Intermittent hypoxia inhibits clearance of triglyceride-rich lipoproteins and inactivates adipose lipoprotein lipase in a mouse model of sleep apnoea

Delayed lipoprotein clearance is associated with atherosclerosis. This study examined whether chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnoea (OSA), can lead to hyperlipidaemia by inhibiting clearance of triglyceride rich lipoproteins (TRLP). Male C57BL/6J mice on high-cholesterol diet were exposed to 4 weeks of CIH or chronic intermittent air (control). FIO2 was decreased to 6.5 once per minute during the 12 h light phase in the CIH group. After the exposure, we measured fasting lipid profile. TRLP clearance was assessed by oral gavage of retinyl palmitate followed by serum retinyl esters (REs) measurements at 0, 1, 2, 4, 10, and 24 h. Activity of lipoprotein lipase (LpL), a key enzyme of lipoprotein clearance, and levels of angiopoietin-like protein 4 (Angptl4), a potent inhibitor of the LpL activity, were determined in the epididymal fat pads, skeletal muscles, and heart. Chronic intermittent hypoxia induced significant increases in levels of total cholesterol and triglycerides, which occurred in TRLP and LDL fractions (P 0.05 for each comparison). Compared with control mice, animals exposed to CIH showed increases in REs throughout first 10 h after oral gavage of retinyl palmitate (P 0.05), indicating that CIH inhibited TRLP clearance. CIH induced a 5-fold decrease in LpL activity (P 0.01) and an 80 increase in Angptl4 mRNA and protein levels in the epididymal fat, but not in the skeletal muscle or heart. CIH decreases TRLP clearance and inhibits LpL activity in adipose tissue, which may contribute to atherogenesis observed in OSA.

Determination of Opiates in Whole Blood and Vitreous Humor: A Study of the Matrix Effect and an Experimental Design to Optimize Conditions for the Enzymatic Hydrolysis of Glucuronides

Faculty of Medicine University of Sao Paulo

THE HOUSE OF JOANA DARK: DRAMA AND PRODUCTION

While discussing images of Our Lady and of the mothers and women of the Garden of Flowers (or "Devils' Hole"), a peripheral district of a city in the interior of Sao Paulo state, this paper intends to explore the specificity of dramatic aesthetics. Rather than depend upon the aesthetics of social drama, as discussed in the works of Victor Turner, the present paper deals with a concept of montage that is inspired by the cinema of Sergei Eisenstein in order to illuminate a selection of field notes... and, along with Eisenstein, Julia Kristeva, Walter Benjamin, Michael Taussig and Antonin Artaud. Wit regards to those readers interested in hearing what these women may have to say, caution is suggested, for the words of these women may ring in our ears as the sounds of musket shots

Blood transfusions increase circulating plasma free hemoglobin levels and plasma nitric oxide consumption: a prospective observational pilot study

