Ecosystem CO2 release driven by wind occurs in drylands at global scale.

Subterranean ventilation is a non-diffusive transport process that provokes the abrupt transfer of CO2 -rich air (previously stored) through water-free soil pores and cracks from the vadose zone to the atmosphere, under high-turbulence conditions. In dryland ecosystems, whose biological carbon exchanges are poorly characterized, it can strongly determine eddy-covariance CO2 fluxes that are used to validate remote sensing products and constrain models of gross primary productivity. Although subterranean ventilation episodes (VE) may occur in arid and semi-arid regions, which are unsung players in the global carbon cycle, little research has focused on the role of VE CO2 emissions in land-atmosphere CO2 exchange. This study shows clear empirical evidence of globally occurring VE. To identify VE, we used in situ quality-controlled eddy-covariance open data of carbon fluxes and ancillary variables from 145 sites in different open land covers (grassland, cropland, shrubland, savanna, and barren) across the globe. We selected the analyzed database from the FLUXNET2015, AmeriFlux, OzFlux, and AsiaFlux networks. To standardize the analysis, we designed an algorithm to detect CO2 emissions produced by VE at all sites considered in this study. Its main requirement is the presence of considerable and non-spurious correlation between the friction velocity (i.e., turbulence) and CO2 emissions. Of the sites analyzed, 34% exhibited the occurrence of VE. This vented CO2 emerged mainly from arid ecosystems (84%) and sites with hot and dry periods. Despite some limitations in data availability, this research demonstrates that VE-driven CO2 emissions occur globally. Future research should seek a better understanding of its drivers and the improvement of partitioning models, to reduce uncertainties in estimated biological CO2 exchanges and infer their contribution to the global net ecosystem carbon balance.

Magnetic properties of nanoparticles as a function of their spatial distribution on liposomes and cells.

The aggregation processes of magnetic nanoparticles in biosystems are analysed by comparing the magnetic properties of three systems with different spatial distributions of the nanoparticles. The first one is iron oxide nanoparticles (NPs) of 14 nm synthesized by coprecipitation with two coatings, (3-aminopropyl)trimethoxysilane (APS) and dimercaptosuccinic acid (DMSA). The second one is liposomes with encapsulated nanoparticles, which have different configurations depending on the NP coating (NPs attached to the liposome surface or encapsulated in its aqueous volume). The last system consists of two cell lines (Pan02 and Jurkat) incubated with the NPs. Dynamic magnetic behaviour (AC) was analysed in liquid samples, maintaining their colloidal properties, while quasi-static (DC) magnetic measurements were performed on lyophilised samples. AC measurements provide a direct method for determining the effect of the environment on the magnetization relaxation of nanoparticles. Thus, the imaginary (χ'') component shifts to lower frequencies as the aggregation state increases from free nanoparticles to those attached or embedded into liposomes in cell culture media and more pronounced when internalized by the cells. DC magnetization curves show no degradation of the NPs after interaction with biosystems in the analysed timescale. However, the blocking temperature is shifted to higher temperatures for the nanoparticles in contact with the cells, regardless of the location, the incubation time, the cell line and the nanoparticle coating, supporting AC susceptibility data. These results indicate that the simple fact of being in contact with the cells makes the nanoparticles aggregate in a non-controlled way, which is not the same kind of aggregation caused by the contact with the cell medium nor inside liposomes.

Extension of human lncRNA transcripts by RACE coupled with long-read high-throughput sequencing (RACE-Seq).

Long non-coding RNAs (lncRNAs) constitute a large, yet mostly uncharacterized fraction of the mammalian transcriptome. Such characterization requires a comprehensive, high-quality annotation of their gene structure and boundaries, which is currently lacking. Here we describe RACE-Seq, an experimental workflow designed to address this based on RACE (rapid amplification of cDNA ends) and long-read RNA sequencing. We apply RACE-Seq to 398 human lncRNA genes in seven tissues, leading to the discovery of 2,556 on-target, novel transcripts. About 60% of the targeted loci are extended in either 5' or 3', often reaching genomic hallmarks of gene boundaries. Analysis of the novel transcripts suggests that lncRNAs are as long, have as many exons and undergo as much alternative splicing as protein-coding genes, contrary to current assumptions. Overall, we show that RACE-Seq is an effective tool to annotate an organism's deep transcriptome, and compares favourably to other targeted sequencing techniques.

267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation.

