The Level of NMDA Receptor in the Membrane Modulates Amyloid-β Association and Perforation

Alzheimer’s disease is a neurodegenerative disorder that affects mostly the elderly. The main histopathological markers are the senile plaques formed by amyloid-β peptide (Aβ) aggregates that can perforate the plasma membrane of cells, increasing the intracellular calcium levels and releasing synaptic vesicles that finally lead to a delayed synaptic failure. Several membrane proteins and lipids interact with Aβ affecting its toxicity in neurons. Here, we focus on NMDA receptors (NMDARs) as proteins that could be modulating the association and neurotoxic perforation induced by Aβ on the plasma membrane. In fact, our results showed that decreasing NMDARs, using enzymatic or siRNA approaches, increased the association of Aβ to the neurons. Furthermore, overexpression of NMDARs also resulted in an enhanced association between NMDA and Aβ. Functionally, the reduction in membrane NMDARs augmented the process of membrane perforation. On the other hand, overexpressing NMDARs had a protective effect because Aβ was now unable to cause membrane perforation, suggesting a complex relationship between Aβ and NMDARs. Because previous studies have recognized that Aβ oligomers are able to increase membrane permeability and produce amyloid pores, the present study supports the conclusion that NMDARs play a critical protective role on Aβ actions in hippocampal neurons. These results could explain the lack of correlation between brain Aβ burden and clinically observed dementia

On special partitions of [0, 1] and lineability within families bounded variation functions

We show that there exists large algebraic structures (vector spaces, algebras, closed subspaces, etc.) formed entirely (except for 0), on one hand, by singular, nowhere monotonic functions on [0, 1] and, on the other hand, by absolutely continuous nowhere monotonic functions. Several tools, of independent interest, related to obtaining special partitions of R into uncountable collections will be provided and used. The results obtained in this note are either new or improved version of already existing ones.Depto. de Análisis Matemático y Matemática AplicadaFac. de Ciencias MatemáticasFALSEMinisterio de Ciencia e Innovación (MICINN)Junta de AndalucíaWISS 2025 projectunpu

Landslides induced by the 2010 Chile megathrust earthquake: a comprehensive inventory and correlations with geological and seismic factors

The 2010 Mw=8.8 Maule earthquake, which occurred in the subduction contact between the Nazca and the South American tectonic plates off the coast of Chile, represents an important opportunity to improve understanding of the distribution and controls for the generation of landslides triggered by large megathrust earthquakes in subduction zones. This paper provides the analysis of the comprehensive landslide inventory for the Maule earthquake between 32.5° S and 38.5° S°. In total 1226 landslides were mapped over a total area of c.120,500 km2 , dominantly disrupted slides. The total landslide volume is c. 10.6 Mm3. The events are unevenly distributed in the study area, the majority of landslides located in the Principal Andean Cordillera and a very constrained region near the coast on the Arauco Peninsula, forming landslide clusters. Statistical analysis of our database suggests that relief and lithology are the main geological factors controlling coseismic landslides, while the seismic factor with higher correlation with landslide occurrence is the ratio between peak horizontal and peak vertical ground accelerations. The results and comparison with other seismic events elsewhere suggest that the number of landslides generated by megathrust earthquakes is lower than events triggered by shallow crustal earthquakes by at least one or two orders of magnitude, which is very important to consider in future seismic landslide hazard analysis

A new class of semiclassical wave function uniformizations

We present a new semiclassical technique which relies on replacing complicated classical manifold structure with simpler manifolds, which are then evaluated by the usual semiclassical rules. Under circumstances where the original manifold structure gives poor or useless results semiclassically the replacement manifolds can yield remarkable accuracy. We give several working examples to illustrate the theory presented here.Comment: 12 pages (incl. 12 figures

Solution and Asymptotic Behavior for a Nonlocal Coupled System of Reaction-Diffusion

This paper concerns with existence, uniqueness and asymptotic behavior of the solutions for a nonlocal coupled system of reaction-diffusion. We prove the existence and uniqueness of weak solutions by the Faedo-Galerkin method and exponential decay of solutions by the classic energy method. We improve the results obtained by Chipot-Lovato and Menezes for coupled systems. A numerical scheme is presented

Nature of the Neurotoxic Membrane Actions of Amyloid-β on Hippocampal Neurons in Alzheimer\u27s Disease

