MicroRNA-365 regulates human cardiac action potential duration

Abnormalities of ventricular action potential cause malignant cardiac arrhythmias and sudden cardiac death. Here, we aim to identify microRNAs that regulate the human cardiac action potential and ask whether their manipulation allows for therapeutic modulation of action potential abnormalities. Quantitative analysis of the microRNA targetomes in human cardiac myocytes identifies miR-365 as a primary microRNA to regulate repolarizing ion channels. Action potential recordings in patient-specific induced pluripotent stem cell-derived cardiac myocytes show that elevation of miR-365 significantly prolongs action potential duration in myocytes derived from a Short-QT syndrome patient, whereas specific inhibition of miR-365 normalizes pathologically prolonged action potential in Long-QT syndrome myocytes. Transcriptome analyses in these cells at bulk and single-cell level corroborate the key cardiac repolarizing channels as direct targets of miR-365, together with functionally synergistic regulation of additional action potential-regulating genes by this microRNA. Whole-cell patch-clamp experiments confirm miR-365-dependent regulation of repolarizing ionic current Iks. Finally, refractory period measurements in human myocardial slices substantiate the regulatory effect of miR-365 on action potential in adult human myocardial tissue. Our results delineate miR-365 to regulate human cardiac action potential duration by targeting key factors of cardiac repolarization.

Rational design of self-assembled surfactant film in nanopipettes: a combined fluorescence and electrochemical sensing

Herein, a generalizable method based on the formation of self-assembled surfactant film was reported to build a nanopipette system, which was applicable for both ionic current and fluorescent analysis of...

The Streaming Potential of Fluid through a Microchannel with Modulated Charged Surfaces

In this paper, the effects of asymmetrically modulated charged surfaces on streaming potential, velocity field and flow rate are investigated under the axial pressure gradient and vertical magnetic field. In a parallel-plate microchannel, modulated charged potentials on the walls are depicted by the cosine function. The flow of incompressible Newtonian fluid is two-dimensional due to the modulated charged surfaces. Considering the Debye–Hückel approximation, the Poisson–Boltzmann (PB) equation and the modified Navier–Stokes (N-S) equation are established. The analytical solutions of the potential and velocities (u and v) are obtained by means of the superposition principle and stream function. The unknown streaming potential is determined by the condition that the net ionic current is zero. Finally, the influences of pertinent dimensionless parameters (modulated potential parameters, Hartmann number and slip length) on the flow field, streaming potential, velocity field and flow rate are discussed graphically. During the flow process and under the impact of the charge-modulated potentials, the velocity profiles present an oscillating characteristic, and vortexes are generated. The results show that the charge-modulated potentials are beneficial for the enhancement of the streaming potential, velocity and flow rate, which also facilitate the mixing of fluids. Meanwhile, the flow rate can be controlled through the use of a low-amplitude magnetic field.

Transport receptor occupancy in Nuclear Pore Complex mimics

Nuclear Pore Complexes (NPCs) regulate all molecular transport between the nucleus and the cytoplasm in eukaryotic cells. Intrinsically disordered Phe-Gly nucleoporins (FG Nups) line the central conduit of NPCs to impart a selective barrier where large proteins are excluded unless bound to a transport receptor (karyopherin; Kap). Here, we assess 'Kap-centric' NPC models, which postulate that Kaps participate in establishing the selective barrier. We combine biomimetic nanopores, formed by tethering Nsp1 to the inner wall of a solid-state nanopore, with coarse-grained modeling to show that yeast Kap95 exhibits two populations in Nsp1-coated pores: one population that is transported across the pore in milliseconds, and a second population that is stably assembled within the FG mesh of the pore. Ionic current measurements show a conductance decrease for increasing Kap concentrations and noise data indicate an increase in rigidity of the FG-mesh. Modeling reveals an accumulation of Kap95 near the pore wall, yielding a conductance decrease. We find that Kaps only mildly affect the conformation of the Nsp1 mesh and that, even at high concentrations, Kaps only bind at most 8% of the FG-motifs in the nanopore, indicating that Kap95 occupancy is limited by steric constraints rather than by depletion of available FG-motifs. Our data provide an alternative explanation of the origin of bimodal NPC binding of Kaps, where a stable population of Kaps binds avidly to the NPC periphery, while fast transport proceeds via a central FG-rich channel through lower affinity interactions between Kaps and the cohesive domains of Nsp1.

MSRCall: A Multi-scale Deep Neural Network to Basecall Oxford Nanopore Sequences

MinION, a third-generation sequencer from Oxford Nanopore Technologies, is a portable device that can provide long nucleotide read data in real-time. It primarily aims to deduce the makeup of nucleotide sequences from the ionic current signals generated when passing DNA/RNA fragments through nanopores charged with a voltage difference. To determine the nucleotides from the measured signals, a translation process known as basecalling is required. However, compared to NGS basecallers, the calling accuracy of MinION still needs to be improved. In this work, a simple but powerful neural network architecture called MSRCall is proposed. MSRCall comprises a multi-scale structure, recurrent layers, a fusion block, and a CTC decoder. To better identify both short-range and long-range dependencies, the recurrent layer is redesigned to capture various time-scale features with a multi-scale structure. The results show that MSRCall outperforms other basecallers in terms of both read and consensus accuracies.

