Estudio de la fusión celular en respuesta a diversas condiciones patológicas

La hipótesis de la fusión celular considera que una célula derivada de la médula ósea se fusiona con un precursor local o con una célula madura, transfiriendo su material genético y mezclando sus citoplasmas. La fusión celular supone un cambio conceptual en los campos de la terapia celular y de la genética, ya que las células de la médula, al fusionarse, aportarían material genético nuevo que podría permitir el rescate de una célula en proceso de degeneración, o corregir un defecto genético de la misma. Por tanto, la fusión celular posee un gran potencial terapéutico. Sin embargo, el papel de la fusión celular en el tratamiento de sintomatologías del sistema nervioso esta aun en fase de estudio. La fusión celular tiene como principal diana en el cerebro a las neuronas de Purkinje. La fusión celular en el cerebelo, al igual que ocurre en el hígado, podría revertir procesos degenerativos y rescatar mutaciones recesivas que afecten a las neuronas de Purkinje, como es el caso de algunas Ataxia. Por ello, en este trabajo hemos estudiado la fusión celular producida tras un trasplante de médula ósea en animales que presentan ataxia causada por la degeneración de neuronas de Purkinje. También hemos observado que, pese a la ausencia de eventos de fusión celular, se producen mejoras funcionales en el comportamiento de dichos animales. Por otra parte, la isquemia cerebral es la tercera causa de muerte en los países industrializados y constituye la principal causa de discapacidad en el adulto. Aunque se desconoce si el mecanismo de fusión celular también participa activamente en la recuperación y generación de tejido vascular tras la isquemia cerebral. Por ello en este trabajo hemos estudiado la fusión celular producida tras un trasplante de médula ósea bajo condiciones normales y tras un evento de isquemia cerebral. También hemos logrado caracterizar que los pericitos son el tipo celular que presenta mecanismos de fusión celular tanto en condiciones fisiológicas como tras un proceso isquémico. Por último, el proceso de fusión celular no se ha estudiado en detalle dentro del propio sistema hematopoyético, pese a que una de las parejas en los eventos de fusión es de este origen. Por ello hemos investigado en profundidad la presencia de eventos de fusión celular dentro de este sistema y comprobado que un proceso inflamatorio puede tener consecuencias en los niveles de fusión celular dentro del sistema hematopoyético

Transplant of GABAergic Precursors Restores Hippocampal Inhibitory Function in a Mouse Model of Seizure Susceptibility

16 páginas, 8 figuras.-- Licencia Creative Commons Reconocimiento-No comercial.Defects in GABAergic function can cause epilepsy. In the last years, cell-based therapies have attempted to correct these defects with disparate success on animal models of epilepsy. Recently, we demonstrated that medial ganglionic eminence (MGE)-derived cells grafted into the neonatal normal brain migrate and differentiate into functional mature GABAergic interneurons. These cells are able to modulate the local level of GABA-mediated synaptic inhibition, which suggests their suitability for cell-based therapies. However, it is unclear whether they can integrate in the host circuitry and rescue the loss of inhibition in pathological conditions. Thus, as proof of principle, we grafted MGE-derived cells into a mouse model of seizure susceptibility caused by specific elimination of GABAergic interneuron subpopulations in the mouse hippocampus after injection of the neurotoxic saporin conjugated to substance P (SSP-Sap). This ablation was associated with significant decrease in inhibitory postsynaptic currents (IPSC) on CA1 pyramidal cells and increased seizure susceptibility induced by pentylenetetrazol (PTZ). Grafting of GFP+ MGE-derived cells in SSP-Sap-treated mice repopulates the hippocampal ablated zone with cells expressing molecular markers of mature interneurons. Interestingly, IPSC kinetics on CA1 pyramidal cells of ablated hippocampus significantly increased after transplantation, reaching levels similar to the normal mice. More importantly, this was associated with reduction in seizure severity and decrease in postseizure mortality induced by PTZ. Our data show that MGE-derived cells fulfill most of the requirements for an appropriate cell-based therapy, and indicate their suitability for neurological conditions where a modulation of synaptic inhibition is needed, such as epilepsy.This work was supported by grants from Spanish Ministry of Science and Innovation (SAF 07/61880 and FIS 07/0079), and the Regenerative Medicine Programme from CIPF. M.E.C. and I.Z. were recipients of Miguel Servet contract from Carlos III Institute (Spanish Ministry of Science and Innovation) and Ph.D. fellowship from Generalitat Valenciana, respectively.Peer reviewe

Formación inicial docente en educación física a través del aprendizaje-servicio

A punto de arrancar la tercera década del siglo XXI es incuestionable que el aprendizaje-servicio (ApS) está conquistando, con paso firme, los distintos campus universitarios del escenario europeo. Esta realidad queda patente en los diferentes planes de formación e innovación docente, así como en el nacimiento y expansión de diversas iniciativas de investigación educativa (Chiva-Bartoll y Gil-Gómez, 2018 en prensa). Entre las principales definiciones de ApS destacan las de autores internacionales como Furco (2002) o Furco y Billig (2002), quienes lo definen como un método pedagógico caracterizado por imbricar el aprendizaje con la realización de un servicio social. Dicho método es protagonizado tanto por los estudiantes que ofrecen el servicio como por los colectivos sociales que lo reciben. Según estos autores, el ApS persigue la aplicación y desarrollo de las competencias educativas y la comprensión de los contenidos curriculares en contextos reales, de manera experiencial y con el objetivo de ofrecer un beneficio social

Transplant of GABAergic Precursors Restores Hippocampal Inhibitory Function in a Mouse Model of Seizure Susceptibility

Defects in GABAergic function can cause epilepsy. in the last years, cell-based therapies have attempted to correct these defects with disparate success on animal models of epilepsy. Recently, we demonstrated that medial ganglionic eminence (MGE)-derived cells grafted into the neonatal normal brain migrate and differentiate into functional mature GABAergic interneurons. These cells are able to modulate the local level of GABA-mediated synaptic inhibition, which suggests their suitability for cell-based therapies. However, it is unclear whether they can integrate in the host circuitry and rescue the loss of inhibition in pathological conditions. Thus, as proof of principle, we grafted MGE-derived cells into a mouse model of seizure susceptibility caused by specific elimination of GABAergic interneuron subpopulations in the mouse hippocampus after injection of the neurotoxic saporin conjugated to substance P (SSP-Sap). This ablation was associated with significant decrease in inhibitory postsynaptic currents (IPSC) on CA1 pyramidal cells and increased seizure susceptibility induced by pentylenetetrazol (PTZ). Grafting of GFP(+) MGE-derived cells in SSP-Sap-treated mice repopulates the hippocampal ablated zone with cells expressing molecular markers of mature interneurons. Interestingly, IPSC kinetics on CA1 pyramidal cells of ablated hippocampus significantly increased after transplantation, reaching levels similar to the normal mice. More importantly, this was associated with reduction in seizure severity and decrease in postseizure mortality induced by PTZ. Our data show that MGE-derived cells fulfill most of the requirements for an appropriate cell-based therapy, and indicate their suitability for neurological conditions where a modulation of synaptic inhibition is needed, such as epilepsy.Spanish Ministry of Science and InnovationCIPFCarlos III Institute (Spanish Ministry of Science and Innovation)Generalitat ValencianaAndalusian Ctr Mol Biol & Regenerat Med CABIMER, Dept Cell Therapy & Regenerat Med, Seville, SpainCIPF, Valencia, SpainUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilSpanish Ministry of Science and Innovation: SAF 07/61880Spanish Ministry of Science and Innovation: FIS 07/0079Web of Scienc

Stereodivergent addition of 4-Silyloxy-1,2-Allenes to aldehydes by hydroboration

We have established a new stereodivergent approach to 2-vinyl-1,3-diols based on a hydroboration of allene/addition of aldehyde tandem process. The stereocenter present next to the allenyl moiety (C1) in the starting allene effectively determines the configuration of the new formed carbinol (C3) whereas the relative configuration of C2 and C3 is determined by the configuration (E/Z) of the transient 2- alkenylborane intermediate. It should be noted that the order of mixing of the reagents and the kind of aldehyde used allowed us to obtain three out of the four possible diastereomers of the 1,3- diol

Oración que en las solemnes exequias ... por ... Don Fray Joaquín Company celebradas en 11 de marzo de 1815

SignaturizadoGrab. calc. en port. con esc. arzobispal y grab. alegórico en cabecera de p. 1, con letra inic. grabLa h. de grab. calc. es el retrato de Fray Joaquín Company, "Arzobispo antes de Zaragoza y después de Valencia": "J. Piquer lo dib. ; V. Capilla lo g.º

Cribado de Maltrato en urgencias, una asignatura pendiente

La detección del maltrato infantil es esencial para permitir una intervención adecuada destinada a mejorar la situación del paciente y prevenir la recurrencia. Los Servicios de Urgencias (SU) son la puerta de entrada principal al sistema sanitario de muchos pacientes; sin embargo, varios estudios han demostrado que la detección de maltrato es mejorable en urgencias1. La dificultad en el diagnóstico diferencial de muchas lesiones, que pueden confundirse con etiología accidental, infecciosa o neurológica, junto con la presión asistencial de los SU, favorece que en ocasiones pasen desapercibidos, con las potenciales consecuencias para el niño. A raíz de estas dificultades, se han desarrollado diferentes métodos de cribado que son de uso habitual en algunos países1, 2 pero no en España, donde se desconoce su aplicación. En este contexto, desde el Grupo de trabajo de maltrato de la Sociedad Española de Urgencias Pediátricas (SEUP) se ha llevado a cabo un estudio multicéntrico para valorar los métodos de cribado de maltrato utilizados en los SU pediátricos de España

Association between serum copper levels and risk of cardiovascular disease: A nested case-control study in the PREDIMED trial