Introduction: The increasing number of reports on the relation between transfusion of stored red blood cells (RBCs) and adverse patient outcome has sparked an intense debate on the benefits and risks of blood transfusions. Meanwhile, the pathophysiological mechanisms underlying this postulated relation remain unclear. The development of hemolysis during storage might contribute to this mechanism by release of free hemoglobin (fHb), a potent nitric oxide (NO) scavenger, which may impair vasodilation and microcirculatory perfusion after transfusion. The objective of this prospective observational pilot study was to establish whether RBC transfusion results in increased circulating fHb levels and plasma NO consumption. In addition, the relation between increased fHb values and circulating haptoglobin, its natural scavenger, was studied. Methods: Thirty patients electively received 1 stored packed RBC unit (n = 8) or 2 stored packed RBC units (n = 22). Blood samples were drawn to analyze plasma levels of fHb, haptoglobin, and NO consumption prior to transfusion, and 15, 30, 60 and 120 minutes and 24 hours after transfusion. Differences were compared using Pearson's chi-square test or Fisher's exact test for dichotomous variables, or an independent-sample t test or Mann-Whitney U test for continuous data. Continuous, multiple-timepoint data were analyzed using repeated one-way analysis of variance or the Kruskall-Wallis test. Correlations were analyzed using Spearman or Pearson correlation. Results: Storage duration correlated significantly with fHb concentrations and NO consumption within the storage medium (r = 0.51, P < 0.001 and r = 0.62, P = 0.002). fHb also significantly correlated with NO consumption directly (r = 0.61, P = 0.002). Transfusion of 2 RBC units significantly increased circulating fHb and NO consumption in the recipient (P < 0.001 and P < 0.05, respectively), in contrast to transfusion of 1 stored RBC unit. Storage duration of the blood products did not correlate with changes in fHb and NO consumption in the recipient. In contrast, pre-transfusion recipient plasma haptoglobin levels inversely influenced post-transfusion fHb concentrations. Conclusion: These data suggest that RBC transfusion can significantly increase post-transfusion plasma fHb levels and plasma NO consumption in the recipient. This finding may contribute to the potential pathophysiological mechanism underlying the much-discussed adverse relation between blood transfusions and patient outcome. This observation may be of particular importance for patients with substantial transfusion requirements.

Development and evolution of caste dimorphism in honeybees - a modeling approach

The difference in phenotypes of queens and workers is a hallmark of the highly eusocial insects. The caste dimorphism is often described as a switch-controlled polyphenism, in which environmental conditions decide an individual's caste. Using theoretical modeling and empirical data from honeybees, we show that there is no discrete larval developmental switch. Instead, a combination of larval developmental plasticity and nurse worker feeding behavior make up a colony-level social and physiological system that regulates development and produces the caste dimorphism. Discrete queen and worker phenotypes are the result of discrete feeding regimes imposed by nurses, whereas a range of experimental feeding regimes produces a continuous range of phenotypes. Worker ovariole numbers are reduced through feeding-regime-mediated reduction in juvenile hormone titers, involving reduced sugar in the larval food. Based on the mechanisms identified in our analysis, we propose a scenario of the evolutionary history of honeybee development and feeding regimes.

Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC

We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.

The effect of sodium fluoride preservative and storage temperature on the stability of cocaine in horse blood, sheep vitreous and deer muscle

The in vitro stability of cocaine in horse blood, sheep vitreous humour (VH) and homogenised deer muscle is described. The stability of cocaine in horse blood was of interest because many toxicology laboratories utilise horse blood for the preparation of calibration and check standards and the latter are typically stored during routine use. The storage stability of cocaine in human VH and muscle has not been previously reported. In the absence of blank human VH and muscle, cocaine stability under varying conditions was demonstrated in animal tissues. Blood and VH were stored with and without addition of NaF at room temperature (RT), 4 degrees C and -18 degrees C for 84 days. Muscle homogenates were prepared in water, water/2% NaF, and phosphate buffer (pH 6.0)/2% NaF, and stored for 31 days at RT, 4 degrees C and -18 degrees C. Cocaine stability in human muscle obtained from cocaine positive forensic cases was assessed following storage at -18 degrees C for 13 months. Cocaine and benzoylecgonine (BZE) were extracted using SPE and quantified by GC-MS/MS. Cocaine was stable for 7 days in refrigerated (4 degrees C) horse blood fortified with 1 and 2% NaF. In the absence of NaF, cocaine was not detectable by day 7 in blood stored at RT and 4 degrees C and had declined by 81% following storage at -18 degrees C. At 4 degrees C the rate of cocaine degradation in blood preserved with 2% NaF was significantly slower than with 1% NaF. The stability of cocaine in horse blood appeared to be less than that reported for human blood, probably attributable to the presence of carboxylesterase in horse plasma. Cocaine stored in VH at -18 degrees C was essentially stable for the study period whereas at 4 degrees C concentrations decreased by >50% in preserved and unpreserved VH stored for longer than 14 days. Fluoride did not significantly affect cocaine stability in VH. The stability of cocaine in muscle tissue homogenates significantly exceeded that in blood and VH at every temperature. In preserved and unpreserved samples stored at 4 degrees C and below, cocaine loss did not exceed 2%. The increased stability of cocaine in muscle was attributed to the low initial pH of post-mortem muscle. In tissue from one human case stored for 13 months at -18 degrees C the muscle cocaine concentration declined by only 15% (range: 5-22%). These findings promote the use of human muscle as a toxicological specimen in which cocaine may be detected for longer compared with blood or VH. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Neutral pion and eta meson production in proton-proton collisions at root s=0.9 TeV and root s=7 TeV

