Epistasis between intracellular cholesterol trafficking-related genes (NPC1 and ABCA1) and Alzheimer's disease risk

Aberrant cholesterol metabolism has been implicated in Alzheimer´s disease (AD). Recent findings have suggested an interaction of Niemann-Pick C1 (NPC1) and ATP-binding cassette transporter A1 (ABCA1) proteins in intracellular cholesterol transport and in maintaining cell cholesterol balance. Underexpression of NPC1 in concert with underexpression of ABCA1 would result in increased cholesterol accumulation and increased AD risk. We examined a functional polymorphism in the ABCA1 promoter region (−477, rs2422493), and four NPC1 polymorphisms in exon 6 (rs18050810), intron 20 (rs4800488), intron 22 (rs2236707), and intron 24 (rs2510344) capturing 85% of genetic variability in Hap Map CEU population, in a group of 631 Spanish AD patients and 731 controls. Subjects carrying both the ABCA1 (−477) TT genotype and the NPC1 (exon 6) GG genotype (OR = 1.89; 95% CI 1.04-3.41), NPC1 (intron 20) AA genotype (OR = 2.05; 95% CI 1.26-3.33), NPC1 (intron 22) AA genotype (OR = 2.05; 95% CI 1.18-3.58), or NPC1 (intron 24) GG genotype (OR = 1.89; 95% CI 1.16-3.07) had a higher risk of developing AD than subjects without these risk genotypes. Testing for epistatic interaction between genes in the pathway of cholesterol metabolism might be useful for predicting AD risk

ZnO Nanowires/N719 dye with different aspect ratio as a possible photoelectrode for Dye-Sensitized Solar Cells

The vapor-liquid-solid (VLS) process was applied to fabricate zinc oxide nanowires (ZnO NWs) with a different aspect ratio (AR), morphological, and optical properties. The ZnO NWs were grown on a system that contains a quartz substrate with transparent conductive oxide (TCO) thin film followed by an Al-doped ZnO (AZO) seed layer; both films were grown by magnetron sputtering at room temperature. It was found that the ZnO NWs presented high crystalline quality and vertical orientation from different structural and morphological characterizations. Also, NWs showed a good density distribution of 69 NWs/μm2 with a different AR that offers their capability to be used as possible photoelectrode (anode) in potential future device applications. The samples optical properties were studied using various techniques such as photoluminescence (PL), absorption, and transmittance before and after sensitization with N719 dye. The results demonstrated that NW with 30 nm diameter had the best characteristics as feasible photoelectrode (anode) (high absorption, minimum recombination, high crystallinity). Also, the present samples optical properties were found to be improved due to the existence of N719 dye and Au nanoparticles on the tip of NWs. NWs grown in this work can be used in different photonic and optoelectronic applications

The partial volume effect in the quantification of 1H magnetic resonance spectroscopy in Alzheimer's disease and aging

[Abstract] 1H-MRS variability increases due to normal aging and also as a result of atrophy in grey and white matter caused by neurodegeneration. In this work, an automatic process was developed to integrate data from spectra and high-resolution anatomical images to quantify metabolites, taking into account tissue partial volumes within the voxel of interest avoiding additional spectra acquisitions required for partial volume correction. To evaluate this method, we use a cohort of 135 subjects (47 male and 88 female, aged between 57 and 99 years) classified into 4 groups: 38 healthy participants, 20 amnesic mild cognitive impairment patients, 22 multi-domain mild cognitive impairment patients, and 55 Alzheimer's disease patients. Our findings suggest that knowing the voxel composition of white and grey matter and cerebrospinal fluid is necessary to avoid partial volume variations in a single-voxel study and to decrease part of the variability found in metabolites quantification, particularly in those studies involving elder patients and neurodegenerative diseases. The proposed method facilitates the use of 1H-MRS techniques in statistical studies in Alzheimer's disease, because it provides more accurate quantitative measurements, reduces the inter-subject variability, and improves statistical results when performing group comparisons

Caspase-1 genetic variation is not associated with Alzheimer's disease risk

BACKGROUND: Interleukin (IL)-1beta is a potent proinflammatory cytokine markedly overexpressed in the brains of patients with Alzheimer's disease (AD), and also involved in development of atherosclerosis and coronary artery disease. Caspase-1 (CASP1), formerly called IL-1beta converting enzyme (ICE), mediates the cleavage of the inactive precursor of IL-1beta into the biologically active form. CASP1 genetic variation (G+7/in6A, rs501192) has been associated with susceptibility to myocardial infarction and cardiovascular death risk. We examined the contribution of this gene to the susceptibility for AD. METHODS: We examined genetic variations of CASP1 by genotyping haplotype tagging SNPs (htSNPs) (rs501192, rs556205 and rs530537) in a group of 628 Spanish AD cases and 722 controls. RESULTS: There were no differences in the genotypic, allelic or haplotypic distributions between cases and controls in the overall analysis or after stratification by age, gender or APOE epsilon4 allele. CONCLUSION: Our negative findings in the Spanish population argue against the hypothesis that CASP1 genetic variations are causally related to AD risk

Refining memory assessment of elderly people with cognitive impairment:Insights from the short-term memory binding test

Alzheimer’s disease (AD) affects temporary memory for bound features more remarkably than for individual features. Such selective impairments manifest from presymptomatic through dementia stages via titration procedures. A recent study suggested that without titration and with high memory load the binding selectivity may disappear in people at risk of AD such as those with Mild Cognitive Impairment (MCI). We compared data from two studies on temporary binding which assessed people with MCI and controls using different memory loads (2 or 3 items). Selective binding impairments were found in MCI, but relative to controls, such selectivity was contingent upon memory load (i.e., present with 2 items). Further analysis with MCI people who tested positive to neuroimaging biomarkers (i.e., hippocampal atrophy) confirmed that this specific binding impairments are a feature of prodromal AD. The temporary binding task has been recently suggested by consensus papers as a potential screening tool for AD. The results presented here inform on task properties that can maximise the reliability of this new assessment tool for the detection of memory impairments in prodromal cases of AD

LAMP2 deficiency attenuates the neurodegeneration markers induced by HSV-1 infection

Mounting evidence suggests a major role of infectious agents in the pathogenesis of sporadic Alzheimer's disease (AD). Among them, herpes simplex virus type 1 (HSV-1) infection has emerged as a major factor in the etiology of AD. HSV-1 is able to induce some of the main alterations of the disease such as hyperphosphorylation of tau protein and accumulation of amyloid-β peptide. Functional genomic analysis of a cell model of HSV-1 infection and oxidative stress developed in our laboratory revealed lysosomal system to be the main pathway altered, and the lysosome-associated membrane protein 2 (LAMP2) gene one of the most strongly modulated genes. The aim of this work is to study LAMP2 as an AD candidate gene and to investigate its role in the neurodegeneration induced by HSV-1 using a LAMP2 knockdown cell model. LAMP2 deficiency led to a significant reduction of viral DNA replication and formation of infectious particles. In addition, tau hyperphosphorylation and inhibition of Aβ secretion induced by the virus were attenuated by the absence of LAMP2. Finally, genetic association studies revealed LAMP2 genetic variants to be associated with AD risk. In summary, our data indicate that LAMP2 could be a suitable candidate to mediate the AD-like phenotype caused by HSV-1.This work was supported by the Spanish Ministerio de Ciencia e Innovación (SAF 2017-85747-R); and the Ramon Areces Foundatio

Estrategia de capacitación metodológica para profesores de Inglés

Introducción: la enseñanza del inglés, como disciplina de formación general en las carreras de Ciencias Médicas, ha evolucionado para un constante perfeccionamiento. La capacitación de estos profesores debe avanzar al ritmo de las ciencias médicas y pedagógicas para formar un profesional integral. Objetivo: desarrollar una estrategia metodológica con los profesores de inglés para fortalecer el vocabulario técnico y las habilidades lingüísticas del inglés con fines específicos del pregrado y postgrado de las ciencias de la salud, y el dominio de términos pedagógicos en este idioma. Métodos: se utilizó el método de análisis documental para llegar a conclusiones sobre la literatura consultada. Se aplicaron encuestas para identificar necesidades de aprendizaje sobre las habilidades y el uso de vocabulario técnico relacionado con las ciencias médicas, seleccionar textos científicos y uso del vocabulario pedagógico en idioma inglés. Se impartió un curso de postgrado para su capacitación metodológica. Fueron evaluados mediante una prueba integradora. Resultados: las encuestas muestran que los profesores carecen de preparación para seleccionar textos científicos, trabajar las habilidades lingüísticas en los procesos de enseñanza del Inglés con fines específicos, vocabulario de términos técnicos de las Ciencias Médicas y Pedagógicas. Los resultados de la evaluación integradora fueron excelentes. Conclusiones: la estrategia de capacitación metodológica dirigida a los profesores para fortalecer el vocabulario técnico y habilidades lingüísticas del inglés con fines específicos del pregrado y postgrado de las ciencias médicas, elevar el dominio de términos técnicos de las Ciencias dela Salud, y los propios de las ciencias pedagógicas tuvo excelentes resultados

The mycotoxin phomoxanthone A disturbs the form and function of the inner mitochondrial membrane.

Mitochondria are cellular organelles with crucial functions in the generation and distribution of ATP, the buffering of cytosolic Ca2+ and the initiation of apoptosis. Compounds that interfere with these functions are termed mitochondrial toxins, many of which are derived from microbes, such as antimycin A, oligomycin A, and ionomycin. Here, we identify the mycotoxin phomoxanthone A (PXA), derived from the endophytic fungus Phomopsis longicolla, as a mitochondrial toxin. We show that PXA elicits a strong release of Ca2+ from the mitochondria but not from the ER. In addition, PXA depolarises the mitochondria similarly to protonophoric uncouplers such as CCCP, yet unlike these, it does not increase but rather inhibits cellular respiration and electron transport chain activity. The respiration-dependent mitochondrial network structure rapidly collapses into fragments upon PXA treatment. Surprisingly, this fragmentation is independent from the canonical mitochondrial fission and fusion mediators DRP1 and OPA1, and exclusively affects the inner mitochondrial membrane, leading to cristae disruption, release of pro-apoptotic proteins, and apoptosis. Taken together, our results suggest that PXA is a mitochondrial toxin with a novel mode of action that might prove a useful tool for the study of mitochondrial ion homoeostasis and membrane dynamics

Genetic variation in the tau kinases pathway may contribute to the risk of Alzheimer´s disease

Tau abnormal hyperphosphorylation and the formation of neurofibrillary tangles in Alzheimer´s disease (AD) brain is the result of upregulation of tau kinases. In a group of 729 Spanish late-onset AD patients and 670 healthy controls, we examined variations into a set of 20 candidate genes of kinases involved in tau phosphorylation at AD-related sites (PRKACB; CAMK2A; MARK1, 2, 3 and 4; CSNK1D; CDC2; RPS6KB1 and 2; p38α and β; IB1; JNK1, 2 and 3; MEK1 and 2; ERK1 and 2), to address hypotheses of genetic variation that might influence AD risk. There was an increased frequency of RPS6KB2 (intron 2, rs917570) minor allele in patients (50%) versus controls (39%) (OR = 1.52; 95% CI 1.30-1.77; p = 1.24×10−5 Bonferroni corrected), and the CDC2 AGC haplotype derived from SNPs in introns 3 (rs2448347), 5 (rs2456772), and 7 (rs1871447) showed a protective effect against AD in APOE ε4 allele noncarriers (permutation p = 1.0×10-4) with a frequency of 9% in cases and 15% in controls. Common genetic variation in the tau kinases pathway does underlie individual differences in susceptibility to AD

Impacto de materiales de apoyo a la docencia elaborados por profesores del departamento de Idiomas

Introducción: los retos de la universidad del siglo XXI plantean la necesidad de un nuevo proceso educativo, principios de excelencia, calidad y pertinencia. La excelencia universitaria pasa por la de los procesos docente educativo y la investigación científica.Objetivo: evaluar el impacto de la elaboración y aplicación de materiales de apoyo a la docencia confeccionados por profesores del departamento de Idiomas. Método: se realizó una investigación descriptiva transversal donde se utilizaron métodos teóricos y empíricos para la actualización de aspectos en la preparación y desarrollo de profesores y estudiantes, pertinencia y calidad de la educación médica superior, de la enseñanza del inglés y se utilizó como método empírico la encuesta. Resultados: las encuestas a los profesores de inglés del departamento muestran que un elevado por ciento de utilización de la mayor parte de los mismos, y su evaluación de 1 a 5, en su mayoría fue entre 4 y 5 puntos. Están satisfechos con los materiales elaborados y en su gran mayoría los utilizan muchas y algunas veces. Los estudiantes, egresados de los últimos 10 años y profesionales que recibieron posgrados de inglés también mostraron buenas opiniones. Conclusiones: se evaluó el impacto de los materiales de apoyo a la docencia elaborados y utilizados por profesores del departamento de idiomas y aunque hay algunas respuestas negativas, en general, si mantienen en su gran mayoría su vigencia y calidad para utilizarse en los procesos de enseñanza aprendizaje de estas disciplinas