Activity of ammonia-oxidizing bacteria in enriched cultures exposed to 3,4-dimethyl-1H-pyrazole dihydrogen phosphate nitrification inhibitor

The use of nitrification inhibitors is an interesting tool to achieve a higher N efficiency in plants while decreasing the environmental impact of N fertilization. However, an integrated evaluation of the efficiency of nitrification inhibitors over time, understood as the period in which the nitrifying activity is inhibited or slows down, is necessary to assess whether their use is ecofriendly and sustainable. To test the direct efficiency of 3,4-dimethyl-1H-pyrazole dihydrogen phosphate (DMPP) on nitrification, a study has been carried out in two cultures enriched with ammonia-oxidizing bacteria (AOB) obtained from a soil with continuous N fertilization (80 kg N ha−1 year−1 as NH4NO3) and from soil without N fertilization. In addition, Cu has been evaluated as a cofactor of ammonia monoxygenase, a key enzyme in the nitrifying activity of AOBs. On the other hand, the stability of DMP has been studied both in the cultivation system enriched in AOBs and in soil to assess the efficiency of the inhibitor due to its persistence over time. Our work reveals that nitrification rates observed in cultures enriched in AOBs from genus Nitrosospira isolated from soils with continuous N fertilization were not higher than those of cultures without N fertilization. In AOB cultures, DMPP was a very efficient inhibitor of nitrification (> 50 % inhibition of integrated AMO activity), mainly due to the stability of DMP (3,4-dimethyl-1 H-pyrazole) in the cultures. However, DMP stability was significantly lower under soil conditions (> 90 % of DMP was degraded in the first 30 days of incubation). Other metals are suggested as cofactors of the enzyme ammonia monooxygenase alternatively to Cu.This work was supported by Spanish Government-Ministry of Science, Innovation and Universities (RTI2018-094623-B-C22), Spain. MCIN/AEI/10.130039/501100011033/FEDER, EU. J.M.R. was supported by a doctoral fellowship from Coordination for the Improvement of Higher Education Personnel (CAPES), of Brazilian Government (1I11903/13-9), Brazil. Open access funding provided by the Public University of Navarra

Functional Insight into and Refinement of the Genomic Boundaries of the JARID2-Neurodevelopmental Disorder Episignature

DNA methylation; Episignature; Intellectual disabilityMetilació de l'ADN; Episignatura; Discapacitat intel·lectualMetilación del ADN; Epifirma; Discapacidad intelectualJARID2 (Jumonji, AT-rich interactive domain 2) haploinsufficiency is associated with a clinically distinct neurodevelopmental syndrome. It is characterized by intellectual disability, developmental delay, autistic features, behavior abnormalities, cognitive impairment, hypotonia, and dysmorphic features. JARID2 acts as a transcriptional repressor protein that is involved in the regulation of histone methyltransferase complexes. JARID2 plays a role in the epigenetic machinery, and the associated syndrome has an identified DNA methylation episignature derived from sequence variants and intragenic deletions involving JARID2. For this study, our aim was to determine whether patients with larger deletions spanning beyond JARID2 present a similar DNA methylation episignature and to define the critical region involved in aberrant DNA methylation in 6p22–p24 microdeletions. We examined the DNA methylation profiles of peripheral blood from 56 control subjects, 13 patients with (likely) pathogenic JARID2 variants or patients carrying copy number variants, and three patients with JARID2 VUS variants. The analysis showed a distinct and strong differentiation between patients with (likely) pathogenic variants, both sequence and copy number, and controls. Using the identified episignature, we developed a binary model to classify patients with the JARID2-neurodevelopmental syndrome. DNA methylation analysis indicated that JARID2 is the driver gene for aberrant DNA methylation observed in 6p22–p24 microdeletions. In addition, we performed analysis of functional correlation of the JARID2 genome-wide methylation profile with the DNA methylation profiles of 56 additional neurodevelopmental disorders. To conclude, we refined the critical region for the presence of the JARID2 episignature in 6p22–p24 microdeletions and provide insight into the functional changes in the epigenome observed when regulation by JARID2 is lost.Funding for this study is provided in part by the Government of Canada through Genome Canada and the Ontario Genomics Institute (OGI-188)

Novel Somatic Genetic Variants as Predictors of Resistance to EGFR-Targeted Therapies in Metastatic Colorectal Cancer Patients

Background: About 40% of RAS/BRAF wild-type metastatic colorectal cancer (mCRC) patients undergoing anti-EGFR-based therapy have poor outcomes. Treatment failure is not only associated with poorer prognosis but higher healthcare costs. Our aim was to identify novel somatic genetic variants in the primary tumor and assess their effect on anti-EGFR response. Patients and Methods: Tumor (somatic) and blood (germline) DNA samples were obtained from two well-defined cohorts of mCRC patients, those sensitive and those resistant to EGFR blockade. Genetic variant screening of 43 EGFR-related genes was performed using targeted next-generation sequencing (NGS). Relevant clinical data were collected through chart review to assess genetic results. Results: Among 61 patients, 38 were sensitive and 23 were resistant to treatment. We identified eight somatic variants that predicted non-response. Three were located in insulin-related genes (I668N and E1218K in IGF1R, T1156M in IRS2) and three in genes belonging to the LRIG family (T152T in LRIG1, S697L in LRIG2 and V812M in LRIG3). The remaining two variants were found in NRAS (G115Efs*46) and PDGFRA (T301T). We did not identify any somatic variants related to good response. Conclusions: This study provides evidence that novel somatic genetic variants along the EGFR-triggered pathway could modulate the response to anti-EGFR drugs in mCRC patients. It also highlights the influence of insulin-related genes and LRIG genes on anti-EGFR efficacy. Our findings could help characterize patients who are resistant to anti-EGFR blockade despite harboring RAS/BRAF wild-type tumors

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Is nitrogen source the key for overcoming photosynthetic acclimation in Arabidopsis plants exposed to elevated CO2?

