118 research outputs found

    Electrometric Titration of Sulfurous Acid with Permanganate

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    The purpose of this work was to determine whether sulfurous acid in acid solution is completely oxidized to sulfuric acid by an excess of permanganate as stated in the literature. If so the excess of permanganate should be easily and accurately determinable electrometrically with potassium iodide thus giving a simple method for determining sulfur dioxide, sulfurous acid or sulfites. The results show that with a small or large excess of permanganate only about 90 per cent is oxidized to sulfuric acid, the remainder of the sulfurous acid probably forming dithionic acid

    The Electrometric Standardizing of Titanous Solutions

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    The great value of titanous salts in analytical chemistry has become well known through the work of many chemists. Titanous chloride has been used in determining not only inorganic but also many organic substances, which are likely to be colored or to give colored solution on reduction, thus interfering in the accurate determination of end-points in the usual methods of analysis where colored indicators are used. Such difficulties would, of course, be removed by the application of the voltage method. Moreover, so intensely reducing is the titanous ion that an interval of nearly one volt is given between a slight excess of titanous ion and excess of such oxidizing agents as dichromate and permanganate, when the calomel-platinum cell is used, and this wide interval permits the determination with titanium of two oxidizing agents of quite different intensities when present in the same solution

    Targeted ASO-mediated Atp1a2 knockdown in astrocytes reduces SOD1 aggregation and accelerates disease onset in mutant SOD1 mice

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    Astrocyte-specific ion pump α2-Na+/K+-ATPase plays a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Here, we test the effect of Atp1a2 mRNA-specific antisense oligonucleotides (ASOs) to induce α2-Na+/K+-ATPase knockdown in the widely used ALS animal model, SOD1*G93A mice. Two ASOs led to efficient Atp1a2 knockdown and significantly reduced SOD1 aggregation in vivo. Although Atp1a2 ASO-treated mice displayed no off-target or systemic toxicity, the ASO-treated mice exhibited an accelerated disease onset and shorter lifespan than control mice. Transcriptomics studies reveal downregulation of genes involved in oxidative response, metabolic pathways, trans-synaptic signaling, and upregulation of genes involved in glutamate receptor signaling and complement activation, suggesting a potential role for these molecular pathways in de-coupling SOD1 aggregation from survival in Atp1a2 ASO-treated mice. Together, these results reveal a role for α2-Na+/K+-ATPase in SOD1 aggregation and highlight the critical effect of temporal modulation of genetically validated therapeutic targets in neurodegenerative diseases

    Defective proteostasis in induced pluripotent stem cell models of frontotemporal lobar degeneration

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    Impaired proteostasis is associated with normal aging and is accelerated in neurodegeneration. This impairment may lead to the accumulation of protein, which can be toxic to cells and tissue. In a subset of frontotemporal lobar degeneration with tau pathology (FTLD-tau) cases, pathogenic mutations in the microtubule-associated protein tau (MAPT) gene are sufficient to cause tau accumulation and neurodegeneration. However, the pathogenic events triggered by the expression of the mutant tau protein remain poorly understood. Here, we show that molecular networks associated with lysosomal biogenesis and autophagic function are disrupted in brains from FTLD-tau patients carrying a MAPT p.R406W mutation. We then used human induced pluripotent stem cell (iPSC)-derived neurons and 3D cerebral organoids from patients carrying the MAPT p.R406W mutation and CRISPR/Cas9, corrected controls to evaluate proteostasis. MAPT p.R406W was sufficient to induce morphological and functional deficits in the lysosomal pathway in iPSC-neurons. These phenotypes were reversed upon correction of the mutant allele with CRISPR/Cas9. Treatment with mTOR inhibitors led to tau degradation specifically in MAPT p.R406W neurons. Together, our findings suggest that MAPT p.R406W is sufficient to cause impaired lysosomal function, which may contribute to disease pathogenesis and serve as a cellular phenotype for drug screening

    Mechanism for etching of exfoliated graphene on substrates by low-energy electron irradiation from helium plasma electron sources

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    Article investigating the mechanism for etching of exfoliated graphene multilayers on SiO₂ by low-energy (50 eV) electron irradiation using He plasma systems for electron sources

    An Introduction to Sphingolipid Metabolism and Analysis by New Technologies

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    Sphingolipids (SP) are a complex class of molecules found in essentially all eukaryotes and some prokaryotes and viruses where they influence membrane structure, intracellular signaling, and interactions with the extracellular environment. Because of the combinatorial nature of their biosynthesis, there are thousands of SP subspecies varying in the lipid backbones and complex phospho- and glycoheadgroups. Therefore, comprehensive or “sphingolipidomic” analyses (structure-specific, quantitative analyses of all SP, or at least all members of a critical subset) are needed to know which and how much of these subspecies are present in a system as a step toward understanding their functions. Mass spectrometry and related novel techniques are able to quantify a small fraction, but nonetheless a substantial number, of SP and are beginning to provide information about their localization. This review summarizes the basic metabolism of SP and state-of-art mass spectrometric techniques that are producing insights into SP structure, metabolism, functions, and some of the dysfunctions of relevance to neuromedicine
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