Las capas de "Margas Verdes" del Cenomanense de la zona central de ka Cadeba Ibérica: su significado en la evolución de la Plataforma Levantina

En este sector de la Cordillera Ibérica, dentro del conjunto de los materiales carbonatados litorales y marinos proximales, del Cenomanense inferior-medio, se intercalan hasta cuatro litosomas de «margas verdes  con un espesor variable (5-50 m) y una distribución geográfica no siempre  coincidente. Litológicamente están formadas por margas de un acusado color verde, a veces con intercalaciones de calcarenitas, biomicritas o calizas lumaquélicas, habiéndose considerado como depósitos de llanuras mareales, lagoon o plataformas someras restringidas. Estos materiales se interpretan como depósitos de baja tasa de sedimentación, formados durante intervalos de mínimos eustáticos y depositados a favor de una subsidencia isostática generalizada en esta región pudiéndose obtener a partir de ellos una curva eustática compleja, de traza sinuosa, con cinco valores máximos, que son progresivamentemenos acusados

Hyperbaric Oxygen Therapy Does Not Have a Negative Impact on Bone Signaling Pathways in Humans

Introduction: Oxygen is emerging as an important factor in the local regulation of bone remodeling. Some preclinical data suggest that hyperoxia may have deleterious effects on bone cells. However, its clinical relevance is unclear. Hence, we studied the effect of hyperbaric oxygen therapy (HBOT) on serum biomarkers reflecting the status of the Wnt and receptor activator of NF-?B ligand (RANKL) pathways, two core pathways for bone homeostasis. Materials and methods: This was a prospective study of 20 patients undergoing HBOT (mean age 58 yrs., range 35?82 yrs.) because of complications of radiotherapy or chronic anal fissure. Patients were subjected to HBOT (100% oxygen; 2.4 atmospheres absolute for 90 min). The average number of HBOT sessions was 20 ± 5 (range 8?31). Serum hypoxia-inducible factor 1-? (HIF1-?), osteoprotegerin (OPG), RANKL, and the Wnt inhibitors sclerostin and dickkopf-1 (DKK1) were measured at baseline and after HBOT by using specific immunoassays. Results: HIF-1? in eight patients with measurable serum levels increased from 0.084 (0.098) ng/mL at baseline to 0.146 (0.130) ng/mL after HBOT (p = 0.028). However, HBOT did not induce any significant changes in the serum levels of OPG, RANKL, sclerostin or DKK1. This was independent of the patients? diagnosis, either neoplasia or benign. Conclusion: Despite the potential concerns about hyperoxia, we found no evidence that HBOT has any detrimental effect on bone homeostasis

Effects of systemic or local administration of mesenchymal stem cells from patients with osteoporosis or osteoarthritis on femoral fracture healing in a mouse model

The purpose of this study was to analyze the regenerative capacity of mesenchymal stem cells (MSCs) in the treatment of fractures. MSCs extracted from patients with osteoporotic hip fractures or hip osteoarthritis undergoing hip replacement surgeries were cultured and injected into mice with femoral fracture. Two experimental models were established, one for the systemic administration of MSCs (n = 29) and another one for local administration (n = 30). Fracture consolidation was assessed by micro-CT and histology. The degree of radiological consolidation and corticalization was better with MSCs from osteoporosis than from osteoarthritis, being significant after systemic administration (p = 0.0302 consolidation; p = 0.0243 corticalization). The histological degree of consolidation was also better with MSCs from osteoporosis than from osteoarthritis. Differences in histological scores after systemic infusion were as follows: Allen, p = 0.0278; Huo, p = 0.3471; and Bone Bridge, p = 0.0935. After local administration at the fracture site, differences in histological scores were as follows: Allen, p = 0.0764; Huo, p = 0.0256; and Bone Bridge, p = 0.0012. As osteoporosis and control groups were similar, those differences depended on an inhibitory influence by MSCs from patients with osteoarthritis. In conclusion, we found an unexpected impairment of consolidation induced by MSCs from patients with osteoarthritis. However, MSCs from patients with osteoporosis compared favorably with cells from patients with osteoarthritis. In other words, based on this study and previous studies, MSCs from patients with osteoporosis do not appear to have worse bone-regenerating capabilities than MSCs from non-osteoporotic individuals of similar age.Funding: This work was supported by a grant from Instituto de Salud Carlos III [PI16-915], which can be cofounded by EU Feder funds. Acknowledgments: Álvaro del Real received support from the postdoctoral grant “Augusto González de Linares” of the University of Cantabria

Inflammatory cytokines and organ dysfunction associate with the aberrant DNA methylome of monocytes in sepsis

