p22phox C242T Single-Nucleotide Polymorphism Inhibits Inflammatory Oxidative Damage to Endothelial Cells and Vessels.

BACKGROUND: The NADPH oxidase, by generating reactive oxygen species, is involved in the pathophysiology of many cardiovascular diseases and represents a therapeutic target for the development of novel drugs. A single-nucleotide polymorphism, C242T of the p22(phox) subunit of NADPH oxidase, has been reported to be negatively associated with coronary heart disease and may predict disease prevalence. However, the underlying mechanisms remain unknown. METHODS AND RESULTS: With the use of computer molecular modeling, we discovered that C242T single-nucleotide polymorphism causes significant structural changes in the extracellular loop of p22(phox) and reduces its interaction stability with Nox2 subunit. Gene transfection of human pulmonary microvascular endothelial cells showed that C242T p22(phox) significantly reduced Nox2 expression but had no significant effect on basal endothelial O2 (.-) production or the expression of Nox1 and Nox4. When cells were stimulated with tumor necrosis factor-α (or high glucose), C242T p22(phox) significantly inhibited tumor necrosis factor-α-induced Nox2 maturation, O2 (.-) production, mitogen-activated protein kinases and nuclear factor κB activation, and inflammation (all P<0.05). These C242T effects were further confirmed using p22(phox) short-hairpin RNA-engineered HeLa cells and Nox2(-/-) coronary microvascular endothelial cells. Clinical significance was investigated by using saphenous vein segments from non-coronary heart disease subjects after phlebotomies. TT (C242T) allele was common (prevalence of ≈22%) and, in comparison with CC, veins bearing TT allele had significantly lower levels of Nox2 expression and O2 (.-) generation in response to high-glucose challenge. CONCLUSIONS: C242T single-nucleotide polymorphism causes p22(phox) structural changes that inhibit endothelial Nox2 activation and oxidative response to tumor necrosis factor-α or high-glucose stimulation. C242T single-nucleotide polymorphism may represent a natural protective mechanism against inflammatory cardiovascular diseases

3D Spectroscopic Observations of Star-Forming Dwarf Galaxies

We give an introduction into the observational technique of integral field or 3D spectroscopy. We discuss advantages and drawbacks of this type of observations and highlight a few science projects enabled by this method. In the second part we describe our 3D spectroscopic survey of Blue Compact Dwarf Galaxies. We show preliminary results from data taken with the VIMOS integral field unit and give an outlook on how automated spectral analysis and forthcoming instruments can provide a new view on star formation and associated processes in dwarf galaxies.Comment: To appear in the proceedings of the JENAM 2010 Symposium "Dwarf Galaxies: Keys to Galaxy Formation and Evolution" (Lisbon, 9-10 September 2010), P. Papaderos, S. Recchi, G. Hensler (eds.), Springer Verlag (2011), in pres

Recombinant factorVIII Fc fusion protein for the prevention and treatment of bleeding in children with severe hemophilia A

This work was supported by funding from Biogen, including funding for the editorial and writing support in the the development of this paper

Retinal nerve fibre layer thinning is associated with drug resistance in epilepsy.

Retinal nerve fibre layer (RNFL) thickness is related to the axonal anterior visual pathway and is considered a marker of overall white matter 'integrity'. We hypothesised that RNFL changes would occur in people with epilepsy, independently of vigabatrin exposure, and be related to clinical characteristics of epilepsy

Identifying as in, out, or sexually inexperienced: Perception of sex-related personal disclosures

The current research explored perceptions of disclosing the information of "I am gay", "I am heterosexual", and "I am a virgin" to a variety of audiences. Participants were 842 undergraduate students who evaluated the valence of each disclosure, listed the associated feelings, and rated the comfort of disclosing such information to various audiences (e.g., a family member, online community). Participants rated the statement consistent with their own sexual orientation as being significantly more positive. No significant difference was found between gay and heterosexual participants’ ratings about disclosing virginity, and disclosure of virginity status was ranked as the most uncomfortable of the three disclosures. Both heterosexual and gay respondents indicated it would be more comfortable to disclose a heterosexual orientation than a gay one, despite gay participants rating a gay orientation as more positive. The audience ranked most to least comfortable to disclose varied with sexual orientation and disclosure content. Perceived closeness of audience was correlated with comfort of disclosure for known (family, partner, friend, colleague) audiences, but not professional (counsellor) or unknown (stranger, online) audiences. These findings are discussed with reference to the literature on “coming out”, addressing important differences in the perceptions of in-group and out-group disclosure of sexual orientation, and sex-related personal information

