Hinge–Linker Elements in the AAA+ Protein Unfoldase ClpX Mediate Intersubunit Communication, Assembly, and Mechanical Activity

Ventricular fibrillation (VF) is a type of fatal arrhythmia that can cause sudden death within minutes. The study of a VF detection algorithm has important clinical significance. This study aimed to develop an algorithm for the automatic detection of VF based on the acquisition of cardiac mechanical activity-related signals, namely ballistocardiography (BCG), by non-contact sensors. BCG signals, including VF, sinus rhythm, and motion artifacts, were collected through electric defibrillation experiments in pigs. Through autocorrelation and S transform, the time-frequency graph with obvious information of cardiac rhythmic activity was obtained, and a feature set of 13 elements was constructed for each 7 s segment after statistical analysis and hierarchical clustering. Then, the random forest classifier was used to classify VF and non-VF, and two paradigms of intra-patient and inter-patient were used to evaluate the performance. The results showed that the sensitivity and specificity were 0.965 and 0.958 under 10-fold cross-validation, and they were 0.947 and 0.946 under leave-one-subject-out cross-validation. In conclusion, the proposed algorithm combining feature extraction and machine learning can effectively detect VF in BCG, laying a foundation for the development of long-term self-cardiac monitoring at home and a VF real-time detection and alarm system.

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Real-time imaging of cellular forces using optical interference

Nature Communications ◽

10.1038/s41467-021-23734-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Andrew T. Meek ◽

Nils M. Kronenberg ◽

Andrew Morton ◽

Philipp Liehm ◽

Jan Murawski ◽

...

Keyword(s):

Cell Culture ◽

Real Time ◽

High Throughput ◽

Mechanical Activity ◽

Dynamic Processes ◽

Imaging Method ◽

Neonatal Cardiomyocytes ◽

A Cell ◽

Cellular Forces ◽

Time Acquisition

AbstractImportant dynamic processes in mechanobiology remain elusive due to a lack of tools to image the small cellular forces at play with sufficient speed and throughput. Here, we introduce a fast, interference-based force imaging method that uses the illumination of an elastic deformable microcavity with two rapidly alternating wavelengths to map forces. We show real-time acquisition and processing of data, obtain images of mechanical activity while scanning across a cell culture, and investigate sub-second fluctuations of the piconewton forces exerted by macrophage podosomes. We also demonstrate force imaging of beating neonatal cardiomyocytes at 100 fps which reveals mechanical aspects of spontaneous oscillatory contraction waves in between the main contraction cycles. These examples illustrate the wider potential of our technique for monitoring cellular forces with high throughput and excellent temporal resolution.

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Vasorelaxing Activity of R-(−)-3′-Hydroxy-2,4,5-trimethoxydalbergiquinol from Dalbergia tonkinensis: Involvement of Smooth Muscle CaV1.2 Channels

Planta Medica ◽

10.1055/a-1099-2929 ◽

2020 ◽

Vol 86 (04) ◽

pp. 284-293 ◽

Cited By ~ 2

Author(s):

Nguyen Manh Cuong ◽

Ninh The Son ◽

Ngu Truong Nhan ◽

Pham Ngoc Khanh ◽

Tran Thu Huong ◽

...

Keyword(s):

Patch Clamp ◽

Antihypertensive Drugs ◽

Docking Simulation ◽

Mechanical Activity ◽

Dependent Manner ◽

Vascular Effects ◽

Patch Clamp Technique ◽

Spasmolytic Activity ◽

Cav1.2 Channels ◽

Dalbergia Tonkinensis

Abstract Dalbergia species heartwood, widely used in traditional medicine to treat various cardiovascular diseases, might represent a rich source of vasoactive agents. In Vietnam, Dalbergia tonkinensis is an endemic tree. Therefore, the aim of the present work was to investigate the vascular activity of R-(−)-3′-hydroxy-2,4,5-trimethoxydalbergiquinol isolated from the heartwood of D. tonkinensis and to provide circular dichroism features of its R absolute configuration. The vascular effects of R-(−)-3′-hydroxy-2,4,5-trimethoxydalbergiquinol were assessed on the in vitro mechanical activity of rat aorta rings, under isometric conditions, and on whole-cell Ba2+ currents through CaV1.2 channels (IBa1.2) recorded in single, rat tail main artery myocytes by means of the patch-clamp technique. R-(−)-3′-Hydroxy-2,4,5-trimethoxydalbergiquinol showed concentration-dependent, vasorelaxant activity on both endothelium-deprived and endothelium intact rings precontracted with the α 1 receptor agonist phenylephrine. Neither the NO (nitric oxide) synthase inhibitor Nω-nitro-L-arginine methyl ester nor the cyclooxygenase inhibitor indomethacin affected its spasmolytic activity. R-(−)-3′-Hydroxy-2,4,5-trimethoxydalbergiquinol-induced vasorelaxation was antagonized by (S)-(−)-Bay K 8644 and unaffected by tetraethylammonium plus glibenclamide. In patch-clamp experiments, R-(−)-3′-hydroxy-2,4,5-trimethoxydalbergiquinol inhibited IBa1.2 in a concentration-dependent manner and significantly decreased the time constant of current inactivation. R-(−)-3′-Hydroxy-2,4,5-trimethoxydalbergiquinol likely stabilized the channel in its closed state, as suggested by molecular modelling and docking simulation to the CaV1.2 channel α 1c subunit. In conclusion, D. tonkinensis species may represent a source of agents potentially useful for the development of novel antihypertensive drugs.

