The N-terminal cysteine is a dual sensor of oxygen and oxidative stress

Cellular homeostasis requires the sensing of and adaptation to intracellular oxygen (O2) and reactive oxygen species (ROS). The Arg/N-degron pathway targets proteins that bear destabilizing N-terminal residues for degradation by the proteasome or via autophagy. Under normoxic conditions, the N-terminal Cys (Nt-Cys) residues of specific substrates can be oxidized by dioxygenases such as plant cysteine oxidases and cysteamine (2-aminoethanethiol) dioxygenases and arginylated by ATE1 R-transferases to generate Arg-CysO2(H) (R-CO2). Proteins bearing the R-CO2 N-degron are targeted via Lys48 (K48)–linked ubiquitylation by UBR1/UBR2 N-recognins for proteasomal degradation. During acute hypoxia, such proteins are partially stabilized, owing to decreased Nt-Cys oxidation. Here, we show that if hypoxia is prolonged, the Nt-Cys of regulatory proteins can be chemically oxidized by ROS to generate Arg-CysO3(H) (R-CO3), a lysosomal N-degron. The resulting R-CO3 is bound by KCMF1, a N-recognin that induces K63-linked ubiquitylation, followed by K27-linked ubiquitylation by the noncanonical N-recognin UBR4. Autophagic targeting of Cys/N-degron substrates is mediated by the autophagic N-recognin p62/SQTSM-1/Sequestosome-1 through recognition of K27/K63-linked ubiquitin (Ub) chains. This Cys/N-degron–dependent reprogramming in the proteolytic flux is important for cellular homeostasis under both chronic hypoxia and oxidative stress. A small-compound ligand of p62 is cytoprotective under oxidative stress through its ability to accelerate proteolytic flux of K27/K63-ubiquitylated Cys/N-degron substrates. Our results suggest that the Nt-Cys of conditional Cys/N-degron substrates acts as an acceptor of O2 to maintain both O2 and ROS homeostasis and modulates half-lives of substrates through either the proteasome or lysosome by reprogramming of their Ub codes.

Estimation of Pulmonary Arterial Wave Reflection by Echo-Doppler: A Preliminary Study in Dogs With Experimentally-Induced Acute Pulmonary Embolism

Background: Pulmonary arterial (PA) wave reflection provides additional information for assessing right ventricular afterload, but its applications is hampered by the need for invasive pressure and flow measurements. We tested the hypothesis that PA pressure and flow waveforms estimated by Doppler echocardiography could be used to quantify PA wave reflection.Methods: Doppler echocardiographic images of tricuspid regurgitation and right ventricular outflow tract flow used to estimate PA pressure and flow waveforms were acquired simultaneously with direct measurements with a dual sensor-tipped catheter under various hemodynamic conditions in a canine model of pulmonary hypertension (n = 8). Wave separation analysis was performed on echo-Doppler derived as well as catheter derived waveforms to separate PA pressure into forward (Pf) and backward (Pb) pressures and derive wave reflection coefficient (RC) defined as the ratio of peak Pb to peak Pf.Results: Wave reflection indices by echo-Doppler agreed well with corresponding indices by catheter (Pb: mean difference = 0.4 mmHg, 95% limits of agreement = −4.3 to 5.0 mmHg; RC: bias = 0.13, 95% limits of agreement = −0.25 to 0.26). RC correlated negatively with PA compliance.Conclusion: This echo-Doppler method yields reasonable measurement of reflected wave in the pulmonary circulation, paving the way to a more integrative assessment of pulmonary hemodynamics in the clinical setting.

