Restoring cholesterol efflux in vascular smooth muscle cells transitioning into foam cells through Liver X receptor activation

Macrophage foam cells derived from vascular smooth muscle cells (VSMCs) account for 30–70 % of foam cells in atherosclerotic lesions. Liver X receptor (LXR) agonists promote high-density lipoprotein (HDL)-mediated cholesterol efflux from macrophages. This study aimed to investigate the effects of LXR activation on the reverse cholesterol transport (RCT) rate from VSMCs to feces in vivo. Both human and mouse VSMCs exhibited similar levels of cholesterol efflux when exposed to serum and HDL. However, cholesterol efflux was significantly reduced following methyl-β-cyclodextrin (MBD)-cholesterol loading, while treatment with the LXR agonist T090137 markedly enhanced efflux. Radiolabeled foam-like VSMCs injected intraperitoneally into mice exhibited impaired cholesterol transfer to serum, HDL, and feces compared to non-lipid-laden VSMCs. Pre-treatment with the LXR agonist increased radiolabeled cholesterol levels in serum and HDL and doubled its fecal excretion. Furthermore, LXR activation restored RCT from MBD-cholesterol-loaded VSMCs to feces, reaching levels comparable to those of non-lipid-laden cells. Treatment with an acyl-coenzyme A: cholesterol acyltransferase (ACAT) inhibitor fully restored RCT rates in foam-like VSMCs, and the combination of the ACAT inhibitor and the LXR agonist further enhanced RCT. These findings indicate that HDL-mediated cholesterol efflux is significantly impaired during the transition of VSMCs into foam cells. Pharmacological activation of LXR enhances RCT from VSMCs to feces in vivo and restores the impaired RCT from transitioning VSMCs. The combination of LXR agonists and ACAT inhibitors holds promise as a synergistic therapeutic approach to restoring cholesterol homeostasis in lipid-laden VSMCs, offering potential strategies to mitigate atherosclerosis.This work was partly funded by the Instituto de Salud Carlos III and FEDER "Una manera de hacer Europa" grants PI2100140 (to F.B-V and M.T), PI2300232 (to M.C and J.E-G), JR22/00003 (to M.C.), PI2101523 (to V.Ll-C.) and the Ministerio de Ciencia, Innovación y Universidades, grants PID2022–137186OB-I00 and CNS2023–144119 (to N.R.). C.B. was funded with a Formación de Profesorado Universitario grant FPU20/07440 from Ministerio de Universidades. N.R was funded by Agencia Estatal de Investigación (AEI/10.13039/501100011033) within the Subprograma Ramón y Cajal (RYC-201722879). Q.Z. and C.D. were supported by the State Scholarship Fund from the China Scholarship Council (Grant Nos. 202406170068 and 202408370068, respectively). CIBERDEM and CIBERCV are Instituto de Salud Carlos III projects. All authors declare that they have no relationships relevant to the contents of this paper to disclose and have approved the final version of the article.Peer reviewe

Deep immune cell profiling in blood and bone marrow of early stage monoclonal gammopathy: an iStopMM and ECRIN-M3 collaborative study

This work was supported by a grant of the International Myeloma Foundation, the EuroFlow Consortium and The Binding Site Group. It was also partially supported by the “Early Cancer Research Initiative Network on MBL (ECRIN-M3)” ACCELERATOR award -CRUK (UK), Fundación AECC (Spain) and Associazione Italiana per la Ricerca Sul Cancro (Italy)- and the PI22/00674 grant from the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, (Madrid, Spain). O. Pérez-Escurza was supported by a grant of the Government of Castilla y León (Orden EDU/601/2020), Spain. We thank the members of the iStopMM program for their support in sample and data collection. The iStopMM study is funded by the Black Swan Research Initiative by the International Myeloma Foundation and the Icelandic Centre for Research (grant agreement No 173857, 217897-051 and 228521-051). We thank our laboratory colleagues for their collaboration in the recruitment of healthy adult samples. Screening tests were performed by The Binding Site Ltd. Birmingham, UK.Peer reviewe

Mean change in under global and no migration [Dataset]

For both a) no and b) global migration the mean of is initially higher than the stationary value of zero, though the mean relaxes to zero by transfer six for both treatments and does not appear to change after the cessation of global migration. This result is consistent with predicted consequences of global migration.Peer reviewe