The first measurements of the invariant differential cross sections of inclusive pi(0) and eta meson production at mid-rapidity in proton-proton collisions root s = 0.9 TeV and root s = 7 TeV are reported. The pi(0) measurement covers the ranges 0.4 < p(T) < 7 GeV/c and 0.3 < p(T) < 25 GeV/c for these two energies, respectively. The production of eta mesons was measured at root s = 7 TeV in the range 0.4 < p(T) < 15 GeV/c. Next-to-Leading Order perturbative QCD calculations, which are consistent with the pi(0) spectrum at root s = 0.9 TeV, overestimate those of pi(0) and eta mesons at root s = 7 TeV, but agree with the measured eta/pi(0) ratio at root s = 7 TeV. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved.

Expression of tlr4, md2 and cd14 in equine blood leukocytes during endotoxin infusion and in intestinal tissues from healthy horses

The expression of tlr4, md2 and cd14 was studied in equine blood leukocytes and in intestinal samples using real time PCR. The stability of three commonly used reference genes, glyceraldehyde-3P-dehydrogenase (GAPDH), hypoxantine ribosyltransferase (HPRT) and succinate dehydrogenase complex subunit A (SDHA), was evaluated using qbase(PLUS). The equine peripheral blood mononuclear cells (eqPBMC) examined were either stimulated in vitro with Phorbol 12-myristate 13-acetate (PMA) and ionomycin or with the CpG oligodeoxynuclotide 2216 (CpG-ODN 2216) or obtained from horses before, during and after infusion of endotoxin. Intestinal tissue from healthy horses was sampled at ileum, right dorsal colon and rectum. Ranking of the three reference genes used for normalisation identified the combination HPRT/SDHA as most suitable both when determined ex vivo in leukocytes obtained from experimentally induced endotoxaemia and in eqPBMC activated in vitro while HPRT/GAPDH were most appropriate for the intestinal samples. The relative amounts of mRNA for TLR4 and MD-2 increased threefold during in vitro activation of the cells with CpG-ODN 2216 but was decreased in cultures stimulated with PMA/ionomycin. A transient elevation in the transcription of tlr4 and md2 was also evident for equine blood leukocytes following endotoxaemia. The levels of mRNA for CD14 on the other hard remained unaffected both during the induction of endotoxaemia and in the in vitro stimulated PBMCs. A low steady expression of TLR4, MD-2 and CD14 mRNA was demonstrated for the intestinal samples with no variation between the intestinal segments analysed. Thus, the foundation for real time PCR based levels of analysis of mRNA for all three components in the equine LPS receptor complex in different intestinal segments was set, making it possible to carry out future expression studies on clinical material. (C) 2012 Elsevier B.V. All rights reserved.

The Role of Molecular Conformation and Polarizable Embedding for One- and Two-Photon Absorption of Disperse Orange 3 in Solution

