Genetic variants of the promoter of the heme oxygenase-1 gene and their influence on cardiovascular disease (The Ludwigshafen Risk and Cardiovascular Health Study)

Background Heme oxygenase-1 is an inducible cytoprotective enzyme which handles oxidative stress by generating anti-oxidant bilirubin and vasodilating carbon monoxide. A (GT)n dinucleotide repeat and a -413A>T single nucleotide polymorphism have been reported in the promoter region of HMOX1 to both influence the occurrence of coronary artery disease and myocardial infarction. We sought to validate these observations in persons scheduled for coronary angiography. Methods We included 3219 subjects in the current analysis, 2526 with CAD including a subgroup of CAD and MI (n = 1339) and 693 controls. Coronary status was determined by coronary angiography. Risk factors and biochemical parameters (bilirubin, iron, LDL-C, HDL-C, and triglycerides) were determined by standard procedures. The dinucleotide repeat was analysed by PCR and subsequent sizing by capillary electrophoresis, the -413A>T polymorphism by PCR and RFLP. Results In the LURIC study the allele frequency for the -413A>T polymorphism is A = 0,589 and T = 0,411. The (GT)n repeats spread between 14 and 39 repeats with 22 (19.9%) and 29 (47.1%) as the two most common alleles. We found neither an association of the genotypes or allelic frequencies with any of the biochemical parameters nor with CAD or previous MI. Conclusion Although an association of these polymorphisms with the appearance of CAD and MI have been published before, our results strongly argue against a relevant role of the (GT)n repeat or the -413A>T SNP in the HMOX1 promoter in CAD or MI

Conodonts from the “Pelmatozoan Limestone” (Upper Ordovician), northern Sevilla, Ossa-Morena Zone (Spain)

27 páginas, 1 figura, 2 tablas, 2 láminas.[EN] Several limestone levels of the “Caliza de Pelmatozoos” were sampled for conodonts in sections of the Cerrón del Hornillo and Valle synclines. The conodont fauna includes: Amorphognathus ordovicicus, A. aff. ordovicicus, Amorphognathus sp., Amorphognathus? sp., Drepanoistodus cf. suberectus, Drepanoistodus? sp., Hamarodus europaeus, Icriodella cf. superba, Istorinus erectus, Panderodus gracilis, Plectodina tenuis?, Sagittodontina robusta, Scabbardella altipes, Scabbardella sp A., Walliserodus amplissimus? y Walliserodus? sp. This association is attributed to the Amorphognathus ordovicus Zone by the presence of the index species, and to the Sagittodontina-Scabbardella Biofacies of the Mediterranean Province of conodonts by the relative abundance of these two taxa. This fauna is close related to coeval associations from several localities of the Iberian Peninsula, except that of the Malaguide Complex, but the presence of Plectodina and Drepanoistodus suggest possible faunal exchange with Anglo-Baltic faunas.[ES] El estudio para conodontos de numerosos niveles de la “Caliza de Pelmatozoos” en secciones de los sinclinales del Cerrón del Hornillo y del Valle ha permitido identificar los taxones: Amorphognathus ordovicicus, A. aff. ordovicicus, Amorphognathus sp., Amorphognathus? sp., Drepanoistodus cf. suberectus, Drepanoistodus? sp., Hamarodus europaeus, Icriodella cf. superba, Istorinus erectus, Panderodus gracilis, Plectodina tenuis?, Sagittodontina robusta, Scabbardella altipes, Scabbardella sp A., Walliserodus amplissimus? y Walliserodus? sp. Esta asociación, que se adscribe a la Provincia Mediterránea de conodontos, es atribuida a la Zona de Amorphognahus ordovicicus, Kralodvoriense, por la presencia del taxón nominal. Dentro de esta provincia ha sido posible identificar la Biofacies de Sagittodontina-Scabbardella por la abundancia relativa de ambos taxones. Si bien existe una gran similitud entre esta fauna y las de edad equivalente reconocidas en el ámbito de dicha provincia, la presencia de Plectodina y Drepanoistodus sugieren que el área de estudio se encontraba emplazada en latitudes más bajas que el resto de la Península Ibérica, exceptuando la del Complejo Maláguide, y que este hecho favoreció el intercambio faunal con las provincias Británica y Báltica de conodontos.Este trabajo es una contribución al proyecto PATRIORSI (CGL2006-07628/BTE) del Ministerio de Ciencia e Innovación, al proyecto IGCP 503 “Ordovician Palaeogeography and Palaeoclimatology” y Grupo UCM 910231.Peer reviewe

787-5 Systemic Effect of Ramipril on Endothelin, but not on Elcosanoid Levels in Patients with Coronary Artery Disease

Study aimNeurohumoral effects of ramipril (R) alone or in combination with isosorbide dinitrate (ISDN) compared to ISDN or placebo.Study designPlacebo-controlled double-blind parallel group trial.Methods32 patients with coronary artery disease (CAD) received placebo, R5mg, ISDN 20mg slow release b.i.d. or R+ISDN for one week. A 24 hour kinetic profile of ramipril and its metabolite, of ace activity (ACE-A) and of related hormones (renin and aldosterone), of endothelin and of prostaglandins (PG), thromboxane B2 (TXB2), PGF2a, 6-keto PGF1a, the stable metabolite of prostacyclin (PGI2-M) was studied after the first dose. Measurements were repeated after 8 days of treatment before and 3 hours after the morning dose.ResultsHormone measurements are presented as means of percent difference of patients treated with R (n=16) vs. those without ace-inhibitor (n=16).Time (hrs)0123468240–83–8Ramipril (mg/l)08543210.417Ramiprilat (mg/l)0611108751214ACE-A (%)-6-78-95-98-98-97-96-80-82-98Aldosteron (%)9-5-31-34-21-27-23-34--Renin (%)-9-771913175332--Endothelin (%)-17-13-25-19-16-15-40--TXB2 (%)41045-5012-3PGF2a (%)101700-8-22-9PGI2-M (%)70-38--59-1-713-=not done; significant differences are printed in italics (two-tailed t-test)A single oral dose of 5mg R reduced ACE activity (p<0.001), decreased aldosterone and increased renin (p<0.1). R did not influence plasma levels of the vasoconstricting (TXB2, PGF2a) or vasodilating (PGI2-M) eicosanoid mediators, but decreased endothelin (p<0.1).ConclusionR, in a dose that results in significant systemic inhibition of the renin angiotensin aldosteron system, does not induce measurable changes of circulating eicosanoid concentrations, but seems to diminish systemic release of endothelin

Association of RANTES G-403A gene polymorphism with increased risk of coronary arteriosclerosis

Aims Polymorphisms in the RANTES (G-403A), monocyte chemoattractant protein-1 (MCP-1; A-2518G), stromal cell-derived factor-1β (SDF-1β; G801A), and C-C chemokine receptor-5 (CCR5; Δ32) genes have been associated with functional effects. These chemokines have been implicated in leucocyte recruitment to arterial lesions. In a case-control study, we explored relations between these polymorphisms and coronary artery disease (CAD), with respect to angiographic abnormalities and acute coronary syndromes (ACS). Methods and Results The LUdwigshafen Risk and Cardiovascular health (LURIC) cohort was genotyped by RFLP-PCR. Based on coronary angiography, individuals were sub-divided into CAD cases \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $(n=2694)$ \end{document} and controls \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $(n=530)$ \end{document}. RANTES-403 genotype frequencies were significantly different in cases and controls \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $({\chi}^{2}=4.17,p=0.041)$ \end{document}, as were A allele carrier frequencies (36.01% vs. 30.19%, OR=1.30 [95%-CI=1.06-1.60], \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $p=0.010$ \end{document}). By multivariate analysis, RANTES A-403 retained significant association with CAD \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $({\chi}^{2}=8.40,p=0.0038)$ \end{document}. RANTES A-403 was associated with increased ACS prevalence (OR=1.36 [95%-CI=1.08-1.71], \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $p=0.0073$ \end{document}). MCP-1 G-2518, SDF-1β A801, and CCR5 Δ32 were not associated with CAD. Conclusions RANTES A-403 was associated with CAD independently from conventional risk factors and CRP or fibrinogen as inflammatory biomarkers. The association was enhanced in smokers and ACS, conditions where platelet activation and inflammation predominate. RANTES A-403 may increase genetic susceptibility to CA

Genetic variation in Fcγ receptor IIa and risk of coronary heart disease: negative results from two large independent populations

