RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair

Cellular DNA is under constant attack by a wide variety of agents, both endogenous and exogenous. To counteract DNA damage, human cells have a large collection of DNA repair factors. Among them, DNA polymerase lambda (Polλ) stands out for its versatility, as it participates in different DNA repair and damage tolerance pathways in which gap-filling DNA synthesis is required. In this work we show that human Polλ is conjugated with Small Ubiquitin-like MOdifier (SUMO) proteins both in vitro and in vivo, with Lys27 being the main target of this covalent modification. Polλ SUMOylation takes place in the nuclear pore complex and is mediated by the E3 ligase RanBP2. This post-translational modification promotes Polλ entry into the nucleus, which is required for its recruitment to DNA lesions and stimulated by DNA damage induction. Our work represents an advance in the knowledge of molecular pathways that regulate cellular localization of human Polλ, which are essential to be able to perform its functions during repair of nuclear DNA, and that might constitute an important point for the modulation of its activity in human cells

A Test Vector Generation Method Based on Symbol Error Probabilities for Low-Complexity Chase Soft-Decision Reed-Solomon Decoding

© 2019 IEEE. Personal use of this material is permitted. Permissíon from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertisíng or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.[EN] This paper presents a low-complexity chase (LCC) decoder for Reed-Solomon (RS) codes, which uses a novel method for the selection of test vectors that is based on the analysis of the symbol error probabilities derived from simulations. Our results show that the same performance as the classical LCC is achieved with a lower number of test vectors. For example, the amount of test vectors is reduced by half and by 1/16 for the RS(255,239) and RS(255,129) codes, respectively. We provide an evidence that the proposed method is suitable for RS codes with different rates and Galois fields. In order to demonstrate that the proposed method results in a reduction of the complexity of the decoder, we also present a hardware architecture for an RS(255,239) decoder that uses 16 test vectors. This decoder achieves a coding gain of 0.56 dB at the frame error rate that is equal to 10(-6) compared with hard-decision decoding, which is higher than that of an eta = 5 LCC. The implementation results in ASIC show that a throughput of 3.6 Gb/s can be reached in a 90-nm process and 29.1XORs are required. The implementation results in Virtex-7 FPGA devices show that the decoder reaches 2.5 Gb/s and requires 5085 LUTs.This work was supported by the Spanish Ministerio de Economia y Competitividad and FEDER under Grant TEC2015-70858-C2-2-R. This paper was recommended by Associate Editor M. Boukadoum.Valls Coquillat, J.; Torres Carot, V.; Canet Subiela, MJ.; García-Herrero, FM. (2019). A Test Vector Generation Method Based on Symbol Error Probabilities for Low-Complexity Chase Soft-Decision Reed-Solomon Decoding. IEEE Transactions on Circuits and Systems I Regular Papers. 66(6):2198-2207. https://doi.org/10.1109/TCSI.2018.2882876S2198220766

Severa complicación neurológica tras vertebroplastia percutánea

La vertebroplastia percutánea como tratamiento de las fracturas acuñamientos vertebrales osteoporóticos tras fracaso del tratamiento sintomático y ortopédico así como para el tratamiento de lesiones tumorales del caquis ha tomado un auge importante debido a los buenos resultados publicados y la baja tasa de complicaciones. Este hecho ha llevado a las casas comerciales a desarrollar productos específicos para esta técnica que simplifican su utilización y disminuyen en lo posible las dificultades técnicas del procedimiento así como sus complicaciones. A pesar de ello, en nuestra opinión es una técnica que requiere una alta demanda de entrenamiento y que puede dar lugar a graves complicaciones a pesar de que no existan prácticamente en la literatura complicaciones severas con la utilización de esta técnica. Presentamos un caso ocurrido en nuestra serie de una paraplejia completa no resuelta tras una vertebroplastia percutanea torácica para una fractura osteoporótica.The technique of percutaneous vertebroplasty for osteoporotic fractures and spine tumors was develop an important increase because there were a lot of publications with good results and low rate of complications. This fact was done a fast developing of instruments and new PMMA cements to simplify this technique and decreased the rate of complications. In our opinion the percutaneous vertebroplasty is a high demand technique and have a high potential of major neurological complications if it is not performed with use of appropriate safeguards, but the purpose of this article is not to condemn the technique because we have had a good results using it in this pathologies and the majority of publications have shown a high rate of excellent results

Consensus of experts from the Spanish pharmacogenetics and pharmacogenomics society and the Spanish society of medical oncology for the genotyping of DPYD in cancer patients who are candidates for treatment with fluoropyrimidines

5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidinesThis project has been financed with SEOM and SEFF resource

Consensus of experts from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology for the genotyping of DPYD in cancer patients who are candidates for treatment with fluoropyrimidines

