Distinct Microglial Responses in Two Transgenic Murine Models of TAU Pathology

Microglial cells are crucial players in the pathological process of neurodegenerative diseases, such as Alzheimer’s disease (AD). Microglial response in AD has been principally studied in relation to amyloid-beta pathology but, comparatively, little is known about inflammatory processes associated to tau pathology. In the hippocampus of AD patients, where tau pathology is more prominent than amyloid-beta pathology, a microglial degenerative process has been reported. In this work, we have directly compared the microglial response in two different transgenic tau mouse models: ThyTau22 and P301S. Surprisingly, these two models showed important differences in the microglial profile and tau pathology. Where ThyTau22 hippocampus manifested mild microglial activation, P301S mice exhibited a strong microglial response in parallel with high phospho-tau accumulation. This differential phospho-tau expression could account for the different microglial response in these two tau strains. However, soluble (S1) fractions from ThyTau22 hippocampus presented relatively high content of soluble phospho-tau (AT8-positive) and were highly toxic for microglial cells in vitro, whereas the correspondent S1 fractions from P301S mice displayed low soluble phosphotau levels and were not toxic for microglial cells. Therefore, not only the expression levels but the aggregation of phospho-tau should differ between both models. In fact, most of tau forms in the P301S mice were aggregated and, in consequence, forming insoluble tau species.We conclude that different factors as tau mutations, accumulation, phosphorylation, and/or aggregation could account for the distinct microglial responses observed in these two tau models. For this reason, deciphering the molecular nature of toxic tau species for microglial cells might be a promising therapeutic approach in order to restore the deficient immunological protection observed in AD hippocampus.CIBERNEDJunta de Andalucía. Consejería de Economía, Innovación, Ciencia y Empleo CTS-2035Fundación Tatiana Pérez de Guzmán el BuenoMinisterio de Ciencia, Innovación y UniversidadesInstituto de Salud Carlos III. Fondo de Investigación Sanitaria. PI15/00957 PI15/00796Fondo Europeo de Desarrollo Regional PI15/00957 PI15/0079