Deconvoluting and Quantifying the Real-time Fluxes and Ionic Currents of Various Species Using In Situ Electrochemical Quartz Crystal Microbalance Measurements

Electrochemical quartz crystal microbalance (EQCM) is a powerful technique to screen the gravimetric response of electrochemical electrodes. In this study, a straightforward mathematical method is proposed for extracting and deconvoluting the real-time fluxes and ionic currents of two species based on the EQCM measurement results. We creatively propose the concept of flux cyclic voltammograms (CVs) and ionic current CVs of various species and apply them to the real-time analyses of molecules/ions dynamics. For proof of concept, Ti3C2Tx MXene, a most studied two-dimensional metal carbide, is investigated as a supercapacitor electrode in a 1M H2SO4 electrolyte. The H2O and H+ flux CV plots are highly symmetrical, indicating reversible inserting/deserting species fluxes. The highest fluxes along with maximum hydration numbers are obtained at the peak current potential. This suggests the significant contribution of double-layer capacitance originates from the insertion of hydrated H+. The H+ CV with the ionic current induced by H+ flux overlaps the real CV, confirming that H+ is the only interactive ion for screening the electrode charge. Lastly, we also validate the proposed strategy using Ti3C2Tx MXene electrode in 1M KCl electrolyte and YP80 porous carbon electrode in 1 M LiCl electrolyte.

The hyperpolarization-activated current shifts the dynamic range of a voltage-dependent electrical synapse

Like their chemical counterparts, electrical synapses show complex dynamics such as rectification and voltage dependence that interact with other electrical processes in neurons. The consequences arising from these interactions for the electrical behavior of the synapse, and the dynamics they create, remain largely unexplored. Using a voltage-dependent electrical synapse between a descending modulatory projection neuron (MCN1) and a motor neuron (LG) in the crustacean stomatogastric ganglion, we find that the influence of the hyperpolarization-activated inward current (Ih) is critical to the function of the electrical synapse. When we blocked Ih with CsCl, the voltage dependence of the electrical synapse shifted by 18.7 mV to more hyperpolarized voltages, placing the dynamic range of the electrical synapse outside of the range of voltages used by the LG motor neuron (-60.2 mV to -44.9 mV). With dual electrode current- and voltage-clamp recordings, we demonstrate that this voltage shift is due to a sustained effect of Ih on the presynaptic MCN1 axon terminal membrane potential. Ih-induced depolarization of the axon terminal membrane potential increased the electrical postsynaptic potentials and currents. With Ih present, the axon terminal resting membrane potential depolarized, shifting the dynamic range of the electrical synapse towards the functional range of the motor neuron. We thus demonstrate that the function of an electrical synapse is critically influenced by a voltage-dependent ionic current (Ih).

An Experimental and Numerical Study of Polyelectrolyte Hydrogel Ionic Diodes: Towards Electrical Detection of Charged Biomolecules

Polyelectrolyte hydrogel ionic diodes (PHIDs) have recently emerged as a unique set of iontronic devices. Such diodes are built on microfluidic chips that feature polyelectrolyte hydrogel junctions and rectify ionic currents owing to the heterogeneous distribution and transport of ions across the junctions. In this paper, we provide the first account of a study on the ion transport behavior of PHIDs through an experimental investigation and numerical simulation. The effects of bulk ionic strength and hydrogel pore confinement are experimentally investigated. The ionic current rectification (ICR) exhibits saturation in a micromolar regime and responds to hydrogel pore size, which is subsequently verified in a simulation. Furthermore, we experimentally show that the rectification is sensitive to the dose of immobilized DNA with an exhibited sensitivity of 1 ng/μL. We anticipate our findings would be beneficial to the design of PHID-based biosensors for electrical detection of charged biomolecules.

Integrity Challenges Associated with Stray Current Corrosion Across Monolithic IJ's and Resolutions

Corrosion and subsequent failures is one of the main factors affecting uninterrupted operations of Oil & Gas Industries. Pipelines are considered as most convenient means of crude and gas transportation in Oil & Gas Industry. Buried pipelines generally made of low carbon steel material are protected externally by coating and applying impressed current cathodic protection (ICCP). Monitoring and maintaining adequate level of Cathodic Protection (CP) for such pipelines remains challenging for corrosion engineers due to increased level of field congestion, complexity in accurate current mapping and mitigation of corrosion phenomena. Failure of pipelines due to corrosion can be catastrophic with following consequences: Loss of containment fluid and thereby probable fatalityDamage to asset/company reputationSafety and Environment (Fire, Toxic gases and Oil Spill)Resource and downtime cost impact Isolation joints IJ's are designed with very high insulating material at mating areas and installed on pipelines by welding to avoid loss of Cathodic Protection (CP) current. Due to high electrical insulation, a potential difference is formed across of IJ's due to applied CP current and stray currents. In upstream Oil & Gas Industry, multiphase crude transported via pipeline will have certain percentage of water and will induce an internal conductive path across the IJs resulting in ionic current discharge at anodic areas within internal surface. This study focuses on factors contributing to such internal stray current corrosion, limitation in monitoring methodology and mitigation programs. The study concludes with recommendations such as design modifications, improvement in internal lining properties and improved installation guidelines. The study practically illustrates effectiveness of combined resistive bonding and zinc earthing cells installation for controlling stray current propagation in order to reduce the corrosion rate so as to maintain Integrity of pipelines.