Estudio para la mejora de la calidad del vino albariño

Premio de Investigación, Real Academia Galega de Ciencias, convocatoria 2009.[EN]Twenty-two clones from Albariño variety (Vitis vinifera L.), from an initial collection of 115 clones, were selected on the basis of their ampelographic, molecular and sanitary characteristics. These selected clones were studied from the agronomic and oenological point of view, and were also quantified for their levels of susceptibility to Powdery Mildew, Oidium and Botrytis. An ecotypic yeast was selected, its use has been patented and it is being exploited. Musts obtained from the previously selected Albariño clones were fermented with this yeast, essentially by increasing the content in volatile substances of interest (terpens: linalool and geraniol; norisoprenoids: α-ionone and β- damascenone), leading to wines with improved fermentative dynamic and sensorial attributes.[ES]En base a características ampelográficas, moleculares y sanitarias, se seleccionaron 22 clones de la variedad Albariño (Vitis vinifera L.), partiendo de 115 iniciales. Sobre los clones seleccionados se ha llevado a cabo un estudio agronómico y enológico, así como la cuantificación de los niveles de susceptibilidad a Mildiu, Oídio y Botrytis. Se ha seleccionado una levadura ecotípica, cuyo uso ha sido patentado y se encuentra en explotación. Con ella se fermentaron los mostos obtenidos a partir de los clones de Albariño previamente seleccionados, dando lugar a vinos con una dinámica fermentativa xPremio de Investigación, Real Academia Galega de Ciencias, convocatoria 2009 y unos atributos sensoriales mejorados, fundamentalmente en base al aumento del contenido en sustancias volátiles de interés (terpenos: linalool y geraniol; norisoprenoides: α-ionona y β- damascenona).La actividad realizada ha sido financiada, además de por la Bodega Terras Gauda S.A., por la Xunta de Galicia (PGIDIT04TAL035E), y por el propio CSIC (PIE 2004 7 0E 214).Peer reviewe

Breast cancer PAM50 signature: Correlation and concordance between RNA-Seq and digital multiplexed gene expression technologies in a triple negative breast cancer series

Background: Full RNA-Seq is a fundamental research tool for whole transcriptome analysis. However, it is too costly and time consuming to be used in routine clinical practice. We evaluated the transcript quantification agreement between RNA-Seq and a digital multiplexed gene expression platform, and the subtype call after running the PAM50 assay in a series of breast cancer patients classified as triple negative by IHC/FISH. The goal of this study is to analyze the concordance between both expression platforms overall, and for calling PAM50 triple negative breast cancer intrinsic subtypes in particular. Results: The analyses were performed in paraffin-embedded tissues from 96 patients recruited in a multicenter, prospective, non-randomized neoadjuvant triple negative breast cancer trial (NCT01560663). Pre-treatment core biopsies were obtained following clinical practice guidelines and conserved as FFPE for further RNA extraction. PAM50 was performed on both digital multiplexed gene expression and RNA-Seq platforms. Subtype assignment was based on the nearest centroid classification following this procedure for both platforms and it was concordant on 96% of the cases (N = 96). In four cases, digital multiplexed gene expression analysis and RNA-Seq were discordant. The Spearman correlation to each of the centroids and the risk of recurrence were above 0.89 in both platforms while the agreement on Proliferation Score reached up to 0.97. In addition, 82% of the individual PAM50 genes showed a correlation coefficient > 0.80. Conclusions: In our analysis, the subtype calling in most of the samples was concordant in both platforms and the potential discordances had reduced clinical implications in terms of prognosis. If speed and cost are the main driving forces then the preferred technique is the digital multiplexed platform, while if whole genome patterns and subtype are the driving forces, then RNA-Seq is the preferred method

Breast cancer PAM50 signature: correlation and concordance between RNA-Seq and digital multiplexed gene expression technologies in a triple negative breast cancer series

