Fundamental Reference AGN Monitoring Experiment (FRAMEx) III: Radio Emission in the Immediate Vicinity of Radio Quiet AGNs

We present follow-up results from the first Fundamental Reference AGN Monitoring Experiment (FRAMEx) X-ray/radio snapshot program of a volume-complete sample of local hard X-ray-selected active galactic nuclei (AGNs). Here, we added 9 new sources to our previous volume-complete snapshot campaign, two of which are detected in the 6 cm Very Long Baseline Array (VLBA) observations. We also obtained deeper VLBA observations for a sample of 9 AGNs not detected by our previous snapshot campaign. We recovered 3 sources with approximately twice the observing sensitivity. In contrast with lower angular resolution Very Large Array (VLA) studies, the majority of our sources continue to be undetected with the VLBA. The sub-parsec radio (6 cm) and X-ray (2-10 keV) emission show no significant correlation, with L_R/L_X ranging from 10^-8 to 10^-4, and the majority of our sample lies well below the fiducial 10^-5 relationship for coronal synchrotron emission. Additionally, our sources are not aligned with any of the proposed "fundamental" planes of black hole activity, which purport to unify black hole accretion in the M_BH-L_X-L_R parameter space. The new detections in our deeper observations suggest that the radio emission may be produced by the synchrotron radiation of particles accelerated in low luminosity outflows. Non-detections may be a result of synchrotron self-absorption at 6 cm in the radio core, similar to what has been observed in X-ray binaries (XRBs) transitioning from the radiatively inefficient state to a radiatively efficient state.Comment: 18 pages, 9 figures; Accepted for publication in Ap

Electromagnetic navigation bronchoscopy in the European cohort of the prospective, multicenter NAVIGATE study

n/

DNA methylation map of mouse and human brain identifies target genes in Alzheimer’s disease

The central nervous system has a pattern of gene expression that is closely regulated with respect to functional and anatomical regions. DNA methylation is a major regulator of transcriptional activity, and aberrations in the distribution of this epigenetic mark may be involved in many neurological disorders, such as Alzheimer’s disease. Herein, we have analysed 12 distinct mouse brain regions according to their CpG 5’-end gene methylation patterns and observed their unique epigenetic landscapes. The DNA methylomes obtained from the cerebral cortex were used to identify aberrant DNA methylation changes that occurred in two mouse models of Alzheimer’s disease. We were able to translate these findings to patients with Alzheimer’s disease, identifying DNA methylation-associated silencing of three targets genes: thromboxane A2 receptor (TBXA2R), sorbin and SH3 domain containing 3 (SORBS3) and spectrin beta 4 (SPTBN4). These hypermethylation targets indicate that the cyclic AMP response element-binding protein (CREB) activation pathway and the axon initial segment could contribute to the disease

Role of muscle IL-6 in gender-specific metabolism in mice

The aim of the present work was to further explore the physiological roles of muscle-derived IL-6. Adult-floxed and conditional skeletal muscle IL-6 knock out male and female mice were used to study energy expenditure (indirect calorimetry at rest and during treadmill exercise, and body temperature cycle during the light phase) and energy intake (response to fast/ refeeding). We also evaluated the responses to leptin and the activity of the insulin signalling pathway in skeletal muscle and liver by phosphorylation of Akt at Ser 473. The stress response was also studied. Results indicate a relevant role of muscle IL-6 in maintaining energy homeostasis, especially in males. Absence of muscle IL-6 in male mice results in lower core body temperature in the light phase, increased respiratory exchange ratio (RER) both at rest and during exercise, increased expression of TCA cycle marked gene, citrate synthase in muscle, reduced fat storage and decreased body weight and food consumption in response to leptin. In females, muscle IL-6 deficiency increases VO and CO levels similarly. Also in contrast to males, energy expenditure (EE) measured over 48h reveals a significant elevation in female mice with muscle IL-6 deficiency; moreover, they show a modified response to fasting-refeeding and to restraint stress. The present results contribute to the understanding of the role of muscle IL-6 in male and female mouse metabolism, not only during exercise but also in the basal state and in situations where energy balance is altered

Global hyperactivation of enhancers stabilizes human and mouse naïve pluripotency through inhibition of CDK8/19 Mediator kinases

Pluripotent stem cells (PSCs) transition between cell states in vitro and reflect developmental changes in the early embryo. PSCs can be stabilized in the naïve state by blocking extracellular differentiation stimuli, particularly FGF-MEK signaling. Here, we report that multiple features of the naïve state in human and mouse PSCs can be recapitulated without affecting FGF-MEK-signaling or global DNA methylation. Mechanistically, chemical inhibition of CDK8 and CDK19 kinases removes their ability to repress the Mediator complex at enhancers. Thus CDK8/19 inhibition increases Mediator-driven recruitment of RNA Pol II to promoters and enhancers. This efficiently stabilizes the naïve transcriptional program and confers resistance to enhancer perturbation by BRD4 inhibition. Moreover, naïve pluripotency during embryonic development coincides with a reduction in CDK8/19. We conclude that global hyperactivation of enhancers drives naïve pluripotency, and this can be achieved in vitro by inhibiting CDK8/19 kinase activity. These principles may apply to other contexts of cellular plasticity

Surface indicators are correlated with soil multifunctionality in global drylands

Multiple ecosystem functions need to be considered simultaneously to manage and protect the several ecosystem services that are essential to people and their environments. Despite this, cost effective, tangible, relatively simple and globally relevant methodologies to monitor in situ soil multifunctionality, that is, the provision of multiple ecosystem functions by soils, have not been tested at the global scale. We combined correlation analysis and structural equation modelling to explore whether we could find easily measured, field-based indicators of soil multifunctionality (measured using functions linked to the cycling and storage of soil carbon, nitrogen and phosphorus). To do this, we gathered soil data from 120 dryland ecosystems from five continents. Two soil surface attributes measured in situ (litter incorporation and surface aggregate stability) were the most strongly associated with soil multifunctionality, even after accounting for geographic location and other drivers such as climate, woody cover, soil pH and soil electric conductivity. The positive relationships between surface stability and litter incorporation on soil multifunctionality were greater beneath the canopy of perennial vegetation than in adjacent, open areas devoid of vascular plants. The positive associations between surface aggregate stability and soil functions increased with increasing mean annual temperature. Synthesis and applications. Our findings demonstrate that a reduced suite of easily measured in situ soil surface attributes can be used as potential indicators of soil multifunctionality in drylands world-wide. These attributes, which relate to plant litter (origin, incorporation, cover), and surface stability, are relatively cheap and easy to assess with minimal training, allowing operators to sample many sites across widely varying climatic areas and soil types. The correlations of these variables are comparable to the influence of climate or soil, and would allow cost-effective monitoring of soil multifunctionality under changing land-use and environmental conditions. This would provide important information for evaluating the ecological impacts of land degradation, desertification and climate change in drylands world-wide.Fil: Eldridge, David J.. University of New South Wales; AustraliaFil: Delgado Baquerizo, Manuel. Universidad Rey Juan Carlos; EspañaFil: Quero, José L.. Universidad de Córdoba; EspañaFil: Ochoa, Victoria. Universidad Rey Juan Carlos; España. Universidad de Alicante; EspañaFil: Gozalo, Beatriz. Universidad Rey Juan Carlos; España. Universidad de Alicante; EspañaFil: García Palacios, Pablo. Universidad Rey Juan Carlos; EspañaFil: Escolar, Cristina. Universidad Rey Juan Carlos; EspañaFil: García Gómez, Miguel. Universidad Politécnica de Madrid; EspañaFil: Prina, Aníbal. Universidad Nacional de La Pampa; ArgentinaFil: Bowker, Mathew A.. Northern Arizona University; Estados UnidosFil: Bran, Donaldo Eduardo. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche; ArgentinaFil: Castro, Ignacio. Universidad Experimental Simón Rodríguez; VenezuelaFil: Cea, Alex. Universidad de La Serena; ChileFil: Derak, Mchich. No especifíca;Fil: Espinosa, Carlos I.. Universidad Técnica Particular de Loja; EcuadorFil: Florentino, Adriana. Universidad Central de Venezuela; VenezuelaFil: Gaitán, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Recursos Naturales. Instituto de Suelos; Argentina. Universidad Nacional de Luján. Departamento de Tecnología; ArgentinaFil: Gatica, Mario Gabriel. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Departamento de Biología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; ArgentinaFil: Gómez González, Susana. Universidad de Cádiz; EspañaFil: Ghiloufi, Wahida. Université de Sfax; TúnezFil: Gutierrez, Julio R.. Universidad de La Serena; ChileFil: Guzman, Elizabeth. Universidad Técnica Particular de Loja; EcuadorFil: Hernández, Rosa M.. Universidad Experimental Simón Rodríguez; VenezuelaFil: Hughes, Frederic M.. Universidade Estadual de Feira de Santana; BrasilFil: Muiño, Walter. Universidad Nacional de La Pampa; ArgentinaFil: Monerris, Jorge. No especifíca;Fil: Ospina, Abelardo. Universidad Central de Venezuela; VenezuelaFil: Ramírez, David A.. International Potato Centre; PerúFil: Ribas Fernandez, Yanina Antonia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; ArgentinaFil: Romão, Roberto L.. Universidade Estadual de Feira de Santana; BrasilFil: Torres Díaz, Cristian. Universidad del Bio Bio; ChileFil: Koen, Terrance B.. No especifíca;Fil: Maestre, Fernando T.. Universidad Rey Juan Carlos; España. Universidad de Alicante; Españ

