natural environments, including, for pathogens, their hosts. These stresses elicit a variety of specific and highly regulated adaptive responses that not only protect bacteria from the offending stress, but also manifest changes in the cell that impact innate antimicrobial susceptibility. Thus exposure to nutrient starvation/limitation (nutrient stress), reactive oxygen and nitrogen species (oxidative/nitrosative stress), membrane damage (envelope stress), elevated temperature (heat stress) and ribosome disruption (ribosomal stress) all impact bacterial susceptibility to a variety of antimicrobials through their initiation of stress responses that positively impact recruitment of resistance determinants or promote physiological changes that compromise antimicrobial activity.

Availability of complementary and alternative medicine for people with cancer in the British National Health Service: results of a national survey.

This study assessed access to Complementary and Alternative Medicine (CAM) therapies for people with cancer within the British National Health Service. CAM units were identified through an internet search in 2009. A total of 142 units, providing 62 different therapies, were identified: 105 (74.

Rapid method for proline determination in grape juice and wine.

Proline is typically the most abundant amino acid present in grape juice and wine. The amount present is influenced by viticultural and winemaking factors and can be of diagnostic importance. A method for rapid routine quantitation of proline would therefore be of benefit for wine researchers and the industry in general.

Imaging the femoral cortex: thickness, density and mass from clinical CT.

There is growing evidence that focal thinning of cortical bone in the proximal femur may predispose a hip to fracture. Detecting such defects in clinical CT is challenging, since cortices may be significantly thinner than the imaging system's point spread function. We recently proposed a model-fitting technique to measure sub-millimetre cortices, an ill-posed problem which was regularized by assuming a specific, fixed value for the cortical density.

Stress responses as determinants of antimicrobial resistance in Gram-negative bacteria.

Bacteria encounter a myriad of potentially growth-compromising conditions in nature and in hosts of pathogenic bacteria. These 'stresses' typically elicit protective and/or adaptive responses that serve to enhance bacterial survivability. Because they impact upon many of the same cellular components and processes that are targeted by antimicrobials, adaptive stress responses can influence antimicrobial susceptibility.

Pentachlorophenol induction of the Pseudomonas aeruginosa mexAB-oprM efflux operon: involvement of repressors NalC and MexR and the antirepressor ArmR.

Pentachlorophenol (PCP) induced expression of the NalC repressor-regulated PA3720-armR operon and the MexR repressor-controlled mexAB-oprM multidrug efflux operon of Pseudomonas aeruginosa. PCP's induction of PA3720-armR resulted from its direct modulation of NalC, the repressor's binding to PA3720-armR promoter-containing DNA as seen in electromobility shift assays (EMSAs) being obviated in the presence of this agent. The NalC binding site was localized to an inverted repeat (IR) sequence upstream of PA3720-armR and overlapping a promoter region whose transcription start site was mapped.

Complete immunosuppression withdrawal and subsequent allograft function among pediatric recipients of parental living donor liver transplants.

Context: Although life-saving, liver transplantation burdens children with lifelong immunosuppression and substantial potential for morbidity and mortality.

Objective: To establish the feasibility of immunosuppression withdrawal in pediatric living donor liver transplant recipients.

Design, Setting, And Patients: Prospective, multicenter, open-label, single-group pilot trial conducted in 20 stable pediatric recipients (11 male; 55%) of parental living donor liver transplants for diseases other than viral hepatitis or an autoimmune disease who underwent immunosuppression withdrawal.

Attenuation of neurovirulence, biodistribution, and shedding of a poliovirus:rhinovirus chimera after intrathalamic inoculation in Macaca fascicularis.

A dependence of poliovirus on an unorthodox translation initiation mode can be targeted selectively to drive viral protein synthesis and cytotoxicity in malignant cells. Transformed cells are naturally susceptible to poliovirus, due to widespread ectopic upregulation of the poliovirus receptor, Necl-5, in ectodermal/neuroectodermal cancers. Viral tumor cell killing and the host immunologic response it engenders produce potent, lasting antineoplastic effects in animal tumor models.

Microwave-Assisted Synthesis of N-Phenylsuccinimide.

