Libro de ejercicios de Sistemas de Información Geográfica (SIG) aplicado al ámbito de la hidrología

DIRECCIÓN URL donde se encuentran los archivos necesarios para seguir el libro de prácticas: https://cloudiepcc.unex.es/index.php/s/HHj4JB3LLKQBTi6El objetivo del presente libro es reunir en un documento las prácticas que se han ido diseñando a lo largo de varios años en la especialidad de Hidrología del Grado de Ingeniería Civil que se imparte en la Escuela Politécnica de Cáceres (Universidad de Extremadura). Es necesario advertir al lector que con este libro no se pretende crear un manual de ningún programa concreto, sino recopilar un conjunto de procedimientos que ayuden a comprender el empleo de los sistemas de información geográfica en el ámbito de la Ingeniería Civil en general y de la Hidrología en particular. El programa elegido para el desarrollo de las prácticas es QGIS, un software de código abierto y gratuito que permite la captura, almacenamiento, actualización, manipulación, análisis y visualización de los datos geográficos. Para facilitar la mejor comprensión de la información se ha dividido el libro en dos bloques, uno primero que introduce al usuario a QGIS mediante la realización de una serie de ejercicios generales y un segundo bloque con prácticas más específicas de la especialidad de hidrología.The aim of this book is to bring together in one document the practices that have been designed over several years in the Hydrology speciality of the Civil Engineering Degree taught at the Polytechnic School of Cáceres (University of Extremadura). It is necessary to warn the reader that the aim of this book is not to create a manual of any specific programme, but to compile a set of procedures that help to understand the use of geographic information systems in the field of Civil Engineering in general and Hydrology in particular. The programme chosen for the development of the practices is QGIS, a free and open source software that allows the capture, storage, updating, manipulation, analysis and visualisation of geographic data. To facilitate a better understanding of the information, the book has been divided into two blocks, the first one introducing the user to QGIS by means of a series of general exercises and the second block with practices more specific to the speciality of hydrology.peerReviewe

Optimizing the procedure to manufacture clinical‐grade NK cells for adoptive immunotherapy

Natural killer (NK) cells represent promising tools for cancer immunotherapy. We report the optimization of an NK cell activation–expansion process and its validation on clinical‐scale. Methods: RPMI‐1640, stem cell growth medium (SCGM), NK MACS and TexMACS were used as culture mediums. Activated and expanded NK cells (NKAE) were obtained by coculturing total peripheral blood mononuclear cells (PBMC) or CD45RA+ cells with irradiated K562mbIL15‐41BBL or K562mbIL21‐41BBL. Fold increase, NK cell purity, activation status, cytotoxicity and transcriptome profile were analyzed. Clinical‐grade NKAE cells were manufactured in CliniMACS Prodigy. Results: NK MACS and TexMACs achieved the highest NK cell purity and lowest T cell contamination. Obtaining NKAE cells from CD45RA+ cells was feasible although PBMC yielded higher total cell numbers and NK cell purity than CD45RA+ cells. The highest fold expansion and NK purity were achieved by using PBMC and K562mbIL21‐41BBL cells. However, no differences in activation and cytotoxicity were found when using either NK cell source or activating cell line. Transcriptome profile showed to be different between basal NK cells and NKAE cells expanded with K562mbIL21‐41BBL or K562mbIL15‐41BBL. Clinical‐grade manufactured NKAE cells complied with the specifications from the Spanish Regulatory Agency. Conclusions: GMP‐grade NK cells for clinical use can be obtained by using different starting cells and aAPCThis work was supported by the National Health Service of Spain, Instituto de Salud Carlos III (ISCIII), FONDOS FEDER grant (FIS) PI18/01301 to Pérez-Martínez A, CRIS Foundation to Beat Cancer to Escudero A, Fernández A; Navarro A, Mirones I, and Fundación Mari Paz Jiménez Casado and La Sonrisa de Álex to Vela

Serum amyloid a1/toll-like receptor-4 Axis, an important link between inflammation and outcome of TBI patients

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability world-wide without any validated biomarker or set of biomarkers to help the diagnosis and evaluation of the evolution/prognosis of TBI patients. To achieve this aim, a deeper knowledge of the biochemical and pathophysiological processes triggered after the trauma is essential. Here, we identified the serum amyloid A1 protein-Toll-like receptor 4 (SAA1-TLR4) axis as an important link between inflammation and the outcome of TBI patients. Using serum and mRNA from white blood cells (WBC) of TBI patients, we found a positive correlation between serum SAA1 levels and injury severity, as well as with the 6-month outcome of TBI patients. SAA1 levels also correlate with the presence of TLR4 mRNA in WBC. In vitro, we found that SAA1 contributes to inflammation via TLR4 activation that releases inflammatory cytokines, which in turn increases SAA1 levels, establishing a positive proinflammatory loop. In vivo, post-TBI treatment with the TLR4-antagonist TAK242 reduces SAA1 levels, improves neurobehavioral outcome, and prevents blood–brain barrier disruption. Our data support further evaluation of (i) post-TBI treatment in the presence of TLR4 inhibition for limiting TBI-induced damage and (ii) SAA1-TLR4 as a biomarker of injury progression in TBI patientsThis work was supported by grants from Fundación Mutua Madrileña and Fondo de Investigaciones Sanitarias (FIS) (ISCIII/FEDER) (Programa Miguel Servet CP14/00008; CPII19/00005; PI16/00735; PI19/00082) to JE, RYC2019-026870-I to JMR and PI18/01387 to A

Mitochondrial Na+ controls oxidative phosphorylation and hypoxic redox signalling

All metazoans depend on O2 delivery and consumption by the mitochondrial oxidative phosphorylation (OXPHOS) system to produce energy. A decrease in O2 availability (hypoxia) leads to profound metabolic rewiring. In addition, OXPHOS uses O2 to produce reactive oxygen species (ROS) that can drive cell adaptations through redox signalling, but also trigger cell damage1–4, and both phenomena occur in hypoxia4–8. However, the precise mechanism by which acute hypoxia triggers mitochondrial ROS production is still unknown. Ca2+ is one of the best known examples of an ion acting as a second messenger9, yet the role ascribed to Na+ is to serve as a mere mediator of membrane potential and collaborating in ion transport10. Here we show that Na+ acts as a second messenger regulating OXPHOS function and ROS production by modulating fluidity of the inner mitochondrial membrane (IMM). We found that a conformational shift in mitochondrial complex I during acute hypoxia11 drives the acidification of the matrix and solubilization of calcium phosphate precipitates. The concomitant increase in matrix free-Ca2+ activates the mitochondrial Na+/Ca2+ exchanger (NCLX), which imports Na+ into the matrix. Na+ interacts with phospholipids reducing IMM fluidity and mobility of free ubiquinone between complex II and complex III, but not inside supercomplexes. As a consequence, superoxide is produced at complex III, generating a redox signal. Inhibition of mitochondrial Na+ import through NCLX is sufficient to block this pathway, preventing adaptation to hypoxia. These results reveal that Na+ import into the mitochondrial matrix controls OXPHOS function and redox signalling through an unexpected interaction with phospholipids, with profound consequences in cellular metabolism

Topical Ocular Administration of Progesterone Decreases Photoreceptor Cell Death in Retinal Degeneration Slow (rds) Mice

