Minimal ureagenesis is necessary for survival in the murine model of hyperargininemia treated by AAV-based gene therapy.

Hyperammonemia is less severe in arginase 1 deficiency compared with other urea cycle defects. Affected patients manifest hyperargininemia and infrequent episodes of hyperammonemia. Patients typically suffer from neurological impairment with cortical and pyramidal tract deterioration, spasticity, loss of ambulation, seizures and intellectual disability; death is less common than with other urea cycle disorders. In a mouse model of arginase I deficiency, the onset of symptoms begins with weight loss and gait instability, which progresses toward development of tail tremor with seizure-like activity; death typically occurs at about 2 weeks of life. Adeno-associated viral vector gene replacement strategies result in long-term survival of mice with this disorder. With neonatal administration of vector, the viral copy number in the liver greatly declines with hepatocyte proliferation in the first 5 weeks of life. Although the animals do survive, it is not known from a functional standpoint how well the urea cycle is functioning in the adult animals that receive adeno-associated virus. In these studies, we administered [1-13C] acetate to both littermate controls and adeno-associated virus-treated arginase 1 knockout animals and examined flux through the urea cycle. Circulating ammonia levels were mildly elevated in treated animals. Arginine and glutamine also had perturbations. Assessment 30 min after acetate administration demonstrated that ureagenesis was present in the treated knockout liver at levels as low at 3.3% of control animals. These studies demonstrate that only minimal levels of hepatic arginase activity are necessary for survival and ureagenesis in arginase-deficient mice and that this level of activity results in control of circulating ammonia. These results may have implications for potential therapy in humans with arginase deficiency

Comparative study of two proteomic quantitative methods, Dige and Itraq using 2-D gel or Lc-Esi Qtof

Comunicaciones a congreso

Endmember extraction algorithms from hyperspectral images

During the last years, several high-resolution sensors have been developed for hyperspectral remote sensing applications. Some of these sensors are already available on space-borne devices. Space-borne sensors are currently acquiring a continual stream of hyperspectral data, and new efficient unsupervised algorithms are required to analyze the great amount of data produced by these instruments. The identification of image endmembers is a crucial task in hyperspectral data exploitation. Once the individual endmembers have been identified, several methods can be used to map their spatial distribution, associations and abundances. This paper reviews the Pixel Purity Index (PPI), N-FINDR and Automatic Morphological Endmember Extraction (AMEE) algorithms developed to accomplish the task of finding appropriate image endmembers by applying them to real hyperspectral data. In order to compare the performance of these methods a metric based on the Root Mean Square Error (RMSE) between the estimated and reference abundance maps is used

A white dwarf catalogue from Gaia-DR2 and the Virtual Observatory

We present a catalogue of 73¿221 white dwarf candidates extracted from the astrometric and photometric data of the recently published Gaia-DR2 catalogue. White dwarfs were selected from the Gaia Hertzsprung–Russell diagram with the aid of the most updated population synthesis simulator. Our analysis shows that Gaia has virtually identified all white dwarfs within 100¿pc from the Sun. Hence, our sub-population of 8555 white dwarfs within this distance limit and the colour range considered, -0.52<(GBP-GRP)<0.80¿, is the largest and most complete volume-limited sample of such objects to date. From this sub-sample, we identified 8343 CO-core and 212 ONe-core white dwarf candidates and derived a white dwarf space density of 4.9±0.4×10-3pc-3¿. A bifurcation in the Hertzsprung–Russell diagram for these sources, which our models do not predict, is clearly visible. We used the Virtual Observatory SED Analyzer tool to derive effective temperatures and luminosities for our sources by fitting their spectral energy distributions, that we built from the ultraviolet to the near-infrared using publicly available photometry through the Virtual Observatory. From these parameters, we derived the white dwarf radii. Interpolating the radii and effective temperatures in hydrogen-rich white dwarf cooling sequences, we derived the surface gravities and masses. The Gaia 100¿pc white dwarf population is clearly dominated by cool (~8000¿K) objects and reveals a significant population of massive (¿M~0.8M¿¿) white dwarfs, of which no more than ~30--40 per cent can be attributed to hydrogen-deficient atmospheres, and whose origin remains uncertain.Peer ReviewedPreprin

