Human cerebral organoids and neural 3D tissues in basic research, and their application to study neurological diseases

descripción no proporcionada por scopusSpanish Ministry of Science, Economy and Competitiveness, call Retos, Ref: SAF2017-83241-R

Functionalization and Characterization of Magnetic Nanoparticles for the Detection of Ferritin Accumulation in Alzheimer's Disease

Early diagnosis in Alzheimer's disease (AD), prior to the appearance of marked clinical symptoms, is critical to prevent irreversible neuronal damage and neural malfunction that lead to dementia and death. Therefore, there is an urgent need to generate new contrast agents which reveal by a noninvasive method the presence of some of the pathological signs of AD. In the present study, we demonstrate for the first time a new nanoconjugate composed of magnetic nanoparticles bound to an antiferritin antibody, which has been developed based on the existence of iron deposits and high levels of the ferritin protein present in areas with a high accumulation of amyloid plaques (particularly the subiculum in the hippocampal area) in the brain of a transgenic mouse model with five familial AD mutations. Both in vitro and after intravenous injection, functionalized magnetic nanoparticles were able to recognize and bind specifically to the ferritin protein accumulated in the subiculum area of the AD transgenic mice.Fil: Fernández Cabada, Tamara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Politécnica de Madrid; EspañaFil: Martínez Serrano, Alberto. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; EspañaFil: Cussó, Lorena. Instituto de Investigacion Sanitaria Gregorio Marañón; España. Universidad Carlos III de Madrid; España. Centro de Investigación Biomédica en Red de Salud Mental; EspañaFil: Desco, Manuel. Instituto de Investigacion Sanitaria Gregorio Marañón; España. Centro de Investigación Biomédica en Red de Salud Mental; España. Universidad Carlos III de Madrid; EspañaFil: Ramos Gómez, Milagros. Universidad Politécnica de Madrid; Españ

Multifactoriality of Parkinson’s disease as explored through human neural stem cells and their transplantation in middle-aged parkinsonian mice

Parkinson’s disease (PD) is an age-associated neurodegenerative disorder for which there is currently no cure. Cell replacement therapy is a potential treatment for PD; however, this therapy has more clinically beneficial outcomes in younger patients with less advanced PD. In this study, hVM1 clone 32 cells, a line of human neural stem cells, were characterized and subsequently transplanted in middle-aged Parkinsonian mice in order to examine cell replacement therapy as a treatment for PD. In vitro analyses revealed that these cells express standard dopamine-centered markers as well as others associated with mitochondrial and peroxisome function, as well as glucose and lipid metabolism. Four months after the transplantation of the hVM1 clone 32 cells, striatal expression of tyrosine hydroxylase was minimally reduced in all Parkinsonian mice but that of dopamine transporter was decreased to a greater extent in buffer compared to cell-treated mice. Behavioral tests showed marked differences between experimental groups, and cell transplant improved hyperactivity and gait alterations, while in the striatum, astroglial populations were increased in all groups due to age and a higher amount of microglia were found in Parkinsonian mice. In the motor cortex, nonphosphorylated neurofilament heavy was increased in all Parkinsonian mice. Overall, these findings demonstrate that hVM1 clone 32 cell transplant prevented motor and non-motor impairments and that PD is a complex disorder with many influencing factors, thus reinforcing the idea of novel targets for PD treatment that tend to be focused on dopamine and nigrostriatal damag

Group i metabotropic glutamate receptors: A potential target for regulation of proliferation and differentiation of an immortalized human neural stem cell line

