Oligodendrocytes Do Not Export NAA-Derived Aspartate In Vitro.

Oligodendroglial cells are known to de-acetylate the N-acetylaspartate (NAA) synthesized and released by neurons and use it for lipid synthesis. However, the role of NAA regarding their intermediary metabolism remains poorly understood. Two hypotheses were proposed regarding the fate of aspartate after being released by de-acetylation: (1) aspartate is metabolized in the mitochondria of oligodendrocyte lineage cells; (2) aspartate is released to the medium. We report here that aspartoacylase mRNA expression increases when primary rat oligodendrocyte progenitor cells (OPCs) differentiate into mature cells in culture. Moreover, characterising metabolic functions of acetyl coenzyme A and aspartate from NAA catabolism in mature oligodendrocyte cultures after 5 days using isotope-labelled glucose after 5-days of differentiation we found evidence of extensive NAA metabolism. Incubation with [1,6-13C]glucose followed by gas chromatography-mass spectrometry and high performance liquid chromatography analyses of cell extracts and media in the presence and absence of NAA established that the acetate moiety produced by hydrolysis of NAA does not enter mitochondrial metabolism in the form of acetyl coenzyme A. We also resolved the controversy concerning the possible release of aspartate to the medium: aspartate is not released to the medium by oligodendrocytes in amounts detectable by our methods. Therefore we propose that: aspartate released from NAA joins the cytosolic aspartate pool rapidly and takes part in the malate-aspartate shuttle, which transports reducing equivalents from glycolysis into the mitochondria for ATP production and enters the tricarboxylic acid cycle at a slow rate.This work was supported by grants from the UK Multiple Sclerosis Society and from Qatar Foundation. The work was further supported by core funding from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute. The authors acknowledge the excellent technical support in GC-MS and HPLC analysis from Lars Evje (NTNU, Norway).This is the final version of the article. It first appeared from Springer at http://dx.doi.org/10.1007/s11064-016-1985-y

Long-term TNT and DNT contamination: 1-D modeling of natural attenuation in the vadose zone: case study, Portugal

The vadose zone of a trinitrotoluene (TNT) and dinitrotoluene (DNT) contaminated site was investigated to assess the mobility of those explosives under natural conditions. Located in the left margin of the River Tejo Basin, Portugal, the site is located on unconsolidated sediments. Wastewaters associated with the 50-year explosives production were disposed in excavated ponds, from where water would infiltrate and pollute the unsaturated and saturated parts of the local aquifers. Two boreholes were drilled to 9 m depth in such a former waste pond to investigate the contaminant's fate in the vadose zone. Sediment samples were taken every 1-2 m for analysis of the polynitroaromatics (p-NACs) and organic volatile compounds, pH, organic carbon content, cation exchange capacity and grain size analysis. The main contaminant was TNT representing >70 % of the total p-NACs concentration that peaked approximately 7 mg/kg in one borehole, even if the median in both boreholes was of similar to 1 mg/kg. DNT was 4-30 % of the total p-NACs and nitrotoluene (NT), up to 5 %. No other (volatile) organic compound was detected. The predominance of TNT as the main contaminant implies that any natural mass reduction has been inefficient to clean the site. Several 1-D model simulations of p-NACs cleaning of the vadose zone under natural conditions indicated that the most probable scenario of combined advection and partitioning will only remove TNT after 10's of years, whereas DNT and NT will hardly be removed. Such low concentrations and long times for the p-NACs removal, suggest that by now those compounds have been washed-out to a level below standard limits

Low pH immobilizes and kills human leukocytes and prevents transmission of cell-associated HIV in a mouse model

BACKGROUND: Both cell-associated and cell-free HIV virions are present in semen and cervical secretions of HIV-infected individuals. Thus, topical microbicides may need to inactivate both cell-associated and cell-free HIV to prevent sexual transmission of HIV/AIDS. To determine if the mild acidity of the healthy vagina and acid buffering microbicides would prevent transmission by HIV-infected leukocytes, we measured the effect of pH on leukocyte motility, viability and intracellular pH and tested the ability of an acidic buffering microbicide (BufferGel(®)) to prevent the transmission of cell-associated HIV in a HuPBL-SCID mouse model. METHODS: Human lymphocyte, monocyte, and macrophage motilities were measured as a function of time and pH using various acidifying agents. Lymphocyte and macrophage motilities were measured using video microscopy. Monocyte motility was measured using video microscopy and chemotactic chambers. Peripheral blood mononuclear cell (PBMC) viability and intracellular pH were determined as a function of time and pH using fluorescent dyes. HuPBL-SCID mice were pretreated with BufferGel, saline, or a control gel and challenged with HIV-1-infected human PBMCs. RESULTS: Progressive motility was completely abolished in all cell types between pH 5.5 and 6.0. Concomitantly, at and below pH 5.5, the intracellular pH of PBMCs dropped precipitously to match the extracellular medium and did not recover. After acidification with hydrochloric acid to pH 4.5 for 60 min, although completely immotile, 58% of PBMCs excluded ethidium homodimer-1 (dead-cell dye). In contrast, when acidified to this pH with BufferGel, a microbicide designed to maintain vaginal acidity in the presence of semen, only 4% excluded dye at 10 min and none excluded dye after 30 min. BufferGel significantly reduced transmission of HIV-1 in HuPBL-SCID mice (1 of 12 infected) compared to saline (12 of 12 infected) and a control gel (5 of 7 infected). CONCLUSION: These results suggest that physiologic or microbicide-induced acid immobilization and killing of infected white blood cells may be effective in preventing sexual transmission of cell-associated HIV

