Effects of nonselective and selective cyclooxygenase inhibitors on the contractions of isolated bronchial smooth muscle in the horse

We evaluated the effects of nonselective cyclooxygenase (COX)-1/COX-2 inhibitors (acetylsalicylic acid, indomethacin, ibuprofen, flunixin meglumine, phenylbutazone), preferential COX-2 inhibitors (diclofenac, meloxicam, carprofen), selective COX-1 inhibitor (SC-560), and selective COX-2 inhibitors (celecoxib, firocoxib, parecoxib) on the contractions of isolated bronchi induced by electrical field stimulation (EFS). Bronchial rings, obtained from lungs of slaughtered horses, were put in isolated organ baths, and the mechanical activity was measured by means of isotonic transducers. Electrical Field Stimulation was applied to the preparations, and the effects of drugs on the amplitude of evoked contractions were measured. Nonselective COX inhibitors did not modify EFS-induced contractions to a relevant degree, except indomethacin which caused a concentration-dependent decrease of the contraction amplitude. Conversely, preferential COX-2 inhibitors enhanced the contractions in a concentration-related fashion, whilst the selective COX-1 inhibitor reduced them. Among selective COX-2 inhibitors, parecoxib increased EFS-evoked contractions whereas celecoxib and firocoxib were ineffective. These results suggest that the inhibition of prostanoid synthesis does not modify the electrical field-stimulated contractions of isolated horse bronchi. Since EFS-induced contractions of horse bronchi were previously shown to be of full cholinergic nature, the increase caused by diclofenac, meloxicam, carprofen, and parecoxib could be due to an inhibition of acetylcholinesterase; in accordance, these drugs potentiated exogenous acetylcholine-induced but not carbachol-induced bronchial contraction. Indomethacin and SC-560 might instead decrease bronchial contractions by inhibiting calcium currents. Clinical use of meloxicam and carprofen in horses with bronchial hyper-responsiveness requires caution for a potential risk of causing adverse effects due to bronchoconstriction

High-resolution tracking in a GEM-Emulsion detector

SHiP (Search for Hidden Particles) is a beam dump experiment proposed at the CERN SPS aiming at the observation of long lived particles very weakly coupled with ordinary matter mostly produced in the decay of charmed hadrons. The beam dump facility of SHiP is also a copious factory of neutrinos of all three kinds and therefore a dedicated neutrino detector is foreseen in the SHiP apparatus. The neutrino detector exploits the Emulsion Cloud Chamber technique with a modular structure, alternating walls of target units and planes of electronic detectors providing the time stamp to the event. GEM detectors are one of the possible choices for this task. This paper reports the results of the first exposure to a muon beam at CERN of a new hybrid chamber, obtained by coupling a GEM chamber and an emulsion detector. Thanks to the micrometric accuracy of the emulsion detector, the position resolution of the GEM chamber as a function of the particle inclination was evaluated in two configurations, with and without the magnetic fiel

The Relationship Between Widespread Pollution Exposure and Oxidized Products of Nucleic Acids in Seminal Plasma and Urine in Males Attending a Fertility Center

BACKGROUND: In recent decades, there has been an increase in male infertility, and in many cases, the etiology remains unclear. Several studies relate male hypo-fertility to xenobiotic exposure, even if no data exist about multiple exposure at the environmental level. METHODS: The study involved 86 males with diagnosis of idiopathic male infertility (IMI), and 46 controls with no alteration in sperm characteristics. Seminal plasma (SP) and urine samples were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) to quantify biomarkers of exposure (the main metabolites of benzene, toluene, 1,3-butadiene, 3-monochloropropanediol, styrene, and naphthol) and effect (oxidized products of nucleic acids). RESULTS: Biomarker concentrations were similar in subjects with IMI and controls even if a stronger correlation between biomarkers of exposure and effects were observed in SP. Data show that, both in SP and urine, most metabolites were inter-correlated, indicating a simultaneous co-exposure to the selected substances at the environmental level. Principal component analysis showed in SP the clustering of mercapturic acids indicating a preferential metabolic pathway with Glutathione (GSH) depletion and, consequently, an increase of oxidative stress. This result was also confirmed by multivariable analysis through the development of explanatory models for oxidized products of nucleic acids. CONCLUSIONS: This study highlights how oxidative stress on the male reproductive tract can be associated with a different representation of metabolic pathways making the reproductive tract itself a target organ for different environmental pollutants. Our results demonstrate that SP is a suitable matrix to assess the exposure and evaluate the effects of reproductive toxicants in environmental/occupational medicine. The statistical approach proposed in this work represents a model appropriate to study the relationship between multiple exposure and effect, applicable even to a wider variety of chemicals

