Identificación de marcadores predictivos de toxicidad y eficacia del paclitaxel: regulación y variación genética de la ß-tubulina y estudio de asociación del genoma completo

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica y realizada en el Centro Nacional de Investigaciones Oncológicas (CNIO). Fecha de lectura: 22 de Octubre de 2012

Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers

TERT promoter mutation; Subtelomeric gene expression; Telomere shorteningMutació del promotor TERT; Expressió gènica subtelomèrica; Escurçament dels telòmersMutación del promotor TERT; Expresión génica subtelomérica; Acortamiento de los telómerosBackground Comprehensive molecular studies on tumours are needed to delineate immortalization process steps and identify sensitive prognostic biomarkers in thyroid cancer. Methods and Results In this study, we extensively characterize telomere-related alterations in a series of 106 thyroid tumours with heterogeneous clinical outcomes. Using a custom-designed RNA-seq panel, we identified five telomerase holoenzyme-complex genes upregulated in clinically aggressive tumours compared to tumours from long-term disease-free patients, being TERT and TERC denoted as independent prognostic markers by multivariate regression model analysis. Characterization of alterations related to TERT re-expression revealed that promoter mutations, methylation and/or copy gains exclusively co-occurred in clinically aggressive tumours. Quantitative-FISH (fluorescence in situ hybridization) analysis of telomere lengths showed a significant shortening in these carcinomas, which matched with a high proliferative rate measured by Ki-67 immunohistochemistry. RNA-seq data analysis indicated that short-telomere tumours exhibit an increased transcriptional activity in the 5-Mb-subtelomeric regions, site of several telomerase-complex genes. Gene upregulation enrichment was significant for specific chromosome-ends such as the 5p, where TERT is located. Co-FISH analysis of 5p-end and TERT loci showed a more relaxed chromatin configuration in short telomere-length tumours compared to normal telomere-length tumours. Conclusions Overall, our findings support that telomere shortening leads to a 5p subtelomeric region reorganization, facilitating the transcription and accumulation of alterations at TERT-locus.This work was supported by Projects PI17/01796 and PI20/01169 [Instituto de Salud Carlos III (ISCIII), Acción Estratégica en Salud, cofinanciado a través del Fondo Europeo de Desarrollo Regional (FEDER)] and Comunidad de Madrid (S2017/BMD-3724; TIRONET2-CM) to MR. CM-C was partially supported by a grant from the Fundación Científica Asociación Española Contra el Cáncer (AIO15152858 MONT). LJL-G was supported both by the Banco Santander Foundation – CNIO Fellowship and by ‘la Caixa’ Foundation (ID 100010434), under agreement LCF/BQ/PI20/11760011. AMM-M was supported by CAM (S2017/BMD-3724; TIRONET2-CM). MM was supported by the Ministerio de Ciencia, Innovación y Universidades (Spain; ‘Formación del Profesorado Universitario – FPU’ fellowship (FPU18/00064)). We thank CNIO Biobank for their support with the frozen specimens processing. We thank the Spanish National Tumor Bank Network (RD09/0076/00047) for the support in obtaining tumour samples, and all patients, physicians and tumour biobanks involved in the study

Desarrollo de API de consulta a fuentes de información en la web para sistemas de argumentación rebatible

Es cada vez más necesario automatizar los procesos que integran la información que se encuentra disponible en diferentes formatos, descentralizada, con orígenes heterogéneos y administraciones diferentes. Uno de los grandes desafíos al integrar fuentes de datos heterogénea, es poder manejar la inconsistencia informacional y la posible incompletitud que puede trasladarse de las fuentes locales. Los formalismos de Argumentación son adecuados para manejar este tipo de problemas. En particular, pensar en formalismos de argumentación rebatible (como DeLP) para la definición y automatización de la integración de fuentes de datos heterogéneas, inconsistentes entre sí e incompletas, es una opción aceptable. El trabajo de esta línea de investigación propone desarrollar interfaces para vincular DeLP con fuentes de datos en formatos web. En especial, fuentes de sitios web descriptas en HTML y en Servicios Web. La información obtenidas de estas fuentes, podrán ser utilizadas como hechos o presunciones en la base de conocimiento que utiliza el sistema argumentativo.Eje: Agentes y Sistemas InteligentesRed de Universidades con Carreras en Informática (RedUNCI