© 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Human neural stem cells (NSCs) from the developing embryo or the subventricular zone of the adult brain can potentially elicit brain repair after injury or disease, either via endogenous cell proliferation or by cell transplantation. Profound knowledge of the diverse signals affecting these cells is, however, needed to realize their therapeutic potential. Glutamate and group I metabotropic glutamate receptors (mGluRs) affect proliferation and survival of rodent NSCs both during embryonic and post-natal development. To investigate the role of group I mGluRs (mGluR1 and mGluR5) on human NSCs, we differentiated an immortalized, forebrain-derived stem cell line in the presence or absence of glutamate and with addition of either the group I mGluR agonist DHPG or the selective antagonists, MPEP (mGluR5) and LY367385 (mGluR1). Characterization of differentiated cells revealed that both mGluR1 and mGluR5 were present on the cells. Addition of glutamate to the growth medium significantly increased cell proliferation and reduced cell death, resulting in increased cell numbers. In the presence of glutamate, selective activation of group I mGluRs reduced gliogenesis, whereas selective inhibition of group I mGluRs reduced neurogenesis. Our results substantiate the importance of glutamate signalling in the regulation of human NSCs and may as such be applied to promote proliferation and neuronal differentiation.This research was supported by the Danish Parkinson Association, IMK Almene Fond, Hørslev-Fonden, Kirsten og Freddy Johansens Fond, Grosserer Brogaard og Hustrus Mindefond and Fonden for Lægevidenskabens Fremme.Peer Reviewe

V-Myc immortalizes human neural stem cells in the absence of pluripotency-associated traits

© 2015 Pino-Barrio et al. A better understanding of the molecular mechanisms governing stem cell self-renewal will foster the use of different types of stem cells in disease modeling and cell therapy strategies. Immortalization, understood as the capacity for indefinite expansion, is needed for the generation of any cell line. In the case of v-myc immortalized multipotent human Neural Stem Cells (hNSCs), we hypothesized that v-myc immortalization could induce a more dedifferentiated state in v-myc hNSC lines. To test this, we investigated the expression of surface, biochemical and genetic markers of stemness and pluripotency in v-myc immortalized and control hNSCs (primary precursors, that is, neurospheres) and compared these two cell types to human Embryonic Stem Cells (hESCs) and fibroblasts. Using a Hierarchical Clustering method and a Principal Component Analysis (PCA), the v-myc hNSCs associated with their counterparts hNSCs (in the absence of v-myc) and displayed a differential expression pattern when compared to hESCs. Moreover, the expression analysis of pluripotency markers suggested no evidence supporting a reprogramming-like process despite the increment in telomerase expression. In conclusion, v-myc expression in hNSC lines ensures self-renewal through the activation of some genes involved in the maintenance of stem cell properties in multipotent cells but does not alter the expression of key pluripotency-associated genes.Spanish Ministry of Economy and Competitiveness (PLE2009–0101, SAF2010–17167); Comunidad Autónoma Madrid (S2011—BMD—2336); Instituto Salud Carlos III (RETICS TerCel, RD12/0019/0013) and European Union (Excell, NMP4—SL—2008–214706); (to PM): Instituto Salud Carlos III (RETICS TerCel, RD12/0019/0006; FISPeer Reviewe

Evaluation of MIRACLE approach results for CLEF 2003

This paper describes MIRACLE (Multilingual Information RetrievAl for the CLEf campaign) approach and results for the mono, bi and multilingual Cross Language Evaluation Forum tasks. The approach is based on the combination of linguistic and statistic techniques to perform indexing and retrieval tasks

V-Myc immortalizes human neural stem cells in the absence of pluripotency-associated traits

