Coagulation factor XII protease domain crystal structure

Background: Coagulation factor XII is a serine protease that is important for kinin generation and blood coagulation, cleaving the substrates plasma kallikrein and FXI.Objective: To investigate FXII zymogen activation and substrate recognition by determining the crystal structure of the FXII protease domain.Methods and results: A series of recombinant FXII protease constructs were characterized by measurement of cleavage of chromogenic peptide and plasma kallikrein protein substrates. This revealed that the FXII protease construct spanning the light chain has unexpectedly weak proteolytic activity compared to β‐FXIIa, which has an additional nine amino acid remnant of the heavy chain present. Consistent with these data, the crystal structure of the light chain protease reveals a zymogen conformation for active site residues Gly193 and Ser195, where the oxyanion hole is absent. The Asp194 side chain salt bridge to Arg73 constitutes an atypical conformation of the 70‐loop. In one crystal form, the S1 pocket loops are partially flexible, which is typical of a zymogen. In a second crystal form of the deglycosylated light chain, the S1 pocket loops are ordered, and a short α‐helix in the 180‐loop of the structure results in an enlarged and distorted S1 pocket with a buried conformation of Asp189, which is critical for P1 Arg substrate recognition. The FXII structures define patches of negative charge surrounding the active site cleft that may be critical for interactions with inhibitors and substrates.Conclusions: These data provide the first structural basis for understanding FXII substrate recognition and zymogen activation

Effect of event selection on jetlike correlation measurement in d+Au collisions at sNN=200 GeV

AbstractDihadron correlations are analyzed in sNN=200 GeV d+Au collisions classified by forward charged particle multiplicity and zero-degree neutral energy in the Au-beam direction. It is found that the jetlike correlated yield increases with the event multiplicity. After taking into account this dependence, the non-jet contribution on the away side is minimal, leaving little room for a back-to-back ridge in these collisions

Beam-energy Dependence Of Charge Balance Functions From Au + Au Collisions At Energies Available At The Bnl Relativistic Heavy Ion Collider

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Balance functions have been measured in terms of relative pseudorapidity (Δη) for charged particle pairs at the BNL Relativistic Heavy Ion Collider from Au + Au collisions at sNN=7.7GeV to 200 GeV using the STAR detector. These results are compared with balance functions measured at the CERN Large Hadron Collider from Pb + Pb collisions at sNN=2.76TeV by the ALICE Collaboration. The width of the balance function decreases as the collisions become more central and as the beam energy is increased. In contrast, the widths of the balance functions calculated using shuffled events show little dependence on centrality or beam energy and are larger than the observed widths. Balance function widths calculated using events generated by UrQMD are wider than the measured widths in central collisions and show little centrality dependence. The measured widths of the balance functions in central collisions are consistent with the delayed hadronization of a deconfined quark gluon plasma (QGP). The narrowing of the balance function in central collisions at sNN=7.7 GeV implies that a QGP is still being created at this relatively low energy. © 2016 American Physical Society.942CNPq, Conselho Nacional de Desenvolvimento Científico e TecnológicoMinistry of Education and Science of the Russian FederationMOE, Ministry of Education of the People's Republic of ChinaMOST, Ministry of Science and Technology of the People's Republic of ChinaNRF-2012004024, National Research FoundationNSF, National Stroke FoundationConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Health in times of uncertainty in the eastern Mediterranean region, 1990�2013: a systematic analysis for the Global Burden of Disease Study 2013

Background The eastern Mediterranean region is comprised of 22 countries: Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, the United Arab Emirates, and Yemen. Since our Global Burden of Disease Study 2010 (GBD 2010), the region has faced unrest as a result of revolutions, wars, and the so-called Arab uprisings. The objective of this study was to present the burden of diseases, injuries, and risk factors in the eastern Mediterranean region as of 2013. Methods GBD 2013 includes an annual assessment covering 188 countries from 1990 to 2013. The study covers 306 diseases and injuries, 1233 sequelae, and 79 risk factors. Our GBD 2013 analyses included the addition of new data through updated systematic reviews and through the contribution of unpublished data sources from collaborators, an updated version of modelling software, and several improvements in our methods. In this systematic analysis, we use data from GBD 2013 to analyse the burden of disease and injuries in the eastern Mediterranean region specifically. Findings The leading cause of death in the region in 2013 was ischaemic heart disease (90·3 deaths per 100�000 people), which increased by 17·2 since 1990. However, diarrhoeal diseases were the leading cause of death in Somalia (186·7 deaths per 100�000 people) in 2013, which decreased by 26·9 since 1990. The leading cause of disability-adjusted life-years (DALYs) was ischaemic heart disease for males and lower respiratory infection for females. High blood pressure was the leading risk factor for DALYs in 2013, with an increase of 83·3 since 1990. Risk factors for DALYs varied by country. In low-income countries, childhood wasting was the leading cause of DALYs in Afghanistan, Somalia, and Yemen, whereas unsafe sex was the leading cause in Djibouti. Non-communicable risk factors were the leading cause of DALYs in high-income and middle-income countries in the region. DALY risk factors varied by age, with child and maternal malnutrition affecting the younger age groups (aged 28 days to 4 years), whereas high bodyweight and systolic blood pressure affected older people (aged 60�80 years). The proportion of DALYs attributed to high body-mass index increased from 3·7 to 7·5 between 1990 and 2013. Burden of mental health problems and drug use increased. Most increases in DALYs, especially from non-communicable diseases, were due to population growth. The crises in Egypt, Yemen, Libya, and Syria have resulted in a reduction in life expectancy; life expectancy in Syria would have been 5 years higher than that recorded for females and 6 years higher for males had the crisis not occurred. Interpretation Our study shows that the eastern Mediterranean region is going through a crucial health phase. The Arab uprisings and the wars that followed, coupled with ageing and population growth, will have a major impact on the region's health and resources. The region has historically seen improvements in life expectancy and other health indicators, even under stress. However, the current situation will cause deteriorating health conditions for many countries and for many years and will have an impact on the region and the rest of the world. Based on our findings, we call for increased investment in health in the region in addition to reducing the conflicts. Funding Bill & Melinda Gates Foundation. © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY licens

Structure, electronic and elastic properties of the NbRu shape memory alloys

The phase stability and electronic structure of NbRu shape memory alloys are studied by self-consistent full-potential linearized augmented plane wave method (FP-LAPW) on the basis of the density functional theory (DFT). The calculated equilibrium volumes are about 32 Å3 and 30 Å3 for β-, β′ and β′′ phases using the generalized gradient approximation (GGA) and local density approximation (LDA), respectively, which are in good agreement with the experimental values. The β′′-phase is favored by about 65 meV/formula than the β-phase. The value of the density of states at the Fermi energy, confirms that the β′′ phase is the ground state equilibrium phase of NbRu at low temperatures, in agreement with the experimental findings. Our results put an end to the experimental debate regarding the β′′ phase whether it is orthorhombic or monoclinic. By optimizing the angle γ, we found that the β′′ structure is monoclinic of (P21/m) symmetry