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MeCP2 gene therapy ameliorates disease phenotype in mouse model for Pitt Hopkins syndrome
No full textThe neurodevelopmental disorder Pitt Hopkins syndrome (PTHS) causes clinical symptoms similar to Rett syndrome (RTT) patients. However, RTT is caused by MECP2 mutations whereas mutations in the TCF4 gene lead to PTHS. The mechanistic commonalities underling these two disorders are unknown, but their shared symptomology suggest that convergent pathway-level disruption likely exists. We reprogrammed patient skin derived fibroblasts into induced neuronal progenitor cells. Interestingly, we discovered that MeCP2 levels were decreased in PTHS patient iNPCs relative to healthy controls and that both iNPCs and iAstrocytes displayed defects in function and differentiation in a mutation-specific manner. When Tcf4þ+/- mice were genetically crossed with mice overexpressing MeCP2, molecular and phenotypic defects were significantly ameliorated, underlining and important role of MeCP2 in PTHS pathology. Importantly, post-natal intracerebroventricular gene replacement therapy with adeno-associated viral vector serotype 9 (AAV9)-expressing MeCP2 (AAV9.P546.MeCP2) significantly improved iNPC and iAstrocyte function and effectively ameliorated histological and behavioral defects in Tcf4þ+/- mice. Combined, our data suggest a previously unknown role of MeCP2 in PTHS pathology and common pathways that might be affected in multiple neurodevelopmental disorders. Our work highlights potential novel therapeutic targets for PTHS, including upregulation of MeCP2 expression or its downstream targets or, potentially, MeCP2-based gene therapy
is it within the purview of the registrar of real estate to decline the registration of a sale if the property’s historical registry evidences a recorded lease contract for the same property?
No full textNuestro sistema registral reposa en el mandato que se le dirige al Conservador de Bienes Raíces, cual corresponde a su deber de inscribir sin re- tardo los títulos que se le presenten. En el marco de lo indicado, el funcionario en referencia puede, sin embargo, negarse a inscribir excepcionalmente, cuan- do concurren algunas de las hipótesis consignadas en los artículos 13 (objeto de nuestro estudio) y 14 del Reglamento Conservatorio de Bienes Raíces. Cabe referir que el evocado artículo 13 habilita al funcionario en referencia a objetar una solicitud de inscripción en atención de defectos formales que hagan de algún modo inadmisible la inscripción solicitada, o que de la lectura del título se desprenda que concurre un vicio que lo anula absolutamente, llegándose a afirmar que lo mismo acontece respecto de un vicio de nulidad relativa. El análisis que se plantea persigue abordar si es que el rechazo puede ser amparado en la constatación de un arrendamiento que recae sobre el inmueble que tiene relación con inscripción que se requiere
Modification of thermal and electrical characteristics of hybrid polymer nanocomposites through gamma irradiation for advanced applications
Get PDFIn this article, we present a straightforward in-situ approach for producing Ag NPs incorporated in graphene oxide (GO) blended with glutaraldehyde (GA) cross-linked polyvinyl alcohol (PVA) matrix. Samples are γ-irradiated by doses of 2, 5, and 10 kGy and in comparison with the pristine films, the thermal conductivity (‘k’) and effusivity are measured. ‘k’ decreases with irradiation doses up to 5 kGy and further increase in the dosage results increase in ‘k’. We performed FDTD modeling to verify the effect of polarization and periodicity on the absorptivity and emissivity spectra that are correlated to the ‘k’ and effusivity, empirically. Hence, we can confess that the structural properties of the prepared hybrid nanocomposite are manipulated by γ-irradiation. This attests that the PVA/GO-Ag/GA nanocomposite is radiation-sensitive and could be employed for thermal management systems. Moreover, their strong electrical insulation, as the measured dc conductivity of the γ-irradiated samples is found to be in the range of 2.66 × 10−8–4.319 × 10−7 Sm−1, which is below the percolation threshold of 1.0 × 10−6 Sm−1, demonstrates that they are excellent candidates for the use of thermal management materials. The low ‘k’ values allow us to use this promising material as thermal insulating substrates in microsensors and microsystems. They are also great choices for usage as wire and cable insulation in nuclear reactors due to their superior electrical insulation
In situ synthesis of Cu2O nanoparticles using eucalyptus globulus extract to remove a dye via advanced oxidation
