Novel statistical methodology reveals that hip shape is associated with incident radiographic hip osteoarthritis among African American women

Hip shape is a risk factor for the development of hip osteoarthritis (OA), and current methods to assess hip shape from radiographs are limited; therefore this study explored current and novel methods to assess hip shape

Proteolysis of the endothelial cell protein C receptor by neutrophil proteinase 3

BACKGROUND: The endothelial cell protein C receptor (EPCR) presents protein C to the thrombin:thrombomodulin complex on the endothelium of large vessels, and enhances the generation of activated protein C (APC) and activation of protease-activated receptor-1. A previous report has demonstrated binding of soluble (s) EPCR to activated neutrophils via surface proteinase 3 (PR3). METHODS: We now report further characterization of this interaction. Activated neutrophils and purified PR3 both decrease endothelial cell (EC) surface EPCR, suggestive of its proteolysis. RESULTS: When added to purified recombinant sEPCR, PR3 produced multiple cleavages, with early products including 20 kDa N-terminal and C-terminal (after Lys(176)) fragments. The binding of active site blocked PR3 to sEPCR was studied by surface plasmon resonance. Estimates of the K(D) of 18.5–102 nm were obtained with heterogeneous binding, suggestive of more than a single interaction site. CONCLUSIONS: This work demonstrates PR3 binding to and proteolysis of EPCR and suggests a mechanism by which anticoagulant and cell protective pathways can be down-regulated during inflammation

Clinical features and prognosis in patients with atrial fibrillation and prior stroke: Comparing the Fushimi and Darlington AF Registries

Background: Ethnic differences in clinical characteristics, stroke risk profiles and outcomes among atrial fibrillation (AF) patients may exist. We therefore compared AF patients with previous stroke from Japan and the United Kingdom (UK). Methods: We compared clinical characteristics, stroke risk and outcomes among AF patients from the Fushimi AF registry who had experienced a previous stroke (Japan; n = 688; 19.7%) and the Darlington AF registry (UK; n = 428; 19.0%). Results: AF patients with previous stroke in Fushimi were significantly younger (76.8 and 79.6 years of age in Fushimi and Darlington; p < 0.01) with a lower proportion of females (37.4% vs. 45.1%; p = 0.01) than those from Darlington. Although the CHA2DS2-VASc score was lower in AF patients in Fushimi than those in Darlington (5.18 vs. 5.57; p < 0.01), oral anticoagulation (OAC) was prescribed significantly more frequently in Fushimi (68.3%) than Darlington (61.7%) (p = 0.02). Multivariate logistic regression analysis showed that Japanese ethnicity was associated with a significantly decreased risk of recurrent stroke (OR 0.59. 95% CI 0.36–0.97; p = 0.04) but a significantly increased risk of all-cause mortality (OR 1.76, 95% CI 1.18–2.66; p < 0.01) in AF patients with previous stroke. Conclusions: AF patients with previous stroke in the UK were at higher risk of recurrent stroke compared to Japanese patients, but OAC was utilised less frequently. There was a lower risk of recurrent stroke in the secondary prevention cohort from the Fushimi registry, but an increased risk of all-cause mortality

Mouse hepatitis virus neurovirulence: evidence of a linkage between S glycoprotein expression and immunopathology.

Differences in disease outcome between the highly neurovirulent MHV-JHM and mildly neurovirulent MHV-A59 have been attributed to variations within the spike (S) glycoprotein. Previously, we found that MHV-JHM neurovirulence was marked by diminished expression of interferon-gamma (IFN-gamma) mRNA and a reduced presence of CD8 T cells in the CNS concomitant with heightened macrophage inflammatory protein (MIP)-1 transcript levels and greater macrophage infiltration relative to MHV-A59 infection. Here, the ability of the S and non-spike genes to regulate these immune responses was evaluated using chimeric viruses. Chimeric viruses WTR13 and S4R22 were made on MHV-A59 variant backgrounds and, respectively, contained the S gene of MHV-A59 and MHV-JHM. Unexpectedly, genes other than S appeared to modulate events critical to viral replication and survival. Unlike unresolving MHV-JHM infections, the clearance of WTR13 and S4R22 infections coincided with strong IFN-gamma transcription and an increase in the number of CD8 T cells infiltrating into the CNS. However, despite the absence of detectable viral titers, approximately 40% of S4R22-infected mice succumbed within 3 weeks, indicating that the enhanced mortality following S4R22 infection was not associated with high viral titers. Instead, similar to the MHV-JHM infection, reduced survival following S4R22 infection was observed in the presence of elevated MIP-1alpha and MIP-1beta mRNA accumulation and enhanced macrophage numbers within infected brains. These observations suggest that the S protein of MHV-JHM influences neurovirulence through the induction of MIP-1alpha- and MIP-1beta-driven macrophage immunopathology