Trabajo presentado en el XIII Congreso Hispano-Luso de Fisiología Vegetal, celebrado en Oeiras (Portugal) en julio de 2013.Although the current [CO 2 ] in the atmosphere is generally limiting for C available information suggests that the predicted [ CO 2 ] increase will enhance rates in plants. However, it has been previously (B loom 2010, Stitt Krapp 1999) observed that responsiveness of plants to elevated [CO 2 ] will me mediated by its interaction with other li miting environmental factors, such as nitrogen availabilit y. According to those studies, N availability might decrease or eliminate the positive effect of elevated CO 2 on photosynthetic rates and consequently plant growth. The ‘capacity’ to adjust photosynthetic activity with plant C requirements has been described as a key process co nditioning photosynthetic performance under elevated [CO 2 ]. From this point of view, the reduction in photos ynthetic rates would be conditioned by a plant’s ability to develop new sin ks, or to expand the storage capacity or rate of existing sinks. According to Bloom et al . (2010), photosynthetic down might be conditioned by nitrate reductase activity and the inhibition of NO nt decline in plant N compounds. Furthermore, accor ding to those authors, the kind of nitrogen form applied to plants has a key role in r esponsiveness of plants to elevated [CO order to test the relevancy of N fertilization form in photosynthetic performance under elevated ] conditions, Arabidopsis thaliana (Columbia 0), grown hydroponically were exposed to ambient versus elevated [CO 2 ] concentrations (380 and 800 ppm respectively). Tw o different N forms were supplied at 0.75 mM, KNO 3 and NH 4 NO 3 . The plants were grown in a growth chamber (Hereaus Vötsch HPS 1500) at 16/8h (d/n) ph otoperiod, 22/18ºC (d/n) thermoperiod, 80% rH, 200 μmol photons m -2 s -1 PPDF, during 8 weeks (prior to flowering). Our resu lts revealed that Arabiopsis responsiveness to N fertili zation form was larger than that to elevated ], being the plants fertilized with NH 4 NO 3 and [CO 2 ] the ones with the largest biomass production and photosynthetic rates. More specifica lly, in NO 3 fed plants exposure to 800 ppm had significant effect in net photosynthesis (A N ) and electron transport rate (ETR), but Rubisco maximum carboxylation rate (Vc max ) and electron transport rate contributing to RuBP regeneration (J max ) had no significative effect. Furthermore, in thos e plants Rubisco and tot soluble protein (TSP) content was depleted by 35 an d 25 % respectively. In the other hand, A , J max such parameters were stimulated in NH 4 NO 3 fed plants. The larger responsiveness of photosynthetic apparatus observed in ammonium nitrate feed plants at 800 ppm was explained by their capacity to maintain con trol Rubisco and TSP content values. Those results remark the crucial influence of N sou rce on photosynthesis and its implications on protein metabolism of Arabidopsis plants grown in elevated CO 2.This study was supported in part by the the Spanish National Research and Development Programme (AGL2009-13339-C02-02) and AGL2011-30386-CO2-O2). Ivan Jauregui was the recipient of a FPI grant whereas Iker Aranjuelo was the recipient of a Ramón y Cajal research grant (Economy and Competitiveness Ministry).Peer Reviewe

Yield and quality of sugar snap pea in the Ebro Valley: sowing date and seed density

Sugar snap pea (Pisum sativum L. var. macrocarpon Ser.) is an edible-podded sweet pea that is being considered as a new totally mechanized crop to supply raw material to the agri-food industry of the Ebro Valley (Northern Spain). It is of great interest from an agronomic and commercial standpoint but neither its agronomic behaviour nor its adaptation to the area are known. The objective of this study was to determine the effect of sowing date and seed density on the growth and yield of the sugar snap pea at industrial scale. Six randomized blocks experiments with four replicates were conducted on irrigated land in Villafranca (Navarra, Spain) in 1998, 1999, and 2000. Three experiments for testing sowing dates (Mar., Apr., and May) and another three for seed densities (from 75 to 150 plants m-2) were performed. Phenological development, thermal integral and qualitative and quantitative yield controls were performed. Sugar snap pea required 960 ºC d-1 (Tb = 3 ºC) from sowing to harvest. The early sowings gave more biomass, but yield was similar. However, Harvest Index and crop morphology varied. The sowing densities had similar yields sowing that sugar snap pea has a bigger adaptation availability. Sugar snap peas can be satisfactorily cultivated at industrial scale in the zone with sowings between Mar. and May and with seeding densities between 75 and 150 plants m-2

Influence of stage of development in the efficiency of nitrogen fertilization on poplar

Poplar cuttings (Populus x euroamericana) were planted in pots and grown in a greenhouse for four months with drip irrigation. Two nitrogen (N) doses of 60 and 120 kg nitrate (N-NO3−) ha−1 (labeling with 15N stable isotopes) were applied at one (time I), two (time II) and three months after of the plantation (time III). The aim of this study was to determine the N-fertilizer application method that resulted in optimal N-uptake by a short-rotation of poplar crop during first year of growth. Our data revealed that NUE (N use efficiency) was largest in the last part of the experiment. The larger development of those plants at this stage enabled the improved absorption and assimilation of N. Furthermore, 15N also revealed that supply of N at three months post-planting generated more biomass and increased the N reserves in the stem; a key factor for ensuring the optimum regrowth during the second year