The role of the chemokine receptor CXCR4 in infection with feline immunodeficiency virus

Infection with feline immunodeficiency virus (FIV) leads to the development of a disease state similar to AIDS in man. Recent studies have identified the chemokine receptor CXCR4 as the major receptor for cell culture-adapted strains of FIV, suggesting that FIV and human immunodeficiency virus (HIV) share a common mechanism of infection involving an interaction between the virus and a member of the seven transmembrane domain superfamily of molecules. This article reviews the evidence for the involvement of chemokine receptors in FIV infection and contrasts these findings with similar studies on the primate lentiviruses HIV and SIV (simian immunodeficiency virus)

New data on OZI rule violation in bar{p}p annihilation at rest

The results of a measurement of the ratio R = Y(phi pi+ pi-) / Y(omega pi+ pi-) for antiproton annihilation at rest in a gaseous and in a liquid hydrogen target are presented. It was found that the value of this ratio increases with the decreasing of the dipion mass, which demonstrates the difference in the phi and omega production mechanisms. An indication on the momentum transfer dependence of the apparent OZI rule violation for phi production from the 3S1 initial state was found.Comment: 11 pages, 3 PostScript figures, submitted to Physics Letter

Antiproton slowing Down in H2 and He and evidence of nuclear stopping power

We report stopping powers of hydrogen and helium for antiprotons of kinetic energies ranging from about 0.5 keV to 1.1 MeV. The Barkas effect, i.e., a difference in the stopping power for antiprotons and protons of the same energy in the same material, shows up clearly in either of the gases. Moreover, below ≈0.5 keV there is indirect evidence for an increase of the antiproton stopping power. This "nuclear" effect, i.e., energy losses in quasimolecular interactions, shows up in fair agreement with theoretical predictions

Chemokine Transfer by Liver Sinusoidal Endothelial Cells Contributes to the Recruitment of CD4+ T Cells into the Murine Liver

Leukocyte adhesion and transmigration are central features governing immune surveillance and inflammatory reactions in body tissues. Within the liver sinusoids, chemokines initiate the first crucial step of T-cell migration into the hepatic tissue. We studied molecular mechanisms involved in endothelial chemokine supply during hepatic immune surveillance and liver inflammation and their impact on the recruitment of CD4+ T cells into the liver. In the murine model of Concanavalin A-induced T cell-mediated hepatitis, we showed that hepatic expression of the inflammatory CXC chemokine ligands (CXCL)9 and CXCL10 strongly increased whereas homeostatic CXCL12 significantly decreased. Consistently, CD4+ T cells expressing the CXC chemokine receptor (CXCR)3 accumulated within the inflamed liver tissue. In histology, CXCL9 was associated with liver sinusoidal endothelial cells (LSEC) which represent the first contact site for T-cell immigration into the liver. LSEC actively transferred basolaterally internalized CXCL12, CXCL9 and CXCL10 via clathrin- coated vesicles to CD4+ T cells leading to enhanced transmigration of CXCR4+ total CD4+ T cells and CXCR3+ effector/memory CD4+ T cells, respectively in vitro. LSEC-expressed CXCR4 mediated CXCL12 transport and blockage of endothelial CXCR4 inhibited CXCL12-dependent CD4+ T-cell transmigration. In contrast, CXCR3 was not involved in the endothelial transport of its ligands CXCL9 and CXCL10. The clathrin-specific inhibitor chlorpromazine blocked endothelial chemokine internalization and CD4+ T-cell transmigration in vitro as well as migration of CD4+ T cells into the inflamed liver in vivo. Moreover, hepatic accumulation of CXCR3+ CD4+ T cells during T cell-mediated hepatitis was strongly reduced after administration of chlorpromazine. These data demonstrate that LSEC actively provide perivascularly expressed homeostatic and inflammatory chemokines by CXCR4- and clathrin-dependent intracellular transport mechanisms thereby contributing to the hepatic recruitment of CD4+ T-cell populations during immune surveillance and liver inflammation

Experimental antiproton nuclear stopping power in H2 and D2

Data about antiprotons slowing down in gaseous targets at very low energies (E<1 keV) show that the stopping power in D2 is lower than in H2; the right way to explain this behavior seems to be through a nuclear stopping power derived from the classical Rutherford formula

Hyper-Osmotic Stress Elicits Membrane Depolarization and Decreased Permeability in Halotolerant Marine Debaryomyces hansenii Strains and in Saccharomyces cerevisiae

