e5: euskararen komunitatearen garapenerako marko interpretatibo berria

Lan honetan «Euskararen Etorkizuneko Eszenarioak Elkarrekin Eraikitzen» (e5) egitasmoa aurkeztuko da. e5 bi helburu nagusiren inguruan ardaztu zen: batetik, hurrengo hamarkadetarako euskalgintzaren aro berria konfiguratzen laguntzea, eta bestetik, euskararen biziberritze prozesua ulertzeko eta garatzeko marko interpretatibo berri bat lantzea. Artikuluan KOHiKoGa Eredua (Kapitaletan Oinarritutako Hizkuntz Komunitatearen Garapena) izendatu dugun marko berriaren oinarri teoriko-metodologikoak aurkeztuko ditugu eta e5 egitasmoa nola egikaritu zen azaldu. Azkenik, marko berri hau maila mikroan euskara biziberritzeko tresna egokia dela iradokiko dugu

A Drastic Shift in Lipid Adducts in Colon Cancer Detected by MALDI-IMS Exposes Alterations in Specific K+ Channels

Even though colorectal cancer (CRC) is one of the most preventable cancers, it is one of the deadliest, and recent data show that the incidence in people <50 years has unexpectedly increased. While new techniques for CRC molecular classification are emerging, no molecular feature is as yet firmly associated with prognosis. Imaging mass spectrometry (IMS) lipidomic analyses have demonstrated the specificity of the lipid fingerprint in differentiating pathological from healthy tissues. During IMS lipidomic analysis, the formation of ionic adducts is common. Of particular interest is the [Na+]/[K+] adduct ratio, which already functions as a biomarker for homeostatic alterations. Herein, we show a drastic shift of the [Na+]/[K+] adduct ratio in adenomatous colon mucosa compared to healthy mucosa, suggesting a robust increase in K+ levels. Interrogating public databases, a strong association was found between poor diagnosis and voltage-gated potassium channel subunit beta-2 (KCNAB2) overexpression. We found this overexpression in three CRC molecular subtypes defined by the CRC Subtyping Consortium, making KCNAB2 an interesting pharmacological target. Consistently, its pharmacological inhibition resulted in a dramatic halt in commercial CRC cell proliferation. Identification of potential pharmacologic targets using lipid adduct information emphasizes the great potential of IMS lipidomic techniques in the clinical field.This study was supported in part by the Institute of Health Carlos III (CP12/03338 and PI16/02200), Basque Government (IT1162-19), and the EC (European Regional Development Fund, ERDF, CP12/03338). A.M.B. and J.B-E. hold predoctoral fellowships of the Govern Balear (Direcció General d’Innovació i Recerca, FPI/2160/2018 and FPI/1787/2015, respectively), co-funded by the ESF (European Social Fund). K.P.-R. contract was supported by the Govern Balear (Servei d’Ocupació de les IIles Balears and Garantia Juvenil, JQ-SP 18/17), co-funded by the ESF. G.B.-C. and D.H.L.’s contracts were supported by the Institute of Health Carlos III, co-funded by ERDF (Miguel Servet II program, CPII17/00005 and PI16/02200, respectively). We are grateful to SGiker Lipidomic Service (UPV/EHU, MICINN, GV/EG, ESF) for the expert advice and technical and human support in MALDI-IMS analysis. The publication fee in this Open Access journal is fully supported by the Liberi Call of the IdISBa

Effects of Platelet-Rich Plasma on Cellular Populations of the Central Nervous System: The Influence of Donor Age

first_page settings Open AccessArticle Effects of Platelet-Rich Plasma on Cellular Populations of the Central Nervous System: The Influence of Donor Age by Diego Delgado 1, Ane Miren Bilbao 2, Maider Beitia 1, Ane Garate 1, Pello Sánchez 1, Imanol González-Burguera 3,4, Amaia Isasti 4,5, Maider López De Jesús 4,5,6, Jone Zuazo-Ibarra 7, Alejandro Montilla 7 [OrcID] , María Domercq 7 [OrcID] , Estibaliz Capetillo-Zarate 7,8, Gontzal García del Caño 3,4 [OrcID] , Joan Sallés 4,5,6, Carlos Matute 7 and Mikel Sánchez 1,2,* 1 Advanced Biological Therapy Unit, Hospital Vithas Vitoria, 01008 Vitoria-Gasteiz, Spain 2 Arthroscopic Surgery Unit, Hospital Vithas Vitoria, 01008 Vitoria-Gasteiz, Spain 3 Department of Neurosciences, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), 01008 Vitoria-Gasteiz, Spain 4 Bioaraba, Neurofarmacología Celular y Molecular, 01008 Vitoria-Gasteiz, Spain 5 Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), 01008 Vitoria-Gasteiz, Spain 6 Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), 28029 Madrid, Spain 7 Achucarro Basque Center for Neuroscience, CIBERNED and Departamento de Neurociencias, Universidad del País Vasco (UPV/EHU), 48940 Leioa, Spain 8 IKERBASQUE, Basque Foundation for Science, 48009 Bilbao, Spain * Author to whom correspondence should be addressed. Academic Editor: Francesca Santilli Int. J. Mol. Sci. 2021, 22(4), 1725; https://doi.org/10.3390/ijms22041725 Received: 24 November 2020 / Revised: 12 January 2021 / Accepted: 3 February 2021 / Published: 9 February 2021 (This article belongs to the Section Molecular Endocrinology and Metabolism) Download PDF Browse Figures Citation Export Abstract Platelet-rich plasma (PRP) is a biologic therapy that promotes healing responses across multiple medical fields, including the central nervous system (CNS). The efficacy of this therapy depends on several factors such as the donor’s health status and age. This work aims to prove the effect of PRP on cellular models of the CNS, considering the differences between PRP from young and elderly donors. Two different PRP pools were prepared from donors 65–85 and 20–25 years old. The cellular and molecular composition of both PRPs were analyzed. Subsequently, the cellular response was evaluated in CNS in vitro models, studying proliferation, neurogenesis, synaptogenesis, and inflammation. While no differences in the cellular composition of PRPs were found, the molecular composition of the Young PRP showed lower levels of inflammatory molecules such as CCL-11, as well as the presence of other factors not found in Aged PRP (GDF-11). Although both PRPs had effects in terms of reducing neural progenitor cell apoptosis, stabilizing neuronal synapses, and decreasing inflammation in the microglia, the effect of the Young PRP was more pronounced. In conclusion, the molecular composition of the PRP, conditioned by the age of the donors, affects the magnitude of the biological response.This work was funded by the Provincial Council of Alava through the AlavaInnova Program, Basque Government through the GAITEK Program, Ministry of Economy, Industry and Competitiveness (CTQ2017-85686-R), Spanish Ministry of Education and Science (PID2019-109724RB-I00), Basque Government (IT1203-19, IT1230-19, and KK-2020/00034) and Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Microarray and Mass Spectrometry-Based Methodology for Lipid Profiling of Tissues and Cell Cultures

The recent developments in mass spectrometry have revealed the importance of lipids as biomarkers in the context of different diseases and as indicators of the cell's homeostasis. However, further advances are required to unveil the complex relationships between lipid classes and lipid species with proteins. Here, we present a new methodology that combines microarrays with mass spectrometry to obtain the lipid fingerprint of samples of a different nature in a standardized and fast way, with minimal sample consumption. As a proof of concept, we use the methodology to obtain the lipid fingerprint of 20 rat tissues and to create a lipid library for tissue classification. Then, we combine those results with immunohistochemistry and enzymatic assays to unveil the relationship between some lipid species and two enzymes. Finally, we demonstrate the performance of the methodology to explore changes in lipid composition of the nucleus accumbens from mice subjected to two lipid diets.Impact de la composition lipidique membranaire sur la transmission dopaminergique dépendante du récepteur D2 et la motivatio

Deciphering the Lipid Architecture of the Rat Sciatic Nerve Using Imaging Mass Spectrometry

Knowledge on the normal structure and molecular composition of the peripheral nerves is essential to understand their pathophysiology and to select the regeneration strategies after injury. However, the precise lipid composition of the normal peripheral nerve is still poorly known. Here, we present the first study of distribution of individual lipids in the mature sciatic nerve of rats by imaging mass spectrometry. Both positive and negative ion modes were used to detect, identify and in situ map 166 molecular species of mainly glycerophospholipids, sphingomyelins, sulfatides, and diacyl and triacylglycerols. In parallel, lipid extracts were analyzed by LC-MS/MS to verify and complement the identification of lipids directly from the whole tissue. Three anatomical regions were clearly identified by its differential lipid composition: the nerve fibers, the connective tissue and the adipose tissue that surrounds the nerve. Unexpectedly, very little variety of phosphatidylcholine (PC) species was found, being by far PC 34:1 the most abundant species. Also, a rich composition on sulfatides was detected in fibers, probably due to the important role they play in the myelin cover around axons, as well as an abundance of storage lipids in the adipose and connective tissues. The database of lipids here presented for each region and for the whole sciatic nerve is a first step toward understanding the variety of the peripheral nerves’ lipidome and its changes associated with different diseases and mechanical injuries

Influence of the Cation Adducts in the Analysis of Matrix-Assisted Laser Desorption Ionization Imaging Mass Spectrometry Data from Injury Models of Rat Spinal Cord

Imaging mass spectrometry (IMS) is quickly becoming a technique of reference to visualize the lipid distribution in tissue sections. Still, many questions remain open, and data analysis has to be optimized to avoid interpretation pitfalls. Here we analyze how the variation on the [Na⁺]/[K⁺] relative abundance affects the detection of lipids between sections of spinal cord of (uninjured) control rats and of models of spinal cord demyelination and traumatic contusion injury. The [M + Na]⁺/[M + K]⁺ adducts ratio remained approximately constant along transversal and longitudinal sections of spinal cord from control animals, but it strongly changed depending on the type of lesion. A substantial increase in the abundance of [M + Na]⁺ adducts was observed in samples from spinal cord with demyelination, while the intensity of the [M + K]⁺ adducts was stronger in those sections from mechanically injured spinal cords. Such changes masked the modifications in the lipid profile due to the injury and only after summing the signal intensity of all adducts and corresponding monoprotonated molecular ions of each detected lipid in a single variable, it was possible to unveil the real changes in the lipid profile due to the lesion. Such lipids included glycerophospholipids (both diacyl and aryl-acyl), sphingolipids, and nonpolar lipids (diacyl and triacylglycerols), which are the main lipid classes detected in positive-ion mode. Furthermore, the results demonstrate the sensitivity of the technique toward modification in tissue homeostasis and that the [M + Na]⁺/[M + K]⁺ ratio may be used to detect alterations in such homeostasis

MALDI-IMS files of 53 experiments over sections of nevus, primary melanoma and melanoma metastasis in imzml format

&lt;p&gt;MALDI-IMS files of 53 experiments over sections of nevus, primary melanoma and melanoma metastasis in imzml format. The experiments were recorded in negative-ion mode with a MALDI LTQ-orbitrap XL (ThermoFisher) at 25 um/pixel of spatial resolution. We also uploaded three .ppt with a comparison between the eosin-hematoxilin images, the IHC (MelanA and HMB45) and the segmentation images&lt;/p&gt