Social comparison processes and catastrophising in fibromyalgia:A path analysis

Introduction: In addition to coping strategies, social comparison may play a role in illness adjustment. However, little is known about the role of contrast and identification in social comparison in adaptation to fibromyalgia.Aim: To evaluate through a path analysis in a sample of fibromyalgia patients, the association between identification and contrast in social comparison, catastrophising and specific health outcomes (fibromyalgia illness impact and psychological distress).Material and Method: 131 Spanish fibromyalgia outpatients (mean age: 50.15, SD=11.1) filled out a questionnaire.Results: We present a model that explained 33% of the variance in catastrophising by direct effects of more use of upward contrast and downward identification. In addition, 35% of fibromyalgia illness impact variance was explained by less upward identification, more upward contrast and more catastrophising and 42% of the variance in psychological distress by a direct effect of more use of upward contrast together with higher fibromyalgia illness impact.Discussion: We suggest that intervention programmes with chronic pain and fibromyalgia patients should focus on enhancing the use of upward identification in social comparison, and on minimising the use of upward contrast and downward identification in social comparison

Random Forest identification of the thin disk, thick disk and halo Gaia-DR2 white dwarf population

Gaia-DR2 has provided an unprecedented number of white dwarf candidates of our Galaxy. In particular, it is estimated that Gaia-DR2 has observed nearly 400,000 of these objects and close to 18,000 up to 100 pc from the Sun. This large quantity of data requires a thorough analysis in order to uncover their main Galactic population properties, in particular the thin and thick disk and halo components. Taking advantage of recent developments in artificial intelligence techniques, we make use of a detailed Random Forest algorithm to analyse an 8-dimensional space (equatorial coordinates, parallax, proper motion components and photometric magnitudes) of accurate data provided by Gaia-DR2 within 100 pc from the Sun. With the aid of a thorough and robust population synthesis code we simulated the different components of the Galactic white dwarf population to optimize the information extracted from the algorithm for disentangling the different population components. The algorithm is first tested in a known simulated sample achieving an accuracy of 85.3%. Our methodology is thoroughly compared to standard methods based on kinematic criteria demonstrating that our algorithm substantially improves previous approaches. Once trained, the algorithm is then applied to the Gaia-DR2 100 pc white dwarf sample, identifying 12,227 thin disk, 1,410 thick disk and 95 halo white dwarf candidates, which represent a proportion of 74:25:1, respectively. Hence, the numerical spatial densities are $(3.6\pm0.4)\times10^{-3}\,{\rm pc^{-3}}$, $(1.2\pm0.4)\times10^{-3}\,{\rm pc^{-3}}$ and $(4.8\pm0.4)\times10^{-5}\,{\rm pc^{-3}}$ for the thin disk, thick disk and halo components, respectively. The populations thus obtained represent the most complete and volume-limited samples to date of the different components of the Galactic white dwarf population.Comment: 18 pages, 11 figures and 3 tables. Accepted for publication in MNRA

CMV matrices in random matrix theory and integrable systems: a survey

We present a survey of recent results concerning a remarkable class of unitary matrices, the CMV matrices. We are particularly interested in the role they play in the theory of random matrices and integrable systems. Throughout the paper we also emphasize the analogies and connections to Jacobi matrices.Comment: Based on a talk given at the Short Program on Random Matrices, Random Processes and Integrable Systems, CRM, Universite de Montreal, 200

Endmember extraction algorithms from hyperspectral images

During the last years, several high-resolution sensors have been developed for hyperspectral remote sensing applications. Some of these sensors are already available on space-borne devices. Space-borne sensors are currently acquiring a continual stream of hyperspectral data, and new efficient unsupervised algorithms are required to analyze the great amount of data produced by these instruments. The identification of image endmembers is a crucial task in hyperspectral data exploitation. Once the individual endmembers have been identified, several methods can be used to map their spatial distribution, associations and abundances. This paper reviews the Pixel Purity Index (PPI), N-FINDR and Automatic Morphological Endmember Extraction (AMEE) algorithms developed to accomplish the task of finding appropriate image endmembers by applying them to real hyperspectral data. In order to compare the performance of these methods a metric based on the Root Mean Square Error (RMSE) between the estimated and reference abundance maps is used

The cAMP Signaling pathway and direct protein kinase a phosphorylation regulate polycystin-2 (TRPP2) Channel Function

Polycystin-2 (PC2) is aTRP-type, Ca2+-permeable non-selective cation channel that plays an important role in Ca2+ signaling in renal and non-renal cells. The effect(s) of the cAMP pathway and kinase mediated phosphorylation of PC2 seem to be relevant to PC2 trafficking and its interaction with polycystin-1. However, the role of PC2 phosphorylation in channel function is still poorly defined. Here we reconstituted apical membranes of term human syncytiotrophoblast (hST), containing endogenous PC2 (PC2hst), and in vitro translated channel protein (PC2iv). Addition of the catalytic subunit of PKA increased by 566% the spontaneous PC2hst channel activity in the presence of ATP. Interestingly, 8-Br-cAMP also stimulated spontaneous PC2hst channel activity in the absence of the exogenous kinase. Either stimulation was inhibited by addition of alkaline phosphatase, which in turn, was reversed by the phosphatase inhibitor vanadate. Neither maneuver modified the single channel conductance but instead increased channel mean open time. PKA directly phosphorylated PC2, which increased the mean open time but not the single channel conductance of the channel. PKA phosphorylation did not modify either R742X truncated or S829A-mutant PC2iv channel function. The data indicate that the cAMP pathway regulates PC2-mediated cation transport in the hST. The relevant PKA site for PC2 channel regulation centers on a single residue serine 829, in the carboxyl terminus.Fil: Cantero, Maria del Rocio. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Biofísica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Velázquez, Irina Florencia. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Biofísica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Streets, Andrew J.. University of Sheffield Medical School; Reino UnidoFil: Ong, Albert C. M.. University of Sheffield Medical School; Reino UnidoFil: Cantiello, Horacio Fabio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Biofísica; Argentin

Application of a non destructive method for developing physical properties ofbone tissue based on Imagenology tecniques and Cad software tools

Los ensayos mecánicos son usados para la caracterización de propiedades mecánicas de tejidos óseos, sin embargo, debido al carácter destructivo del ensayo, las probetas usadas son generalmente de tejidos óseos de cadáver humano o animales. La caracterización resultante de estos ensayos por lo tanto, es válida solo en los especímenes probados, porque el tejido óseo presenta alta variabilidad en sus propiedades debido al cambio de su densidad. Por este argumento y la naturaleza destructiva de los ensayos mecánicos, este tipo de ensayo no es apropiado para realizar la caracterización mecánica de tejidos vivos, lo cual limita las posibilidades de desarrollo en proyectos de investigación en vivo. El presente estudio fue desarrollado con el propósito de evaluar la viabilidad del uso de un método no destructivo, propuesto para calcular los valores de densidad aparente a partir de la densidad radiográfica. El método no destructivo tuvo su fundamento en la implementación de técnicas diagnósticas de imágenes tomográficas de hueso de mandíbula y el posterior reconocimiento de estas imágenes en un software Bio-CAD. A través del software MIMIC´S, se cuantificaron los valores de densidad a escala Hounsfield; los datos obtenidos fueron usados para deducir la curva de calibración lineal, permitiendo de esta forma, calcular el valor de densidad aparente de los especímenes. A partir de esta caracterización y la revisión de literatura, fue posible definir las propiedades mecánicas de la probeta ósea. De acuerdo con los resultados obtenidos en el presente trabajo de investigación, se estableció una alternativa para la caracterización mecánica de tejidos rígidos como el hueso. De acuerdo a la naturaleza no destructiva del método, el uso de este método podría ser extendido a experimentación con tejidos vivos, la cual estaba restringida, por las limitaciones existentes con el método destructivo basado en ensayos mecánicos.Abstract: Mechanical tests are used for characterization of mechanical properties of bone tissue; however, due to the destructive nature of the test, the specimens are generally used human cadaver bone tissues or animals. Furthermore the resultant characterization of these tests is valid only in the specimens tested, because the bone tissue shows high variability in their properties, so, the density change. This argument and the destructive nature of the mechanical tests are reason that this type of test is not appropriated for the mechanical characterization of living tissue, which limits the possibilities of development in live research projects. The present study was developed with the purpose of assessing the feasibility of using a non-destructive method to deduce the values of apparent density from radiographic density, supported by tomographic imaging diagnostic techniques in jaw bone and recognition these images in Bio-CAD software. Through software MIMIC’S, were quantified scale density values Hounsfield; these data were used to derive the linear calibration curve allowing calculating the apparent density of the specimens. From this characterization and review of literature, it was possible to determine the mechanical properties of the bone specimen. According to the results obtained in the present investigation, it was established an alternative to mechanical characterization through the application of non-destructive techniques, based on the analysis of Bio-CAD software and the calibration curve. Using this method could be extended to experiment with living tissue, which was restricted by the constraints with the destructive method based on mechanical tests