Blowing on Embers: Commensal Microbiota and Our Immune System

Vertebrates have co-evolved with microorganisms resulting in a symbiotic relationship, which plays an important role in health and disease. Skin and mucosal surfaces are colonized with a diverse population of commensal microbiota, over 1000 species, outnumbering the host cells by 10-fold. In the past 40 years, studies have built on the idea that commensal microbiota is in constant contact with the host immune system and thus influence immune function. Recent studies, focusing on mutualism in the gut, have shown that commensal microbiota seems to play a critical role in the development and homeostasis of the host immune system. In particular, the gut microbiota appears to direct the organization and maturation of lymphoid tissues and acts both locally and systemically to regulate the recruitment, differentiation, and function of innate and adaptive immune cells. While the pace of research in the area of the mucosal–immune interface has certainly intensified over the last 10 years, we are still in the early days of this field. Illuminating the mechanisms of how gut microbes shape host immunity will enhance our understanding of the causes of immune-mediated pathologies and improve the design of next-generation vaccines. This review discusses the recent advances in this field, focusing on the close relationship between the adaptive immune system and commensal microbiota, a constant and abundant source of foreign antigens

Molecular mechanisms underlying anti-tumor promoting activities of heat-processed Panax ginseng C.A. Meyer.

Recently, there have been considerable efforts to search for naturally occurring substances that can inhibit, reverse, or retard the multi-stage carcinogenesis. A wide array of phenolic substances derived from edible and medicinal plants have been reported to possess anticarcinogenic and antimutagenic activities and in many cases, the chemopreventive activities of phytochemicals are associated with their anti-inflammatory and/or antioxidative properties. Panax ginseng C.A. Meyer cultivated in Korea has been widely used in traditional herbal medicine for the treatment of various diseases. Certain fractions or purified ingredients of ginseng have been shown to exert anticarcinogenic and antimutagenic activities. Our previous studies have revealed that the methanol extract of heat-processed Panax ginseng C.A. Meyer attenuates the lipid peroxidation in rat brain homogenates and is also capable of scavenging superoxide generated by xanthine- xanthine oxidase or by 12-O-tetradecanoylphorbol-13-acetate (TPA) in differentiated human promyelocytic leukemia (HL-60) cells. Topical application of the same extract onto shaven backs of female ICR mice also suppressed TPA-induced skin tumor promotion. Likewise, topical application of ginsenoside Rg3, one of the constituents of heat-treated ginseng, significantly inhibited TPA-induced mouse epidermal ornithine decarboxylase activity and skin tumor promotion. Expression of cyclooxygenase-2 (COX-2) in TPA-stimulated mouse skin was markedly suppressed by Rg3 pretreatment. In addition, Rg3 inhibited TPA-stimulated activation of NF-kappaB and extracellular-regulated protein kinase (ERK), one of the mitogen-activated protein (MAP) kinase in mouse skin and also in cultured human breast epithelial cells (MCF-10A)

Dynamic Density Functional Theory of Multicomponent Cellular Membranes

We present a continuum model trained on molecular dynamics (MD) simulations for cellular membranes composed of an arbitrary number of lipid types. The model is constructed within the formalism of dynamic density functional theory and can be extended to include features such as the presence of proteins and membrane deformations. This framework represents a paradigm shift by enabling simulations that can access cellular length-scales ($\mu$m) and time-scales on the order of seconds, all while maintaining near-fidelity to the underlying MD models. Membrane interactions with RAS, a potentially oncogenic protein, are considered as an application. Simulation results are presented and verified with MD simulations, and implications of this new capability are discussed

SOCS-1 regulates IL-15–driven homeostatic proliferation of antigen-naive CD8 T cells, limiting their autoimmune potential

Mice that are deficient in suppressor of cytokine signaling–1 (SOCS-1) succumb to neonatal mortality that is associated with extensive cellular infiltration of many tissues. T cells seem to be necessary for disease, which can be alleviated largely by neutralizing interferon-γ. Examining T cell receptor (TCR) specificity shows that even monospecific T cells can mediate disease in SOCS-1–deficient mice, although disease onset is substantially faster with a polyclonal T cell repertoire. A major phenotype of SOCS-1−/− mice is the accumulation of CD44highCD8+ peripheral T cells. We show that SOCS-1–deficient CD8, but not CD4, T cells proliferate when transferred into normal (T cell–sufficient) mice, and that this is dependent on two signals: interleukin (IL)-15 and self-ligands that are usually only capable of stimulating homeostatic expansion in T cell–deficient mice. Our findings reveal that SOCS-1 normally down-regulates the capacity of IL-15 to drive activation and proliferation of naive CD8 T cells receiving TCR survival signals from self-ligands. We show that such dysregulated proliferation impairs the deletion of a highly autoreactive subset of CD8 T cells, and increases their potential for autoimmunity. Therefore, impaired deletion of highly autoreactive CD8 T cells, together with uncontrolled activation of naive CD8 T cells by homeostatic survival ligands, may provide a basis for the T cell–mediated disease of SOCS-1−/− mice