[Background]: Full RNA-Seq is a fundamental research tool for whole transcriptome analysis. However, it is too costly and time consuming to be used in routine clinical practice. We evaluated the transcript quantification agreement between RNA-Seq and a digital multiplexed gene expression platform, and the subtype call after running the PAM50 assay in a series of breast cancer patients classified as triple negative by IHC/FISH. The goal of this study is to analyze the concordance between both expression platforms overall, and for calling PAM50 triple negative breast cancer intrinsic subtypes in particular.[Results]: The analyses were performed in paraffin-embedded tissues from 96 patients recruited in a multicenter, prospective, non-randomized neoadjuvant triple negative breast cancer trial (NCT01560663). Pre-treatment core biopsies were obtained following clinical practice guidelines and conserved as FFPE for further RNA extraction. PAM50 was performed on both digital multiplexed gene expression and RNA-Seq platforms. Subtype assignment was based on the nearest centroid classification following this procedure for both platforms and it was concordant on 96% of the cases (N = 96). In four cases, digital multiplexed gene expression analysis and RNA-Seq were discordant. The Spearman correlation to each of the centroids and the risk of recurrence were above 0.89 in both platforms while the agreement on Proliferation Score reached up to 0.97. In addition, 82% of the individual PAM50 genes showed a correlation coefficient > 0.80.[Conclusions]: In our analysis, the subtype calling in most of the samples was concordant in both platforms and the potential discordances had reduced clinical implications in terms of prognosis. If speed and cost are the main driving forces then the preferred technique is the digital multiplexed platform, while if whole genome patterns and subtype are the driving forces, then RNA-Seq is the preferred method.M.M was supported by two research grants from Ministry of Economy and Competitiveness ISCIII-FIS grants (PI 12/02684): “Predictores genómicos de respuesta a la quimioterapia neoadyuvante con docetaxel-carboplatino en pacientes con cáncer de mama triple negativo”/“Genomic predictors of response to neoadjuvant chemotherapy with docetaxel-carboplatin in patients with triple negative breast cancer”; and (PI 15/00117): “Cáncer de mama triple negative: Predicción de respuesta a docetaxel-carboplatino neoadyuvante mediante caracterización de TILs y firmas inmunes basadas en secuenciación masiva de RNA”/” Triple negative breast cancer: Prediction of response to neoadjuvant docetaxel-carboplatin by characterization of TILs and immune signatures based on massive RNA sequencing”. C.M.P was supported by funds from the NCI Breast SPORE program (P50-CA58223).Peer reviewe

Pathological response in a triple-negative breast cancer cohort treated with neoadjuvant carboplatin and docetaxel according to Lehmann's refined classification

Purpose: Triple-negative breast cancer (TNBC) requires the identification of reliable predictors of response to neoadjuvant chemotherapy (NACT). For this purpose, we aimed to evaluate the performance of the TNBCtype-4 classifier in a cohort of patients with TNBC treated with neoadjuvant carboplatin and docetaxel (TCb). Methods: Patients with TNBC were accrued in a nonrandomized trial of neoadjuvant carboplatin AUC 6 and docetaxel 75 mg/m2 for six cycles. Response was evaluated in terms of pathologic complete response (pCR, ypT0/is ypN0) and residual cancer burden by Symmans and colleagues. Lehmann's subtyping was performed using the TNBCtype online tool from RNAseq data, and germline sequencing of a panel of seven DNA damage repair genes was conducted. Results: Ninety-four out of the 121 patients enrolled in the trial had RNAseq available. The overall pCR rate was 44.7%. Lehmann subtype distribution was 34.0% BL1, 20.2% BL2, 23.4% M, 14.9% LAR, and 7.4% were classified as ERþ. Response to NACT with TCb was significantly associated with Lehmann subtype (P ¼ 0.027), even in multivariate analysis including tumor size and nodal involvement, with BL1 patients achieving the highest pCR rate (65.6%), followed by BL2 (47.4%), M (36.4%), and LAR (21.4%). BL1 was associated with a significant younger age at diagnosis and higher ki67 values. Among our 10 germline mutation carriers, 30% were BL1, 40% were BL2, and 30% were M. Conclusions: TNBCtype-4 is associated with significantly different pCR rates for the different subtypes, with BL1 and LAR displaying the best and worse responses to NACT, respectively