Solvent effects on the one- and two-photon absorption (IPA and 2PA) of disperse orange 3 (DO3) in dimethyl sulfoxide (DMSO) are studied using a discrete polarizable embedding (PE) response theory. The scheme comprises a quantum region containing the chromophore and an atomically granulated classical region for the solvent accounting for full interactions within and between the two regions. Either classical molecular dynamics (MD) or hybrid Car-Parrinello (CP) quantum/classical (QM/MM) molecular dynamics simulations are employed to describe the solvation of DO3 in DMSO, allowing for an analysis of the effect of the intermolecular short-range repulsion, long-range attraction, and electrostatic interactions on the conformational changes of the chromophore and also the effect of the solute-solvent polarization. PE linear response calculations are performed to verify the character, solvatochromic shift, and overlap of the two lowest energy transitions responsible for the linear absorption spectrum of DO3 in DMSO in the visible spectral region. Results of the PE linear and quadratic response calculations, performed using uncorrelated solute-solvent configurations sampled from either the classical or hybrid CP QM/MM MD simulations, are used to estimate the width of the line shape function of the two electronic lowest energy excited states, which allow a prediction of the 2PA cross-sections without the use of empirical parameters. Appropriate exchange-correlation functionals have been employed in order to describe the charge-transfer process following the electronic transitions of the chromophore in solution.

Validation and comparison of two soil-vegetation-atmosphere transfer models for tropical Africa

This study aims to compare and validate two soil-vegetation-atmosphere-transfer (SVAT) schemes: TERRA-ML and the Community Land Model (CLM). Both SVAT schemes are run in standalone mode (decoupled from an atmospheric model) and forced with meteorological in-situ measurements obtained at several tropical African sites. Model performance is quantified by comparing simulated sensible and latent heat fluxes with eddy-covariance measurements. Our analysis indicates that the Community Land Model corresponds more closely to the micrometeorological observations, reflecting the advantages of the higher model complexity and physical realism. Deficiencies in TERRA-ML are addressed and its performance is improved: (1) adjusting input data (root depth) to region-specific values (tropical evergreen forest) resolves dry-season underestimation of evapotranspiration; (2) adjusting the leaf area index and albedo (depending on hard-coded model constants) resolves overestimations of both latent and sensible heat fluxes; and (3) an unrealistic flux partitioning caused by overestimated superficial water contents is reduced by adjusting the hydraulic conductivity parameterization. CLM is by default more versatile in its global application on different vegetation types and climates. On the other hand, with its lower degree of complexity, TERRA-ML is much less computationally demanding, which leads to faster calculation times in a coupled climate simulation.

Production of Muons from Heavy Flavor Decays at Forward Rapidity in pp and Pb-Pb Collisions at root s(NN)=2.76 TeV

The ALICE Collaboration has measured the inclusive production of muons from heavy-flavor decays at forward rapidity, 2.5 < y < 4, in pp and Pb-Pb collisions at root s(NN) = 2.76 TeV. The p(t)-differential inclusive cross section of muons from heavy-flavor decays in pp collisions is compared to perturbative QCD calculations. The nuclear modification factor is studied as a function of p(t) and collision centrality. A weak suppression is measured in peripheral collisions. In the most central collisions, a suppression of a factor of about 3-4 is observed in 6 < p(t) < 10 GeV/c. The suppression shows no significant p(t) dependence.

A novel microdeletion syndrome at 3q13.31 characterised by developmental delay, postnatal overgrowth, hypoplastic male genitals, and characteristic facial features

Background Congenital deletions affecting 3q11q23 have rarely been reported and only five cases have been molecularly characterised. Genotype. phenotype correlation has been hampered by the variable sizes and breakpoints of the deletions. In this study, 14 novel patients with deletions in 3q11q23 were investigated and compared with 13 previously reported patients. Methods Clinical data were collected from 14 novel patients that had been investigated by high resolution microarray techniques. Molecular investigation and updated clinical information of one cytogenetically previously reported patient were also included. Results The molecular investigation identified deletions in the region 3q12.3q21.3 with different boundaries and variable sizes. The smallest studied deletion was 580 kb, located in 3q13.31. Genotype. phenotype comparison in 24 patients sharing this shortest region of overlapping deletion revealed several common major characteristics including significant developmental delay, muscular hypotonia, a high arched palate, and recognisable facial features including a short philtrum and protruding lips. Abnormal genitalia were found in the majority of males, several having micropenis. Finally, a postnatal growth pattern above the mean was apparent. The 580 kb deleted region includes five RefSeq genes and two of them are strong candidate genes for the developmental delay: DRD3 and ZBTB20. Conclusion A newly recognised 3q13.31 microdeletion syndrome is delineated which is of diagnostic and prognostic value. Furthermore, two genes are suggested to be responsible for the main phenotype.

