Structural/functional analysis of the human OXR1 protein: identification of exon 8 as the anti-oxidant encoding function

BACKGROUND: The human OXR1 gene belongs to a class of genes with conserved functions that protect cells from reactive oxygen species (ROS). The gene was found using a screen of a human cDNA library by its ability to suppress the spontaneous mutator phenotype of an E. coli mutH nth strain. The function of OXR1 is unknown. The human and yeast genes are induced by oxidative stress and targeted to the mitochondria; the yeast gene is required for resistance to hydrogen peroxide. Multiple spliced isoforms are expressed in a variety of human tissues, including brain. RESULTS: In this report, we use a papillation assay that measures spontaneous mutagenesis of an E. coli mutM mutY strain, a host defective for oxidative DNA repair. Papillation frequencies with this strain are dependent upon a G-\u3eT transversion in the lacZ gene (a mutation known to occur as a result of oxidative damage) and are suppressed by in vivo expression of human OXR1. N-terminal, C-terminal and internal deletions of the OXR1 gene were constructed and tested for suppression of the mutagenic phenotype of the mutM mutY strain. We find that the TLDc domain, encoded by the final four exons of the OXR1 gene, is not required for papillation suppression in E. coli. Instead, we show that the protein segment encoded by exon 8 of OXR1 is responsible for the suppression of oxidative damage in E. coli. CONCLUSION: The protein segment encoded by OXR1 exon 8 plays an important role in the anti-oxidative function of the human OXR1 protein. This result suggests that the TLDc domain, found in OXR1 exons 12-16 and common in many proteins with nuclear function, has an alternate (undefined) role other than oxidative repair

Direct simulation of ion beam induced stressing and amorphization of silicon

Using molecular dynamics (MD) simulation, we investigate the mechanical response of silicon to high dose ion-irradiation. We employ a realistic and efficient model to directly simulate ion beam induced amorphization. Structural properties of the amorphized sample are compared with experimental data and results of other simulation studies. We find the behavior of the irradiated material is related to the rate at which it can relax. Depending upon the ability to deform, we observe either the generation of a high compressive stress and subsequent expansion of the material, or generation of tensile stress and densification. We note that statistical material properties, such as radial distribution functions are not sufficient to differentiate between different densities of amorphous samples. For any reasonable deformation rate, we observe an expansion of the target upon amorphization in agreement with experimental observations. This is in contrast to simulations of quenching which usually result in denser structures relative to crystalline Si. We conclude that although there is substantial agreement between experimental measurements and most simulation results, the amorphous structures being investigated may have fundamental differences; the difference in density can be attributed to local defects within the amorphous network. Finally we show that annealing simulations of our amorphized samples can lead to a reduction of high energy local defects without a large scale rearrangement of the amorphous network. This supports the proposal that defects in amorphous silicon are analogous to those in crystalline silicon.Comment: 13 pages, 12 figure

Classical Tensors and Quantum Entanglement I: Pure States

The geometrical description of a Hilbert space asociated with a quantum system considers a Hermitian tensor to describe the scalar inner product of vectors which are now described by vector fields. The real part of this tensor represents a flat Riemannian metric tensor while the imaginary part represents a symplectic two-form. The immersion of classical manifolds in the complex projective space associated with the Hilbert space allows to pull-back tensor fields related to previous ones, via the immersion map. This makes available, on these selected manifolds of states, methods of usual Riemannian and symplectic geometry. Here we consider these pulled-back tensor fields when the immersed submanifold contains separable states or entangled states. Geometrical tensors are shown to encode some properties of these states. These results are not unrelated with criteria already available in the literature. We explicitly deal with some of these relations.Comment: 16 pages, 1 figure, to appear in Int. J. Geom. Meth. Mod. Phy

IAMAS: a century of international cooperation in atmospheric sciences

The International Association of Meteorology and Atmospheric Sciences (IAMAS) was founded in 1919 as the Section of Meteorology of the International Union of Geodesy and Geophysics (IUGG). Significant advances over human history, particularly during the 19th century, in the gathering, communication, assembly and analysis of observations of the changing weather and in theoretical understanding of the fundamental physical relationships and processes governing atmospheric circulation had been driven by the need for improved weather and climate forecasts to support the expansion of global trade, better public warnings of extreme weather, and safer and more effective military operations. Since its foundation, in parallel and cooperation with intergovernmental development under the auspices of what is now the World Meteorological Organization (WMO), IAMAS and its 10 international commissions have provided the international organizational framework for the convening of the general and scientific assemblies and other meetings that bring together expert scientists from around the world to further advance scientific understanding and prediction of the behaviour of the atmosphere and its connections to and effects on other components of the Earth's intercoupled geophysical system.</p

Vielfalt sucht Rat : Ratsmitglieder mit Migrationshintergrund in deutschen Großstädten

Deutschland ist ein Entwicklungsland, wenn es um die Repräsentanz von Migrantinnen und Migranten in der kommunalen Demokratie geht. Sie stellen nur knapp vier Prozent der Ratsmitglieder in den deutschen Großstädten. Dabei hat bereits rund ein Drittel der Bevölkerung einen Migrationshintergrund. Von gelungener Integration kann aber erst die Rede sein, wenn Migrantinnen und Migranten auch ganz selbstverständlich in den Parlamenten vertreten sind. Die vorliegende Studie „Vielfalt sucht Rat. Ratsmitglieder mit Migrationshintergrund in deutschen Großstädten“, angefertigt vom Max-Planck-Institut zur Erforschung multireligiöser und multiethnischer Gesellschaften, liefert die empirischen Grundlagen für die überfällige Debatte um die politische Teilhabe von Migrantinnen und Migranten. Eine Studie des Max-Planck-Instituts zur Erforschung multireligiöser und multiethnischer Gesellschaften in Kooperation mit der Heinrich-Böll-Stiftung und gefördert durch die Stiftung Mercator

