Procesos de Gestión de Datos.(Data Management Plans)

Presentación de Alex Sánchez-Pla en la Jornada de Ciencia abierta en los Institutos de Investigación Sanitaria el día 29 /06/2021.La gestión de los datos durante la investigación. Así pues, ¿qué es un Plan de Gestión de Datos?. ¿Por qué es bueno disponer de un PGD?. ¿Qué debe contener un PGD?. Un PGD debe responder algunas preguntas. Sin olvidar la FAIRificación. Resumiendo, hasta aquí. ¿Cómo se elabora un PGD?. Herramientas libres para elaborar PGD. ¿Qué herramienta escoger? ¿Quién desarrolla el PGD?. El papel de las InstitucionesN

Molecular mechanisms of tungstate-induced pancreatic plasticity: a transcriptomics approach

<p>Abstract</p> <p>Background</p> <p>Sodium tungstate is known to be an effective anti-diabetic agent, able to increase beta cell mass in animal models of diabetes, although the molecular mechanisms of this treatment and the genes that control pancreas plasticity are yet to be identified. Using a transcriptomics approach, the aim of the study is to unravel the molecular mechanisms which participate in the recovery of exocrine and endocrine function of streptozotocin (STZ) diabetic rats treated with tungstate, determining the hyperglycemia contribution and the direct effect of tungstate.</p> <p>Results</p> <p>Streptozotocin (STZ)-diabetic rats were treated orally with tungstate for five weeks. Treated (STZ)-diabetic rats showed a partial recovery of exocrine and endocrine function, with lower glycemia, increased insulinemia and amylasemia, and increased beta cell mass achieved by reducing beta cell apoptosis and raising beta cell proliferation. The microarray analysis of the pancreases led to the identification of three groups of differentially expressed genes: genes altered due to diabetes, genes restored by the treatment, and genes specifically induced by tungstate in the diabetic animals. The results were corroborated by quantitative PCR. A detailed description of the pathways involved in the pancreatic effects of tungstate is provided in this paper. Hyperglycemia contribution was studied in STZ-diabetic rats treated with phloridzin, and the direct effect of tungstate was determined in INS-1E cells treated with tungstate or serum from untreated or treated STZ-rats, observing that tungstate action in the pancreas takes places via hyperglycemia-independent pathways and via a combination of tungstate direct and indirect (through the serum profile modification) effects. Finally, the MAPK pathway was evaluated, observing that it has a key role in the tungstate-induced increase of beta cell proliferation as tungstate activates the mitogen-activated protein kinase (MAPK) pathway directly by increasing p42/p44 phosphorylation and indirectly by decreasing the expression of raf kinase inhibitor protein (Rkip), a negative modulator of the pathway.</p> <p>Conclusion</p> <p>In conclusion, tungstate improves pancreatic function through a combination of hyperglycemia-independent pathways and through its own direct and indirect effects, whereas the MAPK pathway has a key role in the tungstate-induced increase of beta cell proliferation.</p

CSF SERPINA3 Levels Are Elevated in Patients With Progressive MS

Multiple sclerosis; SERPINA3Esclerosi múltiple; SERPINA3Esclerosis múltiple; SERPINA3Objective To identify biomarkers associated with progressive phases of MS and with neuroprotective potential. Methods Combined analysis of the transcriptional and proteomic profiles obtained in CNS tissue during chronic progressive phases of experimental autoimmune encephalomyelitis (EAE) with the transcriptional profile obtained during the differentiation of murine neural stem cells into neurons. Candidate biomarkers were measured by ELISA in the CSF of 65 patients with MS (29 with relapsing-remitting MS [RRMS], 20 with secondary progressive MS, and 16 with primary progressive MS [PPMS]) and 30 noninflammatory neurologic controls (NINCs). Results Integrative analysis of gene and protein expression data identified 2 biomarkers, the serine protease inhibitor Serpina3n and the calcium-binding protein S100A4, which were upregulated in chronic progressive EAE and whose expression was induced during neuronal differentiation. Immunofluorescence studies revealed a primarily neuronal expression of S100A4 and Serpina3n during EAE. CSF levels of SERPINA3, the human ortholog of murine Serpina3n, and S100A4 were increased in patients with MS compared with NINCs (SERPINA3: 1,320 vs 838.6 ng/mL, p = 0.0001; S100A4: 1.6 vs 0.8 ng/mL, p = 0.02). Within the MS group, CSF SERPINA3 levels were significantly elevated in patients with progressive forms, mainly patients with PPMS compared with patients with RRMS (1,617 vs 1,129 ng/mL, p = 0.02) and NINCs (1,617 vs 838.6 ng/mL, p = 0.0001). Of interest, CSF SERPINA3 levels significantly correlated with CSF neurofilament light chain levels only in the PPMS group (r = 0.62, p = 0.01). Conclusion These results point to a role of SERPINA3 as a biomarker associated with the progressive forms of MS, particularly PPMS.This work was supported by grants from the Fondo de Investigación Sanitaria (FIS; grant number PI17/00596), Ministry of Science and Innovation, Spain; Generalitat de Catalunya Suport Grups de Recerca (2017 SGR 0527); and the Red Española de Esclerosis Múltiple (RD16/0015/0004) funded by the FIS