DUAL SPHERICAL ELECTRIC FIELD VOLTAGE SENSOR

Мы живем в мире высоких энергетических технологий, способных передавать электрическую энергию на большие расстояния. Эту энергию невозможно сосредоточить только внутри передающих энергетических систем. Она выплескивается наружу в виде электрических полей. Эти электрические поля неблагоприятно воздействуют на окружающую среду, технические и биологические объекты. В связи с этим необходимо контролировать уровни электрических полей, важной характеристикой которых является напряженность электрического поля. Для восприятия электрического поля необходимы датчики напряженности электрического поля. Существующие датчики неудобны в эксплуатации и имеют высокую погрешность восприятия напряженности электрического поля, достигающую ± 20%. Bыдвигается идея создания универсального датчика нового вида, относящeгося к виду сдвоенных датчиков. Его универсальность заключается в том, что он воплощает в себе все виды известных датчиков - одинарные, сдвоенные и теперь еще двойные. Погрешность восприятия напряженности неоднородного электрического поля сдвоенных датчиков не превышает +5 % во всем пространственном диапазоне измерения 0£ a £1. При этом расстояние d до источника поля ограничено только радиусом сферического основания датчика, т.е. d » R , в то время как для датчиков, входящих в состав сдвоенного датчика, в том же пространственном диапазоне измерение погрешности составляет ± 35 %. Используя сдвоенный датчик, можно добиться значительного повышения точности измерения напряженности неоднородных электрических полей в широком пространственном диапазоне измерений по сравнению с известными датчиками We live in a world of high energy technologies capable of transmitting electrical energy over long distances. This energy cannot be concentrated only within the transmitting energy systems. It spills out in the form of electric fields. These electric fields adversely affect the environment, technical and biological objects. In this regard, it is necessary to control the levels of electric fields, an important characteristic of which is the strength of the electric field. Sensors of the electric field strength are required to sense the electric field. The existing sensors are inconvenient in operation and have a high error in the perception of the electric field strength, reaching ± 20%. In the work under consideration, the idea of creating a universal sensor of a new type, related to the type of dual sensors, is put forward. Its versatility lies in the fact that it embodies all types of known sensors - single, twin, and now dual. The error in the perception of the intensity of the inhomogeneous electric field of the dual sensors does not exceed + 5% in the entire spatial measurement range 0£ a £1. In this case, the distance d to the field source is limited only by the radius of the spherical base of the sensor, i.e. d » R . At the same time, for sensors that are part of a dual sensor in the same spatial measurement range, the error is ± 35%. Using a dual sensor, it is possible to achieve a significant increase in the accuracy of measuring the strength of inhomogeneous electric fields in a wide spatial measurement range in comparison with known sensors.

Analysis of Complex Solid-Gas Flow under the Influence of Gravity through Inclined Channel and Comparison with Real-Time Dual-Sensor System

Gas-solid flow is used in the chemical industry, food industry, pharmaceuticals, vehicles, and power generation. The calculation of flow has aroused great interest in contemporary industry. In recent decades, researchers have been seeking to build an effective system to monitor and calculate gas-solid flow. Attempts have been extended from computational modeling to the creation of flow pattern visualization methods and mass flow (MFR) quantification. MFR is usually studied by volume flow concentration (VFC) and velocity distribution of solid particles. A non-invasive device is used for testing MFR, in which electronic and mechanical sensors are used to balance the shortcomings related to each other. This study investigates the simulation of flow patterns to demonstrate the behavior of solid particles as they pass through the channel. The particles are allowed to slide longitudinally in the insulated tending channel. This slippage is due to the influence of natural gravity. Electronic sensor components are used to measure the velocity distribution and concentration of volumetric flow. The load cell is used as an auxiliary sensor for measuring MFR. In addition, ANSYS fluent is used to analyze streaming queries. The experimental results are related to evaluating the accuracy and relative error of the data collected from various sensors under different conditions. However, the simulation results can help explain the movement of the gas-solid mixture and can understand the cause of pipeline blockage during the slow movement of solid particles.

A Comparison Between Pressure Wire and Microcatheter Measurements for Evaluating the Cerebral Venous Pressure Gradient

Introduction: A pressure gradient of over 8 mm Hg across the stenosis (usually located in the transverse-sigmoid junction) is one of the criteria for cerebral venous stenting in idiopathic intracranial hypertension (IIH) patients. The possible inaccuracy of the traditional microcatheter-based pressure measurements has been discussed in previous studies. In the cardiology field, a dual-sensor pressure wire is routinely used for the evaluation of stenotic lesions. Using a pressure wire for cerebral vasculature was previously discussed in a small case series and case reports. In this study, we compared venous pressure measurements obtained using both a microcatheter and a pressure wire in patients who were candidates for stenting.Methods: A retrospective study was conducted, comparing the two methods of pressure measurements in 26 patients with venous stenosis. Altogether, 120 measurements were performed using both methods. Demographic characteristics, medical history, procedural details, medications, indications for the procedure, and complications were collected from the patient charts.Results: Based on an 8-mm Hg pressure gradient cutoff indication, 19 patients were found eligible to go through unilateral venous stenting based on catheter measurements alone. The wire results corroborated the catheter results in detecting all cases indicated for a stent. This finding implies a sensitivity equal to 100% for the wire measurements. There were no wire-related complications, demonstrating its safety.Conclusions: We conclude that the pressure wire is as safe as the microcatheter and can identify cases requiring intervention. A larger-scale study is needed to assess the measurement accuracy of the pressure wire in brain vasculature.