Lignosulfonic Acid Exhibits Broadly Anti-HIV-1 Activity – Potential as a Microbicide Candidate for the Prevention of HIV-1 Sexual Transmission

Some secondary metabolites from plants show to have potent inhibitory activities against microbial pathogens, such as human immunodeficiency virus (HIV), herpes simplex virus (HSV), Treponema pallidum, Neisseria gonorrhoeae, etc. Here we report that lignosulfonic acid (LSA), a polymeric lignin derivative, exhibits potent and broad activity against HIV-1 isolates of diverse subtypes including two North America strains and a number of Chinese clinical isolates values ranging from 21.4 to 633 nM. Distinct from other polyanions, LSA functions as an entry inhibitor with multiple targets on viral gp120 as well as on host receptor CD4 and co-receptors CCR5/CXCR4. LSA blocks viral entry as determined by time-of-drug addiction and cell-cell fusion assays. Moreover, LSA inhibits CD4-gp120 interaction by blocking the binding of antibodies specific for CD4-binding sites (CD4bs) and for the V3 loop of gp120. Similarly, LSA interacts with CCR5 and CXCR4 via its inhibition of specific anti-CCR5 and anti-CXCR4 antibodies, respectively. Interestingly, the combination of LSA with AZT and Nevirapine exhibits synergism in viral inhibition. For the purpose of microbicide development, LSA displays low in vitro cytotoxicity to human genital tract epithelial cells, does not stimulate NF-κB activation and has no significant up-regulation of IL-1α/β and IL-8 as compared with N-9. Lastly, LSA shows no adverse effect on the epithelial integrity and the junctional protein expression. Taken together, our findings suggest that LSA can be a potential candidate for tropical microbicide

First Measurement of the Electron Neutrino Charged-Current Pion Production Cross Section on Carbon with the T2K Near Detector

International audienceThe T2K Collaboration presents the first measurement of electron neutrino-induced charged-current pion production on carbon in a restricted kinematical phase space. This is performed using data from the 2.5$^{\deg}$ off-axis near detector, ND280. The differential cross sections with respect to the outgoing electron and pion kinematics, in addition to the total flux-integrated cross section, are obtained. Comparisons between the measured and predicted cross section results using the Neut, Genie and NuWro Monte Carlo event generators are presented. The measured total flux-integrated cross section is [2.52 $\pm$ 0.52 (stat) $\pm$ 0.30 (sys)] x $10^{-39}$ cm$^2$ nucleon$^{-1}$, which is lower than the event generator predictions

First measurement of neutron capture multiplicity in neutrino-oxygen neutral-current quasi-elastic-like interactions using an accelerator neutrino beam

International audienceWe report the first measurement of neutron capture multiplicity in neutrino-oxygen neutral-current quasi-elastic-like interactions at the gadolinium-loaded Super-Kamiokande detector using the T2K neutrino beam, which has a peak energy of about 0.6 GeV. A total of 30 neutral-current quasi-elastic-like event candidates were selected from T2K data corresponding to an exposure of $1.76\times10^{20}$ protons on target. The $\gamma$ ray signals resulting from neutron captures were identified using a neural network. The flux-averaged mean neutron capture multiplicity was measured to be $1.37\pm0.33\text{ (stat.)}$$(^{+0.17}_{-0.27})$, which is compatible within $2.3\,\sigma$ than predictions obtained using our nominal simulation. We discuss potential sources of systematic uncertainty in the prediction and demonstrate that a significant portion of this discrepancy arises from the modeling of hadron-nucleus interactions in the detector medium

First measurement of neutron capture multiplicity in neutrino-oxygen neutral-current quasielasticlike interactions using an accelerator neutrino beam

We report the first measurement of neutron capture multiplicity in neutrino-oxygen neutral-current quasielasticlike interactions at the gadolinium-loaded Super-Kamiokande detector using the T2K neutrino beam, which has a peak energy of about 0.6 GeV. A total of 30 neutral-current quasielasticlike event candidates were selected from T2K data corresponding to an exposure of 1.76×1020 protons on target. The γ ray signals resulting from neutron captures were identified using a neural network. The flux-averaged mean neutron capture multiplicity was measured to be 1.37±0.33 (stat.)−0.27+0.17 (syst.), which is compatible within 2.3 sigma than predictions obtained using our nominal simulation. We discuss potential sources of systematic uncertainty in the prediction and demonstrate that a significant portion of this discrepancy arises from the modeling of hadron-nucleus interactions in the detector medium.</jats:p