Dysfunction of Endothelial Progenitor Cells from Smokers and Chronic Obstructive Pulmonary Disease Patients Due to Increased DNA Damage and Senescence

Cardiovascular disease (CVD) is a major cause of death in smokers, particularly in those with chronic obstructive pulmonary disease (COPD). Circulating endothelial progenitor cells (EPC) are required for endothelial homeostasis, and their dysfunction contributes to CVD. To investigate EPC dysfunction in smokers, we isolated and expanded blood outgrowth endothelial cells (BOEC) from peripheral blood samples from healthy nonsmokers, healthy smokers, and COPD patients. BOEC from smokers and COPD patients showed increased DNA double-strand breaks and senescence compared to nonsmokers. Senescence negatively correlated with the expression and activity of sirtuin-1 (SIRT1), a protein deacetylase that protects against DNA damage and cellular senescence. Inhibition of DNA damage response by silencing of ataxia telangiectasia mutated (ATM) kinase resulted in upregulation of SIRT1 expression and decreased senescence. Treatment of BOEC from COPD patients with the SIRT1 activator resveratrol or an ATM inhibitor (KU-55933) also rescued the senescent phenotype. Using an in vivo mouse model of angiogenesis, we demonstrated that senescent BOEC from COPD patients are dysfunctional, displaying impaired angiogenic ability and increased apoptosis compared to cells from healthy nonsmokers. Therefore, this study identifies epigenetic regulation of DNA damage and senescence as pathogenetic mechanisms linked to endothelial progenitors' dysfunction in smokers and COPD patients. These defects may contribute to vascular disease and cardiovascular events in smokers and could therefore constitute therapeutic targets for intervention. 

Longitudinal relations between sectarian and nonsectarian community violence and child adjustment in Northern Ireland

Although relations between political violence and child adjustment are well documented, longitudinal research is needed to adequately address the many questions remaining about the contexts and developmental trajectories underlying the effects on children in areas of political violence. The study examined the relations between sectarian and nonsectarian community violence and adolescent adjustment problems over 4 consecutive years. Participants included 999 mother-child dyads (482 boys, 517 girls), M ages = 12.18 (SD = 1.82), 13.24 (SD = 1.83), 13.61 (SD = 1.99), and 14.66 (SD = 1.96) years, respectively, living in socially deprived neighborhoods in Belfast, Northern Ireland, a context of historical and ongoing political violence. In examining trajectories of adjustment problems, including youth experience with both sectarian and nonsectarian antisocial behaviors, sectarian antisocial behavior significantly predicted more adjustment problems across the 4 years of the study. Experiencing sectarian antisocial behavior was related to increased adolescent adjustment problems, and this relationship was accentuated in neighborhoods characterized by higher crime rates. The discussion considers the implications for further validating the distinction between sectarian and nonsectarian violence, including consideration of neighborhood crime levels, from the child's perspective in a setting of political violence. Copyright © Cambridge University Press 2013.

Landfill cap models under simulated climate change precipitation::Impacts of cracks and root growth

Desiccation crack formation is a key process that needs to be understood in assessment of landfill cap performance under anticipated future climate change scenarios. The objectives of this study were to examine: (a) desiccation cracks and impacts that roots may have on their formation and resealing, and (b) their impacts on hydraulic conductivity under anticipated climate change precipitation scenarios. Visual observations, image analysis of thin sections and hydraulic conductivity tests were carried out on cores collected from two large-scale laboratory trial landfill cap models (∼80 × 80 × 90 cm) during a year of four simulated seasonal precipitation events. Extensive root growth in the topsoil increased percolation of water into the subsurface, and after droughts, roots grew deep into low-permeability layers through major cracks which impeded their resealing. At the end of 1 year, larger cracks had lost resealing ability and one single, large, vertical crack made the climate change precipitation model cap inefficient. Even though the normal precipitation model had developed desiccation cracks, its integrity was preserved better than the climate change precipitation model.

Acquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer

Failure to efficiently induce apoptosis contributes to cisplatin resistance in non-small-cell lung cancer (NSCLC). Although BCL-2-associated X protein (BAX) and BCL-2 antagonist killer (BAK) are critical regulators of the mitochondrial apoptosis pathway, their requirement has not been robustly established in relation to cisplatin. Here, we show that cisplatin can efficiently bypass mitochondrial apoptosis block caused by loss of BAX and BAK, via activation of the extrinsic death receptor pathway in some model cell lines. Apoptosis resistance following cisplatin can only be observed when both extrinsic and intrinsic pathways are blocked, consistent with redundancy between mitochondrial and death receptor pathways in cisplatin-induced apoptosis. In H460 NSCLC cells, caspase-8 cleavage was shown to be induced by cisplatin and is dependent on death receptor 4, death receptor 5, Fas-associated protein with death domain, acid sphingomyelinase and ceramide synthesis. In contrast, cisplatin-resistant cells fail to activate caspase-8 via this pathway despite conserving sensitivity to death ligand-driven activation. Accordingly, caspase-8 activation block acquired during cisplatin resistance, can be bypassed by death receptor agonism. © 2012 Macmillan Publishers Limited

Modeling target bulk heating resulting from ultra-intense short pulse laser irradiation of solid density targets

Isochoric heating of solid-density matter up to a few tens of eV is of interest for investigating astrophysical or inertial fusion scenarios. Such ultra-fast heating can be achieved via the energy deposition of short-pulse laser generated electrons. Here, we report on experimental measurements of this process by means of time-and space-resolved optical interferometry. Our results are found in reasonable agreement with a simple numerical model of fast electron-induced heating. (C) 2013 AIP Publishing LLC.

Laser-driven generation of collimated ultra-relativistic positron beams

We report on recent experimental results concerning the generation of collimated (divergence of the order of a few mrad) ultra-relativistic positron beams using a fully optical system. The positron beams are generated exploiting a quantum-electrodynamic cascade initiated by the propagation of a laser-accelerated, ultra-relativistic electron beam through high-Z solid targets. As long as the target thickness is comparable to or smaller than the radiation length of the material, the divergence of the escaping positron beam is of the order of the inverse of its Lorentz factor. For thicker solid targets the divergence is seen to gradually increase, due to the increased number of fundamental steps in the cascade, but it is still kept of the order of few tens of mrad, depending on the spectral components in the beam. This high degree of collimation will be fundamental for further injection into plasma-wakefield afterburners.

A device to investigate the axial strain dependence of the critical current density in superconductors

We have developed an instrument to study the behavior of the critical current density (J(c)) in superconducting wires and tapes as a function of field (mu(0)H), temperature (T), and axial applied strain (epsilon(a)). The apparatus is an improvement of similar devices that have been successfully used in our institute for over a decade. It encompasses specific advantages such as a simple sample layout, a well defined and homogeneous strain application, the possibility of investigating large compressive strains and the option of simple temperature variation, while improving the main drawback in our previous systems by increasing the investigated sample length by approximately a factor of 10. The increase in length is achieved via a design change from a straight beam section to an initially curved beam, placed perpendicular to the applied field axis in the limited diameter of a high field magnet bore. This article describes in detail the mechanical design of the device and its calibrations. Additionally initial J(c)(epsilon(a)) data, measured at liquid helium temperature, are presented for a bronze processed and for a powder-in-tube Nb3Sn superconducting wire. Comparisons are made with earlier characterizations, indicating consistent behavior of the instrument. The improved voltage resolution, resulting from the increased sample length, enables J(c) determinations at an electric field criterion E-c=10 muV/m, which is substantially lower than a criterion of E-c=100 muV/m which was possible in our previous systems. (C) 2004 American Institute of Physics.

Characterisation of deuterium spectra from laser driven multi-species sources by employing differentially filtered image plate detectors in Thomson spectrometers

A novel method for characterising the full spectrum of deuteron ions emitted by laser driven multi-species ion sources is discussed. The procedure is based on using differential filtering over the detector of a Thompson parabola ion spectrometer, which enables discrimination of deuterium ions from heavier ion species with the same charge-to-mass ratio (such as C^{6 +}, O^{8 +}, etc.). Commonly used Fuji Image plates were used as detectors in the spectrometer, whose absolute response to deuterium ions over a wide range of energies was calibrated by using slotted CR-39 nuclear track detectors. A typical deuterium ion spectrum diagnosed in a recent experimental campaign is presented, which was produced from a thin deuterated plastic foil target irradiated by a high power laser.

Multiple mycotoxin exposure determined by urinary biomarkers in rural subsistence farmers in the former Transkei, South Africa

Subsistence farmers are exposed to a range of mycotoxins. This study applied novel urinary multi-mycotoxin LC-MS/MS methods to determine multiple exposure biomarkers in the high oesophageal cancer region, Transkei, South Africa. Fifty-three female participants donated part of their maize-based evening meal and first void morning urine, which was analysed both with sample clean-up (single and multi-biomarker) and by a 'dilute-and-shoot' multi-biomarker method. Results were corrected for recovery with LOD for not detected. A single biomarker method detected fumonisin B1 (FB1) (87% incidence; mean±standard deviation 0.342±0.466 ng/mg creatinine) and deoxynivalenol (100%; mean 20.4±49.4 ng/mg creatinine) after hydrolysis with β-glucuronidase. The multi-biomarker 'dilute-and-shoot' method indicated deoxynivalenol-15-glucuronide was predominantly present. A multi-biomarker method with β-glucuronidase and immunoaffinity clean-up determined zearalenone (100%; 0.529±1.60 ng/mg creatinine), FB1 (96%; 1.52±2.17 ng/mg creatinine), α-zearalenol (92%; 0.614±1.91 ng/mg creatinine), deoxynivalenol (87%; 11.3±27.1 ng/mg creatinine), β-zearalenol (75%; 0.702±2.95 ng/mg creatinine) and ochratoxin A (98%; 0.041±0.086 ng/mg creatinine). These demonstrate the value of multi-biomarker methods in measuring exposures in populations exposed to multiple mycotoxins. This is the first finding of urinary deoxynivalenol, zearalenone, their conjugates, ochratoxin A and zearalenols in Transkei.

The EU economic and social model in the global crisis: Interdisciplinary perspectives:Interdisciplinary perspectives

This book addresses the viability of the EU economic and social model within and after the global economic crisis. It identifies four key issues which warrant further discussion: (1) the asymmetry of the legal and policy framework of the euro and potential recalibration; (2) substantive tensions between the EU 'economic constitution' and its normative aim of social justice and impacts on national policy; (3) the role of civil society, including the two sides of industry in overcoming these tensions and (4) the EU's global aspirations towards the creation of a viable socio-economic model. Its chapters offer two perspectives on each of the four main issues. In drawing these debates together, the book provides a broad understanding as well as starting points for future research. Bringing together different disciplinary approaches, ranging from legal studies to political economy, sociology and macroeconomics, it is a valuable contribution to the debate on the European social model and introduces new insights by focusing on legal and political tensions, the impact of the financial crisis and other economic contexts as well as global dimensions. 

Autonomous collective agreements as a regulatory device in European labour law:How to read Article 139 EC

This article discusses whether European social partners can derive the competence to autonomously devise European collective labour agreements from Article 139 EC (equals Article III-212 Constitution of Europe). Placing the question in the context of discussions of EU governance and private lawmaking in general, the author starts with a comparative overview of legal conceptions for collective labour agreements in Europe, focusing on three Member States' orders where their effects are not or only partly regulated by state legislation. Based on this comparison, she analyses Article 139(2) and offers a new interpretation of its provisions concerning autonomous implementation of European social partner agreements. She concludes that European social partners do have the competence to agree on a basic agreement stating the rules for European collective bargaining autonomously.

Water and temperature relations of soil Actinobacteria

Actinobacteria perform essential functions within soils, and are dependent on available water to do so. We determined the water-activity (a_w) limits for cell division of Streptomyces albidoflavus, Streptomyces rectiviolaceus, Micromonospora grisea and Micromonospora (JCM 3050) over a range of temperatures, using culture media supplemented with a biologically permissive solute (glycerol). Each species grew optimally at 0.998 a_w (control; no added glycerol) and growth rates were near-optimal in the range 0.971–0.974 (1 M glycerol) at permissive temperatures. Each was capable of cell division at 0.916–0.924 a_w (2 M glycerol), but only S. albidoflavus grew at 0.895 or 0.897 a_w (3 M glycerol, at 30 and 37°C respectively). For S. albidoflavus, however, no growth occurred on media at ≤ 0.870 (4 M glycerol) during the 40-day assessment period, regardless of temperature, and a theoretical limit of 0.877 a_w was derived by extrapolation of growth curves. This level of solute tolerance is high for non-halophilic bacteria, but is consistent with reported limits for the growth and metabolic activities of soil microbes. The limit, within the range 0.895–0.870 a_w, is very much inferior to those for obligately halophilic bacteria and extremely halophilic or xerophilic fungi, and is inconsistent with earlier reports of cell division at 0.500 a_w. These findings are discussed in relation to planetary protection policy for space exploration and the microbiology of arid soils.