A microwave-assisted synthesis of N-phenylsuccinimide has been developed for the second-semester organic teaching laboratory. Utilizing this procedure, N-phenylsuccinimide can be synthesized by heating a mixture of aniline and succinic anhydride in a domestic microwave oven for four minutes in moderate yields (40-60%). This technique reduces the reaction time as compared to the traditional synthesis by several hours, which allows the preparation to be achieved in a single organic chemistry laboratory period.

Research-intensive cancer care in the NHS in the UK.

In the late 1990 s, in response to poor national cancer survival figures, government monies were invested to enhance recruitment to clinical cancer research. Commencing with England in 2001 and then rolling out across all four countries, a network of clinical cancer research infrastructure was created, the new staff being linked to existing clinical care structures including multi-disciplinary teams. In parallel, a UK-wide co-ordination of cancer research funders driven by the 'virtual' National Cancer Research Institute, combined to create a 'whole-system approach' linking research funders, researchers and NHS clinicians all working to the same ends.

Molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) among patients admitted to adult intensive care units: the STAR*ICU trial.

Background: The multicenter, cluster-randomized Strategies to Reduce Transmission of Antimicrobial Resistant Bacteria in Intensive Care Units (STAR*ICU) trial was performed in 18 U.S. adult intensive care units (ICUs).

Exposure assessment in health assessments for hand-arm vibration syndrome.

Background: Assessing past cumulative vibration exposure is part of assessing the risk of hand-arm vibration syndrome (HAVS) in workers exposed to hand-arm vibration and invariably forms part of a medical assessment of such workers.

Aims: To investigate the strength of relationships between the presence and severity of HAVS and different cumulative exposure metrics obtained from a self-reporting questionnaire.

Methods: Cumulative exposure metrics were constructed from a tool-based questionnaire applied in a group of HAVS referrals and workplace field studies.

Uptake and quality of health surveillance for noise and hand-arm vibration.

Background: Health surveillance (HS) is required for employees if noise or hand-arm vibration (HAV) exposures are likely to be above exposure action levels. The extent to which employers comply with Health and Safety Executive (HSE) regulations is unclear.

Aims: To establish the uptake and quality of HS for noise and HAV in high-risk industries.

Pseudomonas aeruginosa: resistance to the max.

Pseudomonas aeruginosa is intrinsically resistant to a variety of antimicrobials and can develop resistance during anti-pseudomonal chemotherapy both of which compromise treatment of infections caused by this organism. Resistance to multiple classes of antimicrobials (multidrug resistance) in particular is increasingly common in P. aeruginosa, with a number of reports of pan-resistant isolates treatable with a single agent, colistin.

Laminin-332 coordinates mechanotransduction and growth cone bifurcation in sensory neurons.

Laminin-332 is a major component of the dermo-epidermal skin basement membrane and maintains skin integrity. The transduction of mechanical force into electrical signals by sensory endings in the skin requires mechanosensitive channels. We found that mouse epidermal keratinocytes produce a matrix that is inhibitory for sensory mechanotransduction and that the active molecular component is laminin-332.

Stomatin-domain proteins.

The stomatin-domain defines a family of proteins that are found in all classes of life. The ubiquity of stomatin-family proteins and their high degree of homology suggest that they have a unifying cellular function, which has yet to be defined. The five stomatin family proteins in mammals show varying expression patterns and different sub-cellular distributions.

Distribution of cortical bone in the femoral neck and hip fracture: a prospective case-control analysis of 143 incident hip fractures; the AGES-REYKJAVIK Study.

In this prospective nested case-control study we analyzed the circumferential differences in estimated cortical thickness (Est CTh) of the mid femoral neck as a risk factor for osteoporotic hip fractures in elderly women and men. Segmental QCT analysis of the mid femoral neck was applied to assess cortical thickness in anatomical quadrants. The superior region of the femoral neck was a stronger predictor for hip fracture than the inferior region, particularly in men.

'Sink or swim': an evaluation of the clinical characteristics of individuals with high bone mass.

Summary: High bone mineral density on routine dual energy X-ray absorptiometry (DXA) may indicate an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained high bone mass (HBM), 236 relatives (41% with HBM) and 58 spouses were studied. Cases could not float, had mandible enlargement, extra bone, broad frames, larger shoe sizes and increased body mass index (BMI).