Grazing Modulates the Multiscale Spatial Structure of Dryland Vegetation

Plants can facilitate their local environment and create a two-phase spatial structure of vegetation and bare soil in drylands, which largely influences ecosystem functioning. Although an increasing number of studies have examined how global change drivers like aridity influence vegetation spatial structure in drylands (e.g., the patch size distribution), it remains unclear how grazing impacts differ from those of climatic gradients, how these effects vary with herbivore feeding habits, and which plant-level traits—such as size and life form—mediate these spatial responses. Here, we coupled spatial vegetation pattern analyses of ecosystem images with field data analyses of the size distribution and dominant life forms of plants from 326 plots sampled across 25 countries and six continents to explore the effects of herbivores on the spatial structure of dryland vegetation. The effects of herbivores on vegetation spatial structure were opposite to the effects of aridity. Specifically, vegetation in grazed areas was clustered into larger patches, with fewer small patches, which skewed the patch-size distribution towards larger patches. These effects differed between browsing and grazing herbivores. Grazing effects were partially explained by the fact that grazing reduced average plant size, increased shrub density, and promoted facilitation among species of contrasting sizes. Similar effects were also confirmed by using model simulations that accounted for positive plant interactions. By linking remotely sensed images, a global field survey, and a mathematical model, our study uncovers the species-level mechanisms by which herbivores shape ecosystem-level spatial patterns and provides insights into the consequence of herbivory pressure on the resilience of drylands.This research benefited from the support of the Chair Modelisation Mathématique et Biodiversite VEOLIA~Ecole Polytechnique~MNHN~F-X. The BIODESERT global survey was funded by the European Research Council (ERC Grant agreement 647038). FTM acknowledges support by the King Abdullah University of Science and Technology (KAUST) and the KAUST Climate and Livability Initiative. D.E. is supported by the Hermon Slade Foundation. Fernando T. Maestre and Sophie Donnet shared co-last equal contribution.Peer reviewe

Experimental summer fires do not affect fungal diversity but do shape fungal community composition in Mediterranean Pinus nigra forests

[Background] Fire regimes (in terms of frequency, severity, and intensity) in ecosystems are changing. Summer fires are occurring in Mediterranean forests more frequently and are more severe than spring or autumn fires. Soil microbial communities provide essential ecosystem services and are essential in post-fire recovery. However, to date, studies to determine the impact of summer fires on soil microbial communities have been limited. To explore how more severe fires may affect fungal diversity and community composition, we conducted an experimental summer fire in June 2019 at an experimental site that had been previously established in a pure stand of black pine (Pinus nigra Arn.) in 2016 in the Cuenca Mountains in Spain (Central-Eastern Spain).[EN] [Results] Metabarcode DNA analyses of soil samples collected in three blocks (with three plots sampled in unburned and burned areas per block) in spring 2020 revealed that total soil fungi richness and diversity were not affected by summer burning; although no significant, summer burning did have a contrary influence on the most dominant fungal trophic groups. The relative abundance of ectomycorrhizal (ECM) fungi was negatively affected by burning, whereas saprotrophic fungi were positively affected by burning. Fire also had a significant effect on the composition of the total community and when analyzed by the trophic group. Multilevel pattern analysis showed that ECM fungi were significantly correlated with unburned plots. Physicochemical analyses revealed that there were no changes in the main edaphic variables measured.[EN] [Conclusions] The application of fire under more critical summer conditions (out of typical prescribed fire weather windows in Europe) did not produce significant differences in the diversity of the fungal community, being ECM fungi more sensitive to heat than other trophic groups. However, the composition of the fungal community differed significantly between burned and unburned plots. Overall, burned plots showed an adaptation to fire with a rapid proliferation of several pyrophilous genera that are able to improve soil conditions, which would enhance post-fire regeneration of the stand. These pioneering results can inform managers in conducting controlled summer fires to surrogate low to medium surface fire in Pinus nigra stands, knowing that the fungal diversity of the ecosystem is not affected, and thus the key ecological role of these organisms is not significantly harmed.[ES] [Antecedentes] Los regímenes de fuego en ecosistemas (en términos de frecuencia, severidad, e intensidad), están cambiando. Los fuegos de verano están ocurriendo en los bosques del Mediterráneo con mucha mayor frecuencia y severidad que en primavera u otoño. Las comunidades microbianas del suelo proveen de servicios ecosistémicos esenciales y son también esenciales en la recuperación post-fuego. Sin embargo y hasta ahora, los estudios que determinan el impacto de los fuegos de verano en las comunidades microbianas han sido limitados. Para explorar cómo fuegos más severos pueden afectar la diversidad de hongos y la composición de la comunidad, condujimos una quema experimental de verano en junio de 2019 en un sitio experimental que había sido establecido previamente en un rodal puro de pino negro (Pinus nigra Arn.) en 2016 en las montañas de Cuenca en España (Centro-Este de España).[ES] [Resultados] Análisis de codificación mediante AND de muestras de suelo colectadas en tres bloques (con tres parcelas muestreadas en áreas quemadas y sin quemar por bloque) en la primavera de 2020, revelaron que la riqueza total de hongos y la diversidad no fueron afectadas por la quema de verano; sin embargo, la quema de verano si tuvo una influencia significativa en los grupos tróficos de hongos más dominantes. La abundacia relativa de hongos ectomicorrícicos (ECM) fue negativamente afectada por las quemas, mientras que los hongos saprofíticos fueron positivamente afectados por las quemas. El fuego tuvo también efectos significativos en la composición total de la comunidad y cuando fue analizada por grupos tróficos. El análisis de patrones reveló que no hubo cambios en las principales variables edáficas medidas.[ES ][Conclusiones] La aplicación de quemas bajo las condiciones críticas del verano (por fuera de las ventanas de prescripción en Europa) no produjo diferencias significativas en la diversidad de la comunidad fúngica, siendo los hongos (ECM) más sensibles al fuego que otros grupos tróficos. Sin embargo, la composición de la comunidad fúngica difirió significativamente entre parcelas quemadas y no quemadas. En general, las parcelas quemadas mostraron una adaptación al fuego con una rápida proliferación de varios géneros de pirófilos, que son capaces de mejorar las condiciones del suelo, los cuales pueden aumentar la regeneración post fuego del rodal.This research was funded by: Spanish R&D projects MYCOINFOR (Mycosilviculture Applied to Forest Fire Prevention in Mediterranean Systems; PID2019-105188RB-I00); VIS4FIRE(Integrated Vulnerability of Forest Systems to Wildfire: Implications on Forest ManagementTools; RTA2017-00042-C05-01, ENFIRES (Enhancing Fire Resilience of Mediterranean Forest Systems, PID2020-116494RRC41/AEI/10.13039/501100011033) and MITECO2023-AF. 20234TE001. TC MITECO-CSIC. Prevención de incendios forestales: Evaluación de quemas prescritas y puntos estratégicos de gestión. This study was also financed by European Social Fund “NextGenerationEU” through a grant “Margarita Salas” awarded to Juncal Espinosa (project GFIRE; Gestión Forestal para la adaptación a los incendios forestales en el marco del cambio climático en el área mediterránea; UVa-2022-MS-TEZ02).Peer reviewe