Recent results from large-scale genomic projects suggest that allele frequencies, which are highly relevant for medical purposes, differ considerably across different populations. The need for a detailed catalog of local variability motivated the whole-exome sequencing of 267 unrelated individuals, representative of the healthy Spanish population. Like in other studies, a considerable number of rare variants were found (almost one-third of the described variants). There were also relevant differences in allelic frequencies in polymorphic variants, including ∼10,000 polymorphisms private to the Spanish population. The allelic frequencies of variants conferring susceptibility to complex diseases (including cancer, schizophrenia, Alzheimer disease, type 2 diabetes, and other pathologies) were overall similar to those of other populations. However, the trend is the opposite for variants linked to Mendelian and rare diseases (including several retinal degenerative dystrophies and cardiomyopathies) that show marked frequency differences between populations. Interestingly, a correspondence between differences in allelic frequencies and disease prevalence was found, highlighting the relevance of frequency differences in disease risk. These differences are also observed in variants that disrupt known drug binding sites, suggesting an important role for local variability in population-specific drug resistances or adverse effects. We have made the Spanish population variant server web page that contains population frequency information for the complete list of 170,888 variant positions we found publicly available (http://spv.babelomics.org/), We show that it if fundamental to determine population-specific variant frequencies to distinguish real disease associations from population-specific polymorphisms.

A randomized study to compare bioactive titanium stents and everolimus-eluting stents in diabetic patients (TITANIC XV): 1-year results.

INTRODUCTION AND OBJECTIVES: Up to 25% of patients who undergo a percutaneous coronary intervention show some limitation in the use of drug-eluting stents. The aim of this study was to evaluate if titanium-nitride-oxide-coated stents could be a good alternative to everolimus-eluting stents in diabetic patients. METHODS: A total of 173 diabetic patients with lesions at moderate risk of restenosis (exclusion criteria: diameter < 2.5 mm or length > 28 mm in vessels < 3mm, chronic occlusion) were randomized to a titanium group (83 patients) or an everolimus group (90 patients). RESULTS: Baseline characteristics were well balanced; 28.3% of patients were insulin dependent. At 1 year, the incidence of major adverse cardiac events (death, nonfatal myocardial infarction, stroke, or repeat target vessel revascularization) was significantly higher in the titanium group than in the everolimus group (total, 14.5% vs 4.4%; P = .02; noninsulin-dependent subgroup, 9.7% vs 3.2%; P = .14; insulin-dependent subgroup, 28.6% vs 7.1%; P = .04). The incidence of death, nonfatal myocardial infarction, stroke, or any revascularization was 16.9% in the titanium group and 7.8% in the everolimus group (P = .06). Target lesion and vessel revascularizations occurred in 8.4% compared with 3.3% (P = .15) and in 13.3% compared with 3.3% (P = .01) in the titanium and everolimus groups, respectively. Angiographic follow-up at 9 months showed significantly less late lumen loss in the everolimus group (in-segment, 0.52 [standard deviation, 0.58) mm vs -0.05 [0.32] mm; in-stent, 0.76 [0.54] mm vs 0.13 [0.31] mm; P < .0001). CONCLUSIONS: The everolimus-eluting stent is superior to the titanium stent for clinical and angiographic end points in diabetic patients with lesions at moderate risk of restenosis.

Ecological functioning in grass-shrub Mediterranean ecosystems measured by eddy covariance.

Climate change may alter ecosystem functioning, as assessed via the net carbon (C) exchange (NEE) with the atmosphere, composed of the biological processes photosynthesis (GPP) and respiration (R(eco)). In addition, in semi-arid Mediterranean ecosystems, a significant fraction of respired CO2 is stored in the vadose zone and emitted afterwards by subsoil ventilation (VE), contributing also to NEE. Such conditions complicate the prediction of NEE for future change scenarios. To evaluate the possible effects of climate change on annual NEE and its underlying processes (GPP, R(eco) and VE) we present, over a climate/altitude range, the annual and interannual variability of NEE, GPP, R(eco) and VE in three Mediterranean sites. We found that annual NEE varied from a net source of around 130 gC m(-2) in hot and arid lowlands to a net sink of similar magnitude for alpine meadows (above 2,000 m a.s.l) that are less water stressed. Annual net C fixation increased because of increased GPP during intermittent and several growth periods occurring even during winter, as well as due to decreased VE. In terms of interannual variability, the studied subalpine site behaved as a neutral C sink (from emission of 49 to fixation of 30 gC m(-2) year(-1)), with precipitation as the main factor controlling annual GPP and R(eco). Finally, the importance of VE as 0-23% of annual NEE is highlighted, indicating that this process could shift some Mediterranean ecosystems from annual C sinks to sources.

ngsCAT: a tool to assess the efficiency of targeted enrichment sequencing.

