Deoxycholic acid liganded HBs contributes to HBV maturation

Understanding the underlying mechanism of HBV maturation and subviral particle production is critical to control HBV infection and develop new antiviral strategies. Here, we demonstrate that deoxycholic acid (DCA) plays a central role in HBV production. HBV infection increased DCA levels, whereas elimination of DCA-producing microbiome decreased HBV viral load. DCA can bind to HBs antigen via LXXLL motif at TM1 and TM2 region to regulate HBs-HBc interaction and the production of mature HBV. Plasma DCA levels from patients undergoing antiviral therapy were significantly higher in those with positive HBV viral load. These results suggest that intestinal DCA-producing microbiome can affect the efficiency of antiviral therapy and provide a potential novel strategy for HBV antiviral therapy.

How Sensitive Global Observables are to the Event Topology in Heavy-ion Collisions at the Large Hadron Collider: A Case Study

Particle production and event topology are very strongly correlated in high-energy hadronic and nuclear collisions. Event topology is decided by the underlying particle production dynamics and medium effects. Transverse spherocity is an event shape observable, which has been used in pp and heavy-ion collisions to separate the events based on their geometrical shapes. It has the unique capability to distinguish between jetty and isotropic events. In this work, we have implemented transverse spherocity in Pb-Pb collisions at √ sNN = 5.02 TeV using A Multi-Phase Transport Model (AMPT). While awaiting for experimental explorations, we perform a feasibility study of dependence of transverse spherocity on some of the global observables in heavy-ion collisions at the Large Hadron Collider energies. These global observables include the Bjorken energy density (εBj), speed of sound (cs2) in the medium and the kinetic freeze-out properties for different collision centralities. The present study reveals about the usefulness of event topology dependent measurements in heavy-ion collisions in contrast to proton-proton collisions.

Epigallocatechin Gallate (EGCG), a Green Tea Polyphenol, Reduces Coronavirus Replication in a Mouse Model

The COVID-19 pandemic has resulted in a huge number of deaths from 2020 to 2021; however, effective antiviral drugs against SARS-CoV-2 are currently under development. Recent studies have demonstrated that green tea polyphenols, particularly EGCG, inhibit coronavirus enzymes as well as coronavirus replication in vitro. Herein, we examined the inhibitory effect of green tea polyphenols on coronavirus replication in a mouse model. We used epigallocatechin gallate (EGCG) and green tea polyphenols containing more than 60% catechin (GTP60) and human coronavirus OC43 (HCoV-OC43) as a surrogate for SARS-CoV-2. Scanning electron microscopy analysis results showed that HCoV-OC43 infection resulted in virion particle production in infected cells. EGCG and GTP60 treatment reduced coronavirus protein and virus production in the cells. Finally, EGCG- and GTP60-fed mice exhibited reduced levels of coronavirus RNA in mouse lungs. These results demonstrate that green tea polyphenol treatment is effective in decreasing the level of coronavirus in vivo.

Gravitational waves and dark photon dark matter from axion rotations

An axion rotating in field space can produce dark photons in the early universe via tachyonic instability. This explosive particle production creates a background of stochastic gravitational waves that may be visible at pulsar timing arrays or other gravitational wave detectors. This scenario provides a novel history for dark photon dark matter. The dark photons may be warm at a level detectable in future 21-cm line surveys. For a consistent cosmology, the radial direction of the complex field containing the axion must be thermalized. We explore a concrete thermalization mechanism in detail and also demonstrate how this setup can be responsible for the generation of the observed baryon asymmetry.

Model emulation to understand the joint effects of ice-nucleating particles and secondary ice production on deep convective anvil cirrus

Ice crystal formation in the mixed-phase region of deep convective clouds can affect the properties of climatically important convectively generated anvil clouds. Small ice crystals in the mixed-phase cloud region can be formed by heterogeneous ice nucleation by ice-nucleating particles (INPs) and secondary ice production (SIP) by, for example, the Hallett–Mossop process. We quantify the effects of INP number concentration, the temperature dependence of the INP number concentration at mixed-phase temperatures, and the Hallett–Mossop splinter production efficiency on the anvil of an idealised deep convective cloud using a Latin hypercube sampling method, which allows optimal coverage of a multidimensional parameter space, and statistical emulation, which allows us to identify interdependencies between the three uncertain inputs. Our results show that anvil ice crystal number concentration (ICNC) is determined predominately by INP number concentration, with the temperature dependence of ice-nucleating aerosol activity having a secondary role. Conversely, anvil ice crystal size is determined predominately by the temperature dependence of ice-nucleating aerosol activity, with INP number concentration having a secondary role. This is because in our simulations ICNC is predominately controlled by the number concentration of cloud droplets reaching the homogeneous freezing level which is in turn determined by INP number concentrations at low temperatures. Ice crystal size, however, is more strongly affected by the amount of liquid available for riming and the time available for deposition growth which is determined by INP number concentrations at higher temperatures. This work indicates that the amount of ice particle production by the Hallett–Mossop process is determined jointly by the prescribed Hallett–Mossop splinter production efficiency and the temperature dependence of ice-nucleating aerosol activity. In particular, our sampling of the joint parameter space shows that high rates of SIP do not occur unless the INP parameterisation slope (the temperature dependence of the number concentration of particles which nucleate ice) is shallow, regardless of the prescribed Hallett–Mossop splinter production efficiency. A shallow INP parameterisation slope and consequently high ice particle production by the Hallett–Mossop process in our simulations leads to a sharp transition to a cloud with extensive glaciation at warm temperatures, higher cloud updraughts, enhanced vertical mass flux, and condensate divergence at the outflow level, all of which leads to a larger convectively generated anvil comprised of larger ice crystals. This work highlights the importance of quantifying the full spectrum of INP number concentrations across all mixed-phase altitudes and the ways in which INP and SIP interact to control anvil properties.

