Utility of Induced Pluripotent Stem Cells for the Study and Treatment of Genetic Diseases: Focus on Childhood Neurological Disorders

The study of neurological disorders often presents with significant challenges due to the inaccessibility of human neuronal cells for further investigation. Advances in cellular reprogramming techniques, have however provided a new source of human cells for laboratory-based research. Patient-derived induced pluripotent stem cells (iPSCs) can now be robustly differentiated into specific neural subtypes, including dopaminergic, inhibitory GABAergic, motorneurons and cortical neurons. These neurons can then be utilized for in vitro studies to elucidate molecular causes underpinning neurological disease. Although human iPSC-derived neuronal models are increasingly regarded as a useful tool in cell biology, there are a number of limitations, including the relatively early, fetal stage of differentiated cells and the mainly two dimensional, simple nature of the in vitro system. Furthermore, clonal variation is a well-described phenomenon in iPSC lines. In order to account for this, robust baseline data from multiple control lines is necessary to determine whether a particular gene defect leads to a specific cellular phenotype. Over the last few years patient-derived neural cells have proven very useful in addressing several mechanistic questions related to central nervous system diseases, including early-onset neurological disorders of childhood. Many studies report the clinical utility of human-derived neural cells for testing known drugs with repurposing potential, novel compounds and gene therapies, which then can be translated to clinical reality. iPSCs derived neural cells, therefore provide great promise and potential to gain insight into, and treat early-onset neurological disorders

Arl13b interferes with α-tubulin acetylation

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Wavelets techniques for pointwise anti-Holderian irregularity

In this paper, we introduce a notion of weak pointwise Holder regularity, starting from the de nition of the pointwise anti-Holder irregularity. Using this concept, a weak spectrum of singularities can be de ned as for the usual pointwise Holder regularity. We build a class of wavelet series satisfying the multifractal formalism and thus show the optimality of the upper bound. We also show that the weak spectrum of singularities is disconnected from the casual one (denoted here strong spectrum of singularities) by exhibiting a multifractal function made of Davenport series whose weak spectrum di ers from the strong one

Unusual Kondo physics in a Co impurity atom embedded in noble-metal chains

We analyze the conduction bands of the one dimensional noble-metal chains that contain a Co magnetic impurity by means of ab initio calculations. We compare the results obtained for Cu and Ag pure chains, as well as O doped Cu, Ag and Au chains with those previously found for Au pure chains. We find similar results in the case of Cu and Au hosts, whereas for Ag chains a different behavior is obtained. Differences and similarities among the different systems are analyzed by comparing the electronic structure of the three noble-metal hosts. The d-orbitals of Cu chains at the Fermi level have the same symmetry as in the case of Au chains. These orbitals hybridize with the corresponding ones of the Co impurity, giving rise to the possibility of exhibiting a two-channel Kondo physics.Comment: Accepted in IEEE Trans. Magn. - April 201

Fruit set and development of tomato grown in greenhouse : application of variable doses of plant growth regulators.

Las hormonas vegetales son capaces de controlar el desarrollo reproductivo, desde la diferenciación floral hasta los últimos estadios del desarrollo de los frutos. En particular, la etapa de fructificación y desarrollo depende del contenido endógeno de estas sustancias, y es posible manipular la iniciación del desarrollo del fruto por aplicación externa de hormonas. Previamente se evaluó el proceso de fructificación y desarrollo en el cultivo de tomate en invernadero en respuesta a la aplicación de b-NOA y AG3 en dosis fijas: se observó sensibilidad diferencial dependiendo del genotipo y tipo de regulador. El objetivo de este trabajo fue establecer dosis y momento óptimo para la aplicación de b-NOA y AG3 como formas de mejorar la fructificación y el desarrollo de frutos partenocárpicos. Como factores se consideraron tipo de regulador -b-NOA y AG3- en dosis y momentos de aplicación variables. Empleando ovarios no polinizados como sistema experimental fue posible concluir que la aplicación de 40 ppm de b-NOA a 7 días post antesis ofrece las mayores ventajas desde el punto de vista del rendimiento y menor impacto fisiológico, sin alterar el período de desarrollo de los frutos.Vegetable hormones are capable of controlling the reproductive development, from the flower differentiation until the last stages in the fruit development. In particular, the fruit set and development stage depends on the endogenous content of this substance, being possible to manipulate the beginning of the fruit development by external application of hormones. We have previously evaluated the fruit set and development process in tomato cultivation in greenhouse in response to the application of b-NOA and GA3 in fixed doses. Differential sensitivity was observed depending on the genotype and regulator type. The purpose of this work is to establish the optimum dose and moment for the application of b-NOA and GA3 as ways to improve the fruit set and development of parthenocarpic fruits. Regulator types b-NOA and GA3 in variable doses and application moments were considered as factors. Using unpollinated ovaries as an experimental system, it was possible to conclude that the application of 40 ppm of b-NOA at 7 days post antesis would offer the best advantages from a performance point of view and a lower physiologic impact, not altering the period of fruit development.Fil: Agüero, Marta S..Fil: Barral, Gabriela.Fil: Miguelisse, Nancy E..Fil: Castillo, Oscar E.

Fruit set and development of tomato grown in greenhouse : effect of plant growth regulators

El proceso de fructificación y desarrollo en tomate puede ser inducido naturalmente por polinización o partenocarpia y artificialmente por aplicación de reguladores; esta respuesta es variable según tipo y dosis de hormona, momento de aplicación y cultivar involucrado. El objetivo de este trabajo fue evaluar la capacidad de auxinas y giberelinas para inducir el desarrollo partenocárpico en genotipos de crecimiento indeterminado. Como factores se consideraron tipo de regulador -AG3 y β-NOA- en dosis fija, momento de aplicación -0, 5, 12, 19, 26 dpa- y genotipo -Rutgers, Fortaleza F1 y Colt 45-. Las mejores respuestas a nivel de porcentaje de fructificación y peso fresco se obtuvieron con β-NOA en comparación con AG3. Considerando todos los factores analizados, solamente la aplicación de β-NOA a 5 dpa permitió alcanzar porcentajes de fructificación y tamaño final de frutos similares a los obtenidos por autopolinización. El período de sensibilidad y el tamaño final de los frutos presentaron interacción con las variables genotipo, momento de aplicación y tipo de regulador. Se observó además que AG3 provocó un escaso desarrollo placentario y ausencia de óvulos mientras que β-NOA indujo un desarrollo de placentas y óvulos similar al de los frutos obtenidos por autopolinización.The process of fruit set and development in tomato can be naturally induced by pollination or parthenocarpy and artificiall y by hormonal application; this response is variable according to type and dose of the hormone, moment of application and cultivar involved. The purpose of this work was to evaluate the capacity of auxins and gibberellins to induce the parthenocarpic development in genotypes of undetermined growth. The considered factors were type of regulator -AG3 and β-NOAin set dose, moment of application -0, 5, 12, 19, 26 dpa-, and genotype -Rutgers, Fortaleza F1 and Colt 45-. The best responses regarding percentage of fructification and fresh weight are obtained with β-NOA in comparison with AG3. Considering all the analyzed factors, only the application of β-NOA to 5 dpa allowed to obtain the percentages of fruit set and final size of fruits similar to the ones obtained by autopollination. The period of sensitivity and the final size of fruits presented interaction with the genotype variables, moment of application and type of regulator. It was also observed that AG3 caused a scarce placental development and ovule absence while β-NOA induced a placenta and ovule development similar to the one in fruits obtained by autopollination.Fil: Castillo, Oscar E..Fil: Barral, Gabriela.Fil: Rodríguez, Gustavo.Fil: Miguelisse, Nancy E..Fil: Agüero, Marta S.

Whole lifespan microscopic observation of budding yeast aging through a microfluidic dissection platform

Important insights into aging have been generated with the genetically tractable and short-lived budding yeast. However, it is still impossible today to continuously track cells by high-resolution microscopic imaging (e.g., fluorescent imaging) throughout their entire lifespan. Instead, the field still needs to rely on a 50-y-old laborious and time-consuming method to assess the lifespan of yeast cells and to isolate differentially aged cells for microscopic snapshots via manual dissection of daughter cells from the larger mother cell. Here, we are unique in achieving continuous and high-resolution microscopic imaging of the entire replicative lifespan of single yeast cells. Our microfluidic dissection platform features an optically prealigned single focal plane and an integrated array of soft elastomer-based micropads, used together to allow for trapping of mother cells, removal of daughter cells, monitoring gradual changes in aging, and unprecedented microscopic imaging of the whole aging process. Using the platform, we found remarkable age-associated changes in phenotypes (e.g., that cells can show strikingly differential cell and vacuole morphologies at the moment of their deaths), indicating substantial heterogeneity in cell aging and death. We envision the microfluidic dissection platform to become a major tool in aging research.

Three-dimensional CFD simulations with large displacement of the geometries using a connectivity-change moving mesh approach

This paper deals with three-dimensional (3D) numerical simulations involving 3D moving geometries with large displacements on unstructured meshes. Such simulations are of great value to industry, but remain very time-consuming. A robust moving mesh algorithm coupling an elasticity-like mesh deformation solution and mesh optimizations was proposed in previous works, which removes the need for global remeshing when performing large displacements. The optimizations, and in particular generalized edge/face swapping, preserve the initial quality of the mesh throughout the simulation. We propose to integrate an Arbitrary Lagrangian Eulerian compressible flow solver into this process to demonstrate its capabilities in a full CFD computation context. This solver relies on a local enforcement of the discrete geometric conservation law to preserve the order of accuracy of the time integration. The displacement of the geometries is either imposed, or driven by fluid–structure interaction (FSI). In the latter case, the six degrees of freedom approach for rigid bodies is considered. Finally, several 3D imposed-motion and FSI examples are given to validate the proposed approach, both in academic and industrial configurations

Characterization of the boundary layer at Dome C (East Antarctica) during the OPALE summer campaign

The regional climate model MAR was run for the region of Dome C located on the East Antarctic plateau, during Antarctic summer 2011–2012, in order to refine our understanding of meteorological conditions during the OPALE observation campaign. A very high vertical resolution is set up in the lower troposphere, with a grid spacing of roughly 2 m. Comparisons are made with observed temperatures and winds near the surface and from a 45 m high tower as well as sodar and radiation data. MAR is generally in very good agreement with the observations but sometimes underestimates cloud formation, leading to an underestimation of the simulated downward long-wave radiation. Absorbed short-wave radiation may also be slightly overestimated due to an underestimation of the snow albedo and this influences the surface energy budget and atmospheric turbulence. Nevertheless the model provides sufficiently reliable information that represent key parameters when discussing the representativeness of chemical measurements made nearby the ground surface during field campaigns conducted at the Concordia site located at Dome C (3233 m a.s.l.)

Assessment of human influenza pandemic scenarios in Europe

The response to the emergence of the 2009 influenza A(H1N1) pandemic was the result of a decade of pandemic planning, largely centred on the threat of an avian influenza A(H5N1) pandemic. Based on a literature review, this study aims to define a set of new pandemic scenarios that could be used in case of a future influenza pandemic. A total of 338 documents were identified using a searching strategy based on seven combinations of keywords. Eighty-three of these documents provided useful information on the 13 virus-related and health-system-related parameters initially considered for describing scenarios. Among these, four parameters were finally selected (clinical attack rate, case fatality rate, hospital admission rate, and intensive care admission rate) and four different levels of severity for each of them were set. The definition of six most likely scenarios results from the combination of four different levels of severity of the four final parameters (256 possible scenarios). Although it has some limitations, this approach allows for more flexible scenarios and hence it is far from the classic scenarios structure used for pandemic plans until 2009