A comparative study of the in vitro localization of mercury from phenylmercuric acetate and mercuric salt in rat kidney and liver subcellular fractions and their effect on alkaline phosphatase

Studies were undertaken to determine the extent and rate of binding of Hg-203 labeled phenylmercuric acetate and mercuric ace tate in rat kidney and liver slices and their subcellular fractions after 37°C incubation of the slices in Krebs-Ringer -phosphate solutions containing the mercurials at 10⁻⁴ molar. A fast and parallel rate of uptake of both mercurials in kidney slices between 1 to 3 hour periods was observed. The uptake of the two mercurials into liver slices was much less than that found in kidney slices, The binding rate of phenylmercuric acetate was almost double the rate of inorganic mercury. The subcellular fractions (nuclear, mitochondrial, microsomal, and soluble) of the tissue slices were prepared by homogenizing in 0.25 molar sucrose with subsequent differential centrifugation. Even though the two mercurials showed similar binding in kidney slices, it was found that phenylmercuric acetate was bound to almost twice the extent that of inorganic mercury in the mitochondria, micro-somal, and soluble fractions, with the preponderate of the inorganic mercury being bound in the nuclear. Phenylmercuric acetate was also bound to twice the extent of inorganic mercury in the mitochondrial, microsomal, and soluble fractions from incubated liver slices; however, the binding of the two mercurials in the liver nuclear fraction was similar during the first hours. Also, there was a decrease of the binding of inorganic mercury in the soluble fraction from incubated liver slices as the incubation time increased. Sephadex G-100 elution patterns of the soluble protein fractions from incubated kidney and liver slices were determined. The mercury binding patterns in the elution fractions were also determined. There was found to be three main peaks in the elution pattern from liver and kidney soluble proteins. The first peak represents proteins with molecular weights of 100,000 or greater. The second peak consists of 15,000 to 30,000 molecular weight proteins followed by a trough or dip in the pattern representing large polypeptides (molecular weights of 2,000 to 3,000). The last peak consists of small polypeptides. The specific binding of phenylmercuric acetate in the proteins of the elution pattern corresponding to a molecular weight of 100,000 or larger is greater than inorganic mercury by as much as two-fold. The 15,000 to 30,000 molecular weight proteins in the Sephadex G-100 elution patterns show 2.5 to five times as much specific binding of phenylmercuric acetate as compared to mercuric ion. There was no other area in the patterns in which the mercurials were bound to any significant extent. The binding patterns of the two mercury compounds in the soluble proteins of incubated kidney slices filtered through Sephadex G-100 columns, were similar to those of the liver soluble proteins, except for a very high specific binding of both in the region of the elution pattern corresponding to large polypeptides (2,000 to 3,000 molecular weight). Sephadex G-100 filtration of the incubation soluble proteins leached from liver slices indicated that phenylmercuric acetate caused a greater loss of large molecular weight proteins as compared to the control or inorganic mercury incubated slices. The migration characteristics of soluble proteins from kidney slices with and without mercurial treatment were measured by disc electrophorosis on polyacrylamide gel columns. The results indicated that phenylmercuric acetate caused a possible loss of large molecular weight proteins from the soluble fraction as compared to control or inorganic mercury incubated kidney slices. There was found to be no correlation between the specific binding of the two mercurials with the enzymatic activity of alkaline phosphatase in the soluble and microsomal fractions. It was found that kidney slices incubated in solutions of inorganic mercury resulted in approximately 83 percent enhancement of alkaline phosphatase activity in the soluble fraction as compared to control. Phenylmercuric acetate caused about a 40 percent increase. The microsomal fractions from inorganic mercury treated kidney slices showed a greater decrease in the alkaline phosphatase activity than did phenyl-mercuric acetate as compared to that of control. Twenty to 30 percent of the alkaline phosphatase activity of the 35,000 X G soluble fraction was removed by ultracentrifugation at 150,000 X G. It is possible that the apparent activation of alkaline phosphatase in the soluble fraction was due to a solubilization of the enzyme, with its genesis possibly being in the microsomes. Addition of phenylmercuric acetate to the reaction mixture at concentrations up to 10⁻³ molar caused no significant decrease in the activity of alkaline phosphatase from kidney soluble proteins, while inorganic mercury showed 20 percent inhibition at 10⁻⁵ molar and almost 75 percent inhibition at 5 X 10⁻⁵ molar. There was no significant stimulation of the enzyme when either of the mercurials was added to the reaction mixture

Huntington's disease: A clinical primer for acute and general physicians

Huntington's disease (HD) usually manifests in adulthood and is characterised by progressive neurodegeneration in the brain that causes worsening involuntary movements, mental health and cognition over many years. Depression, anxiety and apathy are common. HD is autosomal dominant and affects about 1 in 8,000 people in the UK. There are currently no disease-modifying treatments and so patient care centres on multidisciplinary therapy support and medical treatments to relieve distressing symptoms. Progression of HD is usually slow, and so acute deteriorations often indicate another problem, such as intercurrent infections, constipation, urinary retention, gastro-oesophageal reflux disease or poor dentition. In this review we outline common presentations in HD patients, both acute and chronic, consider therapeutic options and discuss specific considerations in advanced HD

