358 research outputs found

    Determination of qPCR Reference Genes Suitable for Normalizing Gene Expression in a Canine Model of Duchenne Muscular Dystrophy

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    Background:Dogs with dystrophin-deficient muscular dystrophy are valuable models of the equivalent human disease, Duchenne Muscular Dystrophy (DMD): unlike the mdx mouse, these animals present a disease severity and progression that closely matches that found in human patients. Canine models are however less thoroughly characterised than the established mdx mouse in many aspects, including gene expression. Analysis of expression in muscle plays a key role in the study of DMD, allowing monitoring and assessment of disease progression, evaluation of novel biomarkers and gauging of therapeutic intervention efficacy. Appropriate normalization of expression data via carefully selected reference genes is consequently essential for accurate quantitative assessment. Unlike the expression profile of healthy skeletal muscle, the dystrophic muscle environment is highly dynamic: transcriptional profiles of dystrophic muscle might alter with age, disease progression, disease severity, genetic background and between muscle groups. Objectives:The aim of this work was to identify reference genes suitable for normalizing gene expression in healthy and dystrophic dogs under various comparative scenarios. Methods:Using the delta-E50 MD canine model of DMD, we assessed a panel of candidate reference genes for stability of expression across healthy and dystrophic animals, at different ages and in different muscle groups. Results:We show that the genes HPRT1, SDHA and RPL13a appear universally suitable for normalizing gene expression in healthy and dystrophic canine muscle, while other putative reference genes are exceptionally poor, and in the case of B2M, actively disease-correlated. Conclusions:Our findings suggest consistent cross-sample normalization is possible even throughout the dynamic progression of dystrophic pathology, and furthermore highlight the importance of empirical determination of suitable reference genes for neuromuscular diseases

    Identificación de reacciones adversas de los productos homeopáticos árnica montana y stramonium compositum en los meses de agosto, septiembre y octubre de 2023 en la farmacia homeopática nivel 1 la esperanza sede Neiva

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    La farmacovigilancia está destinada a identificar, prevenir y finalmente a evaluar los riesgos que estén asociados a los medicamentos que se comercializan a nivel mundial, sin embargo, este proceso tan importante para la seguridad farmacéutica no se aplica de la manera adecuada en algunas instituciones, ubicando en peligro la salud de la población que adquiere dichos medicamentos, las reacciones adversas identificadas por el consumo de los medicamentos deben ser cuantificadas y reportadas por todos los servicios farmacéuticos para así contribuir a la seguridad en su uso. Este proyecto de investigación se centra en la identificación de las principales reacciones adversas desencadenadas por el consumo de dos de los medicamentos más vendidos en la farmacia homeopática nivel 1 la esperanza sede Neiva, el árnica montaña y stramonium compositum, de esta manera sentando las bases para que dicha farmacia de alguna manera pueda empezar a adoptar medidas necesarias para que sus usuarios estén más seguros al momento de consumir los medicamentos que allí se comercializan, este es un proyecto descriptivo con un enfoque cuantitativo, la principal herramienta utilizada fue la encuesta, por medio de la cual se obtuvieron datos relevantes para la investigación, esta encuesta se aplicó a 81 usuarios que adquirieron los productos homeopáticos árnica montaña y stramonium compositum en la farmacia homeopática la esperanza sede Neiva en los meses de agosto, septiembre y octubre del año 2023. Palabras claves: Farmacovigilancia, homeopático, reacciones adversas, seguridad, medicamentos.Pharmacovigilance is designed to identify, evaluate and prevent the risks associated with drugs that are marketed worldwide; however, this important process for pharmaceutical safety is not adequately applied in some institutions, putting at risk the health of the population that acquires these drugs, adverse reactions identified by the consumption of medicines should be quantified and reported by all pharmaceutical services in order to contribute to the safety of their use. This research project focuses on the identification of the main adverse reactions triggered by the consumption of two of the most sold medicines in the homeopathic pharmacy level 1 La Esperanza, Neiva, Arnica montana and Stramonium compositum, thus laying the foundations so that the pharmacy can somehow begin to adopt the necessary measures so that its users are safer when consuming the medicines that are marketed there, this is a descriptive project with a quantitative approach, the main tool used was the survey, by means of which relevant data were obtained for the research, this survey was applied to 81 users who acquired the homeopathic products Arnica Montana and stramonium compositum in the homeopathic pharmacy la esperanza headquarters Neiva in the months of August, September and October of the year 2023. Keywords: pharmacovigilance, homeopathic, adverse reactions, safety, medications