Production of K*(892)(0) and phi(1020) in pp collisions at root s=7 TeV

The production of K*(892)(0) and phi(1020) in pp collisions at root s = 7 TeV was measured by the ALICE experiment at the LHC. The yields and the transverse momentum spectra d(2)N/dydp(T) at midrapidity vertical bar y vertical bar < 0.5 in the range 0 < p(T) < 6 GeV/c for K*(892)(0) and 0.4 < p(T) < 6 GeV/c for phi(1020) are reported and compared to model predictions. Using the yield of pions, kaons, and Omega baryons measured previously by ALICE at root s = 7 TeV, the ratios K*/K-, phi/K*, phi/ K-, phi/pi(-), and (Omega + <(Omega)over bar>)/phi are presented. The values of the K*/K-, phi/K* and phi/K- ratios are similar to those found at lower centre-of-mass energies. In contrast, the phi/pi(-) ratio, which has been observed to increase with energy, seems to saturate above 200 GeV. The (Omega + (Omega) over bar)/phi ratio in the p(T) range 1-5 GeV/ c is found to be in good agreement with the prediction of the HIJING/B (B) over bar v2.0model with a strong colour field.

High precision astrometry mission for the detection and characterization of nearby habitable planetary systems with the Nearby Earth Astrometric Telescope (NEAT)

A complete census of planetary systems around a volume-limited sample of solar-type stars (FGK dwarfs) in the Solar neighborhood (d a parts per thousand currency signaEuro parts per thousand 15 pc) with uniform sensitivity down to Earth-mass planets within their Habitable Zones out to several AUs would be a major milestone in extrasolar planets astrophysics. This fundamental goal can be achieved with a mission concept such as NEAT-the Nearby Earth Astrometric Telescope. NEAT is designed to carry out space-borne extremely-high-precision astrometric measurements at the 0.05 mu as (1 sigma) accuracy level, sufficient to detect dynamical effects due to orbiting planets of mass even lower than Earth's around the nearest stars. Such a survey mission would provide the actual planetary masses and the full orbital geometry for all the components of the detected planetary systems down to the Earth-mass limit. The NEAT performance limits can be achieved by carrying out differential astrometry between the targets and a set of suitable reference stars in the field. The NEAT instrument design consists of an off-axis parabola single-mirror telescope (D = 1 m), a detector with a large field of view located 40 m away from the telescope and made of 8 small movable CCDs located around a fixed central CCD, and an interferometric calibration system monitoring dynamical Young's fringes originating from metrology fibers located at the primary mirror. The mission profile is driven by the fact that the two main modules of the payload, the telescope and the focal plane, must be located 40 m away leading to the choice of a formation flying option as the reference mission, and of a deployable boom option as an alternative choice. The proposed mission architecture relies on the use of two satellites, of about 700 kg each, operating at L2 for 5 years, flying in formation and offering a capability of more than 20,000 reconfigurations. The two satellites will be launched in a stacked configuration using a Soyuz ST launch vehicle. The NEAT primary science program will encompass an astrometric survey of our 200 closest F-, G- and K-type stellar neighbors, with an average of 50 visits each distributed over the nominal mission duration. The main survey operation will use approximately 70% of the mission lifetime. The remaining 30% of NEAT observing time might be allocated, for example, to improve the characterization of the architecture of selected planetary systems around nearby targets of specific interest (low-mass stars, young stars, etc.) discovered by Gaia, ground-based high-precision radial-velocity surveys, and other programs. With its exquisite, surgical astrometric precision, NEAT holds the promise to provide the first thorough census for Earth-mass planets around stars in the immediate vicinity of our Sun.