Neural correlates of executive function and working memory in the 'at risk mental state'

Background and Aims: People with ‘prodromal’ symptoms have a very high risk of developing psychosis. We used functional MRI to examine the neurocognitive basis of this vulnerability. Method: Cross-sectional comparison of subjects with an ARMS (n=17), first episode schizophreniform psychosis (n=10) and healthy volunteers (n=15). Subjects were studied using functional MRI while they performed an overt verbal fluency task, a random movement generation paradigm and an N-Back working memory task. Results: During an N-Back task the ARMS group engaged inferior frontal and posterior parietal cortex less than controls but more than the first episode group. During a motor generation task, the ARMS group showed less activation in the left inferior parietal cortex than controls, but greater activation than the first episode group. During verbal fluency using ‘Easy’ letters, the ARMS group demonstrated intermediate activation in the left inferior frontal cortex, with first episode groups showing least, and controls most, activation. When processing ‘Hard’ letters, differential activation was evident in two left inferior frontal regions. In its dorsolateral portion, the ARMS group showed less activation than controls but more than the first episode group, while in the opercular part of the left inferior frontal gyrus / anterior insula activation was greatest in the first episode group, weakest in controls and intermediate in the ARMS group. Conclusions: The ARMS is associated with abnormalities of regional brain function that are qualitatively similar to those in patients who have just developed psychosis but less severe

Macro- And Microvascular Functions In Cystic Fibrosis Adults Without Cardiovascular Risk Factors: A Case-Control Study.

Increasing survival from cystic fibrosis show untypical systems involvement, such as cardiocirculatory. In particular, the presence of CFTR in smooth muscle and endothelial cells, systemic inflammation and oxidative stress could explain vascular alterations in these patients. We aimed at noninvasely evaluating macro- and microvascular dysfunction in cystic fibrosis adults without cardiovascular risk factors. Twenty-twoadults affected by cystic fibrosis and 24 healthy volunteers matched for age and sex were enrolled. None had known cardiovascular risk factors. All people underwent blood pressure measurement, microvascular function assessment by EndoPAT-2000 device (calculating RH-PAT index) and macrovascular evaluation by pulse wave velocity (PWV). RH-PAT index was significantly lower in patients than in controls (1.74±0.59 vs 2.33±0.34; p<0.001). Thirteen patients of 22 had a value inferior to the threshold of 1.67 (59.1%), while no controls had (p<0.001). Carotid-femoral PWV did not differ between the two groups (5.2±1.5 m/s vs 5.4±1.1; p=0.9), while brachial-ankle one did (11.0±2.2 m/s vs 10.1±0.8 m/s; p=0.04).Adults patients affected by cystic fibrosis show peripheral endothelial dysfunction, which is the first alteration in atherosclerotic phenomenon. Moreover, arterial stiffness measured by PWV unclearly seems to differ respect of healthy people, perhaps because PWV alterations are typical of above 50 years old people. It is unclear what prognostic role of future developing of atherosclerotic disease these findings could be, but it seems evident that cystic fibrosis directly affects cardiovascular system itself

Lipid profile and antimicrobial activity of microbial oils from 16 oleaginous yeasts isolated from artisanal cheese

