Característiques dels sòls de conreu de cereals de Catalunya i llur fertilització

Hom estudia els sòls més representatius de Catalunya dedicats al conreu de cereals, tot posant-hi de manifest una baixa fertilitat i una abundància de carbonats. S'inclou també un resum de les característiques més importants dels sòls naturals dels quals deriven els sòls agrícoles.This paper relates the yield of winter cereals to soil classes in Catalonia. The basic criteria for fertility is exposed and a summary of the most important properties of natural soils related with agricultural ones is included. Data from 50 agricultural soils show that the most common limitations to the growth are: low fertility and excessive carbonates.Se estudian los suelos más representativos de Cataluña dedicados al cultivo de cereales evidenciandose una baja fertilidad y su alto contenido en carbonatos. Se incluye un resumen de las características más importantes de los suelos naturales de los que proceden los suelos agrícolas

Determinació del contingut de metalls pesants en fangs residuals per a poder ésser aplicats al sòl

Hom anomena fangs residuals el subproducte de la depuració d'aigües. Són materials molt heterogènis que, per llur riquesa en matèria orgànica, nitrogen, fòsfor i altres nutrients, poden esser emprats com a fertilitzants i condicionadors de sòls; però aquesta aplicació resta limitada per llur contingut en metalls pesants, el qual pot ésser variable principalment en funció de l'origen de 1'aigua. En aquest treball hom ha estudiat, al llarg d'un any, la concentració en diferents metalls, de fangs procedents de catorze depuradores, la majoria de Catalunya, i n'han estat preses mostres cada dos mesos; ha estat posat de manifest que són materials molt heterogenis respecte a llur contingut en metalls pesants, i que la majoria de fangs estudiats podrien ésser reutilitzats a través del sòl per la baixa concentració que presenten en metalls pesants

DNMT3A mutations mediate the epigenetic reactivation of the leukemogenic factor MEIS1 in acute myeloid leukemia

Close to half of de novo acute myeloid leukemia (AML) cases do not exhibit any cytogenetic aberrations. In this regard, distortion of the DNA methylation setting and the presence of mutations in epigenetic modifier genes can also be molecular drivers of the disease. In recent years, somatic missense mutations of the DNA methyltransferase 3A (DNMT3A) have been reported in ~20% of AML patients; however, no obvious critical downstream gene has been identified that could explain the role of DNMT3A in the natural history of AML. Herein, using whole-genome bisulfite sequencing and DNA methylation microarrays, we have identified a key gene undergoing promoter hypomethylation-associated transcriptional reactivation in DNMT3 mutant patients, the leukemogenic HOX cofactor MEIS1. Our results indicate that, in the absence of mixed lineage leukemia fusions, an alternative pathway for engaging an oncogenic MEIS1-dependent transcriptional program can be mediated by DNMT3A mutations

MethCORR modelling of methylomes from formalin-fixed paraffin-embedded tissue enables characterization and prognostication of colorectal cancer

Transcriptional characterization and classification has potential to resolve the inter-tumor heterogeneity of colorectal cancer and improve patient management. Yet, robust transcriptional profiling is difficult using formalin-fixed, paraffin-embedded (FFPE) samples, which complicates testing in clinical and archival material. We present MethCORR, an approach that allows uniform molecular characterization and classification of fresh-frozen and FFPE samples. MethCORR identifies genome-wide correlations between RNA expression and DNA methylation in fresh-frozen samples. This information is used to infer gene expression information in FFPE samples from their methylation profiles. MethCORR is here applied to methylation profiles from 877 fresh-frozen/FFPE samples and comparative analysis identifies the same two subtypes in four independent cohorts. Furthermore, subtype-specific prognostic biomarkers that better predicts relapse-free survival (HR = 2.66, 95%CI [1.67-4.22], P value < 0.001 (log-rank test)) than UICC tumor, node, metastasis (TNM) staging and microsatellite instability status are identified and validated using DNA methylation-specific PCR. The MethCORR approach is general, and may be similarly successful for other cancer types

Gene amplification-associated overexpression of the RNA editing enzyme ADAR1 enhances human lung tumorigenesis

