Comparison of metabolomic reconfiguration between Columbia and Landsberg ecotypes subjected to the combination of high salinity and increased irradiance

Background: Plants growing in the field are subjected to combinations of abiotic stresses. These conditions pose a devastating threat to crops, decreasing their yield and causing a negative economic impact on agricultural production. Metabolic responses play a key role in plant acclimation to stress and natural variation for these metabolic changes could be key for plant adaptation to fluctuating environmental conditions. Results: Here we studied the metabolomic response of two Arabidopsis ecotypes (Columbia-0 [Col] and Landsberg erecta-0 [Ler]), widely used as genetic background for Arabidopsis mutant collections, subjected to the combination of high salinity and increased irradiance. Our findings demonstrate that this stress combination results in a specific metabolic response, different than that of the individual stresses. Although both ecotypes displayed reduced growth and quantum yield of photosystem II, as well as increased foliar damage and malondialdehyde accumulation, different mechanisms to tolerate the stress combination were observed. These included a relocation of amino acids and sugars to act as potential osmoprotectants, and the accumulation of different stress-protective compounds such as polyamines or secondary metabolites. Conclusions: Our findings reflect an initial identification of metabolic pathways that differentially change under stress combination that could be considered in studies of stress combination of Arabidopsis mutants that include Col or Ler as genetic backgrounds.Metabolomic analysis was perform at Max Planck Institute of Molecular Plant Physiology in Potsdam, Germany. Hormone measurements were carried out at the central facilities (Servei Central d’Instrumentació Científica, SCIC) of the Universitat Jaume I, Spain. SIZ was supported by a Ramón y Cajal contract (RYC2020-029967-I). JLR was supported by a Juan de la Cierva-Incorporación contract (IJC2020-045612-I)

Abscisic acid promotes plant acclimation to the combination of salinity and high light stress

Plants encounter combinations of different abiotic stresses such as salinity (S) and high light (HL). These environmental conditions have a detrimental effect on plant growth and development, posing a threat to agricultural production. Metabolic changes play a crucial role in enabling plants to adapt to fluctuations in their environment. Furthermore, hormones such as abscisic acid (ABA), jasmonic acid (JA) and salicylic acid (SA) have been previously identified as regulators of plant responses to different abiotic stresses. Here we studied the response of Arabidopsis wild type (Col and Ler) plants and mutants impaired in hormone biosynthesis (aba2-11 and aba1-1 in ABA, aos in JA and sid2 in SA) to the combination of S and HL (S + HL). Our findings showed that aba2-11 plants displayed reduced growth, impaired photosystem II (PSII) function, increased leaf damage, and decreased survival compared to Col when subjected to stress combination. However, aos and sid2 mutants did not display significant changes in response to S + HL compared to Col, indicating a key role for ABA in promoting plant tolerance to S + HL and suggesting a marginal role for JA and SA in this process. In addition, we revealed differences in the metabolic response of plants to S + HL compared to S or HL. The analysis of altered metabolic pathways under S + HL suggested that the accumulation of flavonoids is ABA-dependent, whereas the accumulation of branched-chain amino acids (BCAAs) and proline is ABA-independent. Therefore, our study uncovered a key function for ABA in regulating the accumulation of different flavonoids in plants during S + HL.Funding for open access charge: CRUE-Universitat Jaume

Setup and validation of shake-flask procedures for the determinationof partition coefficients (log D) from low drug amounts

Several procedures based on the shake-flask method and designed to require a minimum amount of drug for octanol-water partition coefficient determination have been established and developed. The procedures have been validated by a 28 substance set with a lipophilicity range from -2.0 to 4.5 (logD7.4). The experimental partition is carried out using aqueous phases buffered with phosphate (pH 7.4) and n-octanol saturated with buffered water and the analysis is performed by liquid chromatography. In order to have accurate results, four procedures and eight different ratios between phase volumes are proposed. Each procedure has been designed and optimized (for partition ratios) for a specific range of drug lipophilicity (low, regular and high lipophilicity) and solubility (high and low aqueous solubility). The procedures have been developed to minimize the measurement in the octanolic phase. Experimental logD7.4 values obtained from different procedures and partition ratios show a standard deviation lower than 0.3 and there is a nice agreement when these values are compared with the reference literature one

Hydroxychloroquine is associated with a lower risk of polyautoimmunity: data from the RELESSER Registry

Objectives. This article estimates the frequency of polyautoimmunity and associated factors in a large retrospective cohort of patients with SLE. Methods. RELESSER (Spanish Society of Rheumatology Lupus Registry) is a nationwide multicentre, hospital-based registry of SLE patients. This is a cross-sectional study. The main variable was polyautoimmunity, which was defined as the co-occurrence of SLE and another autoimmune disease, such as autoimmune thyroiditis, RA, scleroderma, inflammatory myopathy and MCTD. We also recorded the presence of multiple autoimmune syndrome, secondary SS, secondary APS and a family history of autoimmune disease. Multiple logistic regression analysis was performed to investigate possible risk factors for polyautoimmunity. Results. Of the 3679 patients who fulfilled the criteria for SLE, 502 (13.6%) had polyautoimmunity. The most frequent types were autoimmune thyroiditis (7.9%), other systemic autoimmune diseases (6.2%), secondary SS (14.1%) and secondary APS (13.7%). Multiple autoimmune syndrome accounted for 10.2% of all cases of polyautoimmunity. A family history was recorded in 11.8%. According to the multivariate analysis, the factors associated with polyautoimmunity were female sex [odds ratio (95% CI), 1.72 (1.07, 2.72)], RP [1.63 (1.29, 2.05)], interstitial lung disease [3.35 (1.84, 6.01)], Jaccoud arthropathy [1.92 (1.40, 2.63)], anti-Ro/SSA and/or anti-La/SSB autoantibodies [2.03 (1.55, 2.67)], anti-RNP antibodies [1.48 (1.16, 1.90)], MTX [1.67 (1.26, 2.18)] and antimalarial drugs [0.50 (0.38, 0.67)]. Conclusion. Patients with SLE frequently present polyautoimmunity. We observed clinical and analytical characteristics associated with polyautoimmunity. Our finding that antimalarial drugs protected against polyautoimmunity should be verified in future studies

Epigenetic clocks in relapse after a first episode of schizophrenia

The main objective of the present study was to investigate the association between several epigenetic clocks, covering different aspects of aging, with schizophrenia relapse evaluated over a 3-year follow-up period in a cohort of ninety-one first-episode schizophrenia patients. Genome-wide DNA methylation was profiled and four epigenetic clocks, including epigenetic clocks of chronological age, mortality and telomere length were calculated. Patients that relapsed during the follow-up showed epigenetic acceleration of the telomere length clock (p = 0.030). Shorter telomere length was associated with cognitive performance (working memory, r = 0.31 p = 0.015; verbal fluency, r = 0.28 p = 0.028), but no direct effect of cognitive function or symptom severity on relapse was detected. The results of the present study suggest that epigenetic age acceleration could be involved in the clinical course of schizophrenia and could be a useful marker of relapse when measured in remission stages

Tuberculosis in pediatric patients treated with anti-TNFα drugs: a cohort study

Background: Adult patients receiving anti-TNFα drugs are at increased risk of tuberculosis (TB), but studies in pediatric populations are limited, and the best strategy for latent tuberculosis infection (LTBI) screening in this population remains controversial. We describe the prevalence of LTBI prior to anti-TNFα therapy and the long-term follow-up after biological treatment initiation in a cohort of children and adolescents. Methods: Cohort observational study in children and adolescents receiving anti-TNFα agents in a tertiary-care pediatric hospital. LTBI was ruled out prior to the implementation of anti-TNFα drugs by tuberculin skin test (TST), and, from March 2012 on, QuantiFERON Gold-In Tube® test (QTF-G). During anti-TNFα treatment, patients were evaluated every 6 months for TB with history and physical examination. TST/QTF-G were not repeated unless signs or symptoms consistent with TB arose or there was proven TB contact. Results: The final cohort consisted of 221 patients (56.1 % female; 261 treatments), of whom 51.7 %/30.0 %/17.3 % were treated with etanercept/adalimumab/infliximab, respectively, for a variety of rheumatic diseases (75.6 %), inflammatory bowel disease (20.8 %), and inflammatory eye diseases (3.6 %). The median (IQR) age at diagnosis of the primary condition was 6.8 years (2.7-11.0) and the duration of the disease before implementing the anti-TNFα agent was 1.8 years (0.6-4.2). LTBI was diagnosed in 3 adolescent girls (prevalence rate: 1.4 %; 95 % CI: 0.4-4.2) affected with juvenile idiopathic arthritis: TST tested positive in only 1, while QTF-G was positive in all cases (including 2 patients already on etanercept). They all received antiTB chemoprophylaxis and were later (re)treated with etanercept for 24-29 months, without incidences. No incident cases of TB disease were observed during the follow-up period under anti-TNFα treatment of 641 patients-year, with a median (IQR) time per patient of 2.3 years (1.4-4.3). Conclusions: In our study, the prevalence of LTBI (1.4 %) was similar to that reported in population screening studies in Spain; no incident cases of TB disease were observed. In low-burden TB settings, initial screening for TB in children prior to anti-TNFα treatment should include both TST and an IGRA test, but systematic repetition of LTBI immunodiagnostic tests seems unnecessary in the absence of symptoms or known TB contact

Lugar(es)

Catálogo de la exposición colectiva celebrada en la sala de exposiciones de la Facultad de Bellas Artes de la Universidad Complutense de Madrid entre el 14 y el 30 de enero de 201

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Potenciar la oralidad en Infantil mediante los proyectos de trabajo

Treball Final de Grau en Mestre o Mestra d'Educació Infantil. Codi: MI1040. Curs acadèmic 2013-2014En el siguiente trabajo presento una investigación dirigida al análisis del contexto y actuaciones que podrían explicar cómo incluyen los maestros la oralidad en los proyectos de trabajo en la etapa de Educación Infantil. Es decir: ¿Qué función tiene el lenguaje oral en el aprendizaje por proyectos en un aula de tres años