Retinitis pigmentosa (RP) is an inherited eye disorder which triggers a cascade of retinal disorders leading to photoreceptor cell death and for which there is currently no effective treatment. The purpose of this research was to study whether ocular administration of a solution of progesterone (PG) in β-cyclodextrins (CD) could delay photoreceptor cell death and counteract the gliosis process in an animal model of RP (rds mice). The possible effect of PG reaching the contralateral eye through the circulatory system was also evaluated. Finally, this research discusses and evaluates the diffusion of the drug from possible topical formulations for ocular administration of PG. A group of rds mice received one drop of a solution of PG in CD every 12 h for 10 days to the left eye, while the right eye was left untreated. Another group of rds mice (control) received the drug vehicle (PBS) on the left eye and, again, the right eye was left untreated. Once the treatment was finished on postnatal day 21, the animals were euthanized and histological immunofluorescence studies (TUNEL, GFAP, and DAPI staining) were carried out. Our results showed that the administration of a solution of PG in CD (CD-PG) as drops significantly decreased cell death and inflammation in the retina of the PG-treated eyes of rds mice. No effect was seen in the contralateral eye from PG that may have entered systemic circulation. In conclusion, CD-PG applied topically as drops to the eye decreases photoreceptor cell death in the early stages of RP, delaying vision loss and decreasing gliosis

Evaluation of an O 2-Substituted (1-3)-β-D-Glucan, Produced by Pediococcus parvulus 2.6, in ex vivo Models of Crohn's Disease

1,3-β-glucans are extracellular polysaccharides synthesized by microorganisms and plants, with therapeutic potential. Among them, the O 2-substituted-(1-3)-β-D-glucan, synthesized by some lactic acid bacteria (LAB), has a prebiotic effect on probiotic strains, an immunomodulatory effect on monocyte-derived macrophages, and potentiates the ability of the producer strain to adhere to Caco-2 cells differentiated to enterocytes. In this work, the O 2-substituted-(1-3)-β-D-glucan polymers produced by GTF glycoyltransferase in the natural host Pediococcus parvulus 2.6 and in the recombinant strain Lactococcus lactis NZ9000[pNGTF] were tested. Their immunomodulatory activity was investigated in an ex vivo model using human biopsies from patients affected by Crohn's disease (CD). Both polymers had an anti-inflammatory effect including, a reduction of Interleukine 8 both at the level of its gene expression and its secreted levels. The overall data indicate that the O 2-substituted-(1-3)-β-D-glucan have a potential role in ameliorating inflammation via the gut immune system cell modulatio

Insulin resistance and metabolic syndrome are related to non-alcoholic fatty liver disease, but not visceral adiposity index, in severely obese patients

The visceral adiposity index (VAI) is a marker of visceral fat distribution and dysfunction. Visceral adiposity is related to non-alcoholic fatty liver disease (NAFLD); however, there is some controversy regarding the association between VAI and NAFLD. The aim of this study was to analyse the relationship between VAI and NAFLD and to describe the related factors in severely obese patients. A total of 139 patients who underwent bariatric surgery were included in this cross-sectional study. Liver biopsy was performed during surgery. Univariate and multivariate analysis were conducted to study the features related to VAI. A univariate analysis was conducted to identify which factors were associated with liver histology. In the univariate analysis, steatosis, liver inflammation, non-alcoholic steatohepatitis (NASH) and fibrosis were associated with VAI. In the multivariate analysis, only HOMA (Beta: 0.06; p < 0.01) and metabolic syndrome (Beta: 1.23; p < 0.01) were related to VAI. HOMA, the presence of metabolic syndrome, and waist circumference (WC) were statistically related to the NAFLD activity score (NAS score): HOMA: 0-2: 5.04; 3-4: 7.83; ≥ 5: 11,32; p < 0.01; MS: 0-2: 37 %; 3-4: 33.3 %; ≥ 5: 76%; p < 0.01; WC: 0-2: 128.7 cm; 3-4: 130.7; ≥ 5: 140.6; p < 0.01). For the prediction of NASH (NAS score ≥ 5), the AUROC curve were 0.71 (CI 95 %: 0.63-0.79) for VAI and 0.7 (CI 95 %: 0.62-0.78) for WC. In conclusion, HOMA, WC and metabolic syndrome are related to liver histology in patients with severe obesity. In the multivariate analysis, VAI was associated with HOMA and metabolic syndrome, but not with liver histology