Calcium-gated calcium channels in sarcoplasmic reticulum of rabbit skinned skeletal muscle fibers

The action of ruthenium red (RR) on Ca2+ loading by and Ca2+ release from the sarcoplasmic reticulum (SR) of chemically skinned skeletal muscle fibers of the rabbit was investigated. Ca2+ loading, in the presence of the precipitating anion pyrophosphate, was monitored by a light-scattering method. Ca2+ release was indirectly measured by following tension development evoked by caffeine. Stimulation of the Ca2+ loading rate by 5 microM RR was dependent on free Ca2+, being maximal at pCa 5.56. Isometric force development induced by 5 mM caffeine was reversibly antagonized by RR. IC50 for the rate of tension rise was 0.5 microM; that for the extent of tension was 4 microM. RR slightly shifted the steady state isometric force/pCa curve toward lower pCa values. At 5 microM RR, the pCa required for half-maximal force was 0.2 log units lower than that of the control, and maximal force was depressed by approximately 16%. These results suggest that RR inhibited Ca2+ release from the SR and stimulated Ca2+ loading into the SR by closing Ca2+-gated Ca2+ channels. Previous studies on isolated SR have indicated the selective presence of such channels in junctional terminal cisternae

Capgras-like syndrome in a patient with an acute urinary tract infection.

Delusional misidentification syndromes are a group of delusional phenomena in which patients misidentify familiar persons, objects, or themselves, believing that they have been replaced or transformed. In 25%-40% of cases, misidentification syndromes have been reported in association with organic illness. We report an acute episode of Capgras-like delusion lasting 8 days, focused on the idea that people were robots with human bodies, in association with an acute urinary infection. To our knowledge, this is the first case report associating urinary tract infection with Capgras-like syndrome. Awareness of the prevalence of delusional misidentification syndromes associated with acute medical illness should promote diligence on the part of clinicians in recognizing this disorder

CFD Modeling of a Laboratory-Scale Setup for Thermochemical Materials Performance Analysis

The search for energy saving is nowadays mandatory because of the constant growth of CO2 emissions caused by an inefficient energy management. Thermal Energy Storage (TES) has an important role in designing of energy efficient systems, including solar energy storage (daily or seasonal) and waste heat from industrial batch processes. Different solutions are possible for thermal storage, based on sensible heat (e.g. water tanks), latent heat (phase change materials) or reaction enthalpy (thermochemical systems). In Thermochemical TES, a material is chosen so that it shows a high-enthalpy reversible chemical reaction at a desired temperature. In particular, water sorption in some inorganic salt hydrates is pointed out as one of the most suitable reactions for low temperature energy storage (60-120 °C). The reaction products, water and salt in a less hydrated form, are kept separated and consequently the heat is stored. Energy release is obtained with salt hydration. The main advantages are an energy storage capacity higher than other TES technologies and the possibility to control the energy release. On the other hand, one of the main issues is the difficulty to test materials performance, because standard characterization techniques use small amount of samples and their properties change dramatically when the system is scaled up to large reactors. The aim of this work is to realize a laboratory scale setup to test the performance of salt hydrate composites. A scheme of the system is reported in the attached figure (above). The active material is kept in an evaporator at a temperature sufficient to generate the dehydration reaction. Extracted water mass is measured in time in a condenser at 0°C. Air flow, temperature and humidity are measured with sensors in the system. The system was simulated using COMSOL® software. In particular the simulation was inspired by two models from the Application Library, Degradation of DNA in Plasma and Protein Adsorption. At first, a zero dimensional component was created with the Reaction Engineering module with two reactions to evaluate both the dehydration and condensation steps: H2Ocry->H2Ovap H2Ovap->H2Oliq Where H2Ocry is the crystallization water in the salt hydrate, H2Ovap is the air humidity and H2Oliq is the condensed water. Using a Parameter Estimation module, experimental data about dehydration were imported in the software and used to estimate the reactions kinetics constants. After that, using a Generate Space Dependent Model module we obtained a 3D component with a realistic system geometry (see attached figure below) including the modules Chemistry, Transport of Diluted Species, Surface Reactions, Heat transfer in Fluids and Single Phase Laminar Flow. Rate constants calculated in the zero-dimension model were used as first guess for the 3D model reactions. We verified that the model is able to evaluate temperature, flow and water concentration as well as the evolution of the two reactions in time. We expect that this model will allow us to classify different Thermochemical TES materials about their efficiency in heat and mass exchange, as well as to refine the design of the thermal storage system

Two unusual cases of Gitelman's syndrome with a complex inheritance: how the phenotype can help interpret the genotype: lesson for the clinical nephrologist

