A large conformational change of the translocation ATPase SecA

The ATPase SecA mediates the posttranslational translocation of a wide range of polypeptide substrates through the SecY channel in the cytoplasmic membrane of bacteria. We have determined the crystal structure of a monomeric form of Bacillus subtilis SecA at a 2.2-Å resolution. A comparison with the previously determined structures of SecA reveals a nucleotide-independent, large conformational change that opens a deep groove similar to that in other proteins that interact with diverse polypeptides. We propose that the open form of SecA represents an activated state

A modified scoring system to describe gross pathology in the rabbit model of tuberculosis

<p>Abstract</p> <p>Background</p> <p>The rabbit model is an ideal means to study the pathogenesis of tuberculosis due to its semblance to the disease in humans. We have previously described the results using a bronchoscopic route of infection with live bacilli as a reliable means of generating lung cavities in sensitized rabbits. The role of sensitization in the development of disease outcomes has been well established in several animal models. We have described here the varying gross pathology that result from lack of sensitization with heat-killed <it>M. bovis </it>prior to high-dose bronchoscopic infection with live bacilli.</p> <p>Results</p> <p>Rabbits lacking sensitization did not generate lung cavities, but instead formed solely a tuberculoid pneumonia that replaced the normal lung parenchyma in the area of infection. Extrapulmonary dissemination was seen in approximately equal frequency and distribution in both rabbit populations. Notable differences include the lack of intestinal lesions in non-sensitized rabbits likely due to the lack of ingestion of expectorated bacilli from cavitary lesions. The experiment also employed a modified scoring system developed initially in the primate model of tuberculosis to allow for the quantification of findings observed at necropsy.</p> <p>Conclusions</p> <p>To date, no such scoring system has been employed in the rabbit model to describe gross pathology. The quantitative methodology would allow for rapid comparative analyses and standardization of thoracic and extrapulmonary pathology that could be evaluated for statistical significance. The aim is to use such a scoring system as the foundation for all future rabbit studies describing gross pathology at all stages in TB pathogenesis.</p

Cell morphology drives spatial patterning in microbial communities

The clearest phenotypic characteristic of microbial cells is their shape, but we do not understand how cell shape affects the dense communities, known as biofilms, where many microbes live. Here, we use individual-based modeling to systematically vary cell shape and study its impact in simulated communities. We compete cells with different cell morphologies under a range of conditions and ask how shape affects the patterning and evolutionary fitness of cells within a community. Our models predict that cell shape will strongly influence the fate of a cell lineage: we describe a mechanism through which coccal (round) cells rise to the upper surface of a community, leading to a strong spatial structuring that can be critical for fitness. We test our predictions experimentally using strains of Escherichia coli that grow at a similar rate but differ in cell shape due to single amino acid changes in the actin homolog MreB. As predicted by our model, cell types strongly sort by shape, with round cells at the top of the colony and rod cells dominating the basal surface and edges. Our work suggests that cell morphology has a strong impact within microbial communities and may offer new ways to engineer the structure of synthetic communities

A large conformational change of the translocation ATPase SecA

The ATPase SecA mediates the posttranslational translocation of a wide range of polypeptide substrates through the SecY channel in the cytoplasmic membrane of bacteria. We have determined the crystal structure of a monomeric form of Bacillus subtilis SecA at a 2.2-Å resolution. A comparison with the previously determined structures of SecA reveals a nucleotide-independent, large conformational change that opens a deep groove similar to that in other proteins that interact with diverse polypeptides. We propose that the open form of SecA represents an activated state

Measuring the cosmological bulk flow using the peculiar velocities of supernovae

We study large-scale coherent motion in our universe using the existing Type IA supernovae data. If the recently observed bulk flow is real, then some imprint must be left on supernovae motion. We run a series of Monte Carlo Markov Chain runs in various redshift bins and find a sharp contrast between the z 0.05 data. The$z < 0.05 data are consistent with the bulk flow in the direction (l,b)=({290^{+39}_{-31}}^{\circ}, {20^{+32}_{-32}}^{\circ}) with a magnitude of v_bulk = 188^{+119}_{-103} km/s at 68% confidence. The significance of detection (compared to the null hypothesis) is 95%. In contrast, z > 0.05 data (which contains 425 of the 557 supernovae in the Union2 data set) show no evidence for bulk flow. While the direction of the bulk flow agrees very well with previous studies, the magnitude is significantly smaller. For example, the Kashlinsky, et al.'s original bulk flow result of v_bulk > 600 km/s is inconsistent with our analysis at greater than 99.7% confidence level. Furthermore, our best-fit bulk flow velocity is consistent with the expectation for the \Lambda CDM model, which lies inside the 68% confidence limit.Comment: Version published in JCA

Biochemical characterization of the human carbonic anhydrase variant CA ih Hiroshima