5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidines

Evaluation and assessment of professional skills in the Final Year Project

In this paper, we present a methodology for Final Year Project (FYP) monitoring and assessment that considers the inclusion of the professional skills required in the particular engineering degree. This proper monitoring and clear evaluation framework provides the student with valuable support for the project implementation as well as for improving the quality of the projects, thereby reducing the academic drop-out rate. The proposed methodology has been implemented at the Barcelona School of Informatics at the Universitat Politècnica de Catalunya - BarcelonaTech. The FYP is structured around three milestones: project definition, project monitoring and project completion. Skills are assigned to each milestone according to the tasks required in that phase, and a list of indicators is defined for each phase. The evaluation criteria for each indicator at each phase are specified in a rubric, and are made public both to students and teachers. Thus, the FYP includes an exhaustive evaluation method distributed throughout the whole project implementation, thereby facilitating project organization for the student as well as providing a clear and homogeneous assessment framework. The methodology for the FYP organization, assessment and evaluation was launched and piloted over two semesters. We believe the experience to be general in the sense that it has been conducted as part of an ICT engineering degree, but may easily be extended to any other engineering degree.Postprint (author’s final draft

Hif-1α knockdown reduces glycolytic metabolism and induces cell death of human synovial fibroblasts under normoxic conditions

[Abstract] Increased glycolysis and HIF-1α activity are characteristics of cells under hypoxic or inflammatory conditions. Besides, in normal O2 environments, elevated rates of glycolysis support critical cellular mechanisms such as cell survival. The purpose of this study was to analyze the contribution of HIF-1α to the energy metabolism and survival of human synovial fibroblasts (SF) under normoxic conditions. HIF-1α was silenced using lentiviral vectors or small-interfering RNA (siRNA) duplexes. Expression analysis by qRT-PCR and western blot of known HIF-1α target genes in hypoxia demonstrated the presence of functional HIF-1α in normoxic SF and confirmed the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a HIF-1α target even in normoxia. HIF-1α silencing induced apoptotic cell death in cultured SF and, similarly, treatment with glycolytic, but not with OXPHOS inhibitors, induced SF death. Finally, in vivo HIF-1α targeting by siRNA showed a significant reduction in the viability of human SF engrafted into a murine air pouch. Our results demonstrate that SF are highly dependent on glycolytic metabolism and that HIF-1α plays a regulatory role in glycolysis even under aerobic conditions. Local targeting of HIF-1α provides a feasible strategy to reduce SF hyperplasia in chronic arthritic diseases.Instituto de Salud Carlos III; FIS 12/439Instituto de Salud Carlos III; RETICS RD12/009Instituto de Salud Carlos III; CP13/00014Comunidad de Madrid; RAPHYME-CM S2010/BMD235

Non-conventional yeasts as hosts for heterologous protein production.

Yeasts are an attractive group of lower eukaryotic microorganisms, some of which are used in several industrial processes that include brewing, baking and the production of a variety of biochemical compounds. More recently, yeasts have been developed as host organisms for the production of foreign (heterologous) proteins. Saccharomyces cerevisiae has usually been the yeast of choice, but an increasing number of alternative non-Saccharomyces yeasts has now become accessible for modern molecular genetics techniques. Some of them exhibit certain favourable traits such as high-level secretion or very strong and tightly regulated promoters, offering significant advantages over traditional bakers' yeast. In the present work, the current status of Kluyveromyces lactis, Yarrowia lipolytica, Hansenula polymorpha and Pichia pastoris (the best-known alternative yeast systems) is reviewed. The advantages and limitations of these systems are discussed in relation to S. cerevisiae.Spanish Society for Microbiolog

Guía de las actividades de los contenidos del segundo cuatrimestre de la asignatura de Citología e Histología Vegetal y Animal

En este trabajo recogemos las principales pautas y metodología seguida para la elaboración de la Guía de Estudio de parte de los contenidos del segundo cuatrimestre de la asignatura de Citología e Histología Animal y Vegetal de los estudios de Biología. En dicha guía se recoge el desarrollo de las actividades docentes que han sido llevadas a cabo utilizando la plataforma informática Campos Virtual de la Universidad de Alicante. Se trata del ensayo de una nueva manera de abordar el proceso de enseñanza/aprendizaje de nuestros alumnos, tendente a la adaptación de los contenidos de Histología al Espacio Europeo de Educación Superior (EEES). El método empleado ha sido introducir a nuestros alumnos a ser los artífices de su propia formación, mediante la realización tanto de tareas de autoaprendizaje como la exposición de sus resultados al resto de sus compañeros en una serie de seminarios. La metodología empleada se expone en cada uno de los apartados de esta guía