Clinical outcomes in pediatric hemodialysis patients in the USA: lessons from CMS’ ESRD CPM Project

Although prospective randomized trials have provided important information and allowed the development of evidence-based guidelines in adult hemodialysis (HD) patients, with approximately 800 prevalent pediatric HD patients in the United States, such studies are difficult to perform in this population. Observational data obtained through the Center for Medicare & Medicaid Services’ (CMS’) End Stage Renal Disease (ESRD) Clinical Performance Measures (CPM) Project have allowed description of the clinical care provided to pediatric HD patients as well as identification of risk factors for failure to reach adult targets for clinical parameters such as hemoglobin, single-pool Kt/V (spKt/V) and serum albumin. In addition, studies linking data from the ESRD CPM Project and the United States Renal Data System have allowed evaluation of associations between achievement of those targets and the outcomes of hospitalization and death. The results of those studies, while unable to prove cause and effect, suggest that the adult ESRD CPM targets may assist in identifying pediatric HD patients at risk for poor outcomes

Diffractive Dijet Production at sqrt(s)=630 and 1800 GeV at the Fermilab Tevatron

We report a measurement of the diffractive structure function $F_{jj}^D$ of the antiproton obtained from a study of dijet events produced in association with a leading antiproton in $\bar pp$ collisions at $\sqrt s=630$ GeV at the Fermilab Tevatron. The ratio of $F_{jj}^D$ at $\sqrt s=630$ GeV to $F_{jj}^D$ obtained from a similar measurement at $\sqrt s=1800$ GeV is compared with expectations from QCD factorization and with theoretical predictions. We also report a measurement of the $\xi$ ($x$-Pomeron) and $\beta$ ($x$ of parton in Pomeron) dependence of $F_{jj}^D$ at $\sqrt s=1800$ GeV. In the region $0.035<\xi<0.095$, $|t|<1$ GeV$^2$ and $\beta<0.5$, $F_{jj}^D(\beta,\xi)$ is found to be of the form $\beta^{-1.0\pm 0.1} \xi^{-0.9\pm 0.1}$, which obeys $\beta$-$\xi$ factorization.Comment: LaTeX, 9 pages, Submitted to Phys. Rev. Letter

Evaluation of vaccination strategies for SIR epidemics on random networks incorporating household structure

This paper is concerned with the analysis of vaccination strategies in a stochastic SIR (susceptible → infected → removed) model for the spread of an epidemic amongst a population of individuals with a random network of social contacts that is also partitioned into households. Under various vaccine action models, we consider both household-based vaccination schemes, in which the way in which individuals are chosen for vaccination depends on the size of the households in which they reside, and acquaintance vaccination, which targets individuals of high degree in the social network. For both types of vaccination scheme, assuming a large population with few initial infectives, we derive a threshold parameter which determines whether or not a large outbreak can occur and also the probability and fraction of the population infected by such an outbreak. The performance of these schemes is studied numerically, focusing on the influence of the household size distribution and the degree distribution of the social network. We find that acquaintance vaccination can significantly outperform the best household-based scheme if the degree distribution of the social network is heavy-tailed. For household-based schemes, when the vaccine coverage is insufficient to prevent a major outbreak and the vaccine is imperfect, we find situations in which both the probability and size of a major outbreak under the scheme which minimises the threshold parameter are \emph{larger} than in the scheme which maximises the threshold parameter

A Study of B0 -> J/psi K(*)0 pi+ pi- Decays with the Collider Detector at Fermilab

We report a study of the decays B0 -> J/psi K(*)0 pi+ pi-, which involve the creation of a u u-bar or d d-bar quark pair in addition to a b-bar -> c-bar(c s-bar) decay. The data sample consists of 110 1/pb of p p-bar collisions at sqrt{s} = 1.8 TeV collected by the CDF detector at the Fermilab Tevatron collider during 1992-1995. We measure the branching ratios to be BR(B0 -> J/psi K*0 pi+ pi-) = (8.0 +- 2.2 +- 1.5) * 10^{-4} and BR(B0 -> J/psi K0 pi+ pi-) = (1.1 +- 0.4 +- 0.2) * 10^{-3}. Contributions to these decays are seen from psi(2S) K(*)0, J/psi K0 rho0, J/psi K*+ pi-, and J/psi K1(1270)