3,251 research outputs found
Consumption of Acorns by Finishing Iberian Pigs and Their Function in the Conservation of the Dehesa Agroecosystem
Circulating concentrations of free triiodothyronine are associated with central adiposity and cardiometabolic risk factors in young euthyroid adults
Funding for open access charge: Universidad de Granada/CBUA. This study was funded by the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III (PI13/01393), by the Retos de la Sociedad program (DEP2016-79512-R), European Regional Development Funds (ERDF), the Spanish Ministry of Education (FPU13/04365), the Fundacion Iberoamericana de Nutricion (FINUT), the Redes Tematicas de Investigacion Cooperativa RETIC (Red SAMID RD16/0022), the AstraZeneca HealthCare Foundation, the University of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES)-and Plan Propio de Investigacion 2018-the Programa Contratos-Puente and Contratos Perfeccionamiento de Doctores, the Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades (ERDF; ref. SOMM17/6107/UGR), and the Fundacion Alfonso Martin Escudero (grant awarded to GSD).Thyroid dysfunction is associated with classic cardiometabolic risk factors in humans. However, this relationship remains
unclear in young euthyroid adults. The present work examines the associations of circulating thyroid hormones (THs) and
thyroid-stimulating hormone (TSH) concentrations with body composition and cardiometabolic risk factors in young euthyroid
adults. A total of 106 sedentary, euthyroid adults (72 women; 22 ± 2 years old) participated in this cross-sectional study. THs
and TSH serum concentrations were determined in fasting conditions (6 h). Body composition (fat mass (FM), lean mass (LM),
and visceral adipose tissue (VAT)) was determined by dual-energy X-ray absorptiometry, anthropometric parameters (weight,
height, and waist circumference) were measured, and neck adipose tissue mass was quantified through computed tomography
(CT) scanning. Cardiometabolic risk factors including fasting glucose and lipid metabolism markers, hepatic phosphatase and
transaminases, and blood pressure were also assessed. Free triiodothyronine (FT3) concentration was positively associated with
body mass index, LM, VAT, and waist circumference (all P ≤ 0.038). FT3 was also associated with glucose, insulin, HOMA-IR,
fatty liver index, and blood pressure (all P < 0.024). All the associations were attenuated when adjusting for sex. In contrast,
we found no associations of TSH or free thyroxine with any body composition parameter or cardiometabolic risk factors. In
conclusion, FT3 is associated with central adiposity and cardiometabolic risk factors including insulin resistance, fatty liver
index, and mean, systolic and diastolic blood pressure in young euthyroid adults. ClinicalTrials.gov identifier: NCT02365129.Universidad de Granada/CBUASpanish Government PI13/01393Retos de la Sociedad program DEP2016-79512-REuropean CommissionSpanish Government FPU13/04365Fundacion Iberoamericana de Nutricion (FINUT)Redes Tematicas de Investigacion Cooperativa RETIC Red SAMID RD16/0022AstraZenecaUniversity of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES)Plan Propio de Investigacion 2018-the Programa Contratos-PuenteContratos Perfeccionamiento de DoctoresJunta de AndaluciaConsejeria de Conocimiento, Investigacion y Universidades (ERDF) SOMM17/6107/UGRFundacion Alfonso Martin Escuder
A palaeoecological approach to understanding the past and present of Sierra Nevada, a Southwestern European biodiversity hotspot
Mediterranean mountainous environments are biodiversity hotspots and priority areas in conservation agendas. Although they are fragile and threatened by forecasted global change scenarios, their sensitivity to long-term environmental variability is still understudied. The Sierra Nevada range, located in southern Spain on the north-western European flanks of the Mediterranean basin, is a biodiversity hotspot. Consequently, Sierra Nevada provides an excellent model system to apply a palaeoecological approach to detect vegetation changes, explore the drivers triggering those changes, and how vegetation changes link to the present landscape in such a paradigmatic mountain system. A multi-proxy strategy (magnetic susceptibility, grain size, loss-on-ignition, macroremains, charcoal and palynological analyses) is applied to an 8400-year long lacustrine environmental archive from the Laguna de la Mosca (2889 masl). The long-term ecological data show how the Early Holocene pine forests transitioned towards mixed Pinus-Quercus submediterranean forests as a response to a decrease in seasonality at ~7.3 cal. kyr BP. The mixed Pinus-Quercus submediterranean forests collapsed drastically giving way to open evergreen Quercus formations at ~4.2 cal. kyr BP after a well-known aridity crisis. Under the forecasted northward expansion of the Mediterranean area due to global change-related aridity increase, mountain forests inhabiting territories adjacent to the Mediterranean Region could experience analogous responses to those detected in the Sierra Nevada forests to the Mid to Late Holocene aridification, moving from temperate to submediterranean and then Mediterranean formations
