Levels of carbonaceous aerosols in remote, rural, urban and industrial sites of Spain

Comunicación presentada en: 2012 European Aerosol Conference (EAC-2012), B-WG01S2P30, celebrada del 2 al 7 de septiembre de 2012 en Granada.This work was funded by the Spanish Ministry of Science and Innovation (VAMOS CGL2010-19464/CLI; DAURE CGL2007-30502-E/CLI, GRACCIE- CSD2007-00067), the Ministry of the Economy Competitivity, the Generalitat de Catalunya, Gobierno de Canarias and Junta de Andalucía

YES1 drives lung cancer growth and progression and predicts sensitivity to dasatinib

Rationale: The characterization of new genetic alterations is essential to assign effective personalized therapies in non–small cell lung cancer (NSCLC). Furthermore, finding stratification biomarkers is essential for successful personalized therapies. Molecular alterations of YES1, a member of the SRC (proto-oncogene tyrosine-protein kinase Src) family kinases (SFKs), can be found in a significant subset of patients with lung cancer. Objectives: To evaluate YES1 (v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1) genetic alteration as a therapeutic target and predictive biomarker of response to dasatinib in NSCLC. Methods: Functional significance was evaluated by in vivo models of NSCLC and metastasis and patient-derived xenografts. The efficacy of pharmacological and genetic (CRISPR [clustered regularly interspaced short palindromic repeats]/Cas9 [CRISPR-associated protein 9]) YES1 abrogation was also evaluated. In vitro functional assays for signaling, survival, and invasion were also performed. The association between YES1 alterations and prognosis was evaluated in clinical samples. Measurements and Main Results: We demonstrated that YES1 is essential for NSCLC carcinogenesis. Furthermore, YES1 overexpression induced metastatic spread in preclinical in vivo models. YES1 genetic depletion by CRISPR/Cas9 technology significantly reduced tumor growth and metastasis. YES1 effects were mainly driven by mTOR (mammalian target of rapamycin) signaling. Interestingly, cell lines and patient-derived xenograft models with YES1 gene amplifications presented a high sensitivity to dasatinib, an SFK inhibitor, pointing out YES1 status as a stratification biomarker for dasatinib response. Moreover, high YES1 protein expression was an independent predictor for poor prognosis in patients with lung cancer. Conclusions: YES1 is a promising therapeutic target in lung cancer. Our results provide support for the clinical evaluation of dasatinib treatment in a selected subset of patients using YES1 status as predictive biomarker for therapy

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung cancer

Single nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We designed a genome-wide association study to characterize individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced non-small cell lung cancer (NSCLC), and we validated our results. We hypothesized that this strategy would enrich the frequencies of the alleles that contribute to the observed traits. We genotyped 2.37 million SNPs in 95 extreme phenotype individuals, that is: heavy smokers that either developed NSCLC at an early age (extreme cases); or did not present NSCLC at an advanced age (extreme controls), selected from a discovery set (n=3631). We validated significant SNPs in 133 additional subjects with extreme phenotypes selected from databases including >39,000 individuals. Two SNPs were validated: rs12660420 (p(combined)=5.66x10(-5); ORcombined=2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (p(combined)=1.02x10(-4); ORcombined=2.57), an intronic variant in ATP10D. We assessed the relevance of both proteins in early-stage NSCLC. PDE10A and ATP10D mRNA expressions correlated with survival in 821 stage I-II NSCLC patients (p=0.01 and p<0.0001). PDE10A protein expression correlated with survival in 149 patients with stage I-II NSCLC (p=0.002). In conclusion, we validated two variants associated with extreme phenotypes of high and low risk of developing tobacco-induced NSCLC. Our findings may allow to identify individuals presenting high and low risk to develop tobacco-induced NSCLC and to characterize molecular mechanisms of carcinogenesis and resistance to develop NSCLC

Combined clinical and genomic signatures for the prognosis of early stage non-small cell lung cancer based on gene copy number alterations