Virtual visualization of La Quintilla

[ES] En este artículo damos una visión general del proceso productivo de la reconstrucción virtual en la arqueología virtual. Utilizando como referencia la villa romana de la Quintilla de Lorca mostramos los pasos necesarios para una correcta virtualización.[EN] In this article we give an overview of the production process of the virtual reconstrucción virtual archeology. While Referring to the Roman town of Lorca Limerick show the proper steps virtualizatión purchase.Flores Gutiérrez, M.; Romero Soria, Á.; Martínez García, J.; Ramallo Asensio, SF.; Fernández Díaz, A. (2013). Visualización virtual de la Quintilla. Virtual Archaeology Review. 4(9):143-147. https://doi.org/10.4995/var.2013.4265OJS14314749BIRN, J. (2007): Iluminación y Render Edición 2007. Anaya Multimedia. Madrid.FERNÁNDEZ DÍAZ, A. (2004): "Programa ornamental: pintura y mosaico", en Iberia, Hispania, Spania. Una mirada desde Ilici, pp. 167-174.FERNÁNDEZ DÍAZ, A. (2008): La pintura mural romana de Carthago Noua: evolución de los programas pictóricos a través de los estilos, talleres y técnicas decorativas, Murcia.FERNÁNDEZ DÍAZ, A., RAMALLO ASENSIO, S.F., MARTÍNEZ RODRÍGUEZ, A. y PONCE GARCÍA, J. (2012): La pintura mural romana: un indicador funcional y/o decorativo. Pintura mural de la habitación 32 de la villa romana de La Quintilla (Lorca, Murcia), MARQ, Alicante.GARCÍA SANDOVAL, J., PLAZA SANTIAGO, R. y FERNÁNDEZ DÍAZ, A. (2004): "La musealización de las pinturas romanas de La Quintilla (Lorca): Restauración y montaje expositivo", AlbercA, 2, pp. 125-138.GUIRLA PELEGRÍN, C., FERNÁNDEZ DÍA, A. y CÁNOVAS UTRERA, A., (2013): "En torno a los estilos locales en la pintura romana: el caso de Hispania en el siglo II d.C.", en XIe Colloque International de l'AIPMA, Éfeso, Turquía, 2010.MOORMANN, E.M. (ed.) (1993): Functional and spatial analysis of wall-painting. Proceedings of the Fifth International Congress on ancient Wall-Painting (Amsterdam, 8-12 septembre 1992), BABesch, Supplément, 3.PLAZA SANTIAGO, R., GARCÍA SANDOVAL, J. y FERNÁNDEZ DÍAZ, A. (2004):"Recuperación, extracción y consolidación en yacimientos arqueológicos: el caso práctico de la villa romana de La Quintilla, Lorca (Murcia)", AlbercA, 2, pp. 105-124.PLAZA SANTIAGO, R., GARCÍA SANDOVAL, J., FERNÁNDEZ DÍAZ, A., MARTÍNEZ RODRÍGUEZ, A., PONCE GARCÍA, J. y RAMALLO ASENSIO, S.F. (2003-2005): "Las pinturas murales de La Quintilla (Lorca): Restauración y montaje expositivo", en Memorias de Patrimonio Intervenciones en el Patrimonio Cultural de la Región de Murcia, nº 7, pp. 247-262.RAMALLO ASENSIO, S.F. (1987): "La villa romana de La Quintilla (Lorca). Informe de la campaña de 1984", MemAMurcia, 1 (1984), pp. 295-303.RAMALLO ASENSIO, S.F. (1995a): "La villa romana de La Quintilla (Lorca): una aproximación a su proyecto arquitectónico y al programa ornamental", en J.M. Noguera (ed.), Poblamiento rural romano en el Sudeste de Hispania, Murcia, 1993, pp. 49-79.RAMALLO ASENSIO, S.F. (1995b): "La villa romana de La Quintilla (Lorca, Murcia)", JRA, 8, pp. 310-312. http://dx.doi.org/10.1017/s1047759400016093RAMALLO ASENSIO, S.F., MARTÍNEZ RODRÍGUEZ, A., FERNÁNDEZ DÍAZ, A. y PONCE GARCÍA, J. (2003): "Villa romana de La Quintilla (Lorca)", XIV Jornadas de Patrimonio y Arqueología de la Región de Murcia. Murcia, pp. 58-60.RAMALLO ASENSIO, S.F., MARTÍNEZ RODRÍGUEZ, A., FERNÁNDEZ DÍAZ, A. y PONCE GARCÍA, J. (2004a): "Campaña de excavaciones en La Quintilla (Lorca)", XV Jornadas de Patrimonio y Arqueología de la Región de Murcia. Murcia, pp. 73 y 74.RAMALLO ASENSIO, S.F., MARTÍNEZ RODRÍGUEZ, A., FERNÁNDEZ DÍAZ, A. y PONCE GARCÍA, J. (2004b): "Extracción, excavación y labores de consolidación de las pinturas murales de la habitación 35 de la villa romana de La Quintilla (Lorca)", MemAMurcia, 13, pp. 107-122.RAMALLO, S.F., FERNÁNDEZ DÍAZ, A., MARTÍNEZ RODRÍGUEZ, A. y PONCE GARCÍA, J. (2003): "La villa romana de La Quintilla (Lorca, Murcia): programa decorativo y ornamental", en Ixe Colloque Internationale de l'AIEMA (Roma, 2001), Roma, pp. 1001-1021

Virtual reconstruction of the roman villa in La Quintilla (Lorca) based on the existing physical evidence and related scientific comparisons as a reference

