Predominance of weakly cytotoxic, T-betLowEomesNeg CD8+ T-cells in human gastrointestinal mucosa: implications for HIV infection.

The gastrointestinal mucosa is an important site of HIV acquisition, viral replication, and pathogenesis. Immune cells in mucosal tissues frequently differ in phenotype and function from their non-mucosal counterparts. Although perforin-mediated cytotoxicity as measured in blood is a recognized correlate of HIV immune control, its role in gastrointestinal tissues is unknown. We sought to elucidate the cytotoxic features of rectal mucosal CD8+ T-cells in HIV infected and uninfected subjects. Perforin expression and lytic capacity were significantly reduced in rectal CD8+ T-cells compared with their blood counterparts, regardless of HIV clinical status; granzyme B (GrzB) was reduced to a lesser extent. Mucosal perforin and GrzB expression were higher in participants not on antiretroviral therapy compared with those on therapy and controls. Reduction in perforin and GrzB was not explained by differences in memory/effector subsets. Expression of T-bet and Eomesodermin was significantly lower in gut CD8+ T-cells compared with blood, and in vitro neutralization of TGF-β partially restored perforin expression in gut CD8+ T-cells. These findings suggest that rectal CD8+ T-cells are primarily non-cytotoxic, and phenotypically shaped by the tissue microenvironment. Further elucidation of rectal immune responses to HIV will inform the development of vaccines and immunotherapies targeted to mucosal tissues

DAzLE: The Dark Ages z (redshift) Lyman-alpha Explorer

DAzLE is an near infrared narrowband differential imager being built by the Institute of Astronomy, Cambridge, in collaboration with the Anglo-Australian observatory. It is a special purpose instrument designed with a sole aim; the detection of redshifted Lyman-alpha emission from star forming galaxies at z>7. DAzLE will use pairs of high resolution (R=1000) narrowband filters to exploit low background `windows' in the near infrared sky emission spectrum. This will enable it to reach sensitivities of ~2E-21 W/m^2, thereby allowing the detection of z>7 galaxies with star formation rates as low as a few solar masses per year. The design of the instrument, and in particular the crucial narrowband filters, are presented. The predicted performance of DAzLE, including the sensitivity, volume coverage and expected number counts, is discussed. The current status of the DAzLE project, and its projected timeline, are also presented.Comment: 11 pages, 7 figures, to appear in Proceedings of SPIE Vol. 5492, Ground-based Instrumentation for Astronom

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel.In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime: we compute the two-point correlation functions for the linearized Einstein tensor and for the metric perturbations. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a quasi-static black hole.Comment: 75 pages, no figures, submitted to Living Reviews in Relativit

The differential contribution of tumour necrosis factor to thermal and mechanical hyperalgesia during chronic inflammation

Therapies directed against tumour necrosis factor (TNF) are effective for the treatment of rheumatoid arthritis and reduce pain scores in this condition. In this study, we sought to explore mechanisms by which TNF contributes to inflammatory pain in an experimental model of arthritis. The effects of an anti-TNF agent, etanercept, on behavioural pain responses arising from rat monoarthritis induced by complete Freund's adjuvant were assessed and compared with expression of TNF receptors (TNFRs) by dorsal root ganglion (DRG) cells at corresponding time points. Etanercept had no effect on evoked pain responses in normal animals but exerted a differential effect on the thermal and mechanical hyperalgesia associated with rat arthritis induced by complete Freund's adjuvant (CFA). Joint inflammation was associated with increased TNFR1 and TNFR2 expression on DRG cells, which was maintained throughout the time course of the model. TNFR1 expression was increased in neuronal cells of the DRG bilaterally after arthritis induction. In contrast, TNFR2 expression occurred exclusively on nonneuronal cells of the macrophage-monocyte lineage, with cell numbers increasing in a TNF-dependent fashion during CFA-induced arthritis. A strong correlation was observed between numbers of macrophages and the development of mechanical hyperalgesia in CFA-induced arthritis. These results highlight the potential for TNF to play a vital role in inflammatory hyperalgesia, both by a direct action on neurons via TNFR1 and by facilitating the accumulation of macrophages in the DRG via a TNFR2-mediated pathway

