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

Cell walls of the dimorphic fungal pathogens Sporothrix schenckii and Sporothrix brasiliensis exhibit bilaminate structures and sloughing of extensive and intact layers

This work was supported by the Fundação Carlos Chagas de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), grants E-26/202.974/2015 and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grants 229755/2013-5, Brazil. LMLB is a senior research fellow of CNPq and Faperj. NG acknowledged support from the Wellcome Trust (Trust (097377, 101873, 200208) and MRC Centre for Medical Mycology (MR/N006364/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Acute presentation of a solitary caecal diverticulum: a case report

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Introduction: Solitary caecal diverticulitis is a rare cause of abdominal pain in Caucasian patients. The condition is often misdiagnosed and only correctly identified on exploration for suspected acute appendicitis. Our aim is to improve awareness of this condition amongst surgical trainees to ensure that its first encounter is not in the operating theatre. We review the role of pre-operative radiological imaging in this condition and the wide and controversial management options are als

A combined analysis technique for the search for fast magnetic monopoles with the MACRO detector

We describe a search method for fast moving ($\beta > 5 \times 10^{-3}$) magnetic monopoles using simultaneously the scintillator, streamer tube and track-etch subdetectors of the MACRO apparatus. The first two subdetectors are used primarily for the identification of candidates while the track-etch one is used as the final tool for their rejection or confirmation. Using this technique, a first sample of more than two years of data has been analyzed without any evidence of a magnetic monopole. We set a 90% CL upper limit to the local monopole flux of $1.5 \times 10^{-15} cm^{-2} s^{-1} sr^{-1}$ in the velocity range $5 \times 10^{-3} \le \beta \le 0.99$ and for nucleon decay catalysis cross section smaller than $\sim 1 mb$.Comment: 29 pages (12 figures). Accepted by Astroparticle Physic

Academic Performance and Behavioral Patterns

Identifying the factors that influence academic performance is an essential part of educational research. Previous studies have documented the importance of personality traits, class attendance, and social network structure. Because most of these analyses were based on a single behavioral aspect and/or small sample sizes, there is currently no quantification of the interplay of these factors. Here, we study the academic performance among a cohort of 538 undergraduate students forming a single, densely connected social network. Our work is based on data collected using smartphones, which the students used as their primary phones for two years. The availability of multi-channel data from a single population allows us to directly compare the explanatory power of individual and social characteristics. We find that the most informative indicators of performance are based on social ties and that network indicators result in better model performance than individual characteristics (including both personality and class attendance). We confirm earlier findings that class attendance is the most important predictor among individual characteristics. Finally, our results suggest the presence of strong homophily and/or peer effects among university students

Final results of magnetic monopole searches with the MACRO experiment

We present the final results obtained by the MACRO experiment in the search for GUT magnetic monopoles in the penetrating cosmic radiation, for the range $4\times 10^{-5}< \beta < 1$. Several searches with all the MACRO sub-detectors (i.e. scintillation counters, limited streamer tubes and nuclear track detectors) were performed, both in stand alone and combined ways. No candidates were detected and a 90% Confidence Level (C.L.) upper limit to the local magnetic monopole flux was set at the level of $1.4\times 10^{-16}$ cm$^{-2}$ s$^{-1}$ sr$^{-1}$. This result is the first experimental limit obtained in direct searches which is well below the Parker bound in the whole $\beta$ range in which GUT magnetic monopoles are expected.Comment: 12 pages, Latex, 9 figures and 2 Table

The Observation of Up-going Charged Particles Produced by High Energy Muons in Underground Detectors

An experimental study of the production of up-going charged particles in inelastic interactions of down-going underground muons is reported, using data obtained from the MACRO detector at the Gran Sasso Laboratory. In a sample of 12.2 10^6 single muons, corresponding to a detector livetime of 1.55 y, 243 events are observed having an up-going particle associated with a down-going muon. These events are analysed to determine the range and emission angle distributions of the up-going particle, corrected for detection and reconstruction efficiency. Measurements of the muon neutrino flux by underground detectors are often based on the observation of through-going and stopping muons produced in $\nu_\mu$ interactions in the rock below the detector. Up-going particles produced by an undetected down-going muon are a potential background source in these measurements. The implications of this background for neutrino studies using MACRO are discussed.Comment: 18 pages, 9 figures. Accepted by Astrop. Physic

Nuclearite search with the MACRO detector at Gran Sasso

In this paper we present the results of a search for nuclearites in the penetrating cosmic radiation using the scintillator and track-etch subdetectors of the MACRO apparatus. The analyses cover the beta =v/c range at the detector depth (3700 hg/cm^2) 10^-5 < beta < 1; for beta = 2 x 10^-3 the flux limit is 2.7 x 10^-16 cm^-2 s^-1 sr^-1 for an isotropic flux of nuclearites, and twice this value for a flux of downgoing nuclearites.Comment: 16 pages, 4 Encapsulated Postscript figures, uses article.sty. Submitted to The European Physical Journal

Atmospheric neutrino induced muons in the MACRO detector

A measurement of the flux of neutrino-induced muons using the MACRO detector is presented. Different event topologies, corresponding to different neutrino parent energies can be detected. The upward throughgoing muon sample is the larger event sample. The observed upward-throughgoing muons are 26% fewer than expected and the zenith angle distribution does not fit with the expected one. Assuming neutrino oscillations, both measurements suggest maximum mixing and Dm2 of a few times 10-3 eV2. The other samples are due to the internally produced events and to upward-going stopping muons. These data show a regular deficit of observed events in each angular bin, as expected assuming neutrino oscillations with maximum mixing, in agreement with the analysis of the upward-throughgoing muon sample.Comment: 7 pages 6 figures to appear in the proceedings of XVIII International Conference on Neutrino Physics and Astrophysics (Neutrino'98), Takayama, Japan 4-9 June, 199

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH