Governance and safety assessment

Depto. de Ciencia Política y de la AdministraciónFac. de Ciencias Políticas y SociologíaTRUEpu

Gene Therapy for Inherited Retinal and Optic Nerve Degenerations

Introduction: The eye is a target for investigational gene therapy due to the monogenic nature of many inherited retinal and optic nerve degenerations (IRD), its accessibility, tight blood-ocular barrier, the ability to non-invasively monitor for functional and anatomic outcomes, as well as its relative immune privileged state.Vectors currently used in IRD clinical trials include adeno-associated virus (AAV), small single-stranded DNA viruses, and lentivirus, RNA viruses of the retrovirus family. Both can transduce non-dividing cells, but AAV are non-integrating, while lentivirus integrate into the host cell genome, and have a larger transgene capacity. Areas covered: This review covers Leber’s congenital amaurosis, choroideremia, retinitis pigmentosa, Usher syndrome, Stargardt disease, Leber’s hereditary optic neuropathy, Achromatopsia, and X-linked retinoschisis. Expert opinion: Despite great potential, gene therapy for IRD raises many questions, including the potential for less invasive intravitreal versus subretinal delivery, efficacy, safety, and longevity of response, as well as acceptance of novel study endpoints by regulatory bodies, patients, clinicians, and payers. Also, ultimate adoption of gene therapy for IRD will require widespread genetic screening to identify and diagnose patients based on genotype instead of phenotype

Una experiència de partir de sí en un context educatiu

Dins deis credits del Master en Estudis de les dones, com a professores de I'assignatura de 'Subjectivitat, experiencia í saber docent', vam propasar per iniciar el trebaU partir de les experiencies que han estat significatives tant en positiu Gom en negatiu en la nostra trajeetoria educativa com a alumnes ¡ com a docents -en el cas de les que ha f055in-. Aquest text que ara presentem és fruit de j'etaboració de les idees que van sorgir en les primeres sessions en que vam compartir, professores i alumnes, les nas tres experiencies educatives1 Els temes més rellevants que van emergir fan referencia a!s tres aspectes que desenvolupem en el text: l'experiencla de partir de sí com a necessitat de nomenar-nos en primera persona; el sentlt de la mediació femenina en la relació educativa; l la negació com a subjectes en I'educació, la negació del desig

Lack of liver glycogen causes hepatic insulin resistance and steatosis in mice

Disruption of the Gys2 gene encoding the liver isoform of glycogen synthase generates a mouse strain (LGSKO) that almost completely lacks hepatic glycogen, has impaired glucose disposal, and is pre-disposed to entering the fasted state. This study investigated how the lack of liver glycogen increases fat accumulation and the development of liver insulin resistance. Insulin signaling in LGSKO mice was reduced in liver, but not muscle, suggesting an organ-specific defect. Phosphorylation of components of the hepatic insulin-signaling pathway, namely IRS1, Akt, and GSK3, was decreased in LGSKO mice. Moreover, insulin stimulation of their phosphorylation was significantly suppressed, both temporally and in an insulin dose response. Phosphorylation of the insulin-regulated transcription factor FoxO1 was somewhat reduced and insulin treatment did not elicit normal translocation of FoxO1 out of the nucleus. Fat overaccumulated in LGSKO livers, showing an aberrant distribution in the acinus, an increase not explained by a reduction in hepatic triglyceride export. Rather, when administered orally to fasted mice, glucose was directed toward hepatic lipogenesis as judged by the activity, protein levels, and expression of several fatty acid synthesis genes, namely, acetyl-CoA carboxylase, fatty acid synthase, SREBP1c, chREBP, glucokinase, and pyruvate kinase. Furthermore, using cultured primary hepatocytes, we found that lipogenesis was increased by 40% in LGSKO cells compared with controls. Of note, the hepatic insulin resistance was not associated with increased levels of pro-inflammatory markers. Our results suggest that loss of liver glycogen synthesis diverts glucose toward fat synthesis, correlating with impaired hepatic insulin signaling and glucose disposal

Discursos crítics, pràctiques ètiques. Repensant la funció docent a la Universitat

El nexe d'unió com a professores va ser a partir de la preocupació i reflexió que anavem compartint sobre les nostres practiques a l'aula. El que sovint ens preguntavem era com podíem assumir el compromís perqué els nostres pressuposits educatius no ens tra'issin a I'hora de posar-los a la practica. La recerca d'aquesta coheréncia va fer-nos plantejar, analitzar i compartir els nostres suposits, sobretot pel que fa al sentit i a la visió del coneixement que transmetem relacionats amb un tipus determinat d'entendre la practica, és a dir, d'entendre les relacions amb I'alumnat, el tipus de tasques que es realitzen a classe i els processos d'avaluació que portem a terme. El que plantejarem a continuació és fruit, com hem dit, de les converses i reflexions que periodicament compartíem, pero també de les valoracions que, de manera anomina, realitzava I'alumnat de les nostres classes i d'algunes observacions que ens féiem mútuament. Agruparem les nostres reflexions a partir d'explorar tres temes: la transmissió del saber, I'enfocament pedagogic de la practica i les dificultats o limitacions d'uns estils determinats d'ensenyanya

New Syntheses of rac-Huperzine A and its rac-7-Ethyl-Derivative. Evaluation of Several Huperzine A Analogues as Acetylcholinesterase Inhibitors

rac-Huperzine A, its rac-7-ethyl-derivative and two regioisomeric analogues have been prepared through synthetic sequences involving the elaboration of the pyridone ring in a late stage, by reaction of an intermediate pyrrolidine enamine with propiolamide, which gave mixtures of regioisomeric pyridone derivatives. The acetylcholinesterase inhibitory activity of these and two other recently described 11-unsubstituted huperzine A analogues was determined, the rac-7-ethyl analogue of huperzine A being the most active compound, although it is about 12-fold less active than (−)-huperzine A

Cuadernos de pedagogía

Resumen tomado de la revistaQuince mujeres se sienten en deuda con Ana Mañeru Méndez, antigua directora del Programa de Educación y Cultura del Instituto de la Mujer, y le agradecen, en este texto, el impulso para reencontrar su propia voz pedagógica, dialogar y compartir la posibilidad de crear y recrear vida desde la práctica educativa. La relación con ella les ha permitido 'ir viendo lo que no se ve y escuchando lo que apenas se escucha' y hoy lamentan profundamente su cese 'injustificado'.CataluñaES