المؤلفون: del Puerto, Ana, López Fonseca, Coral, Simón-García, Ana, Martí-Prado, Beatriz, Barrios Muñoz, Ana Laura, Pose-Utrilla, Julia, López-Menéndez, Celia, Alcover-Sanchez, Berta, Cesca, Fabrizia, Schiavo, Giampietro, Campanero, Miguel R., Fariñas, Isabel, Iglesias, Teresa, Porlán Alonso, Eva

المساهمون: UAM. Departamento de Biología Molecular

مصطلحات موضوعية: Adult, adult stem cells, animals, epidermal growth factor, glycogen synthase kinase 3, hippocampus, humans, mammals, mice, neural stem cells, neurogenesis, neurons, Biología y Biomedicina / Biología

الوصف: In the adult mammalian brain, neural stem cells (NSCs) located in highly restricted niches sustain the generation of new neurons that integrate into existing circuits. A reduction in adult neurogenesis is linked to ageing and neurodegeneration, whereas dysregulation of proliferation and survival of NSCs have been hypothesized to be at the origin of glioma. Thus, unravelling the molecular underpinnings of the regulated activation that NSCs must undergo to proliferate and generate new progeny is of considerable relevance. Current research has identified cues promoting or restraining NSCs activation. Yet, whether NSCs depend on external signals to survive or if intrinsic factors establish a threshold for sustaining their viability remains elusive, even if this knowledge could involve potential for devising novel therapeutic strategies. Kidins220 (Kinase D-interacting substrate of 220 kDa) is an essential effector of crucial pathways for neuronal survival and differentiation. It is dramatically altered in cancer and in neurological and neurodegenerative disorders, emerging as a regulatory molecule with important functions in human disease. Herein, we discover severe neurogenic deficits and hippocampal-based spatial memory defects accompanied by increased neuroblast death and high loss of newly formed neurons in Kidins220 deficient mice. Mechanistically, we demonstrate that Kidins220-dependent activation of AKT in response to EGF restraints GSK3 activity preventing NSCs apoptosis. We also show that NSCs with Kidins220 can survive with lower concentrations of EGF than the ones lacking this molecule. Hence, Kidins220 levels set a molecular threshold for survival in response to mitogens, allowing adult NSCs growth and expansion. Our study identifies Kidins220 as a key player for sensing the availability of growth factors to sustain adult neurogenesis, uncovering a molecular link that may help paving the way towards neurorepair ; This work was funded by grants RYC2014-15991 (MINECO/ESF), SAF2015-67756-R (MCIN/AEI ...

وصف الملف: application/pdf

العلاقة: Cell Death and Disease; https://doi.org/10.1038/s41419-023-05995-7Test; Gobierno de España. AEI /10.13039/501100011033; Gobierno de España. PID2019-104763RB-I00; Gobierno de España. PID2020-115218RB-I00; Gobierno de España. PID2020-117937GB-I00; Gobierno de España. PID2020-115217RB-I00; Cell Death and Disease 14.8 (2023): 500; http://hdl.handle.net/10486/712194Test; 500-1; 500-17; 14

الإتاحة: https://doi.org/10.1038/s41419-023-05995-7Test
http://hdl.handle.net/10486/712194Test

المؤلفون: Pose Utrilla, Julia, García Guerra, Lucía, Del Puerto, Ana, Martín, Abraham, Jurado Arjona, Jerónimo, De León-Reyes, Noelia S., Gamir Morralla, Andrea, Sebastián Serrano, Álvaro, García Gallo, Mónica, Kremer, Leonor, Fielitz, Jens, Ireson, Christofer, Pérez Álvarez, Mª José, Ferrer, Isidro, Hernández Pérez, Félix, Ávila, Jesús, Lasa Benito, Marina Paloma, Campanero, Miguel R., Iglesias, Teresa

المساهمون: UAM. Departamento de Bioquímica

مصطلحات موضوعية: Medicina

الوصف: Excitotoxicity, a critical process in neurodegeneration, induces oxidative stress and neuronal death through mechanisms largely unknown. Since oxidative stress activates protein kinase D1 (PKD1) in tumor cells, we investigated the effect of excitotoxicity on neuronal PKD1 activity. Unexpectedly, we find that excitotoxicity provokes an early inactivation of PKD1 through a dephosphorylation-dependent mechanism mediated by protein phosphatase-1 (PP1) and dual specificity phosphatase-1 (DUSP1). This step turns off the IKK/NF-κB/SOD2 antioxidant pathway. Neuronal PKD1 inactivation by pharmacological inhibition or lentiviral silencing in vitro, or by genetic inactivation in neurons in vivo, strongly enhances excitotoxic neuronal death. In contrast, expression of an active dephosphorylation-resistant PKD1 mutant potentiates the IKK/NF-κB/SOD2 oxidative stress detoxification pathway and confers neuroprotection from in vitro and in vivo excitotoxicity. Our results indicate that PKD1 inactivation underlies excitotoxicity-induced neuronal death and suggest that PKD1 inactivation may be critical for the accumulation of oxidation-induced neuronal damage during aging and in neurodegenerative disorders ; This work was supported by grants SAF2014-52737-P to T.I., SAF2013-45258-P to M.R. C., BFU2016-77885-P to F.H., SAF2014-54070-JIN to A.M. from Ministerio de Economía, Industria y Competitividad (Spain). It was also funded by P2010/BMD-2332 (Neurodegmodels) from Comunidad de Madrid to T.I., F.H. and J.A.) and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, Instituto de Salud Carlos III, Spain) to T.I., F.H., J.A., and I.F.). J.P.-U. is a recipient of a predoctoral contract from SAF2014-52737-P; L.G.-G. was funded by a contract from CIBERNED; A.G.-M. and A.S.S. were funded by contracts from CIBERNED cooperative projects 2013/07 and CIBERNED 2015-2/06, respectively. A.M., A.D.P. is a recipient of a Juan de la Cierva formación fellowship (Ministerio de Economía, Industria y Competitividad, ...

وصف الملف: application/pdf

العلاقة: Nature Communications; https://doi.org/10.1038/s41467-017-02322-5Test; Comunidad de Madrid. P2010/BMD-2332; Nature Communications 8 (2017): 2275; 2041-1723 (online); http://hdl.handle.net/10486/711352Test; 2275-1; 2275-18

الإتاحة: https://doi.org/10.1038/s41467-017-02322-5Test
http://hdl.handle.net/10486/711352Test

المؤلفون: Cilleros-Rodríguez, Darío, Toledo-Lobo, María Val, Martínez-Martínez, Desirée, Baquero, Pablo, Angulo, Javier C., Chiloeches, Antonio, Iglesias, Teresa, Lasa, Marina

المصدر: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ; volume 1870, issue 1, page 166851 ; ISSN 0925-4439

مصطلحات موضوعية: Molecular Biology, Molecular Medicine

الإتاحة: https://doi.org/10.1016/j.bbadis.2023.166851Test
https://api.elsevier.com/content/article/PII:S092544392300217X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S092544392300217X?httpAccept=text/plainTest

المؤلفون: Warren, Dan L, Eytan, Ron I, Dornburg, Alex, Iglesias, Teresa L, Brandley, Matthew C, Wainwright, Peter C

المصدر: Ecology and Evolution. 11(16)

مصطلحات موضوعية: Biological Sciences, Ecology, Genetics, Life Below Water, Evolutionary Biology, Evolutionary biology, Ecological applications

الوصف: Allopatry has traditionally been viewed as the primary driver of speciation in marine taxa, but the geography of the marine environment and the larval dispersal capabilities of many marine organisms render this view somewhat questionable. In marine fishes, one of the earliest and most highly cited empirical examples of ecological speciation with gene flow is the slippery dick wrasse, Halichoeres bivittatus. Evidence for this cryptic or incipient speciation event was primarily in the form of a deep divergence in a single mitochondrial locus between the northern and southern Gulf of Mexico, combined with a finding that these two haplotypes were associated with different habitat types ("tropical" vs. "subtropical") in the Florida Keys and Bermuda, where they overlap. Here, we examine habitat assortment in the Florida Keys using a broader sampling of populations and habitat types than were available for the original study. We find no evidence to support the claim that haplotype frequencies differ between habitat types, and little evidence to support any differences between populations in the Keys. These results undermine claims of ecological speciation with gene flow in Halichoeres bivittatus. Future claims of this type should be supported by multiple lines of evidence that illuminate potential mechanisms and allow researchers to rule out alternative explanations for spatial patterns of genetic differences.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4jv114tkTest

المؤلفون: Coll Iglesias, Teresa

المساهمون: University/Department: Universitat de Barcelona. Departament de Farmacologia i Química Terapèutica

مرشدي الرسالة: Laguna Egea, Juan Carlos, Vázquez Carrera, Manuel

المصدر: TDX (Tesis Doctorals en Xarxa)

مصطلحات موضوعية: PGC-1alfa, PPAR, Oleat miotub, Palmitat, Inflamació, Resistència a ia insulina, COX-2, Ciències de la Salut

الوصف: La Diabetis Mellitus tipus 2 (DM2) és una malaltia metabòlica complexa que afecta entre un 4 i un 5% de la població en les societats industrialitzades. Aquesta patologia es caracteritza per la presència, en la seva fase inicial, de resistència a la insulina (RI). Freqüentment, una de les primeres alteracions que s´observen en els individus amb predisposició a patir RI/DM2 és l´acumulació de grassa intraabdominal. De fet, la relació epidemiològica entre l´obesitat i la RI és molt sòlida. A més, en l´última dècada nombroses evidències han posat de manifest l´existència d´una estreta relació entre un estat d´inflamació crònic de baixa intensitat i la presència d´obesitat-RI-DM2. De tota manera, tot i que el vincle entre l´increment d´àcids grassos lliures en plasma i la diabetis està ben acceptat, els mecanismes implicats en l´aparició de RI i DM2 induïdes per aquests àcids grassos no són ben coneguts. Per aquest motiu, l´objectiu d´aquesta tesi doctoral ha estat aprofundir en els mecanismes implicats en l´aparició de RI induïda per l´àcid gras saturat palmitat i estudiar la funció de l´enzim COX-2 en aquestes condicions, així com també determinar la capacitat de l´àcid gras monoinsaturat oleat i de l´agonista PPARdelta GW501516 per a prevenir la inflamació i la RI induïdes pel palmitat en miotubs de ratolí C2C12.Els estudis realitzats indiquen que la presència elevada de l´àcid gras saturat palmitat provoca una disminució de PGC-1alfa(coactivador que controla l´expressió de gens mitocondrials) a través de l´activació de la via ERK-MAPK-NF-kB, així com també l´acumulació de diacilglicerol intramiocel·lular, fent que apareguin estats d´inflamació i RI. A més, s´ha observat que un augment agut de determinats marcadors inflamatoris, com la COX-2, contribueixen a resoldre aquest procés inflamatori generat per l´acumulació de lípids, tot i que la seva presència de manera crònica accentua l´estat inflamatori. Segons hem pogut constatar amb el nostre model in vitro de RI, l´àcid gras monoinsaturat oleat i el GW501516 podrien ser dues noves possibilitats terapèutiques per evitar la inflamació induïda per àcids grassos i millorar la sensibilitat a la insulina, ja que tenen la capacitat d´incrementar la beta-oxidació mitocondrial impedint així que s´acumulin metabolits lipotòxics com el diacilglicerol.

الوصف (مترجم): Insulin resistance (IR) is a major characteristic of type 2 diabetes mellitus and is also associated with obesity. Impairment of glucose utilization and insulin sensitivity has been related to the presence of high free fatty acids in plasma and a low-grade chronic systemic inflammation. However, the mechanisms by which free fatty results in inflammation and IR are not well understood. After exposing C2C12 cells (mouse myotubes) to the saturated fatty acid palmitate, we observed, on the one hand, a reduction in PGC-1-alpha gene expression through the activation of ERK-MAPK-NF-kB pathway, and on the other hand, an increase in diacylglycerol accumulation. Moreover, we observed that the presence of palmitate increased COX-2 expression, which seems to contribute to resolve the acute, but not chronic, inflammation. Our in vitro model of IR also showed that the monounsaturated fatty acid oleate and the PPAR-delta agonist GW501516, could avoid the development of inflammation and IR induced by fatty acids through an increase in mitochondrial beta-oxidation, thus preventing the accumulation of lipotoxic metabolites, such as dicylglycerol.

وصف الملف: application/pdf

الوصول الحر: http://www.tdx.cat/TDX-1104109-105738Test
http://hdl.handle.net/10803/1644Test

المؤلفون: Queirós, Ângela, Coelho, Maria de Fátima, Iglesias, Teresa Perez

المساهمون: Repositório Científico do Instituto Politécnico do Porto

مصطلحات موضوعية: Nanoparticles, Nanofluids, Stability, Copper oxide

الوصف: (Introduction) Due to the physical properties of nanoparticles and their tendency to aggregate and form clusters, the stability of nanofluids is controversial and demanding. Different techniques are used to improve stability and nanofluids. Sonication with probe has been shown to be the technique that improve nanofluid stability. Thus, following our study [1-5] in this work the stability of copper oxide (40 nm) nanoproperties in water is studied. As not to mask the effect of the nanoparticles the experimental data were carried out without addition of surfactants.

وصف الملف: application/pdf

العلاقة: Queirós, A., Coelho, M.F., &, Iglesias, T.P. (2023, Junho 13-16). Stability study of copper oxide nanofluids in water for different sonication times [Poster presentation]. IV Congresso Digital de Nanobiotecnologia e Bioengenharia, Online

الإتاحة: http://hdl.handle.net/10400.22/25233Test

المؤلفون: Queirós, Ângela, Coelho, M. Fátima, Iglesias, Teresa P.

المساهمون: Repositório Científico do Instituto Politécnico do Porto

مصطلحات موضوعية: Thermophysical properties

الوصف: (Excerpt of introduction) At nanometric scale the materials present properties distinctively different from those in the bulk. The literature has shown that the main factors involved in the behavior of their thermophysical properties are the size, morphology, and content of nanoparticles, the purity of the base fluid and also the possibility of addition of surfactnts. From a fundamental standpoint, it is discussed whether the positive values of p/pw, fig 1, can be considered greater than what would be expected. (...)

وصف الملف: application/pdf

العلاقة: Queirós, A., Coelho, M.F., & Iglesias, T.P. (2023, September 10-13). Density of aqueous alumina (15nm) nanofluids at different temperatures [Poster]. ECTP 2023 - 22nd European Conference on Thermophysical Properties, Venice, Italy

الإتاحة: http://hdl.handle.net/10400.22/25201Test

المؤلفون: Del Puerto, Ana, Lopez-Fonseca, Coral, Simón-García, Ana, Martí-Prado, Beatriz, Barrios-Muñoz, Ana L, Pose-Utrilla, Julia, López-Menéndez, Celia, Alcover-Sanchez, Berta, Cesca, Fabrizia, Schiavo, Giampietro, Campanero, Miguel R, Fariñas, Isabel, Iglesias, Teresa, Porlan, Eva

المساهمون: Del Puerto, Ana, Lopez-Fonseca, Coral, Simón-García, Ana, Martí-Prado, Beatriz, Barrios-Muñoz, Ana L, Pose-Utrilla, Julia, López-Menéndez, Celia, Alcover-Sanchez, Berta, Cesca, Fabrizia, Schiavo, Giampietro, Campanero, Miguel R, Fariñas, Isabel, Iglesias, Teresa, Porlan, Eva

مصطلحات موضوعية: Kidins220, neural stem cell, progenitor cell, neurogenesis

الوصف: In the adult mammalian brain, neural stem cells (NSCs) located in highly restricted niches sustain the generation of new neurons that integrate into existing circuits. A reduction in adult neurogenesis is linked to ageing and neurodegeneration, whereas dysregulation of proliferation and survival of NSCs have been hypothesized to be at the origin of glioma. Thus, unravelling the molecular underpinnings of the regulated activation that NSCs must undergo to proliferate and generate new progeny is of considerable relevance. Current research has identified cues promoting or restraining NSCs activation. Yet, whether NSCs depend on external signals to survive or if intrinsic factors establish a threshold for sustaining their viability remains elusive, even if this knowledge could involve potential for devising novel therapeutic strategies. Kidins220 (Kinase D-interacting substrate of 220 kDa) is an essential effector of crucial pathways for neuronal survival and differentiation. It is dramatically altered in cancer and in neurological and neurodegenerative disorders, emerging as a regulatory molecule with important functions in human disease. Herein, we discover severe neurogenic deficits and hippocampal-based spatial memory defects accompanied by increased neuroblast death and high loss of newly formed neurons in Kidins220 deficient mice. Mechanistically, we demonstrate that Kidins220-dependent activation of AKT in response to EGF restraints GSK3 activity preventing NSCs apoptosis. We also show that NSCs with Kidins220 can survive with lower concentrations of EGF than the ones lacking this molecule. Hence, Kidins220 levels set a molecular threshold for survival in response to mitogens, allowing adult NSCs growth and expansion. Our study identifies Kidins220 as a key player for sensing the availability of growth factors to sustain adult neurogenesis, uncovering a molecular link that may help paving the way towards neurorepair.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/37542079; info:eu-repo/semantics/altIdentifier/wos/WOS:001042568300006; volume:14/2023; issue:8; firstpage:1; lastpage:17; numberofpages:17; journal:CELL DEATH & DISEASE; https://hdl.handle.net/11368/3056938Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85166597417; https://www.nature.com/articles/s41419-023-05995-7Test

الإتاحة: https://doi.org/10.1038/s41419-023-05995-7Test
https://hdl.handle.net/11368/3056938Test
https://www.nature.com/articles/s41419-023-05995-7Test

المؤلفون: Martínez, Natalia, Gragera, Teresa, de Lucas, María Pilar, Cámara, Ana Belén, Ballester, Alicia, Anta, Berta, Fernández Medarde, Alberto, López-Briones, Tania, Ortega, Judith, Peña-Jiménez, Daniel, Barbáchano, Antonio, Montero-Calle, Ana, Cordero, Víctor, Barderas, Rodrigo, Iglesias, Teresa, Yunta, Mónica, Oliva, José Luís, Muñoz, Alberto, Santos de Dios, Eugenio Miguel, Zarich, Natasha, Rojas-Cabañeros, José M.

مصطلحات موضوعية: PKD, COP9/Signalosome, Spry2, Protein stability, 14-3-3 Proteins, proteínas 14-3-3, cancerinismo

الوصف: Article number: 20 (2023) ; [ES]Spry2 es un modulador molecular de las vías de señalización de receptores tirosina quinasa que tiene efectos específicos de cada tipo de cáncer. La proteína Spry2 de mamíferos sufre fosforilación de tirosina y serina en respuesta a la estimulación por factores de crecimiento, y la expresión de Spry2 está claramente alterada en varios tipos de cáncer. La inhibición de la funcionalidad del proteasoma da como resultado una menor degradación intracelular de Spry2. Utilizando ensayos in vitro e in vivo, mostramos que la proteína quinasa D (PKD) fosforila Spry2 en la serina 112 e interactúa in vivo con la mitad C-terminal de esta proteína. Es importante destacar que la mutación sin sentido en Ser112 disminuye la tasa de degradación de la proteína intracelular Spry2. Reducir la expresión de las tres isoformas de PKD de los mamíferos o bloquear su actividad quinasa con un inhibidor específico contribuye a la estabilización de la proteína Spry2 endógena. La regulación negativa mediante CSN3, un componente del COP9/Signalosoma que se une a la PKD, aumenta significativamente la vida media de la proteína Spry2 endógena, pero no afecta la estabilidad de un Spry2 después de mutar Ser112 al residuo alanina no fosforilable. Nuestros datos demuestran que tanto PKD como COP9/Signalosoma desempeñan un papel importante en el control de la estabilidad intracelular de Spry2 y respaldan la consideración del complejo PKD/COP9 como un objetivo terapéutico potencial en tumores donde se reduce la expresión de Spry2. ; [EN]Spry2 is a molecular modulator of tyrosine kinase receptor signaling pathways that has cancer-type-specific effects. Mammalian Spry2 protein undergoes tyrosine and serine phosphorylation in response to growth factor stimulation. Spry2 expression is distinctly altered in various cancer types. Inhibition of the proteasome functionality results in reduced intracellular Spry2 degradation. Using in vitro and in vivo assays, we show that protein kinase D (PKD) phosphorylates Spry2 at serine 112 ...

العلاقة: https://doi.org/10.1038/s41389-023-00465-3Test; PI19/00934; Martínez, N., Gragera, T., de Lucas, M. P., Cámara, A. B., Ballester, A., Anta, B., . & Rojas-Cabañeros, J. M. (2023). PKD phosphorylation and COP9/Signalosome modulate intracellular Spry2 protein stability. Oncogenesis, 12(1), 20. doi:10.1038/s41389-023-00465-3; http://hdl.handle.net/10366/156457Test

الإتاحة: https://doi.org/10.1038/s41389-023-00465-3Test
http://hdl.handle.net/10366/156457Test

المؤلفون: García-Bonilla, María, Ojeda-Pérez, Betsaida, Shumilov, Kirill, Rodríguez-Pérez, Luis Manuel, Domínguez-Pinos, Dolores, Vitorica Ferrández, Javier, Jiménez, Sebastián, Ramírez-Lorca, Reposo, Echevarría, Miriam, Cárdenas García, Casimiro, Iglesias, Teresa, Gutiérrez-Pérez, Antonia, McAllister, James P. (II), Limbrick, David D. (Jr.), Páez-González, Patricia, Jiménez-Lara, Antonio Jesús

مصطلحات موضوعية: Hidrocefalia -- Tratamiento, Células madre -- Uso terapéutico, Terapia celular, Medicina regenerativa, Experimentación animal, Hydrocephalus, Aquaporin 4, Astrocyte reaction, Mesenchymal stem cell, Stem cell therapy, Proteomic

الوصف: Aquaporin-4 (AQP4) plays a crucial role in brain water circulation and is considered a therapeutic target in hydrocephalus. Congenital hydrocephalus is associated with a reaction of astrocytes in the periventricular white matter both in experimental models and human cases. A previous report showed that bone marrow-derived mesenchymal stem cells (BM-MSCs) transplanted into the lateral ventricles of hyh mice exhibiting severe congenital hydrocephalus are attracted by the periventricular astrocyte reaction, and the cerebral tissue displays recovery. The present investigation aimed to test the effect of BM-MSC treatment on astrocyte reaction formation. BM-MSCs were injected into the lateral ventricles of four-day-old hyh mice, and the periventricular reaction was detected two weeks later. A protein expression analysis of the cerebral tissue differentiated the BM-MSC-treated mice from the controls and revealed effects on neural development. In in vivo and in vitro experiments, BM-MSCs stimulated the generation of periventricular reactive astrocytes overexpressing AQP4 and its regulatory protein kinase D-interacting substrate of 220 kDa (Kidins220). In the cerebral tissue, mRNA overexpression of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 (HIF1α), and transforming growth factor beta 1 (TGFβ1) could be related to the regulation of the astrocyte reaction and AQP4 expression. In conclusion, BM-MSC treatment in hydrocephalus can stimulate a key developmental process such as the periventricular astrocyte reaction, where AQP4 overexpression could be implicated in tissue recovery. ; The present work was supported by grants PI15/00619 and PI19/00778 (to A.J.J. and P.P.-G.), PI21/000914 (to J.V.) and PI21/000915 (to A.G.) from the Instituto de Salud Carlos III, Spain, co-financed by FEDER funds from the European Union; PI18-RT-2233 from Junta de Andalucía (to A.G.) co-financed by Programa Operativo FEDER 2014–2020; PID2020-115218RB-I00 to T.I., funded by ...

العلاقة: García-Bonilla M, Ojeda-Pérez B, Shumilov K, Rodríguez-Pérez L-M, Domínguez-Pinos D, Vitorica J, Jiménez S, Ramírez-Lorca R, Echevarría M, Cárdenas-García C, Iglesias T, Gutiérrez A, McAllister JP II, Limbrick DD Jr., Páez-González P, Jiménez AJ. Generation of Periventricular Reactive Astrocytes Overexpressing Aquaporin 4 Is Stimulated by Mesenchymal Stem Cell Therapy. International Journal of Molecular Sciences. 2023; 24(6):5640. https://doi.org/10.3390/ijms24065640Test; https://hdl.handle.net/10630/26802Test

الإتاحة: https://doi.org/10.3390/ijms24065640Test
https://hdl.handle.net/10630/26802Test