Protocolo de cribado, diagnóstico y tratamiento de la enfermedad de Chagas en mujeres embarazadas latinoamericanas y en sus hijos

Malaltia de Chagas; Dones embarassades llatinoamericanes; Salut maternoinfantilEnfermedad de Chagas; Mujeres embarazadas latinoamericanas; Salud maternoinfantilChagas disease; Latin american pregnant women; Maternal and child healthLa malaltia de Chagas (MCH) continua sent un problema important de salut pública. L’OMS estima que en el món hi ha 8 milions de persones infectades per Trypanosoma cruzi, la majoria a l’Amèrica Llatina. En països no endèmics, com és el cas del nostre entorn, l’MCH s’observa en persones infectades que provenen de països endèmics o en infants nascuts en països no endèmics, però la mare dels quals ha estat infectada (transmissió congènita). A Catalunya, per tal de fer el control i la vigilància de l’MCH, l’any 2010 es va posar en marxa el Programa de prevenció i control de la malaltia de Chagas congènita a Catalunya, coordinat pel Departament de Salut i que inclou el diagnòstic, el control, el seguiment i el tractament de l’MCH congènita dirigits a les dones embarassades i als seus fills. En el marc del Programa, es va elaborar el Protocol de cribratge i diagnòstic de malaltia de Chagas en dones embarassades llatinoamericanes i en els seus fills, que es va editar el 2010. Aquest document va ser fruit de l’esforç conjunt de professionals sanitaris experts en la malaltia, de diferents societats científiques i de professionals del Departament de Salut de la Generalitat de Catalunya, amb el suport del Grup de Treball de Països No Endèmics i del Departament de Control de Malalties Tropicals Oblidades de l’OMS. El Protocol que es presenta, a més d’incloure les mateixes línies que la primera edició, disposa d’actualitzacions de diferents aspectes clínics, de diagnòstic i de vigilància epidemiològica basats en l’experiència i l’evidència observades durant aquests vuit anys del Programa de prevenció i control de la malaltia de Chagas congènita a Catalunya. Durant aquests darrers anys, s’ha reforçat la perspectiva de salut pública en el Programa, en el qual han participat un gran nombre de professionals de la xarxa assistencial i agents comunitaris de salut amb l’objectiu de reduir l’efecte de la transmissió vertical de l’MCH a Catalunya. La primera part del document recull les característiques clíniques de l’MCH que, encara que és d’aparició relativament recent en el nostre entorn, gràcies a la informació facilitada tant en l’àmbit sanitari com en l’àmbit comunitari durant els últims anys, ha deixat de ser una malaltia oblidada i desconeguda a Catalunya. En els darrers anys, els avenços i l’experiència en el nostre entorn en el diagnòstic de l’MCH ens han fet arribar a un consens sobre la utilització de mètodes directes moleculars, tal com es descriu en aquest Protocol. Així mateix, la concreció de dades epidemiològiques sobre prevalença d’infecció i incidència de casos de la malaltia ha millorat molt gràcies a la vigilància i notificació de dades recollides en el marc del Programa de prevenció i control de la malaltia de Chagas congènita a Catalunya pels professionals que formen part del Grup de Treball de la Malaltia de Chagas Congènita. En aquest aspecte i per tal de millorar-ne el control s’han incorporat els metges de família i salut comunitària, ja que són uns dels professionals clau que es troben més propers als pacients. Un aspecte fonamental que es desprèn d’aquest document i del funcionament del Programa és la multidisciplinarietat. El repte del sistema de salut i de la vigilància de la salut pública és la coordinació i el treball dels professionals de diferents àmbits sanitaris, com poden ser els ginecòlegs, els microbiòlegs, els llevadors, els pediatres d’atenció primària i hospitalària, els metges de família i salut comunitària, el personal d’infermeria, els infectòlegs, els epidemiòlegs i els agents de salut comunitària que treballen de manera conjunta per a l’assoliment de l’objectiu plantejat. El present Protocol constitueix un document eminentment pràctic, mitjançant el qual els professionals sanitaris disposen dels elements essencials per a la realització del cribratge en la dona embarassada. A partir d’aquest Protocol s’espera també aconseguir la detecció i el tractament precoç dels casos d’MCH en la població pediàtrica, nadons i altres fills a Catalunya, amb l’objectiu últim de millorar la salut maternoinfantil