Influence of climatic variables on crown condition in pine forests of Northern Spain

Producción CientíficaThe aim of this study was to find relationships between crown condition and some climatic parameters to identify which are those having a main influence on crown condition, and how this influence is shown in the tree (crown transparency), and to contribute to the understanding of how these parameters will affect under future climate change scenarios

HIF pathway and c-Myc as biomarkers for response to sunitinib in metastatic clear-cell renal cell carcinoma

Clear-cell renal cell carcinoma (ccRCC) is a heterogeneous disease with a different clinical behavior and response to targeted therapies. Differences in hypoxia-inducible factor (HIF) expression have been used to classify von Hippel-Lindau gene (VHL)-deficient ccRCC tumors. c-Myc may be driving proliferation in HIF-2α-expressing tumors in a growth factor-independent manner. To explore the HIF-1α, HIF-2α and c-Myc baseline expression as potential predictors of sunitinib outcome as well as the effectiveness and safety with sunitinib in patients with metastatic ccRCC in routine clinical practice. This was an observational and prospective study involving 10 Spanish hospitals. Formalin-fixed, paraffin-embedded primary tumor samples from metastatic ccRCC patients who received sunitinib as first-line treatment were analyzed. Association between biomarker expression and sunitinib treatment outcomes was evaluated. Kaplan-Meier method was applied to measure progression-free survival (PFS) and overall survival. Eighty-one patients were included: median PFS was 10.8 months (95% CI: 7.4-13.5 months), median overall survival was 21.8 months (95% CI: 14.7-29.8 months) and objective response rate was 40.7%, with 7.4% of patients achieving a complete response. Molecular marker staining was performed in the 69 available tumor samples. Significant association with lower PFS was identified for double c-Myc/HIF-2α-positive staining tumors (median 4.3 vs 11.5 months, hazard ratio =2.64, 95% CI: 1.03-6.80, P =0.036). A trend toward a lower PFS was found in positive c-Myc tumors (median 5.9 vs 10.9 months, P =0.263). HIF-1α and HIF-2α expression levels were not associated with clinical outcome. These preliminary results suggest that predictive subgroups might be defined based on biomarkers such as c-Myc/HIF-2α. Further validation with more patients will be needed in order to confirm it. Outcomes with sunitinib in metastatic ccRCC in daily clinical practice resemble those obtained in clinical trials

The stellar and sub-stellar IMF of simple and composite populations

The current knowledge on the stellar IMF is documented. It appears to become top-heavy when the star-formation rate density surpasses about 0.1Msun/(yr pc^3) on a pc scale and it may become increasingly bottom-heavy with increasing metallicity and in increasingly massive early-type galaxies. It declines quite steeply below about 0.07Msun with brown dwarfs (BDs) and very low mass stars having their own IMF. The most massive star of mass mmax formed in an embedded cluster with stellar mass Mecl correlates strongly with Mecl being a result of gravitation-driven but resource-limited growth and fragmentation induced starvation. There is no convincing evidence whatsoever that massive stars do form in isolation. Various methods of discretising a stellar population are introduced: optimal sampling leads to a mass distribution that perfectly represents the exact form of the desired IMF and the mmax-to-Mecl relation, while random sampling results in statistical variations of the shape of the IMF. The observed mmax-to-Mecl correlation and the small spread of IMF power-law indices together suggest that optimally sampling the IMF may be the more realistic description of star formation than random sampling from a universal IMF with a constant upper mass limit. Composite populations on galaxy scales, which are formed from many pc scale star formation events, need to be described by the integrated galactic IMF. This IGIMF varies systematically from top-light to top-heavy in dependence of galaxy type and star formation rate, with dramatic implications for theories of galaxy formation and evolution.Comment: 167 pages, 37 figures, 3 tables, published in Stellar Systems and Galactic Structure, Vol.5, Springer. This revised version is consistent with the published version and includes additional references and minor additions to the text as well as a recomputed Table 1. ISBN 978-90-481-8817-

Identifying Signatures of Natural Selection in Tibetan and Andean Populations Using Dense Genome Scan Data

High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. Although these responses have been well characterized physiologically, their underlying genetic basis remains unknown. We performed a genome scan to identify genes showing evidence of adaptation to hypoxia. We looked across each chromosome to identify genomic regions with previously unknown function with respect to altitude phenotypes. In addition, groups of genes functioning in oxygen metabolism and sensing were examined to test the hypothesis that particular pathways have been involved in genetic adaptation to altitude. Applying four population genetic statistics commonly used for detecting signatures of natural selection, we identified selection-nominated candidate genes and gene regions in these two populations (Andeans and Tibetans) separately. The Tibetan and Andean patterns of genetic adaptation are largely distinct from one another, with both populations showing evidence of positive natural selection in different genes or gene regions. Interestingly, one gene previously known to be important in cellular oxygen sensing, EGLN1 (also known as PHD2), shows evidence of positive selection in both Tibetans and Andeans. However, the pattern of variation for this gene differs between the two populations. Our results indicate that several key HIF-regulatory and targeted genes are responsible for adaptation to high altitude in Andeans and Tibetans, and several different chromosomal regions are implicated in the putative response to selection. These data suggest a genetic role in high-altitude adaption and provide a basis for future genotype/phenotype association studies necessary to confirm the role of selection-nominated candidate genes and gene regions in adaptation to altitude

HIF pathway and c-Myc as biomarkers for response to sunitinib in metastatic clear-cell renal cell carcinoma

P Maroto,1 E Esteban,2 E Fernández Parra,3 MJ Mendez-Vidal,4 M Domenech,5 B Pérez-Valderrama,6 V Calderero,7 JL Pérez-Gracia,8 E Grande,9 F Algaba10 1Department of Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, 2Department of Oncology, Nuevo HUCA, Oviedo, 3Department of Oncology, H. U. Nuestra Señora de Valme, Sevilla, 4Department of Oncology, H. U. Reina Sofía, Córdoba, 5Department of Oncology, Hospital de Althaia Xarxa Asistencial Manresa, Barcelona, 6Department of Oncology, H. U. Virgen del Rocio, Sevilla, 7Department of Oncology, H. Fundación Miguel Servet, Zaragoza, 8Department of Oncology, Clinica Universitaria de Pamplona, Pamplona, 9Department of Oncology, H. Ramón y Cajal, Madrid, 10Pathology Unit, Fundació Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain Background: Clear-cell renal cell carcinoma (ccRCC) is a heterogeneous disease with a different clinical behavior and response to targeted therapies. Differences in hypoxia-inducible factor (HIF) expression have been used to classify von Hippel–Lindau gene (VHL)-deficient ccRCC tumors. c-Myc may be driving proliferation in HIF-2α-expressing tumors in a growth factor-independent manner. Objective: To explore the HIF-1α, HIF-2α and c-Myc baseline expression as potential predictors of sunitinib outcome as well as the effectiveness and safety with sunitinib in patients with metastatic ccRCC in routine clinical practice. Methods: This was an observational and prospective study involving 10 Spanish hospitals. Formalin-fixed, paraffin-embedded primary tumor samples from metastatic ccRCC patients who received sunitinib as first-line treatment were analyzed. Association between biomarker expression and sunitinib treatment outcomes was evaluated. Kaplan–Meier method was applied to measure progression-free survival (PFS) and overall survival. Results: Eighty-one patients were included: median PFS was 10.8 months (95% CI: 7.4–13.5 months), median overall survival was 21.8 months (95% CI: 14.7–29.8 months) and objective response rate was 40.7%, with 7.4% of patients achieving a complete response. Molecular marker staining was performed in the 69 available tumor samples. Significant association with lower PFS was identified for double c-Myc/HIF-2α-positive staining tumors (median 4.3 vs 11.5 months, hazard ratio =2.64, 95% CI: 1.03–6.80, P=0.036). A trend toward a lower PFS was found in positive c-Myc tumors (median 5.9 vs 10.9 months, P=0.263). HIF-1α and HIF-2α expression levels were not associated with clinical outcome.Conclusion: These preliminary results suggest that predictive subgroups might be defined based on biomarkers such as c-Myc/HIF-2α. Further validation with more patients will be needed in order to confirm it. Outcomes with sunitinib in metastatic ccRCC in daily clinical practice resemble those obtained in clinical trials. Keywords: c-Myc, clear-cell renal cell carcinoma, HIF, sunitinib&nbsp

Analysis of the precipitation and cloudiness associated with COLs occurrence in the Iberian Peninsula

The Iberian Peninsula is one of the regions in the world with higher occurrence of cut-off low systems (COL). The aim of this paper is to analyse the weather events (rainfall and cloudiness layer) associated to COLs in the Iberian Peninsula with tools not previously used: (a) the use of the new multidecadal COLs database developed by Nieto et al (2005) that permit us to study a 41 years period (1958-1998), (b) the checking of the expected weather events (rainfall and cloudiness layer) associated with COLs in a conceptual model (Winkler et al, 2005) and (c) the extensive use of radiosoundings to analyse convective instability in areas inside and close to the COL. Two points of view are used to make the analysis: (1) a source oriented method, when a particular COL is followed and its associated precipitation and cloudiness is analysed over four quadrants in which Iberia was divided and (2) a receptor oriented method, when the precipitation associated to COLs is analysed in given areas, defined by patterns of precipitation. Results reveal that the precipitation and cloudiness patterns associated to COLs in the conceptual model reproduce quite well the main characteristics found over the Iberian Peninsula. The generalized idea that most of the COLs produce intense convective rainfall is show to be misleading. Convective phenomena are important usually when the centre of the COL is located on the Mediterranean region. Most of the rainfall associated with COLs comes from the baroclinic shield; specially in cases located over the west half of the Iberian Peninsula. It is shown that nearly 30% of COLs do not induce any rainfall; most of them located in the southern half of the Peninsula, and mainly during autumn. Only 30% of COLs produce generalized rainfall over the whole analysed territory, being most of them (about 90%) located over the western half of the Iberian Peninsula