Insulin receptor membrane retention by a traceable chimeric mutant

Background: The insulin receptor (IR) regulates glucose homeostasis, cell growth and differentiation. It has been hypothesized that the specific signaling characteristics of IR are in part determined by ligand-receptor complexes localization. Downstream signaling could be triggered from the plasma membrane or from endosomes. Regulation of activated receptor's internalization has been proposed as the mechanism responsible for the differential isoform and ligand-specific signaling. Results: We generated a traceable IR chimera that allows the labeling of the receptor at the cell surface. This mutant binds insulin but fails to get activated and internalized. However, the mutant heterodimerizes with wild type IR inhibiting its auto-phosphorylation and blocking its internalization. IR membrane retention attenuates AP-1 transcriptional activation favoring Akt activation. Conclusions: These results suggest that the mutant acts as a selective dominant negative blocking IR internalization-mediated signaling.Fil: Giudice, Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica; ArgentinaFil: Jares, Elizabeth Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono; ArgentinaFil: Coluccio Leskow, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica; Argentina. Universidad Nacional de Luján. Departamento de Ciencias Básicas; Argentin

RISC-Vlim, a RISC-V Framework for Logic-in-Memory Architectures

Most modern CPU architectures are based on the von Neumann principle, where memory and processing units are separate entities. Although processing unit performance has improved over the years, memory capacity has not followed the same trend, creating a performance gap between them. This problem is known as the "memory wall" and severely limits the performance of a microprocessor. One of the most promising solutions is the "logic-in-memory" approach. It consists of merging memory and logic units, enabling data to be processed directly inside the memory itself. Here we propose an RISC-V framework that supports logic-in-memory operations. We substitute data memory with a circuit capable of storing data and of performing in-memory computation. The framework is based on a standard memory interface, so different logic-in-memory architectures can be inserted inside the microprocessor, based both on CMOS and emerging technologies. The main advantage of this framework is the possibility of comparing the performance of different logic-in-memory solutions on code execution. We demonstrate the effectiveness of the framework using a CMOS volatile memory and a memory based on a new emerging technology, racetrack logic. The results demonstrate an improvement in algorithm execution speed and a reduction in energy consumption

Octantis: An Exploration Tool for Beyond von Neumann architectures

Nowadays, the modern electronic systems are facing an important limitation in terms of performance, known as von Neumann bottleneck. It affects the communications between two crucial elements, the CPU and the memory, which suffer from a saturation in bandwidth. Many solutions are currently under investigation and among them the concept of Logic-in-Memory (LiM) has been introduced: a memory enriched in its array of computational elements which enable the implementation of a flexible distributed processing system. The current work introduces Octantis, a High-Level Synthesizer useful for the exploration of LiM architectures. The proposed software analyzes an input algorithm described in standard C language and identifies which LiM architecture would implement it better. At its output, the synthesized solution is provided together with a test-bench, to properly characterize it, in terms of performance, spatial occupation and power consumption. Many algorithms have been successfully synthesized by Octantis and some of the results achieved will be discussed along the document

DUX-family transcription factors regulate zygotic genome activation in placental mammals

In animal embryos, transcription is mostly silent for several cell divisions, until the release of the first major wave of embryonic transcripts through so-called zygotic genome activation (ZGA). Maternally provided ZGA-triggering factors have been identified in Drosophila melanogaster and Danio rerio, but their mammalian homologs are still undefined. Here, we provide evidence that the DUX family of transcription factors is essential to this process in mice and potentially in humans. First, human DUX4 and mouse Dux are both expressed before ZGA in their respective species. Second, both orthologous proteins bind the promoters of ZGA-associated genes and activate their transcription. Third, Dux knockout in mouse embryonic stem cells (mESCs) prevents the cells from cycling through a 2-cell-like state. Finally, zygotic depletion of Dux leads to impaired early embryonic development and defective ZGA. We conclude that DUX-family proteins are key inducers of zygotic genome activation in placental mammals

Microbiological and chemical characterization of fermented quinoa beverages obtained with kefir microorganisms