Integrative Multi-omics Analysis to Characterize Human Brain Ischemia

Stroke is a major cause of death and disability. A better comprehension of stroke pathophysiology is fundamental to reduce its dramatic outcome. The use of high-throughput unbiased omics approaches and the integration of these data might deepen the knowledge of stroke at the molecular level, depicting the interaction between different molecular units. We aimed to identify protein and gene expression changes in the human brain after ischemia through an integrative approach to join the information of both omics analyses. The translational potential of our results was explored in a pilot study with blood samples from ischemic stroke patients. Proteomics and transcriptomics discovery studies were performed in human brain samples from six deceased stroke patients, comparing the infarct core with the corresponding contralateral brain region, unveiling 128 proteins and 2716 genes significantly dysregulated after stroke. Integrative bioinformatics analyses joining both datasets exposed canonical pathways altered in the ischemic area, highlighting the most influential molecules. Among the molecules with the highest fold-change, 28 genes and 9 proteins were selected to be validated in five independent human brain samples using orthogonal techniques. Our results were confirmed for NCDN, RAB3C, ST4A1, DNM1L, A1AG1, A1AT, JAM3, VTDB, ANXA1, ANXA2, and IL8. Finally, circulating levels of the validated proteins were explored in ischemic stroke patients. Fluctuations of A1AG1 and A1AT, both up-regulated in the ischemic brain, were detected in blood along the first week after onset. In summary, our results expand the knowledge of ischemic stroke pathology, revealing key molecules to be further explored as biomarkers and/or therapeutic targets

Molecular mechanisms of tungstate-induced pancreatic plasticity: A transcriptomics approach

Background: Sodium tungstate is known to be an effective anti-diabetic agent, able to increase beta cell mass in animal models of diabetes, although the molecular mechanisms of this treatment and the genes that control pancreas plasticity are yet to be identified. Using a transcriptomics approach, the aim of the study is to unravel the molecular mechanisms which participate in the recovery of exocrine and endocrine function of streptozotocin (STZ) diabetic rats treated with tungstate, determining the hyperglycemia contribution and the direct effect of tungstate. Results: Streptozotocin (STZ)-diabetic rats were treated orally with tungstate for five weeks. Treated (STZ)-diabetic rats showed a partial recovery of exocrine and endocrine function, with lower glycemia, increased insulinemia and amylasemia, and increased beta cell mass achieved by reducing beta cell apoptosis and raising beta cell proliferation. The microarray analysis of the pancreases led to the identification of three groups of differentially expressed genes: genes altered due to diabetes, genes restored by the treatment, and genes specifically induced by tungstate in the diabetic animals. The results were corroborated by quantitative PCR. A detailed description of the pathways involved in the pancreatic effects of tungstate is provided in this paper. Hyperglycemia contribution was studied in STZ-diabetic rats treated with phloridzin, and the direct effect of tungstate was determined in INS-1E cells treated with tungstate or serum from untreated or treated STZ-rats, observing that tungstate action in the pancreas takes places via hyperglycemia-independent pathways and via a combination of tungstate direct and indirect (through the serum profile modification) effects. Finally, the MAPK pathway was evaluated, observing that it has a key role in the tungstate-induced increase of beta cell proliferation as tungstate activates the mitogen-activated protein kinase (MAPK) pathway directly by increasing p42/p44 phosphorylation and indirectly by decreasing the expression of raf kinase inhibitor protein (Rkip), a negative modulator of the pathway. Conclusion: In conclusion, tungstate improves pancreatic function through a combination of hyperglycemia-independent pathways and through its own direct and indirect effects, whereas the MAPK pathway has a key role in the tungstate-induced increase of beta cell proliferation.Centro de Endocrinología Experimental y Aplicad

Assessing Adherence to Healthy Dietary Habits Through the Urinary Food Metabolome:Results From a European Two-Center Study

BACKGROUND: Diet is one of the most important modifiable lifestyle factors in human health and in chronic disease prevention. Thus, accurate dietary assessment is essential for reliably evaluating adherence to healthy habits. OBJECTIVES: The aim of this study was to identify urinary metabolites that could serve as robust biomarkers of diet quality, as assessed through the Alternative Healthy Eating Index (AHEI-2010). DESIGN: We set up two-center samples of 160 healthy volunteers, aged between 25 and 50, living as a couple or family, with repeated urine sampling and dietary assessment at baseline, and 6 and 12 months over a year. Urine samples were subjected to large-scale metabolomics analysis for comprehensive quantitative characterization of the food-related metabolome. Then, lasso regularized regression analysis and limma univariate analysis were applied to identify those metabolites associated with the AHEI-2010, and to investigate the reproducibility of these associations over time. RESULTS: Several polyphenol microbial metabolites were found to be positively associated with the AHEI-2010 score; urinary enterolactone glucuronide showed a reproducible association at the three study time points [false discovery rate (FDR): 0.016, 0.014, 0.016]. Furthermore, other associations were found between the AHEI-2010 and various metabolites related to the intake of coffee, red meat and fish, whereas other polyphenol phase II metabolites were associated with higher AHEI-2010 scores at one of the three time points investigated (FDR < 0.05 or β ≠ 0). CONCLUSION: We have demonstrated that urinary metabolites, and particularly microbiota-derived metabolites, could serve as reliable indicators of adherence to healthy dietary habits. CLINICAL TRAIL REGISTRATION: www.ClinicalTrials.gov, Identifier: NCT03169088