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Mechanical activity in heart regulates translation of α-myosin heavy chain mRNA but not its localization

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1999.276.6.h2013 ◽

1999 ◽

Vol 276 (6) ◽

pp. H2013-H2019 ◽

Cited By ~ 4

Author(s):

Gordana Nikcevic ◽

Maria C. Heidkamp ◽

Merja Perhonen ◽

Brenda Russell

Keyword(s):

Myosin Heavy Chain ◽

Heavy Chain ◽

Mrna Translation ◽

Neonatal Rat ◽

Mechanical Activity ◽

Mrna Levels ◽

Rat Cardiomyocytes ◽

Significant Difference ◽

Polysomal Fraction ◽

Mechanical Transduction

Mechanical inactivity depresses protein expression in cardiac muscle tissue and results in atrophy. We explore the mechanical transduction mechanism in spontaneously beating neonatal rat cardiomyocytes expressing the α-myosin heavy chain (α-MyHC) isoform by interfering with cross-bridge function [2,3-butanedione monoxime (BDM), 7.5 mM] without affecting cell calcium. The polysome content and α-MyHC mRNA levels in fractions from a sucrose gradient were analyzed. BDM treatment blocked translation at initiation (162 ± 12% in the nonpolysomal RNA fraction and 43 ± 6% in the polysomal fraction, relative to control as 100%; P < 0.05). There was an increase in α-MyHC mRNA from the nonpolysomal fraction (120.5 ± 7.7%; P < 0.05 compared with control) with no significant change in the heavy polysomes. In situ hybridization of α-MyHC mRNA was used to estimate message abundance as a function of the distance from the nucleus. The mRNA was dispersed through the cytoplasm in spontaneously beating cells as well as in BDM-treated cells (no significant difference). We conclude that direct inhibition of contractile machinery, but not calcium, regulates initiation of α-MyHC mRNA translation. However, calcium, not pure mechanical signals, appears to be important for message localization.

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Outward current and repolarization in hypoxic rat myocardium

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1983.244.3.h341 ◽

1983 ◽

Vol 244 (3) ◽

pp. H341-H350

Author(s):

C. H. Conrad ◽

R. G. Mark ◽

O. H. Bing

Keyword(s):

Action Potential ◽

Action Potentials ◽

Outward Current ◽

Iodoacetic Acid ◽

Mechanical Activity ◽

Potential Range ◽

Papillary Muscles ◽

Rat Myocardium ◽

Cable Properties ◽

Sucrose Gap

We studied the effects of brief periods (20-30 min) of hypoxia in the presence of 5 and 50 mM glucose and of glycolytic blockade (10(-4) M iodoacetic acid, IAA) on action potentials, membrane currents, and mechanical activity in rat ventricular papillary muscles using a single sucrose gap voltage-clamp technique. Steady-state outward current (iss) was determined at the end of a 500-ms clamp to the test potential following a 600-ms clamp to a holding potential of -50 mV. In the presence of 5 mM glucose, hypoxia resulted in a decrease in action potential duration (APD) and an increase in iss (on the order of 60% at 0 mV) over the potential range studied. The increase in iss did not appear to be due to an increase in leakage current or to a change in the cable properties of the preparation. Addition of 50 mM glucose prevented the change in both APD and iss with hypoxia. In addition, glycolytic blockade with IAA did not alter iss in the presence of oxygen. We conclude that an increase in iss appears to be a major factor in the abbreviation of rat ventricular action potential seen with hypoxia. Glycolysis appears to be a sufficient (with 50 mM glucose) but not necessary source of energy for the maintenance of normal iss.

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