Quinoa is an Andean pseudocereal considered a natural food resource of high nutritional value whose importance is recognized in food security for present and future generations. In this study we combined the nutritional power of quinoa with the potential beneficial effects of kefir. Microbiological and physico-chemical properties of fermented quinoa beverages with kefir grains, acid mother cultures thereof, or lactobacilli isolated from kefir, with reported potential probiotic effects, were evaluated. Fermented quinoa beverages obtained with Lactiplantibacillus plantarum CIDCA 83114 or acid mother cultures were comparable, although the Lb. plantarum strain demonstrated better growth at fermentation (to 8.63 ± 0.07 log CFU·ml-1 against 6.13 ± 0.07 log CFU·ml-1, respectively). Furthermore, the quinoa suspensions fermented with Lb. plantarum CIDCA 83114 showed more significant improvements on total phenolics, antioxidant activity, proteolysis and amylolytic activity than those fermented with acid mother cultures. In contrast, Lactobacillus kefiri CIDCA 8348 and kefir grains CIDCA AGK1 were not able to ferment the substrate. Kefir grains lost biomass integrity during repeated inoculations into quinoa suspensions and the viability of the lactic acid bacteria decreased. The present study revealed suitable characteristics of Lb. plantarum CIDCA 83114 as a starter to obtain nutritious and potentially health-promoting fermented quinoa beverages.Fil: Pugliese, Andrea. Universidad Nacional de Lanus. Departamento de Desarrollo Productivo y Tecnológico; ArgentinaFil: Ulzurrun, Mauro Javier. Universidad Nacional de Lanus. Departamento de Desarrollo Productivo y Tecnológico; ArgentinaFil: Coluccio Leskow, Federico. Universidad Nacional de Luján. Departamento de Ciencias Básicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Antoni, Graciela. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos; ArgentinaFil: Kakisu, Emiliano Javier. Universidad Nacional de Lanus. Departamento de Desarrollo Productivo y Tecnológico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Microbiological and chemical characterization of fermented quinoa beverages obtained with kefir microorganisms

Quinoa is an Andean pseudocereal considered a natural food resource of high nutritional value whose importance is recognized in food security for present and future generations. In this study we combined the nutritional power of quinoa with the potential beneficial effects of kefir. Microbiological and physico-chemical properties of fermented quinoa beverages with kefir grains, acid mother cultures thereof, or lactobacilli isolated from kefir, with reported potential probiotic effects, were evaluated. Fermented quinoa beverages obtained with Lactiplantibacillus plantarum CIDCA 83114 or acid mother cultures were comparable, although the Lb. plantarum strain demonstrated better growth at fermentation (to 8.63 ± 0.07 log CFU·ml-1 against 6.13 ± 0.07 log CFU·ml-1, respectively). Furthermore, the quinoa suspensions fermented with Lb. plantarum CIDCA 83114 showed more significant improvements on total phenolics, antioxidant activity, proteolysis and amylolytic activity than those fermented with acid mother cultures. In contrast, Lactobacillus kefiri CIDCA 8348 and kefir grains CIDCA AGK1 were not able to ferment the substrate. Kefir grains lost biomass integrity during repeated inoculations into quinoa suspensions and the viability of the lactic acid bacteria decreased. The present study revealed suitable characteristics of Lb. plantarum CIDCA 83114 as a starter to obtain nutritious and potentially health-promoting fermented quinoa beverages.Fil: Pugliese, Andrea. Universidad Nacional de Lanus. Departamento de Desarrollo Productivo y Tecnológico; ArgentinaFil: Ulzurrun, Mauro Javier. Universidad Nacional de Lanus. Departamento de Desarrollo Productivo y Tecnológico; ArgentinaFil: Coluccio Leskow, Federico. Universidad Nacional de Luján. Departamento de Ciencias Básicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Antoni, Graciela. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos; ArgentinaFil: Kakisu, Emiliano Javier. Universidad Nacional de Lanus. Departamento de Desarrollo Productivo y Tecnológico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Individual retrotransposon integrants are differentially controlled by KZFP/KAP1-dependent histone methylation, DNA methylation and TET-mediated hydroxymethylation in naïve embryonic stem cells

Abstract BACKGROUND: The KZFP/KAP1 (KRAB zinc finger proteins/KRAB-associated protein 1) system plays a central role in repressing transposable elements (TEs) and maintaining parent-of-origin DNA methylation at imprinting control regions (ICRs) during the wave of genome-wide reprogramming that precedes implantation. In naïve murine embryonic stem cells (mESCs), the genome is maintained highly hypomethylated by a combination of TET-mediated active demethylation and lack of de novo methylation, yet KAP1 is tethered by sequence-specific KZFPs to ICRs and TEs where it recruits histone and DNA methyltransferases to impose heterochromatin formation and DNA methylation. RESULTS: Here, upon removing either KAP1 or the cognate KZFP, we observed rapid TET2-dependent accumulation of 5hmC at both ICRs and TEs. In the absence of the KZFP/KAP1 complex, ICRs lost heterochromatic histone marks and underwent both active and passive DNA demethylation. For KAP1-bound TEs, 5mC hydroxylation correlated with transcriptional reactivation. Using RNA-seq, we further compared the expression profiles of TEs upon Kap1 removal in wild-type, Dnmt and Tet triple knockout mESCs. While we found that KAP1 represents the main effector of TEs repression in all three settings, we could additionally identify specific groups of TEs further controlled by DNA methylation. Furthermore, we observed that in the absence of TET proteins, activation upon Kap1 depletion was blunted for some TE integrants and increased for others. CONCLUSIONS: Our results indicate that the KZFP/KAP1 complex maintains heterochromatin and DNA methylation at ICRs and TEs in naïve embryonic stem cells partly by protecting these loci from TET-mediated demethylation. Our study further unveils an unsuspected level of complexity in the transcriptional control of the endovirome by demonstrating often integrant-specific differential influences of histone-based heterochromatin modifications, DNA methylation and 5mC oxidation in regulating TEs expression