Insulin and GLP-1 infusions demonstrate the onset of adipose-specific insulin resistance in a large fasting mammal: potential glucogenic role for GLP-1.

Prolonged food deprivation increases lipid oxidation and utilization, which may contribute to the onset of the insulin resistance associated with fasting. Because insulin resistance promotes the preservation of glucose and oxidation of fat, it has been suggested to be an adaptive response to food deprivation. However, fasting mammals exhibit hypoinsulinemia, suggesting that the insulin resistance-like conditions they experience may actually result from reduced pancreatic sensitivity to glucose/capacity to secrete insulin. To determine whether fasting results in insulin resistance or in pancreatic dysfunction, we infused early- and late-fasted seals (naturally adapted to prolonged fasting) with insulin (0.065 U/kg), and a separate group of late-fasted seals with low (10 pM/kg) or high (100 pM/kg) dosages of glucagon-like peptide-1 (GLP-1) immediately following a glucose bolus (0.5g/kg), and measured the systemic and cellular responses. Because GLP-1 facilitates glucose-stimulated insulin secretion, these infusions provide a method to assess pancreatic insulin-secreting capacity. Insulin infusions increased the phosphorylation of insulin receptor and Akt in adipose and muscle of early and late fasted seals; however the timing of the signaling response was blunted in adipose of late fasted seals. Despite the dose-dependent increases in insulin and increased glucose clearance (high dose), both GLP-1 dosages produced increases in plasma cortisol and glucagon, which may have contributed to the glucogenic role of GLP-1. Results suggest that fasting induces adipose-specific insulin resistance in elephant seal pups, while maintaining skeletal muscle insulin sensitivity, and therefore suggests that the onset of insulin resistance in fasting mammals is an evolved response to cope with prolonged food deprivation

Análisis comparativo del potencial de siete variedades de triticale para usos agroenergéticos.

Se han realizado ensayos de campo durante 2008 y 2009 para evaluar la producción de biomasa seca y de los principales componentes celulósicos de la biomasa, y el rendimiento en grano de 7 variedades de triticale y 5 variedades de otros cereales (centeno, avena forrajera y trigo blando). Los centenos analizados, en particular la variedad híbrida ‘Picasso’, han sido los materiales más productivos, tanto en lo que respecta a su posible rendimiento energético, como en su condición de cereal para grano. No obstante, los triticales ‘Forricale’ y ‘Misionero’ han mostrado un buen potencial como cultivo agroenergé- tico, especialmente en condiciones climatológicas adversas. También destacan en cuanto a su posible utilización como variedades de doble uso: biocombustible y cereal-grano

Análisis de la diversidad para proteínas de endospermo en los citotipos 2N=10 y 2N=30 de Brachipodium

Se han analizado mediante electroforesis las proteínas del endospermo de 38 poblaciones españolas de brachypodium, correspondientes a los citotipos de 10 y 30 cromosomas. En total, se han identificado 40 bandas de proteínas diferentes, ninguna de las cuales ha resultado ser específica de uno de los dos citotipos. Se ha encontrado una alta variabilidad intra- e interpoblacional, siendo las poblaciones de 30 cromosomas las que muestran el mayor grado de diversidad genétic

Calidad semolera y nuevas variantes alélicas prolaminas en variedades indígenas españolas d trigo duro (Triticum Turgidum L. Tell.)

Las prolaminas son las principales proteínas del endospermo de los trigos panaderos que están relacionadas con la calidad panadera. El objetivo de este trabajo es caracterizar gluteninas LMW según la nomenclatura de Liu et al y relacionarlas con la fuerza panadera

Characterization of endosperm proteins and bread-making quality in wheat breeding lines carrying resistance genes for Mayetiola destructor and/or Heterodera avenae.

