DNA methylation profiling of the human major histocompatibility complex: A pilot study for the Human Epigenome Project

The Human Epigenome Project aims to identify, catalogue, and interpret genome-wide DNA methylation phenomena. Occurring naturally on cytosine bases at cytosine-guanine dinucleotides, DNA methylation is intimately involved in diverse biological processes and the aetiology of many diseases. Differentially methylated cytosines give rise to distinct profiles, thought to be specific for gene activity, tissue type, and disease state. The identification of such methylation variable positions will significantly improve our understanding of genome biology and our ability to diagnose disease. Here, we report the results of the pilot study for the Human Epigenome Project entailing the methylation analysis of the human major histocompatibility complex. This study involved the development of an integrated pipeline for high-throughput methylation analysis using bisulphite DNA sequencing, discovery of methylation variable positions, epigenotyping by matrix-assisted laser desorption/ionisation mass spectrometry, and development of an integrated public database available at http://www.epigenome.org. Our analysis of DNA methylation levels within the major histocompatibility complex, including regulatory exonic and intronic regions associated with 90 genes in multiple tissues and individuals, reveals a bimodal distribution of methylation profiles (i.e., the vast majority of the analysed regions were either hypo- or hypermethylated), tissue specificity, inter-individual variation, and correlation with independent gene expression data

Statins increase the frequency of circulating CD4+ FOXP3+ regulatory T cells in healthy individuals

RESUMEN: Las estatinas se han demostrado para modular el número y la función supresora de células T CD4 + FOXP3 (Treg) en condiciones inflamatorias. Sin embargo, no está bien establecido si estatinas también podría afectar Treg en ausencia de inflamación. Para abordar esta cuestión, dieciocho sujetos masculinos normocolesterolémicos fueron tratados con lovastatina o atorvastatina al día durante 45 días. La frecuencia y el fenotipo de circulación Treg se evaluaron en los días 0, 7, 30, y 45. Los niveles de ARNm de FOXP3, IDO, TGF-β, e IL-10 se midieron en las células T CD4 +. Se encontró que tanto los que aumenta significativamente los niveles de ARNm y de frecuencia de Treg FOXP3 en el día 30. En el día 45, los números de Treg volvieron a los valores basales; Sin embargo, el TGF-β y los niveles de ARNm de FOXP3 se mantuvo alta, acompañada por el aumento de los porcentajes de CTLA-4 y GITR que expresan Treg. Treg expresión de Ki-67 se redujo tras el tratamiento con estatinas. la frecuencia de Treg correlacionó positivamente con los niveles plasmáticos de colesterol de lipoproteínas de alta densidad (HDL-C), lo que sugiere un papel para el HDL-C en la homeostasis de Treg. Por lo tanto, las estatinas parecen tener efectos inmunomoduladores inflamación independiente. Por lo tanto, el aumento de la frecuencia de Treg células probablemente contribuye a inmunomoduladores efecto de las estatinas, incluso en individuos sanos.ABSTRACT: Statins have been shown to modulate the number and the suppressive function of CD4+FOXP3+ T cells (Treg) in inflammatory conditions. However, it is not well established whether statin could also affect Treg in absence of inflammation. To address this question, eighteen normocholesterolemic male subjects were treated with lovastatin or atorvastatin daily for 45 days. The frequency and phenotype of circulating Treg were evaluated at days 0, 7, 30, and 45. mRNA levels of FOXP3, IDO, TGF-β, and IL-10 were measured in CD4+ T cells. We found that both statins significantly increased Treg frequency and FOXP3 mRNA levels at day 30. At day 45, Treg numbers returned to baseline values; however, TGF-β and FOXP3 mRNA levels remained high, accompanied by increased percentages of CTLA-4- and GITR-expressing Treg. Treg Ki-67 expression was decreased upon statin treatment. Treg frequency positively correlated with plasma levels of high-density lipoprotein cholesterol (HDL-c), suggesting a role for HDL-c in Treg homeostasis. Therefore, statins appear to have inflammation-independent immune-modulatory effects. Thus, the increase in Treg cells frequency likely contributes to immunomodulatory effect of statins, even in healthy individual

Carbon supported CdSe nanocrystals

Insights to the mechanism of CdSe nanoparticle attachment to carbon nanotubes following the hot injection method are discussed. It was observed that the presence of water improves the nanotube coverage while Cl containing media are responsible for the shape transformation of the nanoparticles and further attachment to the carbon lattice. The experiments also show that the mechanism taking place involves the right balance of several factors, namely, low passivated nanoparticle surface, particles with well-defined crystallographic facets, and interaction with an organics-free sp2 carbon lattice. Furthermore, this procedure can be extended to cover graphene by quantum dots.Comment: 5 pages, 5 figure