The introduction of new therapies against particular genetic mutations in non-small-cell lung cancer is a promising avenue for improving patient survival, but the target population is small. There is a need to discover new potential actionable genetic lesions, to which end, non-conventional cancer pathways, such as RNA editing, are worth exploring. Herein we show that the adenosine-toinosine editing enzyme ADAR1 undergoes gene amplification in non-small cancer cell lines and primary tumors in association with higher levels of the corresponding mRNA and protein. From a growth and invasion standpoint, the depletion of ADAR1 expression in amplified cells reduces their tumorigenic potential in cell culture and mouse models, whereas its overexpression has the opposite effects. From a functional perspective, ADAR1 overexpression enhances the editing frequencies of target transcripts such as NEIL1 and miR-381. In the clinical setting, patients with early-stage lung cancer, but harboring ADAR1 gene amplification, have poor outcomes. Overall, our results indicate a role for ADAR1 as a lung cancer oncogene undergoing gene amplification-associated activation that affects downstream RNA editing patterns and patient prognosis.This work was supported by the European Research Council under the European Community's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 268626—EPINORC project, the Grant agreement number HEALTH-F2-2010-258677—CURELUNG project, the Spanish Ministry of Economy and Competitiveness (MINECO Projects no. SAF2011-22803, PI13-01339 and SAF2014-55000- R), the Institute of Health Carlos III (ISCIII)—PI10/02992, Ministerio de Educación, Ciencia e Innovación Grant SAF2010-14935, the Cellex Foundation, the National Cancer Center Research and Development Fund (NCC Biobank: 23 A-1) and the Health and Science Departments of the Catalan Government (Generalitat de Catalunya) AGAUR—project no. 2009SGR1315 and 2014SGR633.Peer Reviewe

Epigenetic inactivation of the splicing RNA-binding protein CELF2 in human breast cancer

Altres ajuts: This work was co-finaced by the European Development Regional Fund, "A way to achieve Europe" ERDF; the Cellex Foundation; and "la Caixa" Banking Foundation (LCF/PR/PR15/ 11100003).Human tumors show altered patterns of protein isoforms that can be related to the dysregulation of messenger RNA alternative splicing also observed in transformed cells. Although somatic mutations in core spliceosome components and their associated factors have been described in some cases, almost nothing is known about the contribution of distorted epigenetic patterns to aberrant splicing. Herein, we show that the splicing RNA-binding protein CELF2 is targeted by promoter hypermethylation-associated transcriptional silencing in human cancer. Focusing on the context of breast cancer, we also demonstrate that CELF2 restoration has growth-inhibitory effects and that its epigenetic loss induces an aberrant downstream pattern of alternative splicing, affecting key genes in breast cancer biology such as the autophagy factor ULK1 and the apoptotic protein CARD10. Furthermore, the presence of CELF2 hypermethylation in the clinical setting is associated with shorter overall survival of the breast cancer patients carrying this epigenetic lesion

Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR

Metastasis is respoMetastasis is responsible for most cancer-related deaths, and, among common tumor types, melanoma is one with great potential to metastasize. Here we study the contribution of epigenetic changes to the dissemination process by analyzing the changes that occur at the DNA methylation level between primary cancer cells and metastases. We found a hypomethylation event that reactivates a cryptic transcript of the Rab GTPase activating protein TBC1D16 (TBC1D16-47 kDa; referred to hereafter as TBC1D16-47KD) to be a characteristic feature of the metastatic cascade. This short isoform of TBC1D16 exacerbates melanoma growth and metastasis both in vitro and in vivo. By combining immunoprecipitation and mass spectrometry, we identified RAB5C as a new TBC1D16 target and showed that it regulates EGFR in melanoma cells. We also found that epigenetic reactivation of TBC1D16-47KD is associated with poor clinical outcome in melanoma, while conferring greater sensitivity to BRAF and MEK inhibitors

Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program

Altres ajuts: This work was supported by the Obra Social "La Caixa" (to M. Esteller).Tumors have aberrant proteomes that often do not match their corresponding transcriptome profiles. One possible cause of this discrepancy is the existence of aberrant RNA modification landscapes in the so-called epitranscriptome. Here, we report that human glioma cells undergo DNA methylation-associated epigenetic silencing of NSUN5, a candidate RNA methyltransferase for 5-methylcytosine. In this setting, NSUN5 exhibits tumor-suppressor characteristics in vivo glioma models. We also found that NSUN5 loss generates an unmethylated status at the C3782 position of 28S rRNA that drives an overall depletion of protein synthesis, and leads to the emergence of an adaptive translational program for survival under conditions of cellular stress. Interestingly, NSUN5 epigenetic inactivation also renders these gliomas sensitive to bioactivatable substrates of the stress-related enzyme NQO1. Most importantly, NSUN5 epigenetic inactivation is a hallmark of glioma patients with long-term survival for this otherwise devastating disease

Epigenetic loss of the RNA decapping enzyme NUDT16 mediates C-MYC activation in T-cell acute lymphoblastic leukemia

Altres ajuts: La Marató de TV3 Foundation #20131610, the Cellex Foundation, Obra Social 'La Caixa