World-class long- distance running performances are best predicted by volume of easy runs and deliberate practice of short interval and tempo runs

The aim of this novel study was to analyze the effect of deliberate practice (DP) and easy runs completed by elite-standard and world-class long-distance runners on competitive performances during the first 7 years of their sport careers. Eighty-five male runners reported their best times in different running events and the amounts of different DP activities (tempo runs and short and long interval sessions) and 1 non-DP activity (easy continuous runs) after 3, 5 and 7 years of systematic training. Pearson’s correlations were calculated between performances (calculated using the IAAF scoring tables) and the distances run for the different activities (and overall total). Simple and Multiple Linear Regression Analysis calculated how well these activities predicted performance. Pearson’s correlations showed consistently large effects on performance of total distance (r ≥ 0.75, P < 0.001), easy runs (r ≥ 0.68, P < 0.001), tempo runs (r ≥ 0.50, P < 0.001) and short interval training (r ≥ 0.53, P < 0.001). Long interval training was not strongly correlated (r ≥ 0.22). Total distance accounted for significant variance in performance (R2 ≥ 0.57, P < 0.001). Of the training modes, Hierarchical Regression Analysis showed that easy runs and tempo runs were the activities that accounted for significant variance in performance (P < 0.01). Although DP activities, particularly tempo runs and short interval training, are important for improving performance, coaches should note that the non-DP activity of easy running was crucial in better performances, partly because of its contribution to total distance run

Parentage test in broad-snouted caimans (Caiman latirostris, Crocodylidae) using microsatellite DNA

In this study, microsatellite markers, developed for Alligator mississipiensis and Caiman latirostris, were used to assess parentage among individuals from the captive colony of Caiman latirostris at the University of São Paulo, in Piracicaba, São Paulo, Brazil. Many of the females in the colony were full siblings, which made maternal identification difficult due to genotypic similarity. Even so, the most likely mother could be identified unambiguously among offspring in most of the clutches studied. Two non-parental females displayed maternal behavior which would have misled managers in assigning maternity based on behavior alone. This set of variable loci demonstrates the utility of parentage testing in captive propagation programs

Systematic study of constitutive cyclo-oxygenase-2 expression: role of NFκB and NFAT transcriptional pathways

Cyclooxygenase-2 (COX-2) is an inducible enzyme that drives inflammation and is the therapeutic target for widely used nonsteroidal antiinflammatory drugs (NSAIDs). However, COX-2 is also constitutively expressed, in the absence of overt inflammation, with a specific tissue distribution that includes the kidney, gastrointestinal tract, brain, and thymus. Constitutive COX-2 expression is therapeutically important because NSAIDs cause cardiovascular and renal side effects in otherwise healthy individuals. These side effects are now of major concern globally. However, the pathways driving constitutive COX-2 expression remain poorly understood. Here we show that in the kidney and other sites, constitutive COX-2 expression is a sterile response, independent of commensal microorganisms and not associated with activity of the inflammatory transcription factor NF-κB. Instead, COX-2 expression in the kidney but not other regions colocalized with nuclear factor of activated T cells (NFAT) transcription factor activity and was sensitive to inhibition of calcineurin-dependent NFAT activation. However, calcineurin/NFAT regulation did not contribute to constitutive expression elsewhere or to inflammatory COX-2 induction at any site. These data address the mechanisms driving constitutive COX-2 and suggest that by targeting transcription it may be possible to develop antiinflammatory therapies that spare the constitutive expression necessary for normal homeostatic functions, including those important to the cardiovascular-renal system

Freezing and chemical preservatives alter the stable isotope values of carbon and nitrogen of the Asiatic clam (Corbicula fluminea)

We tested the impacts of most common sample preservation methods used for aquatic sample materials on the stable isotope ratios of carbon and nitrogen in clams, a typical baseline indicator organism for many aquatic food web studies utilising stable isotope analysis (SIA). In addition to common chemical preservatives ethanol and formalin, we also assessed the potential impacts of freezing on δ¹³C and δ¹⁵N values and compared the preserved samples against freshly dried and analysed samples. All preservation methods, including freezing, had significant impacts on δ¹³C and δ¹⁵N values and the effects in general were greater on the carbon isotope values (1.3-2.2% difference) than on the nitrogen isotope values (0.9-1.0% difference). However, the impacts produced by the preservation were rather consistent within each method during the whole 1 year experiment allowing these to be accounted for, if clams are intended for use in retrospective stable isotope studies