Efecto genotóxico y mutagénico de la desnutrición moderada y grave en reticulocitos y eritrocitos de rata

UN is a condition that damages the cellular functions of the body progressive way. Is the cause of 45% of global deaths in children under 5 years of age; It has been widely studied the effects at cytogenetic level, however for gene level not have enough reports to show if it is possible to relate the UN degree and susceptibility gene. In managing the UN, antibiotics are part of most protocols, however, there is not enough analysis regarding the evidence behind the current treatment method of different routine antibiotics such as TMP-SMX. In this report, genotoxic and mutagenic effects of UN2° and UN3° were evaluated with the combination of MN and Pig-a assays to determine DNA damage in RET and RBC in WN rats and UN rats with UN2° or UN3° exposed and not exposed to ENU and TMP-SMX. Wistar rats were evaluated for 65 days after ENU exposed and 45 days after treatment with TMP-SMX, MN index and Pig-a mutant frequencies were monitored. Results show that UN2° and UN3° are relate to genotoxic and mutagenic effect by increasing the MN index and Pig-a mutant frequency. Animals exposed to mutagen, showed dose-dependent increases for ENU, there were not significant differences between UN2° and WN rats. A persistent mutagenic effect was found with the doses 100/500 mg TPM-SMX and UN3°. The UN3° has high genotoxic effect compared to the effect produced by the UN2°. We did not find differences between mutagenic effect related to UN degree. According to the results, it is necessary to continue with complementary studies in order to evaluate both UN degrees to strengthen the findings found in this study.La DN es un padecimiento que daña las funciones celulares de manera progresiva en el organismo. Es la causa del 45 % de las muertes en los niños menores de 5 años de edad, y aunque se han estudiado ampliamente sus efectos a nivel citogenético, a nivel génico no se cuenta con suficientes reportes que muestren si es posible relacionar el grado de DN con la susceptibilidad génica. En el manejo clínico de la DN, los antibióticos forman parte de la mayoría de los protocolos, no obstante, existe poco análisis de los efectos del actual método de tratamiento en los que se emplean diferentes antibióticos de rutina como la TMP SMX. En este trabajo se evaluaron los efectos genotóxico y mutagénico del DN2° y del DN3° con la combinación de los ensayos de MN y Pig-a para determinar el daño al ADN en RET y E de ratas BN y con DN2° ó DN3° expuestas y no expuestas a ENU ó a TMP-SMX. Ratas de la cepa Wistar fueron evaluadas por 63 días después de la exposición a ENU y 45 días después de ser tratadas con TMP-SMX donde se monitorearon los porcentajes de MN y las frecuencias de mutantes Pig a. Los resultados muestran que la DN2° y la DN3° se relacionan con un efecto genotóxico y mutagénico al incrementar el porcentaje de MN y la frecuencia de mutantes Pig-a. Los animales expuestos al ENU presentaron incrementos dosis y tiempo dependientes. Al comparar los efectos inducidos entre estos grupos se observó que no hubo diferencias significativas entre los animales BN y con DN2°. Por otra parte, se encontró un efecto mutagénico persistente con la dosis de 100/500 mg TPM-SMX y DN3°. El DN3° tiene mayor efecto genotóxico en comparación con el efecto producido por la DN2°. No se observaron diferencias en el efecto mutagénico relacionado con el grado de DN. De acuerdo a los resultados obtenidos, es necesario continuar con estudios complementarios en ambos grados de DN que fortalezcan los hallazgos obtenidos en este estudio

Detección de mutación somática Pig-a en eritrocitos de sangre periférica de ratas desnutridas

La asimilación deficiente de alimentos por el organismo conduce a un estado patológico con distintos grados y manifestaciones clínicas, conocido como Desnutrición (Gómez, 1946). Los estudios en el área de la toxicología genética han generado un número importante de procedimientos in vivo e in vitro, los cuales han sido diseñados para monitorear los efectos que diversos agentes físicos y químicos tienen sobre la integridad genética de las células, así como los posibles riesgos que estos representan para los organismos (Abramsson y cols., 2000; Krishna y Hayashi, 2000). Entre estos procedimientos se incluyen: la medición de proteínas asociadas al ADN, localización de mutaciones puntuales o eventos genéticos que afectan a un gen específico (Abramsson y cols., 2000). El gen glucosilfosfatidilinositol de clase A (Pig-a) se localiza en el brazo corto del cromosoma X (Takahaski y cols., 1993; Rosee, 1997; Tomita, 1999; Phonethepswath y cols., 2008). Este gen codifica para la subunidad catalítica que participa en la primera etapa de la síntesis de de glucosilfosfatidilinositol (GPI) (Takahaski y cols., 1993; Hernández y cols., 2008). GPI es esencial para el anclaje de una gran variedad de proteínas de la membrana citoplasmática (Hernández y cols., 2008). En los últimos años ha surgido un nuevo ensayo in vivo de detección de mutación somática basado en el gen Pig-a (Pig-a en los roedores, PIG-A en los seres humanos). El ensayo consiste en detectar mutaciones somáticas por medio de citometría de flujo. En una célula normal un número de proteínas sintetizadas en el retículo endoplásmico llegan a unirse covalentemente a la molécula de GPI. Estas proteínas dependientes de GPI aparecen en la superficie celular, y pueden ser detectadas por los anticuerpos apropiados conjugados con fluorocromos (Karadimitris y Luzzatto, 2001). En este estudio se utilizó el ensayo Pig-a como una herramienta para analizar el daño génico en un modelo de desnutrición grave expuesto a un potente mutágeno. El ensayo se basó en realizar un marcaje diferencial de reticulocitos y eritrocitos usando un anticuerpo conjugado con un fluorocromo (antiCD59-PE). Se tomó como indicador de daño al material genético de las células, el incremento en las frecuencias de mutantes Pig-a, que fueron analizadas en un millón de células, procedentes de sangre periférica de ratas cepa Wistar expuestas a un mutágeno durante 8 semanas. Los resultados muestran que la desnutrición grave por sí misma tiene un efecto dañino sobre la integridad del material genético. Las frecuencias de mutantes se incrementaron en el tiempo. El ensayo Pig-a es de reciente introducción como método génico de evaluación genotóxica. De acuerdo a los resultados obtenidos, es necesario continuar el estudio del efecto de la desnutrición sobre el material genético, apoyándose en estudios complementarios

Helium-Iron Compounds at Terapascal Pressures.

We investigate the binary phase diagram of helium and iron using first-principles calculations. We find that helium, which is a noble gas and inert at ambient conditions, forms stable crystalline compounds with iron at terapascal pressures. A FeHe compound becomes stable above 4 TPa, and a FeHe_{2} compound above 12 TPa. Melting is investigated using molecular dynamics simulations, and a superionic phase with sublattice melting of the helium atoms is predicted. We discuss the implications of our predicted helium-iron phase diagram for interiors of giant (exo)planets and white dwarf stars

Electrical characterization and modeling of 1T-1R RRAM arrays with amorphous and poly-crystalline HfO2

In this work, a comparison between 1T-1R RRAM arrays, manufactured either with amorphous or poly-crystalline Metal–Insulator–Metal cells, is reported in terms of performance, reliability, Set/Reset operations energy requirements, intra-cell and inter-cell variability during 10k endurance cycles and 100k read disturb cycles. The modeling of the 1T-1R RRAM array cells has been performed with two different approaches: (i) a physical model like the Quantum Point Contact (QPC) model was used to find the relationship between the reliability properties observed during the endurance and the read disturb tests with the conductive filament properties; (ii) a compact model to be exploited in circuit simulations tools which models the I–V characteristics of each memory cells technology

Estimating the Relative Stiffness between a Hepatic Lesion and the Liver Parenchyma through Biomechanical Simulations of the Breathing Process

[EN] In this paper, a method to in vivo estimate the relative stifness between a hepatic lesion and the liver parenchyma is presented. Tis method is based on the fnite element simulation of the deformation that the liver undergoes during the breathing process. Boundary conditions are obtained through a registration algorithm known as Coherent Point Drif (CPD), which compares the liver form in two phases of the breathing process. Finally, the relative stifness of the tumour with respect to the liver parenchyma is calculated by means of a Genetic Algorithm, which does a blind search of this parameter. Te relative stifness together with the clinical information of the patient can be used to establish the type of hepatic lesion. Te developed methodology was frst applied to a test case, i.e., to a control case where the parameters were known, in order to verify its validity. Afer that, the method was applied to two real cases and low errors were obtained.This work has been funded by the Spanish Ministry of Economy and Competitiveness (MINECO) through research projects DPI2013-40859-R and TIN2014-52033-R, both also supported by European FEDER funds.Martinez-Sanchis, S.; Rupérez Moreno, MJ.; Nadal, E.; Pareja, E.; Brugger, S.; Borzacchiello, D.; López, R.... (2018). Estimating the Relative Stiffness between a Hepatic Lesion and the Liver Parenchyma through Biomechanical Simulations of the Breathing Process. Mathematical Problems in Engineering. 1-10. https://doi.org/10.1155/2018/5317324S110Kmieć, Z. (2001). Introduction — Morphology of the Liver Lobule. Advances in Anatomy Embryology and Cell Biology, 1-6. doi:10.1007/978-3-642-56553-3_1Cequera, A., & García de León Méndez, M. C. (2014). Biomarkers for liver fibrosis: Advances, advantages and disadvantages. 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A new methodology for the in vivo estimation of the elastic constants that characterize the patient-specific biomechanical behavior of the human cornea

