Farmacocinética comparada de prograf y advagraf y desarrollo de modelos clínico-genéticos para la predicción de la disposición de tacrolimus en niños trasplantados

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Farmacología. Fecha de lectura: 23-10-201

Listeriosis in Portugal: an existing but under reported infection

BACKGROUND: Listeriosis is a rare disease caused by the bacterium Listeria monocytogenes, the normal vehicle of which is food. The disease, which is largely confined to its risk groups of pregnant women, the elderly and immunocompromised individuals, has increased in incidence in recent years. In Portugal, listeriosis is not a notifiable infection and available data are scarce. The objective of this work was to collate the available information concerning listeriosis in Portugal by compiling a retrospective study of cases recorded over a decade. METHODS: Requests for case data on clinically confirmed listeriosis, recorded over the previous decade, were replied to by 23 hospitals and a National Institute of Health delegation. RESULTS: 35 cases of listeriosis were identified for the period between 1994 and 2003 inclusive, the mortality rate being greater than 17%. According to the data collected in this study for the year 2003, the incidence of this disease in Portugal was at least 1.4 cases per million inhabitants in that year. CONCLUSION: The study demonstrates, for the first time in the widely available literature, that despite their being no cases of listeriosis in Portugal recorded in official reports, the threat of L. monocytogenes to public health is of a similar dimension to that in other countries

Rendimento de milho em consórcio com forrageiras dos gêneros Brachiaria e Panicum.

O objetivo deste estudo foi avaliar o rendimento do milho em consórcio com Brachiaria ruziziensis e Panicum maximum cv. BRS Zuri em comparação ao cultivo de milho solteiro.IX SIMPA

ER Stress-Inducible Factor CHOP Affects the Expression of Hepcidin by Modulating C/EBPalpha Activity

Endoplasmic reticulum (ER) stress induces a complex network of pathways collectively termed the unfolded protein response (UPR). The clarification of these pathways has linked the UPR to the regulation of several physiological processes. However, its crosstalk with cellular iron metabolism remains unclear, which prompted us to examine whether an UPR affects the expression of relevant iron-related genes. For that purpose, the HepG2 cell line was used as model and the UPR was activated by dithiothreitol (DTT) and homocysteine (Hcys). Here, we report that hepcidin, a liver secreted hormone that shepherds iron homeostasis, exhibits a biphasic pattern of expression following UPR activation: its levels decreased in an early stage and increased with the maintenance of the stress response. Furthermore, we show that immediately after stressing the ER, the stress-inducible transcription factor CHOP depletes C/EBPα protein pool, which may in turn impact on the activation of hepcidin transcription. In the later period of the UPR, CHOP levels decreased progressively, enhancing C/EBPα-binding to the hepcidin promoter. In addition, analysis of ferroportin and ferritin H revealed that the transcript levels of these iron-genes are increased by the UPR signaling pathways. Taken together, our findings suggest that the UPR can have a broad impact on the maintenance of cellular iron homeostasis

A new strategy for enhancing imputation quality of rare variants from next-generation sequencing data via combining SNP and exome chip data

Background: Rare variants have gathered increasing attention as a possible alternative source of missing heritability. Since next generation sequencing technology is not yet cost-effective for large-scale genomic studies, a widely used alternative approach is imputation. However, the imputation approach may be limited by the low accuracy of the imputed rare variants. To improve imputation accuracy of rare variants, various approaches have been suggested, including increasing the sample size of the reference panel, using sequencing data from study-specific samples (i.e., specific populations), and using local reference panels by genotyping or sequencing a subset of study samples. While these approaches mainly utilize reference panels, imputation accuracy of rare variants can also be increased by using exome chips containing rare variants. The exome chip contains 250 K rare variants selected from the discovered variants of about 12,000 sequenced samples. If exome chip data are available for previously genotyped samples, the combined approach using a genotype panel of merged data, including exome chips and SNP chips, should increase the imputation accuracy of rare variants. Results: In this study, we describe a combined imputation which uses both exome chip and SNP chip data simultaneously as a genotype panel. The effectiveness and performance of the combined approach was demonstrated using a reference panel of 848 samples constructed using exome sequencing data from the T2D-GENES consortium and 5,349 sample genotype panels consisting of an exome chip and SNP chip. As a result, the combined approach increased imputation quality up to 11 %, and genomic coverage for rare variants up to 117.7 % (MAF < 1 %), compared to imputation using the SNP chip alone. Also, we investigated the systematic effect of reference panels on imputation quality using five reference panels and three genotype panels. The best performing approach was the combination of the study specific reference panel and the genotype panel of combined data. Conclusions: Our study demonstrates that combined datasets, including SNP chips and exome chips, enhances both the imputation quality and genomic coverage of rare variants

Identification of boosted, hadronically decaying W bosons and comparisons with ATLAS data taken at √s = 8 TeV

This paper reports a detailed study of techniques for identifying boosted, hadronically decaying W bosons using 20.3 fb −¹ of proton–proton collision data collected by the ATLAS detector at the LHC at a centre-of-mass energy √s = 8 TeV. A range of techniques for optimising the signal jet mass resolution are combined with various jet substructure variables. The results of these studies in Monte Carlo simulations show that a simple pairwise combination of groomed jet mass and one substructure variable can provide a 50 % efficiency for identifying W bosons with transverse momenta larger than 200 GeV while maintaining multijet background efficiencies of 2–4 % for jets with the same transverse momentum. These signal and background efficiencies are confirmed in data for a selection of tagging techniques

BacHBerry: BACterial Hosts for production of Bioactive phenolics from bERRY fruits

BACterial Hosts for production of Bioactive phenolics from bERRY fruits (BacHBerry) was a 3-year project funded by the Seventh Framework Programme (FP7) of the European Union that ran between November 2013 and October 2016. The overall aim of the project was to establish a sustainable and economically-feasible strategy for the production of novel high-value phenolic compounds isolated from berry fruits using bacterial platforms. The project aimed at covering all stages of the discovery and pre-commercialization process, including berry collection, screening and characterization of their bioactive components, identification and functional characterization of the corresponding biosynthetic pathways, and construction of Gram-positive bacterial cell factories producing phenolic compounds. Further activities included optimization of polyphenol extraction methods from bacterial cultures, scale-up of production by fermentation up to pilot scale, as well as societal and economic analyses of the processes. This review article summarizes some of the key findings obtained throughout the duration of the project