161 research outputs found

    Magnetic pinning of flux lattice in superconducting- nanomagnet hybrids

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    Strong superconducting pinning effects are observed from magnetic landscapes produced by arrays of circular rings with varying magnetic remanent states. The collective and the background pinning of superconducting Nb films is strongly enhanced by the stray magnetic field produced by an array of circular Ni rings magnetized to form “onion” (bidomain) states. On the other hand, when the same rings are magnetized into vortex (flux-closed) states, or are randomly magnetized, the superconducting pinning is much smaller. The greatest pinning is produced when the superconducting vortex lattice motion is along a direction in which there is a strong magnetic field variation

    Rare Germline DICER1 Variants in Pediatric Patients With Cushing's Disease: What Is Their Role?

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    Context: The DICER1 syndrome is a multiple neoplasia disorder caused by germline mutations in the DICER1 gene. In DICER1 patients, aggressive congenital pituitary tumors lead to neonatal Cushing's disease (CD). The role of DICER1 in other corticotropinomas, however, remains unknown. Objective: To perform a comprehensive screening for DICER1 variants in a large cohort of CD patients, and to analyze their possible contribution to the phenotype. Design, setting, patients, and interventions: We included 192CD cases: ten young-onset (age <30 years at diagnosis) patients were studied using a next generation sequencing panel, and 182 patients (170 pediatric and 12 adults) were screened via whole-exome sequencing. In seven cases, tumor samples were analyzed by Sanger sequencing. Results: Rare germline DICER1 variants were found in seven pediatric patients with no other known disease-associated germline defects or somatic DICER1 second hits. By immunohistochemistry, DICER1 showed nuclear localization in 5/6 patients. Variant transmission from one of the parents was confirmed in 5/7 cases. One patient had a multinodular goiter; another had a family history of melanoma; no other patients had a history of neoplasms. Conclusions: Our findings suggest that DICER1 gene variants may contribute to the pathogenesis of non-syndromic corticotropinomas. Clarifying whether DICER1 loss-of-function is disease-causative or a mere disease-modifier in this setting, requires further studies.This work was supported by the Intramural Research Programs of Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and National Institute for Neurological Diseases and Stroke, National Institutes of Health, a grant from the Basque Department of Education (IT795-13), a grant from the Basque Department of Health (GV2018111082), the Merck Serono Research award from Fundacion Salud 2000 (15-EP-004) and the Jose Igea 2018 grant, sponsored by Pfizer, from Fundacion Sociedad Espanola de Endocrinologia Pediatrica (SEEP)

    Detailed Characterization of Mesenchymal Stem/Stromal Cells from a Large Cohort of AML Patients Demonstrates a Definitive Link to Treatment Outcomes

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    Altres ajuts: Health Canada's Genomics Research and Development Initiative Phase VI (H4080-144541-2014-2019); Obra Social La Caixa-Fundació Josep Carreras and the Generalitat de Catalunya (SGR330); Asociación Española Contra el Cáncer (AECC-CI-2015)Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are key components of the hematopoietic niche thought to have a direct role in leukemia pathogenesis. BM-MSCs from patients with acute myeloid leukemia (AML) have been poorly characterized due to disease heterogeneity. We report a functional, genetic, and immunological characterization of BM-MSC cultures from 46 AML patients, stratified by molecular/cytogenetics into low-risk (LR), intermediate-risk (IR), and high-risk (HR) subgroups. Stable MSC cultures were successfully established and characterized from 40 of 46 AML patients irrespective of the risk subgroup. AML-derived BM-MSCs never harbored tumor-specific cytogenetic/molecular alterations present in blasts, but displayed higher clonogenic potential than healthy donor (HD)-derived BM-MSCs. Although HD- and AML-derived BM-MSCs equally provided chemoprotection to AML cells in vitro, AML-derived BM-MSCs were more immunosuppressive/anti-inflammatory, enhanced suppression of lymphocyte proliferation, and diminished secretion of pro-inflammatory cytokines. Multivariate analysis revealed that the level of interleukin-10 produced by AML-derived BM-MSCs as an independent prognostic factor negatively affected overall survival. Collectively our data show that AML-derived BM-MSCs are not tumor related, but display functional differences contributing to therapy resistance and disease evolution. In this article, Díaz de la Guardia and colleagues report a functional, genetic, and immunological characterization of BM-MSC cultures from 46 AML patients, stratified by molecular/cytogenetics into low-risk (LR), intermediate-risk (IR), and high-risk (HR) subgroups. BM-MSCs never harbored tumor-specific cytogenetic/molecular alterations present in blasts, and IL-10 produced by AML-derived BM-MSCs is an independent prognostic factor negatively impacting on overall survival

    Introducción al patrimonio geológico de interés turístico de la Red Española de Reservas de la Biosfera

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    160 p.Esta publicación se ha realizado con el objetivo de describir el origen y formación de una buena parte del patrimonio geológico de interés turístico de la Red Española de Reservas de la Biosfera para que éste sea conocido y pueda ser utilizado como motor de desarrollo económico local. La necesidad de dar a conocer este sorprendente patrimonio natural de la Red español de Reservas de la Biosfera fue constatada por su Consejo de Gestores que encargó el trabajo a su Consejo Científico. La publicación tiene la vocación de ser accesible para todos los públicos. Sin embargo, parte de un trabajo bibliográfico profundo abordado con una rigurosa metodología científica. Es además el fruto de una continua colaboración de los editores con las personas gestoras de las Reservas de la Biosfera españolas, así como con varios miembros de su Consejo Científico asesor.Instituto Geológico y Minero de España, Españ