Hydrolysis of precipitated phytate by three distinct families of phytases

While genetically modified plants that secrete histidine acid phosphatases (HAPs), β-propeller phytases (BPPs) and purple acid phosphatases (PAPs) have been shown to assimilate soluble phytate, little is known about whether these plants have the ability to hydrolyze precipitated phytate. In this study, the ability of representative members of these three classes of phytases to hydrolyze metal-phytate salts and to hydrolyze phytate adsorbed to aluminum precipitates was compared. All three phytases were able to hydrolyze Ca 2+-, Mg 2+-, and Mn 2+-phytates, but were unable to hydrolyze Al 3+-, Fe 2+-, Fe 3+-, Cu 2+-, and Zn 2+-phytates. When these ions were present, the hydrolysis of Ca 2+-phytate was prevented. Citrate was more potent than malate and oxalate in solubilizing some of these phytate salts for enzyme hydrolysis. Phytate adsorbed to aluminum precipitates was resistant to all three enzymes, except when organic acids were added (citrate>oxalate>malate). While increasing concentrations of organic acids were inhibitory to enzyme activity (oxalate >citrate>malate), PAP was more resistant to citrate than HAP. As desorption of phytate from a solid surface by organic acids is essential for phytase activity, the genetic engineering of plants that enhances the secretion of both citrate and phytases from the root may be a feasible approach to improving soil phytate assimilation. © 2005 Elsevier Ltd. All rights reserved.postprin

A Case of Urogenital Human Schistosomiasis from a Non-endemic Area

© 2015 Calvo-Cano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

CARMA1 is a novel regulator of T-ALL disease and leukemic cell migration to the CNS

No abstract available

Fate and transport of volatile organic compounds in glacial till and groundwater at an industrial site in Northern Ireland

Volatile organic compound (VOC) contamination of subsurface geological material and groundwater was discovered on the Nortel Monkstown industrial site, Belfast, Northern Ireland. The objectives of this study were to (1) investigate the characteristics of the geological material and its influences on contaminated groundwater flow across the site using borehole logs and hydrological evaluations, and (2) identify the contaminants and examine their distribution in the subsurface geological material and groundwater using chemical analysis. This report focuses on the eastern car park (ECP) which was a former storage area associated with trichloroethene (TCE) degreasing operations. This is where the greatest amount of volatile organic compounds (VOCs), particularly TCE, were detected. The study site is on a complex deposit of clayey glacial till with discontinuous coarser grained lenses, mainly silts, sands and gravel, which occur at 0.45-7.82 m below ground level (bgl). The lenses overall form an elongated formation that acts as a small unconfined shallow aquifer. There is a continuous low permeable stiff clayey till layer beneath the lenses that performs as an aquitard to the groundwater. Highest concentrations of VOCs, mainly TCE, in the geological material and groundwater are in these coarser lenses at similar to 4.5-7 m bgl. Highest TCE measurements at 390,000 mu g L-1 for groundwater and at 39,000 mu g kg(-1) at 5.7 m for geological material were in borehole GA19 in the coarse lens zone. It is assumed that TCE gained entrance to the subsurface near this borehole where the clayey till was thin to absent above coarse lenses which provided little retardation to the vertical migration of this dense non-aqueous phase liquid (DNAPL) into the groundwater. However, TCE is present in low concentrations in the geological material overlying the coarse lens zone. Additionally, VOCs appear to be associated with poorly drained layers and in peat < 3.0 m bgl in the ECP. Some indication of natural attenuation as VOCs degradation products vinyl chloride (VC) and dichloromethane (DCM) also occur on the site

Adaptive Optics for Astronomy

Adaptive Optics is a prime example of how progress in observational astronomy can be driven by technological developments. At many observatories it is now considered to be part of a standard instrumentation suite, enabling ground-based telescopes to reach the diffraction limit and thus providing spatial resolution superior to that achievable from space with current or planned satellites. In this review we consider adaptive optics from the astrophysical perspective. We show that adaptive optics has led to important advances in our understanding of a multitude of astrophysical processes, and describe how the requirements from science applications are now driving the development of the next generation of novel adaptive optics techniques.Comment: to appear in ARA&A vol 50, 201