Detección múltiple de SNPS relacionados con crecimiento y calidad de carne en porcino.

This work describes a method based on primer extension analyses to genotype simul-taneously seven SNPs associated with growth and meat quality in pigs. Genomic DNA samples were obtained from 193 animals belonging to several porcine breeds (54 Iberian, 63 Duroc and 47 Large White-Landrace x Large White) and 29 wild board. Four pairs of primers have been designed from the sequences of the genes H-FABP, MC4R and LEPR and were used for the multiplex amplification of regions in the pig genome containing seven SNPs. Primer extension reaction (ABI PRISM SNaPshot Multiplex™ kit. Applied Biosystems) was realized with primers designed in the flanking regions to each of the SNP of interest. The genotypes were identified by minisequencing with ABIPrism 3130 and GeneMapper 3.7. (Applied Biosystems) and the different alleles of the seven SNPs were discriminated in a sole reaction. In this work have been detected, for the first time, the polymorphisms T221C and C233T of the LEPR gene (Genbank AF092422), which are not recognizable by restriction. This method allows identifying the carrying animals with the best desirable genotypes for selection.Se describe un método basado en análisis por primer extension para genotipar simultáneamente 7 SNPs relacionados con el crecimiento y la calidad de la carne en porcino. Las muestras de ADN genómico fueron obtenidas de 193 animales pertenecientes a varias razas (54 Ibérico, 63 Duroc, 47 Large White-Landrace x Large White) y a jabalí (29). A partir de las secuencias de los genes H-FABP, MC4R y LEPR, se diseñaron 4 parejas de cebadores con el fin de amplificar las regiones del genoma porcino que contienen esos 7 SNPs. La reacción de minisecuenciación primer extension (ABI PRISM SNaPshot MultiplexTM kit. Applied Biosystem) se realizó con cebadores diseñados en las regiones flanqueantes de cada uno de los SNPs de interés. Los genotipos fueron identificados por mini-secuenciación con ABIPrism 3130 y GeneMapper 3.7 (Applied Biosystems) pudiéndose así discriminar, en una sola reacción, los diferentes alelos de los 7 SNPs de cada animal. Gracias a esta técnica han sido detectados los polimorfismos T221C y C233T del gen LEPR (Genbank AF092422), que no eran reconocibles por enzimas de restricción. Este método permite identificar los animales con genotipo más deseables para la selección

External validity of docetaxel triplet trials in advanced gastric cancer : are there patients who still benefit?

Background: The purpose of our study was to develop an online calculator to estimate the effect of docetaxel triplets (DPF) in first line of advanced gastric cancer (AGC), and to assess the external validity of docetaxel trials in individual patients. Methods: The study includes patients with HER2(-) AGC treated with platin and fluoropyrimidine (PF) or with DPF in first line. Treatment effect and interactions were assessed using Bayesian accelerated failure time models. Result: The series comprises 1376 patients; 238 treated with DPF and 1138 with PF between 2008 and 2019. DPF was associated with increased progression-free survival (PFS) and overall survival (OS) with time ratio (TR) 1.27 (95% credible interval [CrI], 1.15-1.40), and TR 1.19 (95% CrI, 1.09-1.27), respectively. Serious adverse events were more common with DPF, particularly hematological effects (32% vs 22%). Younger participants received greater DPF dose density without achieving greater disease control, while severe toxicity was likewise higher. DPF yielded superior OS in Lauren intestinal (TR 1.27, 95% CrI, 1.08-1.11) vs diffuse subtype (TR 1.17, 95% CrI, 1.09-1.24) and the probability of increasing OS > 15% was 90% vs 67% in each subtype, respectively. The effect dwindles over time, which can be attributed to pathological changes and clinical practice changes. Conclusion: Our study confirms the effect of DPF is highly dependent on several clinical-pathological variables, with discreet and gradually declining benefit over platinum doublets in later years, at the expense of increased toxicity. These results may help to underpin the idea that external validity of AGC trials should be revised regularly

Role of age and comorbidities in mortality of patients with infective endocarditis

[eng] Purpose: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. Methods: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. Results: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32-3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39-1.88),and non-performed surgery (HR:1.64;95% CI:11.16-1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. Conclusion: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death

Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment

Altres ajuts: Fundación Científica de la AECC (to R.G.U.); Fundación Ramón Areces (to M.F.F); FICYT (to E.G.T., M.G.G., A.C.); Asturias Regional Government [GRUPIN14-052 to M.F.F.]; Gobierno del Principado de Asturias, PCTI-Plan de Ciencia, Tecnología e Innovación co-funding Fondos FEDER (grant number IDI/2018/146 to M.F.F. and IDI/2018/144 to C.L.); Asociación Española Contra el Cáncer [AECC-CI-2015]; P.M. acknowledges financial support from The Obra Social La Caixa-Fundaciò Josep Carreras. P.M. an investigator from the Spanish Cell Therapy cooperative network (TERCEL). The IUOPA is supported by the Obra Social Liberbank-Cajastur, Spain.Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death

Front-end process modeling in silicon

Front-end processing mostly deals with technologies associated to junction formation in semiconductor devices. Ion implantation and thermal anneal models are key to predict active dopant placement and activation. We review the main models involved in process simulation, including ion implantation, evolution of point and extended defects, amorphization and regrowth mechanisms, and dopant-defect interactions. Hierarchical simulation schemes, going from fundamental calculations to simplified models, are emphasized in this Colloquium. Although continuum modeling is the mainstream in the semiconductor industry, atomistic techniques are starting to play an important role in process simulation for devices with nanometer size features. We illustrate in some examples the use of atomistic modeling techniques to gain insight and provide clues for process optimization