Resultados de investigación

Studying intraspecific trait variation across environments is key for understanding how resource-use strategies evolve. It is hypothesized that plants from mesic environments have evolved towards a more acquisitive strategy with high growth potential and phenotypic plasticity, while populations from xeric continental climates exhibit a conservative strategy with slower growth and better physiological performance under drier conditions. We tested this hypothesis through the phenotypical characterization of 14-year-old Pinus pinaster Aiton trees from twenty range-wide populations growing in two climatically contrasting common gardens. We measured twenty-one traits related to growth, leaf morphology, gas exchange, photochemistry, and hydraulics. Consistent with our hypothesis, we found that populations from mesic oceanic areas exhibited higher growth rates and higher allocation to leaf surface area under mesic conditions, along with greater plasticity in these traits. In contrast, xeric continental populations had better physiological status showing higher gas exchange rates and photochemical efficiency, but lower sapwood-specific hydraulic conductivity under drier conditions. Together, our results provide evidence that climate drives the joint evolution of leaf and stem traits and their plasticity following an acquisitive-conservative axis of resource use. Overall, trait coordination is found to be highly plastic likely to maximize plant performance under contrasting environmental conditions., Peer reviewed

The dataset includes Pan-European maps of timber volume (Vol), above-ground biomass (AGB), and deciduous-coniferous proportion (DCP) with a pixel size of 10×10 m for the reference year 2020. In addition, a measure of prediction uncertainty is provided for each pixel. The maps have been created using a combination of a Sentinel-2 mosaic, Copernicus layers, and National Forest Inventory (NFI) data. The mapping was done with the k-Nearest Neighbour (kNN, k=7) approach with harmonized data of species-specific Vol and AGB from 14 NFIs consisting of approximately 151 000 field plots across Europe. The maps cover 40 European countries, forming a continuous coverage of the western part of the European continent. A sample of 1/3 of NFI plots was left out for validation, whereas 2/3 of the plots were used for mapping. Maps were created independently for 13 multi-country processing areas. Root-mean-squared-errors (RMSEs) for AGB ranged from 53 % in the Nordic processing area to 73 % in the South-Eastern area. The maps are on average nearly unbiased on European level (1.0 % of the mean AGB), but show significant overestimation for small biomass values (53 % bias for forests with AGB less than 150 t/ha) and underestimation for high biomass values (-55 % bias for forests with AGB higher than 500 t/ha). The created maps are the first of their kind as they are utilizing a large number of harmonized NFI plot observations and consistent remote sensing data for high-resolution forest attribute mapping. While the published maps can be useful for visualization and other purposes, they are primarily meant as auxiliary information in model-assisted estimation where model-related biases can be mitigated, and field-based estimates improved. Therefore, additional calibration procedures were not applied, and especially high Vol and AGB values tend to be underestimated. We therefore discourage from summarizing map values (pixel counting) over areas in interest, as this may inadvertently result in biased estimates., This study received funding from the EU under GA101056907 (PathFinder)., Peer reviewed

[Methods] For mapping, we used the k-Nearest Neighbor (kNN, k=7) approach with a harmonized database of species-specific V and AGB from 14 NFIs across Europe. This database encompasses approximately 151,000 sample plots, which were intersected with the above-mentioned Earth observation data. The maps cover 40 European countries, forming a continuous coverage of the western part of the European continent. A sample of 1/3 of NFI plots was left out for validation, whereas 2/3 of the plots were used for mapping. Maps were created independently for 13 multi-country processing areas. Root-mean-squared-errors (RMSEs) for AGB ranged from 53 % in the Nordic processing area to 73 % the South-Eastern area. The created maps are the first of their kind as they are utilizing a huge amount of harmonized NFI observations and consistent remote sensing data for high-resolution forest attribute mapping. While the published maps can be useful for visualization and other purposes, they are primarily meant as auxiliary information in model-assisted estimation where model-related biases can be mitigated, and field-based estimates improved. Therefore, additional calibration procedures were not applied, and especially high V and AGB values tend to be underestimated. Summarizing map values (pixel counting) over large regions such as countries or whole Europe will consequently result in biased estimates that need to be interpreted with care., El dataset se puede consultar y descargar en el siguiente enlace https://doi.org/10.5281/zenodo.13143235, We developed Pan-European maps of timber volume (V), above-ground biomass (AGB), and deciduous-coniferous proportion (DCP) with a pixel size of 10 x 10 m2 for the reference year 2020 using a combination of a Sentinel 2 mosaic, Copernicus layers, and National Forest Inventory (NFI) data., European Commission: PathFinder – Towards an Integrated Consistent European LULUCF Monitoring and Policy Pathway Assessment Framework., Peer reviewed

Quality controlled temperature data at daily resolution at CTS, HRR, HYS, NVC, RSI and SGV and the most relevant codes for data processing used in: García-Pereira, F., González-Rouco, J. F., Schmid, T., Melo-Aguilar, C, Vegas-Cañas, C., Steinert, N. J., Roldán-Gómez, P. J., Cuesta-Valero, F. J., García-García, A., Beltrami, H., and de Vrese, H.: "Thermodynamic and hydrological drivers of the subsurface thermal regime in Central Spain". Earth Surf. Dynam., submitted, 2023., All data can be also freely obtained for research from the original data sources, GuMNet (https://www.ucm.es/gumnet/) and AEMET (https://www.aemet.es/en/datos_abiertos). Further details of the code are available upon request to the corresponding author (Félix García-Pereira, felgar03@ucm.es)., Peer reviewed

Data and codes of the paper "Global trends of trait matching in avian frugivory and its consequences for the complementarity and irreplaceability of birds", which quantifies trait-matching in avian frugivory from 59 communities across the globe in order to (i) evaluate if trait-matching is generalizable, (ii) if its strengths varies with latitude and insularity, (iii) and explore the functional consequences of such trait-matching between birds and plants. The data contains information of 6883 pairwise interactions between 799 plant and 733 bird species from 84 and 76 families. It also contains information about interaction-relevant traits of birds (beak width, degree of frugivory in birds) and plants (fruit diameter and lipid content of fruit pulps), and matrices of species phylogenectic correlations and distances. We also include the scripts to generate the joint species frugivory model in stan and fit it to data., National Agency for Technological Development“ Using the community assembly framework to elucidate the mechanisms of naturalization of fleshy fruited species”. PICT 2018-01566 project; Foundation for the Promotion of Applied Scientific Research and Technology in Asturias REWILDING project, FEDERGRUPIN AYUD/2021/51261, Peer reviewed

Alzheimer´s disease (AD) is characterized by neuronal function loss and degeneration. The integrity of the axon initial segment (AIS) is essential to maintain neuronal function and output. AIS alterations are detected in human post-mortem AD brains and mice models, as well as, neurodevelopmental and mental disorders. However, the mechanisms leading to AIS deregulation in AD and the extrinsic glial origin are elusive. We studied early postnatal differences in AIS cellular/molecular mechanisms in wild-type or APP/PS1 mice and combined neuron-astrocyte co-cultures. We observed AIS integrity alterations, reduced ankyrinG expression and shortening, in APP/PS1 mice from P21 and loss of AIS integrity at 21 DIV in wild-type and APP/PS1 neurons in the presence of APP/PS1 astrocytes. AnkyrinG decrease is due to mRNAs and protein reduction of retinoic acid synthesis enzymes Rdh1 and Aldh1b1, as well as ADNP (Activity-dependent neuroprotective protein) in APP/PS1 astrocytes. This effect was mimicked by wild-type astrocytes expressing ADNP shRNA. In the presence of APP/PS1 astrocytes, wild-type neurons AIS is recovered by inhibition of retinoic acid degradation, and Adnp-derived NAP peptide (NAPVSIPQ) addition or P2X7 receptor inhibition, both regulated by retinoic acid levels. Moreover, P2X7 inhibitor treatment for 2 months impaired AIS disruption in APP/PS1 mice. Our findings extend current knowledge on AIS regulation, providing data to support the role of astrocytes in early postnatal AIS modulation. In conclusion, AD onset may be related to very early glial cell alterations that induce AIS and neuronal function changes, opening new therapeutic approaches to detect and avoid neuronal function loss., Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was carried out with the following funding sources: Grant PID2021-123140NB-I00 to J.J.G. and PID2021-124801NB-I00 to FW funded by MCIN/AEI/https://doi. org/10.13039/501100011033, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBER-ISCIII) Grant PI2016/01., Peer reviewed

Eukaryotic cell function and survival rely on the use of a mitochondrial H+ electrochemical gradient (Δp), which is composed of an inner mitochondrial membrane (IMM) potential (ΔΨmt) and a pH gradient (ΔpH). So far, ΔΨmt has been assumed to be composed exclusively of H+. Here, using a rainbow of mitochondrial and nuclear genetic models, we have discovered that a Na+ gradient equates with the H+ gradient and controls half of ΔΨmt in coupled-respiring mammalian mitochondria. This parallelism is controlled by the activity of the long-sought Na+-specific Na+/H+ exchanger (mNHE), which we have identified as the P-module of complex I (CI). Deregulation of this mNHE function, without affecting the canonical enzymatic activity or the assembly of CI, occurs in Leber's hereditary optic neuropathy (LHON), which has profound consequences in ΔΨmt and mitochondrial Ca2+ homeostasis and explains the previously unknown molecular pathogenesis of this neurodegenerative disease., We thank Dr. Cogliati (CMBSO, UAM-CSIC) for helping with TEM imaging; Dr. Curtabbi, Drs. Castillo & Priori (CNIC), and Dr. Rial (CIB-CSIC) for fruitful discussion; and MM Muñoz-Hernandez, R Martínez-de-Mena, E.R. Martínez-Jiménez, and C. Jiménez for technical assistance. We acknowledge Dr. Moreno-Los huertos and Dr. Sancho for kindly providing cell line models. Scheme figures were made with BioRender. We thank Dr. Calvo-Adiego from Incarlopsa Slaughterhouse for the generous gift of fresh porcine heart. Microscopy was performed in the Microscopy and Dynamic Imaging Unit. Funding is as follows: this study was supported by competitive grants from the Ministerio de Ciencia e Innovación (MCIN) RTI2018-099357-B-I00, CIBERFES (CB16/10/00282), Human Frontier Science Program (grant RGP0016/2018), and Leducq Transatlantic Networks (17CVD04) to J.A.E. P.H.-A. is supported by a JdC IJC2020-042679-I, and Y.M.-M. is supported by an FPI-SO fellowship PRE2018-083478. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MICIU), and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIU/AEI/ 10.13039/501100011033). I.L.-M. acknowledges financial support through the TECNOLOGÍAS 2018 program funded by the Regional Government of Madrid (grant S2018/BAA-4403 SINOXPHOS-CM)., Peer reviewed

Peer reviewed

The differential vulnerability of dopaminergic neurons of the substantia nigra pars compacta (SNc) is a critical and unresolved question in Parkinson´s disease. Studies in mice show diverse susceptibility of subpopulations of nigral dopaminergic neurons to various toxic agents. In the primate midbrain, the molecular phenotypes of dopaminergic neurons and their differential vulnerability are poorly characterized. We performed a detailed histological study to determine the anatomical distribution of different molecular phenotypes within identified midbrain neurons and their selective vulnerability in control and MPTP-treated monkeys. In the ventral tier of the SNc (nigrosome), neurons rich in Aldh1a1 and Girk2 are intermingled, whereas calbindin is the marker that best identifies the most resilient neurons located in the dorsal tier and ventral tegmental area, recapitulating the well-defined dorsoventral axis of susceptibility to degeneration of dopaminergic neurons. In particular, a loss of Aldh1a1+ neurons in the ventral SNc was observed in parallel to the progressive development of parkinsonism. Aldh1a1+ neurons were the main population of vulnerable dopaminergic nigrostriatal-projecting neurons, while Aldh1a1- neurons giving rise to nigropallidal projections remained relatively preserved. Moreover, bundles of entwined Aldh1a1+ dendrites with long trajectories extending towards the substantia nigra pars reticulata emerged from clusters of Aldh1a1+ neurons and colocalized with dense cannabinoid receptor 1 afferent fibers likely representing part of the striatonigral projection that is affected in human disorders, including Parkinson´s disease. In conclusion, vulnerable nigrostriatal-projecting neurons can be identified by using Aldh1a1 and Girk2. Further studies are needed to define the afferent/efferent projection patterns of these most vulnerable neurons., N.L.G.R was funded by grant S2017/BMD-3700 (NEUROMETAB-CM) from Comunidad de Madrid; N.H.P by Ayudantes de Investigacion from Comunidad de Madrid; N.E.G by Instituto de Salud Carlos III PFIS (FI21/ 000919); C.C by Chair in Neuroscience UAM-Fundacion Tatiana Pérez de Guzmán el Bueno; J.A.O by Ministerio de Ciencia e Innovación y Universidades (PID2019–111045RB-I00); and J.B. by Instituto de Salud Carlos III Miguel Servet Program (CP19/00200) and FIS (PI23/00672). Expert technical assistance was kindly provided by Raquel Márquez, Maria Ciorraga, Noelia Mercado, Elvira Roda, and Adriana Honrubia. Tireless support ensuring the highest standards of animal welfare was provided by Cristina Gil, Jennifer Ribeiro, Juan Santos, Eduardo Alvarez, and Goiaz Ariznabarreta. Alberto J. Rico, PhD, assisted us during ventriculography-guided stereotaxic surgical deliveries of tracer. We also recognize expert support received from Lola Morales and Alejandro Nieto-Guerrero from the Confocal Microscopy Core Unit at Universidad Autonoma de Madrid. Assistance received from Lawrence Phillips, MD, for English language editing of this manuscript is gratefully acknowledged. Finally, we thank Dr. Rajeshwar Awatramani for helpful discussions and insightful comments on the manuscript., Peer reviewed

Lafora disease is a rare and fatal form of progressive myoclonic epilepsy typically occurring early in adolescence. The disease results from mutations in the EPM2A gene, encoding laforin, or the EPM2B gene, encoding malin. Laforin and malin work together in a complex to control glycogen synthesis and prevent the toxicity produced by misfolded proteins via the ubiquitin-proteasome system. Disruptions in either protein cause alterations in this complex, leading to the formation of Lafora bodies containing abnormal, insoluble, and hyperphosphorylated forms of glycogen. We used the Epm2a-/- knockout mouse model of Lafora disease to apply gene therapy by administering intracerebroventricular injections of a recombinant adeno-associated virus carrying the human EPM2A gene. We evaluated the effects of this treatment through neuropathological studies, behavioral tests, video-electroencephalography, electrophysiological recordings, and proteomic/phosphoproteomic analysis. Gene therapy ameliorated neurological and histopathological alterations, reduced epileptic activity and neuronal hyperexcitability, and decreased the formation of Lafora bodies. Moreover, differential quantitative proteomics and phosphoproteomics revealed beneficial changes in various molecular pathways altered in Lafora disease. Our results represent proof of principle for gene therapy with the coding region of the human EPM2A gene as a treatment for EPM2A-related Lafora disease., This work was supported by grants from the Spanish Ministry of Economy (Rti2018-095784b-100SAF MCI/AEI/FEDER, UE) to J.M.S. and M.P.S.; from the Tatiana Perez de Guzman el Bueno Foundation to M.P.S. and J.M.S.; from the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) (ACCI 2020, 23 - U744) to M.P.S.; from the Fondazione Malattie Rare Mauro Baschirotto BIRD Onlus to M.P.S., C.C., M.S., and L.Z.P.; and a grant from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (P01NS097197), which established the Lafora Epilepsy Cure Initiative (LECI), to J.M.S. and M.P.S. We thank Pascual Sanz Bigorra (Institute of Biomedicine of Valencia [IBV]) and Manuel Soto Catalán (Instituto de Investigación Sanitaria-Fundación Jiménez Díaz) for their generous gift of GS, BiP, and cleaved caspase-3 antibodies, and to Miguel Chillón Rodríguez (Viral Vector Production Unit or UPV-UAB-VHIR) for the generation of rAAVs and technical advice. We also thank Juan Antonio López del Olmo (CNIC Proteomics Unit), Ariadna Martín Blázquez (Instituto de Investigación Sanitaria-Fundación Jiménez Díaz), and the Animal Facility of Instituto de Investigación Sanitaria-Fundación Jiménez Díaz for their technical assistance., Peer reviewed