Post-glacial evolution of alpine environments in the western Mediterranean region : The Laguna Seca record
In an effort to understand how alpine environments from the western Mediterranean region responded to climate variations since the last glacial-interglacial transition, a detailed chronological control and sedimentological analysis, supported by magnetic susceptibility, total organic carbon and C/N data, were carried out on the sedimentary record of Laguna Seca (LS). This is a latitudinal and altitudinally (2259 masl) key alpine wetland site located in the easternmost area of the Sierra Nevada, southern Iberian Peninsula, where sediments accumulated during Heinrich Stadial 1, Bolling-Allerod (B-A) and the Younger Dryas (YD) previously unrecorded in alpine Sierra Nevada. Climate controlled sedimentation in LS and three coarse-grained and one fine-grained facies association are differentiated, which help us decipher the paleoenvironmental evolution of LS: (1) subaerial cohesionless debris flows during a paraglacial stage; (2) till or nival diamicton during a small glacier/nivation hollow stage; (3) massive mudstone by suspension settling of clays into standing water during a lacustrine stage; and (4) frost-shattering breccia deposited inside the lacustrine stage, probably during the YD, and linked to a periglacial substage. The development of a previously existing small glacial cirque during the Last Glacial Maximum (LGM) in the LS basin at an elevation between 2500 and 2300 m could be supported by the important availability of slope sediments glacially-conditioned such as debris flows, reworked by paraglacial slope processes during the first deglaciation stages, confirming previous studies of landforms in the catchment area and the LGM-Equilibrium Line Altitude estimation above 2400 masl in Sierra Nevada. Mean sediment accumulation rates in the LS sedimentary units (4.21 and 0.28 mm/yr during the paraglacial small glacier/nivation stage and the lacustrine stage, respectively) confirm that geomorphic activity accelerated just after glaciers retreated due to a slope adjustment and high availability of glacially conditioned sediments. An abrupt change in paleoenvironmental and paleoclimatic conditions occurred in LS at ~ 15.7 cal kyr BP. This change was probably due to an increase in temperature and precipitation in the western Mediterranean region during the B-A. At LS, this resulted in significant ice-melt, forming a deep-water lake in LS with important organic matter contribution until the end of the Early Holocene (except in the YD when the lake level probably dropped), but elsewhere a general glacier recession in the Sierra Nevada and an expansion of the Mediterranean forest in the southern Iberian Peninsula. Finally, the general long-term aridification that occurred during the Middle Holocene until the present in the western Mediterranean region triggered an important environmental change transforming LS into an ephemeral wetland with an increase in aquatic productivity.Peer reviewe
RNase H2, mutated in Aicardi-Goutières syndrome, promotes LINE-1 retrotransposition
Long INterspersed Element class 1 (LINE-1) elements are a type of
abundant retrotransposons active in mammalian genomes. An
average human genome contains ~100 retrotransposition-competent
LINE-1s, whose activity is influenced by the combined action
of cellular repressors and activators. TREX1, SAMHD1 and ADAR1
are known LINE-1 repressors and when mutated cause the autoinflammatory
disorder Aicardi-Goutières syndrome (AGS). Mutations
in RNase H2 are the most common cause of AGS, and its activity
was proposed to similarly control LINE-1 retrotransposition. It has
therefore been suggested that increased LINE-1 activity may be
the cause of aberrant innate immune activation in AGS. Here, we
establish that, contrary to expectations, RNase H2 is required for
efficient LINE-1 retrotransposition. As RNase H1 overexpression
partially rescues the defect in RNase H2 null cells, we propose a
model in which RNase H2 degrades the LINE-1 RNA after reverse
transcription, allowing retrotransposition to be completed. This
also explains how LINE-1 elements can retrotranspose efficiently
without their own RNase H activity. Our findings appear to be at
odds with LINE-1-derived nucleic acids driving autoinflammation
in AGS.M.B.-G. is funded by a “Formacion Profesorado
Universitario” (FPU) PhD fellowship from the Government of Spain (MINECO,
Ref FPU15/03294), and this paper is part of her thesis project (“Epigenetic
control of the mobility of a human retrotransposon”). R.V.-A. is funded by a
PFIS Fellowship from the Government of Spain (ISCiii, FI16/00413). O.M. is
funded by an EMBO Long-Term Fellowship (ALTF 7-2015), the European
Commission FP7 (Marie Curie Actions, LTFCOFUND2013, GA-2013-609409) and
the Swiss National Science Foundation (P2ZHP3_158709). S.R.H. is funded by
the Government of Spain (MINECO, RYC-2016-21395 and SAF2015-71589-P).