MOTIVATION: Targeted enrichment sequencing by next-generation sequencing is a common approach to interrogate specific loci or the whole exome in the human genome. The efficiency and the lack of bias in the enrichment process need to be assessed as a quality control step before performing downstream analysis of the sequence data. Tools that can report on the sensitivity, specificity, uniformity and other enrichment-specific features are needed. RESULTS: We have implemented the next-generation sequencing data Capture Assessment Tool (ngsCAT), a tool that takes the information of the mapped reads and the coordinates of the targeted regions as input files, and generates a report with metrics and figures that allows the evaluation of the efficiency of the enrichment process. The tool can also take as input the information of two samples allowing the comparison of two different experiments. AVAILABILITY AND IMPLEMENTATION: Documentation and downloads for ngsCAT can be found at http://www.bioinfomgp.org/ngscat.

Whole-exome sequencing identifies novel compound heterozygous mutations in USH2A in Spanish patients with autosomal recessive retinitis pigmentosa.

PURPOSE: Retinitis pigmentosa (RP) is an inherited retinal dystrophy characterized by extreme genetic and clinical heterogeneity. Thus, the diagnosis is not always easily performed due to phenotypic and genetic overlap. Current clinical practices have focused on the systematic evaluation of a set of known genes for each phenotype, but this approach may fail in patients with inaccurate diagnosis or infrequent genetic cause. In the present study, we investigated the genetic cause of autosomal recessive RP (arRP) in a Spanish family in which the causal mutation has not yet been identified with primer extension technology and resequencing. METHODS: We designed a whole-exome sequencing (WES)-based approach using NimbleGen SeqCap EZ Exome V3 sample preparation kit and the SOLiD 5500×l next-generation sequencing platform. We sequenced the exomes of both unaffected parents and two affected siblings. Exome analysis resulted in the identification of 43,204 variants in the index patient. All variants passing filter criteria were validated with Sanger sequencing to confirm familial segregation and absence in the control population. In silico prediction tools were used to determine mutational impact on protein function and the structure of the identified variants. RESULTS: Novel Usher syndrome type 2A (USH2A) compound heterozygous mutations, c.4325T>C (p.F1442S) and c.15188T>G (p.L5063R), located in exons 20 and 70, respectively, were identified as probable causative mutations for RP in this family. Family segregation of the variants showed the presence of both mutations in all affected members and in two siblings who were apparently asymptomatic at the time of family ascertainment. Clinical reassessment confirmed the diagnosis of RP in these patients. CONCLUSIONS: Using WES, we identified two heterozygous novel mutations in USH2A as the most likely disease-causing variants in a Spanish family diagnosed with arRP in which the cause of the disease had not yet been identified with commonly used techniques. Our data reinforce the clinical role of WES in the molecular diagnosis of highly heterogeneous genetic diseases where conventional genetic approaches have previously failed in achieving a proper diagnosis.

Late gadolinium enhancement-cardiovascular magnetic resonance identifies coronary artery disease as the aetiology of left ventricular dysfunction in acute new-onset congestive heart failure.

AIMS: We evaluated the ability of late gadolinium enhancement (LGE) using cardiovascular magnetic resonance (CMR) to identify acute new-onset heart failure (HF) with left ventricular systolic dysfunction (LVSD), whether or not in relation to underlying coronary artery disease (CAD), in patients with no clinical evidence of associated ischaemic cardiomyopathy. METHODS AND RESULTS: Hundred consecutive patients admitted with acute new-onset decompensated HF and EF <40%, with no clinical or electrocardiographic data suggestive of CAD. The patients were classified according to the presence or absence of significant CAD (stenosis > or =70% in at least one major vessel). Twenty-one patients (21%) had significant CAD. Seventy-nine (79%) had no lesions. Eighteen of the 21 patients (85%) with CAD had subendocardial/transmural LGE. In the diagnosis of CAD, LGE has a sensitivity of 85.7% (95% CI, 80-91) and specificity of 92.4% (95% CI, 87-96), respectively, with a negative predictive value of 96% (95% CI, 90-99). It has an area under the receiver operating characteristic curve of 0.906 (95% CI, 0.814-0.998). CONCLUSION: In patients with new-onset HF and LVSD for whom there are no clinical and exploratory data suggestive of ischaemic heart disease, CMR with LGE is an excellent means of ruling out significant CAD and is a valid alternative to angiography.