Automatic System for the D.C. High Voltage Qualification of the Superconducting Electrical Circuits of the LHC Machine

A d.c. high voltage test system has been developed to verify automatically the insulation resistance of the powering circuits of the LHC. In the most complex case, up to 72 circuits share the same volume inside cryogenic lines. Each circuit can have an insulation fault versus any other circuit or versus ground. The system is able to connect up to 80 circuits and apply a voltage up to 2 kV D.C. The leakage current flowing through each circuit is measured within a range of 1 nA to 1.6 mA. The matrix of measurements allows characterizing the paths taken by the currents and locating weak points of the insulation between circuits. The system is composed of a D.C. voltage source and a data acquisition card. The card is able to measure with precision currents and voltages and to drive up to 5 high voltage switching modules offering 16 channels each. A LabVIEW application controls the system for an automatic and safe operation. This paper describes the hardware and software design, the testing methodology and the results obtained during the qualification of the LHC superconducting circuits

Superabsorbent Polymers for Internally Cured Concrete

Two commercial superabsorbent polymer (SAP) formulations were used to internally cure cement pastes, mortars, and concretes with a range of water-to-cement ratios (w/c 0.35–0.52). The following properties were determined as a function of cement chemistry and type, use of chemical admixtures, use of slag, and batching parameters: SAP absorption capacity, fresh mixture workability and consistency, degree of hydration, volumetric stability, cracking tendency, compressive and flexural strength, and pumpability. SAP internal curing agents resulted in cementitious mixtures with improved hydration, accelerated strength gain, greater volumetric stability, and improved cracking resistance while maintaining sufficient workability to be pumped and placed without sacrificing compressive or flexural strength. When using SAP, batching adjustments prioritized the use of water reducing admixture instead of extra water to tune workability. While the benefits of SAP internal curing agents for low w/c mixtures were expected, SAP-containing mixtures with w/c ≥ 0.42 displayed accelerated strength development and decreased cracking tendency

Plasma Trimethylamine-N-oxide following Cessation of L-carnitine Supplementation in Healthy Aged Women.

L-carnitine supplementation elevates plasma trimethylamine-N-oxide (TMAO), which may participate in atherosclerosis development by affecting cholesterol metabolism. The aim of the current study was to determine the effect of increased plasma TMAO on biochemical markers in the blood following cessation of L-carnitine supplementation. The follow-up measurements were performed on subjects who completed 24 weeks of L-carnitine or placebo supplementation protocol. Blood samples were taken after finishing the supplementation and then 4 and 12 months following the supplementation withdrawal. Four months after cessation of L-carnitine supplementation, plasma TMAO concentration reached a normal level which was stable for the following eight months. During this period, no modifications in serum lipid profile and circulating leukocyte count were noted. TMAO implications in health and disease is widely discussed. The results of this study demonstrate no adverse effects of elevated plasma TMAO, induced by L-carnitine, on the measured parameters at 4 and 12 months after withdrawal of supplementation

The LHC Continuous Cryostat Interconnections: The Organization of a Logistically Complex Worksite Requiring Strict Quality Standards and High Output

The interconnections of the Large Hadron Collider (LHC) continuous cryostat have been completed in fall 2007: 1695 interconnections magnet to magnet and 224 interconnections between the continuous cryostat and the cryogenic distribution line have been executed along the 27 km of the LHC. The very tight schedule, the complexity of the interconnection sequence, the strict quality standards applied have required the creation of an ad hoc organization in order to steer and coordinate the activities on the worksite dispersed along the whole accelerator ring. The concatenation of construction and test phases carried out by CERN staff, CERN collaborating institutes and contractors have led to the necessity of a common approach and of a very effective information flow. In this paper, after having recalled the main technical challenges, we review the organizational choices that have been taken and we briefly analyze the development of the worksite in term of allocated resources and production

The Quality Control of the LHC Continuous Cryostat Interconnections

The interconnections between the Large Hadron Collider (LHC) magnets have required some 40 000 TIG welded joints and 65 000 electrical splices. At the level of single joints and splices, non-destructive techniques find limited application: quality control is based on the qualification of the process and of operators, on the recording of production parameters and on production samples. Visual inspection and process audits were the main techniques used. At the level of an extended chain of joints and splices - from a 53.5 m half-cell to a complete 2.7 km arc sector - quality control is based on vacuum leak tests, electrical tests and RF microwave reflectometry that progressively validated the work performed. Subsequent pressure tests, cryogenic circuits flushing with high pressure helium and cool-downs revealed a few unseen or new defects. This paper presents an overview of the quality control techniques used, seeking lessons applicable to similar large, complex projects