Reference values for lysosomal enzymes activities using dried blood spots samples - a Brazilian experience

Background: Lysosomal storage diseases (LSD) are inherited disorders caused by deficiency of lysosomal enzymes in which early diagnosis is essential to provide timely treatment. This study reports interval values for the activity of lysosomal enzymes that are deficient in Mucopolysaccharidosis type I, Fabry, Gaucher and Pompe disease, using dried blood spots on filter paper (DBS) samples in a Brazilian population.Results: Reference activity values were obtained from healthy volunteers samples for alpha-galactosidase A (4.57 +/- 1.37 umol/L/h), beta-glucosidase (3.06 +/- 0.99 umol/L/h), alpha-glucosidase (ratio: 13.19 +/- 4.26; % inhibition: 70.66 +/- 7.60), alpha-iduronidase (3.45 +/- 1.21 umol/L/h) and beta-galactosidase (14.09 +/- 4.36 umol/L/h).Conclusion: Reference values of five lysosomal enzymes were determined for a Brazilian population sample. However, as our results differ from other laboratories, it highlights the importance of establishing specific reference values for each center

Pair production in laser fields oscillating in space and time

The production of electron-positron pairs from vacuum by counterpropagating laser beams of linear polarization is calculated. In contrast to the usual approximate approach, the spatial dependence and magnetic component of the laser field are taken into account. We show that the latter strongly affects the creation process at high laser frequency: the production probability is reduced, the kinematics is fundamentally modified, the resonant Rabi-oscillation pattern is distorted and the resonance positions are shifted, multiplied and split.Comment: 5 pages, 5 figure

Hole dynamics in generalized spin backgrounds in infinite dimensions

We calculate the dynamical behaviour of a hole in various spin backgrounds in infinite dimensions, where it can be determined exactly. We consider hypercubic lattices with two different types of spin backgrounds. On one hand we study an ensemble of spin configurations with an arbitrary spin probability on each sublattice. This model corresponds to a thermal average over all spin configurations in the presence of staggered or uniform magnetic fields. On the other hand we consider a definite spin state characterized by the angle between the spins on different sublattices, i.e a classical spin system in an external magnetic field. When spin fluctuations are considered, this model describes the physics of unpaired particles in strong coupling superconductors.Comment: Accepted in Phys. Rev. B. 18 pages of text (1 fig. included) in Latex + 2 figures in uuencoded form containing the 2 postscripts (mailed separately

Quartz chemistry of granitic pegmatites: Implications for classification, genesis and exploration

Quartz from 254 pegmatites representing eight pegmatite fields and provinces worldwide was investigated by laser-ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS) to determine concentrations of trace elements Al, Ti, Li, Ge, B, Be, Rb, Na, K, Ca, P, Ga, Sb, Zn and U. A total of 271 new analyses combined with 535 published LA-ICP-MS quartz chemistry data were evaluated with binary and ternary trace element discrimination plots and principal component analysis (PCA). The classifications applied for discrimination of pegmatite types include the widely applied NYF(Nb-Y-F) - LCT(Li-Cs-Ta) classification and the new RMG (pegmatites derived from residual melts of granite magmatism) - DPA (pegmatites as direct products of anatexis) grouping. Pegmatites of both classifications can be well distinguished via Al-Ti, Al-Li and Al/Ti-Ge/Ti binary trace element plots and the Ti - Al/10 - 10*Ge ternary diagram. PCA applied to Al, Li, Ti, Be, B, Ge and Rb contents in quartz allowed to further distinguish between anatectic DPA-1 (Li-enriched DPA) and granite-pluton-derived RMG-1 (Li-enriched RMG) pegmatites. Some pegmatite fields and provinces (Hagendorf-Pleystein, Oxford County) are distinguishable by region-specific Li, Ge and Al contents. The results imply that the chemistry of pegmatite quartz is mainly controlled by the origin (source rock chemistry) of pegmatite melts and, to a much lesser extent, by the geodynamic setting of the pegmatite fields and provinces. Chemically primitive NYF and DPA-2 type pegmatites contain quartz with the lowest total trace-element contents and lowest internal-pegmatite trace-element variation, making it potentially suitable for high-tech application. Pegmatite quartz containing >30 μgg-1 Li and >100 μgg-1 Al is strongly indicative of economic spodumene/montebrasite mineralization and, thus, serves as a strong Li-mineralization pathfinder mineral. Quartz with >5 μgg-1 B may be a potential indicator for gem-quality tourmaline mineralization.Fil: Müller, Axel. University of Oslo; Noruega. Natural History Museum; Reino UnidoFil: Keyser, William. University of Oslo; NoruegaFil: Simmons, William B.. Maine Mineral And Gem Museum; Estados UnidosFil: Webber, Karen. Maine Mineral And Gem Museum; Estados UnidosFil: Wise, Michael. Smithsonian Institution; Estados UnidosFil: Beurlen, Hartmut. Universidade Federal de Pernambuco; BrasilFil: Garate Olave, Idoia. Universidad del País Vasco; EspañaFil: Roda Robles, Encarnación. Universidad del País Vasco; EspañaFil: Galliski, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; Argentin

Muon pair creation from positronium in a circularly polarized laser field

We study elementary particle reactions that result from the interaction of an atomic system with a very intense laser wave of circular polarization. As a specific example, we calculate the rate for the laser-driven reaction $e^+e^- \to \mu^+\mu^-$, where the electron and positron originate from a positronium atom or, alternatively, from a nonrelativistic $e^+e^-$ plasma. We distinguish accordingly between the coherent and incoherent channels of the process. Apart from numerical calculations, we derive by analytical means compact formulas for the corresponding reaction rates. The rate for the coherent channel in a laser field of circular polarization is shown to be damped because of the destructive interference of the partial waves that constitute the positronium ground-state wave packet. Conditions for the observation of the process via the dominant incoherent channel in a circularly polarized field are pointed out

Density matrix algorithm for the calculation of dynamical properties of low dimensional systems

I extend the scope of the density matrix renormalization group technique developed by White to the calculation of dynamical correlation functions. As an application and performance evaluation I calculate the spin dynamics of the 1D Heisenberg chain.Comment: 4 pages + 4 figures in one Latex + 4 postscript file

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

Comparative Studies in the A30P and A53T α-Synuclein C. elegans Strains to Investigate the Molecular Origins of Parkinson's Disease.

The aggregation of α-synuclein is a hallmark of Parkinson's disease (PD) and a variety of related neurological disorders. A number of mutations in this protein, including A30P and A53T, are associated with familial forms of the disease. Patients carrying the A30P mutation typically exhibit a similar age of onset and symptoms as sporadic PD, while those carrying the A53T mutation generally have an earlier age of onset and an accelerated progression. We report two C. elegans models of PD (PDA30P and PDA53T), which express these mutational variants in the muscle cells, and probed their behavior relative to animals expressing the wild-type protein (PDWT). PDA30P worms showed a reduced speed of movement and an increased paralysis rate, control worms, but no change in the frequency of body bends. By contrast, in PDA53T worms both speed and frequency of body bends were significantly decreased, and paralysis rate was increased. α-Synuclein was also observed to be less well localized into aggregates in PDA30P worms compared to PDA53T and PDWT worms, and amyloid-like features were evident later in the life of the animals, despite comparable levels of expression of α-synuclein. Furthermore, squalamine, a natural product currently in clinical trials for treating symptomatic aspects of PD, was found to reduce significantly the aggregation of α-synuclein and its associated toxicity in PDA53T and PDWT worms, but had less marked effects in PDA30P. In addition, using an antibody that targets the N-terminal region of α-synuclein, we observed a suppression of toxicity in PDA30P, PDA53T and PDWT worms. These results illustrate the use of these two C. elegans models in fundamental and applied PD research