Environmental Microbiology and Environmental Microbiology Reports: Two Journals, One Goal

Environmental Microbiology (EMI) has, for over 25 years, consistently sought to publish groundbreaking research in microbial ecology and environmental microbiology (Timmis and Stahl 1999, 2002; Timmis and Timmis 2018a; Ramos 2022; Timmis 2023), which becomes a point of reference for the field. Paired with this approach, Environmental Microbiology Reports (EMIR) was launched in 2009 as a venue for ‘short and direct science’ (Ramos 2009) to be prioritised. This has evolved into a mission to avoid making subjective evaluations of perceived impact, and instead focus on high ethical standards, methodological rigour and the utility of the reported conclusions to advance our field.Peer reviewe

Microwave-assisted green solvents extraction as a sustainable approach to obtain antioxidants and enhance advanced bioethanol production from steam-exploded biomass

Achieving sustainable and economically viable bioethanol production from lignocellulosic biomass relies on efficient pre-treatments, e.g., steam explosion. However, these can generate inhibitors that hinder enzymatic hydrolysis and fermentation stages. To overcome this challenge, we explored an integrated approach combining physical extraction (microwave irradiation) with chemical solvents (green solvents) to enhance bioethanol production from steam-exploded eucalypt wood. Green solvents, such as bio-based and eutectic solvents, were essential for extracting phenolic inhibitors that can be revalorized as antioxidants. Notably, ethyl lactate emerged as the most effective extraction agent in a microwave-assisted extraction process at 100 °C for 6 min, followed by a distilled water washing step. A certain delignification effect was also observed. After separate hydrolysis and fermentation process of the extracted sample, a maximum bioethanol production of 15.7 ± 0.3 g/L was achieved compared to 12.7 ± 0.0 g/L for the control sample. In addition, the samples were characterised through chemical composition and FTIR analysis. Overall, this study marks a significant advancement in producing environmentally friendly biofuels by integrating innovative extraction techniques with green solvents. This opens new possibilities for second-generation biofuels. At the same time, valuable by-products like antioxidants contribute to the broader goal of making bioethanol production economically feasible.This work is collaborative research which is part of different projects: coordinated research projects (PID2022-141965OB-C21 and PID2022-141965OB-C22) funded by MCIN/AEI/https://doi.org/10.13039/501100011033 and by “ERDF A way of making Europe”, TED 2021-132122B-C1 funded by MCIN/AEI/https://doi.org/10.13039/501100011033 and by the “European UnionNextGenerationEU/PRTR”; as well as the SUSTEC-CM S2018/EMT-4348 project and the AgroSUSTEC-CM TEC-2024/BIO-27 project funded by Comunidad de Madrid. The authors gratefully acknowledge the aforementioned financial support Raquel Martín-Sampedro, María E. Eugenio and David Ibarra are grateful for the support of the Interdisciplinary Platform for Sustainable Plastics towards a Circular Economy-Spanish National Research Council (SusPlast-CSIC), Madrid, Spain and Interdisciplinary Platform for Sustainability and Circular Economy (SosEcoCir-CSIC). The authors from UPM acknowledge Comunidad Autónoma de Madrid (Spain) for funding under the Multiannual Agreement with Universidad Politécnica de Madrid in the line Excellence Programme for University Professors, in the context of the V PRICIT (Regional Programme of Research and Technological Innovation).Peer reviewe

