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The role of alpha-synuclein in synucleinopathy: Impact on lipid regulation at mitochondria–ER membranes
15 p.-4 fig.The protein alpha-synuclein (αSyn) plays a pivotal role in the pathogenesis of synucleinopathies, including Parkinson’s disease and multiple system atrophy, with growing evidence indicating that lipid dyshomeostasis is a key phenotype in these neurodegenerative disorders. Previously, we identified that αSyn localizes, at least in part, to mitochondria-associated endoplasmic reticulum membranes (MAMs), which are transient functional domains containing proteins that regulate lipid metabolism, including the de novo synthesis of phosphatidylserine. In the present study, we analyzed the lipid composition of postmortem human samples, focusing on the substantia nigra pars compacta of Parkinson’s disease and controls, as well as three less affected brain regions of Parkinson’s donors. To further assess synucleinopathy-related lipidome alterations, similar analyses were performed on the striatum of multiple system atrophy cases. Our data reveal region- and disease-specific changes in the levels of lipid species. Specifically, our data revealed alterations in the levels of specific phosphatidylserine species in brain areas most affected in Parkinson’s disease. Some of these alterations, albeit to a lesser degree, are also observed in multiple system atrophy. Using induced pluripotent stem cell-derived neurons, we show that αSyn regulates phosphatidylserine metabolism at MAM domains, and that αSyn dosage parallels the perturbation in phosphatidylserine levels. These findings support the notion that αSyn pathophysiology is linked to the dysregulation of lipid homeostasis, which may contribute to the vulnerability of specific brain regions in synucleinopathy. These findings have significant therapeutic implications.This research was supported by the William N. and Bernice E. Bumpus Foundation (P.B is a recipient of the Early Career Investigator Innovation Award (WBBF CU22-0241), plus grants from the Fonds National de Recherche within the INTER program (INTER/LEIR/18/12719318) to PB and RK, and PEARL (FNR/P13/6682797) to RK, and the National Center for Excellence in Research on Parkinson’s disease (NCER-PD/11264123) program and by the European Union’s Horizon 2020 research and innovation program under Grant Agreement No 692320 (WIDESPREAD; CENTER-PD) to RK. This work was further supported by the US National Institutes of Health (NS107442, NS117583, NS111176, AG064596) to SP, (NS121826, NS133979) to UD, and (AG056387) to EAG, the DoD (W81XWH-22-1-0127) and the Parkinson Foundation to SP (PF-RCE-1948), the Ludwig Family Foundation (GT006761) to SP and PB, the Michael J Fox Foundation to CG-L (MJFOXFD CU18-0258), the Leir Foundation (GT006967) and Art2Cure to PB, CG-L, RK and SP.Peer reviewe
A Multilevel Biodiversity Approach of the Hermit Crabs in the Iberian Peninsula and Ultraperipheral Territories
The crustaceans of the superfamily Paguroidea constitute one of the most diverse groups within the Decapoda, exhibiting remarkable morphological and ecological diversity. Despite the relatively high number of described species worldwide, there are still many gaps in the knowledge of this group, particularly regarding genetic information. This study aims to update the geographic distribution information currently available for the hermit crab species in the Iberian Peninsula, Azores, Canary Islands, and Madeira, and generate a molecular database supported by morphological identification. The results are summarized in an updated list of Paguroidea recorded in the study area, which comprises a total of 55 species, representing a significant increase from previous compilations. Newly generated sequences, including those from the study area and closely related species from other areas, provide the first molecular information for 35 out of the 70 species analyzed. Phylogenetic analyses provide evidence of the species delimitation capabilities of molecular tools when reliable morphology-based information is available. Molecular analyses using two mitochondrial markers largely corresponded, supporting most traditionally established species and validating the morphological characters used for delimitation. Specifically, the COI gene showed better results and clearer topologies, suggesting greater utility for exploring species delimitation when using single-gene identification as a DNA barcode. Overall, the results of this long-term study will improve the capabilities for species delimitation, in addition to updating the composition and richness of species in the area.Peer reviewe
Supporting Information for Clustering and nanoscale vitrimeric behavior in telechelic polybutadiene model vitrimers
S1. Detailed description of the materials, instrumentation and methods used for the synthesis and characterization of the prepared materials. S2. Supplementary calorimetry, dielectric and viscosity data of the studied PB model vitrimers.Peer reviewe
Stabilization of the Active Ruthenium Oxycarbonate Phase for Low-Temperature CO2 Methanation
Interstitial carbon-doped RuO catalyst with the newly reported ruthenium oxycarbonate phase is a key component for low-temperature CO methanation. However, a crucial factor is the stability of interstitial carbon atoms, which can cause catalyst deactivation when removed during the reaction. In this work, the stabilization mechanism of the ruthenium oxycarbonate active phase under reaction conditions is studied by combining advanced operando spectroscopic tools with catalytic studies. Three sequential processes: carbon diffusion, metal oxide reduction, and decomposition of the oxycarbonate phase and their influence by the reaction conditions, are discussed. We present how the reaction variables and catalyst composition can promote carbon diffusion, stabilizing the oxycarbonate catalytically active phase under steady-state reaction conditions and maintaining catalyst activity and stability over long operation times. In addition, insights into the reaction mechanism and a detailed analysis of the catalyst composition that identifies an adequate balance between the two phases, i.e., ruthenium oxycarbonate and ruthenium metal, are provided to ensure an optimum catalytic behavior.This research was funded by Ministerio de Ciencia, Innovación y Universidades, grant number PID2021-1262350B–C31, and Generalitat Valenciana (GVA), grant number CIAICO/2021/2138. This study formed part of the Advanced Materials programme and was supported by MCIN with funding from European Union Next Generation EU (PRTR-C17.11) and Generalitad Valenciana (ref MFA/2022/016 and TED2021-130756B–C32). C.T.S acknowledges the Polytechnical University of Valencia for the economic support through the grant of an FPI scholarship associated with the PAID programme “Programa de Ayudas de Investigación y Desarrollo.” XAS, XPS, and XRD experiments were performed at the ALBA Synchrotron with the collaboration of ALBA staff. IR experiments were performed at the SOLEIL Synchrotron with the collaboration of the SOLEIL staff. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science user facility operated for the DOE Office of Science by the Argonne National Laboratory under Contract No.DE-AC02-06CH11357.Peer reviewe
"Game of Stones": ¿Quieres descubrir cuánto sabes de Geología?
"Game of Stones" es un videojuego diseñado para servir como herramienta didáctica y recurso adicional
de las asignaturas de los planes de estudio preuniversitarios. Su principal objetivo es ampliar y fortalecer
los conceptos científicos del alumnado. La Comisión Mujeres y Geología de la Sociedad Geológica de
España desarrolló este juego online en formato trivial en 2022 enmarcado en el proyecto Geolodía. Contiene
240 preguntas de múltiple respuesta, organizadas en seis categorías que abarcan todas las disciplinas
geológicas. Cada categoría está representada por una ¿Gema de la Sabiduría¿ y el objetivo principal del
juego es reunirlas todas. Para lograrlo, cada participante debe acertar una pregunta de cada categoría y
superar una ronda final de 6 preguntas. El juego permite la participación de uno a seis jugadores
simultáneamente, y su dinámica está diseñada para ser más rápida que la de un trivial tradicional,
permitiendo que las partidas se realicen en la duración de una clase típica de Educación Secundaria
Obligatoria y Bachillerato. "Game of Stones" se ha convertido en una herramienta de divulgación geológica
ampliamente aceptada tanto por docentes como por el público general, sin restricciones de edad ni
conocimiento científico previo, lo que la posiciona como un modelo a seguir para otras iniciativas didácticas
similares. Este videojuego cuenta con la colaboración de la Fundación Española para la Ciencia y la
Tecnología - Ministerio de Ciencia, Innovación y Universidades
Halo mass distribution reconstruction across the cosmic web
We study the relation between halo mass and its environment from a probabilistic perspective. We find that halo mass depends not only on local dark matter density, but also on nonlocal quantities such as the cosmic web environment and the halo-exclusion effect. Given these accurate relations, we have developed the HADRON-code (Halo mAss Distribution ReconstructiON), a technique which permits us to assign halo masses to a distribution of haloes in three-dimensional space. This can be applied to the fast production of mock galaxy catalogues, by assigning halo masses, and reproducing accurately the bias for different mass cuts. The resulting clustering of the halo populations agree well with that drawn from the BigMultiDark N-body simulation: the power spectra are within 1σ up to scales of k = 0.2 h Mpc-1, when using augmented Lagrangian perturbation theory based mock catalogues. Only the most massive haloes show a larger deviation. For these, we find evidence of the halo-exclusion effect. A clear improvement is achieved when assigning the highest masses to haloes with a minimum distance separation. We also compute the two- and three-point correlation functions, and find an excellent agreement with N-body results. Our work represents a quantitative application of the cosmic web classification. It can have further interesting applications in the multitracer analysis of the large-scale structure for future galaxy surveys. © 2015 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.CZ and CT acknowledge support from Tsinghua University, and 973 programme no. 2013CB834906. CZ also thanks the support from MultiDark summer student programme to visit the Instituto de Física Teórica, (UAM/CSIC), Spain. CC and FP were supported by the Spanish MICINNs Consolider-Ingenio 2010 Programme under grant MultiDark CSD2009-00064 and AYA2010-21231-C02-01 grant, the Comunidad de Madrid under grant HEPHACOS S2009/ESP-1473, and Spanish MINECOs Centro de Excelencia Severo Ochoa Programme under grant SEV-2012-0249. GY acknowledges support from the Spanish MINECO under research grants AYA2012-31101, FPA2012-34694 and Consolider Ingenio SyeC CSD2007-0050. The BigMD simulation suite have been performed in the SuperMUC supercomputer at the Leibniz-Rechenzentrum in Munich, thanks to the CPU time awarded by PRACE (proposal number 2012060963). We also acknowledge PRACE for awarding us access to Curie supercomputer based in France (project PA2259). Some other computations were performed on HYDRA, the HPC-cluster of the IFT-UAM/CSIC.With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (SEV-2012-0249).Peer reviewe
Highly Stable Subnanometric PtIn Clusters for the Selective Dehydrogenation of Alkanes
Subnanometric PtIn clusters have been synthesized within pure silica MFI zeolites by post-synthetic incorporation of In to Pt@K-MFI. The optimized PtIn@K-MFI catalyst outcompetes state-of-the-art PtSn formulations in ethane and propane dehydrogenations, avoiding the need of large excess of Pt promoters and harsh reductive conditions.This work has been supported by the Spanish Government through PID2020113006-RB-I00 and PID2021-122755OB-I00, both funded by MCIN/AEI/10.13039/501100011033, PID2022-142312NB-I00 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”. The authors are also thankful for the Severo Ochoa financial support by the Spanish Ministry of Science and Innovation (CEX2021-001230-S/ funding by MCIN/AEI/10.13039/501100011033) and for the financial support by the Generalitat Valenciana through the Prometeo Program (CIPROM/2023/34). The Electron Microscopy Service of the UPV is acknowledged for their help in sample characterization. HRSTEM data were acquired at the DME-UCA node of the Spanish Unique Infrastructure for Electron Microscopy of Materials (ICTS ELECMI). We appreciate the support of ExxonMobil Technology and Engineering for our efforts in fundamental catalytic research. The XAS results were collected under the PUP-309462 carried out at the National Synchrotron Light Source II, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Brookhaven National Laboratory under Contract No. DE-AC02-98CH10886. RJM and PSM thank Eli Stavitski, Denis Leshchev and Dominik Wierzbicki for their support at the ISS beamline at NSLS-II. RJM and PSM also thank Corey Kaminsky and Alyssa Love of ExxonMobil for their help with collection of the XAS data
Electron-phonon coupling and phonon dynamics in single-layer NbSe2 on graphene: The role of Moiré phonons
The interplay between substrate interactions and electron-phonon coupling in two-dimensional (2D) materials presents a significant challenge in understanding and controlling their electronic properties. Here, we present a comparative study of the structural characteristics, phonon dynamics, and electron-phonon interactions in bulk and monolayer NbSe2 on epitaxial bilayer graphene (BLG) using helium atom scattering (HAS). High-resolution helium diffraction reveals a (9 × 9)0° superstructure within the NbSe2 monolayer, commensurate with the BLG lattice, while out-of-plane HAS diffraction spectra indicate a low-corrugated (3√3 × 3√3)30° substructure. By monitoring the thermal attenuation of the specular peak across a temperature range of 100 to 300 K, we determined the electron-phonon coupling constant (λHAS) as 0.76 for bulk 2H-NbSe2. In contrast, the NbSe2 monolayer on graphene exhibits a reduced λHAS of 0.55, corresponding to a superconducting critical temperature (TC) of 1.56 K according to the MacMillan formula, consistent with transport measurement findings. Inelastic HAS data provide, besides a set of dispersion curves of acoustic and lower optical phonons, a soft, dispersionless branch of phonons at 1.7 meV, attributed to the interface localized defects distributed with the superstructure period, thus termed Moiré phonons. Our data show that Moiré phonons contribute significantly to the electron-phonon coupling in monolayer NbSe2. These results highlight the crucial role of the BLG in the electron-phonon coupling in monolayer NbSe2, attributed to enhanced charge transfer effects, providing valuable insights into substrate-dependent electronic interactions in 2D superconductors.This work has been partially supported by the Spanish Ministerio de Ciencia e Innovación under projects PID2019-109525RB-I00 and PID2023-147466OB-C21. D.F. acknowledges financial support from the Spanish Ministry of Economy and Competitiveness, through the “María de Maeztu” Programme for Units of Excellence in R&D (CEX2018-000805-M). M.M.U. acknowledges support by the ERC Starting grant LINKSPM (Grant 758558) and by grant PID2023-153277NB-I00 funded by the Spanish Ministry of Science, Innovation and Universities.With funding from the Spanish government through the "Unit of Excellence Maria de Maeztu" accreditation (CEX2018-000805-M).Peer reviewe
Tectonic and climatic controls on the paleoceanographic evolution of the South Orkney Microcontinent (southern Scotia Arc, Antarctica)
Póster presentado en X Simposio de Estudios Polares, del 15 al 17 de mayo de 2024 en SalamancaThe opening and deepening of the Drake Passage, framed in the development of the Scotia Arc, facilitated the establishment of the Antarctic Circumpolar Current (ACC). The oceanic basins located at the southern Scotia Arc are today essential conduits for the exchange and interaction of deep water
masses. However, the complex tectonic evolution of the Scotia Arc prevents the reconstruction of when and how these ocean current conduits developed over time. The South Orkney Microcontinent (SOM) is located in the southern Scotia Arc and stands as one of the largest continental blocks resulting from
the separation of South America and the Antarctic Peninsula. Given its key location, studying the sedimentary cover of the SOM can provide new insights into early paleoceanographic reorganization before and during the opening of the surrounding oceanic basins. In this work, the sedimentary infill of the SOM has been analyzed using multichannel seismic reflection profiles. We have identified five seismic units dated by correlation with Ocean Drilling Program Sites 695 and 696. We show that the southern margin of the SOM records the influence of contour currents from the Weddell Sea since the late Eocene, with a major development of contourite deposits during the early and middle Miocene. The influence of contour currents in the SOM would be favored by continued subsidence, as the Powell Basin developed. The cessation of contour current influence in the SOM coincided with widespread development in the southern Scotia Sea basins, indicating the full opening of the surrounding basins, such as Jane and Scan basins. After the middle Miocene, sedimentation in the SOM suggests the proximity of an ice sheet extending into the continental shelf, coinciding with the reported timing for the establishment of more permanent ice sheet in the Antarctic Peninsula region at around 5 Ma.Funding for this research was provided by grants PDI2021-126495NB-C31/C32 and PRE2018-084612 from MCIN/AEI /10.13039/501100011033 / FEDER, U
Exploring the Anti-Chagas Activity of Zanthoxylum chiloperone's Seedlings Through Metabolomics and Protein-Ligand Docking
This publication reports the controlled cultivation of Zanthoxylum chiloperone var. angustifolium Engl. (Rutaceae) in several growth substrates under controlled greenhouse conditions. This plant is well-known for its anti-Chagas (trypanocidal) activity, related to the presence of several β-carboline alkaloids. The metabolomic study of Z. chiloperone seedlings over two years of growth (2018-2020) was performed using comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC × GC-TOFMS). The canthin-6-one alkaloids, canthin-6-one and 5-methoxy-canthin-6-one, were putatively identified in Z. chiloperone extracts. Finally, in vitro and in silico studies of trypanocidal activity were performed, suggesting that canthin-6-one alkaloids could interact with the main pharmacological targets against Trypanosoma cruzi, cruzain protease, dihydroorotate dehydrogenase, lanosterol 14-alpha-demethylase, farnesyl diphosphate, and squalene synthases.This study was supported by PO-FEDER AGROECODIV and CONACYT “(Consejo Nacional de Ciencia y Tecnologia, programa prociencia, convocatoria 2013, proyecto 14-INV-1513)”.Peer reviewe