[ES] La reconstrucción virtual de los yacimientos arqueológicos utilizando la infografía supone una herramienta muy importante para la constatación o refutación de hipótesis en la investigación científica. Así mismo es un medio excelente de difundir el conocimiento del Patrimonio con imágenes realista de gran rigor científico.[EN] The virtual reconstruction of archaeological sites using computer graphics is a very important tool for the verification or refutation of hypotheses in scientific research. It also is an excellent way to spread awareness Heritage with realistic images of scientific rigor.Ramallo Asensio, SF.; Fernández Díaz, A.; Flores Gutiérrez, M.; Romero Soria, Á.; Martínez García, J. (2013). Reconstrucción Virtual de la Villa Romana de la Quintilla de Lorca a partir de las evidencias físicas existentes sobre dicha construcción así como de referencias comparativas científicamente razonadas. Virtual Archaeology Review. 4(9):181-189. https://doi.org/10.4995/var.2013.4272OJS18118949BIRN, J. (2007): Iluminación y Render Edición 2007. Anaya Multimedia. Madrid.FERNÁNDEZ DÍAZ, A. (2004): "Programa ornamental: pintura y mosaico", en Iberia, Hispania, Spania. Una mirada desde Ilici, pp. 167-174.FERNÁNDEZ DÍAZ, A. (2008): La pintura mural romana de Carthago Noua: evolución de los programas pictóricos a través de los estilos, talleres y técnicas decorativas, Murcia.FERNÁNDEZ DÍAZ, A., RAMALLO ASENSIO, S.F., MARTÍNEZ RODRÍGUEZ, A. y PONCE GARCÍA, J. (2012): La pintura mural romana: un indicador funcional y/o decorativo. Pintura mural de la habitación 32 de la villa romana de La Quintilla (Lorca, Murcia), MARQ, Alicante.GARCÍA SANDOVAL, J., PLAZA SANTIAGO, R. y FERNÁNDEZ DÍAZ, A. (2004): "La musealización de las pinturas romanas de La Quintilla (Lorca): Restauración y montaje expositivo", AlbercA, 2, pp. 125-138.GUIRLA PELEGRÍN, C., FERNÁNDEZ DÍA, A. y CÁNOVAS UTRERA, A., (2013): "En torno a los estilos locales en la pintura romana: el caso de Hispania en el siglo II d.C.", en XIe Colloque International de l'AIPMA, Éfeso, Turquía, 2010.MOORMANN, E.M. (ed.) (1993): Functional and spatial analysis of wall-painting. Proceedings of the Fifth International Congress on ancient Wall-Painting (Amsterdam, 8-12 septembre 1992), BABesch, Supplément, 3.PLAZA SANTIAGO, R., GARCÍA SANDOVAL, J. y FERNÁNDEZ DÍAZ, A. (2004): "Recuperación, extracción y consolidación en yacimientos arqueológicos: el caso práctico de la villa romana de La Quintilla, Lorca (Murcia)", AlbercA, 2, pp. 105-124.PLAZA SANTIAGO, R., GARCÍA SANDOVAL, J., FERNÁNDEZ DÍAZ, A., MARTÍNEZ RODRÍGUEZ, A., PONCE GARCÍA, J. y RAMALLO ASENSIO, S.F. (2003-2005): "Las pinturas murales de La Quintilla (Lorca): Restauración y montaje expositivo", en Memorias de Patrimonio. Intervenciones en el Patrimonio Cultural de la Región de Murcia, nº 7, pp. 247-262.RAMALLO ASENSIO, S.F. (1987): "La villa romana de La Quintilla (Lorca). Informe de la campaña de 1984", MemAMurcia, 1 (1984), pp. 295-303.RAMALLO ASENSIO, S.F. (1995a): "La villa romana de La Quintilla (Lorca): una aproximación a su proyecto arquitectónico y al programa ornamental", en J.M. Noguera (ed.), Poblamiento rural romano en el Sudeste de Hispania, Murcia, 1993, pp. 49-79.RAMALLO ASENSIO, S.F. (1995b): "La villa romana de La Quintilla (Lorca, Murcia)", JRA, 8, pp. 310-312. http://dx.doi.org/10.1017/s1047759400016093RAMALLO ASENSIO, S.F., MARTÍNEZ RODRÍGUEZ, A., FERNÁNDEZ DÍAZ, A. y PONCE GARCÍA, J. (2003): "Villa romana de La Quintilla (Lorca)", XIV Jornadas de Patrimonio y Arqueología de la Región de Murcia. Murcia, pp. 58-60.RAMALLO ASENSIO, S.F., MARTÍNEZ RODRÍGUEZ, A., FERNÁNDEZ DÍAZ, A. y PONCE GARCÍA, J. (2004a): "Campaña de excavaciones en La Quintilla (Lorca)", XV Jornadas de Patrimonio y Arqueología de la Región de Murcia. Murcia, pp. 73 y 74.RAMALLO ASENSIO, S.F., MARTÍNEZ RODRÍGUEZ, A., FERNÁNDEZ DÍAZ, A. y PONCE GARCÍA, J. (2004b): "Extracción, excavación y labores de consolidación de las pinturas murales de la habitación 35 de la villa romana de La Quintilla (Lorca)", MemAMurcia, 13, pp. 107-122.RAMALLO, S.F., FERNÁNDEZ DÍAZ, A., MARTÍNEZ RODRÍGUEZ, A. y PONCE GARCÍA, J. (2003): "La villa romana de La Quintilla (Lorca, Murcia): programa decorativo y ornamental", en Ixe Colloque Internationale de l'AIEMA (Roma, 2001), Roma, pp. 1001-102