Risk of ischaemic heart disease and acute myocardial infarction in a Spanish population: observational prospective study in a primary-care setting

BACKGROUND: Ischaemic heart disease is a global priority of health-care policy, because of its social repercussions and its impact on the health-care system. Yet there is little information on coronary morbidity in Spain and on the effect of the principal risk factors on risk of coronary heart disease. The objective of this study is to describe the epidemiology of coronary disease (incidence, mortality and its association with cardiovascular risk factors) using the information gathered by primary care practitioners on cardiovascular health of their population. METHODS: A prospective study was designed. Eight primary-care centres participated, each contributing to the constitution of the cohort with the entire population covered by the centre. A total of 6124 men and women aged over 25 years and free of cardiovascular disease agreed to participate and were thus enrolled and followed-up, with all fatal and non-fatal coronary disease episodes being registered during a 5-year period. Repeated measurements were collected on smoking, blood pressure, weight and height, serum total cholesterol, high-density and low-density lipoproteins and fasting glucose. Rates were calculated for acute myocardial infarction and ischaemic heart disease. Associations between cardiovascular risk factors and coronary disease-free survival were evaluated using Kaplan-Meier and Cox regression analyses. RESULTS: Mean age at recruitment was 51.6 ± 15, with 24% of patients being over 65. At baseline, 74% of patients were overweight, serum cholesterol over 240 was present in 35% of patients, arterial hypertension in 37%, and basal glucose over 126 in 11%. Thirty-four percent of men and 13% of women were current smokers. During follow-up, 155 first episodes of coronary disease were detected, which yielded age-adjusted rates of 362 and 191 per 100,000 person-years in men and women respectively. Disease-free survival was associated with all risk factors in univariate analyses. After multivariate adjustments, age, male gender, smoking, high total cholesterol, high HDL/LDL ratio, diabetes and overweight remained strongly associated with risk. Relative risks for hypertension in women and for diabetes in men did not reach statistical significance. CONCLUSION: Despite high prevalence of vascular risk factors, incidence rates were lower than those reported for other countries and other periods, but similar to those reported in the few population-based studies in Spain. Effect measures of vascular risk factors were mainly as reported worldwide and support the hypothesis that protective factors not considered in this study must exist as to explain low rates. This study shows the feasibility of conducting epidemiological cohort studies in primary-care settings

Longitudinal study of DNA methylation during the first 5 years of life.

Background: Early life epigenetic programming influences adult health outcomes. Moreover, DNA methylation levels have been found to change more rapidly during the first years of life. Our aim was the identification and characterization of the CpG sites that are modified with time during the first years of life. We hypothesize that these DNA methylation changes would lead to the detection of genes that might be epigenetically modulated by environmental factors during early childhood and which, if disturbed, might contribute to susceptibility to diseases later in life. Methods: The study of the DNA methylation pattern of 485577 CpG sites was performed on 30 blood samples from 15 subjects, collected both at birth and at 5 years old, using Illumina® Infinium 450 k array. To identify differentially methylated CpG (dmCpG) sites, the methylation status of each probe was examined using linear models and the Empirical Bayes Moderated t test implemented in the limma package of R/Bioconductor. Surogate variable analysis was used to account for batch effects. Results: DNA methylation levels significantly changed from birth to 5 years of age in 6641 CpG sites. Of these, 36.79 % were hypermethylated and were associated with genes related mainly to developmental ontology terms, while 63.21 % were hypomethylated probes and associated with genes related to immune function. Conclusions: Our results suggest that DNA methylation alterations with age during the first years of life might play a significant role in development and the regulation of leukocyte-specific functions. This supports the idea that blood leukocytes experience genome remodeling related to their interaction with environmental factors, underlining the importance of environmental exposures during the first years of life and suggesting that new strategies should be take into consideration for disease prevention