Dysregulation of photosynthetic genes in oceanic Prochlorococcus populations exposed to organic pollutants

The impact of organic pollutants on oceanic ecosystem functioning is largely unknown. Prochlorococcus, the most abundant known photosynthetic organism on Earth, has been suggested to be especially sensible to exposure to organic pollutants, but the sub-lethal effects of organic pollutants on its photosynthetic function at environmentally relevant concentrations and mixtures remain unexplored. Here we show the modulation of the expression of two photosynthetic genes, rbcL (RuBisCO large subunit) and psbA (PSII D1 protein), of oceanic populations of Prochlorococcus from the Atlantic, Indian and Pacific Oceans when exposed to mixtures of organic pollutants consisting of the non-polar fraction of a seawater extract. This mixture included most persistent organic pollutants, semivolatile aromatic-like compounds, and the unresolved complex mixture of hydrocarbons. Prochlorococcus populations in the controls showed the expected diel cycle variations in expression of photosynthetic genes. However, exposure to a complex mixture at concentrations only 2-fold above the environmental levels resulted in a decrease of expression of both genes, suggesting an effect on the photosynthetic function. While organic pollutant effects on marine phytoplankton have been already demonstrated at the cellular level, this is the first field study showing alterations at the molecular level of the photosynthetic function due to organic pollutants.Versión del edito

Biochemical and structural characterization of a novel thermophilic esterase EstD11 provide catalytic insights for the HSL family

19 pags., 12 figs., 2 tabs.A novel esterase, EstD11, has been discovered in a hot spring metagenomic library. It is a thermophilic and thermostable esterase with an optimum temperature of 60°C. A detailed substrate preference analysis of EstD11 was done using a library of chromogenic ester substrate that revealed the broad substrate specificity of EstD11 with significant measurable activity against 16 substrates with varied chain length, steric hindrance, aromaticity and flexibility of the linker between the carboxyl and the alcohol moiety of the ester. The tridimensional structures of EstD11 and the inactive mutant have been determined at atomic resolutions. Structural and bioinformatic analysis, confirm that EstD11 belongs to the family IV, the hormone-sensitive lipase (HSL) family, from the α/β-hydrolase superfamily. The canonical α/β-hydrolase domain is completed by a cap domain, composed by two subdomains that can unmask of the active site to allow the substrate to enter. Eight crystallographic complexes were solved with different substrates and reaction products that allowed identification of the hot-spots in the active site underlying the specificity of the protein. Crystallization and/or incubation of EstD11 at high temperature provided unique information on cap dynamics and a first glimpse of enzymatic activity in vivo. Very interestingly, we have discovered a unique Met zipper lining the active site and the cap domains that could be essential in pivotal aspects as thermo-stability and substrate promiscuity in EstD11.We thank the staff from ALBA synchrotron facility (Barcelona, Spain) for support during crystallographic data collection. This work was funded by the UE through the HotDrops Project (FP7- PEOPLE-2012-IAPP, project number 324439). Additionally, this work was supported by the BFU2017-90030-P grant to J.A.H. from the Spanish Ministry of Science and Innovatio

Oncogenic Role of Secreted Engrailed Homeobox 2 (EN2) in Prostate Cancer

Engrailed variant-2 (EN2) has been suggested as a potential diagnostic biomarker; however, its presence and functional role in prostate cancer (PCa) cells is still controversial or unknown. Here, we analyzed 1) the expression/secretion profile of EN2 in five independent samples cohorts from PCa patients and controls (prostate tissues and/or urine) to determine its utility as a PCa biomarker; and 2) the functional role of EN2 in normal (RWPE1) and tumor (LNCaP/22Rv1/PC3) prostate cells to explore its potential value as therapeutic target. EN2 was overexpressed in our two cohorts of PCa tissues compared to control and in tumor cell lines compared with normal-like prostate cells. This profile was corroborated in silico in three independent data sets [The Cancer Genome Atlas(TCGA)/Memorial Sloan Kettering Cancer Center (MSKCC)/Grasso]. Consistently, urine EN2 levels were elevated and enabled discrimination between PCa and control patients. EN2 treatment increased cell proliferation in LNCaP/22Rv1/PC3 cells, migration in RWPE1/PC3 cells, and PSA secretion in LNCaP cells. These effects were associated, at least in the androgen-sensitive LNCaP cells, with increased AKT and androgen-receptor phosphorylation levels and with modulation of key cancer-associated genes. Consistently, EN2 treatment also regulated androgen-receptor activity (full-length and splicing variants) in androgen-sensitive 22Rv1 cells. Altogether, this study demonstrates the potential utility of EN2 as a non-invasive diagnostic biomarker for PCa and provides novel and valuable information to further investigate its putative utility to develop new therapeutic tools in PCa

Atención de la urgencia quirúrgica durante la pandemia COVID-19. Recomendaciones de la Asociación Española de Cirujanos

La infección por el nuevo coronavirus SARS-CoV-2 (enfermedad por coronavirus 2019 [COVID-19]) ha determinado la necesidad de la reorganización de muchos centros hospitalarios en el mundo. España, como uno de los epicentros de la enfermedad, ha debido asumir cambios en la práctica totalidad de su territorio. Sin embargo, y desde el inicio de la pandemia, en todos los centros que atienden urgencias quirúrgicas ha sido necesario el mantenimiento de su cobertura, aunque igualmente ha sido inevitable introducir directrices especiales de ajuste al nuevo escenario que permitan el mantenimiento de la excelencia en la calidad asistencial. Este documento desarrolla una serie de indicaciones generales para la cirugía de urgencias y la atención al politraumatizado desarrolladas desde la literatura disponible y consensuadas por un subgrupo de profesionales desde el grupo general Cirugía-AEC-COVID-19. Estas medidas van encaminadas a contemplar un riguroso control de la exposición en pacientes y profesionales, a tener en cuenta las implicaciones de la pandemia sobre diferentes escenarios perioperatorios relacionados con la urgencia y a una adaptación ajustada a la situación del centro en relación con la atención a pacientes infectados. New coronavirus SARS-CoV-2 infection (coronavirus disease 2019 [COVID-19]) has determined the necessity of reorganization in many centers all over the world. Spain, as an epicenter of the disease, has been forced to assume health policy changes in all the territory. However, and from the beginning of the pandemic, every center attending surgical urgencies had to guarantee the continuous coverage adopting correct measures to maintain the excellence of quality of care. This document resumes general guidelines for emergency surgery and trauma care, obtained from the available bibliography and evaluated by a subgroup of professionals designated from the general group of investigators Cirugía-AEC-COVID-19 from the Spanish Association of Surgeons, directed to minimize professional exposure, to contemplate pandemic implications over different urgent perioperative scenarios and to adjust decision making to the occupational pressure caused by COVID-19 patients