Low pressure methane solubility in lithium-ion batteries based solvents and electrolytes as a function of temperature. Measurement and prediction

The methane solubility in five pure electrolyte solvents and one binary solvent mixture for lithium ion batteries – such as ethylene carbonate (EC), propylene carbonate (PC), dimethyl carbonate (DMC), ethyl methyl carbonate (EMC), diethyl carbonate (DEC) and the (50:50 wt%) mixture of EC:DMC was studied experimentally at pressures close to atmospheric and as a function of temperature between (280 and 343) K by using an isochoric saturation technique. The effect of the selected anions of a lithium salt LiX (X = hexafluorophosphate,

Implications of FPS1 deletion and membrane ergosterol content for glycerol efflux from Saccharomyces cerevisiae

The deletion of the gene encoding the glycerol facilitator Fps1p was associated with an altered plasma membrane lipid composition in Saccharomyces cerevisiae. The S. cerevisiae fps1delta strain respectively contained 18 and 26% less ergosterol than the wild-type strain, at the whole-cell level and at the plasma membrane level. Other mutants with deficiencies in glycerol metabolism were studied to investigate any possible link between membrane ergosterol content and intracellular glycerol accumulation. In these mutants a modification in intracellular glycerol concentration, or in intra- to extracellular glycerol ratio was accompanied by a reduction in plasma membrane ergosterol content. However, there was no direct correlation between ergosterol content and intracellular glycerol concentration. Lipid composition influences the membrane permeability for solutes during adaptation of yeast cells to osmotic stress. In this study, ergosterol supplementation was shown to partially suppress the hypo-osmotic sensitivity phenotype of the fps1delta strain, leading to more efficient glycerol efflux, and improved survival. The erg-1 disruption mutant, which is unable to synthesise ergosterol, survived and recovered from the hypo-osmotic shock more successfully when the concentration of exogenously supplied ergosterol was increased. The results obtained suggest that a higher ergosterol content facilitates the flux of glycerol across the plasma membrane of S. cerevisiae cells.

Two potential clinical applications of the alkaline single-cell gel electrophoresis assay .1. Human bladder washings and transitional cell carcinoma of the bladder .2. Human sperm and male infertility

Part 1: The alkaline single-cell gel electrophoresis (comet) assay was used to analyse the integrity and DNA content of exfoliated cells extracted from bladder washing specimens from 9 transitional cell carcinoma patients and 15 control patients. DNA damage, as expressed by % tail DNA and tail moment values, was observed to occur in cells from both control and bladder cancer samples. The extent of the damage was, however, found to be significantly greater in the cancer group than in the control group. Comet optical density values were also recorded for each cell analysed in the comet assay and although differences observed between tumour grades were not found to be statistically significant, the mean comet optical density value was observed to be greater in the cancer group than in the control population studied, These preliminary results suggest that the comet assay may have potential as a diagnostic tool and as a prognostic indicator in transitional cell carcinoma, Part 2: Baseline DNA damage in sperm cells from 13 normozoospermic fertile males, 17 normozoospermic infertile males and 11 asthenozoospermic infertile males were compared using a modified alkaline comet assay technique. No significant difference in the level of baseline DNA damage was observed between the 3 categories of sperm studied; however the untreated sperm cells were observed to display approximately 20% tail DNA. This is notably higher than the background DNA damage observed in somatic cells where the % tail DNA is normally less than 5%. Sperm from the 3 groups of men studied were also compared for sensitivity to DNA breakage, using the modified alkaline comet assay, following X-ray irradiations (5, 10 and 30 Gy) and hydrogen peroxide treatments (40, 100 and 200 mu M). Significant levels of X-ray-induced damage were found relative to untreated control sperm in the two infertile groups following 30 Gy irradiation. Significant damage in hydrogen peroxide-treated sperm was observed in sperm from fertile samples, at 200 mu M and in infertile samples at 100- and 200-mu M doses relative to controls. These results therefore indicate that fertile sperm samples are more resistant to X-ray- and hydrogen peroxide-induced DNA breakage than infertile samples. Further studies involving greater numbers of individuals are currently in progress to confirm these findings.