Get PDFWater pollution, particularly from organic contaminants like dyes, is a pressing issue, prompting exploration into advanced oxidation processes (AOPs) as potential solutions. This study focuses on synthesizing Cu2O on cellulose-based fabric using Eucalyptus globulus leaf extracts. The resulting catalysts effectively degraded methylene blue through photocatalysis under LED visible light and heterogeneous Fenton-like reactions with H2O2, demonstrating reusability. Mechanistic insights were gained through analyses of the extracts before and after Cu2O synthesis, revealing the role of phenolic compounds and reducing sugars in nanoparticle formation. Cu2O nanoparticles on cellulose-based fabric were characterized in terms of their morphology, structure, and bandgap via SEM-EDS, XRD, Raman, FTIR, UV–Vis DRS, and TGA. The degradation of methylene blue was pH-dependent; photocatalysis was more efficient at neutral pH due to hydroxyl and superoxide radical production, while Fenton-like reactions showed greater efficiency at acidic pH, primarily generating hydroxyl radicals. Cu2O used in Fenton-like reactions exhibited lower reusability compared to photocatalysis, suggesting deterioration. This research not only advances understanding of catalytic processes but also holds promise for sustainable water treatment solutions, contributing to environmental protection and resource conservation
Does argumentation change minds? A cognitive and evolutionary approach
No full textOur intuition is straightforward: yes, argumentation changes minds. But many cognitive and discursive habits suggest otherwise. As the literature in the psychology of reasoning incessantly emphasizes, we hardly change our minds because a predisposed robust confirmation bias (or myside bias) is at work when we argue. To adequately answer the questions of why, how, and if argumentation changes minds, I frame the problem from an evolutionary perspective. I argue argumentative competence changes minds because its ultimate goal is to construct the future, to predict more accurately. This converges with evolutionary analyses of other cognitive skills and cultural inventions. To explain my perspective, I use the distinction between ultimate and proximal goals of a trait
Improved feedback quantizer with discrete space vector
Get PDFThe use of advanced modulation and control schemes for power converters, such as a Feedback Quantizer and Predictive Control, is widely studied in the literature. This work focuses on improving the closed-loop modulation scheme called Feedback Quantizer, which is applied to a three-phase voltage source inverter. This scheme has the natural behavior of mitigating harmonics at low frequencies, which are detrimental to electrical equipment such as transformers. This modulation scheme also provides good tracking for the voltage reference at the fundamental frequency. On the other hand, the disadvantage of this scheme is that it has a variable switching frequency, creating a harmonic spectrum in frequency dispersion, and it also needs a small sampling time to obtain good results. The proposed scheme to improve the modulation scheme is based on a Discrete Space Vector with virtual vectors to obtain a better approximation of the optimal vectors for use in the algorithm. The proposal improves the conventional scheme at a high sampling time (200 μs), obtaining a THD less than 2% in the load current, decreases the noise created by the conventional scheme, and provides a fixed switching frequency. Experimental tests demonstrate the correct operation of the proposed scheme
Z-scheme configured iron oxide/g-C3N4 nanocomposite system for solar-driven H2 production through water splitting
Get PDFA nanocomposite composed of α-Fe2O3/g-C3N4 is synthesized using a modified ultrasonication approach, which engineered a robust interfacial contact in the system. Phase formation and morphological features are confirmed via XRD and electron-microscopy techniques. XPS revealed the native oxidation states of the elements and chemisorption-mediated interactions in the system. This developed composite produced hydrogen at a rate of 1494 μmolg− 1 h− 1, which is around 6.6 times higher than the g-C3N4 system. The observed enhancement is attributed to the Z-scheme configuration, leading to the suitable band edge alignments, charge separation and extended lifetime of the carriers in the composite
A simulation study evaluating how population survival and genetic diversity in a newly established population can be affected by propagule size, extinction rates, and initial heterozygosity