Novel DNMT3A Germline Variant in a Patient with Multiple Paragangliomas and Papillary Thyroid Carcinoma

Over the past few years, next generation technologies have been applied to unravel the genetics of rare inherited diseases, facilitating the discovery of new susceptibility genes. We recently found germline DNMT3A gain-of-function variants in two patients with head and neck paragangliomas causing a characteristic hypermethylated DNA profile. Here, whole-exome sequencing identifies a novel germline DNMT3A variant (p.Gly332Arg) in a patient with bilateral carotid paragangliomas, papillary thyroid carcinoma and idiopathic intellectual disability. The variant, located in the Pro-Trp-Trp-Pro (PWWP) domain of the protein involved in chromatin targeting, affects a residue mutated in papillary thyroid tumors and located between the two residues found mutated in microcephalic dwarfism patients. Structural modelling of the variant in the DNMT3A PWWP domain predicts that the interaction with H3K36me3 will be altered. An increased methylation of DNMT3A target genes, compatible with a gain-of-function effect of the alteration, was observed in saliva DNA from the proband and in one independent acute myeloid leukemia sample carrying the same p.Gly332Arg variant. Although further studies are needed to support a causal role of DNMT3A variants in paraganglioma, the description of a new DNMT3A alteration in a patient with multiple clinical features suggests a heterogeneous phenotypic spectrum related to DNMT3A germline variants

Remote Glucose Monitoring Platform for Multiple Simultaneous Patients at Coronavirus Disease 2019 Intensive Care Units: Case Report including Adults and Children

This work focuses on remote glucose monitoring at COVID-19 Intensive Care Units (ICU)in Argentina. We report the first cases using a new emergency platform for multi-centermulti-patient on-line remote glucose monitoring, which is accessible for everyone ondemand and which allows the integration of different glucose sensors. Five critical patientshave been monitored, two children and three adults, together with an ambulatory patient totest the platform versatility. All ICU patients have recovered or have been metabolicallycontrolled by the date of the submission of this report. Relevant lessons have been learnedfor the glucose management of critical patients, resulting in a new protocol in one of theparticipant hospitals.Fil: Garelli, Fabricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: Rosales, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: Fushimi, Emilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: Arambarri, Delfina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: Mendoza, Leandro Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: de Battista, Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: Sanchez Peña, Ricardo Salvador. Instituto Tecnológico de Buenos Aires. Departamento de Matemática. Centro de Sistemas y Control; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: García Arabehety, Julia. Hospital Italiano; ArgentinaFil: DIstefano, Sabrina. Hospital Italiano; ArgentinaFil: Barcala, Consuelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Giunta, Javier. Hospital Italiano; ArgentinaFil: Las Heras, Marcos. Hospital Italiano; ArgentinaFil: Martinez Mateu, Carolina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Prieto, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: San Román, Eduardo. Hospital Italiano; ArgentinaFil: Krochik, Andrea Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Grosembacher, Luis. Hospital Italiano; Argentin

Measurement procedures for an adaptive antenna system: application to WCDMA

Adaptive type smart antennas have not been implemented yet on the deployed UMTS systems, although UTRA-UMTS preview their operation and they also could improve capacity especially in a multiservice environment. This paper describes a set of novel measurement techniques that must be performed to evaluate the correct operation of a smart antenna system. The paper also describes the measurements carried out on a UMTS smart antenna prototype

Allelic variant at −79 (C>T) in CDKN1B (p27Kip1) confers an increased risk of thyroid cancer and alters mRNA levels

The aim of this study is to assess if common genetic variants located in the CDKN1B locus, coding for the cell cycle inhibitor p27Kip1, are involved in thyroid cancer susceptibility. Based on the literature and functional predictions, we selected three polymorphisms within the CDKN1B gene (rs2066827 (T326G, V109G), rs34330 (−79C>T) and rs36228499 (−838C>A)) to perform the first case–control study in thyroid cancer involving this locus. We had 649 Spanish patients with sporadic thyroid cancer and 385 healthy representative controls available. Luciferase reporter gene assays, real-time quantitative reverse transcription-PCR and immunoblot experiments were carried out to demonstrate the putative effect of the associated variant. The polymorphism rs34330 (−79C>T) was identified as a risk factor for developing the follicular variant of papillary thyroid carcinoma (FVPTC), fitting a recessive model (odds ratio=2.12; 95% confidence interval=1.09–4.15; P value=0.023). The risk allele (T) of this single nucleotide polymorphism led to a lower transcription rate in cells transfected with a luciferase reporter driven by the polymorphic p27Kip1 promoter (P value T (rs34330) variant as a novel mechanism underlying p27Kip1 downregulation

