Genome-wide association study identifies five new schizophrenia loci

We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 x 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 x 10(-9)), ANK3 (rs10994359, P = 2.5 x 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 x 10(-9)).

Surface Plasmon Resonance Biosensor Screening Method for Paralytic Shellfish Poisoning Toxins: A Pilot Interlaboratory Study

A surface plasmon resonance (SPR) optical biosensor method was developed for the detection of paralytic shellfish poisoning (PSP) toxins in shellfish. This application was transferred in the form of a prototype kit to seven laboratories using Biacore QSPR optical biosensor instrumentation for interlaboratory evaluation. Each laboratory received 20 shellfish samples across a range of species including blind duplicates for analysis. The samples consisted of 4 noncontaminated samples spiked in duplicate with a low level of PSP toxins (240 mu g STXcliHCl equivalents/kg), a high level of saxitoxin (825 mu g STXdiHCl/kg), 2 noncontarninated, and 14 naturally contaminated samples. All 7 participating laboratories completed the study, and HorRat values obtained were

Confirmation of synthetic glucocorticoids with liquid chromatography/mass spectrometry: Organization and results of an international interlaboratory comparison test

Within the framework of a European Union (EU) research project entitled

The preparation of highly ordered single layer ZSM-5 coating on prefabricated stainless steel microchannels

An elegant way to prepare catalytically active microreactors is by applying a coating of zeolite crystals onto a metal microchannel structure. In this study the hydrothermal formation of ZSM-5 zeolitic coatings on AISI 316 stainless steel plates with a microchannel structure has been investigated at different synthesis mixture compositions. The procedures of coating and thermal treatment have also been optimized. Obtaining a uniform thickness of the coating within 0.5 mm wide microchannels requires a careful control of various synthesis variables. The role of these factors and the problems in the synthesis of these zeolitic coatings are discussed. In general, the synthesis is most sensitive to the H2O/Si ratio as well as to the orientation of the plates with respect to the gravity vector. Ratios of H2O/Si=130 and Si/template=13 were found to be optimal for the formation of a zeolitic film with a thickness of one crystal at a temperature of 130 degreesC and a synthesis time of about 35 h. At such conditions, ZSM-5 crystals were formed with a typical size of 1.5 mu mx1.5 mu mx1.0 mum and a very narrow (within 0.2 mum) crystal size distribution. The prepared samples proved to be active in the selective catalytic reduction (SCR) of NO with ammonia. The activity tests have been carried out in a plate-type microreactor. The microreactor shows no mass transfer limitations and a larger SCR reaction rate is observed in comparison with pelletized Ce-ZSM-5 catalysts; (C) 2001 Elsevier Science B.V. All rights reserved.

Growth Inhibitory Activity of Extracted Material and Isolated Compounds from the Fruits of Kigelia pinnata

A study of the components of the fruits of Kigelia pinnata was undertaken to identify compounds with potential growth inhibitory activity against human melanoma cells, since extracts from the fruits of this plant have been described in traditional medicine to have application in the treatment of skin cancer and other skin ailments. A bioactivity-guided fractionation process yielded a number of crude fractions, which demonstrated cytotoxicity in vitro against human melanoma cells. Compounds isolated and identified included the isocoumarins, demethylkigelin (1) and kigelin 2), fatty acids, oleic (3) and heneicosanoic acids (4), the furonaphthoquinone, 2-(1-hydroxyethyl)-naphtho[2,3-b]furan-4,9-dione (5), and ferulic acid (6). A number of structurally related synthetic compounds were also tested using the MTT assay. The most potent series of these compounds, the furonaphthoquinones, also demonstrated a cytotoxic effect in two human breast cancer cell lines tested.

Synthesis and in Vitro and in Vivo Evaluation of a Series of Dihydroisocoumarin Derivatives Conjugated with Fatty Acids, Alcohols, and Amines as Potential Anticancer Agents

In this paper, we report the synthesis and biological activity of a series of dihydroisocoumarin analogues Conjugated with fatty acids, alcohols, or amines, of varying hydrocarbon chain length and degree of unsaturation, to (he dihydroisocoumarins, kigelin and mellein, at the C-7 and C-8 positions on the core dihydroisocoumarin structure. These compounds were evaluated for their antiproliferative activity against human breast cancer (MCF-7 and MDA-MB-468) and melanoma cells (SK-MEL-28 and Malme-3M) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Two compounds Conjugated with gamma-linolenyl alcohol (18:3 n-6) demonstrated potent antiproliferative activity in vitro with one of these 4-hydroxy-3-oxo-1.3-dihydro-isobenzofuran-5-carboxylic acid octadeca-6,9,12-trienyl ester, demonstrating significant antitumor activity in vivo ill a number of human tumor xenograft models.

