Tectónica de placas, fallas, terremotos y riesgo sísmico. Una estrategia integradora

Los terremotos son uno de los recursos educativos más atractivos en ciencias de la Tierra. El tratamiento integrado de aspectos del currículo como la tectónica de placas, las fallas, los terremotos y el riesgo sísmico permite al alumnado desarrollar un pensamiento crítico. Los terremotos de Turquía de 2023 se han utilizado de ejemplo para que los alumnos y alumnas valoren las causas reales de esta catástrofe humanitaria

Elevated F-EDN correlates with mucosal eosinophil degranulation in patients with IBS - A possible association with microbiota?

Eosinophils have been linked to functional dyspepsia; however, less is known about their role in irritable bowel syndrome (IBS). This study tested the hypothesis of alterations in levels of fecal eosinophil-derived neurotoxin (F-EDN) and eosinophil density and degranulation within the colonic mucosa of IBS patients compared with healthy controls (HC). Colonic biopsies were collected from 37 IBS patients and 20 HC and analyzed for eosinophil numbers and local degranulation of eosinophil cationic protein (ECP) by histologic procedures. Fecal samples were collected for F-EDN and microbiota analysis. Differentiated 15HL-60 cells were used in vitro to investigate the direct effect of live bacteria on eosinophil activation measured by a colorimetric assay with o-phenylenediamine (OPD) substrate. We observed a higher number of eosinophils and increased extracellular ECP in the mucosa of IBS patients compared with HC. Moreover, F-EDN levels in IBS samples were elevated compared with HC and positively correlated to extracellular ECP. Metagenomic analysis showed significant correlations between bacterial composition and eosinophil measurements in both HC and IBS patients. In vitro experiments revealed an increased degranulation of 15HL-60 after stimulation with Salmonella typhimurium, Salmonella enterica, and Yersinia enterocolitica. To conclude, we could demonstrate alterations related to eosinophils in IBS, and, for the first time, a positive correlation between F-EDN levels and degranulated eosinophils in the colonic mucosa of IBS patients. Together our results suggest that eosinophils play a role in the pathophysiology of IBS and the mechanisms might be linked to an altered microbiota.Funding Agencies|Apotekare Hedberg Foundation; Magnus Bergvall Foundation [2018-02604]; Bengt Ihre Foundation [SLS-788111, SLS-882561]; Ruth and Richard Julin Foundation [2017-00350, 2019-00347]; County Council of Ostergotland [Lio-934618]; Mucosa Infection and Inflammation Center-MIIC; Medical Faculty, Uppsala University, Uppsala Sweden</p

Roles of GRK2 in Cell Signaling Beyond GPCR Desensitization: GRK2-HDAC6 Interaction Modulates Cell Spreading and Motility

G protein–coupled receptor kinase 2 (GR K2) is a ubiquitous, essential protein kinase that is emerging as an integrative node in many signaling networks. Moreover, changes in GR K2 abundance and activity have been identified in several inflammatory, cardiovascular disease, and tumor contexts, suggesting that those alterations may contribute to the initiation or development of pathologies. GR Ks were initially identified as key players in the desensitization and internalization of multiple G protein– coupled receptors (GPCR s), but GR K2 also phosphorylates several non-GPCR substrates and dynamically associates with a variety of proteins related to signal transduction. Ongoing research in our laboratory is aimed at understanding how specific GR K2 interactomes are orchestrated in a stimulus-, context-, or cell type– specific manner. We have recently identified an interaction between GR K2 and histone deacetylase 6 (HDAC 6) that modulates cell spreading and motility. HDAC 6 is a major cytoplasmic a-tubulin deacetylase that is involved in cell motility and adhesion. GR K2 dynamically and directly associates with and phosphorylates HDAC 6 to stimulate its a-tubulin deacetylase activity at specific cellular localizations, such as the leading edge of migrating cells, thus promoting local tubulin deacetylation and enhanced motility. GR K2-HDAC 6–mediated regulation of tubulin acetylation also modulates cellular spreading. This GR K2-HDAC 6 functional interaction may have important implications in pathological contexts related to epithelial cell migrationMinisterio de Educación y Ciencia (SAF2011-23800); Fundación Ramón Areces; Instituto de Salud Carlos III (RD06-0014/0037 and PI11/00859); Comunidad de Madrid (S2011/BMD-2332)Peer Reviewe