Incorporation by coordination and release of the iron chelator drug deferiprone from zinc-based metal–organic frameworks

A series of new zinc-based metal–organic framework materials has been prepared in which deferiprone is incorporated as a chelating ligand on infinite or tri-zinc secondary building units following deprotonation. Deferiprone is immediately released from the MOFs on treatments with 1 N hydrochloric acid or buffer, but slow release is observed in ethanoic acid

Analytical relations between nuclear symmetry energy and single-nucleon potentials in isospin asymmetric nuclear matter

Using the Hugenholtz-Van Hove theorem, we derive general expressions for the quadratic and quartic symmetry energies in terms of single-nucleon potentials in isospin asymmetric nuclear matter. These analytical relations are useful for gaining deeper insights into the microscopic origins of the uncertainties in our knowledge on nuclear symmetry energies especially at supra-saturation densities. As examples, the formalism is applied to two model single-nucleon potentials that are widely used in transport model simulations of heavy-ion reactions.Comment: 23 pages with 6 figure

Microbial catabolic activities are naturally selected by metabolic energy harvest rate

The fundamental trade-off between yield and rate of energy harvest per unit of substrate has been largely discussed as a main characteristic for microbial established cooperation or competition. In this study, this point is addressed by developing a generalized model that simulates competition between existing and not experimentally reported microbial catabolic activities defined only based on well-known biochemical pathways. No specific microbial physiological adaptations are considered, growth yield is calculated coupled to catabolism energetics and a common maximum biomass-specific catabolism rate (expressed as electron transfer rate) is assumed for all microbial groups. Under this approach, successful microbial metabolisms are predicted in line with experimental observations under the hypothesis of maximum energy harvest rate. Two microbial ecosystems, typically found in wastewater treatment plants, are simulated, namely: (i) the anaerobic fermentation of glucose and (ii) the oxidation and reduction of nitrogen under aerobic autotrophic (nitrification) and anoxic heterotrophic and autotrophic (denitrification) conditions. The experimentally observed cross feeding in glucose fermentation, through multiple intermediate fermentation pathways, towards ultimately methane and carbon dioxide is predicted. Analogously, two-stage nitrification (by ammonium and nitrite oxidizers) is predicted as prevailing over nitrification in one stage. Conversely, denitrification is predicted in one stage (by denitrifiers) as well as anammox (anaerobic ammonium oxidation). The model results suggest that these observations are a direct consequence of the different energy yields per electron transferred at the different steps of the pathways. Overall, our results theoretically support the hypothesis that successful microbial catabolic activities are selected by an overall maximum energy harvest rate

The velocity dispersion and mass function of the outer halo globular cluster Palomar 4

We obtained precise line-of-sight radial velocities of 23 member stars of the remote halo globular cluster Palomar 4 (Pal 4) using the High Resolution Echelle Spectrograph (HIRES) at the Keck I telescope. We also measured the mass function of the cluster down to a limiting magnitude of V~28 mag using archival HST/WFPC2 imaging. We derived the cluster's surface brightness profile based on the WFPC2 data and on broad-band imaging with the Low-Resolution Imaging Spectrometer (LRIS) at the Keck II telescope. We find a mean cluster velocity of 72.55+/-0.22 km/s and a velocity dispersion of 0.87+/-0.18 km/s. The global mass function of the cluster, in the mass range 0.55<=M<=0.85 M_solar, is shallower than a Kroupa mass function and the cluster is significantly depleted in low-mass stars in its center compared to its outskirts. Since the relaxation time of Pal 4 is of the order of a Hubble time, this points to primordial mass segregation in this cluster. Extrapolating the measured mass function towards lower-mass stars and including the contribution of compact remnants, we derive a total cluster mass of 29800 M_solar. For this mass, the measured velocity dispersion is consistent with the expectations of Newtonian dynamics and below the prediction of Modified Newtonian Dynamics (MOND). Pal 4 adds to the growing body of evidence that the dynamics of star clusters in the outer Galactic halo can hardly be explained by MOND.Comment: 17 pages, accepted for publication in MNRAS; Fig. 8 surface brightness/density data at github.com/matthiasjfrank/pal4_surface_brightnes