The data discussed in this publication have been deposited in NCBI’s Gene Expression Omnibus (GEO) and are accessible through GEO Series accession number GSE63710A better understanding of the molecular mechanisms governing stem cell self-renewal will foster the use of different types of stem cells in disease modeling and cell therapy strategies. Immortalization, understood as the capacity for indefinite expansion, is needed for the generation of any cell line. In the case of v-myc immortalized multipotent human Neural Stem Cells (hNSCs), we hypothesized that v-myc immortalization could induce a more dedifferentiated state in v-myc hNSC lines. To test this, we investigated the expression of surface, biochemical and genetic markers of stemness and pluripotency in v-myc immortalized and control hNSCs (primary precursors, that is, neurospheres) and compared these two cell types to human Embryonic Stem Cells (hESCs) and fibroblasts. Using a Hierarchical Clustering method and a Principal Component Analysis (PCA), the v-myc hNSCs associated with their counterparts hNSCs (in the absence of v-myc) and displayed a differential expression pattern when compared to hESCs. Moreover, the expression analysis of pluripotency markers suggested no evidence supporting a reprogramming-like process despite the increment in telomerase expression. In conclusion, v-myc expression in hNSC lines ensures self-renewal through the activation of some genes involved in the maintenance of stem cell properties in multipotent cells but does not alter the expression of key pluripotency-associated genesThis work was supported by grants from (to AMS): Spanish Ministry of Economy and Competitiveness (PLE2009–0101, SAF2010–17167), Comunidad Autónoma Madrid (S2011—BMD— 2336), Instituto Salud Carlos III (RETICS TerCel, RD12/0019/0013) and European Union (Excell, NMP4—SL—2008–214706); (to PM): Instituto Salud Carlos III (RETICS TerCel, RD12/0019/0006; FIS P110/0449), ERANEt ISCIII—Fondos FEDER (PI12/ 03112) and the Spanish Association of Cancer Research (CIMEN2011). MJPB was funded by MINECO (PLE2009–0101) and Instituto Salud Carlos III (RETICS TerCel, RD06/0019/0023). This work was also supported by an institutional grant from Fundación Ramón Areces to the Center of Molecular Biology Severo Ochoa. PM lab is supported by: Instituto de Salud Carlos III (ISCIII; E-Rare-2 Call PI12/03112), Ministerio de Economía y Competitividad (MINECO; SAF2013-43065), Generalitat de Catalunya (SGR330) and Obra Social La Caixa-Fundaciò Josep Carrera

Thermo-economic analysis of an oxygen production plant powered by an innovative energy recovery system

[EN] Oxy-fuel combustion is considered an attractive alternative to reduce pollutant emissions, which uses high-purity oxygen mixed instead of air for combustion processes. However, purchasing large amounts of high-purity oxygen may be unprofitable for certain industrial sectors, discouraging its implementation. Considering this, the potential of an oxygen production cycle for factories using oxy-fuel combustion is studied by performing a thermo-economic analysis where high-purity oxygen, electricity, and natural gas prices are considered. Oxygen is produced by membrane means, where mixed ionic-electronic conducting membranes are used, which require high temperatures and pressure gradients to work properly. A set of turbochargers is implemented, chosen by scaling an off-the-shelf model, what introduces an innovative way of waste energy recovering for improving the performance of the cycle. The whole cycle is powered by waste heat from high temperature flue gases, and it is sized for a ceramic manufacturing factory. In this work, two cases are analysed, differentiated by considering additional heating and the vacuum generation method in the oxygen line. The first case exhibits smaller production levels, although better profitability (31¿€t¿1), whereas the second case displays higher production levels and production costs (33¿€t¿1). Both cases are competitive concerning the average price of high-purity oxygen, supposing an average of 50¿€t¿1 in wholesale markets, proving the potential of the proposed alternative for oxygen production.This research work has been supported by Grant PDC2021120821-I00 funded by MCIN/AEI/10.13039/501100011033 and by European Union NextGenerationEU/PRTR. This work has also been supported by Grant UPV-SOLGEN-79674 funded by the Vicerrectorado de Investigacion de la Universitat Politecnica de Valencia (PAID-11-21). The authors want to acknowledge the institution "Conselleria d'Educacio, Investigaci o, Cultura i Esport de la Generalitat Valenciana" and its grant program "Subvenciones para la contratacion de personal investigador de caracter predoctoral" for doctoral studies (ACIF/2020/246) funded by The European Union. Also, this work is part of grant number INNVA1/2021/38 funded by "Agencia Valenciana de la Innovacion (AVI)" and by "ERDF A way of making Europe".Serrano, J.; Arnau Martínez, FJ.; García-Cuevas González, LM.; Gutierrez, FA. (2022). Thermo-economic analysis of an oxygen production plant powered by an innovative energy recovery system. Energy. 255:1-18. https://doi.org/10.1016/j.energy.2022.12441911825