PPARα-targeted mitochondrial bioenergetics mediate repair of intestinal barriers at the host-microbe intersection during SIV infection.

Chronic gut inflammatory diseases are associated with disruption of intestinal epithelial barriers and impaired mucosal immunity. HIV-1 (HIV) causes depletion of mucosal CD4+ T cells early in infection and disruption of gut epithelium, resulting in chronic inflammation and immunodeficiency. Although antiretroviral therapy (ART) is effective in suppressing viral replication, it is incapable of restoring the "leaky gut," which poses an impediment for HIV cure efforts. Strategies are needed for rapid repair of the epithelium to protect intestinal microenvironments and immunity in inflamed gut. Using an in vivo nonhuman primate intestinal loop model of HIV/AIDS, we identified the pathogenic mechanism underlying sustained disruption of gut epithelium and explored rapid repair of gut epithelium at the intersection of microbial metabolism. Molecular, immunological, and metabolomic analyses revealed marked loss of peroxisomal proliferator-activated receptor-α (PPARα) signaling, predominant impairment of mitochondrial function, and epithelial disruption both in vivo and in vitro. To elucidate pathways regulating intestinal epithelial integrity, we introduced probiotic Lactobacillus plantarum into Simian immunodeficiency virus (SIV)-inflamed intestinal lumen. Rapid recovery of the epithelium occurred within 5 h of L. plantarum administration, independent of mucosal CD4+ T cell recovery, and in the absence of ART. This intestinal barrier repair was driven by L. plantarum-induced PPARα activation and restoration of mitochondrial structure and fatty acid β-oxidation. Our data highlight the critical role of PPARα at the intersection between microbial metabolism and epithelial repair in virally inflamed gut and as a potential mitochondrial target for restoring gut barriers in other infectious or gut inflammatory diseases

Using the local density approximation and the LYP, BLYP, and B3LYP functionals within Reference--State One--Particle Density--Matrix Theory

For closed-shell systems, the local density approximation (LDA) and the LYP, BLYP, and B3LYP functionals are shown to be compatible with reference-state one-particle density-matrix theory, where this recently introduced formalism is based on Brueckner-orbital theory and an energy functional that includes exact exchange and a non-universal correlation-energy functional. The method is demonstrated to reduce to a density functional theory when the exchange-correlation energy-functional has a simplified form, i.e., its integrand contains only the coordinates of two electron, say r1 and r2, and it has a Dirac delta function -- delta(r1 - r2) -- as a factor. Since Brueckner and Hartree--Fock orbitals are often very similar, any local exchange functional that works well with Hartree--Fock theory is a reasonable approximation with reference-state one-particle density-matrix theory. The LDA approximation is also a reasonable approximation. However, the Colle--Salvetti correlation-energy functional, and the LYP variant, are not ideal for the method, since these are universal functionals. Nevertheless, they appear to provide reasonable approximations. The B3LYP functional is derived using a linear combination of two functionals: One is the BLYP functional; the other uses exact exchange and a correlation-energy functional from the LDA.Comment: 26 Pages, 0 figures, RevTeX 4, Submitted to Mol. Phy

Self-Diffusion of a Polymer Chain in a Melt

Self-diffusion of a polymer chain in a melt is studied by Monte Carlo simulations of the bond fluctuation model, where only the excluded volume interaction is taken into account. Polymer chains, each of which consists of $N$ segments, are located on an $L \times L \times L$ simple cubic lattice under periodic boundary conditions, where each segment occupies $2 \times 2 \times 2$ unit cells. The results for $N=32, 48, 64, 96, 128, 192, 256, 384$ and 512 at the volume fraction $\phi \simeq 0.5$ are reported, where $L = 128$ for $N \leq 256$ and L=192 for $N \geq 384$. The $N$-dependence of the self-diffusion constant $D$ is examined. Here, $D$ is estimated from the mean square displacements of the center of mass of a single polymer chain at the times larger than the longest relaxation time. From the data for $N = 256$, 384 and 512, the apparent exponent $x_{\rm d}$, which describes the apparent power law dependence of $D$ on $N$ as $D \propto N^{- x_{\rm d}}$, is estimated as $x_{\rm d} \simeq 2.4$. The ratio $D \tau /$ seems to be a constant for $N = 192, 256, 384$ and 512, where $\tau$ and $$ denote the longest relaxation time and the mean square end-to-end distance, respectively.Comment: 4 pages, 3 figures, submitted to J. Phys. Soc. Jp

Relaxation of a Single Knotted Ring Polymer

The relaxation of a single knotted ring polymer is studied by Brownian dynamics simulations. The relaxation rate lambda_q for the wave number q is estimated by the least square fit of the equilibrium time-displaced correlation function to a double exponential decay at long times. The relaxation rate distribution of a single ring polymer with the trefoil knot appears to behave as lambda_q=A(1/N^)x for q=1 and lambda_q=A'(q/N)^x' for q=2 and 3, where x=2.61, x'=2.02 and A>A'. The wave number q of the slowest relaxation rate for each N is given by q=2 for small values of N, while it is given by q=1 for large values of N. This crossover corresponds to the change of the structure of the ring polymer caused by the localization of the knotted part to a part of the ring polymer.Comment: 13 pages, 5 figures, uses jpsj2.cl

OGLE-2014-BLG-0289: Precise Characterization of a Quintuple-peak Gravitational Microlensing Event

We present the analysis of the binary-microlensing event OGLE-2014-BLG-0289. The event light curve exhibits five very unusual peaks, four of which were produced by caustic crossings and the other by a cusp approach. It is found that the quintuple-peak features of the light curve provide tight constraints on the source trajectory, enabling us to precisely and accurately measure the microlensing parallax πE. Furthermore, the three resolved caustics allow us to measure the angular Einstein radius θE. From the combination of πE and θE, the physical lens parameters are uniquely determined. It is found that the lens is a binary composed of two M dwarfs with masses M1 = 0.52 ± 0.04 M⊙ and M2 = 0.42 ± 0.03 M⊙ separated in projection by a⊥ = 6.4 ± 0.5 au. The lens is located in the disk with a distance of DL = 3.3 ± 0.3 kpc. The reason for the absence of a lensing signal in the Spitzer data is that the time of observation corresponds to the flat region of the light curve