IL-10 production in macrophages is regulated by a TLR-driven CREB-mediated mechanism that is linked to genes involved in cell metabolism

IL-10 is produced by macrophages in diverse immune settings and is critical in limiting immune-mediated pathology. In helminth infections, macrophages are an important source of IL-10; however, the molecular mechanism underpinning production of IL-10 by these cells is poorly characterized. In this study, bone marrow–derived macrophages exposed to excretory/secretory products released by Schistosoma mansoni cercariae rapidly produce IL-10 as a result of MyD88-mediated activation of MEK/ERK/RSK and p38. The phosphorylation of these kinases was triggered by TLR2 and TLR4 and converged on activation of the transcription factor CREB. Following phosphorylation, CREB is recruited to a novel regulatory element in the Il10 promoter and is also responsible for regulating a network of genes involved in metabolic processes, such as glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation. Moreover, skin-resident tissue macrophages, which encounter S. mansoni excretory/secretory products during infection, are the first monocytes to produce IL-10 in vivo early postinfection with S. mansoni cercariae. The early and rapid release of IL-10 by these cells has the potential to condition the dermal microenvironment encountered by immune cells recruited to this infection site, and we propose a mechanism by which CREB regulates the production of IL-10 by macrophages in the skin, but also has a major effect on their metabolic state

CD4+ T cell hyporesponsiveness after repeated exposure to Schistosoma mansoni larvae is dependent upon interleukin-10

The effect that multiple percutaneous exposures to Schistosoma larvae has on the development of early CD4+ lymphocyte reactivity is unclear, yet it is important in the context of humans living in areas where schistosomiasis is endemic. In a murine model of multiple infections, we show that exposure of mice to repeated doses (4×) of Schistosoma mansoni cercariae, compared to a single dose (1×), results in CD4+ T cell hyporesponsiveness within the skin-draining lymph nodes (sdLN), manifested as reduced CD4+ cell proliferation and cytokine production. FoxP3+ CD4+ regulatory T cells were present in similar numbers in the sdLN of 4× and 1× mice and thus are unlikely to have a role in effecting hyporesponsiveness. Moreover, anergy of the CD4+ cell population from 4× mice was slight, as proliferation was only partly circumvented through the in vitro addition of exogenous interleukin-2 (IL-2), and the in vivo blockade of the regulatory molecule PD1 had a minimal effect on restoring responsiveness. In contrast, IL-10 was observed to be critical in mediating hyporesponsiveness, as CD4+ cells from the sdLN of 4× mice deficient for IL-10 were readily able to proliferate, unlike those from 4× wild-type cohorts. CD4+ cells from the sdLN of 4× mice exhibited higher levels of apoptosis and cell death, but in the absence of IL-10, there was significantly less cell death. Combined, our data show that IL-10 is a key factor in the development of CD4+ T cell hyporesponsiveness after repeated parasite exposure involving CD4+ cell apoptosis

Nurses\u27 Alumnae Association Bulletin, April 1961

Alumnae Meetings 1960 Social Committee Clara Melville Scholarship Fund Bulletin Committee Private Duty Nurse\u27s Section Report of the School of Nursing and Nursing Service Staff Nurses Association Student Activities Personal Items of Interest Expansion of Jefferson Artificial Kidney Unit Medical Work in the Congo Marriages New Arrivals Necrology Annual Giving Fun

Self-healing in B12P2 through Mediated Defect Recombination

Citation: Self-healing in B12P2 through Mediated Defect Recombination. S. P. Huber, E. Gullikson, C. D. Frye, J. H. Edgar, R. W. E. van de Kruijs, F. Bijkerk, and D. Prendergast. Chemistry of Materials 28 8415--8428 (2016) 10.1021/acs.chemmater.6b04075The icosahedral boride B12P2 has been reported to exhibit “self-healing” properties, after transmission electron microscopy recordings of sample surfaces, which were exposed to highly energetic particle beams, revealed little to no damage. In this work, employing calculations from first-principles within the density functional theory (DFT) framework, the structural characteristics of boron interstitial and vacancy defects in B12P2 are investigated. Using nudged elastic band simulations, the diffusion properties of interstitial and vacancy defects and their combination, in the form of Frenkel defect pairs, are studied. We find that boron icosahedra maintain their structural integrity even when in a degraded state in the presence of a vacancy or interstitial defect and that the diffusion activation energy for the recombination of an interstitial vacany pair can be as low as 3 meV, in line with the previously reported observation of “self-healing”

NLS cycle 1 and NLS 2 base heating technical notes. Appendix 3: Preliminary cycle 1 NLS base heating environments. Cycle 1 NLS base heating environments. NLS 2 650K STME base heating environments