Aberrant epigenome in iPSC-derived dopaminergic neurons from Parkinson's disease patients

The epigenomic landscape of Parkinson's disease (PD) remains unknown. We performed a genomewide DNA methylation and a transcriptome studies in induced pluripotent stem cell (iPSC)-derived dopaminergic neurons (DAn) generated by cell reprogramming of somatic skin cells from patients with monogenic LRRK2-associated PD (L2PD) or sporadic PD (sPD), and healthy subjects. We observed extensive DNA methylation changes in PD DAn, and of RNA expression, which were common in L2PD and sPD. No significant methylation differences were present in parental skin cells, undifferentiated iPSCs nor iPSC-derived neural cultures not-enriched-in-DAn. These findings suggest the presence of molecular defects in PD somatic cells which manifest only upon differentiation into the DAn cells targeted in PD. The methylation profile from PD DAn, but not from controls, resembled that of neural cultures not-enriched-in-DAn indicating a failure to fully acquire the epigenetic identity own to healthy DAn in PD. The PD-associated hypermethylation was prominent in gene regulatory regions such as enhancers and was related to the RNA and/or protein downregulation of a network of transcription factors relevant to PD (FOXA1, NR3C1, HNF4A, and FOSL2). Using a patient-specific iPSC-based DAn model, our study provides the first evidence that epigenetic deregulation is associated with monogenic and sporadic PD

Exposing and Overcoming Limitations of Clinical Laboratory Tests in COVID-19 by Adding Immunological Parameters; A Retrospective Cohort Analysis and Pilot Study

BackgroundTwo years since the onset of the COVID-19 pandemic no predictive algorithm has been generally adopted for clinical management and in most algorithms the contribution of laboratory variables is limited. ObjectivesTo measure the predictive performance of currently used clinical laboratory tests alone or combined with clinical variables and explore the predictive power of immunological tests adequate for clinical laboratories. Methods: Data from 2,600 COVID-19 patients of the first wave of the pandemic in the Barcelona area (exploratory cohort of 1,579, validation cohorts of 598 and 423 patients) including clinical parameters and laboratory tests were retrospectively collected. 28-day survival and maximal severity were the main outcomes considered in the multiparametric classical and machine learning statistical analysis. A pilot study was conducted in two subgroups (n=74 and n=41) measuring 17 cytokines and 27 lymphocyte phenotypes respectively. Findings1) Despite a strong association of clinical and laboratory variables with the outcomes in classical pairwise analysis, the contribution of laboratory tests to the combined prediction power was limited by redundancy. Laboratory variables reflected only two types of processes: inflammation and organ damage but none reflected the immune response, one major determinant of prognosis. 2) Eight of the thirty variables: age, comorbidity index, oxygen saturation to fraction of inspired oxygen ratio, neutrophil-lymphocyte ratio, C-reactive protein, aspartate aminotransferase/alanine aminotransferase ratio, fibrinogen, and glomerular filtration rate captured most of the combined statistical predictive power. 3) The interpretation of clinical and laboratory variables was moderately improved by grouping them in two categories i.e., inflammation related biomarkers and organ damage related biomarkers; Age and organ damage-related biomarker tests were the best predictors of survival, and inflammatory-related ones were the best predictors of severity. 4) The pilot study identified immunological tests (CXCL10, IL-6, IL-1RA and CCL2), that performed better than most currently used laboratory tests. ConclusionsLaboratory tests for clinical management of COVID 19 patients are valuable but limited predictors due to redundancy; this limitation could be overcome by adding immunological tests with independent predictive power. Understanding the limitations of tests in use would improve their interpretation and simplify clinical management but a systematic search for better immunological biomarkers is urgent and feasible

Jardins per a la salut

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia. Assignatura: Botànica farmacèutica. Curs: 2014-2015. Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són el recull de les fitxes botàniques de 128 espècies presents en el Jardí Ferran Soldevila de l’Edifici Històric de la UB. Els treballs han estat realitzats manera individual per part dels estudiants dels grups M-3 i T-1 de l’assignatura Botànica Farmacèutica durant els mesos de febrer a maig del curs 2014-15 com a resultat final del Projecte d’Innovació Docent «Jardins per a la salut: aprenentatge servei a Botànica farmacèutica» (codi 2014PID-UB/054). Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pels professors de l’assignatura. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica. També s’ha pretès motivar els estudiants a través del retorn de part del seu esforç a la societat a través d’una experiència d’Aprenentatge-Servei, deixant disponible finalment el treball dels estudiants per a poder ser consultable a través d’una Web pública amb la possibilitat de poder-ho fer in-situ en el propi jardí mitjançant codis QR amb un smartphone