Herbivory legacy modifies leaf economic spectrum and drought tolerance in two tree species

The concurring effect of herbivory by wild ungulates and drought events is experiencing a notable increase in Mediterranean and temperate forests. While many studies have addressed the influence of drought on plant susceptibility to herbivory, it appears crucial to comprehend the impact of prolonged browsing on the physiological response of plants to increasing water deficit. To this end, we analyzed the effect of long-term recurrent herbivory by ungulates on physiological, biochemical, anatomical and morphological variables of Ilex aquifolium and Fagus sylvatica saplings during the growing seasons of 2018 and 2019 in a mixed sub-Mediterranean forest. We compared plants growing within an exclosure fence since 2006 (unbrowsed) with plants growing outside (browsed) that were also fenced during the study to investigate herbivory legacy. Twelve years of herbivory pressure modified significantly plant functional performance. Independently of the species, browsed plants showed higher root-to-shoot ratio, stem cross-sectional area-to-leaf area ratio, predawn leaf water potential, leaf nitrogen concentration and leaf gas exchange rates than unbrowsed plants. Moreover, browsed plants had lower leaf bulk modulus of elasticity, and higher osmotic potential at full turgor and turgor loss point. Thus, herbivory modified the leaf economic spectrum towards a more resource-acquisitive and less water stress tolerant type. These results suggest that, once browsing has subsided, plants continue to reflect some legacy effects that make them more vulnerable to further abiotic and biotic stresses, which has implications for forest regeneration.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by the Spanish Ministry of Universities [FPU fellowship: FPU19/04020], the European Union-Next Generation EU funds [Maria Zambrano fellowship: RCMZ-21-DJVHZ3-7-90M8PD], and the Regional Government of Environment, Local Administration and Territorial Planning of the Community of Madrid [10/086167.9/18].Peer reviewe

Error estimates [Dataset]

Ecology has historically benefited from the characterization of statistical patterns of biodiversity within and across communities, an approach known as macroecology. Within microbial ecology, macroecological approaches have identified universal patterns of diversity and abundance that can be captured by effective models. Experimentation has simultaneously played a crucial role, as the advent of high-replication community time-series has allowed researchers to investigate underlying ecological forces. However, there remains a gap between experiments performed in the laboratory and macroecological patterns documented in natural systems, as we do not know whether these patterns can be recapitulated in the lab and whether experimental manipulations produce macroecological effects. This work aims at bridging the gap between experimental ecology and macroecology. Using high-replication time-series, we demonstrate that microbial macroecological patterns observed in nature exist in a laboratory setting, despite controlled conditions, and can be unified under the Stochastic Logistic Model of growth (SLM). We found that demographic manipulations (e.g., migration) impact observed macroecological patterns. By modifying the SLM to incorporate said manipulations alongside experimental details (e.g., sampling), we obtain predictions that are consistent with macroecological outcomes. By combining high-replication experiments with ecological models, microbial macroecology can be viewed as a predictive discipline.Peer reviewe

Préstamos, éxitos y reproches compartidos: travesías del indigenismo interamericano en México

En esta contribución me propongo averiguar las travesías del Instituto Indigenista Interamericano (o Instituto), desde su fundación en 1940. El análisis se enfocará en tres aspectos cruciales para definir ese contexto material inicial: a) el establecimiento de la sede del Instituto en la ciudad de México; b) las circunstancias económicas y la financiación; c) los préstamos de personal perteneciente a entidades mexicanas y, en menor medida, estadounidenses, para la organización inicial y para la ejecución de proyectos. Definir y aclarar las relaciones entre el indigenismo interamericano y el ámbito nacional puede ser útil no sólo para ampliar nuestro conocimiento acerca del indigenismo, sino también sobre la institucionalización de la antropología en México y sobre el más amplio entramado institucional mexicano relacionado con el indigenismoEste trabajo es parte del Proyecto de I+D+i HeterQuest “La heterogeneidad en cuestión: saberes y prácticas cruzadas en el derecho, el indigenismo y lo social” PID2019-107783GB-I00, financiado por mcin/aei/10.13039/501100011033Peer reviewe