Effects of lipopolysaccharide and abscisic acid on insulin signaling in SH-SY5Y cell line

Treball Final de Màster Universitari en Investigació en Cervell i Conducta. Codi: SBM024. Curs: 2020/2021.Insulin resistance is a pathophysiological mechanism closely related to neuroinflammation and present in many neurodegenerative diseases like Alzheimer's Disease. Under pathological conditions, abnormal increased phosphorylation of insulin receptor substrate 1 (IRS1) serine residues occurs, leading the disruption of the phosphoinositol 3-kinase/protein kinase B (PI3K/Akt) pathway and resulting in neuronal impairment. Lipopolysaccharide (LPS) is a proinflammatory molecule present in the outer cell wall of Gram-negative bacteria, which is recognized by microglial and neuronal tall-like receptors, thus leading neuroinflammation. Abscisic acid (ABA) is a sesquiterpene that has shown protective effects against peripheral insulin resistance, neuroinflammation and cognitive impairment. Besides, ABA has shown differentiation properties in glioblastoma cell line. In this study, we explored the effects of in vitro LPS and ABA administration on insulin signaling in neurons, acutely and chronically. In addition, we tested ABA as a neuronal differentiating stimulus on a neuroblastoma cell line. For that, functional assays were performed on the SH-SY5Y human neuroblastoma cell line. On the one hand, we pre-treated the cells with ABA (20 μM) and 20 hours later we administrated LPS (1μg/mL) acutely (24h). On the other hand, we treated cells chronically with LPS (1μg/mL) and ABA (20 μM) simultaneously for 5 days. Then, cells were treated with insulin (1 or 10 mU/mL) for 5 minutes and cell lysis was performed. Finally, we analyzed the phosphorylation of insulin signaling key proteins such as IRS1pTyr, IRS1pSer616, pAkt and pERK1/2 by western blot. Moreover, we analyzed qualitatively ABA and retinoic acid (RA, positive control) as neuronal differentiation stimuli in SH-SY5Y cell line by inverted optical microscope images. As a result, the comparison of groups (mean ± SEM) treated with LPS, ABA, ABA+LPS and negative control showed no significant differences in the phosphorylation of IRS1pTyr, IRS1pSer616, pAkt and pERk1/2 after insulin stimulation. On the other side, RA-treated neuroblastoma cells showed a differentiated phenotype, while ABA did not stimulate differentiation. Therefore, our data suggested that LPS did not affect insulin signaling, both acutely and chronically. Since there were no differences in terms of LPS administration, the neuroprotective effects of ABA against LPSinduced neuroinflammation could not be ascertained. Moreover, ABA did not display a neuronal differentiating stimulus on the human neuroblastoma cell line SH-SY5

Aprovechamiento de aguas pluviales

El objetivo principal del proyecto es poder establecer ciertos parámetros que permitan crear un protocolo de dimensionado de depósitos para riego de jardines urbanos. Centraremos el estudio en las zona de mayor concentración urbana de Catalunya, y se incluirán ejemplos prácticos de dimensionado de depósitos para pluviales en jardines urbanos. La diversidad de climas existentes en Catalunya permitirá extrapolar las conclusiones obtenidas a un territorio muy amplio, lo cual aumenta las posibilidades de una aplicación práctica efectiva

Relevancia dos traballos meteorolóxicos de Domingo Fontán Rodríguez

Although it is common to consider Domingo Fontán Rodríguez as a mathematician, politician, geographer, or cartographer, this personage also stood out in other fields of science such as meteorology. In this article we aim to show Fontán’s lesser known contributions in the field of meteorology, both inside and outside the University of Santiago de Compostela, as well as to go over his main biographical data.Aunque es habitual considerar a Domingo Fontán Rodríguez como matemático, político, geógrafo o cartógrafo, este personaje destacó también en otros campos de la ciencia como la meteorología. Pretendemos en este artículo mostrar las contribuciones menos conocidas de Fontán en el ámbito de la meteorología, tanto dentro de la Universidade de Santiago de Compostela como fuera de ella, además de recordar sus principales datos biográficos. [gl] Aínda que é habitual considerar a Domingo Fontán Rodríguez como matemático, político, xeógrafo ou cartógrafo, este persoeiro destacou tamén noutros campos da ciencia como a meteoroloxía. Pretendemos neste artigo amosar as achegas menos coñecidas de Fontán no ámbito da meteoroloxía, tanto dentro da Universidade de Santiago de Compostela como fóra dela, ademais de lembrar os seus principais datos biográficos

Actividade científica do matemático José Rodríguez González durante a súa estadía en Madrid (1819-1823)

Aínda que existen varias biografías sobre José Rodríguez González (1770-1824), natural da parroquia de Santa María de Bermés, bispado de Lugo, como a realizada por Ramón María Aller en 1929, cómpre facer unha profunda revisión sobre os datos biográficos que se coñecen deste persoeiro. Unha vez analizada polo miúdo toda a información dispoñible, semella o momento oportuno para ir incorporando así mesmo os últimos achados atopados sobre a vida deste científico, agora que estase a piques de celebrar o 250 aniversario do seu nacemento. Neste artigo preténdese incorporar novos datos para a súa biografía no relativo a súa estadía en Madrid como profesor de astronomía do Museo de Ciencias Naturales e como director do Observatorio Astronómico de Madrid.NO

