University of Valencia

About: University of Valencia is a education organization based out in Valencia, Spain. It is known for research contribution in the topics: Population & Neutrino. The organization has 27096 authors who have published 65669 publications receiving 1765689 citations. The organization is also known as: Universitat de València & UV.

Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors

Abstract: The success in lung cancer therapy with Programmed Death (PD)-1 blockade suggests that immune escape mechanisms contribute to lung tumor pathogenesis. We identified a correlation between Epidermal Growth Factor Receptor (EGFR) pathway activation and a signature of immunosuppression manifested by upregulation of PD-1, PD-L1, cytotoxic T lymphocyte antigen-4 (CTLA-4), and multiple tumor-promoting inflammatory cytokines. We observed decreased cytotoxic T cells and increased markers of T cell exhaustion in mouse models of EGFR-driven lung cancer. PD-1 antibody blockade improved the survival of mice with EGFR-driven adenocarcinomas by enhancing effector T cell function and lowering the levels of tumor-promoting cytokines. Expression of mutant EGFR in bronchial epithelial cells induced PD-L1, and PD-L1 expression was reduced by EGFR inhibitors in non-small cell lung cancer cell lines with activated EGFR. These data suggest that oncogenic EGFR signaling remodels the tumor microenvironment to trigger immune escape, and mechanistically link treatment response to PD-1 inhibition.

First M87 Event Horizon Telescope Results. VI. The Shadow and Mass of the Central Black Hole

Abstract: We present measurements of the properties of the central radio source in M87 using Event Horizon Telescope data obtained during the 2017 campaign. We develop and fit geometric crescent models (asymmetric rings with interior brightness depressions) using two independent sampling algorithms that consider distinct representations of the visibility data. We show that the crescent family of models is statistically preferred over other comparably complex geometric models that we explore. We calibrate the geometric model parameters using general relativistic magnetohydrodynamic (GRMHD) models of the emission region and estimate physical properties of the source. We further fit images generated from GRMHD models directly to the data. We compare the derived emission region and black hole parameters from these analyses with those recovered from reconstructed images. There is a remarkable consistency among all methods and data sets. We find that >50% of the total flux at arcsecond scales comes from near the horizon, and that the emission is dramatically suppressed interior to this region by a factor >10, providing direct evidence of the predicted shadow of a black hole. Across all methods, we measure a crescent diameter of 42 ± 3 μas and constrain its fractional width to be <0.5. Associating the crescent feature with the emission surrounding the black hole shadow, we infer an angular gravitational radius of GM/Dc2 = 3.8 ± 0.4 μas. Folding in a distance measurement of ${16.8}_{-0.7}^{+0.8}\,\mathrm{Mpc}$ gives a black hole mass of $M=6.5\pm 0.2{| }_{\mathrm{stat}}\pm 0.7{| }_{\mathrm{sys}}\times {10}^{9}\hspace{2pt}{M}_{\odot }$. This measurement from lensed emission near the event horizon is consistent with the presence of a central Kerr black hole, as predicted by the general theory of relativity.

The significance of soils and soil science towards realization of the United Nations sustainable development goals

Abstract: . In this forum paper we discuss how soil scientists can help to reach the recently adopted UN Sustainable Development Goals (SDGs) in the most effective manner. Soil science, as a land-related discipline, has important links to several of the SDGs, which are demonstrated through the functions of soils and the ecosystem services that are linked to those functions (see graphical abstract in the Supplement). We explore and discuss how soil scientists can rise to the challenge both internally, in terms of our procedures and practices, and externally, in terms of our relations with colleague scientists in other disciplines, diverse groups of stakeholders and the policy arena. To meet these goals we recommend the following steps to be taken by the soil science community as a whole: (i) embrace the UN SDGs, as they provide a platform that allows soil science to demonstrate its relevance for realizing a sustainable society by 2030; (ii) show the specific value of soil science: research should explicitly show how using modern soil information can improve the results of inter- and transdisciplinary studies on SDGs related to food security, water scarcity, climate change, biodiversity loss and health threats; (iii) take leadership in overarching system analysis of ecosystems, as soils and soil scientists have an integrated nature and this places soil scientists in a unique position; (iii) raise awareness of soil organic matter as a key attribute of soils to illustrate its importance for soil functions and ecosystem services; (iv) improve the transfer of knowledge through knowledge brokers with a soil background; (v) start at the basis: educational programmes are needed at all levels, starting in primary schools, and emphasizing practical, down-to-earth examples; (vi) facilitate communication with the policy arena by framing research in terms that resonate with politicians in terms of the policy cycle or by considering drivers, pressures and responses affecting impacts of land use change; and finally (vii) all this is only possible if researchers, with soil scientists in the front lines, look over the hedge towards other disciplines, to the world at large and to the policy arena, reaching over to listen first, as a basis for genuine collaboration.

Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults

Abstract: New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus. This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease. In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day, whereas other studies find many fewer putative new neurons. Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons. Here we show that a defined population of progenitor cells does not coalesce in the subgranular zone during human fetal or postnatal development. We also find that the number of proliferating progenitors and young neurons in the dentate gyrus declines sharply during the first year of life and only a few isolated young neurons are observed by 7 and 13 years of age. In adult patients with epilepsy and healthy adults (18-77 years; n = 17 post-mortem samples from controls; n = 12 surgical resection samples from patients with epilepsy), young neurons were not detected in the dentate gyrus. In the monkey (Macaca mulatta) hippocampus, proliferation of neurons in the subgranular zone was found in early postnatal life, but this diminished during juvenile development as neurogenesis decreased. We conclude that recruitment of young neurons to the primate hippocampus decreases rapidly during the first years of life, and that neurogenesis in the dentate gyrus does not continue, or is extremely rare, in adult humans. The early decline in hippocampal neurogenesis raises questions about how the function of the dentate gyrus differs between humans and other species in which adult hippocampal neurogenesis is preserved.