2D copper-imidazolate framework without thermal treatment as an efficient ORR electrocatalyst for Zn–air batteries

To face unmet energy demands, the search for more stable, low-cost, and scalable electrocatalyst materials is imperative. Within this context, single-atom catalysts (SACs) have drawn considerable attention due to their maximum atom utilization. With this idea in mind, we have synthesized a new ultrathin and water-stable 2D Cu-based metal-organic framework (2DCIFs), which presents a notable electrocatalytic activity for oxygen reduction reaction (ORR) in alkaline media without the need of calcination, which makes the difference when compared to most MOF-based electrocatalysts. The designed MOF-based SAC consists of single-atom sites (isolated and accessible Cu) coordinated to imidazole carboxylic ligands, giving rise to Cu-N4O actives sites confined into a 2D-nanostructured network. This unique structure, along with the ultrathin nature of nanosheets that favors mass transport and electrical conductivity, and the high chemical stability of these 2DCIFs are the key features of the excellent ORR performance, which occurs by a direct four-electron transfer pathway, an onset potential of 0.86 V vs RHE and a maximum current density of 6.4 mA·cm-2. These good catalytic properties of 2DCIFs have allowed their use as efficient air electrodes in alkaline flooded and all-solid-state Zn-air batteries. In the former case, 2DCIFsbased air electrodes presented a specific power density of 91.2 kW·cm-2·kg-1 and a specific capacity of 296.2 A·h·g-1, significantly exceeding the specific capacity values reported previously for other Cu-based catalysts. Besides, the specific capacity increased to 389.1 A·h·g-1 when 2DCIFs were tested in an all-solid-state Zn-air battery

Metal-free nanostructured-carbon inks for a sustainable fabrication of zinc/air batteries:

5 figures, 1 table.-- Under a Creative Commons license CC-BY 4.0.Zinc/air batteries are convenient energy storage devices for both small and massive applications. While future perspectives indicate the need for low-cost components and sustainable fabrication processes, the battery performance is in part controlled by the kinetics of the oxygen reduction reaction (ORR), which typically involves transition metals as catalysts. In this context, we prepare a series of metal-free water-based carbon inks, which are tested for their catalytic performance, once deposited on a gas-diffusion substrate, in the air cathode of a simple battery prototype. The inks contain a variety of well-defined carbon nanomaterials and additives, exhibiting different physicochemical properties that critically influence the interaction with the gas diffusion hydrophobic substrate. The intrinsic ORR catalytic activity of the ink material is also analyzed on a glassy carbon electrode by the rotating ring-disc electrode (RRDE) method and specific capacitance measurements. The discharge capacity on our zinc/air battery prototype correlates well with the intrinsic catalytic activity in the RRDE. However, only the activity in the RRDE does not actually assure the performance on the commercial cathode of the prototype, since other chemical compatibility issues play a role. Thus, we highlight the importance of catalyst testing, not only on the RRDE but also under realistic device conditions.This study received financial support from Spanish MICINN under projects PID2019-104272RB-C51, C55AEI/10.13039/501100011033, PID2020-120439-RA-I00, Diputación General de Aragón under project T03_23R (Grupo Reconocido), and Fundación Séneca (Región de Murcia, Spain; Reference: 20985/PI/18). The authors also appreciate the financial support provided by the MICINN and the European Union “NextGenerationEU/PRTR” through the project TED2021–130334B-I00.Peer reviewe

Monocyte-derived cells invade brain parenchyma and amyloid plaques in human Alzheimer’s disease hippocampus

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Microglia are brain-resident myeloid cells and play a major role in the innate immune responses of the CNS and the pathogenesis of Alzheimer's disease (AD). However, the contribution of nonparenchymal or brain-infiltrated myeloid cells to disease progression remains to be demonstrated. Here, we show that monocyte-derived cells (MDC) invade brain parenchyma in advanced stages of AD continuum using transcriptional analysis and immunohistochemical characterization in post-mortem human hippocampus. Our findings demonstrated that a high proportion (60%) of demented Braak V–VI individuals was associated with up-regulation of genes rarely expressed by microglial cells and abundant in monocytes, among which stands the membrane-bound scavenger receptor for haptoglobin/hemoglobin complexes or Cd163. These Cd163-positive MDC invaded the hippocampal parenchyma, acquired a microglial-like morphology, and were located in close proximity to blood vessels. Moreover, and most interesting, these invading monocytes infiltrated the nearby amyloid plaques contributing to plaque-associated myeloid cell heterogeneity. However, in aged-matched control individuals with hippocampal amyloid pathology, no signs of MDC brain infiltration or plaque invasion were found. The previously reported microglial degeneration/dysfunction in AD hippocampus could be a key pathological factor inducing MDC recruitment. Our data suggest a clear association between MDC infiltration and endothelial activation which in turn may contribute to damage of the blood brain barrier integrity. The recruitment of monocytes could be a consequence rather than the cause of the severity of the disease. Whether monocyte infiltration is beneficial or detrimental to AD pathology remains to be fully elucidated. These findings open the opportunity to design targeted therapies, not only for microglia but also for the peripheral immune cell population to modulate amyloid pathology and provide a better understanding of the immunological mechanisms underlying the progression of AD.This study was supported by Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by FEDER funds from European Union, through grants PI18/01556 and PI21/00914 (to JV) and PI18/01557 and PI21/00915 (to AG); by Junta de Andalucia Consejería de Economía y Conocimiento through grants US-1262734 and P20-00843 (to JV), UMA18-FEDERJA-211 (to AG) and PI18-RT-2233 (to AG) co-financed by Programa Operativo FEDER 2014-2020; by Spanish Minister of Science and Innovation grant PID2019-108911RA-100 (to DBV), Beatriz Galindo Program BAGAL18/00052 (to DBV), grant PID2019-107090RA-I00 (to IMG) and Ramon y Cajal Program RYC-2017-21879 (to IMG); and by Malaga University grant B-2019_06 (to ESM).Peer reviewe

IgAV and IgAN: a single entity regarding CD40, BLK and BANK1 polymorphisms.

Congresos y conferencias: Comunicación de congreso - oral

Mucosal immune defence polymorphisms: relevant players in IgA vasculitis?

Congresos y Comunicaciones: Comunicación, Congreso - póster