Dreams may come true...

Per tal de resumir el treball de forma breu m’agradaria d’estacar els objectius principals del projecte que són: principalment la creació d’un curtmetratge d’animació 3D, l’aprenentatge d’un software professional en aquest aspecte i reafirmar i adquirir nous coneixements. La memòria està dividida en quatre punts bàsics. El primer fa referència a tot l’àmbit de preproducció (guionatge, disseny de personatges i escenaris i definició d’estils). El segon bloc és el que fa referència a tot l’apartat de producció, on es parla de tots els aspectes treballats amb el software (modelat, esquelets, animació, renderització, etc.). El tercer bloc és la part de postproducció i és aquí on s’ajunten totes les parts anteriors per crear el producte final. El quart punt és una visió crítica al treball realitzat i el cost del producte, si aquest hagués estat realitzat per una empresa professional

Dreams may come true...

Per tal de resumir el treball de forma breu m’agradaria d’estacar els objectius principals del projecte que són: principalment la creació d’un curtmetratge d’animació 3D, l’aprenentatge d’un software professional en aquest aspecte i reafirmar i adquirir nous coneixements. La memòria està dividida en quatre punts bàsics. El primer fa referència a tot l’àmbit de preproducció (guionatge, disseny de personatges i escenaris i definició d’estils). El segon bloc és el que fa referència a tot l’apartat de producció, on es parla de tots els aspectes treballats amb el software (modelat, esquelets, animació, renderització, etc.). El tercer bloc és la part de postproducció i és aquí on s’ajunten totes les parts anteriors per crear el producte final. El quart punt és una visió crítica al treball realitzat i el cost del producte, si aquest hagués estat realitzat per una empresa professional

Epigenetic clock indicates accelerated aging in glial cells of progressive multiple sclerosis patients

Background: Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system (CNS) characterized by irreversible disability at later progressive stages. A growing body of evidence suggests that disease progression depends on age and inflammation within the CNS. We aimed to investigate epigenetic aging in bulk brain tissue and sorted nuclei from MS patients using DNA methylation-based epigenetic clocks. Methods: We applied Horvath’s multi-tissue and Shireby’s brain-specific Cortical clock on bulk brain tissue (n = 46), sorted neuronal (n = 54), and glial nuclei (n = 66) from post-mortem brain tissue of progressive MS patients and controls. Results: We found a significant increase in age acceleration residuals, corresponding to 3.6 years, in glial cells of MS patients compared to controls (P = 0.0024) using the Cortical clock, which held after adjustment for covariates (Padj = 0.0263). The 4.8-year age acceleration found in MS neurons (P = 0.0054) did not withstand adjustment for covariates and no significant difference in age acceleration residuals was observed in bulk brain tissue between MS patients and controls. Conclusion: While the findings warrant replication in larger cohorts, our study suggests that glial cells of progressive MS patients exhibit accelerated biological aging.This study was supported by grants from the Swedish Research Council, the Swedish Association for Persons with Neurological Disabilities, the Swedish Brain Foundation, the Swedish MS Foundation, the Stockholm County Council – ALF project, the European Union’s Horizon 2020 research, innovation program (grant agreement No. 733161) and the European Research Council (ERC, grant agreement No. 818170), the Knut and Alice Wallenberg Foundation grant, Åke Wilberg Foundation, and Karolinska Institute’s funds. LK was supported by a fellowship from the Margaretha af Ugglas Foundation. DK was supported by an Erasmus fellowship. The funders of the study had no role in study design, sample acquisition, data collection, data analysis, data interpretation, or writing of the manuscript. AU-C was supported by “Doctorados industriales 2018–2020” and “Contrato predoctoral en investigación en ciencias y tecnologías de la salud en el periodo 2019–2022” fellowships, both funded by the Government of Navarra and by an Erasmus fellowship. The computations were enabled by resources provided by the Swedish National Infrastructure for Computing (SNIC) at UPPMAX, partially funded by the Swedish Research Council through grant agreement No. 2018-05973

Structural Characterization of the Enzymes Composing the Arginine Deiminase Pathway in Mycoplasma penetrans

The metabolism of arginine towards ATP synthesis has been considered a major source of energy for microorganisms such as Mycoplasma penetrans in anaerobic conditions. Additionally, this pathway has also been implicated in pathogenic and virulence mechanism of certain microorganisms, i.e. protection from acidic stress during infection. In this work we present the crystal structures of the three enzymes composing the gene cluster of the arginine deiminase pathway from M. penetrans: arginine deiminase (ADI), ornithine carbamoyltransferase (OTC) and carbamate kinase (CK). The arginine deiminase (ADI) structure has been refined to 2.3 Å resolution in its apo-form, displaying an "open" conformation of the active site of the enzyme in comparison to previous complex structures with substrate intermediates. The active site pocket of ADI is empty, with some of the catalytic and binding residues far from their active positions, suggesting major conformational changes upon substrate binding. Ornithine carbamoyltransferase (OTC) has been refined in two crystal forms at 2.5 Å and 2.6 Å resolution, respectively, both displaying an identical dodecameric structure with a 23-point symmetry. The dodecameric structure of OTC represents the highest level of organization in this protein family and in M.penetrans it is constituted by a novel interface between the four catalytic homotrimers. Carbamate kinase (CK) has been refined to 2.5 Å resolution and its structure is characterized by the presence of two ion sulfates in the active site, one in the carbamoyl phosphate binding site and the other in the β-phosphate ADP binding pocket of the enzyme. The CK structure also shows variations in some of the elements that regulate the catalytic activity of the enzyme. The relatively low number of metabolic pathways and the relevance in human pathogenesis of Mycoplasma penetrans places the arginine deiminase pathway enzymes as potential targets to design specific inhibitors against this human parasite

