PARP inhibition enhances tumor cell-intrinsic immunity in ERCC1-deficient non-small cell lung cancer.

The cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway detects cytosolic DNA to activate innate immune responses. Poly(ADP-ribose) polymerase inhibitors (PARPi) selectively target cancer cells with DNA repair deficiencies such as those caused by BRCA1 mutations or ERCC1 defects. Using isogenic cell lines and patient-derived samples, we showed that ERCC1-defective non-small cell lung cancer (NSCLC) cells exhibit an enhanced type I IFN transcriptomic signature and that low ERCC1 expression correlates with increased lymphocytic infiltration. We demonstrated that clinical PARPi, including olaparib and rucaparib, have cell-autonomous immunomodulatory properties in ERCC1-defective NSCLC and BRCA1-defective triple-negative breast cancer (TNBC) cells. Mechanistically, PARPi generated cytoplasmic chromatin fragments with characteristics of micronuclei; these were found to activate cGAS/STING, downstream type I IFN signaling, and CCL5 secretion. Importantly, these effects were suppressed in PARP1-null TNBC cells, suggesting that this phenotype resulted from an on-target effect of PARPi on PARP1. PARPi also potentiated IFN-γ-induced PD-L1 expression in NSCLC cell lines and in fresh patient tumor cells; this effect was enhanced in ERCC1-deficient contexts. Our data provide a preclinical rationale for using PARPi as immunomodulatory agents in appropriately molecularly selected populations

Myliobatis freminvillii, bullnose eagle ray

The Bullnose Eagle Ray (Myliobatis freminvillii) is a medium-sized (to 106 cm disc width) demersal coastal eagle ray that occurs in the Northwest, Western Central, and Southwest Atlantic Oceans from Massachussetts, USA to the Texas coast of the Gulf of Mexico and from Venezuela to Buenos Aires, Argentina and inhabits continental shelves from the surface to a depth of 122 m. Its is captured by artisanal longlines, gillnets, beach seines and also in industrial shrimp trawls. In the Northwest Atlantic, population trend data are available from a deep-water trawl survey in the northern Gulf of Mexico that reveal steep increases in abundance over 2002-2013. There are no known threats in the Northwest and Western Central Atlantic, but in the Southwest Atlantic artisanal fisheries are intense. Further, there are largely unmanaged commercial trawl and longline fisheries in this area. This inshore eagle ray is exposed to intense and often unmanaged fishing pressure throughout the Southwest Atlantic portion of its range, and it has no refuge at depth. Due to the level of exploitation by widespread artisanal fisheries which lack adequate management, it is suspected that this species has undergone a population reduction of >80% over the past three generation lengths (44 years) in the Atlantic South American part of its range, but is stable in the Northwest and Western Central Atlantic. Overall, based on its range, with almost all threats found in the Southwest Atlantic, and the suspected low productivity of the species, the Bullnose Eagle Ray is suspected to have undergone a population reduction of 30-49% in the past three generation lengths (44 years) due to levels of exploitation, and it is assessed as Vulnerable A2bd.Fil: Carlson, J.. National Marine Fisheries Service; Estados UnidosFil: Charvet, P.. Universidade Federal do Paraná; BrasilFil: Avalos, C.. Fundacion Mundo Azul; GuatemalaFil: Blanco Parra, M. P.. Universidad de Quintana Roo; MéxicoFil: Briones Bell lloch, A.. Direccion de Regulaciones Pesqueras y Ciencias; CubaFil: Cardeñosa, D.. Florida International University; Estados UnidosFil: Chiaramonte, Gustavo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia". Estación Hidrobiológica de Puerto Quequén (sede Quequén); ArgentinaFil: Cuevas, J.M.. Wildlife Conservation Society; Estados UnidosFil: Derrick, D.. University Fraser Simon; CanadáFil: Espinoza, E.. Direccion Parque Nacional Galapagos; EcuadorFil: Mejía Falla, P. A.. Wildlife Conservation Society; Estados UnidosFil: Morales Saldaña, J. M.. Smithsonian Tropical Research Institute; PanamáFil: Motta, F.. Universidade Federal de Sao Paulo; BrasilFil: Naranjo Elizondo, B.. Universidad de Costa Rica; Costa RicaFil: Pacoureau, N.. University Fraser Simon; CanadáFil: Paesch, L.. Dirección Nacional de Recursos Acuáticos; UruguayFil: Perez Jiménez, J. C.. El Colegio de la Frontera del Sur; MéxicoFil: Rincon, G.. Universidade Federal Do Maranhao.; BrasilFil: Schneider, E. V. C.. Cape Eleuthera Institute; BahamasFil: Simpson, N. J.. Salvageblue; San Vicente y las GranadinasFil: Talwar, B. S.. Florida International University; Estados UnidosFil: Pollom, R.. University Fraser Simon; Canad

