New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Genetic architecture of human plasma lipidome and its link to cardiovascular disease

Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 x10(-8)), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD

GEMIS 4.0 - Globales Emissions-Modell Integrierter Systeme Ein Computerprogramm zur Umweltanalyse von Energie-, Transport und Stoffsystemen

GEMIS is a computer instrument for environmental impact and cost analysis of energy, transport and materials systems. Primary energy consumption, pollutant emissions and material flows of energy and transportation systems can be compared, and consumption and emissions can be calculated for all stages of energy production, conversion and utilisation. The current version 4.0 contains new data on new technologies, and the computer model was updated so that the data and scenarios can be used also in programs outside GEMIS. Data from other sources were included in the database as well.GEMIS - Globales Emissions-Modell Integrierter Systeme - ist ein Computer-Instrument zur Umwelt- und Kostenanalyse von Energie-, Transport- und Stoffsystemen. Das Modell ermoeglicht es, Primaerenergieverbrauch, Schadstoffemissionen und Stoffstroeme verschiedener Energie- und Verkehrssysteme zu vergleichen sowie Verbrauch und Emissionen auf jeder Stufe der Energiegewinnung, -umwandlung und -nutzung nachzuvollziehen. Mit der aktuellen Version 4.0 wurde GEMIS wiederum um weitere Daten insbesondere zu neuen Technologien ergaenzt. Ausserdem wurde das zu Grunde liegende Computermodell aktualisiert, was es unter anderem ermoeglicht, die Daten und Szenarien auch ausserhalb von GEMIS in fremden Programmen zu nutzen. Auch wurden weitere Daten von Dritten in die Datenbank aufgenommen. (orig.)Available from: http://www.oeko.de/service/gemis / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEHessisches Ministerium fuer Umwelt, Landwirtschaft und Forsten, Wiesbaden (Germany)DEGerman

The choice of absorbents for the purification of waste gases from soda production from hydrogen sulfide

Среди жидкостей, имеющихся в технологическом цикле производства кальцинированной соды, как перспективные абсорбенты для очистки сбросных газов от сероводорода была выбрана жидкость, содержащая карбонат натрия и аммиак, и раствор карбоната натрия в насыщенном растворе хлорида натрия. Показано, что по совокупности свойств, таких как скорость абсорбции, емкость по поглощаемому компоненту и селективность, содосоляной раствор является наиболее подходящим.Among the liquids available in the technological cycle for the production of soda ash, liquid containing sodium carbonate and ammonia and a solution of sodium carbonate in a saturated solution of sodium chloride were chosen as promising absorbents for purifying exhaust gases from hydrogen sulfide. It has been shown that in terms of a combination of properties, such as absorption rate, absorbent component capacity and selectivity, a soda-saline solution is most suitable

MiRNA-149 as a Candidate for Facial Clefting and Neural Crest Cell Migration

Nonsyndromic cleft lip with or without palate (nsCL/P) ranks among the most common human birth defects and has a multifactorial etiology. Human neural crest cells (hNCC) make a substantial contribution to the formation of facial bone and cartilage and are a key cell type in terms of nsCL/P etiology. Based on increasing evidence for the role of noncoding regulatory mechanisms in nsCL/P, we investigated the role of hNCC-expressed microRNAs (miRNA) in cleft development. First, we conducted a systematic analysis of miRNAs expressed in human-induced pluripotent stem cell-derived hNCC using Affymetrix microarrays on cell lines established from 4 unaffected donors. These analyses identified 152 candidate miRNAs. Based on the hypothesis that candidate miRNA loci harbor genetic variation associated with nsCL/P risk, the genomic locations of these candidates were cross-referenced with data from a previous genome-wide association study of nsCL/P. Associated variants were reanalyzed in independent nsCL/P study populations. Jointly, the results suggest that miR-149 is implicated in nsCL/P etiology. Second, functional follow-up included in vitro overexpression and inhibition of miR-149 in hNCC and subsequent analyses at the molecular and phenotypic level. Using 3 ' RNA-Seq, we identified 604 differentially expressed (DE) genes in hNCC overexpressing miR-149 compared with untreated cells. These included TLR4 and JUNB, which are established targets of miR-149, and NOG, BMP4, and PAX6, which are reported nsCL/P candidate genes. Pathway analyses revealed that DE genes were enriched in pathways including regulation of cartilage development and NCC differentiation. At the cellular level, distinct hNCC migration patterns were observed in response to miR-149 overexpression. Our data suggest that miR-149 is involved in the etiology of nsCL/P via its role in hNCC migration