The use of seawater and marine microorganisms can represent a sustainable alternative to avoid large consumption of freshwater performing industrial bioprocesses. Debaryomyces hansenii, which is a known halotolerant yeast, possess metabolic traits appealing for developing such processes. For this purpose, we studied salt stress exposure of two D. hansenii strains isolated from marine fauna. We found that the presence of sea salts during the cultivation results in a slight decrease of biomass yields. Nevertheless, higher concentration of NaCl (2 M) negatively affects other growth parameters, like growth rate and glucose consumption rate. To maintain an isosmotic condition, the cells accumulate glycerol as compatible solute. Flow cytometry analysis revealed that the osmotic adaptation causes a reduced cellular permeability to cell-permeant dye SYBR Green I. We demonstrate that this fast and reversible phenomenon is correlated to the induction of membrane depolarization, and occurred even in presence of high concentration of sorbitol. The decrease of membrane permeability induced by osmotic stress confers to D. hansenii resistance to cationic drugs like Hygromycin B. In addition, we describe that also in Saccharomyces cerevisiae the exposure to hyper-osmotic conditions induced membrane depolarization and reduced the membrane permeability. These aspects are very relevant for the optimization of industrial bioprocesses, as in the case of fermentations and bioconversions carried out by using media/buffers containing high nutrients/salts concentrations. Indeed, an efficient transport of molecules (nutrients, substrates, and products) is the prerequisite for an efficient cellular performance, and ultimately for the efficiency of the industrial process

Antiproton stopping power in hydrogen below 120 keV and the Barkas effect

The simultaneous measurement of the spatial coordinates and times of p¯s annihilating at rest in a H2 target at very low density ρ (ρ/ρ0<10-2, ρ0 being the STP density) gives the possibility of evaluating the behavior of the p¯ stopping power in H2 at low energies (below 120 keV). It is different from that of protons (the Barkas effect). Moreover, it is shown that a rise at low-energy values (≲1 keV) is needed to agree with experimental data

Early Steps of HIV-1 Fusion Define the Sensitivity to Inhibitory Peptides That Block 6-Helix Bundle Formation

The HIV envelope (Env) glycoprotein mediates membrane fusion through sequential interactions with CD4 and coreceptors, followed by the refolding of the transmembrane gp41 subunit into the stable 6-helix bundle (6HB) conformation. Synthetic peptides derived from the gp41 C-terminal heptad repeat domain (C-peptides) potently inhibit fusion by binding to the gp41 pre-bundle intermediates and blocking their conversion into the 6HB. Our recent work revealed that HIV-1 enters cells by fusing with endosomes, but not with the plasma membrane. These studies also showed that, for the large part, gp41 pre-bundles progress toward 6HBs in endosomal compartments and are thus protected from external fusion inhibitors. Here, we examined the consequences of endocytic entry on the gp41 pre-bundle exposure and on the virus' sensitivity to C-peptides. The rates of CD4 and coreceptor binding, as well as the rate of productive receptor-mediated endocytosis, were measured by adding specific inhibitors of these steps at varied times of virus-cell incubation. Following the CD4 binding, CCR5-tropic viruses recruited a requisite number of coreceptors much faster than CXCR4-tropic viruses. The rate of subsequent uptake of ternary Env-CD4-coreceptor complexes did not correlate with the kinetics of coreceptor engagement. These measurements combined with kinetic analyses enabled the determination of the lifetime of pre-bundle intermediates on the cell surface. Overall, these lifetimes correlated with the inhibitory potency of C-peptides. On the other hand, the basal sensitivity to peptides varied considerably among diverse HIV-1 isolates and ranked similarly with their susceptibility to inactivation by soluble CD4. We conclude that both the longevity of gp41 intermediates and the extent of irreversible conformational changes in Env upon CD4 binding determine the antiviral potency of C-peptides

Nuclear physics midterm plan at Legnaro National Laboratories (LNL)

The next years will see the completion of the radioactive ion beam facility SPES (Selective Production of Exotic Species) and the upgrade of the accelerators complex at Istituto Nazionale di Fisica Nucleare – Legnaro National Laboratories (LNL) opening up new possibilities in the fields of nuclear structure, nuclear dynamics, nuclear astrophysics, and applications. The nuclear physics community has organised a workshop to discuss the new physics opportunities that will be possible in the near future by employing state-of-the-art detection systems. A detailed discussion of the outcome from the workshop is presented in this report