Guía a través de sustratos inhibitorios de células de la glía envolvente del bulbo olfatorio por funcionalización de nanofibras de PLA con SDF1α

[EN] Trauma of the spinal cord generates cell death and disruption of blood vessels in the lesioned region. Blood Brain Barrier disorganization recruits neutrophils, macrophages and leukocytes to remove cellular debris and reduce secondary damage of the injured tissue. Days after, a glial scar is generated in the injured area, mostly formed by reactive astrocytes. They secrete several molecules in order to inhibit the aberrant axonal growth, like chondroitin sulfate proteoglycans (CSPG) and myelin-derivated inhibitors associated inhibitors (MAIs). This molecular and physical inhibition of the glial scar is the most important problem in this type of injury s treatment. In this context, one of the last areas of study in the Spinal Cord Injury (SCI) treatment is the cellular therapy, for example using Olfactory Ensheathing Cells (OECs). These cells help olfactory axons to enter into the olfactory bulb. Thus, due to these properties, they were proposed to be transplanted in SCI models to help the injured axons to regrowth. One of the main problems of this cellular therapy is to enhance their migration into the inhibitory substrate of the injured spinal cord as they are also inhibited by CSPG and MAIs. Here, we analyze the potential of poly-lactic acid (PLA) aligned nanofibers, functionalized with SDF1α as a migratory route to aid in vitro OECs migration in inhibitory substrates. The 80L/20D PLA nanofibers were functionalized with the chemokine SDF1α, the CXCR4 ligand. TEG3, the stable OECs line, express CXCR4 receptor and it is able to respond to SDF1α stimulation via pERK ¿. Our results show that TEG3 prefers functionalized nanofibers with SDF1α in gradient. When we test TEG3 migration through inhibitory substrates over functionalized or non-functionalized nanofibers, we observed higher migration in functionalized nanofibers. Next step will be test migratory talent of OECs over functionalized nanofibers in ex vivo medullar injury model.[ES] La lesión de la médula espinal produce muerte celular y disrupción de los vasos sanguíneos de la región afectada. La desorganización de la barrera hematoencefálica recluta neutrófilos, macrófagos y leucocitos para eliminar los restos celulares y reducir daños secundarios en el tejido dañado. Unos días después, se produce la cicatriz glial en la zona de la lesión, formada mayoritariamente por astrocitos reactivos. Estos secretan muchas moléculas, como el proteoglicano condroitin sulfato (CSPG) o inhibidores asociados derivados de la mielina (MAIs), que inhiben el crecimiento axonal aberrante. Esta inhibición molecular y física de la cicatriz glial es uno de los problemas más importantes en el tratamiento en la lesión medular. En este contexto, una de las últimas áreas de estudio en el tratamiento de la lesión medular (Spinal Cord Injury, SCI) es la terapia celular, como la basada en las células de la glía envolvente del bulbo olfatorio (Olfactory Ensheating Cells, OECs). Estas células ayudan a los axones de la vía olfativa a entrar en el bulbo. Debido a estas propiedades se han propuesto para trasplantes en modelos de SCI para ayudar a los axones dañados en la regeneración. Uno de los principales problemas en este tipo de terapia es aumentar la migración a través de los sustratos inhibitorios típicos de la SCI como el CSPG o los MAIs. En el presente estudio analizamos el potencial de nanofibras de ácido poliláctico (PLA) funcionalizadas con SDF1α como una ruta migratoria in vitro para las OECs a través de sustratos inhibitorios. Las nanofibras de 80L/20D se funcionalizan con la quimioquina SDF1α, el ligando de CXCR4. Las TEG3, la línea estable de las OECS, expresan el receptor CXCR4 y son capaces de responder a SDF1 vía pERK ¿. Cuando cuantificamos la migración de TEG3 sobre nanofibras funcionalizadas o no funcionalizadas a través de un sustrato inhibitorio observamos mayor migración en las nanofibras funcionalizadas. Por tanto, la funcionalización de las nanofibras de PLA aporta una ruta migratoria más eficaz para las OECs en la terapia de la lesión medular en un modelo in vitro. El siguiente paso será testar la capacidad migratoria de las OECs sobre las nanofibras funcionalizadas en un modelo de lesión medular ex vivo.López Mengual, A. (2016). Guía a través de sustratos inhibitorios de células de la glía envolvente del bulbo olfatorio por funcionalización de nanofibras de PLA con SDF1α. http://hdl.handle.net/10251/69018TFG

Factores físicos y moleculares implicados en la migración celular y en el desarrollo de la corteza cerebral

Programa de Doctorat en Biomedicina / Tesi realitzada a l'Institut de Bioenginyeria de Catalunya (IBEC)La migración celular adquiere especial relevancia durante el desarrollo embrionario y la regeneración tisular. Durante el desarrollo del individuo adulto, las células se multiplican, se diferencian y maduran, debiéndose de desplazar a sus regiones de destino mediante la migración. Una vez se ha formado el individuo adulto, estos tejidos de los que forman parte pueden sufrir daños, que conlleven a un estado alterado del mismo. En este proceso de regeneración del tejido en un intento de reestablecer la homeostasis tisular, la migración celular es fundamental. Por ellos, en esta tesis se analizan los factores mecánicos durante la migración celular en desarrollo cerebral y en regeneración neural, como una herramienta fundamental para entender estos procesos. En primer lugar, se analiza la idoneidad del uso de nanofibras de PLA 80/20 funcionalizadas con la quimiocina CXCL12 como sistema andamio para la migración de las células de la glía envolvente olfatoria (OECs). Las OECs migran mayores distancias sobre las nanofibras funcionalizadas, respondiendo así al gradiente quimiotáctico. Además, al sembrar las OECs y disponer las nanofibras funcionalizadas paralelas y suspendidas, nos aporta un buen sistema para trasplantar las células de forma direccionada en procesos de daño neural como terapia. En segundo lugar, se analiza el papel de los factores físicos en la migración y disposición de las células de Cajal-Retzius (CRcs) y de su origen migratorio. Se realizan mediciones mediante BIO-AFM del cerebro embrionario de ratón, obteniendo diferencias entre el palio y el subpalio. Estas diferencias determinan las tasas de migración diferenciales al trasplantar explantes de diversos orígenes fuera de su sitio habitual y analizar la migración de las CRcs. Además, las CRcs responden mediante entrada de calcio a la inhibición de canales catiónicos mecanosensibles, cambiando su tasa de migración

Involvement of Mechanical Cues in the Migration of Cajal-Retzius Cells in the Marginal Zone During Neocortical Development

Emerging evidence points to coordinated action of chemical and mechanical cues during brain development. At early stages of neocortical development, angiogenic factors and chemokines such as CXCL12, ephrins, and semaphorins assume crucial roles in orchestrating neuronal migration and axon elongation of postmitotic neurons. Here we explore the intrinsic mechanical properties of the developing marginal zone of the pallium in the migratory pathways and brain distribution of the pioneer Cajal-Retzius cells. These neurons are generated in several proliferative regions in the developing brain (e.g., the cortical hem and the pallial subpallial boundary) and migrate tangentially in the preplate/marginal zone covering the upper portion of the developing cortex. These cells play crucial roles in correct neocortical layer formation by secreting several molecules such as Reelin. Our results indicate that the motogenic properties of Cajal-Retzius cells and their perinatal distribution in the marginal zone are modulated by both chemical and mechanical factors, by the specific mechanical properties of Cajal-Retzius cells, and by the differential stiffness of the migratory routes. Indeed, cells originating in the cortical hem display higher migratory capacities than those generated in the pallial subpallial boundary which may be involved in the differential distribution of these cells in the dorsal-lateral axis in the developing marginal zone

Development of Photonic Multi-Sensing Systems Based on Molecular Gates Biorecognition and Plasmonic Sensors: The PHOTONGATE Project

[EN] This paper presents the concept of a novel adaptable sensing solution currently being developed under the EU Commission-founded PHOTONGATE project. This concept will allow for the quantification of multiple analytes of the same or different nature (chemicals, metals, bacteria, etc.) in a single test with levels of sensitivity and selectivity at/or over those offered by current solutions. PHOTONGATE relies on two core technologies: a biochemical technology (molecular gates), which will confer the specificity and, therefore, the capability to be adaptable to the analyte of interest, and which, combined with porous substrates, will increase the sensitivity, and a photonic technology based on localized surface plasmonic resonance (LSPR) structures that serve as transducers for light interaction. Both technologies are in the micron range, facilitating the integration of multiple sensors within a small area (mm2). The concept will be developed for its application in health diagnosis and food safety sectors. It is thought of as an easy-to-use modular concept, which will consist of the sensing module, mainly of a microfluidics cartridge that will house the photonic sensor, and a platform for fluidic handling, optical interrogation, and signal processing. The platform will include a new optical concept, which is fully European Union Made, avoiding optical fibers and expensive optical components.The micro-nanofabrication capabilities required in the PHOTONGATE project- 101093042 are funded by the Pluri-Regional FEDER funding Plan 2014-2020 European Commission. This research project has received funding from the European Union¿s HORIZON-CL4-2022 research and innovation programme under grant agreement ID 101093042, PHOTONGATE projectNieves-Paniagua, Ó.; Ortiz De Zárate-Díaz, D.; Aznar, E.; Caballos-Gómez, MI.; Garrido-García, EM.; Martínez-Máñez, R.; Dortu, F.... (2023). Development of Photonic Multi-Sensing Systems Based on Molecular Gates Biorecognition and Plasmonic Sensors: The PHOTONGATE Project. Sensors. 23(20):1-13. https://doi.org/10.3390/s23208548113232

The era of reference genomes in conservation genomics

Progress in genome sequencing now enables the large-scale generation of reference genomes. Various international initiatives aim to generate reference genomes representing global biodiversity. These genomes provide unique insights into genomic diversity and architecture, thereby enabling comprehensive analyses of population and functional genomics, and are expected to revolutionize conservation genomics

The era of reference genomes in conservation genomics

Progress in genome sequencing now enables the large-scale generation of reference genomes. Various international initiatives aim to generate reference genomes representing global biodiversity. These genomes provide unique insights into genomic diversity and architecture, thereby enabling comprehensive analyses of population and functional genomics, and are expected to revolutionize conservation genomics

The era of reference genomes in conservation genomics

info:eu-repo/semantics/publishedVersio

How genomics can help biodiversity conservation

The availability of public genomic resources can greatly assist biodiversity assessment, conservation, and restoration efforts by providing evidence for scientifically informed management decisions. Here we survey the main approaches and applications in biodiversity and conservation genomics, considering practical factors, such as cost, time, prerequisite skills, and current shortcomings of applications. Most approaches perform best in combination with reference genomes from the target species or closely related species. We review case studies to illustrate how reference genomes can facilitate biodiversity research and conservation across the tree of life. We conclude that the time is ripe to view reference genomes as fundamental resources and to integrate their use as a best practice in conservation genomics.info:eu-repo/semantics/publishedVersio

Dietary α‐Linolenic Acid, Marine ω‐3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study

Background: Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐3 fatty acids (long‐chain n‐3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all‐cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long‐chain n‐3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9‐y follow‐up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all‐cause mortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long‐chain n‐3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all‐cause mortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all‐cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all‐cause mortality, whereas protection from cardiac mortality is limited to fish‐derived long‐chain n‐3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639

How genomics can help biodiversity conservation

The availability of public genomic resources can greatly assist biodiversity assessment, conservation, and restoration efforts by providing evidence for scientifically informed management decisions. Here we survey the main approaches and applications in biodiversity and conservation genomics, considering practical factors, such as cost, time, prerequisite skills, and current shortcomings of applications. Most approaches perform best in combination with reference genomes from the target species or closely related species. We review case studies to illustrate how reference genomes can facilitate biodiversity research and conservation across the tree of life. We conclude that the time is ripe to view reference genomes as fundamental resources and to integrate their use as a best practice in conservation genomics