Microbial oil is becoming an alternative to the increasing cost of vegetable oils, and it can be used for many applications, as biodiesel production and food supplementation. In particular, oleaginous yeasts, being unicellular, devoid of endotoxins, and suitable for large-scale fermentation, are particularly attractive for biotechnological approaches.  This work aimed to identify, by molecular analyses, sixteen yeast strains as well as analyze the lipid profile and potential antimicrobial activity of the oil produced by them. All strains were identified as Yarrowia lipolytica, a promising single-cell-oil producer. No antimicrobial activity was found for the oil analyzed, although the lipid profile showed interesting results. The major fatty acids identified were oleic (18:1n9) and linoleic (18:2n6c) and the minor fatty acids were palmitic (C16:0), palmitoleic (C16:1), heptadecanoic (C17:1), estearic (C18:0) and α-linolenic (C18:3n3). This last omega-3 fatty acid was identified on two strains (QU22 and QU137), enabling the oil produced by them to be used for dietary applications. Moreover, the oil of the other oleaginous yeasts analyzed in this study appears to be suitable for biodiesel production, since their lipid profiles are similar to the vegetable oils, widely used for that end.O uso de óleo microbiano está se tornando uma alternativa ao aumento do custo de óleos vegetais, e podendo ser utilizado para várias aplicações, como a produção de biodiesel e a suplementação de alimentos. Em particular, as leveduras oleaginosas, sendo unicelulares, desprovidas de endotoxinas e adequadas para a fermentação em grande escala, são particularmente atrativas para abordagens biotecnológicas. Este trabalho teve como objetivo identificar, por meio de técnicas moleculares, dezesseis cepas de leveduras e analisar o perfil lipídico e a potencial atividade antimicrobiana do óleo produzido por elas. Todas as cepas foram identificadas como Yarrowia lipolytica, uma promissora produtora de óleo microbiano. Nenhuma atividade antimicrobiana foi encontrada para o óleo analisado, porém, o perfil lipídico dos óleos apresentaram resultados interessantes. Os principais ácidos graxos identificados foram oléico (18:1n9) e linoléico (18:2n6c) e os ácidos graxos em menor quantidade foram o palmítico (C16:0), palmitoléico (C16:1), heptadecanóico (C17:1), esteárico (C18:0) e α -linolênico (C18:3n3). Este último ácido graxo ômega-3 foi identificado em duas cepas (QU22 e QU137), o que pode permitir que o óleo produzido por estas cepas seja utilizado em aplicações alimentares. Além disso, o óleo das demais leveduras oleaginosas analisadas ​​neste estudo parece ser adequado para a produção de biodiesel, uma vez que o seu perfil lipídico é semelhante ao dos óleos vegetais, largamente utilizados para este fim

Faint Lyman-Break galaxies as a crucial test for galaxy formation models

It has recently been shown that galaxy formation models within the LambdaCDM cosmology predict that, compared to the observed population, small galaxies (with stellar masses < 10^{11} M_sun) form too early, are too passive since z ~ 3 and host too old stellar populations at z=0. We then expect an overproduction of small galaxies at z > 4 that should be visible as an excess of faint Lyman-break galaxies. To check whether this excess is present, we use the MORGANA galaxy formation model and GRASIL spectro-photometric + radiative transfer code to generate mock catalogues of deep fields observed with HST-ACS. We add observational noise and the effect of Lyman-alpha emission, and perform color-color selections to identify Lyman-break galaxies. The resulting mock candidates have plausible properties that closely resemble those of observed galaxies. We are able to reproduce the evolution of the bright tail of the luminosity function of Lyman-break galaxies (with a possible underestimate of the number of the brightest i-dropouts), but uncertainties and degeneracies in dust absorption parameters do not allow to give strong constraints to the model. Besides, our model shows a clear excess with respect to observations of faint Lyman-break galaxies, especially of z_{850} ~ 27 V-dropouts at z ~ 5. We quantify the properties of these "excess" galaxies and discuss the implications: these galaxies are hosted in dark matter halos with circular velocities in excess of 100 km s^{-1}, and their suppression may require a deep re-thinking of stellar feedback processes taking place in galaxy formation.Comment: 17 pages, 13 figures, 1 table; accepted for publication by MNRA