Progress in strength, toughness and lifetime methods for ceramics

Fortschritte auf dem Gebiet der Festigkeit, Risszähigkeit und Lebensdauer von Keramik Zur Charakterisierung des Versagensverhaltens keramischer Werkstoffe sind Festigkeits- und Risszähigkeitsmessungen erforderlich. Weist eine Keramik noch den Effekt des unterkritischen Risswachstums auf, sind auch Lebensdauermessungen unter statischer Belastung von großer Wichtigkeit. Neuere Beiträge der Autoren zur Untersuchungs-Methodik sind in diesem Bericht zusammengefasst. Teil A befasst sich mit der Berechnung der maximalen Spannungen in runden Scheiben unter Kugelbelastung. Hierbei werden der “ball-on-ring test”, der “ball-on-3-balls test” und der kürzlich von den Verfassern entwickelte „3-balls-on-3-balls test“ betrachtet. Als praktische Anwendung der ermittelten Spannungen im “ball-on-3-balls test” wird das bei grobkörnigem Aluminiumoxid gefundene stabile Bruchverhalten als Effekt einer stark ansteigenden Risswiderstandskurve diskutiert. In Teil B wird auf eine von den Verfassern entwickelte Methode eingegangen, die es gestattet, sehr kurze Kerben mit extrem kleinen Kerbradien zu erzeugen. Bei einer ZrO2-Keramik konnten Kerbradien von unter 0.1 μm bei einer Kerbtiefe von nur 40μm erzeugt werden. Derartig kurze und scharfe Kerben sollten geeignet sein, das Verhalten natürlicher Risse in Keramiken anzunähern. Schließlich wird in Teil C über eine Prozedur berichtet, die sich dafür eignet, eine vorhandene Anzahl an Lebensdauer-Versuchsproben optimal auszunutzen. Hierbei kann aus der erneuten Verwendung von auf niederem Lastniveau angefallenen „Durchläufern“ zusätzliche Information über das Risswachstumsgesetz gewonnen werden. Die Methode wird an Lebensdauermessungen von SIALON in destilliertem Wasser von 20°C demonstriert

Selection bias in general practice research : analysis in a cohort of pregnant Danish women

Funding: The Novo Nordic Foundation (NNF130C0002689), Region Zealand (15-000342), The Danish Research Foundation for General Practice (EMN-2017-00265), A.P. Møller Foundation (21.15 12.2016.16-87), Lilly and Herbert Hansen Foundation (07.11.2016-006), and Jacob and Orla Madsen Foundation (11.05.2015. 5421) have financially supported the project. The funding sources were not involved in the research design, collection, analysis and interpretation of data, writing of the report and decision regarding submission for publication. The authors are responsible for the contents of this article.Peer reviewedPublisher PD

The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia : further evidence and meta-analysis

NO is a pleiotropic signaling molecule and has an important role in cognition and emotion. In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ. interactions; this protein-protein interaction is disrupted upon binding of NOS1 adapter protein (encoded by NOS1AP) to NOS-I. As both NOS1 and NOS1AP were associated with schizophrenia, we here investigated these genes in greater detail by genotyping new samples and conducting a meta-analysis of our own and published data. In doing so, we confirmed association of both genes with schizophrenia and found evidence for their interaction in increasing risk towards disease. Our strongest finding was the NOS1 promoter SNP rs41279104, yielding an odds ratio of 1.29 in the meta-analysis. As findings from heterologous cell systems have suggested that the risk allele decreases gene expression, we studied the effect of the variant on NOS1 expression in human post-mortem brain samples and found that the risk allele significantly decreases expression of NOS1 in the prefrontal cortex. Bioinformatic analyses suggest that this might be due the replacement of six transcription factor binding sites by two new binding sites as a consequence of proxy SNPs. Taken together, our data argue that genetic variance in NOS1 resulting in lower prefrontal brain expression of this gene contributes to schizophrenia liability, and that NOS1 interacts with NOS1AP in doing so. The NOS1-NOS1AP PDZ interface may thus well constitute a novel target for small molecules in at least some forms of schizophrenia. PostprintPeer reviewe

Prevalence of Malnutrition in Orally and Tube-Fed Elderly Nursing Home Residents in Germany and Its Relation to Health Complaints and Dietary Intake

Objective. To investigate the prevalence of malnutrition in orally and tube-fed nursing home (NH) residents in Germany and its relation to common health complaints and dietary intake. Methods. In 350 NH residents, subjects' characteristics, Mini Nutritional Assessment (MNA), and several health problems were inquired with the nursing staff using standardised interviews. In a subset of 122 residents, dietary intake was assessed by 3-day weighing records. Results. 7.7% of the participants were tube fed. 24.1% of orally nourished and 57.7% of tube-fed residents were malnourished (MNA < 17 p.). Malnutrition was significantly related to nausea/vomiting, constipation, pressure ulcers, dehydration, infections, antibiotic use, and hospitalisation. Mean daily energy intake was 1535 ± 413 kcal and mean protein intake was 54.2 ± 0.9 g/d irrespective of the nutritional state. Conclusion. In Germany, malnutrition is widespread among NH residents and is related to common health problems. The MNA rather reflects health condition than currently reduced dietary intake