A preliminary analysis of National Launch System ascent plume induced base heating environments has been completed to support the Induced Environments Panel's objective to assist in maturing the NLS vehicle (1.5 stage and heavy launch lift vehicle) design. Environments during ascent have been determined from this analysis for a few selected locations on the engine nozzles and base heat shield for both vehicles. The environments reflect early summer 1991 configurations and performance data and conservative methodology. A more complete and thorough analysis is under way to update these environments for the cycle 1 review in January 1992

The 1991 version of the plume impingement computer program. Volume 2: User's input guide

The Plume Impingement Program (PLIMP) is a computer code used to predict impact pressures, forces, moments, heating rates, and contamination on surfaces due to direct impingement flowfields. Typically, it has been used to analyze the effects of rocket exhaust plumes on nearby structures from ground level to the vacuum of space. The program normally uses flowfields generated by the MOC, RAMP2, SPF/2, or SFPGEN computer programs. It is capable of analyzing gaseous and gas/particle flows. A number of simple subshapes are available to model the surfaces of any structure. The original PLIMP program has been modified many times of the last 20 years. The theoretical bases for the referenced major changes, and additional undocumented changes and enhancements since 1988 are summarized in volume 1 of this report. This volume is the User's Input Guide and should be substituted for all previous guides when running the latest version of the program. This version can operate on VAX and UNIX machines with NCAR graphics ability

The 1991 version of the plume impingement computer program. Volume 1: Description

The objective of this contract was to continue development of a vacuum plume impingement evaluator to provide an analyst with a capability for rapid assessment of thruster plume impingement scenarios. The research was divided into three areas: Plume Impingement Computer Program (PLIMP) modification/validation; graphics development; and documentation in the form of a Plume Handbook and PLIMP Input Guide

An Euler Solver Based on Locally Adaptive Discrete Velocities

A new discrete-velocity model is presented to solve the three-dimensional Euler equations. The velocities in the model are of an adaptive nature---both the origin of the discrete-velocity space and the magnitudes of the discrete-velocities are dependent on the local flow--- and are used in a finite volume context. The numerical implementation of the model follows the near-equilibrium flow method of Nadiga and Pullin [1] and results in a scheme which is second order in space (in the smooth regions and between first and second order at discontinuities) and second order in time. (The three-dimensional code is included.) For one choice of the scaling between the magnitude of the discrete-velocities and the local internal energy of the flow, the method reduces to a flux-splitting scheme based on characteristics. As a preliminary exercise, the result of the Sod shock-tube simulation is compared to the exact solution.Comment: 17 pages including 2 figures and CMFortran code listing. All in one postscript file (adv.ps) compressed and uuencoded (adv.uu). Name mail file `adv.uu'. Edit so that `#!/bin/csh -f' is the first line of adv.uu On a unix machine say `csh adv.uu'. On a non-unix machine: uudecode adv.uu; uncompress adv.tar.Z; tar -xvf adv.ta

Detection of defect populations in superhard semiconductor boron subphosphide B12P2 through X-ray absorption spectroscopy

Citation: Detection of defect populations in superhard semiconductor boron subphosphide B12P2 through X-ray absorption spectroscopy. S. P. Huber, E. Gullikson, J. Meyer-Ilse, C. D. Frye, J. H. Edgar, R. W. E. van de Kruijs, F. Bijkerk, and D. Prendergast J. Mater. Chem. A 5 5737--5749 (2017) 10.1039/c6ta10935gRecent theoretical work has shown for the first time how the experimentally observed property of “self-healing” of the superhard semiconductor boron subphosphide (B12P2) arises through a process of mediated defect recombination. Experimental verification of the proposed mechanism would require a method that can detect and distinguish between the various defect populations that can exist in B12P2. X-ray absorption near-edge spectroscopy (XANES) is such a method and in this work we present experimentally collected spectra of B12P2samples with varying crystalline qualities. By simulating the X-ray spectroscopic signatures of potential crystallographic point defects from first-principles within the density functional theory framework, the presence of defect populations can be determined through spectroscopic fingerprinting. Our results find an increasing propensity for the presence of phosphorus vacancy defects in samples deposited at lower temperatures but no evidence for comparable populations of boron vacancies in all the samples that have been studied. The absence of large amounts of boron vacancies is in line with the “self-healing” property of B12P2

Dynamic IMF production in 24Mg+27Al^{24}Mg + ^{27}Al at intermediate energies

The azimuthal correlations and polar-angle distributions of intermediate-mass fragments (IMFs) produced in Mg+Al at 45 an 95 AMeV were studied. Measurements of $\alpha$-particles and IMFs with $3\le Z\le8$ emmitted in the mid-rapidity region for mid-central events were compared to IQMD results and results from a static-source model. A maximum in the azimuthal-correlation function at 180\degree\/ can not be described by independently emmitted particles. Momentum conservation of a small source as well as target-projectile correlations from IQMD show the same azimuthal correlations as the experimental data. The polar-angle distributions in the experimental data show a target-projectile seperation, thus giving evidence of dynamic IMF production.\\ {\it Keywords:} dynamic multifragmentation, IMF, IQMD, azimuthal correlations