[Long-term clinical and angiographic follow-up of drug-eluting stents in patients with ST-elevation acute myocardial infarction]. / Resultados clínicos y angiográficos tardíos de stents liberadores de fármacos en pacientes con infarto agudo de miocardio con elevación del ST.

INTRODUCTION AND OBJECTIVES: Drug-eluting stents (DES) have proven to be effective in reducing the rate of restenosis and have, therefore, been incorporated into the treatment of patients with ST-elevation acute myocardial infarction (STEMI). The aim of this study was to investigate long-term clinical and angiographic outcomes following the use of DESs in patients with STEMI. METHODS: A prospective study involving clinical and angiographic follow-up was performed in 81 patients with STEMI who underwent percutaneous coronary intervention including DES implantation. This group was compared with 82 patients with similar characteristics who were treated with bare-metal stents (BMS) in an earlier period. RESULTS: At one year, there was no significant difference between the groups in the mortality (2.5% in the DES group vs 7.3% in the BMS group; P=.15) or reinfarction rate (4.8% in the DES group vs. 4.8% in the BMS group; P=.98). The target lesion revascularization rate was significantly lower in the DES group (8.6% vs 23.2% in the BMS group; P=.001), as was the restenosis rate (13.8% vs. 30.9% in the BMS group; P=.02). Acute or subacute stent thrombosis was diagnosed in five patients (3 with a DES and 2 with a BMS; P=.64), and one late stent thrombosis was detected after a year, in a sirolimus-eluting stent. CONCLUSIONS: Implantation of a DES in patients with STEMI did not result in a reduction in either the mortality or reinfarction rate at 1 year compared with BMS implantation. However, there were reductions in the rates of restenosis and target lesion revascularization. The incidence of thrombosis was similar with the two types of stent.

[Stent thrombosis in the modern era: incidence, outcome and predictive factors]. / Trombosis del stent en la era moderna: incidencia, consecuencias y factores predictores.

Coronary stent thrombosis is a catastrophic complication of percutaneous coronary intervention. Its incidence is reported to be about 1%, though it can occur more frequently in high-risk patients, in high-risk lesions, and in multivessel procedures. We investigated the occurrence of stent thrombosis in 404 consecutive patients in a period when conventional and drug-eluting stents were both being used. We found an overall incidence of 2.23%, a mortality rate of 22.2%, and a non-fatal myocardial infarction rate of 66.6%. Predictors of stent thrombosis were acute myocardial infarction, multiple stent placement, poor ejection fraction, small stent diameter, the presence of residual dissection, and premature discontinuation of clopidogrel.

[Anomalous left coronary artery from the right sinus of Valsalva associated with coronary atheromatosis]. / Arteria coronaria izquierda anómala en el seno de Valsalva derecho asociada a ateromatosis coronaria.

Anomalous origin of the left coronary artery from the right sinus of Valsalva is an anatomical abnormality that is usually associated with myocardial ischemia and sudden death. Although this abnormality may coexist with obstructive atherosclerotic coronary disease, disease is not usually found in the anomalous course of the artery. When this coronary anomaly and obstructive coronary disease are both present, it is difficult to determine the cause of ischemic symptoms. We report a case in which three different diagnostic techniques were used to find the cause of ischemic symptoms in a patient whose left coronary artery originated anomalously in the right sinus of Valsalva and followed a course between the aorta and the pulmonary trunk and who had obstructive atherosclerotic lesions in the right coronary artery. The techniques were conventional angiography, which was used for the initial diagnosis, multislice computerized tomography, which was used to determine the anomalous course of the artery and its relationship with vascular structures, and exercise echocardiography, which was used to evaluate ischemia in the left coronary artery territory after treatment of the stenoses in the right coronary artery.

[Prognostic value of persistent ST-segment elevation after successful primary angioplasty]. / Valor pronóstico de la persistencia del segmento ST elevado después de una angioplastia primaria realizada con éxito.

INTRODUCTION AND OBJECTIVES: A variable percentage of patients with myocardial infarction treated with successful primary angioplasty and restoration of coronary flow show persistent ST-segment elevation, probably due to inadequate cellular reperfusion. We studied if persistent ST-segment elevation was a predictor of worse prognosis. PATIENTS AND METHODS: We comparatively studied the clinical and angiographic results of 116 acute myocardial infarction patients after successful primary angioplasty, which were classified into two groups depending on the persistence (> 50%) or reduction (