Tenofovir disoproxil fumarate induces peripheral neuropathy and alters inflammation and mitochondrial biogenesis in the brains of mice.

Mounting evidence suggests that antiretroviral therapy (ART) drugs may contribute to the prevalence of HIV-associated neurological dysfunction. The HIV envelope glycoprotein (gp120) is neurotoxic and has been linked to alterations in mitochondrial function and increased inflammatory gene expression, which are common neuropathological findings in HIV+ cases on ART with neurological disorders. Tenofovir disproxil fumarate (TDF) has been shown to affect neurogenesis in brains of mice and mitochondria in neurons. In this study, we hypothesized that TDF contributes to neurotoxicity by modulating mitochondrial biogenesis and inflammatory pathways. TDF administered to wild-type (wt) and GFAP-gp120 transgenic (tg) mice caused peripheral neuropathy, as indicated by nerve conduction slowing and thermal hyperalgesia. Conversely TDF protected gp120-tg mice from cognitive dysfunction. In the brains of wt and gp120-tg mice, TDF decreased expression of mitochondrial transcription factor A (TFAM). However, double immunolabelling revealed that TFAM was reduced in neurons and increased in astroglia in the hippocampi of TDF-treated wt and gp120-tg mice. TDF also increased expression of GFAP and decreased expression of IBA1 in the wt and gp120-tg mice. TDF increased tumor necrosis factor (TNF) α in wt mice. However, TDF reduced interleukin (IL) 1β and TNFα mRNA in gp120-tg mouse brains. Primary human astroglia were exposed to increasing doses of TDF for 24 hours and then analyzed for mitochondrial alterations and inflammatory gene expression. In astroglia, TDF caused a dose-dependent increase in oxygen consumption rate, extracellular acidification rate and spare respiratory capacity, changes consistent with increased metabolism. TDF also reduced IL-1β-mediated increases in IL-1β and TNFα mRNA. These data demonstrate that TDF causes peripheral neuropathy in mice and alterations in inflammatory signaling and mitochondrial activity in the brain

Strong lensing constraints on the velocity dispersion and density profile of elliptical galaxies

We use the statistics of strong gravitational lensing from the CLASS survey to impose constraints on the velocity dispersion and density profile of elliptical galaxies. This approach differs from much recent work, where the luminosity function, velocity dispersion and density profile were typically {\it assumed} in order to constrain cosmological parameters. It is indeed remarkable that observational cosmology has reached the point where we can consider using cosmology to constrain astrophysics, rather than vice versa. We use two different observables to obtain our constraints (total optical depth and angular distributions of lensing events). In spite of the relatively poor statistics and the uncertain identification of lenses in the survey, we obtain interesting constraints on the velocity dispersion and density profiles of elliptical galaxies. For example, assuming the SIS density profile and marginalizing over other relevant parameters, we find 168 km/s < sigma_* < 200 km/s (68% CL), and 158 km/s < sigma_* < 220 km/s (95% CL). Furthermore, if we instead assume a generalized NFW density profile and marginalize over other parameters, the slope of the profile is constrained to be 1.50 < beta < 2.00 (95% CL). We also constrain the concentration parameter as a function of the density profile slope in these models. These results are essentially independent of the exact knowledge of cosmology. We briefly discuss the possible impact on these constraints of allowing the galaxy luminosity function to evolve with redshift, and also possible useful future directions for exploration.Comment: Uses the final JVAS/CLASS sample, more careful choice of ellipticals, added discussion of possible biases. Final results essentially unchanged. Matches the MNRAS versio

El Mañana: Año III Número 501 - (26/08/30)

Synchronous, time-resolved DRIFTS/MS/XAS cycling studies of the vapor phase selective aerobic oxidation of crotyl alcohol over nanoparticulate palladium reveal surface oxide as the desired catalytically active phase, with dynamic, reaction-induced palladium redox processes controlling selective versus combustion pathways

Electric Dipole Moments in the MSSM at Large tan(beta)

Within the minimal supersymmetric standard model (MSSM), the large tan(beta) regime can lead to important modifications in the pattern of CP-violating sources contributing to low energy electric dipole moments (EDMs). In particular, four-fermion CP-violating interactions induced by Higgs exchange should be accounted for alongside the constituent EDMs of quarks and electrons. To this end, we present a comprehensive analysis of three low energy EDM observables - namely the EDMs of thallium, mercury and the neutron - at large tan(beta), in terms of one- and two-loop contributions to the constituent EDMs and four-fermion interactions. We concentrate on the constrained MSSM as well as the MSSM with non-universal Higgs masses, and include the CP-violating phases of mu and A. Our results indicate that the atomic EDMs receive significant corrections from four-fermion operators, especially when Im(A) is the only CP-violating source, whereas the neutron EDM remains relatively insensitive to these effects. As a consequence, in a large portion of the parameter space, one cannot infer a separate bound on the electron EDM via the experimental constraint on the thallium EDM. Furthermore, we find that the electron EDM can be greatly reduced due to the destructive interference of one- and two-loop contributions with the latter being dominated by virtual staus.Comment: 39 pages, 17 figure

Triton calculations with π\pi and ρ\rho exchange three-nucleon forces

The Faddeev equations are solved in momentum space for the trinucleon bound state with the new Tucson-Melbourne $\pi$ and $\rho$ exchange three-nucleon potentials. The three-nucleon potentials are combined with a variety of realistic two-nucleon potentials. The dependence of the triton binding energy on the $\pi NN$ cut-off parameter in the three-nucleon potentials is studied and found to be reduced compared to the case with pure $\pi$ exchange. The $\rho$ exchange parts of the three-nucleon potential yield an overall repulsive effect. When the recommended parameters are employed, the calculated triton binding energy turns out to be very close to its experimental value. Expectation values of various components of the three-nucleon potential are given to illustrate their significance for binding.Comment: 17 pages Revtex 3.0, 4 figures. Accepted for publication in Phys. Rev.

Proposed Lunar Measurements of rr-Process Radioisotopes to Distinguish Origin of Deep-sea 244Pu

244Pu has recently been discovered in deep-sea deposits spanning the past 10 Myr, a period that includes two 60Fe pulses from nearby supernovae. 244Pu is among the heaviest $r$-process products, and we consider whether it was created in the supernovae, which is disfavored by nucleosynthesis simulations, or in an earlier kilonova event that seeded 244Pu in the nearby interstellar medium that was subsequently swept up by the supernova debris. We discuss how these possibilities can be probed by measuring 244Pu and other $r$-process radioisotopes such as 129I and 182Hf, both in lunar regolith samples returned to Earth by missions such as Chang'e and Artemis, and in deep-sea deposits.Comment: Extensive rewrite of v1 with added emphasis of lunar sample return missions, including Artemis and Chang'e. 11 pages, 4 figures, 2 tabl

Brane-world Cosmologies with non-local bulk effects

It is very common to ignore the non-local bulk effects in the study of brane-world cosmologies using the brane-world approach. However, we shall illustrate through the use of three different scenarios, that the non-local bulk-effect ${\cal P}_{\mu\nu}$ does indeed have significant impact on both the initial and future behaviour of brane-world cosmologies.Comment: 17 pages, no figures, iopart.cls, submitted to CQ