Aplicación de TIG en la generación de indicadores de calidad ambiental de sistemas playa-dunas

Se presentan resultados parciales del subproyecto “Ecosistemas y Biodiversidad: vigilancia de espacios arenosos protegidos de Canarias y África”, incluido en el 'Programa para el desarrollo de redes tecnológicas y de aplicación de datos de teledetección en África Occidental', TELECAN (MAC/3/C181), financiado por el Programa de Cooperación Transnacional Madeira-Azores-Canarias (MAC) 2007/2013. El objetivo principal era definir, mediante el uso de imágenes de satélite, indicadores de calidad ambiental para sistemas playa-dunas, al ser éstos espacios fundamentales en el desarrollo socio-económico de estos territorios, dado su atractivo turístico. En este trabajo se presentan los resultados obtenidos para una de las áreas piloto, Maspalomas (Gran Canaria, islas Canarias). Los indicadores se obtuvieron mediante el procesado de imágenes del satélite WorldView-2, con validación, en 2013, mediante campañas marinas. Asimismo, se utilizaron imágenes de archivo, correspondientes a los años 2010, 2011 y 2012. Estos indicadores se basaron en variables relacionadas con las características físicas y biológicas de las aguas litorales y de las playas y dunas. Los resultados indican una calidad, por lo general, alta y muy alta, tanto para el medio terrestre como para el marino, con superficies dentro de estas categorías del 20,3% y 75,3% y del 26,1% y 70,6%, respectivamente.Esta es una contribución del 'Programa para el desarrollo de redes tecnológicas y de aplicación de datos de teledetección en África Occidental', TELECAN (MAC/3/C181), financiado por el Programa de Cooperación Transnacional Madeira-Azores-Canarias (MAC) 2007/2013

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Synergistic antitumoral effect of epigenetic inhibitors and gemcitabine in pancreatic cancer cells

Epigenetic modifications could drive some of the molecular events implicated in proliferation, drug resistance and metastasis of pancreatic ductal adenocarcinoma (PDAC). Thus, epigenetic enzyme inhibitors could be the key to revert those events and transform PDAC into a drug-sensitive tumor. We performed a systematic study with five different epigenetic enzyme inhibitors (1, UVI5008, MS275, psammaplin A, and BIX01294) targeting either Histone Deacetylase (HDAC) 1 or 1/4, DNA methyltransferase 3a (DNMT3a), Euchromatic histone lysine methyltransferase 2 (EHMT2), or Sirtuin 1 (SIRT1), as well as one drug that restores the p53 function (P53R3), in three different human PDAC cell lines (SKPC-1, MIA PaCa-2, and BxPC-3) using 2D and 3D cell cultures. The synergistic effect of these antitumoral drugs with gemcitabine was tested and the most efficient combinations were characterized by RNA-seq. The inhibition of HDAC1/4 (MS275), HDAC1/4/SIRT1/DNMT3a (UVI5008) or EHMT2 (BIX01294) induced a significant reduction on the cell viability, even in gemcitabine-resistance cells. The combination of UVI5008 or MS275 with gemcitabine induced a synergistic effect at low concentration and the RNA-Seq analysis revealed some synergy candidate genes as potential biomarkers. Reverting aberrant epigenetic modifications in combination with gemcitabine offers an alternative treatment for PDAC patients, with an important reduction of the therapeutic dose.Xunta de Galicia | Ref. ED431C 2020/02Xunta de Galicia | Ref. ED431G2019/06Ministerio de Economía, Industria y Competitividad | Ref. BIO2017-84974-RXunta de Galicia | Ref. ED481A-2021/364Xunta de Galicia | Ref. ED481A-2018/230Ministerio de Economía, Industria y Competitividad | Ref. PID2019-107855RB-I00Xunta de Galicia | Ref. ED431C 2017/6

Probing a polar cluster in the retinal binding pocket of bacteriorhodopsin by a chemical design approach

Bacteriorhodopsin has a polar cluster of amino acids surrounding the retinal molecule, which is responsible for light harvesting to fuel proton pumping. From our previous studies, we have shown that threonine 90 is the pivotal amino acid in this polar cluster, both functionally and structurally. In an attempt to perform a phenotype rescue, we have chemically designed a retinal analogue molecule to compensate the drastic effects of the T90A mutation in bacteriorhodopsin. This analogue substitutes the methyl group at position C13 of the retinal hydrocarbon chain by and ethyl group (20-methyl retinal). We have analyzed the effect of reconstituting the wild-type and the T90A mutant apoproteins with all-trans-retinal and its 20-methyl derivative (hereafter, 13-ethyl retinal). Biophysical characterization indicates that recovering the steric interaction between the residue 90 and retinal, eases the accommodation of the chromophore, however it is not enough for a complete phenotype rescue. The characterization of these chemically engineered chromoproteins provides further insight into the role of the hydrogen bond network and the steric interactions involving the retinal binding pocket in bacteriorhodopsin and other microbial sensory rhodopsins

Probing a Polar Cluster in the Retinal Binding Pocket of Bacteriorhodopsin by a Chemical Design Approach

<div><p>Bacteriorhodopsin has a polar cluster of amino acids surrounding the retinal molecule, which is responsible for light harvesting to fuel proton pumping. From our previous studies, we have shown that threonine 90 is the pivotal amino acid in this polar cluster, both functionally and structurally. In an attempt to perform a phenotype rescue, we have chemically designed a retinal analogue molecule to compensate the drastic effects of the T90A mutation in bacteriorhodopsin. This analogue substitutes the methyl group at position C₁₃ of the retinal hydrocarbon chain by and ethyl group (20-methyl retinal). We have analyzed the effect of reconstituting the wild-type and the T90A mutant apoproteins with all-<em>trans</em>-retinal and its 20-methyl derivative (hereafter, 13-ethyl retinal). Biophysical characterization indicates that recovering the steric interaction between the residue 90 and retinal, eases the accommodation of the chromophore, however it is not enough for a complete phenotype rescue. The characterization of these chemically engineered chromoproteins provides further insight into the role of the hydrogen bond network and the steric interactions involving the retinal binding pocket in bacteriorhodopsin and other microbial sensory rhodopsins.</p> </div

Chemical stability denaturation experiments.

<p><b>A</b>. Kinetics of retinal hydrolysis of the four chromoproteins by hydroxylamine hydrochloride. The molar ratio protein/NH₂OH was 1∶4000. The measurements were done in 5 mM phosphate buffer pH 7.5 in the dark. <b>B</b>. Absorbance spectra of the denaturation process (upper panels) compared to the minus second derivative of the absorbance spectra (lower panels) for each reconstituted protein (as indicated in the figure). For sake of clarity, initial, mid and final spectra of the reaction are plotted with thicker lines.</p