Learning Criteria and Evaluation Metrics for Textual Transfer between Non-Parallel Corpora

We consider the problem of automatically generating textual paraphrases with modified attributes or stylistic properties, focusing on the setting without parallel data (Hu et al., 2017; Shen et al., 2017). This setting poses challenges for learning and evaluation. We show that the metric of post-transfer classification accuracy is insufficient on its own, and propose additional metrics based on semantic content preservation and fluency. For reliable evaluation, all three metric categories must be taken into account. We contribute new loss functions and training strategies to address the new metrics. Semantic preservation is addressed by adding a cyclic consistency loss and a loss based on paraphrase pairs, while fluency is improved by integrating losses based on style-specific language models. Automatic and manual evaluation show large improvements over the baseline method of Shen et al. (2017). Our hope is that these losses and metrics can be general and useful tools for a range of textual transfer settings without parallel corpora

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

Detección precoz de la resistencia de Ulmus minor a Ophiostoma novo-ulmi mediante cultivo in vitro y parámetros de estrés.

Las poblaciones de olmo común (Ulmus minor) en Europa se encuentran amenazadas por la grafiosis, enfermedad vascular causada por Ophiostoma novo-ulmi. La mejora genética es la mejor alternativa para recuperar el uso de la especie. Sin embargo, los métodos de evaluación de la susceptibilidad requieren largos periodos de tiempo (4 años), parcelas experimentales en campo y están condicionados por factores ambientales. Se plantea como alternativa la evaluación de la susceptibilidad en condiciones controladas de cultivo in vitro. En este trabajo se ha inoculado O. novo- ulmi en plantas in vitro, y se ha estudiado el proceso de colonización y la respuesta de la planta a la infección. Se utilizaron dos genotipos, M-DV2.3 (tolerante) y VA-AP38 (susceptible), en los que se recogieron muestras en varios momentos posteriores a la inoculación (1-21 dpi). La detección del patógeno en los distintos órganos de la planta fue realizada mediante PCR. Se determinaron parámetros anatómicos, de estrés oxidativo (peroxidación de lípidos), y se cuantificó el contenido de clorofilas y de compuestos fenólicos totales, con el fin de obtener posibles marcadores de resistencia. No se observaron diferencias en el grado de colonización por el patógeno, ni anatómicas entre los genotipos. VA-AP38 mostró parada de crecimiento, clorosis, aumento significativo de la peroxidación de lípidos y descenso en el contenido en clorofilas. Por el contrario, M-DV2.3 no mostró ninguno de estos síntomas. Ante estas diferencias el uso de plantas cultivadas in vitro para la selección temprana de genotipos tolerantes parece factible. Si se corroboran estos resultados con otros genotipos la búsqueda de genotipos tolerantes a la grafiosis se podría acortar y abaratar sustancialmente

El proyecto LIFE ELM (LIFE 13 BIO/ES/00556): primeros resultados de las plantaciones con clones de olmo común tolerantes a la grafiosis y brinzales de olmo ciliado en la Cuenca del Tajo

El proyecto demostrativo LIFE ELM supone un primer paso para la recuperación de las olmedas en el paisaje español. Se centra en dos especies naturales en nuestro territorio, Ulmus minor y Ulmus laevis. Las actuaciones se han desarrollado en la Cuenca del río Tajo, en los términos municipales de Aranjuez y San Sebastián de los Reyes (Madrid). Se describen las actuaciones realizadas en 2017 y 2018 y un avance provisional de resultados. Se han plantado alrededor de 5.900 ejemplares de U. minor de cinco clones tolerantes al patógeno causante de la grafiosis y cerca de 3.800 plantas de U. laevis. Según la zona, se analizan y discuten las diferencias observadas en el desarrollo de los clones de U. minor y el éxito de las plantaciones de U. laevis

El proyecto LIFE ELM (LIFE 13 BIO/ES/00556): primeros resultados de las plantaciones con clones de olmo común tolerantes a la grafiosis y brinzales de olmo ciliado en la Cuenca del Tajo