The mechanism by which amyloid-β (Aβ) produces brain dysfunction in patients with Alzheimer\u27s disease is largely unknown. According to previous studies, Aβ might share perforating properties with gramicidin, a well-accepted membrane-disrupting peptide. Therefore, we hypothesize that the key steps leading to synaptotoxicity by Aβ and gramicidin involve peptide aggregation, pore formation, and calcium dysregulation. Here, we show that Aβ and gramicidin form aggregates enriched in β-sheet structures using electron microscopy, and Thioflavin and Congo Red staining techniques. Also, we found that Aβ and gramicidin display fairly similar actions in hippocampal cell membranes, i.e. inducing Ca2+ entry and synaptoxicity characterized by the loss of synaptic proteins and a decrease in neuronal viability. These effects were not observed in a Ca2+ free solution, indicating that both Aβ and gramicidin induce neurotoxicity by a Ca2+-dependent mechanism. Using combined perforated patch clamp and imaging recordings, we found that only Aβ produced a perforation that progressed from a small (Cl−-selective pore) to a larger perforation that allowed the entry of fluorescent molecules. Therefore, based on these results, we propose that the perforation at the plasma membrane by Aβ is a dynamic process that is critical in producing neurotoxicity similar to that found in the brains of AD patients

Analycity and smoothing effect for the coupled system of equations of Korteweg - de Vries type with a single point singularity

We study that a solution of the initial value problem associated for the coupled system of equations of Korteweg - de Vries type which appears as a model to describe the strong interaction of weakly nonlinear long waves, has analyticity in time and smoothing effect up to real analyticity if the initial data only has a single point singularity at $x=0.

Diagnóstico genético preimplantacional: análisis de aneuploidías únicas

Known causes of unsuccessful pregnancy in couples undergoing assisted reproduction treatment include embryo aneuploidies. Preimplantation genetic diagnosis (PGD) is a technique used in assisted reproduction in order to detect these abnormalities, select embryos chromosomally normal and subsequently transfer to the patients’ uterus. Embryos with single aneuploidies may have the ability to survive and achieve unnoticed implantation. Objectives: To determine incidence of single aneuploidies in good quality embryos in third day of development to blastocyst. Design: Statistical and experimental study. Setting: Reprogenetics Latin-America and Assisted Reproduction Center - Concebir. Biologic material: Samples of embryo biopsies. Methods: Comparative analysis of results from evaluation of each sample obtained by embryo biopsy on the third and fifth days of embryonic development, performing PGD by respectively in situ hybridization (FISH) and comparative genomics (aCGH). Results: On third day of embryonic development 62.9% of embryos with single monosomy had 8-cell morphology. Though when evaluated by aCGH in the blastocyst stage 42.3% were abnormal and 37.5% of these belonged to the 8-cell stage. Single monosomies index in the blastocyst stage was 57.9% in 84.2% of single aneuploidies. Conclusions: Eight-cell embryos on the third day of embryonic development are most likely to reach blastocyst stage and have single aneuploidies.De las causas más conocidas en cuanto a la falta del éxito en el embarazo con tratamientos de reproducción asistida son aquellas relacionadas a las aneuploidías cromosómicas presentes en los embriones. El diagnóstico genético preimplantacional (PGD) es una técnica empleada en reproducción asistida para detectar estas anomalías, seleccionando aquellos que sean cromosómicamente normales, para luego transferirlos al útero de la paciente. Los embriones con aneuploidías únicas podrían tener la capacidad de sobrevivir y lograr la implantación, y por lo tanto, sin diagnóstico previo, estas podrían pasar desapercibidas. Objetivos: Determinar la incidencia de aneuploidías únicas en embriones de buena calidad embrionaria en el día 3 de desarrollo hasta blastocisto. Diseño: Estadístico y experimental. Instituciones: Reprogenetics Latinoamérica y Centro de Reproducción asistida, de la Clínica Concebir. Material Biológico: Muestras de biopsia embrionaria. Metodología: Análisis comparativo de resultados a partir de la evaluación de cada muestra obtenida por biopsia en el día tercero y día quinto de desarrollo embrionario, realizando el PGD por hibridación in situ (FISH) y genómica comparada (aCGH), respectivamente. Resultados: El 62,9% de embriones que presentaron monosomías únicas al tercer día de desarrollo embrionario resultaron ser de 8 células. Pero cuando se evaluó por aCGH en día cinco, 42,3% resultó anormal, y de estos 37,5% perteneció al estadio de 8 células. El índice de monosomías únicas en blastocisto resultó ser 57,9% de un total de 84,2% de aneuploidías únicas. Conclusiones: Los embriones de 8 células en el tercer día de desarrollo embrionario son los más probables de llegar al estadio de blastocisto, así como presentar aneuploidías únicas