Get PDFThe introduction and establishment of invasive species in regions outside their native range, is one of the major threats for the conservation of ecosystems, affecting native organisms and the habitat where they live in, causing substantial biological and monetary losses worldwide. Due to the impact of invasive species, it is important to understand what makes some species more invasive than others. Here, by simulating populations using a forward-in-time approach combining ecological and single polymorphic nucleotides (SNPs) we evaluated the relation between propagule size (number of individuals = 2, 10, 100, and 1,000), extinction rate (with values 2%, 5%, 10%, and 20%), and initial heterozygosity (0.1, 0.3, and 0.5) on the population survival and maintenance of the heterozygosity of a simulated invasive crab species over 30 generations assuming a single introduction. Our results revealed that simulated invasive populations with initial propagule sizes of 2–1,000 individuals experiencing a high extinction rate (10–20% per generation) were able to maintain over 50% of their initial heterozygosity during the first generations and that under scenarios with lower extinction rates invasive populations with initial propagule sizes of 10–1,000 individuals can survive up to 30 generations and maintain 60–100% of their initial heterozygosity. Our results can help other researchers better understand, how species with small propagule sizes and low heterozygosities can become successful invaders
Chile and the inter-war world: Dynamics of the American international system in the context of the Chaco War and the role of international actors (Neutrals Commission, ABCP, League of Nations)
Get PDFEl período de entreguerras (1919-1939) se caracterizó por importantes modificaciones en la dinámica del funcionamiento del sistema internacional a partir de la irrupción de nuevos actores y organizaciones supranacionales que asumieron roles activos en la búsqueda de soluciones a los conflictos que se desarrollaron en dicho período. En el ámbito del sistema internacional americano uno de los conflictos más relevantes fue la guerra del Chaco (1932-1935) que enfrentó a Bolivia con Paraguay. El presente artículo tiene como objetivo caracterizar dicho sistema internacional americano a partir del estudio de la dinámica que adoptaron los distintos actores internacionales frente a la guerra y la búsqueda de la paz. Planteamos que la política exterior de los estados americanos involucrados en la búsqueda de la paz en la guerra del Chaco (fundamentalmente Chile, Argentina y Estados Unidos) estuvo fuertemente condicionada por sus respectivos objetivos nacionales y hemisféricos, las rivalidades regionales y la desconfianza frente al papel de la Sociedad de Naciones
Behavioral biomarkers in fishes: A non-lethal approach to assess the effects of chemical pollution on freshwater ecosystems
No full textThe expansion of the human population and the escalating use of chemical products pose a considerable threat to aquatic biodiversity. Consequently, there is an imperative need for the implementation of non-lethal, costeffective, and easily deployable biomonitoring tools. In this context, fish and their behavior as biomarkers have gained prominence in monitoring of freshwater ecosystems. The aim of this study was to assess the state of art in the use of behavioral biomarkers in ecotoxicology, emphasizing their role as informative tools for global environmental monitoring. Through a systematic literature search, ninety-two articles focusing on the evaluation of behavioral changes in freshwater fish in response to pollution were identified. The most prevalent keywords were “behavior” (7%) and “zebrafish” (6%). Experiments were conducted in countries with expansive territories, such as the United States (18%) and Brazil (17%). Exotic species were primarily employed (58%), with Danio rerio (26%) being the most frequently studied species. Among pollutants, pesticides (32%) and medicines (25%) were the most frequently studied, while locomotion (38%) and social behaviors (18%) were the most frequently evaluated behaviors. Across these studies, authors consistently reported significant changes in the behavior of fish exposed to contaminants, including decreased swimming speed and compromised feeding efficiency. The review findings affirm that evaluating behavioral biomarkers in freshwater fish offers an informative, non-lethal, cost-effective, and easily implementable approach to understanding pollution impacts on freshwater ecosystems. Although few studies on behavioral biomarkers were available to date, the number has rapidly increased in recent years. Furthermore, a variety of novel approaches and study models are being included. Research into behavioral biomarkers is crucial for understanding and managing environmental risks in freshwater ecosystems. Nevertheless, further studies are needed to enhance our understanding of behavioral toxicity indicators, considering factors such as life stage, sex, and breeding season in the tested species