A.P.J’s laboratory is supported by the UK Medical Research Council (MRC University Unit grant U127527202). J.L.G.P’s laboratory is supported by CICEFEDER-
P12-CTS-2256, Plan Nacional de I+D+I 2008-2011 and 2013-2016 (FISFEDER-
PI14/02152), PCIN-2014-115-ERA-NET NEURON II, the European
Research Council (ERC-Consolidator ERC-STG-2012-233764), by an International
Early Career Scientist grant from the Howard Hughes Medical Institute
(IECS-55007420), by The Wellcome Trust-University of Edinburgh Institutional
Strategic Support Fund (ISFF2) and by a private donation from Ms Francisca
Serrano (Trading y Bolsa para Torpes, Granada, Spain)
Engineered LINE-1 retrotransposition in nondividing human neurons
Half the human genome is made of transposable elements (TEs), whose ongoing activity continues to impact our genome. LINE-1 (or L1) is an autonomous non-LTR retrotransposon in the human genome, comprising 17% of its genomic mass and containing an average of 80-100 active L1s per average genome that provide a source of inter-individual variation. New LINE-1 insertions are thought to accumulate mostly during human embryogenesis. Surprisingly, the activity of L1s can further impact the somatic human brain genome. However, it is currently unknown whether L1 can retrotranspose in other somatic healthy tissues or if L1 mobilization is restricted to neuronal precursor cells (NPCs) in the human brain. Here, we took advantage of an engineered L1 retrotransposition assay to analyze L1 mobilization rates in human mesenchymal (MSCs) and hematopoietic (HSCs) somatic stem cells. Notably, we have observed that L1 expression and engineered retrotransposition is much lower in both MSCs and HSCs when compared to NPCs. Remarkably, we have further demonstrated for the first time that engineered L1s can retrotranspose efficiently in mature nondividing neuronal cells. Thus, these findings suggest that the degree of somatic mosaicism and the impact of L1 retrotransposition in the human brain is likely much higher than previously thought.We thank current members of the J.L.G.-P. laboratory for helpful discussions. We also thank Drs. Geoffrey Faulkner (Mater Research, Australia) and John V. Moran (University of Michigan) for sharing unpublished data and for critical input during the project; Ms. Raquel Marrero (Microscopy Unit, Genyo) for technical support; Simon Mendez-Ferrer (CNIC, Spain) for providing total RNA isolated from human mesenspheres; Dr. Oliver Weichenrieder (Max-Planck, Tubingen, Germany) for providing a polyclonal L1-ORF1p antibody; and Dr. Aurelien Doucet (IRCAN, Nice, France) for providing a plasmid containing an UBC-driven EGFP retrotransposition indicator cassette. J.L.G. was funded by the US Department of Defense, Breast Cancer Research Program (award #BC051386), the National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (1R03NS087290-01), and the ALS Therapy Alliance (2013-F-067). A.M. has been partially funded by a Marie Curie IRG project (FP7-PEOPLE-2007-4-3-IRG: SOMATIC LINE-1). J.L.G.-P's laboratory is supported by CICE-FEDER-P09-CTS-4980, CICE-FEDER-P12-CTS-2256, Plan Nacional de I+D+I 2008–2011 and 2013–2016 (FIS-FEDER-PI11/01489 and FIS-FEDER-PI14/02152), PCIN-2014-115-ERA-NET NEURON II, the European Research Council (ERC-Consolidator ERC-STG-2012-233764), by an International Early Career Scientist grant from the Howard Hughes Medical Institute (IECS-55007420), and by The Wellcome Trust–University of Edinburgh Institutional Strategic Support Fund (ISFF2).S
A strategy for scaling up access to comprehensive care in adults with Chagas disease in endemic countries: The Bolivian Chagas Platform
BACKGROUND: Bolivia has the highest prevalence of Chagas disease
(CD) in the world (6.1%), with more than 607,186 people with
Trypanosoma cruzi infection, most of them adults. In Bolivia CD
has been declared a national priority. In 2009, the Chagas
National Program (ChNP) had neither a protocol nor a clear
directive for diagnosis and treatment of adults. Although
programs had been implemented for congenital transmission and
for acute cases, adults remained uncovered. Moreover, health
professionals were not aware of treatment recommendations aimed
at this population, and research on CD was limited; it was
difficult to increase awareness of the disease, understand the
challenges it presented, and adapt strategies to cope with it.