Cities Ready for Energy Crises - Building Urban energy Resilience

Various sources indicate that threats to modern cities lie in the availability of essential streams, among which energy. Most cities are strongly reliant on fossil fuels; not one case of a fully self-sufficient city is known. Engineering resilience is the rate at which a system returns to a single steady or cyclic state following a perturbation. Certain resilience, for the duration of a crisis, would improve the urban capability to survive such a period without drastic measures.
The capability of cities to prepare for and respond to energy crises in the near future is supported by greater or temporary self-sufficiency. The objective of the underlying research is a model for a city – including its surrounding rural area – that can sustain energy crises. Therefore, accurate monitoring of the current urban metabolism is needed for the use of energy. This can be used to pinpoint problem areas. Furthermore, a sustainable energy system is needed, in which the cycle is better closed. This will require a three-stepped approach of energy savings, energy exchange and sustainable energy generation. Essential is the capacity to store energy surpluses for periods of shortage (crises).
The paper discusses the need for resilient cities and the approach to make cities resilient to energy crises.

The Role of Variation at AβPP, PSEN1, PSEN2, and MAPT in Late Onset Alzheimer's Disease

Rare mutations in AßPP, PSEN1, and PSEN2 cause uncommon early onset forms of Alzheimer's disease (AD), and common variants in MAPT are associated with risk of other neurodegenerative disorders. We sought to establish whether common genetic variation in these genes confer risk to the common form of AD which occurs later in life (>65 years). We therefore tested single-nucleotide polymorphisms at these loci for association with late-onset AD (LOAD) in a large case-control sample consisting of 3,940 cases and 13,373 controls. Single-marker analysis did not identify any variants that reached genome-wide significance, a result which is supported by other recent genome-wide association studies. However, we did observe a significant association at the MAPT locus using a gene-wide approach (p = 0.009). We also observed suggestive association between AD and the marker rs9468, which defines the H1 haplotype, an extended haplotype that spans the MAPT gene and has previously been implicated in other neurodegenerative disorders including Parkinson's disease, progressive supranuclear palsy, and corticobasal degeneration. In summary common variants at AßPP, PSEN1, and PSEN2 and MAPT are unlikely to make strong contributions to susceptibility for LOAD. However, the gene-wide effect observed at MAPT indicates a possible contribution to disease risk which requires further study.

Genome-wide association study identifies a common variant in RAD51B associated with male breast cancer risk

We conducted a genome-wide association study of male breast cancer comprising 823 cases and 2,795 controls of European ancestry, with validation in independent sample sets totaling 438 cases and 474 controls. A SNP in RAD51B at 14q24.1 was significantly associated with male breast cancer risk (P = 3.02 × 10(-13); odds ratio (OR) = 1.57). We also refine association at 16q12.1 to a SNP within TOX3 (P = 3.87 × 10(-15); OR = 1.50).

Genome-wide linkage analysis for human longevity: Genetics of healthy aging study

Clear evidence exists for heritability of humanlongevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118nonagenarian Caucasian sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 (LOD = 3.47), chromosome 17q12-q22 (LOD = 2.95), chromosome 19p13.3-p13.11 (LOD = 3.76), and chromosome 19q13.11-q13.32 (LOD = 3.57). To fine map these regions linked to longevity, we performed association analysis using GWAS data in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls. Using a fixed-effect meta-analysis approach, rs4420638 at the TOMM40/ APOE/APOC1 gene locus showed significant association with longevity (P-value = 9.6 × 10). By combined modeling of linkage and association, we showed that association of longevity with APOEe4 and APOEe2 alleles explain the linkage at 19q13.11-q13.32 with P-value = 0.02 and P-value = 1.0 × 10, respectively. In the largest linkage scan thus far performed for human familial longevity, we confirm that the APOE locus is a longevity gene and that additional longevity loci may be identified at 14q11.2, 17q12-q22, and 19p13.3-p13.11. As the latter linkage results are not explained by common variants, we suggest that rare variants play an important role in human familial longevity.

X-shooting Herbig Ae/Be stars: Accretion probed by near-infrared He I emission

The Herbig Ae/Be stars are intermediate mass pre-main sequence stars that bridge the gap between the low mass T Tauri stars and the Massive Young Stellar Objects. In this mass range, the acting star forming mechanism switches from magnetically controlled accretion to an as yet unknown mechanism, but which is likely to be direct disk accretion onto the star. We observed a large sample of Herbig Ae/Be stars with X-shooter to address this issue from a multi-wavelength perspective. It is the largest such study to date, not only because of the number of objects involved, but also because of the large wavelength coverage from the blue to the near-infrared. This allows many accretion diagnostics to be studied simultaneously. By correlating the various properties with mass, temperature and age, we aim to determine where and whether the magnetically controlled mass accretion mechanism halts and the proposed direct disk accretion takes over. Here, we will give an overview of the background, present some observations and discuss our initial results. We will introduce a new accretion diagnostic for the research of Herbig Ae/Be stars, the HeI 1.083 µm line. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.