ATA homozigosity in the IL-10 gene promoter is a risk factor for schizophrenia in Spanish females: a case control study

Background: Three IL-10 gene promoter single nucleotide polymorphisms -1082G > A, -819C > T and -592C > A and the haplotypes they define in Caucasians, GCC, ACC, ATA, associated with different IL-10 production rates, have been linked to schizophrenia in some populations with conflicting results. On the basis of the evidence of the sex-dependent effect of certain genes in many complex diseases, we conducted a sex-stratified case-control association study to verify the linkage of the IL-10 gene promoter SNPs and haplotypes with schizophrenia and the possible sex-specific genetic effect in a Spanish schizophrenic population. Methods: 241 DSM-IV diagnosed Spanish schizophrenic patients and 435 ethnically matched controls were genotyped for -1082G > A and -592C > A SNPs. Chi squared tests were performed to assess for genetic association of alleles, genotypes and haplotypes with the disease. Results: The -1082A allele (p = 0.027), A/A (p = 0.008) and ATA/ATA (p = 0.003) genotypes were significantly associated with schizophrenia in females while neither allelic nor genotypic frequencies reached statistical significance in the male population. Conclusions: Our results highlight the hypothesis of an imbalance towards an inflammatory syndrome as the immune abnormality of schizophrenia. Anyway, a better understanding of the involvement of the immune system would imply the search of immune abnormalities in endophenotypes in whose sex and ethnicity might be differential factors. It also reinforces the need of performing complex gene studies based on multiple cytokine SNPs, including anti and pro-inflammatory, to clarify the immune system abnormalities direction in the etiology of schizophrenia

A coincidence detection system based on real-time software

Conventional real-time coincidence systems use electronic circuitry to detect coincident pulses (hardware coincidence). In this work, a new concept of coincidence system based on real-time software (software coincidence) is presented. This system is based on the recurrent supervision of the analogue-to-digital converters status, which is described in detail. A prototype has been designed and built using a low-cost development platform. It has been applied to two different experimental sets for cosmic ray muon detection. Experimental muon measurements recorded simultaneously using conventional hardware coincidence and our software coincidence system have been compared, yielding identical results. These measurements have also been validated using simultaneous neutron monitor observations. This new software coincidence system provides remarkable advantages such as higher simplicity of interconnection and adjusting. Thus, our system replaces, at least, three Nuclear Instrument Modules (NIMs) required by conventional coincidence systems, reducing its cost by a factor of 40 and eliminating pulse delay adjustments

Design and structure of an equilibrium protein folding intermediate: a hint into dynamical regions of proteins.

Partly unfolded protein conformations close to the native state may play important roles in protein function and in protein misfolding. Structural analyses of such conformations which are essential for their fully physicochemical understanding are complicated by their characteristic low populations at equilibrium. We stabilize here with a single mutation the equilibrium intermediate of apoflavodoxin thermal unfolding and determine its solution structure by NMR. It consists of a large native region identical with that observed in the X-ray structure of the wild-type protein plus an unfolded region. Small-angle X-ray scattering analysis indicates that the calculated ensemble of structures is consistent with the actual degree of expansion of the intermediate. The unfolded region encompasses discontinuous sequence segments that cluster in the 3D structure of the native protein forming the FMN cofactor binding loops and the binding site of a variety of partner proteins. Analysis of the apoflavodoxin inner interfaces reveals that those becoming destabilized in the intermediate are more polar than other inner interfaces of the protein. Natively folded proteins contain hydrophobic cores formed by the packing of hydrophobic surfaces, while natively unfolded proteins are rich in polar residues. The structure of the apoflavodoxin thermal intermediate suggests that the regions of natively folded proteins that are easily responsive to thermal activation may contain cores of intermediate hydrophobicity

ORCA (Antarctic Cosmic Ray Observatory): 2018 Latitudinal Survey

A set of detectors devoted to investigate secondary cosmic rays has performed a latitudinal observation from Vigo (Spain) to Juan Carlos I Spanish Antarctic Station (Livingston Island, Antarctic Peninsula) aboard the Sarmiento de Gamboa oceanographic vessel from November $14^{th}$ to January $2^{nd}$. The experiment is split into two modules, one composed by a stack of 3NM64, three BF3 bare counters (NEMO) and a muon telescope (MITO) with a mini neutron monitor in a $20^{\prime}$ maritime container on the Sarmiento de Gamboa$^{\prime}$s deck and a second module (TRISTAN) consisting of a set of 3 RPC planes with a lead layer in between the second and the third plane placed in a separate temperature controlled room below the ship$^{\prime}$s deck. The complete set of instruments is the Antarctic Cosmic Ray Observatory (ORCA) that has been be installed in the Juan Carlos I Spanish Antarctic Base in Livingston Island (Antarctica). The latitudinal survey took ORCA throughout the South Atlantic magnetic anomaly along the Brazilian coast. ORCA is able to measure fluxes of neutrons of different energies, charged particles (mostly muons) and muon incident directions on the detector surface. In this work, we present the preliminary results of the latitudinal survey

Association of common genetic variants with risperidone adverse events in a Spanish schizophrenic population

Risperidone non-compliance is often high due to undesirable side effects, whose development is in part genetically determined. Studies with genetic variants involved in the pharmacokinetics and pharmacodynamics of risperidone have yielded inconsistent results. Thus, the aim of this study was to investigate the putative association of genetic markers with the occurrence of four frequently observed adverse events secondary to risperidone treatment: sleepiness, weight gain, extrapyramidal symptoms and sexual adverse events. A series of 111 schizophrenia inpatients were genotyped for genetic variants previously associated with or potentially involved in risperidone response. Presence of adverse events was the main variable and potential confounding factors were considered. Allele 16Gly of ADRB2 was significantly associated with a higher risk of sexual adverse events. There were other non-significant trends for DRD3 9Gly and SLC6A4 S alleles. Our results, although preliminary, provide new candidate variants of potential use in risperidone safety prediction.This study was supported by Fondo de Investigation Sanitaria (FIS) EC07/90393, EC07/90466 and EC07/90604 Grants. Berta Almoguera's work is supported by a Rio Hortega Grant from Instituto de Salud Carlos III. Pedro Dorado is supported by Instituto de Salud Carlos III-FIS and European Union (FEDER) Grant CP06/00030. The contribution from the Extremadura group is coordinated in the frame of the Iberoamerican Network of PharmacogeneticsPeer reviewe