1,615 research outputs found
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PPARĪ±-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-Ī± (PPARĪ±) 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 PPARĪ± activation and restoration of mitochondrial structure and fatty acid Ī²-oxidation. Our data highlight the critical role of PPARĪ± 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
P16-36. Functional genomic immune profile of SIV DNA vaccines delivered by electroporation and combined with molecular adjuvants
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
segments, are located on an simple cubic lattice
under periodic boundary conditions, where each segment occupies unit cells. The results for
and 512 at the volume fraction are reported, where
for and L=192 for . The -dependence of the
self-diffusion constant is examined. Here, 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 , 384
and 512, the apparent exponent , which describes the apparent power
law dependence of on as , is estimated as
. The ratio seems to be a
constant for and 512, where 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
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Report of the third Asian Prostate Cancer study meeting.
The Asian Prostate Cancer (A-CaP) study is an Asia-wide initiative that was launched in December 2015 in Tokyo, Japan, with the objective of surveying information about patients who have received a histopathological diagnosis of prostate cancer (PCa) and are undergoing treatment and clarifying distribution of staging, the actual status of treatment choices, and treatment outcomes. The study aims to clarify the clinical situation for PCa in Asia and use the outcomes for the purposes of international comparison. Following the first meeting in Tokyo in December 2015, the second A-CaP meeting was held in Seoul, Korea, in September 2016. This, the third A-CaP meeting, was held on October 14, 2017, in Chiang Mai, Thailand, with the participation of members and collaborators from 12 countries and regions. In the meeting, participating countries and regions presented the current status of data collection, and the A-CaP office presented a preliminary analysis of the registered cases received from each country and region. Participants discussed ongoing challenges relating to data input and collection, institutional, and legislative issues that may present barriers to data sharing, and the outlook for further patient registrations through to the end of the registration period in December 2018. In addition to A-CaP-specific discussions, a series of special lectures were also delivered on the situation for health insurance in the United States, the correlation between insurance coverage and PCa outcomes, and the outlook for robotic surgery in the Asia-Pacific region. Members also confirmed the principles of authorship in collaborative studies, with a view to publishing original articles based on A-CaP data in the future
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
Nkx3.2 Promotes Primary Chondrogenic Differentiation by Upregulating Col2a1 Transcription
Background: The Nkx3.2 transcription factor promotes chondrogenesis by forming a positive regulatory loop with a crucial chondrogenic transcription factor, Sox9. Previous studies have indicated that factors other than Sox9 may promote chondrogenesis directly, but these factors have not been identified. Here, we test the hypothesis that Nkx3.2 promotes chondrogenesis directly by Sox9-independent mechanisms and indirectly by previously characterized Sox9-dependent mechanisms. Methodology/Principal Findings: C3H10T1/2 pluripotent mesenchymal cells were cultured with bone morphogenetic protein 2 (BMP2) to induce endochondral ossification. Overexpression of wild-type Nkx3.2 (WT-Nkx3.2) upregulated glycosaminoglycan (GAG) production and expression of type II collagen a1 (Col2a1) mRNA, and these effects were evident before WT-Nkx3.2-mediated upregulation of Sox9. RNAi-mediated inhibition of Nkx3.2 abolished GAG production and expression of Col2a1 mRNA. Dual luciferase reporter assays revealed that WT-Nkx3.2 upregulated Col2a1 enhancer activity in a dose-dependent manner in C3H10T1/2 cells and also in N1511 chondrocytes. In addition, WT-Nkx3.2 partially restored downregulation of GAG production, Col2 protein expression, and Col2a1 mRNA expression induced by Sox9 RNAi. ChIP assays revealed that Nkx3.2 bound to the Col2a1 enhancer element. Conclusions/Significance: Nkx3.2 promoted primary chondrogenesis by two mechanisms: Direct and Sox9-independen
Largeāscale calculations of excitation energies in coupled cluster theory : The singlet excited states of benzene
Algorithms for calculating singlet excitation energies in the coupled cluster singles and doubles (CCSD) model are discussed and an implementation of an atomicāintegral direct algorithm is presented. Each excitation energy is calculated at a cost comparable to that of the CCSD groundāstate energy. Singlet excitation energies are calculated for benzene using up to 432 basis functions. Basisāset effects of the order of 0.2 eV are observed when the basis is increased from augmented polarized valence doubleāzeta (augāccāpVDZ) to augmented polarized valence tripleāzeta (augāccāpVTZ) quality. The correlation problem is examined by performing calculations in the hierarchy of coupled cluster models CCS, CC2, CCSD, and CC3, as well as by using the CCSDR(3) perturbative triples corrections. The effect of triple excitations are less than 0.2 eV for all excitations except for the 2ā1E2g state. The calculated excitation energies are compared with experiment and other theoretical [email protected]
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