Viruses Previously Identified in Brazil as Belonging to HIV-1 CRF72_BF1 Represent Two Closely Related Circulating Recombinant Forms, One of Which, Designated CRF122_BF1, Is Also Circulating in Spain

Circulating recombinant forms (CRFs) are important components of the HIV-1 pandemic. Those derived from recombination between subtype B and subsubtype F1, with 18 reported, most of them of South American origin, are among the most diverse. In this study, we identified a HIV-1 BF1 recombinant cluster that is expanding in Spain, transmitted mainly via heterosexual contact, which, analyzed in near full-length genomes in four viruses, exhibited a coincident BF1 mosaic structure, with 12 breakpoints, that fully coincided with that of two viruses (10BR_MG003 and 10BR_MG005) from Brazil, previously classified as CRF72_BF1. The three remaining Brazilian viruses (10BR_MG002, 10BR_MG004, and 10BR_MG008) previously identified as CRF72_BF1 exhibited mosaic structures highly similar, but not identical, to that of the Spanish viruses and to 10BR_MG003 and 10BR_MG005, with discrepant subtypes in two short genome segments, located in pol and gp120env. Based on these results, we propose that the five viruses from Brazil previously identified as CRF72_BF1 actually belong to two closely related CRFs, one comprising 10BR_MG002, 10BR_MG004, and 10BR_MG008, which keep their CRF72_BF1 designation, and the other, designated CRF122_BF1, comprising 10BR_MG003, 10BR_MG005, and the viruses of the identified Spanish cluster. Three other BF1 recombinant genomes, two from Brazil and one from Italy, previously identified as unique recombinant forms, were classified as CRF72_BF1. CRF122_BF1, but not CRF72_BF1, was associated with protease L89M substitution, which was reported to contribute to antiretroviral drug resistance. Phylodynamic analyses estimate the emergence of CRF122_BF1 in Brazil around 1987. Given their close phylogenetic relationship and similar structures, the grouping of CRF72_BF1 and CRF122_BF1 in a CRF family is proposed.This work was funded through Acción Estratégica en Salud Intramural (AESI), Instituto de Salud Carlos III, projects “Estudios Sobre Vigilancia Epidemiológica Molecular del VIH-1 en España”, PI16CIII/00033, and “Epidemiología Molecular del VIH-1 en España y su Utilidad Para Investigaciones Biológicas y en Vacunas“, PI19CIII/00042, and through scientific agreement with Consellería de Sanidade, Government of Galicia (MVI 1004/16).S

Influence of the LILRA3 Deletion on Multiple Sclerosis Risk : Original Data and Meta-Analysis

Altres ajuts: Junta de Andalucía (JA)- Fondos Europeos de Desarrollo Regional (FEDER) (grant number CTS2704 to FM).Multiple sclerosis (MS) is a neurodegenerative, autoimmune disease of the central nervous system. Genome-wide association studies (GWAS) have identified over hundred polymorphisms with modest individual effects in MS susceptibility and they have confirmed the main individual effect of the Major Histocompatibility Complex. Additional risk loci with immunologically relevant genes were found significantly overrepresented. Nonetheless, it is accepted that most of the genetic architecture underlying susceptibility to the disease remains to be defined. Candidate association studies of the leukocyte immunoglobulin-like receptor LILRA3 gene in MS have been repeatedly reported with inconsistent results. In an attempt to shed some light on these controversial findings, a combined analysis was performed including the previously published datasets and three newly genotyped cohorts. Both wild-type and deleted LILRA3 alleles were discriminated in a single-tube PCR amplification and the resulting products were visualized by their different electrophoretic mobilities. Overall, this meta-analysis involved 3200 MS patients and 3069 matched healthy controls and it did not evidence significant association of the LILRA3 deletion [carriers of LILRA3 deletion: p = 0.25, OR (95% CI) = 1.07 (0.95-1.19)], even after stratification by gender and the HLA-DRB1*15 : 01 risk allele

Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms

Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. Video Abstract [Figure presented] Keywords: type 2 diabetes (T2D); genetics; disease mechanism; SLC16A11; MCT11; solute carrier (SLC); monocarboxylates; fatty acid metabolism; lipid metabolism; precision medicin