Genetic modifiers of Mendelian disease: Huntington's disease and the trinucleotide repeat disorders

In the decades since the genes and mutations associated with the commoner Mendelian disorders were first discovered, technological advances in genetic analysis have made finding genomic variation a much less onerous task. Recently, the global efforts to collect subjects with Mendelian disorders, to better define the disorders and to empower appropriate clinical trials, along with improved genetic technologies, have allowed the identification of genetic variation that does not cause disease, but substantially modifies disease presentation. The advantage of this is it identifies biological pathways and molecules, that, if modified in people, might alter disease presentation. In Huntington’s disease (HD), caused by an expanded CAG repeat tract in HTT, genetic variation has been uncovered that is associated with change in the onset or progression of disease. Some of this variation lies in genes that are part of the DNA damage response, previously suggested to be important in modulating expansion of the repeat tract in germline and somatic cells. The genetic evidence implicates a DNA damage response-related pathway in modulating the pathogenicity of the repeat tracts in HD, and possibly, in other trinucleotide repeat disorders. These findings offer new targets for drug development in these currently intractable disorders

Differential Phase Contrast Imaging of the Magnetostructural Transition and Phase Boundary Motion in Uniform and Gradient-doped FeRh-based Thin Films

No abstract available

Quantitative Differential Phase Contrast Imaging of the Magnetostructural Transition and Current-driven Motion of Domain Walls in FeRh Thin Films

No abstract available

Computational Analysis of a Chevron Nozzle Uniquely Tailored for Propulsion Airframe Aeroacoustics

A computational flow field and predicted jet noise source analysis is presented for asymmetrical fan chevrons on a modern separate flow nozzle at take off conditions. The propulsion airframe aeroacoustic asymmetric fan nozzle is designed with an azimuthally varying chevron pattern with longer chevrons close to the pylon. A baseline round nozzle without chevrons and a reference nozzle with azimuthally uniform chevrons are also studied. The intent of the asymmetric fan chevron nozzle was to improve the noise reduction potential by creating a favorable propulsion airframe aeroacoustic interaction effect between the pylon and chevron nozzle. This favorable interaction and improved noise reduction was observed in model scale tests and flight test data and has been reported in other studies. The goal of this study was to identify the fundamental flow and noise source mechanisms. The flow simulation uses the asymptotically steady, compressible Reynolds averaged Navier-Stokes equations on a structured grid. Flow computations are performed using the parallel, multi-block, structured grid code PAB3D. Local noise sources were mapped and integrated computationally using the Jet3D code based upon the Lighthill Acoustic Analogy with anisotropic Reynolds stress modeling. In this study, trends of noise reduction were correctly predicted. Jet3D was also utilized to produce noise source maps that were then correlated to local flow features. The flow studies show that asymmetry of the longer fan chevrons near the pylon work to reduce the strength of the secondary flow induced by the pylon itself, such that the asymmetric merging of the fan and core shear layers is significantly delayed. The effect is to reduce the peak turbulence kinetic energy and shift it downstream, reducing overall noise production. This combined flow and noise prediction approach has yielded considerable understanding of the physics of a fan chevron nozzle designed to include propulsion airframe aeroacoustic interaction effects

Measurements of the Complex Conductivity of NbxSi1-x Alloys on the Insulating Side of the Metal-Insulator Transition

We have conducted temperature and frequency dependent transport measurements in amorphous Nb_x Si_{1-x} samples in the insulating regime. We find a temperature dependent dc conductivity consistent with variable range hopping in a Coulomb glass. The frequency dependent response in the millimeter-wave frequency range can be described by the expression $sigma(omega) \propto (-\imath omega)^alpha$ with the exponent somewhat smaller than one. Our ac results are not consistent with extant theories for the hopping transport.Comment: 4 pages with 3 figures; published version has a different title from original (was: "Electrodynamics in a Coulomb glass"

Computational Analysis of the Flow and Acoustic Effects of Jet-Pylon Interaction

Computational simulation and prediction tools were used to understand the jet-pylon interaction effect in a set of bypass-ratio five core/fan nozzles. Results suggest that the pylon acts as a large scale mixing vane that perturbs the jet flow and jump starts the jet mixing process. The enhanced mixing and associated secondary flows from the pylon result in a net increase of noise in the first 10 diameters of the jet s development, but there is a sustained reduction in noise from that point downstream. This is likely the reason the pylon nozzle is quieter overall than the baseline round nozzle in this case. The present work suggests that focused pylon design could lead to advanced pylon shapes and nozzle configurations that take advantage of propulsion-airframe integration to provide additional noise reduction capabilities

Reconceptualizing Context: A Multilevel Model of the Context of Reception and Second-Generation Educational Attainment

This paper seeks to return scholarly attention to a core intellectual divide between segmented and conventional (or neo-)assimilation approaches, doing so through a theoretical and empirical reconsideration of contextual effects on second-generation outcomes. We evaluate multiple approaches to measuring receiving country contextual effects and measuring their impact on the educational attainment of the children of immigrants. We demonstrate that our proposed measures better predict second-generation educational attainment than prevailing approaches, enabling a multilevel modeling strategy that accounts for the structure of immigrant families nested within different receiving contexts