The experimental material included thirteen bread wheat-breeding lines that carry genes for resistance to M. destruc¬tor and/or H. avenae. The sources of these resistances are the wild species Ae. triuncialis and Ae. ventricosa (lines TR and H-93, respectively) (Delibes et al. 1993, 1997; Romero et al. 1998). We have determined the composition in HMW-glutenin subunits (related with bread-making quality), puroindoline proteins (related with hardness of grain), and waxy proteins (related with starch viscosity). In addition to, of prolamins by electrophoresis SDS-PAGE indicated the homogeneity of the lines

Karyotype characterization of wheat breeding lines carrying resistance genes from Aegilops ventricosa

We have used in situ hybridization combining genomic and repeated DNA fluorescent probes to determine the karyotype composition of two bread wheat introgression lines: H-93-33, which carries the gene H27 for resistance to the Hessian fly M. destructor (Delibes et al. 1997); and H-93-8, carrying the gene Cre2 which confers resistance to the cereal cyst nematode H. avenae (Delibes et al. 1993). Both introgression lines had been derived from an earlier cross between T. aestivum subsp. aestivum (2n=42; genome composition AABBDD) and a semi-fertile hybrid between T. turgidum subsp. turgidum (2n=28; genome composition AABB) and the wild grass Ae. ventricosa (2n=28; genome constitution DvDvN¬vNv). We also have examined several resistant advanced lines that were obtained from H-93-33 (lines ID-2151, ID-2193, Ma-1612-a and Ma-1612-b) or H-93-8 (line ID-2150) after 3 to 5 backcrosses with commercial wheats

Reduced mitochondrial pyruvate carrier expression in hearts with heart failure and reduced ejection fraction patients: ischemic vs. non-ischemic origin

Introduction and objectivesMitochondrial pyruvate carrier (MPC) mediates the entry of pyruvate into mitochondria, determining whether pyruvate is incorporated into the Krebs cycle or metabolized in the cytosol. In heart failure (HF), a large amount of pyruvate is metabolized to lactate in the cytosol rather than being oxidized inside the mitochondria. Thus, MPC activity or expression might play a key role in the fate of pyruvate during HF. The purpose of this work was to study the levels of the two subunits of this carrier, named MPC1 and MPC2, in human hearts with HF of different etiologies.MethodsProtein and mRNA expression analyses were conducted in cardiac tissues from three donor groups: patients with HF with reduced ejection fraction (HFrEF) with ischemic cardiomyopathy (ICM) or idiopathic dilated cardiomyopathy (IDC), and donors without cardiac pathology (Control). MPC2 plasma levels were determined by ELISA.ResultsSignificant reductions in the levels of MPC1, MPC2, and Sirtuin 3 (SIRT3) were observed in ICM patients compared with the levels in the Control group. However, no statistically significant differences were revealed in the analysis of MPC1 and MPC2 gene expression among the groups. Interestingly, Pyruvate dehydrogenase complex (PDH) subunits expression were increased in the ICM patients. In the case of IDC patients, a significant decrease in MPC1 was observed only when compared with the Control group. Notably, plasma MPC2 levels were found to be elevated in both disease groups compared with that in the Control group.ConclusionDecreases in MPC1 and/or MPC2 levels were detected in the cardiac tissues of HFrEF patients, with ischemic or idiopatic origen, indicating a potential reduction in mitochondrial pyruvate uptake in the heart, which could be linked to unfavorable clinical features

Analysis of variants in the HCN4 gene and in three single nucleotide polymorphisms of the CYP3A4 gene for association with ivabradine reduction in heart rate: A preliminary report

Background: Ivabradine, a selective bradycardic drug, inhibits the If. In patients with heart failure (HF), ivabradine reduces the risk of rehospitalization and mortality. The average heart rate (HR) reduction is 8–10 beats, although clinical trials reveal interindividual variability. The aim of the study is to identify variants associated with HR reduction produced by ivabradine in genes involved in the drug metabolism (CYP3A4) or related to the drug target (HCN4). Methods: In an exploratory cohort (n = 11), patients started on ivabradine were genotyped and the HR reduction was studied. Results: The mean HR reduction after the treatment was 18.10 ± 12.26 bpm. The HR reduction was ≥ 15 bpm in 3 patients and > 5 and < 15 bpm in 7 patients. Four synonymous variants, L12L, L520L, P852P, and P1200P, were detected in the HCN4 gene (frequency = 0.045, 0.045, and 0.681, respectively). Moreover, the CYP3A4*1F and CYP3A4*1B were found in one patient each and CYP3A4*1G was presented in 3 patients. Conclusions: This is the first study using an exploratory pharmacogenetic approach that attempts to explain interindividual variability in ivabradine HR reduction. However, more research must be undertaken in order to determine the role of variants in HCN4 and CYP3A4 genes in response to ivabradine

Surgical treatment for colorectal cancer: Analysis of the influence of an enhanced recovery programme on long-term oncological outcomes-a study protocol for a prospective, multicentre, observational cohort study

Introduction The evidence currently available from enhanced recovery after surgery (ERAS) programmes concerns their benefits in the immediate postoperative period, but there is still very little evidence as to whether their correct implementation benefits patients in the long term. The working hypothesis here is that, due to the lower response to surgical aggression and lower rates of postoperative complications, ERAS protocols can reduce colorectal cancer-related mortality. The main objective of this study is to analyse the impact of an ERAS programme for colorectal cancer on 5-year survival. As secondary objectives, we propose to analyse the weight of each of the predefined items in the oncological results as well as the quality of life. Methods and analysis A multicentre prospective cohort study was conducted in patients older than 18 years of age who are scheduled to undergo surgery for colorectal cancer. The study involved 12 hospitals with an implemented enhanced recovery protocol according to the guidelines published by the Spanish National Health Service. The intervention group includes patients with a minimum implementation level of 70%, and the control group includes those who fail to reach this level. Compliance will be studied using 18 key performance indicators, and the results will be analysed using cancer survival indicators, including overall survival, cancer-specific survival and relapse-free survival. The time to recurrence, perioperative morbidity and mortality, hospital stay and quality of life will also be studied, the latter using the validated EuroQol Five questionnaire. The propensity index method will be used to create comparable treatment and control groups, and a multivariate regression will be used to study each variable. The Kaplan-Meier estimator will be used to estimate survival and the log-rank test to make comparisons. A p value of less than 0.05 (two-tailed) will be considered to be significant. Ethics and dissemination Ethical approval for this study was obtained from the Aragon Ethical Committee (C.P.-C.I. PI20/086) on 4 March 2020. The findings of this study will be submitted to peer-reviewed journals (BMJ Open, JAMA Surgery, Annals of Surgery, British Journal of Surgery). Abstracts will be submitted to relevant national and international meetings.The present research study was awarded a Ministerio de Ciencia e Innovación health research project grant (PI19/00291) from the Carlos III Institute of the Spanish National Health Service as part of the 2019 call for Strategic Action in Health

Dynamical dark energy in light of the latest observations

A flat Friedmann-Robertson-Walker universe dominated by a cosmological constant (Λ) and cold dark matter (CDM) has been the working model preferred by cosmologists since the discovery of cosmic acceleration1,2. However, tensions of various degrees ofsignificance are known to be present among existing datasets within the ΛCDM framework3-11. In particular, the Lyman-α forest measurement of the baryon acoustic oscillations (BAO) by the Baryon Oscillation Spectroscopic Survey3 prefers a smaller value of the matter density fraction ΩM than that preferred by cosmic microwave background (CMB). Also, the recently measured value of the Hubble constant, H0 = 73.24 ±1.74 km s-1 Mpc-1 (ref. 12), is 3.4σ higher than the 66.93 ± 0.62 km s-1Mpc-1 inferred from the Planck CMB data7. In this work, we investigate whether these tensions can be interpreted as evidence for a non-constant dynamical dark energy. Using the Kullback-Leibler divergence13 to quantify the tension between datasets, we find that the tensions are relieved by an evolving dark energy, with the dynamical dark energy model preferred at a 3.5σ significance level based on the improvement in the fit alone. While, at present, the Bayesian evidence for the dynamical dark energy is insufficient to favour it over ΛCDM, we show that, if the current best-fit dark energy happened to be the true model, it would be decisively detected by the upcoming Dark Energy Spectroscopic Instrument survey14.PostprintPeer reviewe