γδ T lymphocytes in the diagnosis of human T cell receptor immunodeficiencies

Supported by grants from MINECO (SAF 2011-24235, BES-2012-055054, SAF2014- 54708-R, and SAF2014-53563-REDT) CAM (S2010/BMD-2316) ISCIII (RD08- 0075-0002 and PI12/02761)Peer Reviewe

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Nightside condensation of iron in an ultra-hot giant exoplanet

Ultra-hot giant exoplanets receive thousands of times Earth's insolation. Their high-temperature atmospheres (>2,000 K) are ideal laboratories for studying extreme planetary climates and chemistry. Daysides are predicted to be cloud-free, dominated by atomic species and substantially hotter than nightsides. Atoms are expected to recombine into molecules over the nightside, resulting in different day-night chemistry. While metallic elements and a large temperature contrast have been observed, no chemical gradient has been measured across the surface of such an exoplanet. Different atmospheric chemistry between the day-to-night ("evening") and night-to-day ("morning") terminators could, however, be revealed as an asymmetric absorption signature during transit. Here, we report the detection of an asymmetric atmospheric signature in the ultra-hot exoplanet WASP-76b. We spectrally and temporally resolve this signature thanks to the combination of high-dispersion spectroscopy with a large photon-collecting area. The absorption signal, attributed to neutral iron, is blueshifted by -11+/-0.7 km s-1 on the trailing limb, which can be explained by a combination of planetary rotation and wind blowing from the hot dayside. In contrast, no signal arises from the nightside close to the morning terminator, showing that atomic iron is not absorbing starlight there. Iron must thus condense during its journey across the nightside.Comment: Published in Nature (Accepted on 24 January 2020.) 33 pages, 11 figures, 3 table

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

El cultivo de garbanzo (Cicer arietinum L.) en Argentina

El Programa Transferencia de Resultados de Investigación y Comunicación Pública de la Ciencia (PROTRI), de la Secretaría de Ciencia y Tecnología del Gobierno de la Provincia de Córdoba, financió la realización del libro El cultivo de garbanzo en Argentina con el objeto de promover la transferencia de resultados, experiencias o saberes entre las áreas del sector social y productivo para una mejor calidad de vida. Para la ejecución de esta obra han sido convocados técnicos e investigadores de las Ciencias Agropecuarias, Biológicas y Económicas, quienes en una forma clara y sencilla, aunque no menos consistente, ponen a disposición del lector sus experiencias adquiridas a lo largo de varios años de trabajo. El desarrollo de los diferentes temas se realiza a través de dieciséis Capítulos que abarcan desde la domesticación de Cicer y su llegada a la Argentina (Capítulo 1), pasando por el estudio morfológico de las diferentes partes de la planta en relación a los cultivares locales (Capítulo 2), además del manejo del suelo y sus nutrientes, en cuanto a requerimientos edáficos en los sistemas productivos (Capítulo 3). También se contempla el análisis de la influencia de los diversos factores ambientales para la determinación de zonas productivas (Capítulo 4). En el Capítulo 5 se hace referencia a la ecofisiología del cultivo, sus requerimientos en las diferentes etapas fenológicas, y cuándo y cómo se expresan en los cultivares. Un tema de indudable importancia para las leguminosas en general, y para el garbanzo en particular, es la simbiosis con las bacterias fijadoras de nitrógeno y su influencia en la productividad, el cual se desarrolla en el Capítulo 6. La mejora genética en el país es abordada en el Capítulo 7, donde se exponen sus inicios, desarrollo, disponibilidad de recursos, bondades y potencial del germoplasma disponible. A lo largo del ciclo biológico de la planta, el cultivo es visitado por insectos e infectado por hongos. Identificarlos y conocer sus ciclos biológicos y comportamientos es un aspecto importante para seleccionar las medidas de manejo y control más adecuadas (Capítulos 8 y 9). Quizás pocos sepan que el volumen de semilla genética de un cultivar, alcanza sólo unos pocos gramos (alrededor de 20). Para llevar este pequeño volumen a toneladas, se requiere del trabajo y tesón de investigadores, fitomejoradores y productores. Resultado de ese esfuerzo es la difusión de los seis cultivares obtenidos en el país, y se sigue trabajando para lograr nuevos materiales que se adapten a las diversas áreas y sistemas de producción (Capítulo 10). El desarrollo de los diferentes cultivares, que dan lugar a diversas arquitecturas de plantas, sumado a la adopción de diversos sistemas de producción, hace que el tema de la mecanización ocupe un lugar importante. Maquinas pequeñas y grandes intervienen en las etapas de siembra y de cosecha tratando de lograr la mayor eficiencia posible y un producto de calidad (Capítulo 11). Un cuello de botella para la expansión del cultivo es su comercialización, tanto para consumo interno como externo. En el Capítulo 12 se analizan los diferentes mercados y la necesidad de lograr un producto rentable de alta calidad, para mercados muy diversos. En el Capítulo 13 se hace un recorrido por las diferentes Provincias que actualmente producen garbanzo. Sus autores comentan como se incorporó el cultivo a los sistemas productivos de la región, sobre posibilidades y limitaciones, manejos y potencial de rendimiento, entre otros aportes. Los Capítulos 14 y 15 presentan dos temas de relevancia actual: la composición química del grano y las posibilidades de brindar valor agregado a éste, aspectos reforzados en la última década por el auge de las tendencias que promueven un nuevo estilo de vida y una alimentación sana, con alimentos naturales, bajos en grasa y con un buen balance nutricional. En el último Capítulo (16) se presentan experiencias de investigación en las que se utilizó al garbanzo como materia prima o como sustrato para diversas experimentaciones. La interacción docente-investigador-alumno permitió que vieran la luz diversos trabajos que, además de la formación de recursos humanos, brindan una información útil y novedosa al incursionar en temas tales como manejo de fechas de siembra, riego, alimento para pollos, cerdos y abejas. Estimado lector, tiene en sus manos un libro que es una invitación a un viaje con dieciséis estaciones. En cada una de ellas encontrará información sobre el cultivo del garbanzo en la Argentina. Estos datos fueron obtenidos por docentes, investigadores, productores, estudiantes que trabajaron y siguen trabajando para aportar al conocimiento del cultivo en nuestro país, bajo la realidad local y el contexto regional, ya que la mayoría de los trabajos y publicaciones son de origen extranjero y la aplicación de muchas de las tecnologías de manejo requieren una correcta adaptación y validación. Esperamos que este libro, además de serle útil, pueda ser disfrutado, sintiendo la pasión y el entusiasmo de cada uno de los autores por brindar y compartir sus conocimientos y logros

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Cuba en revolución : miradas en torno a su sesenta aniversario

Cuba en revolución recoge doce ponencias realizadas en el marco de la Octava Conferencia Latinoamericana y Caribeña de CLACSO. Las presentaciones testimonian experiencias y facetas poco conocidas o divulgadas sobre los logros y dilemas económicos, sociales y políticos que, desde 1959 hasta la actualidad, marcaron la vida social y política del pueblo cubano, en su compromiso con la construcción de un modelo basado en el principio de la justicia social y la dignidad humana