Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage

© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes

The burden of diseases and risk factors in Bangladesh, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Bangladesh has made substantial progress in improving socioeconomic and health indicators over the past 50 years, but data on national disease burden are scarce. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to estimate the burden of diseases and risk factors in Bangladesh from 1990 to 2019. / Methods: For this systematic analysis, we analysed data from vital registration systems, surveys, and censuses using multistage modelling processes to estimate life expectancy at birth, mortality rate, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs). Additionally, we compared the health status of Bangladesh with that of the other countries in the GBD south Asia region—Bhutan, India, Nepal, and Pakistan. / Findings: Life expectancy at birth in Bangladesh increased from 58·2 years (95% uncertainty interval 57·1–59·2) in 1990 to 74·6 years (72·4–76·7) in 2019. Between 1990 and 2019, the age-standardised mortality rate decreased from 1509·3 (1428·6–1592·1) to 714·4 (604·9–838·2) deaths per 100 000 population. In 2019, non-communicable diseases represented 14 of the top 20 causes of death; the leading three causes were stroke, ischaemic heart disease, and chronic obstructive pulmonary disease. High blood pressure, high fasting plasma glucose, and smoking were the top three risk factors. From 1990 to 2019, the rate of all-cause DALYs decreased by 54·9% (48·8–60·4). In 2019, the leading causes of DALYs and YLLs were neonatal disorders, stroke, and ischaemic heart disease, whereas musculoskeletal disorders, depressive disorders, and low back pain were the leading causes of YLDs. Bangladesh has the lowest age-standardised rates of mortality, YLDs, and YLLs and the highest life expectancy at birth in south Asia. / Interpretation: Over the past 30 years, mortality rates have reduced by more than half in Bangladesh. Bangladesh must now address the double burden of communicable and non-communicable diseases. Cost-effective, multisectoral efforts are needed to prevent and control non-communicable diseases, promote healthy lifestyles, and prevent premature mortality and disabilities. / Funding: Bill & Melinda Gates Foundation. / Translation: For the Bangla translation of the abstract see Supplementary Materials section

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO

Compressed representation of a partially defined integer function over multiple arguments

In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one

Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy

A search for new physics is performed in events with two same-sign isolated leptons, hadronic jets, and missing transverse energy in the final state. The analysis is based on a data sample corresponding to an integrated luminosity of 4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of 7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of 140 increase in integrated luminosity over previously published results. The observed yields agree with the standard model predictions and thus no evidence for new physics is found. The observations are used to set upper limits on possible new physics contributions and to constrain supersymmetric models. To facilitate the interpretation of the data in a broader range of new physics scenarios, information on the event selection, detector response, and efficiencies is provided.Comment: Published in Physical Review Letter

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Measurement of jet fragmentation into charged particles in pp and PbPb collisions at sqrt(s[NN]) = 2.76 TeV

Jet fragmentation in pp and PbPb collisions at a centre-of-mass energy of 2.76 TeV per nucleon pair was studied using data collected with the CMS detector at the LHC. Fragmentation functions are constructed using charged-particle tracks with transverse momenta pt > 4 GeV for dijet events with a leading jet of pt > 100 GeV. The fragmentation functions in PbPb events are compared to those in pp data as a function of collision centrality, as well as dijet-pt imbalance. Special emphasis is placed on the most central PbPb events including dijets with unbalanced momentum, indicative of energy loss of the hard scattered parent partons. The fragmentation patterns for both the leading and subleading jets in PbPb collisions agree with those seen in pp data at 2.76 TeV. The results provide evidence that, despite the large parton energy loss observed in PbPb collisions, the partition of the remaining momentum within the jet cone into high-pt particles is not strongly modified in comparison to that observed for jets in vacuum.Comment: Submitted to the Journal of High Energy Physic