Simultaneously, migratory flows that led Bolivian patients with
CD to Spain and other European countries forced medical staff to
look for solutions to an emerging problem. INTERVENTION: In this
context, thanks to a Spanish international cooperation
collaboration, the Bolivian platform for the comprehensive care
of adults with CD was created in 2009. Based on the
establishment of a vertical care system under the umbrella of
ChNP general guidelines, six centres specialized in CD
management were established in different epidemiological
contexts. A common database, standardized clinical forms, a and
a protocolized attention to adults patients, together with
training activities for health professionals were essential for
the model success. With the collaboration and knowledge transfer
activities between endemic and non-endemic countries, the
platform aims to provide care, train health professionals, and
create the basis for a future expansion to the National Health
System of a proven model of care for adults with CD. RESULTS:
From 2010 to 2015, a total of 26,227 patients were attended by
the Platform, 69% (18,316) were diagnosed with T. cruzi, 8,567
initiated anti-parasitic treatment, more than 1,616 health
professionals were trained, and more than ten research projects
developed. The project helped to increase the number of adults
with CD diagnosed and treated, produce evidence-based clinical
practice guidelines, and bring about changes in policy that will
increase access to comprehensive care among adults with CD. The
ChNP is now studying the Platform's health care model to adapt
and implement it nationwide. CONCLUSIONS: This strategy provides
a solution to unmet demands in the care of patients with CD,
improving access to diagnosis and treatment. Further scaling up
of diagnosis and treatment will be based on the expansion of the
model of care to the NHS structures. Its sustainability will be
ensured as it will build on existing local resources in Bolivia.
Still human trained resources are scarce and the high staff
turnover in Bolivia is a limitation of the model. Nevertheless,
in a preliminary two-years-experience of scaling up this model,
this limitations have been locally solved together with the
health local authorities
Symmetry Breakdown in Franckeite: Spontaneous Strain, Rippling, and Interlayer Moire
Franckeite is a naturally occurring layered mineral with a structure composed of alternating stacks of SnS2-like and PbS-like layers. Although this superlattice is composed of a sequence of isotropic two-dimensional layers, it exhibits a spontaneous rippling that makes the material structurally anisotropic. We demonstrate that this rippling comes hand in hand with an inhomogeneous in-plane strain profile and anisotropic electrical, vibrational, and optical properties. We argue that this symmetry breakdown results from a spatial modulation of the van der Waals interaction between layers due to the SnS2-like and PbS-like lattices incommensurability
Circulating concentrations of free triiodothyronine are associated with central adiposity and cardiometabolic risk factors in young euthyroid adults
Thyroid dysfunction is associated with classic cardiometabolic risk factors in humans. However, this relationship remains unclear in young euthyroid adults. The present work examines the associations of circulating thyroid hormones (THs) and thyroid-stimulating hormone (TSH) concentrations with body composition and cardiometabolic risk factors in young euthyroid adults. A total of 106 sedentary, euthyroid adults (72 women; 22 +/- 2 years old) participated in this cross-sectional study. THs and TSH serum concentrations were determined in fasting conditions (6 h). Body composition (fat mass (FM), lean mass (LM), and visceral adipose tissue (VAT)) was determined by dual-energy X-ray absorptiometry, anthropometric parameters (weight, height, and waist circumference) were measured, and neck adipose tissue mass was quantified through computed tomography (CT) scanning. Cardiometabolic risk factors including fasting glucose and lipid metabolism markers, hepatic phosphatase and transaminases, and blood pressure were also assessed. Free triiodothyronine (FT3) concentration was positively associated with body mass index, LM, VAT, and waist circumference (all P <= 0.038). FT3 was also associated with glucose, insulin, HOMA-IR, fatty liver index, and blood pressure (all P < 0.024). All the associations were attenuated when adjusting for sex. In contrast, we found no associations of TSH or free thyroxine with any body composition parameter or cardiometabolic risk factors. In conclusion, FT3 is associated with central adiposity and cardiometabolic risk factors including insulin resistance, fatty liver index, and mean, systolic and diastolic blood pressure in young euthyroid adults. ClinicalTrials.gov identifier: NCT02365129
Automatic Selection of Molecular Descriptors using Random Forest: Application to Drug Discovery
The optimal selection of chemical features (molecular descriptors) is an essential pre-processing step for the efficient application of computational intelligence techniques in virtual screening for identification of bioactive molecules in drug discovery. The selection of molecular descriptors has key influence in the accuracy of affinity prediction. In order to improve this prediction, we examined a Random Forest (RF)-based approach to automatically select molecular descriptors of training data for ligands of kinases, nuclear hormone receptors, and other enzymes. The reduction of features to use during prediction dramatically reduces the computing time over existing approaches and consequently permits the exploration of much larger sets of experimental data. To test the validity of the method, we compared the results of our approach with the ones obtained using manual feature selection in our previous study (Perez-Sanchez et al., 2014). The main novelty of this work in the field of drug discovery is the use of RF in two different ways: feature ranking and dimensionality reduction, and classification using the automatically selected feature subset. Our RF-based method out-performs classification results provided by Support Vector Machine (SVM) and Neural Networks (NN) approaches
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