Association of the MYH9 gene polymorphisms with chronic renal disease secondary to hypertensive nephrosclerosis, in a Caucasian population

Background: Hypertensive nephrosclerosis (HN) is a chronic kidney disease (CKD) associated to essential hypertension, but their causal relationship is controversial. New evidence suggests that MYH9 gene alterations are associated with HN in African Americans. The aim of this study is to investigate the role of this gene in Spanish Caucasians. Methods: We compare high-risk MYH9 variants of patients with HN recruited according to standard clinical criteria (CKD stages 3-5), with essential hypertensives without renal disease (estimated glomerular filtration rate (eGFR) > 60 ml/min/1,73m2 and albuminuria < 300 mg/g creatinine), and also CKD patients with HN and progressive impairment of renal function with those who were stable. Diabetics were excluded. Results: A blood sample was obtained for genetic study of 238 patients with HN-CKD and 233 hypertensive controls. The rs3752462-T and rs4821480-T (risk alleles for CKD) were more frequent in the CKD group, but without significant difference. We found no differences for these SPNs with blood pressure, creatinine, albuminuria or renal disease progression. Conclusions: The effect of two common MYH9 single nucleotide polymorphisms (SPNs) on the development of CKD secondary to HN in our Spanish Caucasian population is low or zero; in any case less than that found in other, mainly African Americans.Funding: This work was supported by grant Red de Investigación Renal-REDINREN from the Instituto Carlos III, and with funds from the Fundación Renal Iñigo Álvarez de Toledo (Iñigo Álvarez de Toledo Kidney Foundation) in the Molecular Genetics Grou

La participación laboral de las mujeres: un reto para el bienestar social.

Este trabajo ha sido posible gracias a la cobertura de los proyectos de investigación “Riesgos y oportunidades a lo largo del curso de la vida en las sociedades postindustriales” (CICYT. Sec2003-06799), dirigido por Esping-Andersen (Universitat Pompeu Fabra) y “Nuevos Riesgos Sociales y Trayectorias de las Políticas del Bienestar” (NURSOPOB) (MEC, Plan Nacional de I+D+I), dirigidos por Luis Moreno (Unidad de Políticas Comparadas, CSIC). Agradezco a ambos el apoyo que me han prestado para poderle llevar a cabo, y de forma muy particular, a Ana Arriba y Luis Moreno, por sus comentarios y colaboración en versiones anteriores del mismo

Control of Gene Expression by the Retinoic Acid-Related Orphan Receptor Alpha in HepG2 Human Hepatoma Cells

Retinoic acid-related Orphan Receptor alpha (RORα; NR1F1) is a widely distributed nuclear receptor involved in several (patho)physiological functions including lipid metabolism, inflammation, angiogenesis, and circadian rhythm. To better understand the role of this nuclear receptor in liver, we aimed at displaying genes controlled by RORα in liver cells by generating HepG2 human hepatoma cells stably over-expressing RORα. Genes whose expression was altered in these cells versus control cells were displayed using micro-arrays followed by qRT-PCR analysis. Expression of these genes was also altered in cells in which RORα was transiently over-expressed after adenoviral infection. A number of the genes found were involved in known pathways controlled by RORα, for instance LPA, NR1D2 and ADIPOQ in lipid metabolism, ADIPOQ and PLG in inflammation, PLG in fibrinolysis and NR1D2 and NR1D1 in circadian rhythm. This study also revealed that genes such as G6PC, involved in glucose homeostasis, and AGRP, involved in the control of body weight, are also controlled by RORα. Lastly, SPARC, involved in cell growth and adhesion, and associated with liver carcinogenesis, was up-regulated by RORα. SPARC was found to be a new putative RORα target gene since it possesses, in its promoter, a functional RORE as evidenced by EMSAs and transfection experiments. Most of the other genes that we found regulated by RORα also contained putative ROREs in their regulatory regions. Chromatin immunoprecipitation (ChIP) confirmed that the ROREs present in the SPARC, PLG, G6PC, NR1D2 and AGRP genes were occupied by RORα in HepG2 cells. Therefore these genes must now be considered as direct RORα targets. Our results open new routes on the roles of RORα in glucose metabolism and carcinogenesis within cells of hepatic origin

Choice of the initial antiretroviral treatment for HIV-positive individuals in the era of integrase inhibitors