Some biochemical properties of a new red cell human carbonic anhydrase variant, CA Ih Hiroshima, have been determined. Evidence is presented that the amino acid substitution in the Japanese variant is not the same as the previously characterized CA Ic variant from Guam of similar electrophoretic mobility. Based on a comparison with the normal CA I isoenzyme, a proposal for the site of the amino acid substitution is presented.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47603/1/439_2004_Article_BF00284431.pd

Urinary bisphenol A concentration and risk of future coronary artery disease in apparently healthy men and women

addresses: Epidemiology and Public Health Group, Peninsula College of Medicine and Dentistry, Barrack Road, Exeter, United Kingdom. [email protected]: Comparative Study; Journal Article; Research Support, Non-U.S. Gov'tThe endocrine-disrupting chemical bisphenol A (BPA) is widely used in food and beverage packaging. Higher urinary BPA concentrations were cross-sectionally associated with heart disease in National Health and Nutrition Examination Survey (NHANES) 2003-2004 and NHANES 2005-2006, independent of traditional risk factors.Medical Research Council UKCancer Research UKBritish Heart FoundationPeninsula Medical School, University of ExeterEuropean Regional Development FundEuropean Social Fund Convergence Programme for Cornwall and the Isles of ScillyNational Institute for Health Research Collaborations for Leadership in Applied Health Research and Car

Seminar on Evidence and Trial Practice

Outlines of speaker presentations offered during a series of one day seminars on evidence and trial practice offered by UK/CLE in late 1987-early 1988

Effects of habitat composition and landscape structure on worker foraging distances of five bumblebee species

Bumblebees (Bombus spp.) are important pollinators of both crops and wild flowers. Their contribution to this essential ecosystem service has been threatened over recent decades by changes in land use, which have led to declines in their populations. In order to design effective conservation measures it is important to understand the effects of variation in landscape composition and structure on the foraging activities of worker bumblebees. This is because the viability of individual colonies is likely to be affected by the trade-off between the energetic costs of foraging over greater distances and the potential gains from access to additional resources. We used field surveys, molecular genetics and fine resolution remote sensing to estimate the locations of wild bumblebee nests and to infer foraging distances across a 20 km2 agricultural landscape in southern England. We investigated five species, including the rare B. ruderatus and ecologically similar but widespread B. hortorum. We compared worker foraging distances between species and examined how variation in landscape composition and structure affected foraging distances at the colony level. Mean worker foraging distances differed significantly between species. Bombus terrestris, B. lapidarius and B. ruderatus exhibited significantly greater mean foraging distances (551 m, 536 m, 501 m, respectively) than B. hortorum and B. pascuorum (336 m, 272 m, respectively). There was wide variation in worker foraging distances between colonies of the same species, which was in turn strongly influenced by the amount and spatial configuration of available foraging habitats. Shorter foraging distances were found for colonies where the local landscape had high coverage and low fragmentation of semi-natural vegetation, including managed agri-environmental field margins. The strength of relationships between different landscape variables and foraging distance varied between species, for example the strongest relationship for B. ruderatus being with floral cover of preferred forage plants. Our findings suggest that favourable landscape composition and configuration has the potential to minimise foraging distances across a range of bumblebee species. There is thus potential for improvements in the design and implementation of landscape management options, such as agri-environment schemes, aimed at providing foraging habitat for bumblebees and enhancing crop pollination services

Community pharmacists’ and residents’ decision making and unmet information needs when completing comprehensive medication reviews

Objective To (1) characterize community pharmacists’ and community pharmacy residents’ decision making and unmet information needs when conducting comprehensive medication reviews (CMRs) as part of medication therapy management and (2) explore any differences between community pharmacists and community pharmacy residents in CMR decision making and unmet information needs. Design Thirty-to 60-minute semistructured interviews framed using a clinical decision-making model (CDMM) were conducted with community pharmacists and residents. Setting and participants Participants were recruited from practice-based research networks and researchers’ professional networks. Eligible participants had completed or supported the completion of at least 2 CMRs in the last 30 days. Outcome measures Two researchers independently coded transcripts using a combination of inductive and deductive methods to identify themes pertaining to community pharmacists’ and residents’ decision making and unmet information needs in the provision of CMRs. Discrepancies among researchers’ initial coding decisions were resolved through discussion. Results Sixteen participants (8 pharmacists and 8 residents) were interviewed. Themes were mapped to 5 CDMM steps. Participants primarily used subjective information during “case familiarization”; objective information was secondary. Information used for “generating initial hypotheses” varied by medication therapy problem (MTP) type. During “case assessment,” if information was not readily available, participants sought information from patients. Thus, patients’ levels of self-management and health literacy influenced participants’ ability to identify and resolve MTPs, as described under “identifying final hypotheses.” Finally, participants described “decision-making barriers,” including communication with prescribers to resolve MTPs. Although pharmacist and resident participants varied in the types of MTPs identified, both groups cited the use and need of similar information. Conclusion Community pharmacists and residents often rely primarily on patient-provided information for decision making during CMRs because of unmet information needs, specifically, objective information. Moreover, confidence in MTP identification and resolution is reduced by communication challenges with prescribers and limitations in patients’ ability to convey accurate and necessary information