Fish mesonephric model of polycystic kidney disease in medaka (Oryzias latipes) pc mutant

Fish mesonephric model of polycystic kidney disease in medaka (Oryzias latipes) pc mutant.BackgroundPolycystic kidney disease (PKD) is a common hereditary disease. A number of murine and zebrafish mutants have been generated and used for the study of PKD as metanephric and pronephric models, respectively. Here, we report a medaka (Oryzias latipes) mutant that develops numerous cysts in the kidney in adulthood fish in an autosomal-recessive manner as a mesonephric model of PKD.MethodsThe phenotypes of the medaka pc mutant were described in terms of morphologic, histologic, and ultrastructural features. The pc see-through stock was produced by crossing a pc mutant and a fish from the see-through stock and used for observing the kidney through the transparent body wall of a live fish.ResultsThe mutant developed bilateral massive enlargement of the kidney in adulthood. They sexually matured normally within 2 months of age and died within 6 months of age. The affected kidney was occupied by numerous, fluid-filled cysts, which were lined by attenuated squamous epithelial cells. Developmentally, cystic formation began in the pronephros in 10-day-old fry and in the mesonephros in 20-day-old fry at the microscopic level. The pc see-through stock was useful in observing disease progression in live fish.ConclusionThe kidney disorder that develops in the medaka pc mutant is a mesonephric counterpart of PKD, particularly an autosomal-dominant PKD, based on its morphologic, histologic, and ultrastructural features, and slow progression

OpenPLC based control system testbed for PLC whitelisting system

This paper proposes a security testbed system for industrial control systems. In control systems, controllers are final fortresses to continue the operation of field systems. Then, we need countermeasures of controllers. The whitelisting function is efficient in controller security. The whitelisting function registers normal operations in a list and detects unregistered operations as abnormal. We need a testbed system to check whether the whitelist function does not affect other functions of the controller. The industrial controller and its engineering tool are relatively expensive, and are customized with respect to controller vendors. To enhance the whitelist development, this study proposes a testbed system using OpenPLC which is an open-source software. This system is independent of controller vendors and is applicable for controller programming languages. We implement a whitelist based anomaly detection method for the testbed system and validate that the anomaly detection method operates correctly

RGMa collapses the neuronal actin barrier against disease-implicated protein and exacerbates ALS

Repulsive guidance molecule A (RGMa) was originally identified as a neuronal growth cone–collapsing factor. Previous reports have demonstrated the multifunctional roles of RGMa mediated by neogenin1. However, the pathogenic involvement of RGMa in amyotrophic lateral sclerosis (ALS) remains unclear. Here, we demonstrated that RGMa concentration was elevated in the cerebrospinal fluid of both patients with ALS and transgenic mice overexpressing the mutant human superoxide dismutase1 (mSOD1 mice). Treatment with humanized anti-RGMa monoclonal antibody ameliorated the clinical symptoms in mSOD1 mice. Histochemical analysis revealed that the anti-RGMa antibody significantly decreased mutant SOD1 protein accumulation in the motor neurons of mSOD1 mice via inhibition of actin depolymerization. In vitro analysis revealed that the anti-RGMa antibody inhibited the cellular uptake of the mutant SOD1 protein, presumably by reinforcing the neuronal actin barrier. Collectively, these data suggest that RGMa leads to the collapse of the neuronal actin barrier and promotes aberrant protein deposition, resulting in exacerbation of the ALS pathology.Shimizu Mikito, Shiraishi Naoyuki, Tada Satoru, et al. RGMa collapses the neuronal actin barrier against disease-implicated protein and exacerbates ALS. Science Advances 9, 686 (2023); https://doi.org/10.1126/sciadv.adg3193

Why Does Vascular Access Dysfunction Occur despite Brachial Artery Blood Flow Being Higher than Preset Blood Flow?

Background: In recent years, many reports have investigated the usefulness of brachial artery blood flow (BAF) measured by ultrasonography as an evaluation index for the vascular access (VA) stenosis of hemodialysis patients. However, the mechanism of VA dysfunction, despite BAF being higher than the preset blood flow, has not been clarified to date. Methods: The relationship between actual blood-removal flow and recirculation rate with decreasing VA flow was examined using a VA flow path model and pure water as a model fluid. The blood-flow rate was set at 180 mL/min, and the set VA flow rate was lowered stepwise from 350 to 50 mL/min. VA flow rate, blood-removal flow rate, and flow waveform measured between two needle-puncture sites were recorded, and then the actual blood-removal flow rate and recirculation rate were calculated. Results: Recirculation was observed at a VA flow rate < 300 mL/min. The recirculation was due to the VA flow rate, which was transiently reduced to the level below the blood-removal flow rate, resulting in backflow. In contrast, no decrease in the actual blood-removal flow rate was observed. Conclusion: It is suggested that the mechanism of the VA dysfunction, despite the BAF being higher than the preset blood-flow rate, was due to the diastolic BAF being lower than the blood-removal flow rate