Background and aim: Certain trace elements have been associated with increased cardiovascular risk. The aim of this study was to evaluate the association between serum copper (S-Cu) levels and the risk of a first event of cardiovascular disease (CVD) in a population of older adults with high cardiovascular risk. Methods and results: We conducted a case-control study nested within the PREDIMED trial. During a median follow-up of 4.8 years, a total of 207 incident cases diagnosed with CVD were matched for sex, age, and intervention group with 436 controls. Personal interviews, reviews of medical records, and validated questionnaires were used to assess known CVD risk factors. Biological serum samples were collected annually. Inductively coupled plasma mass spectrometry analysis was used to determine S-Cu levels. Adjusted odds ratios were calculated using multivariate conditional logistic regression models. All participants had S-Cu levels within the reference values, 750 μg/L to 1450 μg/L. Among men, but not among women, the mean S-Cu concentration was higher in cases 1014.1 μg/L than in controls 959.3 μg/L; (p = 0.004). In men, the multivariable-adjusted odds ratio for CVD was 2.36 (95% CI 1.07-5.20 for the comparison of the highest vs. the lowest quartile; p for trend = 0.02), in women, it was 0.43 (95% CI 0.11-1.70; p for trend = 0.165). Conclusion: In older Spanish men with high cardiovascular risk, a significant association was observed between high S-Cu levels, but still within the reference values, and an increased risk of a first event of CVD. Our findings suggest a sex difference in CVD risk and S-Cu levels. To confirm this relationship and to analyze the differences observed between men and women, further studies are needed

Analysis of the Ush2a Gene in Medaka Fish (Oryzias latipes)

Patients suffering from Usher syndrome (USH) exhibit sensorineural hearing loss, retinitis pigmentosa (RP) and, in some cases, vestibular dysfunction. USH is the most common genetic disorder affecting hearing and vision and is included in a group of hereditary pathologies associated with defects in ciliary function known as ciliopathies. This syndrome is clinically classified into three types: USH1, USH2 and USH3. USH2 accounts for well over one-half of all Usher cases and mutations in the USH2A gene are responsible for the majority of USH2 cases, but also for atypical Usher syndrome and recessive non-syndromic RP. Because medaka fish (Oryzias latypes) is an attractive model organism for genetic-based studies in biomedical research, we investigated the expression and function of the USH2A ortholog in this teleost species. Ol-Ush2a encodes a protein of 5.445 aa codons, containing the same motif arrangement as the human USH2A. Ol-Ush2a is expressed during early stages of medaka fish development and persists into adulthood. Temporal Ol-Ush2a expression analysis using whole mount in situ hybridization (WMISH) on embryos at different embryonic stages showed restricted expression to otoliths and retina, suggesting that Ol-Ush2a might play a conserved role in the development and/or maintenance of retinal photoreceptors and cochlear hair cells. Knockdown of Ol-Ush2a in medaka fish caused embryonic developmental defects (small eyes and heads, otolith malformations and shortened bodies with curved tails) resulting in late embryo lethality. These embryonic defects, observed in our study and in other ciliary disorders, are associated with defective cell movement specifically implicated in left-right (LR) axis determination and planar cell polarity (PCP)

Exposure to N-Ethyl-N-Nitrosourea in Adult Mice Alters Structural and Functional Integrity of Neurogenic Sites

BACKGROUND: Previous studies have shown that prenatal exposure to the mutagen N-ethyl-N-nitrosourea (ENU), a N-nitroso compound (NOC) found in the environment, disrupts developmental neurogenesis and alters memory formation. Previously, we showed that postnatal ENU treatment induced lasting deficits in proliferation of neural progenitors in the subventricular zone (SVZ), the main neurogenic region in the adult mouse brain. The present study is aimed to examine, in mice exposed to ENU, both the structural features of adult neurogenic sites, incorporating the dentate gyrus (DG), and the behavioral performance in tasks sensitive to manipulations of adult neurogenesis. METHODOLOGY/PRINCIPAL FINDINGS: 2-month old mice received 5 doses of ENU and were sacrificed 45 days after treatment. Then, an ultrastructural analysis of the SVZ and DG was performed to determine cellular composition in these regions, confirming a significant alteration. After bromodeoxyuridine injections, an S-phase exogenous marker, the immunohistochemical analysis revealed a deficit in proliferation and a decreased recruitment of newly generated cells in neurogenic areas of ENU-treated animals. Behavioral effects were also detected after ENU-exposure, observing impairment in odor discrimination task (habituation-dishabituation test) and a deficit in spatial memory (Barnes maze performance), two functions primarily related to the SVZ and the DG regions, respectively. CONCLUSIONS/SIGNIFICANCE: The results demonstrate that postnatal exposure to ENU produces severe disruption of adult neurogenesis in the SVZ and DG, as well as strong behavioral impairments. These findings highlight the potential risk of environmental NOC-exposure for the development of neural and behavioral deficits