Control optoelectrónico en tiempo real de la transparencia de ventanas: Aplicaciones Domóticas

Publicad

Contribución de la electrónica y fotónica a la tecnología de la rehabilitación

Alrededor de un 15% de la población está afectada en cierto grado por una discapacidad. En la sociedad del bienestar y a las puertas de un nuevo milenio, existe una indudable preocupación por proporcionar a estas personas con discapacidad acceso a servicios similares, y a un mismo grado de independencia que sus conciudadanos. En este sentido, la Tecnología de la Rehabilitación será la encargada de ofrecerles soluciones, productos y servicios que les permitan equipararse con el resto de la sociedad y acceder de forma igualitaria a las mismas tareas, actividades y puestos de trabajo. El soporte tecnológico sobre el que se basarán los citados productos o servicios puede ser variado, aunque disciplinas tradicionales como la electrónica y la fotónica seguirán jugando un papel preponderante.Publicad

Tratamiento ortopodológico sustitutivo de una amputación a nivel de Chopart

Los autores describen todo el proceso de confección de una prótesis funcional a nivel de Chopart en una paciente, que sufrió una amputación traumática a nivel de esta articulación

Myocardial infarction ´through the window´: dual dynamics for cardiac fibroblasts activation

Activated cardiac fibroblasts (CFs) are responsible for the healing of the heart tissue after a myocardial infarction (MI). Based on high throughput technologies, several groups have recently demonstrated their heterogeneity and a unique role of each subpopulation of CFs during the ventricular remodelling process. This is relevant towards the discovery of personalized treatments to control the initial post-MI healing scar that will contribute to preserve ventricular function and prevent the onset of heart failure. However, little is known about the moment that CFs are activated, and which genes are potentially involved in this process. Using a mouse model for MI and single cell RNA-Seq, we demonstrate that the activation of Reparative Cardiac Fibroblasts (RCFs), the CFs responsible for the healing scar, happens within the first week after MI. Interestingly, our data reveals that all CFs show high expression of the top markers genes for RCF in a specific moment, but only few of them finally evolve to an RCF transcriptomic identity. Furthermore, we describe two different molecular dynamics that could give rise to this activation and, in consequence, the appearance of definitive RCFs. Using Spatial Transcriptomics, we localized the genes related to each dynamic in different anatomical regions of the infarcted heart, but, remarkably, only one persists seven days after MI. These results highlight the existence of a specific “window of activation” of RCFs at the beginning of the ventricular remodelling process. This potential ´therapeutical window´ could allow us to regulate the size of the healing scar and, in consequence, the poor prognosis for patients that have suffered an ischemic event.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Serum methylation of GALNT9, UPF3A, WARS, and LDB2 as noninvasive biomarkers for the early detection of colorectal cancer and advanced adenomas

Background Early detection has proven to be the most effective strategy to reduce the incidence and mortality of colorectal cancer (CRC). Nevertheless, most current screening programs suffer from low participation rates. A blood test may improve both the adherence to screening and the selection to colonoscopy. In this study, we conducted a serum-based discovery and validation of cfDNA methylation biomarkers for CRC screening in a multicenter cohort of 433 serum samples including healthy controls, benign pathologies, advanced adenomas (AA), and CRC.Results First, we performed an epigenome-wide methylation analysis with the MethylationEPIC array using a sample pooling approach, followed by a robust prioritization of candidate biomarkers for the detection of advanced neoplasia (AN: AA and CRC). Then, candidate biomarkers were validated by pyrosequencing in independent individual cfDNA samples. We report GALNT9, UPF3A, WARS, and LDB2 as new noninvasive biomarkers for the early detection of AN. The combination of GALNT9/UPF3A by logistic regression discriminated AN with 78.8% sensitivity and 100% specificity, outperforming the commonly used fecal immunochemical test and the methylated SEPT9 blood test.Conclusions Overall, this study highlights the utility of cfDNA methylation for CRC screening. Our results suggest that the combination methylated GALNT9/UPF3A has the potential to serve as a highly specific and sensitive blood-based test for screening and early detection of CRC

Non-parametric combination analysis of multiple data types enables detection of novel regulatory mechanisms in T cells of multiple sclerosis patients

Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system with prominent neurodegenerative components. The triggering and progression of MS is associated with transcriptional and epigenetic alterations in several tissues, including peripheral blood. The combined influence of transcriptional and epigenetic changes associated with MS has not been assessed in the same individuals. Here we generated paired transcriptomic (RNA-seq) and DNA methylation (Illumina 450 K array) profiles of CD4+ and CD8+ T cells (CD4, CD8), using clinically accessible blood from healthy donors and MS patients in the initial relapsing-remitting and subsequent secondary-progressive stage. By integrating the output of a differential expression test with a permutation-based non-parametric combination methodology, we identified 149 differentially expressed (DE) genes in both CD4 and CD8 cells collected from MS patients. Moreover, by leveraging the methylation-dependent regulation of gene expression, we identified the gene SH3YL1, which displayed significant correlated expression and methylation changes in MS patients. Importantly, silencing of SH3YL1 in primary human CD4 cells demonstrated its influence on T cell activation. Collectively, our strategy based on paired sampling of several cell-types provides a novel approach to increase sensitivity for identifying shared mechanisms altered in CD4 and CD8 cells of relevance in MS in small sized clinical materials