Mutating chikungunya virus non‐structural protein produces potent live‐attenuated vaccine candidate

Currently, there are no commercially available live‐attenuated vaccines against chikungunya virus (CHIKV). Here, CHIKVs with mutations in non‐structural proteins (nsPs) were investigated for their suitability as attenuated CHIKV vaccines. R532H mutation in nsP1 caused reduced infectivity in mouse tail fibroblasts but an enhanced type‐I IFN response compared to WT‐CHIKV. Adult mice infected with this nsP‐mutant exhibited a mild joint phenotype with low‐level viremia that rapidly cleared. Mechanistically, ingenuity pathway analyses revealed a tilt in the anti‐inflammatory IL‐10 versus pro‐inflammatory IL‐1β and IL‐18 balance during CHIKV nsP‐mutant infection that modified acute antiviral and cell signaling canonical pathways. Challenging CHIKV nsP‐mutant‐infected mice with WT‐CHIKV or the closely related O'nyong‐nyong virus resulted in no detectable viremia, observable joint inflammation, or damage. Challenged mice showed high antibody titers with efficient neutralizing capacity, indicative of immunological memory. Manipulating molecular processes that govern CHIKV replication could lead to plausible vaccine candidates against alphavirus infection

Depression after low-energy fracture in older women predicts future falls: a prospective observational study

<p>Abstract</p> <p>Background</p> <p>Falls are one of the main causes of fractures in elderly people and after a recent fracture, the risk of another fall is increased, resulting in subsequent fracture. Therefore, risk factors for future falls should be determined. We prospectively investigated the relationship between depression and the incidence of falls in post-menopausal women after a low-energy fracture.</p> <p>Methods</p> <p>At baseline, 181 women aged 60 years and older who presented with a recent low-energy fracture were evaluated at the fracture and osteoporosis outpatient clinics of two hospitals. As well as clinical evaluation and bone mineral density tests, the presence of depression (measured using the Edinburgh Depression Scale, EDS, depression cut-off > 11) and risk factors for falling were assessed. During two years of follow-up, the incidence of falls was registered annually by means of detailed questionnaires and interviews.</p> <p>Results</p> <p>Seventy-nine (44%) of the women sustained at least one fall during follow-up. Of these, 28% (<it>n </it>= 22) suffered from depression at baseline compared to 10% (<it>n </it>= 10) of the 102 women who did not sustain a fall during follow-up (<it>Χ</it>²= 8.76, df = 1, <it>p </it>= .003). Multiple logistic regression showed that the presence of depression and co-morbidity at baseline were independently related to falls (OR = 4.13, 95% CI = 1.58-10.80; OR = 2.25, 95% CI = 1.11-4.56, respectively) during follow-up.</p> <p>Conclusions</p> <p>The presence of depression in women aged 60 years and older with recent low-energy fractures is an important risk factor for future falls. We propose that clinicians treating patients with recent low-energy fractures should anticipate not only on skeletal-related risk factors for fractures, but also on fall-related risk factors including depression.</p

Medium-induced modification of groomed and ungroomed jet mass and angularities in Pb–Pb collisions at s NN = 5.02 Image 1

The ALICE Collaboration presents a new suite of jet substructure measurements in Pb–Pb and pp collisions at a center-of-mass energy per nucleon pair sNN=5.02 [Figure presented]. These measurements provide access to the internal structure of jets via the momentum and angle of their constituents, probing how the quark–gluon plasma modifies jets, an effect known as jet quenching. Jet grooming additionally removes soft wide-angle radiation to enhance perturbative accuracy and reduce experimental uncertainties. We report the groomed and ungroomed jet mass mjet and jet angularities λα κ using κ=1 and α&gt;0. Charged-particle jets are reconstructed at midrapidity using the anti-kT algorithm with resolution parameter R=0.2. A narrowing of the jet mass and angularity distributions in Pb–Pb collisions with respect to pp is observed and is enhanced for groomed results, confirming modification of the jet core. By using consistent jet definitions and kinematic cuts between the mass and angularities for the first time, previous inconsistencies in the interpretation of quenching measurements are resolved, rectifying a hurdle for understanding how jet quenching arises from first principles and highlighting the importance of a well-controlled baseline. These results are compared with a variety of theoretical models of jet quenching, providing constraints on jet energy-loss mechanisms in the quark–gluon plasma

Measurement of the inclusive isolated-photon production cross section in pp collisions at s=13 TeV

The production cross section of inclusive isolated photons has been measured by the ALICE experiment at the CERN LHC in pp collisions at centre-of-momentum energy of s=13&nbsp;TeV collected during the LHC Run 2 data-taking period. The measurement is performed by combining the measurements of the electromagnetic calorimeter EMCal and the central tracking detectors ITS and TPC, covering a pseudorapidity range of |ηγ|&lt;0.67 and a transverse momentum range of

Measurement of ω meson production in pp collisions at s = 13 TeV

The pT-differential cross section of ω meson production in pp collisions at s = 13 TeV at midrapidity (|y| &lt; 0.5) was measured with the ALICE detector at the LHC, covering an unprecedented transverse-momentum range of 1.6 &lt; pT&lt; 50 GeV/c. The meson is reconstructed via the ω → π+π−π0 decay channel. The results are compared with various theoretical calculations: PYTHIA8.2 with the Monash 2013 tune overestimates the data by up to 50%, whereas good agreement is observed with Next-to-Leading Order (NLO) calculations incorporating ω fragmentation using a broken SU(3) model. The ω/π0 ratio is presented and compared with theoretical calculations and the available measurements at lower collision energies. The presented data triples the pT ranges of previously available measurements. A constant ratio of Cω/π0 = 0.578 ± 0.006 (stat.) ± 0.013 (syst.) is found above a transverse momentum of 4 GeV/c, which is in agreement with previous findings at lower collision energies within the systematic and statistical uncertainties

Probing Strangeness Hadronization with Event-by-Event Production of Multistrange Hadrons

This Letter presents the first measurement of event-by-event fluctuations of the net number (difference between the particle and antiparticle multiplicities) of multistrange hadrons Ξ^{-} and Ξ[over ¯]^{+} and its correlation with the net-kaon number using the data collected by the ALICE Collaboration in pp, p-Pb, and Pb-Pb collisions at a center-of-mass energy per nucleon pair sqrt[s_{NN}]=5.02  TeV. The statistical hadronization model with a correlation over three units of rapidity between hadrons having the same and opposite strangeness content successfully describes the results. On the other hand, string-fragmentation models that mainly correlate strange hadrons with opposite strange quark content over a small rapidity range fail to describe the data