BACKGROUND: The development of a more refined prognostic methodology for early non-small cell lung cancer (NSCLC) is an unmet clinical need. An accurate prognostic tool might help to select patients at early stages for adjuvant therapies. RESULTS: A new integrated bioinformatics searching strategy, that combines gene copy number alterations and expression, together with clinical parameters was applied to derive two prognostic genomic signatures. The proposed methodology combines data from patients with and without clinical data with a priori information on the ability of a gene to be a prognostic marker. Two initial candidate sets of 513 and 150 genes for lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC), respectively, were generated by identifying genes which have both: a) significant correlation between copy number and gene expression, and b) significant prognostic value at the gene expression level in external databases. From these candidates, two panels of 7 (ADC) and 5 (SCC) genes were further identified via semi-supervised learning. These panels, together with clinical data (stage, age and sex), were used to construct the ADC and SCC hazard scores combining clinical and genomic data. The signatures were validated in two independent datasets (n = 73 for ADC, n = 97 for SCC), confirming that the prognostic value of both clinical-genomic models is robust, statistically significant (P = 0.008 for ADC and P = 0.019 for SCC) and outperforms both the clinical models (P = 0.060 for ADC and P = 0.121 for SCC) and the genomic models applied separately (P = 0.350 for ADC and P = 0.269 for SCC). CONCLUSION: The present work provides a methodology to generate a robust signature using copy number data that can be potentially used to any cancer. Using it, we found new prognostic scores based on tumor DNA that, jointly with clinical information, are able to predict overall survival (OS) in patients with early-stage ADC and SCC

Comparative study of atmospheric water-soluble organic aerosols composition in contrasting suburban environments in the Iberian Peninsula Coast

This study investigates the structural composition and major sources of water-soluble organic matter (WSOM) from PM2.5 collected, in parallel, during summer and winter, in two contrasting suburban sites at Iberian Peninsula Coast: Aveiro (Portugal) and Coruña (Spain). PM10 samples were also collected at Coruña for comparison. Ambient concentrations of PM2.5, total nitrogen (TN), and WSOM were higher in Aveiro than in Coruña, with the highest levels found in winter at both locations. In Coruña, concentrations of PM10, TN, and WSOM were higher than those from PM2.5. Regardless of the season, stable isotopic δ13C and δ15N in PM2.5 suggested important contributions of anthropogenic fresh organic aerosols (OAs) at Aveiro. In Coruña, δ13C and δ15N of PM2.5 and PM10 suggests decreased anthropogenic input during summer. Although excitation-emission fluorescence profiles were similar for all WSOM samples, multi-dimensional nuclear magnetic resonance (NMR) spectroscopy confirmed differences in their structural composition, reflecting differences in aging processes and/or local sources between the two locations. In PM2.5 WSOM in Aveiro, the relative distribution of non-exchangeable proton functional groups was in the order: H-C (40-43%) > H-C-C= (31-39%) > H-C-O (12-15%) > Ar-H (5.0-13%). However, in PM2.5 and PM10 WSOM in Coruña, the relative contribution of H-C-O groups (24-30% and 23-29%, respectively) equals and/or surpasses that of H-C-C= (25-26% and 25-29%, respectively), being also higher than those of Aveiro. In both locations, the highest aromatic contents were observed during winter due to biomass burning emissions. The structural composition of PM2.5 and PM10 WSOM in Coruña is dominated by oxygenated aliphatic compounds, reflecting the contribution of secondary OAs from biogenic, soil dust, and minor influence of anthropogenic emissions. In contrast, the composition of PM2.5 WSOM in Aveiro appears to be significantly impacted by fresh and secondary anthropogenic OAs. Marine and biomass burning OAs are important contributors, common to both sites.Xunta de Galicia ( Programa de Consolidación y Estructuración de Unidades de Investigación Competitivas Refs. GRC2013-047 and ED431C 2017/28)publishe

Variability of carbonaceous aerosols in remote, rural, urban and industrial environments in Spain: implications for air quality policy