Bartter\u2019s syndrome (BS) and Gitelman\u2019s syndrome (GS) are autosomal recessive disorders with overlapping features, caused by biallelic variants in six genes encoding proteins involved in renal electrolyte homeostasis in different districts of the nephron. Here we describe two patients with a clinical diagnosis of GS with a complex inheritance whose clinical interpretation and treatment proved challenging. In one patient, compound heterozygosity for two known pathogenic variant in the SLC12A3 gene was associated with an uncommon variant in the KCNJ1 gene (one of the known BS genes). The unusual severity of GS phenotype encountered in this patient led us to hypothesize that the missense variant can act as a genetic modifier by exacerbating the severity of the disease and by inducing BS-like clinical manifestations. In the other patient, two novel likely pathogenic variants in the SLC12A3 gene were coupled with a hitherto unreported rare variant in the SLC4A1 gene; the latter\u2019s disease-causing variants have been associated with both dominant and recessive forms of distal renal tubular acidosis (dRTA). Patient\u2019s medical history (he was clinically diagnosed with incomplete hypokalemic dRTA at 10 years old) supports the hypothesis of a dual molecular diagnosis and hence of a blended phenotype

FAbry STabilization indEX (FASTEX) : an innovative tool for the assessment of clinical stabilization in Fabry disease

Two disease severity scoring systems, the Mainz Severity Score Index (MSSI) and Fabry Disease Severity Scoring System (DS3), have been validated for quantifying the disease burden of Fabry disease. We aimed to develop a dynamic mathematical model [the FASTEX (FAbry STabilization indEX)] to assess the clinical stability. A multidisciplinary panel of experts in Fabry disease first defined a novel score of severity [raw score (RS)] based on three domains with a small number items in each domain (nervous system domain: pain, cerebrovascular events; renal domain: proteinuria, glomerular filtration rate; cardiac domain: echocardiography parameters, electrocardiograph parameters and New York Heart Association class) and evaluated the clinical stability over time. The RS was tested in 28 patients (15 males, 13 females) with the classic form of Fabry disease. There was good statistical correlation between the newly established RS and a weighted score (WS), with DS3 and MSSI (R (2) = 0.914, 0.949, 0.910 and 0.938, respectively). In order to refine the RS further, a WS, which was expressed as a percentage value, was calculated. This was based on the relative clinical significance of each item within the domain with the panel agreeing on the attribution of a different weight of clinical damage to a specific organ system. To test the variation of the clinical burden over time, the RS was repeated after 1 year. The panel agreed on a cut-off of a 20% change from baseline as the clinical WS to define clinical stability. The FASTEX model showed good correlation with the clinical assessment and with clinical variation over time in all patients

InAs/InP/InSb Nanowires as Low Capacitance n-n Heterojunction Diodes

Nanowire diodes have been realized by employing an axial heterojunction between InAs and InSb semiconductor materials. The broken-gap band alignment (type III) leads to a strong rectification effect when the current-voltage (I-V) characteristic is inspected at room temperature. The additional insertion of a narrow InP barrier reduces the thermionic contribution, which results in a net decrease of leakage current in the reverse bias with a corresponding enhanced rectification in terms of asymmetry in the I-V characteristics. The investigated diodes compare favorably with the ones realized with p-n heterostructured nanowires, making InAs/InP/InSb devices appealing candidates to be used as building blocks for nanowire-based ultrafast electronics and for the realization of photodetectors in the THz spectral range

Increased mitophagy in the skeletal muscle of spinal and bulbar muscular atrophy patients

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disorder caused by polyglutamine expansion in the androgen receptor (AR) and characterized by the loss of lower motor neurons. Here we investigated pathological processes occurring in muscle biopsy specimens derived from SBMA patients and, as controls, age-matched healthy subjects and patients suffering from amyotrophic lateral sclerosis (ALS) and neurogenic atrophy. We detected atrophic fibers in the muscle of SBMA, ALS and neurogenic atrophy patients. In addition, SBMA muscle was characterized by the presence of a large number of hypertrophic fibers, with oxidative fibers having a larger size compared with glycolytic fibers. Polyglutamine-expanded AR expression was decreased in whole muscle, yet enriched in the nucleus, and localized to mitochondria. Ultrastructural analysis revealed myofibrillar disorganization and streaming in zones lacking mitochondria and degenerating mitochondria. Using molecular (mtDNA copy number), biochemical (citrate synthase and respiratory chain enzymes) and morphological (dark blue area in nicotinamide adenine dinucleotide-stained muscle cross-sections) analyses, we found a depletion of the mitochondria associated with enhanced mitophagy. Mass spectrometry analysis revealed an increase of phosphatidylethanolamines and phosphatidylserines in mitochondria isolated from SBMA muscles, as well as a 50% depletion of cardiolipin associated with decreased expression of the cardiolipin synthase gene. These observations suggest a causative link between nuclear polyglutamine-expanded AR accumulation, depletion of mitochondrial mass, increased mitophagy and altered mitochondrial membrane composition in SBMA muscle patients. Given the central role of mitochondria in cell bioenergetics, therapeutic approaches toward improving the mitochondrial network are worth considering to support SBMA patients