SANAA, Rolex Learning Center

En el curso 2012-2013 el Laboratorio de Crítica centró su atención en el Rolex Learning Center de l´Ecole Polytechnique Fédérale de Lausanne en Suiza, obra de indudable interés del estudio japonés SANAA que constituye en sí misma un auténtico experimento y, consecuentemente, un objeto de observación apropiado para el estudio dentro del Laboratorio. En octubre de 2012 se realizó un viaje para visitar el edificio y, posteriormente, se realizaron por parte de los alumnos, ejercicios críticos y experimentos de los que en esta publicación aparece una muestra representativa. También se recogen en este libro, publicado gracias al apoyo de la ETSAM dentro de su colección de Texto Académicos, algunas aportaciones externas como el escrito y los dibujos del arquitecto Javier Aguilera, así como otros textos de antiguos alumnos del Laboratorio como Rosa Ballester, Berta González Salinero o Daniel Sacristán que, además han contribuido decisivamente en la edición. Se incluye, asimismo, un artículo de Eider Holgado, alumna de doctorado que está realizando su tesis, dentro del G.I. ARKRIT

Novedades corológicas para la flora vascular de la sierra de Gredos (Sistema Central, España)

In the present paper, 58 chorological novelties for Gredos range (Central System, Spain) are showed. Some of them represent important disjunctions with respect to known Iberian distribution, as the cases of Cytinus ruber (Fourr.) Fritsh, Isolepis fluitans (L.) R.Br., Alyssum montanum L. and Lysimachia ephemerum L. Some species, such as Carex lainzii Luceño, E. Rico & T. Romero, Iberodes brassicifolia (Lag.) Serrano, R. Carbajal & S. Ortiz, Lycopodiella inundata (L.) J. Holub and Tephroseris coincyi (Rouy) Holub are of great interest from a conservational point of view. Finally, we present a number of provincial novelties, mainly for Ávil

Management of acute diverticulitis with pericolic free gas (ADIFAS). an international multicenter observational study

Background: There are no specific recommendations regarding the optimal management of this group of patients. The World Society of Emergency Surgery suggested a nonoperative strategy with antibiotic therapy, but this was a weak recommendation. This study aims to identify the optimal management of patients with acute diverticulitis (AD) presenting with pericolic free air with or without pericolic fluid. Methods: A multicenter, prospective, international study of patients diagnosed with AD and pericolic-free air with or without pericolic free fluid at a computed tomography (CT) scan between May 2020 and June 2021 was included. Patients were excluded if they had intra-abdominal distant free air, an abscess, generalized peritonitis, or less than a 1-year follow-up. The primary outcome was the rate of failure of nonoperative management within the index admission. Secondary outcomes included the rate of failure of nonoperative management within the first year and risk factors for failure. Results: A total of 810 patients were recruited across 69 European and South American centers; 744 patients (92%) were treated nonoperatively, and 66 (8%) underwent immediate surgery. Baseline characteristics were similar between groups. Hinchey II-IV on diagnostic imaging was the only independent risk factor for surgical intervention during index admission (odds ratios: 12.5, 95% CI: 2.4-64, P =0.003). Among patients treated nonoperatively, at index admission, 697 (94%) patients were discharged without any complications, 35 (4.7%) required emergency surgery, and 12 (1.6%) percutaneous drainage. Free pericolic fluid on CT scan was associated with a higher risk of failure of nonoperative management (odds ratios: 4.9, 95% CI: 1.2-19.9, P =0.023), with 88% of success compared to 96% without free fluid ( P <0.001). The rate of treatment failure with nonoperative management during the first year of follow-up was 16.5%. Conclusion: Patients with AD presenting with pericolic free gas can be successfully managed nonoperatively in the vast majority of cases. Patients with both free pericolic gas and free pericolic fluid on a CT scan are at a higher risk of failing nonoperative management and require closer observation