Aprovechamiento de aguas pluviales

El objetivo principal del proyecto es poder establecer ciertos parámetros que permitan crear un protocolo de dimensionado de depósitos para riego de jardines urbanos. Centraremos el estudio en las zona de mayor concentración urbana de Catalunya, y se incluirán ejemplos prácticos de dimensionado de depósitos para pluviales en jardines urbanos. La diversidad de climas existentes en Catalunya permitirá extrapolar las conclusiones obtenidas a un territorio muy amplio, lo cual aumenta las posibilidades de una aplicación práctica efectiva

Dúas obras inéditas de José Rodríguez González

Existen importantes contribucións sobre o que, sen dúbida, foi o primeiro gran matemático e xeodesta galego, José Rodríguez González “O matemático do Bermés”, como a extensa biografía preparada polo ilustre astrónomo lalinense Ramón Mª Aller Ulloa ou o traballo de Armando Vázquez Crespo, que podemos atopar no número 1 de Descubrindo Deza. Malia todo, cremos que aínda non se pode dicir que está todo escrito sobre esta figura. Exporemos a continuación uns apuntamentos sobre este persoeiro aínda pouco coñecido na Ciencia galega e falaremos de dúas publicacións inéditas súas que non aparecen nas biografías feitas sobre a vida e obra deste científico: Ueber die Gröfsenverhältnisse des Erd-Sphäroids e Notice géognostique sur la Sierra Nevada.NO

Quantifying the benefits of SPECint distant parallelism in simultaneous multithreading architectures

We exploit the existence of distant parallelism that future compilers could detect and characterise its performance under simultaneous multithreading architectures. By distant parallelism we mean parallelism that cannot be captured by the processor instruction window and that can produce threads suitable for parallel execution in a multithreaded processor. We show that distant parallelism can make feasible wider issue processors by providing more instructions from the distant threads, thus better exploiting the resources from the processor in the case of speeding up single integer applications. We also investigate the necessity of out-of-order processors in the presence of multiple threads of the same program. It is important to notice at this point that the benefits described are totally orthogonal to any other architectural techniques targeting a single thread.Peer ReviewedPostprint (published version

Enhanced production of herpes simplex virus 1 amplicon vectors by gene modification and optimization of packaging cell growth medium

Herpes simplex virus 1 (HSV-1)-derived amplicon vectors are unique in their ability to accommodate large DNA molecules allowing whole genomic loci to be included with all of their regulatory elements. Additional advantages of these amplicons include their minimal toxicity and ability to persist as episomes, with negligible risk of insertional mutagenesis, being particularly well-suited for gene therapy of neurological disorders due to their outstanding ability to deliver genes into neurons and other neural cells. However, extensive gene therapy application has been hindered by difficulties in vector production. This work improved HSV-1 amplicons production by genetic modification of the packaging cell line and optimization of the culture medium. A stably-transfected Vero 2-2 cell line overexpressing the anti-apoptotic Bcl-2 protein was generated, exhibiting an increased resistance to apoptosis, prolonged culture duration, and a significant improvement in viral vector production. Additionally, supplementation of the growth medium with antioxidants, polyamines, amino acids, and reduced glutathione further increased the yield of packaged amplicon vectors. With these modifications, HSV-1 amplicons could be isolated from culture supernatants instead of cell lysates, leading to vector preparations with higher titer and purity and paving the way for generation of stable cell lines that are capable of continuous herpesviral vector productionThis work was supported by grants of the Spanish National Research Plan (SAF 2015–69361-R), Friedreich Ataxia Research Alliance (FARA), FARA Ireland, Spanish FEDAES, GENEFA, and Babel Famil

Can We Treat Neuroinflammation in Alzheimer's Disease?

Alzheimer’s disease (AD), considered the most common type of dementia, is characterized by a progressive loss of memory, visuospatial, language and complex cognitive abilities. In addition, patients often show comorbid depression and aggressiveness. Aging is the major factor contributing to AD; however, the initial cause that triggers the disease is yet unknown. Scientific evidence demonstrates that AD, especially the late onset of AD, is not the result of a single event, but rather it appears because of a combination of risk elements with the lack of protective ones. A major risk factor underlying the disease is neuroinflammation, which can be activated by different situations, including chronic pathogenic infections, prolonged stress and metabolic syndrome. Consequently, many therapeutic strategies against AD have been designed to reduce neuro-inflammation, with very promising results improving cognitive function in preclinical models of the disease. The literature is massive; thus, in this review we will revise the translational evidence of these early strategies focusing in anti-diabetic and anti-inflammatory molecules and discuss their therapeutic application in humans. Furthermore, we review the preclinical and clinical data of nutraceutical application against AD symptoms. Finally, we introduce new players underlying neuroinflammation in AD: the activity of the endocannabinoid system and the intestinal microbiota as neuroprotectors. This review highlights the importance of a broad multimodal approach to treat successfully the neuroinflammation underlying AD