Bacterial safety study of the production process of hemoglobin-based oxygen carriers

Hemoglobin microparticles (HbMP) produced with a three-step procedure including co-precipitation of hemoglobin with manganese carbonate, protein crosslinking and dissolution of the carbonate template were shown to be suitable for application as artificial oxygen carriers. First preclinical safety investigations delivered promising results. Bacterial safety plays a decisive role during the production of the HbMP. Therefore, bioburden and endotoxin content of the starting materials (especially hemoglobin) and the final particle suspension are intensively tested. However, some bacteria may not have been detected by the standard tests due to low concentration. The aim of this study was to investigate how these bacteria would behave in the fabrication process. Biocidal effects are known for glutaraldehyde and for ethylenediaminetetraacetic acid, chemicals that are used in the fabrication process of HbMP. It could be shown that both chemicals prevent bacterial growth at the concentrations used during the HbMP fabrication. In addition, the particle production was carried out with hemoglobin solutions spiked with Escherichia coli or Staphylococcus epidermidis. No living bacteria could be detected in the final particle suspensions. Therefore, we conclude that the HbMP fabrication procedure is safe in respect of a bacterial contamination.

FUSE binding protein FUBP3 is a potent regulator in Japanese encephalitis virus infection

Background The JEV genome is a positive-sense RNA with a highly structured capped 5′UTR, 3′UTR and a large open reading frame. 3′UTR is the untranslated region of flavivirus and has various important functions during viral replication, such as translation, replication and encapsidation. During viral replication, the 3′UTR interacts with viral proteins and host proteins and is required for viral RNA replication and translocation. Methods The expression level of FUBP3 was knocked down by siRNA and Flag-tagged FUBP3 overexpression plasmid was constructed for overexpression. BHK-21 cells were cultured and infected with JEV to investigate the functional role of FUBP3 in the viral infection cycle. Subcellular localization of FUBP3 and viral replication complexes was observed by dual immunofluorescence staining. Results Four host proteins were specifically associated with the 3′UTR of JEV, and FUBP3 was selected to further investigate its potential functional role in the JEV infection cycle. Knockdown of FUBP3 protein resulted in a significant decrease in JEV viral titer, whereas ectopic overexpression of FUBP3 resulted in increased JE viral infectivity. In cells stably knocked down for FUBP3 and then infected with JEV, we found almost no detectable viral NS5 protein. In contrast, when cells stably knocking-down of FUBP3 overexpressed FUBP3, we found a significant increase in viral RNA production over time compared to controls. We also demonstrated that FUBP3 re-localized in the cytoplasm after infection with JEV and co-localized with viral proteins. Exogenous overexpression of FUBP3 was also shown to be located in the JE replication complex and to assist viral replication after JEV infection. Conclusions The overall results suggest that FUBP3 regulates RNA replication of JEV and promotes subsequent viral translation and viral particle production.

Cosmological particle production and pairwise hotspots on the CMB

Heavy particles with masses much bigger than the inflationary Hubble scale H*, can get non-adiabatically pair produced during inflation through their couplings to the inflaton. If such couplings give rise to time-dependent masses for the heavy particles, then following their production, the heavy particles modify the curvature perturbation around their locations in a time-dependent and scale non-invariant manner. This results into a non-trivial spatial profile of the curvature perturbation that is preserved on superhorizon scales and eventually generates localized hot or cold spots on the CMB. We explore this phenomenon by studying the inflationary production of heavy scalars and derive the final temperature profile of the spots on the CMB by taking into account the subhorizon evolution, focusing in particular on the parameter space where pairwise hot spots (PHS) arise. When the heavy scalar has an $$ \mathcal{O} $$ O (1) coupling to the inflaton, we show that for an idealized situation where the dominant background to the PHS signal comes from the standard CMB fluctuations themselves, a simple position space search based on applying a temperature cut, can be sensitive to heavy particle masses M0/H* ∼ $$ \mathcal{O} $$ O (100). The corresponding PHS signal also modifies the CMB power spectra and bispectra, although the corrections are below (outside) the sensitivity of current measurements (searches).