    Upper atmospheres and ionospheres of planets and satellites

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    The upper atmospheres of the planets and their satellites are more directly exposed to sunlight and solar wind particles than the surface or the deeper atmospheric layers. At the altitudes where the associated energy is deposited, the atmospheres may become ionized and are referred to as ionospheres. The details of the photon and particle interactions with the upper atmosphere depend strongly on whether the object has anintrinsic magnetic field that may channel the precipitating particles into the atmosphere or drive the atmospheric gas out to space. Important implications of these interactions include atmospheric loss over diverse timescales, photochemistry and the formation of aerosols, which affect the evolution, composition and remote sensing of the planets (satellites). The upper atmosphere connects the planet (satellite) bulk composition to the near-planet (-satellite) environment. Understanding the relevant physics and chemistry provides insight to the past and future conditions of these objects, which is critical for understanding their evolution. This chapter introduces the basic concepts of upper atmospheres and ionospheres in our solar system, and discusses aspects of their neutral and ion composition, wind dynamics and energy budget. This knowledge is key to putting in context the observations of upper atmospheres and haze on exoplanets, and to devise a theory that explains exoplanet demographics.Comment: Invited Revie

    The Magnus expansion and some of its applications

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    Approximate resolution of linear systems of differential equations with varying coefficients is a recurrent problem shared by a number of scientific and engineering areas, ranging from Quantum Mechanics to Control Theory. When formulated in operator or matrix form, the Magnus expansion furnishes an elegant setting to built up approximate exponential representations of the solution of the system. It provides a power series expansion for the corresponding exponent and is sometimes referred to as Time-Dependent Exponential Perturbation Theory. Every Magnus approximant corresponds in Perturbation Theory to a partial re-summation of infinite terms with the important additional property of preserving at any order certain symmetries of the exact solution. The goal of this review is threefold. First, to collect a number of developments scattered through half a century of scientific literature on Magnus expansion. They concern the methods for the generation of terms in the expansion, estimates of the radius of convergence of the series, generalizations and related non-perturbative expansions. Second, to provide a bridge with its implementation as generator of especial purpose numerical integration methods, a field of intense activity during the last decade. Third, to illustrate with examples the kind of results one can expect from Magnus expansion in comparison with those from both perturbative schemes and standard numerical integrators. We buttress this issue with a revision of the wide range of physical applications found by Magnus expansion in the literature.Comment: Report on the Magnus expansion for differential equations and its applications to several physical problem

    Gene expression divergence and nucleotide differentiation between males of different color morphs and mating strategies in the ruff

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    By next generation transcriptome sequencing, it is possible to obtain data on both nucleotide sequence variation and gene expression. We have used this approach (RNA-Seq) to investigate the genetic basis for differences in plumage coloration and mating strategies in a non-model bird species, the ruff (Philomachus pugnax). Ruff males show enormous variation in the coloration of ornamental feathers, used for individual recognition. This polymorphism is linked to reproductive strategies, with dark males (Independents) defending territories on leks against other Independents, whereas white morphs (Satellites) co-occupy Independent's courts without agonistic interactions. Previous work found a strong genetic component for mating strategy, but the genes involved were not identified. We present feather transcriptome data of more than 6,000 de-novo sequenced ruff genes (although with limited coverage for many of them). None of the identified genes showed significant expression divergence between males, but many genetic markers showed nucleotide differentiation between different color morphs and mating strategies. These include several feather keratin genes, splicing factors, and the Xg blood-group gene. Many of the genes with significant genetic structure between mating strategies have not yet been annotated and their functions remain to be elucidated. We also conducted in-depth investigations of 28 pre-identified coloration candidate genes. Two of these (EDNRB and TYR) were specifically expressed in black- and rust-colored males, respectively. We have demonstrated the utility of next generation transcriptome sequencing for identifying and genotyping large number of genetic markers in a non-model species without previous genomic resources, and highlight the potential of this approach for addressing the genetic basis of ecologically important variation

