Spanish National Research Council

About: Spanish National Research Council is a government organization based out in Madrid, Spain. It is known for research contribution in the topics: Population & Galaxy. The organization has 79563 authors who have published 220470 publications receiving 7698991 citations. The organization is also known as: CSIC & Consejo Superior de Investigaciones Científicas.

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

Abstract: We identified rare coding variants associated with Alzheimer's disease in a three-stage case–control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10−4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10−8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10−10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10−10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10−14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein–protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

Arac/XylS family of transcriptional regulators.

Abstract: The ArC/XylS family of prokaryotic positive transcriptional regulators includes more than 100 proteins and polypeptides derived from open reading frames translated from DNA sequences. Members of this family are widely distributed and have been found in the gamma subgroup of the proteobacteria, low- and high-G + C-content gram-positive bacteria, and cyanobacteria. These proteins are defined by a profile that can be accessed from PROSITE PS01124. Members of the family are about 300 amino acids long and have three main regulatory functions in common: carbon metabolism, stress response, and pathogenesis. Multiple alignments of the proteins of the family define a conserved stretch of 99 amino acids usually located at the C-terminal region of the regulator and connected to a nonconserved region via a linker. The conserved stretch contains all the elements required to bind DNA target sequences and to activate transcription from cognate promoters. Secondary analysis of the conserved region suggests that it contains two potential alpha-helix-turn-alpha-helix DNA binding motifs. The first, and better-fitting motif is supported by biochemical data, whereas existing biochemical data neither support nor refute the proposal that the second region possesses this structure. The phylogenetic relationship suggests that members of the family have recruited the nonconserved domain(s) into a series of existing domains involved in DNA recognition and transcription stimulation and that this recruited domain governs the role that the regulator carries out. For some regulators, it has been demonstrated that the nonconserved region contains the dimerization domain. For the regulators involved in carbon metabolism, the effector binding determinants are also in this region. Most regulators belonging to the AraC/XylS family recognize multiple binding sites in the regulated promoters. One of the motifs usually overlaps or is adjacent to the -35 region of the cognate promoters. Footprinting assays have suggested that these regulators protect a stretch of up to 20 bp in the target promoters, and multiple alignments of binding sites for a number of regulators have shown that the proteins recognize short motifs within the protected region.

Letter of intent for KM3NeT 2.0

Abstract: The main objectives of the KM3NeT Collaboration are (i) the discovery and subsequent observation of high-energy neutrino sources in the Universe and (ii) the determination of the mass hierarchy of neutrinos. These objectives are strongly motivated by two recent important discoveries, namely: (1) the high-energy astrophysical neutrino signal reported by IceCube and (2) the sizable contribution of electron neutrinos to the third neutrino mass eigenstate as reported by Daya Bay, Reno and others. To meet these objectives, the KM3NeT Collaboration plans to build a new Research Infrastructure consisting of a network of deep-sea neutrino telescopes in the Mediterranean Sea. A phased and distributed implementation is pursued which maximises the access to regional funds, the availability of human resources and the synergistic opportunities for the Earth and sea sciences community. Three suitable deep-sea sites are selected, namely off-shore Toulon (France), Capo Passero (Sicily, Italy) and Pylos (Peloponnese, Greece). The infrastructure will consist of three so-called building blocks. A building block comprises 115 strings, each string comprises 18 optical modules and each optical module comprises 31 photo-multiplier tubes. Each building block thus constitutes a three-dimensional array of photo sensors that can be used to detect the Cherenkov light produced by relativistic particles emerging from neutrino interactions. Two building blocks will be sparsely configured to fully explore the IceCube signal with similar instrumented volume, different methodology, improved resolution and complementary field of view, including the galactic plane. One building block will be densely configured to precisely measure atmospheric neutrino oscillations.

Flushing submarine canyons

Abstract: The continental slope is a steep, narrow fringe separating the coastal zone from the deep ocean. During low sea-level stands, slides and dense, sediment-laden flows erode the outer continental shelf and the continental slope, leading to the formation of submarine canyons that funnel large volumes of sediment and organic matter from shallow regions to the deep ocean(1). During high sea-level stands, such as at present, these canyons still experience occasional sediment gravity flows(2-5), which are usually thought to be triggered by sediment failure or river flooding. Here we present observations from a submarine canyon on the Gulf of Lions margin, in the northwest Mediterranean Sea, that demonstrate that these flows can also be triggered by dense shelf water cascading (DSWC)-a type of current that is driven solely by seawater density contrast. Our results show that DSWC can transport large amounts of water and sediment, reshape submarine canyon floors and rapidly affect the deep-sea environment. This cascading is seasonal, resulting from the formation of dense water by cooling and/or evaporation, and occurs on both high- and low-latitude continental margins(6-8). DSWC may therefore transport large amounts of sediment and organic matter to the deep ocean. Furthermore, changes in the frequency and intensity of DSWC driven by future climate change may have a significant impact on the supply of organic matter to deep-sea ecosystems and on the amount of carbon stored on continental margins and in ocean basins.

Analysis and removal of emerging contaminants in wastewater and drinking water

Abstract: The occurrence of trace organic contaminants in wastewaters, their behavior during wastewater treatment and production of drinking water are key issues in the re-use of water resources. Elimination of different classes of emerging contaminants, such as surfactant degradates, pharmaceuticals and polar pesticides in wastewater-treatment plants (WWTPs) was found to be rather low, so sewage effluents are one of the main sources of these compounds and their treatment-resistant metabolites. This article reviews the state-of-the-art in the analysis of several groups of emerging contaminants (acidic pharmaceuticals, antibacterial agents, acidic pesticides and surfactant metabolites) in wastewaters. It also discusses the elimination of emerging contaminants in WWTPs applying conventional activated sludge treatment (AST) and advanced treatment processes, such as membrane bioreactors (MBRs) and advanced oxidation processes (AOPs), as well as during production of drinking water.