Why is the bandwidth of sodium observed to be narrower in photoemission experiments?

The experimentally predicted narrowing in the bandwidth of sodium is interpreted in terms of the non-local self-energy effect on quasi-particle energies of the electron liquid. The calculated self-energy correction is a monotonically increasing function of the wavenumber variable. The usual analysis of photo-emission experiments assumes the final state energies on the nearly-free-electron-like model and hence it incorrectly ascribes the non-local self-energy correction to the final state energies to the occupied state energies, thus leading to a seeming narrowing in the bandwidth.Comment: 9 page

Variational Monte Carlo study of the ground state properties and vacancy formation energy of solid para-H2 using a shadow wave function

A Shadow Wave Function (SWF) is employed along with Variational Monte Carlo techniques to describe the ground state properties of solid molecular para-hydrogen. The study has been extended to densities below the equilibrium value, to obtain a parameterization of the SWF useful for the description of inhomogeneous phases. We also present an estimate of the vacancy formation energy as a function of the density, and discuss the importance of relaxation effects near the vacant site

Dipole-quadrupole interactions and the nature of phase III of compressed hydrogen

A new class of strongly infrared active structures is identified for phase III of compressed molecular H2 by constant-pressure ab initio molecular dynamics and density-functional perturbation calculations. These are planar quadrupolar structures obtained as a distortion of low-pressure quadrupolar phases, after they become unstable at about 150 GPa due to a zone-boundary soft phonon. The nature of the II-III transition and the origin of the IR activity are rationalized by means of simple electrostatics, as the onset of a stabilizing dipole-quadrupole interaction.Comment: 4 pages, 3 figures. To appear in Phys. Rev. Let

BAs and boride III-V alloys

Boron arsenide, the typically-ignored member of the III-V arsenide series BAs-AlAs-GaAs-InAs is found to resemble silicon electronically: its Gamma conduction band minimum is p-like (Gamma_15), not s-like (Gamma_1c), it has an X_1c-like indirect band gap, and its bond charge is distributed almost equally on the two atoms in the unit cell, exhibiting nearly perfect covalency. The reasons for these are tracked down to the anomalously low atomic p orbital energy in the boron and to the unusually strong s-s repulsion in BAs relative to most other III-V compounds. We find unexpected valence band offsets of BAs with respect to GaAs and AlAs. The valence band maximum (VBM) of BAs is significantly higher than that of AlAs, despite the much smaller bond length of BAs, and the VBM of GaAs is only slightly higher than in BAs. These effects result from the unusually strong mixing of the cation and anion states at the VBM. For the BAs-GaAs alloys, we find (i) a relatively small (~3.5 eV) and composition-independent band gap bowing. This means that while addition of small amounts of nitrogen to GaAs lowers the gap, addition of small amounts of boron to GaAs raises the gap (ii) boron ``semi-localized'' states in the conduction band (similar to those in GaN-GaAs alloys), and (iii) bulk mixing enthalpies which are smaller than in GaN-GaAs alloys. The unique features of boride III-V alloys offer new opportunities in band gap engineering.Comment: 18 pages, 14 figures, 6 tables, 61 references. Accepted for publication in Phys. Rev. B. Scheduled to appear Oct. 15 200

Solid molecular hydrogen: The Broken Symmetry Phase

By performing constant-pressure variable-cell ab initio molecular dynamics simulations we find a quadrupolar orthorhombic structure, of $Pca2_1$ symmetry, for the broken symmetry phase (phase II) of solid H2 at T=0 and P =110 - 150 GPa. We present results for the equation of state, lattice parameters and vibronic frequencies, in very good agreement with experimental observations. Anharmonic quantum corrections to the vibrational frequencies are estimated using available data on H2 and D2. We assign the observed modes to specific symmetry representations.Comment: 5 pages (twocolumn), 4 Postscript figures. To appear in Phys. Rev. Let