a Catalunya.La enfermedad de Chagas (ECH) sigue siendo un problema importante de salud pública. La OMS estima que en el mundo hay 8 millones de personas infectadas por Trypanosoma cruzi, la mayoría en América Latina. En países no endémicos, como es el caso de nuestro entorno, la ECH se observa en personas infectadas que provienen de países endémicos o en niños nacidos en países no endémicos, pero cuya madre ha sido infectada (transmisión congénita). En Cataluña, para hacer el control y la vigilancia de la ECH, en 2010 se puso en marcha el Programa de prevención y control de la enfermedad de Chagas congénita en Cataluña, coordinado por el Departamento de Salud y que incluye el diagnóstico, el control, el seguimiento y el tratamiento de la ECH congénita dirigidos a las mujeres embarazadas y a sus hijos. En el marco del Programa, se elaboró el Protocolo de cribado y diagnóstico de enfermedad de Chagas en mujeres embarazadas latinoamericanas y en sus hijos, que se editó en 2010. Este documento fue fruto del esfuerzo conjunto de profesionales sanitarios expertos en la enfermedad, de diferentes sociedades científicas y de profesionales del Departamento de Salud de la Generalidad de Cataluña, con el apoyo del Grupo de Trabajo de Países No Endémicos y del Departamento de Control de Enfermedades Tropicales Olvidadas de la OMS. El Protocolo que se presenta, además de incluir las mismas líneas que la primera edición, dispone de actualizaciones de diferentes aspectos clínicos, de diagnóstico y de vigilancia epidemiológica basados en la experiencia y la evidencia observadas durante estos ocho años del Programa de prevención y control de la enfermedad de Chagas congénita en Cataluña. Durante estos últimos años, se ha reforzado la perspectiva de salud pública en el Programa, en el que han participado un gran número de profesionales de la red asistencial y agentes comunitarios de salud con el objetivo de reducir el efecto de la transmisión vertical del ECH en Cataluña. La primera parte del documento recoge las características clínicas de la ECH que, aunque es de aparición relativamente reciente en nuestro entorno, gracias a la información facilitada tanto en el ámbito sanitario como en el ámbito comunitario durante los últimos años, ha dejado de ser una enfermedad olvidada y desconocida en Cataluña. En los últimos años, los avances y la experiencia en nuestro entorno en el diagnóstico de la ECH nos han hecho llegar a un consenso sobre la utilización de métodos directos moleculares, tal como se describe en el presente Protocolo. Asimismo, la concreción de datos epidemiológicos sobre prevalencia de infección e incidencia de casos de la enfermedad ha mejorado mucho gracias a la vigilancia y notificación de datos recogidos en el marco del Programa de prevención y control de la enfermedad de Chagas congénita en Cataluña por los profesionales que forman parte del Grupo de Trabajo de la Enfermedad de Chagas Congénita. En este aspecto y para mejorar su control se han incorporado los médicos de familia y salud comunitaria, ya que son unos de los profesionales clave que se encuentran más cercanos a los pacientes. Un aspecto fundamental que se desprende de este documento y del funcionamiento del Programa es la multidisciplinariedad. El reto del sistema de salud y de la vigilancia de la salud pública es la coordinación y el trabajo de los profesionales de diferentes ámbitos sanitarios, como pueden ser ginecólogos, microbiólogos, comadrones, pediatras de atención primaria y hospitalaria, médicos de familia y salud comunitaria, personal de enfermería, infectólogos, epidemiólogos y agentes de salud comunitaria que trabajan de manera conjunta para el logro del objetivo planteado. El presente Protocolo constituye un documento eminentemente práctico, mediante el cual los profesionales sanitarios disponen de los elementos esenciales para la realización del cribado en la mujer embarazada. A partir de este Protocolo se espera también conseguir la detección y el tratamiento precoz de los casos de ECH en la población pediátrica, bebés y otros hijos en Cataluña, con el objetivo último de mejorar la salud maternoinfantil en Cataluña.Chagas disease (CHD) continues to be a major public health problem. The WHO estimates that there are 8 million people in the world infected with Trypanosoma cruzi, the majority in Latin America. In non-endemic countries, as is the case in our environment, CHD is seen in infected