We interpret here the variability of levels of carbonaceous aerosols based on a 12 yr database from 78 monitoring stations across Spain specially compiled for this article. Data did not evidence any spatial trends of carbonaceous aerosols across the country. Conversely, results show marked differences in average concentrations from the cleanest, most remote sites (around 1 μg m-3 of non-mineral carbon (nmC), mostly made of organic carbon (OC) with very little elemental carbon (EC), around 0.1 μg m-3; OC/EC Combining double low line 12-15), to the highly polluted major cities (8-10 μg m-3 of nmC; 3-4 μg m-3 of EC; 4-5 μg m-3 of OC; OC/EC Combining double low line 1-2). Thus, urban (and very specific industrial) pollution was found to markedly increase levels of carbonaceous aerosols in Spain, with much lower impact of biomass burning and of biogenic emissions. Correlations between yearly averaged OC/EC and EC concentrations adjust very well to a potential equation (OC Combining double low line 3.37 EC0.326, R2 Combining double low line 0.8). A similar equation is obtained when including average concentrations obtained at other European sites (OC Combining double low line 3.60EC0.491, R2 Combining double low line 0.7). A clear seasonal variability in OC and EC concentrations was detected. Both OC and EC concentrations were higher during winter at the traffic and urban sites, but OC increased during the warmer months at the rural sites. Hourly equivalent black carbon (EBC) concentrations at urban sites accurately depict road traffic contributions, varying with distance from road, traffic volume and density, mixing-layer height and wind speed. Weekday urban rush-hour EBC peaks are mimicked by concentrations of primary gaseous emissions from road traffic, whereas a single midday peak is characteristic of remote and rural sites. Decreasing annual trends for carbonaceous aerosols were observed between 1999 and 2011 at a large number of stations, probably reflecting the impact of the EURO4 and EURO5 standards in reducing the diesel PM emissions. This has resulted in some cases in an increasing trend for NO2/(OC+ EC) ratios as these standards have been much less effective for the abatement of NOx exhaust emissions in passenger diesel cars. This study concludes that EC, EBC, and especially nmC and OC+ EC are very good candidates for new air quality standards since they cover both emission impact and health-related issues.This study was supported by the Ministry of Agriculture, Food and the Environment of Spain, the Ministry of Economy and Competitivity (MINECO) of Spain and FEDER funds under the projects VAMOS (CGL2010-19464/CLI), PRISMA (CGL2012-39623-C02-01), GRACCIE (CSD 200700067), POLLINDUST (CGL2011-26259) and UHU (CGL201128025); and by AGAUR-Generalitat de Catalunya (2009 SGR 00008) and LIFE+ AIRUSE (LIFE11-ENV/ES/000584). The Montseny site forms part of the ACTRIS network (European Union Seventh Framework Programme (FP7/2007-2013) project no. 262254), formerly EUSAAR (EUSAAR R113-CT-2006-026140). Funding was also received for the Andaluc´ıa sites from projects 2007-RNM027329 and 2011-RNM7800 (Department of Innovation Science and Enterprise, Andalusia Autonomous Government) M. C. Minguillón was funded by the JAE-Doc CSIC programme, co-funded by the European Social Fund (ESF).publishe

American palm ethnomedicine: A meta-analysis

<p>Abstract</p> <p>Background</p> <p>Many recent papers have documented the phytochemical and pharmacological bases for the use of palms (<it>Arecaceae</it>) in ethnomedicine. Early publications were based almost entirely on interviews that solicited local knowledge. More recently, ethnobotanically guided searches for new medicinal plants have proven more successful than random sampling for identifying plants that contain biodynamic ingredients. However, limited laboratory time and the high cost of clinical trials make it difficult to test all potential medicinal plants in the search for new drug candidates. The purpose of this study was to summarize and analyze previous studies on the medicinal uses of American palms in order to narrow down the search for new palm-derived medicines.</p> <p>Methods</p> <p>Relevant literature was surveyed and data was extracted and organized into medicinal use categories. We focused on more recent literature than that considered in a review published 25 years ago. We included phytochemical and pharmacological research that explored the importance of American palms in ethnomedicine.</p> <p>Results</p> <p>Of 730 species of American palms, we found evidence that 106 species had known medicinal uses, ranging from treatments for diabetes and leishmaniasis to prostatic hyperplasia. Thus, the number of American palm species with known uses had increased from 48 to 106 over the last quarter of a century. Furthermore, the pharmacological bases for many of the effects are now understood.</p> <p>Conclusions</p> <p>Palms are important in American ethnomedicine. Some, like <it>Serenoa repens </it>and <it>Roystonea regia</it>, are the sources of drugs that have been approved for medicinal uses. In contrast, recent ethnopharmacological studies suggested that many of the reported uses of several other palms do not appear to have a strong physiological basis. This study has provided a useful assessment of the ethnobotanical and pharmacological data available on palms.</p

Global maps of soil temperature.

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km &lt;sup&gt;2&lt;/sup&gt; resolution for 0-5 and 5-15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km &lt;sup&gt;2&lt;/sup&gt; pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications

Global maps of soil temperature

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0–5 and 5–15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world\u27s major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (−0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications