28 research outputs found
Natural Hydrogels Support Kidney Organoid Generation and Promote in vitro Angiogenesis
To date strategies aiming to modulate cell to extracellular matrix (ECM) interactions during organoid derivation remain largely unexplored. Here renal decellularized extracellular matrix (dECM) hydrogels are fabricated from porcine and human renal cortex as biomaterials to enrich cell-to-ECM crosstalk during the onset of kidney organoid differentiation from human pluripotent stem cells (hPSCs). Renal dECM-derived hydrogels are used in combination with hPSC-derived renal progenitor cells to define new approaches for 2D and 3D kidney organoid differentiation, demonstrating that in the presence of these biomaterials the resulting kidney organoids exhibit renal differentiation features, and the formation of an endogenous vascular component. Based on these observations, a new method to produce kidney organoids with vascular-like structures is achieved through the assembly of hPSC-derived endothelial-like organoids with kidney organoids in 3D. Major readouts of kidney differentiation and renal cell morphology are assessed exploiting these culture platforms as new models of nephrogenesis. Overall, this work shows that exploiting cell-to-ECM interactions during the onset of kidney differentiation from hPSCs facilitates and optimizes current approaches for kidney organoid derivation thereby increasing the utility of these unique culture cell platforms for personalized medicine
Gipuzkoa in antiquity: languages and linguistic areas in the light of onomastics
Gaurko zenbait ikertzaileren iritziz, dagoen informazioa urria eta zalantzazkoa izan arren, ezagutzen den apurra aski da Antzinaroan Gipuzkoan latinaren aurreko hizkuntza indoeuropar (zelta) bat gailentzen zelako hipotesia proposatzeko. Lan honetan erromatar garaiko epigrafiatik zein geografo eta historialarien liburuetatik atera daitekeen informazioa modu bateratuan aztertzen dut, eta hura Erdi Aroko nahiz Aro Modernoko euskal onomastikarekin erkatzen, Gipuzkoako Antzinaroko hizkuntza egoeraren ezagutzan argi egiten laguntzeko, bai geografiaren aldetik, bai historiaren aldetik. Orobat, hizkuntza eta arkeologia arloko datuek norabide bera markatzen duten ikusten ahalegintzen naiz, kultura eremu bakarra edota bat baino gehiago zeuden antzematen saiatzeko.Some recent studies claim that a pre-Latin Indo-European (Celtic) language was predominant in Gipuzkoa during antiquity. However, the pertinent information available is scant and often questionable. Here we examine the data that can be drawn from Roman-era epigraphy as well as geographers’ and historians’ books in a unified fashion and compare these data with medieval and Modern Age Basque onomastics. The purpose is to shed light on the linguistic situation of Gipuzkoan antiquity from a geographic as well as historical perspective. In the same vein, we attempt to verify whether linguistic and archeological data point in the same direction, in order to determine the existence of one or several cultural areas
Rac1/p21-activated kinase pathway controls retinoblastoma protein phosphorylation and E2F transcription factor activation in B lymphocytes
Small GTPases of the Ras superfamily are capable of activating E2F-dependent transcription leading to cell proliferation, but the molecular mechanisms are poorly understood. In this study, using immortalized chicken DT40 B cell lines to investigate the role of the Vav/Rac signalling cascade on B cell proliferation, it is shown that the proliferative response triggered by B cell receptor activation is dramatically reduced in the absence of Vav3 expression. Analysis of this proliferative defect shows that in the absence of Vav3 expression, retinoblastoma protein (RB) phosphorylation and the subsequent E2F activation do not take place. By combining pharmacological and genetic approaches, phosphatidylinositol-3-kinase and phospholipase Cγ2 (PLCγ2) were identified as the key regulatory signalling molecules upstream of the Vav3/Rac pathway leading to RB phosphorylation and E2F transcription factor activation. Additionally, vav3(-/-) and plcγ2(-/-) DT40 B cells were not able to activate the RB-E2F complex wild-type phenotype when these genetically modified cells were transfected with constitutively active forms of RhoA or Cdc42. However, when these knockout cells were transfected with different constitutively active versions of PLCγ, Vav or Rac1, not only activation of the RB-E2F complex wild-type phenotype was recovered but also the cellular proliferation. Furthermore, by evaluating the effect of two known effector mutants of Rac1 (Rac1(Q61L/F37A) and Rac1(Q61L/Y40C)), the RB-E2F complex activation dependency on p21-activated kinase (PAK) and protein kinase Cε (PKCε) activities was established, being independent of both actin cytoskeleton reorganization and Ras activity. These results suggest that PAK1 and PKCε may be potential therapeutic targets to stop uncontrolled B cell proliferation mediated by the Vav/Rac pathway.Fil: Zaldua, Natalia. Bizkaia Science and Technology Park; EspañaFil: LLavero, Francisco. Universidad del PaÃs Vasco; España. Bizkaia Science and Technology Park; EspañaFil: Artaso, Alain. Universidad del PaÃs Vasco; EspañaFil: Gálvez, Patricia. Technological Park of Health Sciences; EspañaFil: Lacerda, Hadriano M.. Bizkaia Science and Technology Park; EspañaFil: Parada, Luis Antonio. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Centro CientÃfico Tecnológico Conicet - Salta. Instituto de PatologÃa Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de PatologÃa Experimental; ArgentinaFil: Zugaza, José L.. Universidad del PaÃs Vasco; España. Bizkaia Science and Technology Park; Españ