El proyecto demostrativo LIFE ELM supone un primer paso para la recuperación de las olmedas en el paisaje español. Se centra en dos especies naturales en nuestro territorio, Ulmus minor y Ulmus laevis. Las actuaciones se han desarrollado en la Cuenca del río Tajo, en los términos municipales de Aranjuez y San Sebastián de los Reyes (Madrid). Se describen las actuaciones realizadas en 2017 y 2018 y un avance provisional de resultados. Se han plantado alrededor de 5.900 ejemplares de U. minor de cinco clones tolerantes al patógeno causante de la grafiosis y cerca de 3.800 plantas de U. laevis. Según la zona, se analizan y discuten las diferencias observadas en el desarrollo de los clones de U. minor y el éxito de las plantaciones de U. laevis

The LIFE + ELM project “Elms Alive” for the restoration of Ulmus minor and Ulmus laevis in Spain

The degradation of European elm stands due to the negative impact of humaninduced changes in riparian ecosystems and the emergence of the highly aggressive Dutch elm disease (DED) pathogens prompted several elm breeding programs. In Spain, seven Ulmus minor clones tolerant to DED were recently selected and the small and fragmented Ulmus laevis populations were proven to be native. With this background, the LIFE+ ELM project (2014-2019; slogan “elms alive”; www.olmosvivos.es) has the overall objectives of monitoring acclimation of selected clones to riparian habitats presumed to be suitable for reintroduction (within the Tagus river basin), and to gain experience and ecological knowledge for future implementation of large scale elm restoration activities. It also intends to recover the use of elms as an ornamental shade tree in urban landscaping. By now, 11,156 individuals have been planted in forest and urban green areas, representing 67% of the total planned plantations. Plant material consists of clonal copies of the seven Ulmus minor clones obtained by micropropagation and U. laevis seedlings from two relict populations in the restoration area. The limited attractiveness of this last species for the elm bark beetles points to a low risk of DED damage in U. laevis. Due to the lack of earlier restoration attempts, it will be necessary to evaluate factors such as distance to the river, elevation, soil humidity, and incidence of pests, diseases and herbivory to form conclusions about the adaptability and survival of each elm genotype and species. To this end, experimental plots have been established in the restoration areas and preliminary results show a significant genotype x environment interaction. The ultimate goal is for the populations of both elm species to reach sexual maturity so they can contribute to gene flow and conservation of native genetic resources. Another key aim of LIFE + ELM is to transfer the knowledge and experience gained in the project to other players in forest restoration and the general public

The LIFE + ELM project “Elms Alive” for the restoration of Ulmus minor and Ulmus laevis in Spain

The degradation of European elm stands due to the negative impact of humaninduced changes in riparian ecosystems and the emergence of the highly aggressive Dutch elm disease (DED) pathogens prompted several elm breeding programs. In Spain, seven Ulmus minor clones tolerant to DED were recently selected and the small and fragmented Ulmus laevis populations were proven to be native. With this background, the LIFE+ ELM project (2014-2019; slogan “elms alive”; www.olmosvivos.es) has the overall objectives of monitoring acclimation of selected clones to riparian habitats presumed to be suitable for reintroduction (within the Tagus river basin), and to gain experience and ecological knowledge for future implementation of large scale elm restoration activities. It also intends to recover the use of elms as an ornamental shade tree in urban landscaping. By now, 11,156 individuals have been planted in forest and urban green areas, representing 67% of the total planned plantations. Plant material consists of clonal copies of the seven Ulmus minor clones obtained by micropropagation and U. laevis seedlings from two relict populations in the restoration area. The limited attractiveness of this last species for the elm bark beetles points to a low risk of DED damage in U. laevis. Due to the lack of earlier restoration attempts, it will be necessary to evaluate factors such as distance to the river, elevation, soil humidity, and incidence of pests, diseases and herbivory to form conclusions about the adaptability and survival of each elm genotype and species. To this end, experimental plots have been established in the restoration areas and preliminary results show a significant genotype x environment interaction. The ultimate goal is for the populations of both elm species to reach sexual maturity so they can contribute to gene flow and conservation of native genetic resources. Another key aim of LIFE + ELM is to transfer the knowledge and experience gained in the project to other players in forest restoration and the general public

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

Genetic 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

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