Crystal Structure of Prolyl 4-Hydroxylase from Bacillus anthracis

Prolyl 4-hydroxylases (P4H) catalyze the posttranslational hydroxylation of proline residues and play a role in collagen production, hypoxia response, and cell wall development. P4Hs belong to the Fe(II)/αKG oxygenases and require Fe(II), α-ketoglutarate (αKG), and O2 for activity. We report the 1.40 Å structure of a P4H from Bacillus anthracis, the causative agent of anthrax, whose immunodominant exosporium protein BclA contains collagen-like repeat sequences. The structure reveals the double stranded β-helix core fold characteristic of Fe(II)/αKG oxygenases. This fold positions Fe-binding and αKG-binding residues in what is expected to be catalytically-competent orientations and is consistent with proline peptide substrate binding at the active site mouth. Comparisons of the anthrax-P4H structure with Cr-P4H-1 structures reveal similarities in a peptide surface groove. However, sequence and structural comparisons suggest differences in conformation of adjacent loops may change the interaction with peptide substrates. These differences may be the basis of substantial disparity between the KM values for the Cr-P4H-1 vs. the anthrax and human P4H enzymes. Additionally, while previous structures of P4H enzymes are monomers, Bacillus anthracis P4H forms an α2 homodimer and suggests residues important for interactions between the α2 subunits of the α2β2 human collagen P4H. Thus the anthrax-P4H structure provides insight into the structure and function of the α subunit of human-P4H, which may aid in the development of selective inhibitors of the human-P4H enzyme involved in fibrotic disease

Applying to vascular specialty training in the UK: 12 tips for success

From preparation to accomplishment, maximise your chances of a career in vascular surgery

Re-Examining the Definition of Community Psychology Practice

Throughout the early and mid-2000s, Community Psychology practitioners worked with the Society for Community Research and Action (SCRA) Executive Committee (EC) to revisit relevant organizational goals and objectives.  These conversations resulted in the recognition of the need to more fully operationalize the “action” component of SCRA. Ultimately, a draft statement was brought to the first International Community Psychology Conference in Puerto Rico.  Through a highly participative process, a group of conference attendees emerged with a definition of community psychology practice:  The aim of community psychology practice is to strengthen the capacity of communities to meet the needs of constituents and help them to realize their dreams in order to promote well-being, social justice, economic equity and self-determination through systems, organizational and/or individual change. Since the definition was developed over a decade ago, much has changed. This special issue was conceived as a means for the field to consider the definition of Community Psychology practice in light of these and other advances in our thinking. The special issue editorial team invites the field to ponder proposed changes and new definitions of community psychology practice

Re-Examining the Definition of Community Psychology Practice

Throughout the early and mid-2000s, Community Psychology practitioners worked with the Society for Community Research and Action (SCRA) Executive Committee (EC) to revisit relevant organizational goals and objectives.  These conversations resulted in the recognition of the need to more fully operationalize the “action” component of SCRA. Ultimately, a draft statement was brought to the first International Community Psychology Conference in Puerto Rico.  Through a highly participative process, a group of conference attendees emerged with a definition of community psychology practice:  The aim of community psychology practice is to strengthen the capacity of communities to meet the needs of constituents and help them to realize their dreams in order to promote well-being, social justice, economic equity and self-determination through systems, organizational and/or individual change. Since the definition was developed over a decade ago, much has changed. This special issue was conceived as a means for the field to consider the definition of Community Psychology practice in light of these and other advances in our thinking. The special issue editorial team invites the field to ponder proposed changes and new definitions of community psychology practice

Baffling perforation of the colon

Idiopathic perforation of the colon is extremely unusual and unexpected, with a very limited number of published reports. The condition’s definition depends on the absence of any detectable pathology in the bowel wall that could be responsible for the perforation. A 62-year-old male patient presented with acute thrombosis of the brachial artery. This was successfully treated with an open thrombectomy and systemic anticoagulation, with rapid resolution of the symptoms. During the hospital stay the patient had regular bowel movements and no abdominal complaints. Suddenly he complained of acute abdominal pain. Physical examination and emergency CT scan of the abdomen were consistent with generalized peritonitis. Emergency laparotomy revealed two perforations of the mid-sigmoid colon, each measuring 1.5 x 1.5 cm, an

Quality and readability of online patient information for abdominal aortic aneurysms

ObjectiveWe assessed the quality and readability of patient information for abdominal aortic aneurysms (AAAs) on the World Wide Web, as accessed from the United Kingdom.MethodsWeb sites returned by a simple Web search using the three largest search engines by market share were objectively and subjectively assessed for quality and readability. The Internet search engines Google, Yahoo!, and Bing were interrogated for the term “abdominal aortic aneurysm” and the first 50 hits screened. Organization type and Health on the Net status were recorded. Each unique site containing AAA information was scored for quality using the University of Michigan Consumer Health Web site Evaluation Checklist by two authors, and readability was calculated using the Flesch Reading Ease (FRE) score. Subjective content assessment was also undertaken.ResultsOf 150 hits, 112 were relevant, with 55 unique sites for assessment. Overall, the FRE score was 39 (range, 29-47) and the Michigan score was 36 (range, 25-56), with good interobserver agreement (rs = 0.83; P = .01). Michigan and FRE scores were poorly correlated (rs = 0.064; P = .6). Sites containing discussion on the merits of endovascular/open repair and the concept of an intervention threshold had the highest Michigan scores (58.5 [50-59.75] vs 28 [13-36.5]; P < .001). Search engine ranking, Health on the Net status, country of origin, and organization type did not affect quality or readability.ConclusionsThe current quality and readability of online patient information for AAAs is poor and requires significant improvement. Clinicians treating patients with AAAs should be aware of the limitations of the online “lay literature.