Nuclear DGKα regulates cell cycle progression in K562 cells

The existence of an independent nuclear inositide pathway distinct from the cytoplasmic one has been demonstrated in different physiological systems and in diseases (1). Phosphatidylinositols (PIs) play an important role in nuclear function regulation and behave differently from their counterparts in the cytoplasm. The autonomous nuclear PI cycle in eukaryotic cells is involved in different regulation processes, from cell proliferation to differentiation and many others (2). At nuclear level an array of kinases and phosphatases can modulate PIs. Among these, Diacylglycerol Kinases (DGKs) are a class of phosphotransferases that phosphorylate diacylglycerol (DAG) and induce the synthesis of phosphatidic acid. We Investigated DGKα localization and function in human erythroleukemia cell line K562. Synchronization experiments at different cell cycle checkpoints showed an important expression of DGKα in the nuclear fraction of this cell model, slightly peaking at G2/M. This suggested that DGKα might have a function in nuclear signaling. In particular, nuclear DGKα expression can modulate cell cycle progression, leading to changes in the phosphorylated status of the Retinoblastoma protein (pRb), thus, regulating G1/S transition: DGKα silencing or downregulation leads to impaired G1/S transition and its overexpression leads to S phase progression. The molecular mechanism by which nuclear DGKα controls pRb phosphorylation and therefore cell cycle regulation in K562 cell line are still unclear. Further studies are needed to better understand the role of DGKα in relation to other pivotal PIs involved in cell cycle regulation in the hematopoietic system

Services for people at high risk improve outcomes in patients with first episode psychosis

OBJECTIVE: About one‐third of patients referred to services for people at high risk for psychosis may have already developed a first episode of psychosis (FEP). We compared clinical outcomes in FEP patients who presented to either high risk or conventional mental health services. METHOD: Retrospective study comparing duration of hospital admission, referral‐to‐diagnosis time, need for compulsory hospital admission and frequency of admission in patients with FEP who initially presented to a high‐risk service (n = 164) to patients with FEP who initially presented to conventional mental health services (n = 2779). Regression models were performed, controlling for several confounders. RESULTS: FEP patients who had presented to a high‐risk service spent 17 fewer days in hospital [95% CI: −33.7 to (−0.3)], had a shorter referral‐to‐diagnosis time [B coefficient −74.5 days, 95% CI: −101.9 to −(47.1)], a lower frequency of admission [IRR: 0.49 (95% CI: 0.39–0.61)] and a lower likelihood of compulsory admission [OR: 0.52 (95% CI: 0.34–0.81)] in the 24 months following referral, as compared to FEP patients who were first diagnosed at conventional services. CONCLUSION: Services for people at high risk for psychosis are associated with better clinical outcomes in patients who are already psychotic

Simulations of the galaxy population constrained by observations from z=3 to the present day: implications for galactic winds and the fate of their ejecta

We apply Monte Carlo Markov Chain (MCMC) methods to large-scale simulations of galaxy formation in a LambdaCDM cosmology in order to explore how star formation and feedback are constrained by the observed luminosity and stellar mass functions of galaxies. We build models jointly on the Millennium and Millennium-II simulations, applying fast sampling techniques which allow observed galaxy abundances over the ranges 7<log(M*/Msun)<12 and z=0 to z=3 to be used simultaneously as constraints in the MCMC analysis. When z=0 constraints alone are imposed, we reproduce the results of previous modelling by Guo et al. (2012), but no single set of parameters can reproduce observed galaxy abundances at all redshifts simultaneously, reflecting the fact that low-mass galaxies form too early and thus are overabundant at high redshift in this model. The data require the efficiency with which galactic wind ejecta are reaccreted to vary with redshift and halo mass quite differently than previously assumed, but in a similar way as in some recent hydrodynamic simulations of galaxy formation. We propose a specific model in which reincorporation timescales vary inversely with halo mass and are independent of redshift. This produces an evolving galaxy population which fits observed abundances as a function of stellar mass, B- and K-band luminosity at all redshifts simultaneously. It also produces a significant improvement in two other areas where previous models were deficient. It leads to present day dwarf galaxy populations which are younger, bluer, more strongly star-forming and more weakly clustered on small scales than before, although the passive fraction of faint dwarfs remains too high