Background: Sepsis, a life-threatening organ dysfunction caused by a dysregulated systemic immune response to infection, associates with reduced responsiveness to subsequent infections. How such tolerance is acquired is not well understood but is known to involve epigenetic and transcriptional dysregulation. Methods: Bead arrays were used to compare global DNA methylation changes in patients with sepsis, noninfectious systemic inflammatory response syndrome, and healthy controls. Bioinformatic analyses were performed to dissect functional reprogramming and signaling pathways related to the acquisition of these specific DNA methylation alterations. Finally, in vitro experiments using human monocytes were performed to test the induction of similar DNA methylation reprogramming. Results: Here, we focused on DNA methylation changes associated with sepsis, given their potential role in stabilizing altered phenotypes. Tolerized monocytes from patients with sepsis display changes in their DNA methylomes with respect to those from healthy controls, affecting critical monocyte-related genes. DNA methylation profiles correlate with IL-10 and IL-6 levels, significantly increased in monocytes in sepsis, as well as with the Sequential Organ Failure Assessment score; the observed changes associate with TFs and pathways downstream to toll-like receptors and inflammatory cytokines. In fact, in vitro stimulation of toll-like receptors in monocytes results in similar gains and losses of methylation together with the acquisition of tolerance. Conclusion: We have identified a DNA methylation signature associated with sepsis that is downstream to the response of monocytes to inflammatory signals associated with the acquisition of a tolerized phenotype and organic dysfunction

SilvAdapt.Net: A Site-Based Network of Adaptive Forest Management Related to Climate Change in Spain

[EN] Adaptive forest management (AFM) is an urgent need because of the uncertainty regarding how changes in the climate will affect the structure, composition and function of forests during the next decades. Current research initiatives for the long-term monitoring of impacts of silviculture are scattered and not integrated into research networks, with the consequent losses of opportunities and capacity for action. To increase the scientific and practical impacts of these experiences, it is necessary to establish logical frameworks that harmonize the information and help us to define the most appropriate treatments. In this context, a number of research groups in Spain have produced research achievements and know-how during the last decades that can allow for the improvement in AFM. These groups address the issue of AFM from different fields, such as ecophysiology, ecohydrology and forest ecology, thus resulting in valuable but dispersed expertise. The main objective of this work is to introduce a comprehensive strategy aimed to study the implementation of AFM in Spain. As a first step, a network of 34 experimental sites managed by 14 different research groups is proposed and justified. As a second step, the most important AFM impacts on Mediterranean pines, as one of the most extended natural and planted forest types in Spain, are presented. Finally, open questions dealing with key aspects when attempting to implement an AFM framework are discussed. This study is expected to contribute to better outlining the procedures and steps needed to implement regional frameworks for AFM.A.J. Molina is beneficiary of an "APOSTD" fellowship (APOSTD/2019/111) funded by the Generalitat Valenciana. M. Moreno-de las Heras is beneficiary of a Serra Hunter fellowship (UB-LE-9055) funded by the Generalitat de Catalunya. F.J. Ruiz-Gomez is supported by a postdoctoral fellowship of the Junta de Andalucia (Sevilla, Spain), and the European Social Fund 2014-2020 Program (DOC_0055). The authors received national and international funding through the following projects: SILVADAPT.NET (RED2018-102719-T), ESPECTRAMED (CGL2017-86161-R), Life-FOREST CO2 (LIFE14 CCM/ES/001271), ALTERACLIM (CGL2015-69773-C2-1-P), INERTIA (PID2019-111332RB-C22-BDV), CEHYRFO-MED (CGL2017-86839-C3-2-R), DEHESACLIM (IB16185), RESILIENTFORESTS (LIFE17 CCA/ES/000063), Rhysotto (PID2019-106583RB-I00), AGL2017-83828C2-2-R, RTI2018-096884-B-C31, ESPAS (CGL2015-65569-R), and caRRRascal (RTI2018-095037-B-I00).Molina Herrera, A.; Navarro Cerrillo, R.; Pérez-Romero, J.; Alejano, R.; Bellot, JF.; Blanco, JA.; Camarero, JJ.... (2021). SilvAdapt.Net: A Site-Based Network of Adaptive Forest Management Related to Climate Change in Spain. Forests. 12(12):1-27. https://doi.org/10.3390/f12121807127121

Influencia del oxígeno a alta concentración en cámara hiperbárica sobre el metabolismo óseo

RESUMEN: Objetivos: Conocer las acciones del oxígeno a alta concentración en cámara hiperbárica (CH) sobre la expresión de genes relacionados con el metabolismo óseo en líneas celulares osteoblasticas y hueso trabecular humano. Material y métodos: Se analizó la expresión diferencial de varios genes relacionados con el metabolismo óseo (SOST, RUNX2, MMP14, OPG, HIF‐1α y SIRT1) en dos líneas celulares osteoblasticas humanas (Saos y Super‐Saos) y en fragmentos de hueso trabecular humano sometidos a una, tres o cinco sesiones de CH (90 minutos, oxigeno 100%; 2,3 atmosferas). En cada experimento se utilizó un control que no recibió CH. Resultados: No encontramos diferencias significativas tras la CH en la expresión de los genes estudiados, ni en las células ni en hueso trabecular. Solo en la línea celular Super‐Saos la expresión de OPG tras 5 sesiones de CH descendió 6 veces con respecto a la del grupo control (2‐ΔCt de 72; p=0,01). Conclusiones: El oxígeno a alta concentración en cámara hiperbárica no parece tener influencia en la expresión de genes relacionados con el metabolismo óseo

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality