392 research outputs found

    Arsenite sorption and co-precipitation with calcite

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    Sorption of As(III) by calcite was investigated as a function of As(III) concentration, time and pH. The sorption isotherm, i.e. the log As(III) vs. log [As(OH)3 degrees / Assat] plot is S-shaped and has been modelled on an extended version of the surface precipitation model. At low concentrations, As(OH)3 degrees is adsorbed by complexation to surface Ca surface sites, as previously described by the X-ray standing wave technique. The inflexion point of the isotherm, where As(OH)3 degrees is limited by the amount of surface sites (ST), yields 6 sites nm-2 in good agreement with crystallographic data. Beyond this value, the amount of sorbed arsenic increases linearly with solution concentration, up to the saturation of arsenic with respect to the precipitation of CaHAsO3(s). The solid solutions formed in this concentration range were examined by X-ray and neutron diffraction. The doped calcite lattice parameters increase with arsenic content while c/a ratio remains constant. Our results made on bulk calcite on the atomic displacement of As atoms along [0001] direction extend those published by Cheng et al., (1999) on calcite surface. This study provides a molecular-level explanation for why As(III) is trapped by calcite in industrial treatments.Comment: 9 page

    G-CSF Prevents the Progression of Structural Disintegration of White Matter Tracts in Amyotrophic Lateral Sclerosis: A Pilot Trial

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    Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.Methods: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 mu g/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.Results: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.Conclusions: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors

    Molecular mechanisms and phenotypic variation in RYR1-related congenital myopathies

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    Dominant mutations in the skeletal muscle ryanodine receptor (RYR1) gene are well-recognized causes of both malignant hyperthermia susceptibility (MHS) and central core disease (CCD). More recently, recessive RYR1 mutations have been described in few congenital myopathy patients with variable pathology, including multi-minicores. Although a clinical overlap between patients with dominant and recessive RYR1 mutations exists, in most cases with recessive mutations the pattern of muscle weakness is remarkably different from that observed in dominant CCD. In order to characterize the spectrum of congenital myopathies associated with RYR1 mutations, we have investigated a cohort of 44 patients from 28 families with clinical and/or histopathological features suggestive of RYR1 involvement. We have identified 25 RYR1 mutations, 9 of them novel, including 12 dominant and 13 recessive mutations. With only one exception, dominant mutations were associated with a CCD phenotype, prominent cores and predominantly occurred in the RYR1 C-terminal exons 101 and 102. In contrast, the 13 recessive RYR1 mutations were distributed evenly along the entire RYR1 gene and were associated with a wide range of clinico-pathological phenotypes. Protein expression studies in nine cases suggested a correlation between specific mutations, RyR1 protein levels and resulting phenotype: in particular, whilst patients with dominant or recessive mutations associated with typical CCD phenotypes appeared to have normal RyR1 expression, individuals with more generalized weakness, multi-minicores and external ophthalmoplegia had a pronounced depletion of the RyR1 protein. The phenomenon of protein depletion was observed in some patients compound heterozygous for recessive mutations at the genomic level and silenced another allele in skeletal muscle, providing additional information on the mechanism of disease in these patients. Our data represent the most extensive study of RYR1-related myopathies and indicate complex genotype-phenotype correlations associated with mutations differentially affecting assembly and function of the RyR1 calcium release channe

    Kinnier Wilson's puzzling features of amyotrophic lateral sclerosis

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    Pre-eminent neurologist S.A. Kinnier Wilson’s posthumously published 1940 textbook ‘Neurology’ included a detailed clinicopathological account of the neurodegenerative disorder amyotrophic lateral sclerosis (ALS). In providing a comprehensive discussion of the breadth of the clinical heterogeneity, he highlighted five “puzzling features” that appear prescient of the modern recognition of ALS as a complex multisystem syndrome. The issues he raises span the areas of ongoing debate and active research in ALS, including clinical and pathological discordance, upper versus lower motor neuron loss, and the apparent non-random onset and spread of clinical symptoms. We discuss each of his observations in light of the great advances in histopathology, molecular biology, neurophysiology and neuroimaging over the subsequent 75 years

    Growth hormone secretion is correlated with neuromuscular innervation rather than motor neuron number in early-symptomatic male amyotrophic lateral sclerosis mice

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    GH deficiency is thought to be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). However, therapy with GH and/or IGF-I has not shown benefit. To gain a better understanding of the role of GH secretion in ALS pathogenesis, we assessed endogenous GH secretion in wild-type and hSOD1(G93A) mice throughout the course of ALS disease. Male wild-type and hSOD1(G93A) mice were studied at the presymptomatic, onset, and end stages of disease. To assess the pathological features of disease, we measured motor neuron number and neuromuscular innervation. We report that GH secretion profile varies at different stages of disease progression in hSOD1(G93A) mice; compared with age-matched controls, GH secretion is unchanged prior to the onset of disease symptoms, elevated at the onset of disease symptoms, and reduced at the end stage of disease. In hSOD1(G93A) mice at the onset of disease, GH secretion is positively correlated with the percentage of neuromuscular innervation but not with motor neuron number. Moreover, this occurs in parallel with an elevation in the expression of muscle IGF-I relative to controls. Our data imply that increased GH secretion at symptom onset may be an endogenous endocrine response to increase the local production of muscle IGF-I to stimulate reinnervation of muscle, but that in the latter stages of disease this response no longer occurs

    Lithium suppression of tau induces brain iron accumulation and neurodegeneration

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    Lithium is a first-line therapy for bipolar affective disorder. However, various adverse effects, including a Parkinson-like hand tremor, often limit its use. The understanding of the neurobiological basis of these side effects is still very limited. Nigral iron elevation is also a feature of Parkinsonian degeneration that may be related to soluble tau reduction. We found that magnetic resonance imaging T2 relaxation time changes in subjects commenced on lithium therapy were consistent with iron elevation. In mice, lithium treatment lowers brain tau levels and increases nigral and cortical iron elevation that is closely associated with neurodegeneration, cognitive loss and parkinsonian features. In neuronal cultures lithium attenuates iron efflux by lowering tau protein that traffics amyloid precursor protein to facilitate iron efflux. Thus, tau- and amyloid protein precursor-knockout mice were protected against lithium-induced iron elevation and neurotoxicity. These findings challenge the appropriateness of lithium as a potential treatment for disorders where brain iron is elevated (for example, Alzheimer’s disease), and may explain lithium-associated motor symptoms in susceptible patients

    The influence of nano-additives in strengthening mechanical performance of 3D printed multi-binder geopolymer composites

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    The weak mechanical properties the 3D printed parts can limit the competence of this technology when compared to conventionally cast-in-mold cementitious composites structures. However, experimental results in this study showed that the incorporation of nano additives could improve the mechanical property of printed structures. Six geopolymeric mixtures were designed and tested for their flow-ability, shape stability, buildability and mechanical performance. Different dosage of nano graphite platelets (NGPs) ranging from 0.1% to 1%, by the weight of geopolymer, were incorporated to the best performing geopolymer. The 3D printed geopolymer with 1% of NGPs increased the flexural strength by 89% and 46% compared to the same 3D printed and casted geopolymer without any NGPs, respectively. The same increase for compressive strength was 28% and 12%. Moreover, the geopolymer mix containing 1% of NGPs demonstrated the best shape retention and buildability

    Low-delay Single Holoscopic 3D Computer Generated Image To Multiview Images

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