Myliobatis goodei, southern eagle ray

The Southern Eagle Ray (Myliobatis goodei) is a medium-sized (to at least 115 cm DW) coastal eagle ray that occurs in the Western Central and Southwest Atlantic Oceans from South Carolina and Florida, USA and Quintana Roo, Mexico to San Jorge Gulf, Santa Cruz, Argentina. It inhabits continental shelves from inshore to depths of 181 m. It is captured using artisanal longlines, gillnets, beach seines, and in industrial shrimp trawls. This species is inferred to be stable or increasing in the Western Central Atlantic, based on its similarity to the Bullnose Eagle Ray (Myliobatis freminvillei). In the Southwest Atlantic artisanal fisheries are intense, further there are largely unmanaged commercial trawl and longline fisheries in many areas. In Brazil, landings of eagle rays have been reduced by 60% over 2000?2012 in Santa Catarina State, and a reduction of 91% in Rio Grande do Sul since the 1980s. This inshore eagle ray has no refuge at depth and is exposed to intense and often unmanaged fishing pressure throughout the Atlantic South American portion of its range and there it is suspected that this species has undergone a population reduction of >80% over the past three generation lengths (44 years), but is stable in the Western Central Atlantic. Overall, based its range with the almost all threats found in the Southwest Atlantic, the suspected low productivity of the species, this species is suspected to have undergone a population reduction of 30 49% in three generation lengths (44 years) due to levels of exploitation, and it is assessed as Vulnerable A2d.Fil: Carlson, J.. National Marine Fisheries Service; Estados UnidosFil: Charvet, P.. Universidade Federal do Paraná; BrasilFil: Avalos Castillo, C.. Fundación Mundo Azul; GuatemalaFil: Blanco Parra, M. P.. Universidad de Quintana Roo; MéxicoFil: Briones Bell lloch, A.. Dirección de Regulaciones Pesqueras y Ciencias; CubaFil: Cardeñosa, D.. Florida International University; Estados UnidosFil: Chiaramonte, Gustavo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia". Estación Hidrobiológica de Puerto Quequén (sede Quequén); ArgentinaFil: Cuevas, J.M.. Wildlife Conservation Society; Estados UnidosFil: Derrick, D.. University Fraser Simon; CanadáFil: Espinoza, E.. Galapagos National Park Directorate; EcuadorFil: Mejía Falla, P. A.. Wildlife Conservation Society; Estados UnidosFil: Morales Saldaña, J. M.. Smithsonian Tropical Research Institute; PanamáFil: Motta, F.. Universidade Federal Do Sao Paulo; BrasilFil: Naranjo Elizondo, B.. Universidad de Costa Rica; Costa RicaFil: Pacoureau, N.. University Fraser Simon; CanadáFil: Paesch, L.. Direccion Nacional de Recursos Acuaticos ; UruguayFil: Pérez Jiménez, J. C.. El Colegio de la Frontera del Sur; MéxicoFil: Rincon, G.. Universidade Federal Do Maranhao.; BrasilFil: Schneider, E. V. C.. Cape Eleuthera Institute; BahamasFil: Simpson, N. J.. Salvageblue; San Vicente y las GranadinasFil: Talwar, B. S.. Florida International University; Estados UnidosFil: Pollom, R.. University Fraser Simon; Canad

Parental knowledge of paediatric vaccination

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Emerging research and priorities for elasmobranch conservation.

Over the past 4 decades there has been a growing concern for the conservation status of elasmobranchs (sharks and rays). In 2002, the first elasmobranch species were added to Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). Less than 20 yr later, there were 39 species on Appendix II and 5 on Appendix I. Despite growing concern, effective conservation and management remain challenged by a lack of data on population status for many species, human−wildlife interactions, threats to population viability, and the efficacy of conservation approaches. We surveyed 100 of the most frequently published and cited experts on elasmobranchs and, based on ranked responses, prioritized 20 research questions on elasmobranch conservation. To address these questions, we then convened a group of 47 experts from 35 institutions and 12 countries. The 20 questions were organized into the following broad categories: (1) status and threats, (2) population and ecology, and (3) conservation and management. For each section, we sought to synthesize existing knowledge, describe consensus or diverging views, identify gaps, and suggest promising future directions and research priorities. The resulting synthesis aggregates an array of perspectives on emergent research and priority directions for elasmobranch conservation

Deep Learning Architectures for Diagnosis of Diabetic Retinopathy

For many years, convolutional neural networks dominated the field of computer vision, not least in the medical field, where problems such as image segmentation were addressed by such networks as the U-Net. The arrival of self-attention-based networks to the field of computer vision through ViTs seems to have changed the trend of using standard convolutions. Throughout this work, we apply different architectures such as U-Net, ViTs and ConvMixer, to compare their performance on a medical semantic segmentation problem. All the models have been trained from scratch on the DRIVE dataset and evaluated on their private counterparts to assess which of the models performed better in the segmentation problem. Our major contribution is showing that the best-performing model (ConvMixer) is the one that shares the approach from the ViT (processing images as patches) while maintaining the foundational blocks (convolutions) from the U-Net. This mixture does not only produce better results (DICE=0.83) than both ViTs (0.80/0.077 for UNETR/SWIN-Unet) and the U-Net (0.82) on their own but reduces considerably the number of parameters (2.97M against 104M/27M and 31M, respectively), showing that there is no need to systematically use large models for solving image problems where smaller architectures with the optimal pieces can get better results