This work presents a methodology for the in vivo characterization of the complete biomechanical behavior of the human cornea of each patient. Specifically, the elastic constants of a hyperelastic, second-order Ogden model were estimated for 24 corneas corresponding to 12 patients. The finite element method was applied to simulate the deformation of human corneas due to non-contact tonometry, and an iterative search controlled by a genetic heuristic was used to estimate the elastic parameters that most closely approximates the simulated deformation to the real one. The results from a synthetic experiment showed that these parameters can be estimated with an error of about 5%. The results of 24 in vivo corneas showed an overlap of about 90% between simulation and real deformed cornea and a modified Hausdorff distance of 25 mu m, which indicates the great accuracy of the proposed methodology. (C) 2014 Elsevier Ltd. All rights reserved.This project has been partially funded by MECD (reference AP2009-2414) and MINECO (INNPACTO, IPT-2012-0495-300000).Lago, MA.; Rupérez Moreno, MJ.; Martínez Martínez, F.; Monserrat Aranda, C.; Larra, E.; Gueell, JL.; Peris-Martinez, C. (2015). A new methodology for the in vivo estimation of the elastic constants that characterize the patient-specific biomechanical behavior of the human cornea. Journal of Biomechanics. 48(1):38-43. https://doi.org/10.1016/j.jbiomech.2014.11.009S384348

SARS-CoV-2 immunochromatographic IgM/IgG rapid test in pregnancy: A false friend?

Background: An increasing body of evidence has revealed that SARS-CoV-2 infection in pregnant women could increase the risk of adverse maternal and fetal outcomes. Careful monitoring of pregnancies with COVID-19 and measures to prevent neonatal infection are warranted. Therefore, rapid antibody tests have been suggested as an efficient screening tool during pregnancy. Cases: We analysed the clinical performance during pregnancy of a rapid, lateral-flow immunochromatographic assay for qualitative detection of SARS-CoV-2 IgG/IgM antibodies. We performed a universal screening including 169 patients during their last trimester of pregnancy. We present a series of 14 patients with positive SARS-CoV-2 immunochromatographic assay rapid test result. Immunochromatographic assay results were always confirmed by chemiluminescent microparticle immunoassays for quantitative detection of SARS-CoV-2 IgG and IgM+IgA antibodies as the gold standard. We observed a positive predictive value of 50% and a false positive rate of 50% in pregnant women, involving a significantly lower diagnostic performance than reported in non-pregnant patients. Discussion: Our data suggest that although immunochromatographic assay rapid tests may be a fast and profitable screening tool for SARS-CoV-2 infection, they may have a high false positive rate and low positive predictive value in pregnant women. Therefore, immunochromatographic assay for qualitative detection of SARS-CoV-2 IgG/IgM antibodies must be verified by other test in pregnant patients

Chaotic dynamics of the Hénon map and neuronal input–output: A comparison with neurophysiological data

In this study, the Hénon map was analyzed using quantifiers from information theory in order to compare its dynamics to experimental data from brain regions known to exhibit chaotic behavior. The goal was to investigate the potential of the Hénon map as a model for replicating chaotic brain dynamics in the treatment of Parkinson’s and epilepsy patients. The dynamic properties of the Hénon map were compared with data from the subthalamic nucleus, the medial frontal cortex, and a q-DG model of neuronal input–output with easy numerical implementation to simulate the local behavior of a population. Using information theory tools, Shannon entropy, statistical complexity, and Fisher’s information were analyzed, taking into account the causality of the time series. For this purpose, different windows over the time series were considered. The findings revealed that neither the Hénon map nor the q-DG model could perfectly replicate the dynamics of the brain regions studied. However, with careful consideration of the parameters, scales, and sampling used, they were able to model some characteristics of neural activity. According to these results, normal neural dynamics in the subthalamic nucleus region may present a more complex spectrum within the complexity–entropy causality plane that cannot be represented by chaotic models alone. The dynamic behavior observed in these systems using these tools is highly dependent on the studied temporal scale. As the size of the sample studied increases, the dynamics of the Hénon map become increasingly different from those of biological and artificial neural systems.Instituto de Física La Plat