BACKGROUND: We aimed to describe the most frequently prescribed initial antiretroviral therapy (ART) regimens in recent years in HIV-positive persons in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of each regimen. METHODS: We analyzed initial ART regimens prescribed in adults participating in CoRIS from 2014 to 2017. Only regimens prescribed in >5% of patients were considered. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between sociodemographic and clinical characteristics and the choice of the initial regimen. RESULTS: Among 2874 participants, abacavir(ABC)/lamivudine(3TC)/dolutegavir(DTG) was the most frequently prescribed regimen (32.1%), followed by tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir(EVG)/cobicistat(COBI) (14.9%), TDF/FTC/rilpivirine (RPV) (14.0%), tenofovir alafenamide (TAF)/FTC/EVG/COBI (13.7%), TDF/FTC+DTG (10.0%), TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) (9.8%) and TDF/FTC+raltegravir (RAL) (5.6%). Compared with ABC/3TC/DTG, starting TDF/FTC/RPV was less likely in patients with CD4100.000 copies/mL. TDF/FTC+DTG was more frequent in those with CD4100.000 copies/mL. TDF/FTC+RAL and TDF/FTC+bDRV were also more frequent among patients with CD4<200 cells//muL and with transmission categories other than men who have sex with men. Compared with ABC/3TC/DTG, the prescription of other initial ART regimens decreased from 2014-2015 to 2016-2017 with the exception of TDF/FTC+DTG. Differences in the choice of the initial ART regimen were observed by hospitals' location. CONCLUSIONS: The choice of initial ART regimens is consistent with Spanish guidelines' recommendations, but is also clearly influenced by physician's perception based on patient's clinical and sociodemographic variables and by the prescribing hospital location

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Análisis fenológico de herbaceas en claros de bosque de roble

A partir de la información del cambio fenológico en dos robledales de la provincia de León, en los que se distinguen zonas de claro y de bosque, se hace un análisis comparativo entre las cuatro áreas controladas en función de la evolución del cambio. Se resaltan las características de composición desde el punto de vista agronómica, haciendo especial referencia en el cambio fenológico de las especies mejor clasificadas por su valor pastora

Synthesis and Characterization of Graphene Oxide Derivatives via Functionalization Reaction with Hexamethylene Diisocyanate

Graphene oxide (GO), the oxidized form of graphene, shows unique properties including high mechanical strength, optical transparency, amphiphilicity and surface functionalization capability that make it attractive in fields ranging from medicine to optoelectronic devices and solar cells. However, its insolubility in non-polar and polar aprotic solvents hinders some applications. To solve this issue, novel functionalization strategies are pursued. In this regard, this study deals with the preparation and characterization of hexamethylene diisocyanate (HDI)-functionalized GO. Different reaction conditions were tested to optimize the functionalization degree (FD), and detailed characterizations were conducted via elemental analysis, Fourier-transformed infrared (FT-IR) and Raman spectroscopies to confirm the success of the functionalization reaction. The morphology of HDI-GO was investigated by transmission electron microscopy (TEM), which revealed an increase in the flake thickness with increasing FD. The HDI-GO showed a more hydrophobic nature than pristine GO and could be suspended in polar aprotic solvents such as N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP) and dimethyl sulfoxide (DMSO) as well as in low polar/non-polar solvents like tetrahydrofuran (THF), chloroform and toluene; further, the dispersibility improved upon increasing FD. Thermogravimetric analysis (TGA) confirmed that the covalent attachment of HDI greatly improves the thermal stability of GO, ascribed to the crosslinking between adjacent sheets, which is interesting for long-term electronics and electrothermal device applications. The HDI-GO samples can further react with organic molecules or polymers via the remaining oxygen groups, hence are ideal candidates as nanofillers for high-performance GO-based polymer nanocomposites

Edificio de 15 viviendas con garaje, trastero, piscina y zonas comunes en Madrid

Proyecto constructivo de un edificio de 15 viviendas con garaje, trastero, piscina y zonas comunes en Madrid

Interaction Information Along Lifespan of the Resting Brain Dynamics Reveals a Major Redundant Role of the Default Mode Network

Interaction Information (II) generalizes the univariate Shannon entropy to triplets of variables, allowing the detection of redundant (R) or synergetic (S) interactions in dynamical networks. Here, we calculated II from functional magnetic resonance imaging data and asked whether R or S vary across brain regions and along lifespan. Preserved along lifespan, we found high overlapping between the pattern of high R and the default mode network, whereas high values of S were overlapping with different cognitive domains, such as spatial and temporal memory, emotion processing and motor skills. Moreover, we have found a robust balance between R and S among different age intervals, indicating informational compensatory mechanisms in brain networks.status: publishe