The Gaia mission

Gaia is a cornerstone mission in the science programme of the EuropeanSpace Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page. http://www.cosmos.esa.int/gai

Diagnóstico por imágenes de cáncer de mamas. Comparación entre técnica ecográfica y mamografía

El cáncer de mama es un problema de salud mundial y la principal causa de muerte entre las mujeres a nivel internacional. En el 96% de los casos, el cáncer de mama de tipo tratables si se detectan temprano. Si bien las medidas como el autoexamen pueden alertar sobre la presencia de tumores, generalmente para cuando son palpables ya tienen un tamaño considerable. Las estadísticas indican que el 52% de las mujeres afectadas acuden al hospital en etapas tempranas, esto aumenta la probabilidad de salvar su vida. El cáncer de mama se distingue de otros tipos de cáncer por el hecho de que se produce en un órgano visible y se detecta y se trata en una etapa temprana. Las bajas tasas de supervivencia en los países menos desarrollados pueden ser atribuidas a la falta de detección temprana, así como el diagnóstico inadecuado y las instalaciones de tratamiento. Entre las técnicas diagnósticas implementadas, se encuentra la mamografía utilizada con el fin de buscar o identificar en el seno de la mujer: nódulos, calcificaciones, asimetrías, desestructuración, cambios en la piel y axila. Su uso se basa en un comprensor, rangos de Kv bajos de 25, 28 a 35 (dependiendo), con ayuda de mono emulsión, observadas en una sola pantalla. Por su parte, el eco mamario se basa en un método digital que tiene 15 detectores q transforman los rayos x en señales eléctricas, el proceso de revelado es distinto a la convencional, no se utiliza químicos es mediante una impresora láser; en las dos se utilizan la misma técnica y el mismo equipo, solo que en la convencional el proceso de revelado se usa químicos y agua. La mamografía como método de diagnóstico presuntivo consiste en tomar imágenes comprimiendo el seno en sentido horizontal y luego oblicuo, con un equipo de rayos X, que usa pequeñas dosis de radiación, ofreciendo imágenes de alta calidad; en cambio, el eco mamario se basa en un método digital que tiene 15 detectores q transforman los rayos x en señales eléctrica

Influence of the LILRA3 Deletion on Multiple Sclerosis Risk: Original Data and Meta-Analysis.

BACKGROUND: Multiple sclerosis (MS) is a neurodegenerative, autoimmune disease of the central nervous system. Genome-wide association studies (GWAS) have identified over hundred polymorphisms with modest individual effects in MS susceptibility and they have confirmed the main individual effect of the Major Histocompatibility Complex. Additional risk loci with immunologically relevant genes were found significantly overrepresented. Nonetheless, it is accepted that most of the genetic architecture underlying susceptibility to the disease remains to be defined. Candidate association studies of the leukocyte immunoglobulin-like receptor LILRA3 gene in MS have been repeatedly reported with inconsistent results. OBJECTIVES: In an attempt to shed some light on these controversial findings, a combined analysis was performed including the previously published datasets and three newly genotyped cohorts. Both wild-type and deleted LILRA3 alleles were discriminated in a single-tube PCR amplification and the resulting products were visualized by their different electrophoretic mobilities. RESULTS AND CONCLUSION: Overall, this meta-analysis involved 3200 MS patients and 3069 matched healthy controls and it did not evidence significant association of the LILRA3 deletion [carriers of LILRA3 deletion: p = 0.25, OR (95% CI) = 1.07 (0.95-1.19)], even after stratification by gender and the HLA-DRB1*15:01 risk allele.Financial support for the study was provided by: Fondo de Investigación Sanitaria (FIS)- Instituto de Salud Carlos III (ISCIII)-Fondos Europeos de Desarrollo Regional (FEDER) (grant numbers PI12/00555 to FM; PI13/01527 to AA; PI13/01466 to GI; PI13/0879 to EU and RETICS-REEM RD12/0032/ ) and Junta de Andalucía (JA)- Fondos Europeos de Desarrollo Regional (FEDER) (grant number CTS2704 to FM