    Low temperature, authigenic illite and carbonates in a mixed dolomite-clastic lagoonal and pedogenic setting, Spanish Central System, Spain

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    The aim of this study was to further our understanding of the pedogenic and lacustrine modification of clay minerals. Some of these modifications are of special interest because they constitute reverse weathering reactions, rare in surface environments, and because there is not yet an accurate assessment of their global relevance in mineralogical and geochemical cycles. For this study, two sections from the Central System in Spain were selected. Both are sections through the Uppper Cenomanian-Turonian mixed clastic and carbonate succession, containing both calcite and dolomite, in the Sierra de Guadarrama. Mid-Turonian sea level fall resulted in the formation of a coastal plain environment in which extensive pedogenesis occurred around saline lagoons. The mineralogical changes that have occurred as a result of sedimentation in saline lagoons and as a consequence of pedogenesis are described. Textural relationships indicate that the dolomite cement pre-dates the calcite. Silicate minerals are represented by quartz, kaolinite, illite-smectite, illite, minor plagioclase and alkali feldspar, and trace chlorite and palygorskite. There is a positive correlation between the intensity of pedogenesis and the proportion of illite in the clay assemblage in one of the sections, indicating pedogenic illitisation. In this section, the intensity of the illitisation process increases up, reaching a maximum where pedogenesis is most intense in the middle part, and then decreases as marine influence increases towards the top of the Alcorlo Formation and the overlying marine Tranquera Formation. The clay assemblages are consistent with a slow transformation process from 42 kaolinite to illite by way of illite-smectite, taking place under surface conditions. The illitisation process has resulted in a less Fe-rich, more Mg-, and Al-rich illite than the majority of previously documented cases in the near surface. Formation of Al-rich illite is not therefore restricted to the deep subsurface. The mechanism for low temperature illitisation involves enhanced layer charge resulting from Mg2+ substitution for Al3+ (or Fe3+) and Fe3+ to Fe2+ reduction. Mg2+ enrichment may have occurred principally in saline lagoons or lakes, while Fe3+ to Fe2+ reduction occurred as a result of wetting and drying in a pedogenic environment. So far as it has been possible to establish, this dual mechanism has not previously been documented. This study indicates clearly that the dolomite and calcite are authigenic cements that precipitated in a clastic sediment, probably soon after deposition. Dolomitisation and Mg enrichment of the clay may have occurred at the same time. Seawater is the most probable source of Mg

    A semi-implicit discrete-continuum coupling method for porous media based on the effective stress principle at finite strain

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    Abstract: A finite strain multiscale hydro-mechanical model is established via an extended Hill–Mandel condition for two-phase porous media. By assuming that the effective stress principle holds at unit cell scale, we established a micro-to-macro transition that links the micromechanical responses at grain scale to the macroscopic effective stress responses, while modeling the fluid phase only at the macroscopic continuum level. We propose a dual-scale semi-implicit scheme, which treats macroscopic responses implicitly and microscopic responses explicitly. The dual-scale model is shown to have good convergence rate, and is stable and robust. By inferring effective stress measure and poro-plasticity parameters, such as porosity, Biot’s coefficient and Biot’s modulus from micro-scale simulations, the multiscale model is able to predict effective poro-elasto-plastic responses without introducing additional phenomenological laws. The performance of the proposed framework is demonstrated via a collection of representative numerical examples. Fabric tensors of the representative elementary volumes are computed and analyzed via the anisotropic critical state theory when strain localization occurs. Keywords: Multiscale poromechanics; Semi-implicit scheme; Homogenization; Discrete-continuum coupling; DEM–FEM; Anisotropic critical stat
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