    Central blood pressure and pulse wave velocity: relationship to target organ damage and cardiovascular morbidity-mortality in diabetic patients or metabolic syndrome. An observational prospective study. LOD-DIABETES study protocol

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    <p>Abstract</p> <p>Background</p> <p>Diabetic patients show an increased prevalence of non-dipping arterial pressure pattern, target organ damage and elevated arterial stiffness. These alterations are associated with increased cardiovascular risk.</p> <p>The objectives of this study are the following: to evaluate the prognostic value of central arterial pressure and pulse wave velocity in relation to the incidence and outcome of target organ damage and the appearance of cardiovascular episodes (cardiovascular mortality, myocardial infarction, chest pain and stroke) in patients with type 2 diabetes mellitus or metabolic syndrome.</p> <p>Methods/Design</p> <p><b>Design</b>: This is an observational prospective study with 5 years duration, of which the first year corresponds to patient inclusion and initial evaluation, and the remaining four years to follow-up.</p> <p><b>Setting</b>: The study will be carried out in the urban primary care setting.</p> <p><b>Study population</b>: Consecutive sampling will be used to include patients diagnosed with type 2 diabetes between 20-80 years of age. A total of 110 patients meeting all the inclusion criteria and none of the exclusion criteria will be included.</p> <p><b>Measurements</b>: Patient age and sex, family and personal history of cardiovascular disease, and cardiovascular risk factors. Height, weight, heart rate and abdominal circumference. Laboratory tests: hemoglobin, lipid profile, creatinine, microalbuminuria, glomerular filtration rate, blood glucose, glycosylated hemoglobin, blood insulin, fibrinogen and high sensitivity C-reactive protein. Clinical and 24-hour ambulatory (home) blood pressure monitoring and self-measured blood pressure. Common carotid artery ultrasound for the determination of mean carotid intima-media thickness. Electrocardiogram for assessing left ventricular hypertrophy. Ankle-brachial index. Retinal vascular study based on funduscopy with non-mydriatic retinography and evaluation of pulse wave morphology and pulse wave velocity using the SphygmoCor system. The medication used for diabetes, arterial hypertension and hyperlipidemia will be registered, together with antiplatelet drugs.</p> <p>Discussion</p> <p>The results of this study will help to know and quantify the prognostic value of central arterial pressure and pulse wave velocity in relation to the evolution of the subclinical target organ damage markers and the possible incidence of cardiovascular events in patients with type 2 diabetes mellitus.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: NCT01065155</p

    Local hydrological conditions influence tree diversity and composition across the Amazon basin

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    Tree diversity and composition in Amazonia are known to be strongly determined by the water supplied by precipitation. Nevertheless, within the same climatic regime, water availability is modulated by local topography and soil characteristics (hereafter referred to as local hydrological conditions), varying from saturated and poorly drained to well-drained and potentially dry areas. While these conditions may be expected to influence species distribution, the impacts of local hydrological conditions on tree diversity and composition remain poorly understood at the whole Amazon basin scale. Using a dataset of 443 1-ha non-flooded forest plots distributed across the basin, we investigate how local hydrological conditions influence 1) tree alpha diversity, 2) the community-weighted wood density mean (CWM-wd) – a proxy for hydraulic resistance and 3) tree species composition. We find that the effect of local hydrological conditions on tree diversity depends on climate, being more evident in wetter forests, where diversity increases towards locations with well-drained soils. CWM-wd increased towards better drained soils in Southern and Western Amazonia. Tree species composition changed along local soil hydrological gradients in Central-Eastern, Western and Southern Amazonia, and those changes were correlated with changes in the mean wood density of plots. Our results suggest that local hydrological gradients filter species, influencing the diversity and composition of Amazonian forests. Overall, this study shows that the effect of local hydrological conditions is pervasive, extending over wide Amazonian regions, and reinforces the importance of accounting for local topography and hydrology to better understand the likely response and resilience of forests to increased frequency of extreme climate events and rising temperatures

    The Use of Antihypertensive Medication and the Risk of Breast Cancer in a Case-Control Study in a Spanish Population: The MCC-Spain Study

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    The evidence on the relationship between breast cancer and different types of antihypertensive drugs taken for at least 5 years is limited and inconsistent. Furthermore, the debate has recently been fueled again with new data reporting an increased risk of breast cancer among women with a long history of use of antihypertensive drugs compared with nonusers

    Geography and ecology shape the phylogenetic composition of Amazonian tree communities

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    Aim: Amazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types. Location: Amazonia. Taxon: Angiosperms (Magnoliids; Monocots; Eudicots). Methods: Data for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran\u27s eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny. Results: In the terra firme and várzea forest types, the phylogenetic composition varies by geographic region, but the igapó and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R2^{2} = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R2^{2} = 28%). A greater number of lineages were significant indicators of geographic regions than forest types. Main Conclusion: Numerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions

    Geography and ecology shape the phylogenetic composition of Amazonian tree communities

    Get PDF
    AimAmazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types.LocationAmazonia.TaxonAngiosperms (Magnoliids; Monocots; Eudicots).MethodsData for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran's eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny.ResultsIn the terra firme and várzea forest types, the phylogenetic composition varies by geographic region, but the igapó and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R2 = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R2 = 28%). A greater number of lineages were significant indicators of geographic regions than forest types.Main ConclusionNumerous tree lineages, including some ancient ones (&gt;66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions
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