Chromium exposure and risk of cardiovascular disease in high cardiovascular risk subjects - nested case-control study in the prevention with mediterranean diet (PREDIMED) study

Background: Epidemiological data on chromium (Cr) exposure and the risk of cardiovascular disease (CVD) are still limited. Toenail Cr level (TCL) provides a time-integrated measure reflecting long-term Cr exposure. We measured TCL to assess the hypothesis that long-term Cr exposure was inversely associated with incident CVD in a population at high risk for CVD.Methods and Results: The associations between TCL and CVD were evaluated in a case-control study nested within the 'PREvencion con Dleta MEDiterranea' (PREDIMED) trial. We randomly selected 147 of the 288 patients diagnosed with CVD during follow-up and matched them on age and sex to 271 controls. Instrumental neutron activation analysis was used to assess TCL. In-person interviews, medical record reviews, and validated questionnaires were used to assess covariates. The fully adjusted OR for the highest vs. lowest quartile of toenail Cr was 0.54 (95% CI: 0.26-1.14; P-trend=0.189) for the nested case-control study. On stratification for diabetes mellitus (DM), OR was 1.37 (95% CI: 0.54-3.46; P-trend=0.364) for the DM group, and 0.25 (95% CI: 0.08-0.80; P-trend=0.030) for the non-DM group (P for interaction=0.078).Conclusions: The present findings, although not statistically significant, are consistent with previously reported inverse associations between TCL and CVD. These results, especially for non-DM patients, increase the limited epidemiological knowledge about the possible protective role of Cr against CVD

Increased Colonic Epithelial Permeability and Mucosal Eosinophilia in Ulcerative Colitis in Remission Compared With Irritable Bowel Syndrome and Health

Background Barrier dysfunction is recognized as a pathogenic factor in ulcerative colitis (UC) and irritable bowel syndrome (IBS), but it is unclear to what extent the factors related to barrier dysfunction are disease-specific. The aim of this study was to compare these aspects in UC patients in remission, IBS patients, and healthy controls (HCs). Methods Colonic biopsies were collected from 13 patients with UC in remission, 15 patients with IBS-mixed, and 15 HCs. Ulcerative colitis patients had recently been treated for relapse, and biopsies were taken from earlier inflamed areas. Biopsies were mounted in Ussing chambers for measurements of intestinal paracellular permeability to 51chromium (Cr)-ethylenediaminetetraacetic acid (EDTA). In addition, biopsies were analyzed for mast cells and eosinophils by histological procedures, and plasma tumor necrosis factor (TNF)-α was assessed by ELISA. Results Ussing chamber experiments revealed an increased 51Cr-EDTA permeability in UC and IBS (P &lt; 0.05). The 51Cr-EDTA permeability was higher in UC compared with IBS (P &lt; 0.005). There were increased numbers of mucosal mast cells and eosinophils in UC and IBS and more eosinophils in UC compared with IBS (P &lt; 0.05). Also, increased extracellular granule content was found in UC compared with HCs (P &lt; 0.05). The 51Cr-EDTA permeability correlated significantly with eosinophils in all groups. Plasma TNF-α concentration was higher in UC compared with IBS and HCs (P &lt; 0.0005). Conclusions Results indicate a more permeable intestinal epithelium in inactive UC and IBS compared with HCs. Ulcerative colitis patients, even during remission, demonstrate a leakier barrier compared with IBS. Both eosinophil numbers and activation state might be involved in the increased barrier function seen in UC patients in remission.Funding Agencies|Bengt Ihre research Scholarship; AFA research foundation; Bengt-Ihre fonden, County Council of Ostergotland; Swedish Research Council (VR-Medicine and Health)Swedish Research Council [2017-02475]; Swedish Foundation For Strategic ResearchSwedish Foundation for Strategic Research [RB13-016]; Instituto de Salud Carlos IIIInstituto de Salud Carlos III; Fondo de Investigacion SanitariaInstituto de Salud Carlos III [PI16/00583]; Ministerio de Ciencia, Innovacion y Universidades, Spain [CIBER-EHD CB06/04/0021]</p