Accelerating sustainable and economic development via industrial energy cooperation and shared services – A case study for three European countries
Publisher Copyright: © 2021 Elsevier LtdThe European industry sector is responsible for about one-third of the EU's total energy consumption and process-related Greenhouse Gas emissions, which makes it a central factor in the EU's climate and energy strategies. Energy cooperation, i.e., the mutualised generation, use and/or acquisition of energy by at least two companies, has the potential of significantly supporting the successful achievement of these strategies. This paper presents a concept for moving from a single-company sustainable energy intervention approach to cooperative sustainable energy solutions within the framework of industrial parks. Technical, economic, regulatory, organizational, and social barriers for energy-efficient park design and operation on all levels and instruments to overcome them have been systematically analysed, taking correlation of solutions, and park-specific requirements into account, thus providing a holistic workflow. First results show that technical and economic attractiveness, and an enabling legal and policy context, are not always enough. For promising energy cooperation solutions to flourish, cultural, organizational, social, and behavioural factors also play a significant role. Furthermore, findings show that external facilitators are helpful to pool efforts to achieve greater engagement.The work leading to this research paper was out within the framework of the S-PARCS project which had received funding from the EU's Horizon 2020 research and innovation programme , under grant agreement no 785134 .Peer reviewe
Accelerating sustainable and economic development via industrial energy cooperation and shared services – A case study for three European countries
The European industry sector is responsible for about one-third of the EU's total energy consumption and process-related Greenhouse Gas emissions, which makes it a central factor in the EU's climate and energy strategies. Energy cooperation, i.e., the mutualised generation, use and/or acquisition of energy by at least two companies, has the potential of significantly supporting the successful achievement of these strategies. This paper presents a concept for moving from a single-company sustainable energy intervention approach to cooperative sustainable energy solutions within the framework of industrial parks. Technical, economic, regulatory, organizational, and social barriers for energy-efficient park design and operation on all levels and instruments to overcome them have been systematically analysed, taking correlation of solutions, and park-specific requirements into account, thus providing a holistic workflow. First results show that technical and economic attractiveness, and an enabling legal and policy context, are not always enough. For promising energy cooperation solutions to flourish, cultural, organizational, social, and behavioural factors also play a significant role. Furthermore, findings show that external facilitators are helpful to pool efforts to achieve greater engagement
Effect of selective cholinergic denervation on the serotonergic system: implications for learning and memory
The cholinergic system has been widely implicated in cognitive processes and cholinergic loss is a classical hallmark in Alzheimer disease. Increasing evidence supports a role of the serotonergic system in cognition, possibly through a modulation of cholinergic activity. We compared selective cholinergic denervation by administration of the immunotoxin 192 IgG-saporin in the nucleus basalis of Meynert (NBM) with intracerebroventricular (ICV) lesions of the basal forebrain in male rats 7 days after lesioning. NBM lesions induced significant changes in cholinergic markers in the frontal cortex, whereas ICV lesions produced significant decreases in cholinergic markers both in the frontal cortex and hippocampus. Only ICV lesions lead to memory impairments in passive avoidance and Morris water maze tasks. Both models lead to reductions of serotonin levels in the frontal cortex. Similar changes in 5-hydroxytriptophan levels were observed, suggesting a downregulation of the rate-limiting enzyme for the synthesis of serotonin along with the cholinergic deficit. Neither 5-HT1A nor 5-HT1B receptors seem to mediate this process. These data imply that the serotonergic system in the frontal cortex can compensate for diminished cholinergic function and support the investigation of the serotonergic system as a therapeutic target to treat Alzheimer disease