Measuring Stellar Radial Velocities with a Dispersed Fixed-Delay Interferometer

We demonstrate the ability to measure precise stellar barycentric radial velocities with the dispersed fixed-delay interferometer technique using the Exoplanet Tracker (ET), an instrument primarily designed for precision differential Doppler velocity measurements using this technique. Our barycentric radial velocities, derived from observations taken at the KPNO 2.1 meter telescope, differ from those of Nidever et al. by 0.047 km/s (rms) when simultaneous iodine calibration is used, and by 0.120 km/s (rms) without simultaneous iodine calibration. Our results effectively show that a Michelson interferometer coupled to a spectrograph allows precise measurements of barycentric radial velocities even at a modest spectral resolution of R ~ 5100. A multi-object version of the ET instrument capable of observing ~500 stars per night is being used at the Sloan 2.5 m telescope at Apache Point Observatory for the Multi-object APO Radial Velocity Exoplanet Large-area Survey (MARVELS), a wide-field radial velocity survey for extrasolar planets around TYCHO-2 stars in the magnitude range 7.6<V<12. In addition to precise differential velocities, this survey will also yield precise barycentric radial velocities for many thousands of stars using the data analysis techniques reported here. Such a large kinematic survey at high velocity precision will be useful in identifying the signature of accretion events in the Milky Way and understanding local stellar kinematics in addition to discovering exoplanets, brown dwarfs and spectroscopic binaries.Comment: 9 pages, 4 figures. Accepted for publication in Ap

The XMM Cluster Survey: Evidence for energy injection at high redshift from evolution of the X-ray luminosity-temperature relation

We measure the evolution of the X-ray luminosity-temperature (L_X-T) relation since z~1.5 using a sample of 211 serendipitously detected galaxy clusters with spectroscopic redshifts drawn from the XMM Cluster Survey first data release (XCS-DR1). This is the first study spanning this redshift range using a single, large, homogeneous cluster sample. Using an orthogonal regression technique, we find no evidence for evolution in the slope or intrinsic scatter of the relation since z~1.5, finding both to be consistent with previous measurements at z~0.1. However, the normalisation is seen to evolve negatively with respect to the self-similar expectation: we find E(z)^{-1} L_X = 10^{44.67 +/- 0.09} (T/5)^{3.04 +/- 0.16} (1+z)^{-1.5 +/- 0.5}, which is within 2 sigma of the zero evolution case. We see milder, but still negative, evolution with respect to self-similar when using a bisector regression technique. We compare our results to numerical simulations, where we fit simulated cluster samples using the same methods used on the XCS data. Our data favour models in which the majority of the excess entropy required to explain the slope of the L_X-T relation is injected at high redshift. Simulations in which AGN feedback is implemented using prescriptions from current semi-analytic galaxy formation models predict positive evolution of the normalisation, and differ from our data at more than 5 sigma. This suggests that more efficient feedback at high redshift may be needed in these models.Comment: Accepted for publication in MNRAS; 12 pages, 6 figures; added references to match published versio

Volumetric versus single slice measurements of core abdominal muscle for Sarcopenia

Objectives: We investigated whether total psoas muscle area (TPMA) was representative of the total psoas muscle volume (TPMV). Secondly, we assessed whether there was a relationship between the two commonly used single slice measurements of sarcopenia, TPMA and total abdominal muscle area (TAMA). Methods: Pre-operative CT imaging of 110 patients undergoing elective endovascular aneurysm repair were analysed by two trained independent observers. TPMA was measured at individual vertebral levels between the second lumbar vertebrae and sacrum. TPMV was also estimated between the second lumbar vertebrae and sacrum. TAMA was measured at the third lumbar vertebrae (L3). Observer differences were assessed using Bland-Altman plots. Associations between the different measures were assessed using linear regression and Pearson's correlation. Results: We found single slice measurements of the TPMA to be representative of the TPMV at individual levels between L2 to the sacrum. The strongest association was seen at L3 (adjusted regression coefficient 16.7, 95% CI 12.1 to 21.4, p < 0.001). There was no association between TPMA and TAMA (adjusted regression coefficient - 0.7, 95% CI - 4.1 to 2.8, p = 0.710). Conclusions: We demonstrate that measurements of the TPMA between L2 to the sacrum are representative of the TPMV, with the greatest association at the third lumbar vertebrae. There was no association between the TPMA and TAMA. Advances in Knowledge: We demonstrate that a single slice measurement of TPMA at L3 is representative of the muscle volume, contrary to previous criticism. Future sarcopenia studies can continue to measure TPMA which is representative of the TPMV