people who come from endemic countries or children born in non-endemic countries, but whose mother has been infected (congenital transmission). In Catalonia, in order to control and monitor the CHD, in 2010 the Program for the Prevention and Control of Congenital Chagas' Disease in Catalonia was launched, coordinated by the Department of Health and includes diagnosis, control, follow-up and treatment of congenital CHD directed at pregnant women and their children. Within the framework of the Program, the Protocol for the Screening and Diagnosis of Chagas' Disease in Latin American pregnant women and their children was prepared, which was published in 2010. This document was the result of the joint effort of health professionals who are experts in the disease, of different scientific societies and professionals of the Department of Health of the Government of Catalonia, with the support of the Working Group of Non-endemic Countries and the Department of Control of Forgotten Tropical Diseases of WHO. The Protocol that is presented, in addition to including the same lines as the first edition, has updates on different clinical, diagnostic and epidemiological surveillance aspects based on the experience and evidence observed during these eight years of the Prevention and Control Program. Congenital Chagas disease in Catalonia. During these last years, the perspective of public health in the Program has been reinforced, in which a large number of professionals of the health care network and community health agents have participated with the aim of reducing the effect of the vertical transmission of CHD in Catalonia. The first part of the document includes the clinical characteristics of the CHD that, although it is relatively recent in our environment, thanks to the information provided both in the health field and in the community in recent years, has ceased to be a disease forgotten and unknown in Catalonia. In recent years, the advances and experience in our environment in the diagnosis of CHD have led us to reach a consensus on the use of direct molecular methods, as described in this Protocol. Likewise, the specification of epidemiological data on prevalence of infection and incidence of cases of the disease has improved greatly thanks to the monitoring and reporting of data collected within the framework of the Program for the Prevention and Control of Congenital Chagas' Disease in Catalonia by professionals. that are part of the Working Group on Congenital Chagas Disease. In this aspect and to improve their control, family doctors and community health have been incorporated, since they are one of the key professionals who are closest to patients. A fundamental aspect that emerges from this document and the operation of the Program is multidisciplinarity. The challenge of the health system and public health surveillance is the coordination and work of professionals from different health areas, such as gynecologists, microbiologists, midwives, pediatricians of primary and hospital care, family physicians and community health , nurses, infectious disease specialists, epidemiologists and community health workers who work together to achieve the stated objective. This Protocol is an eminently practical document, through which health professionals have the essential elements for carrying out screening in pregnant women. Based on this Protocol, it is also expected to achieve the detection and early treatment of cases of CHD in the pediatric population, babies and other children in Catalonia, with the ultimate goal of improving maternal and child health in Catalonia

The Type VI secretion system deploys anti-fungal effectors against microbial competitors

This work was supported by the Wellcome Trust (Senior Research Fellowship in Basic Biomedical Science to S.J.C., 104556; 097377, J.Q.; 101873 & 200208, N.A.R.G.), the MRC (MR/K000111X/1, S.J .C; MC_UU_12016/5, M.T.), and the BBSRC (BB/K016393/1 & BB/P020119/1, J.Q.). We thank Maximilian Fritsch, Mario López Martín and Birte Hollmann for help with strain construction; Gary Eitzen for construction of pGED1; Donna MacCallum for the gift of Candida glabrata ATCC2001; Joachim Morschhäuser for the gift of pNIM1; Gillian Milne (Microscopy and Histology facility, University of Aberdeen) for assistance with TEM; and Peter Taylor, Michael Porter, Laura Monlezun and Colin Rickman for advice and technical assistance.Peer reviewedPostprin