Chromium Exposure and Risk of Cardiovascular Disease in High Cardiovascular Risk Subjects - Nested Case-Control Study in the Prevention With Mediterranean Diet (PREDIMED) Study

BACKGROUND: Epidemiological data on chromium (Cr) exposure and the risk of cardiovascular disease (CVD) are still limited. Toenail Cr level (TCL) provides a time-integrated measure reflecting long-term Cr exposure. We measured TCL to assess the hypothesis that long-term Cr exposure was inversely associated with incident CVD in a population at high risk for CVD.Methods and Results:The associations between TCL and CVD were evaluated in a case-control study nested within the "PREvención con DIeta MEDiterránea" (PREDIMED) trial. We randomly selected 147 of the 288 patients diagnosed with CVD during follow-up and matched them on age and sex to 271 controls. Instrumental neutron activation analysis was used to assess TCL. In-person interviews, medical record reviews, and validated questionnaires were used to assess covariates. The fully adjusted OR for the highest vs. lowest quartile of toenail Cr was 0.54 (95% CI: 0.26-1.14; Ptrend=0.189) for the nested case-control study. On stratification for diabetes mellitus (DM), OR was 1.37 (95% CI: 0.54-3.46; Ptrend=0.364) for the DM group, and 0.25 (95% CI: 0.08-0.80; Ptrend=0.030) for the non-DM group (P for interaction=0.078). CONCLUSIONS: The present findings, although not statistically significant, are consistent with previously reported inverse associations between TCL and CVD. These results, especially for non-DM patients, increase the limited epidemiological knowledge about the possible protective role of Cr against CVD. (Trial registration: www.controlled-trials.com; ISRCTN35739639.).This research was supported by the official funding agency for biomedical research of the Spanish Government, Instituto de Salud Carlos III (ISCIII), through grants provided to research networks specifically developed for the trial (RTIC G03/140 to R.E.; RTIC RD 06/0045 “PREDIMED” to M.A.M-G.), and JR14/00008 to O.C., and through Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), and by grants from Centro Nacional de Investigaciones Cardiovasculares (CNIC 06/2007), Fondo de Investigación Sanitaria-Fondo Europeo de Desarrollo Regional (Proyecto de Investigación (PI) 04-2239, PI 05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, P11/02505 and PI13/00462), Ministerio de Ciencia e Innovación (Recursos y teconologia agroalimentarias (AGL)-2009-13906-C02 and AGL2010-22319-C03 and AGL2013-49083C3-1-R), Fundación Mapfre 2010, Consejería de Salud de la Junta de Andalucía (PI0105/2007), Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Generalitat Valenciana (Generalitat Valenciana Ayuda Complementatia GVACOMP) 06109, GVACOMP2010-181, GVACOMP2011-151), Conselleria de Sanitat y AP; Atención Primaria (CS) 2010-AP-111, and CS2011-AP-042), Regional Government of Navarra (P27/2011), and Centre Català de la Nutrició de l’Institut d’Estudis Catalans. Hojiblanca and Patrimonio Communal Olivarero donated extra-virgin olive oil; the California Walnut Commission donated walnuts; Borges donated almonds; La Morella Nuts donated hazelnuts