Background The role of the Fcgamma receptor IIa (FcgammaRIIa), a receptor for C-reactive protein (CRP), the classical acute phase protein, in atherosclerosis is not yet clear. We sought to investigate the association of FcgammaRIIa genotype with risk of coronary heart disease (CHD) in two large population-based samples. Methods FcgammaRIIa-R/H131 polymorphisms were determined in a population of 527 patients with a history of myocardial infarction and 527 age and gender matched controls drawn from a population-based MONICA- Augsburg survey. In the LURIC population, 2227 patients with angiographically proven CHD, defined as having at least one stenosis [greater than or equal to]50%, were compared with 1032 individuals with stenosis H genotype was not independently associated with lower risk of CHD after multivariable adjustments, neither in the MONICA population (odds ratio (OR) 1.08; 95% confidence interval (CI) 0.81 to 1.44), nor in LURIC (OR 0.96; 95% CI 0.81 to 1.14). Conclusion Our results do not confirm an independent relationship between FcgammaRIIa genotypes and risk of CHD in these populations

Dystonia Linked to EIF4A2 Haploinsufficiency: A Disorder of Protein Translation Dysfunction

Background: Protein synthesis is a tightly controlled process, involving a host of translation-initiation factors and microRNA-associated repressors. Variants in the translational regulator EIF2AK2 were first linked to neurodevelopmental-delay phenotypes, followed by their implication in dystonia. Recently, de novo variants in EIF4A2, encoding eukaryotic translation initiation factor 4A isoform 2 (eIF4A2), have been described in pediatric cases with developmental delay and intellectual disability. Objective: We sought to characterize the role of EIF4A2 variants in dystonic conditions. Methods: We undertook an unbiased search for likely deleterious variants in mutation-constrained genes among 1100 families studied with dystonia. Independent cohorts were screened for EIF4A2 variants. Western blotting and immunocytochemical studies were performed in patient-derived fibroblasts. Results: We report the discovery of a novel heterozygous EIF4A2 frameshift deletion (c.896_897del) in seven patients from two unrelated families. The disease was characterized by adolescence- to adulthood-onset dystonia with tremor. In patient-derived fibroblasts, eIF4A2 production amounted to only 50% of the normal quantity. Reduction of eIF4A2 was associated with abnormally increased levels of IMP1, a target of Ccr4-Not, the complex that interacts with eIF4A2 to mediate microRNA-dependent translational repression. By complementing the analyses with fibroblasts bearing EIF4A2 biallelic mutations, we established a correlation between IMP1 expression alterations and eIF4A2 functional dosage. Moreover, eIF4A2 and Ccr4-Not displayed significantly diminished colocalization in dystonia patient cells. Review of international databases identified EIF4A2 deletion variants (c.470_472del, c.1144_1145del) in another two dystonia-affected pedigrees. Conclusions: Our findings demonstrate that EIF4A2 haploinsufficiency underlies a previously unrecognized dominant dystonia-tremor syndrome. The data imply that translational deregulation is more broadly linked to both early neurodevelopmental phenotypes and later-onset dystonic conditions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Measurement of the flavour composition of dijet events in pp collisions at root s=7 TeV with the ATLAS detector

This paper describes a measurement of the flavour composition of dijet events produced in pp collisions at √s=7 TeV using the ATLAS detector. The measurement uses the full 2010 data sample, corresponding to an integrated luminosity of 39 pb−1. Six possible combinations of light, charm and bottom jets are identified in the dijet events, where the jet flavour is defined by the presence of bottom, charm or solely light flavour hadrons in the jet. Kinematic variables, based on the properties of displaced decay vertices and optimised for jet flavour identification, are used in a multidimensional template fit to measure the fractions of these dijet flavour states as functions of the leading jet transverse momentum in the range 40 GeV to 500 GeV and jet rapidity |y|<2.1. The fit results agree with the predictions of leading- and next-to-leading-order calculations, with the exception of the dijet fraction composed of bottom and light flavour jets, which is underestimated by all models at large transverse jet momenta. The ability to identify jets containing two b-hadrons, originating from e.g. gluon splitting, is demonstrated. The difference between bottom jet production rates in leading and subleading jets is consistent with the next-to-leading-order predictions