Insights into the N-Sulfation Mechanism: Molecular Dynamics Simulations of the N-Sulfotransferase Domain of Ndst1 and Mutants

Sulfation patterns along glycosaminoglycan (GAG) chains dictate their functional role. the N-deacetylase N-sulfotransferase family (NDST) catalyzes the initial downstream modification of heparan sulfate and heparin chains by removing acetyl groups from subsets of N-acetylglucosamine units and, subsequently, sulfating the residual free amino groups. These enzymes transfer the sulfuryl group from 3'-phosphoadenosine-5'-phosphosulfate (PAPS), yielding sulfated sugar chains and 3'-phosphoadenosine-5'-phosphate (PAP). for the N-sulfotransferase domain of NDST1, Lys833 has been implicated to play a role in holding the substrate glycan moiety close to the PAPS cofactor. Additionally, Lys833 together with His716 interact with the sulfonate group, stabilizing the transition state. Such a role seems to be shared by Lys614 through donation of a proton to the bridging oxygen of the cofactor, thereby acting as a catalytic acid. However, the relevance of these boundary residues at the hydrophobic cleft is still unclear. Moreover, whether Lys833, His716 and Lys614 play a role in both glycan recognition and glycan sulfation remains elusive. in this study we evaluate the contribution of NDST mutants (Lys833, His716 and Lys614) to dynamical effects during sulfate transfer using comprehensive combined docking and essential dynamics. in addition, the binding location of the glycan moiety, PAPS and PAP within the active site of NDST1 throughout the sulfate transfer were determined by intermediate state analysis. Furthermore, NDST1 mutants unveiled Lys833 as vital for both the glycan binding and subsequent N-sulfotransferase activity of NDST1.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional do Desenvolvimento Cientifico e TecnologicoCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Bioquim, São Paulo, BrazilUniv Fed Rio Grande do Sul, Ctr Biotecnol, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, BrazilFAPESP: 2010/52426-3Web of Scienc

Layer-by-layer functionalized nanotube arrays: A versatile microfluidic platform for biodetection

We demonstrate the layer-by-layer (LbL) assembly of polyelectrolyte multilayers (PEM) on three-dimensional nanofiber scaffolds. High porosity (99%) aligned carbon nanotube (CNT) arrays are photolithographically patterned into elements that act as textured scaffolds for the creation of functionally coated (nano)porous materials. Nanometer-scale bilayers of poly(allylamine hydrochloride)/poly(styrene sulfonate) (PAH/SPS) are formed conformally on the individual nanotubes by repeated deposition from aqueous solution in microfluidic channels. Computational and experimental results show that the LbL deposition is dominated by the diffusive transport of the polymeric constituents, and we use this understanding to demonstrate spatial tailoring on the patterned nanoporous elements. A proof-of-principle application, microfluidic bioparticle capture using N-hydroxysuccinimide-biotin binding for the isolation of prostate-specific antigen (PSA), is demonstrated.National Science Foundation (U.S.) (Award DMR-0819762

Problems in Lattice Gauge Fixing

We review many topics and results about numeric gauge fixing in lattice QCD.Comment: 47 pages, 16 eps figures. Review article sent to IJMP

Formulación de dieta artificial para la crianza de Spodoptera frugiperda utilizando insumos de la región de San Martín

Fall armyworm (Spodoptera frugiperda) is the most important pest of this crop in the San Martín region. Its massive breeding, for the purpose of studying its biology, breeding of natural enemies and others, is limited by the lack of inputs; for this reason, the objective of the study was to evaluate the different physiological and biological parameters of S. frugiperda, raised on an artificial diet made with inputs from the region. 35 first instar larvae were used for each treatment, each larva represented a repetition. For larval development, an incubator was used at 30±1°C and photophase 14h. The percentage of viability and the duration of the different instars, pupal weight and deformations were evaluated; the number of molts was determined by measuring the cephalic capsule of larvae; in adults the duration of the pre-oviposition, oviposition and post-oviposition period, and gross fertility were evaluated. The results suggest that the ESALQ-modified diet is the most suitable for raising S. frugiperda, since it showed a larval viability of 54.3% and 5 instars, the pupae had greater weight and the adults presented higher fecundity (848.2 eggs per female); the pupae on the diet with inputs from the region, presented deficient chitinization of the first abdominal segments and 0% viability.El cogollero del maíz (Spodoptera frugiperda) es la plaga más importante de este cultivo en la región San Martín, su crianza masiva, para fines de estudiar su biología, crianza de enemigos naturales y otros, se ve limitada por la falta de insumos; por esta razón el objetivo del estudio fue evaluar los diferentes parámetros fisiológicos y biológicos de S. frugiperda, criada en una dieta artificial elaborada con insumos de la región. Se utilizó 35 larvas de primer ínstar para cada tratamiento, cada larva representó una repetición. Para el desarrollo larval, se utilizó una incubadora a 30±1 °C y fotofase 14h. Se evaluó el porcentaje de viabilidad y la duración de los diferentes ínstares, peso de pupas y deformaciones; el número de mudas se determinó midiendo la capsula cefálica de larvas; en adultos se evaluó la duración del periodo de pre-oviposición, oviposición y post-oviposición, y la fecundidad bruta. Los resultados sugieren que la dieta ESALQ-modificada es la más adecuada para la crianza S. frugiperda, ya que mostró una viabilidad larval de 54,3% y 5 instares, las pupas tuvieron mayor peso y los adultos presentaron mayor fecundidad (848,2 huevos por hembra); las pupas sobre la dieta con insumos de la región, presentaron deficiente quitinización de los primeros segmentos abdominales y 0% de viabilidad

Potential of AKR1B10 as a Biomarker and Therapeutic Target in Type 2 Leprosy Reaction

The AKR1B10 (aldo-keto reductase family 1 member B10) gene has important functions in carcinogen-induced neoplasia. AKR1B10 is also expressed in type 2 reaction leprosy patients (R2). We measured the expression of AKR1B10 in the skin lesions of patients with leprosy by immunohistochemistry from biopsies that encompassed the spectrum of types of leprosy, based on the Ridley and Jopling classification [10 samples each of tuberculoid (TT), borderline tuberculoid (BT), mid-borderline (BB), and borderline lepromatous (BL) lesions; four samples of lepromatous lesions (LL)], reactional leprosy [14 samples of type 1 Reaction (R1) and 10 samples of type 2 Reaction (R2)], and biopsies from 9 healthy control (HC) subjects. In addition, 46 lepromatous lesions (BL and LL), 45 lepromatous lesions in regression, and 115 R2 lesions were included. Eight of 10 R2 samples (80%), 3 of 46 active BL and LL samples (6%), 23 of 45 BL and LL samples in regression (51%), and 107 of 115 R2 samples (93%) were positive for AKR1B10, differing significantly between all groups (p < 0.05). AKR1B10 expression was highest in the cytoplasm of macrophages. Thus, AKR1B10 is overexpressed on the lepromatous side (BL and LL) in samples that are in regression, especially type 2 reaction-associated lesions, rendering it a potential marker of type 2 reactional episodes of leprosy and a target of drugs against reactional episodes

Observables in 3d spinfoam quantum gravity with fermions

We study expectation values of observables in three-dimensional spinfoam quantum gravity coupled to Dirac fermions. We revisit the model introduced by one of the authors and extend it to the case of massless fermionic fields. We introduce observables, analyse their symmetries and the corresponding proper gauge fixing. The Berezin integral over the fermionic fields is performed and the fermionic observables are expanded in open paths and closed loops associated to pure quantum gravity observables. We obtain the vertex amplitudes for gauge-invariant observables, while the expectation values of gauge-variant observables, such as the fermion propagator, are given by the evaluation of particular spin networks.Comment: 32 pages, many diagrams, uses psfrag

Dual Superconductor Scenario of Confinement: A Systematic Study of Gribov Copy Effects

We perform a study of the effects from maximal abelian gauge Gribov copies in the context of the dual superconductor scenario of confinement, on the basis of a novel approach for estimation of systematic uncertainties from incomplete gauge fixing. We present numerical results, in SU(2) lattice gauge theory, using the overrelaxed simulated annealing gauge fixing algorithm. We find abelian and non-abelian string tensions to differ significantly, their ratio being 0.92(4) at BETA = 2.5115. An approximate factorization of the abelian potential into monopole and photon contributions has been confirmed, the former giving rise to the abelian string tension.Comment: 35 pages uucompressed LaTeX with 10 encapsuled postscript figure

Áreas prioritarias para la conservación de la Provincia de Alto Amazonas, Loreto, Perú

En el presente trabajo se identifican las áreas propicias para la conservación de la Provincia de Alto Amazonas (con una superficie aproximada de: 2004288 ha) a partir del submodelo de Valor Bioecológico de la Meso Zonificación Ecológica y Económica de la Provincia de Alto Amazonas. La identificación se realizó a partir de las siguientes capas de información: Diversidad biológica, Especies endémicas, Especies amenazadas, Biomasa, Ecosistemas Singulares, Importancia hídrica, las especificaciones del Decreto Supremo 087-2004-PCM, y la capa de información de Áreas Naturales Protegidas por el Estado. Casi un tercio de  la superficie de la provincia de Alto Amazonas (28.20%) presenta  el grado de muy alto valor para la conservación debido a la presencia de especies endémicas de flora y fauna, alta diversidad de flora y fauna, ecosistemas singulares, áreas naturales protegidas y áreas con importancia hídrica. Los sectores con áreas para la conservación se distribuyen principalmente hacia la cuenca del Nucuray, la cuenca del Marañón y la parte baja del Huallaga. Se recomienda conservar estos sectores por presentar muchas características relevantes para la conservación

Timeless standards for species delimitation

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