An intra-cytoplasmic route for SARS-CoV-2 transmission unveiled by Helium-ion microscopy

SARS-CoV-2 virions enter the host cells by docking their spike glycoproteins to the membrane-bound Angiotensin Converting Enzyme 2. After intracellular assembly, the newly formed virions are released from the infected cells to propagate the infection, using the extra-cytoplasmic ACE2 docking mechanism. However, the molecular events underpinning SARS-CoV-2 transmission between host cells are not fully understood. Here, we report the findings of a scanning Helium-ion microscopy study performed on Vero E6 cells infected with mNeonGreen-expressing SARS-CoV-2. Our data reveal, with unprecedented resolution, the presence of: 1)-long tunneling nanotubes that connect two or more host cells over submillimeter distances; 2)-large scale multiple cell fusion events (syncytia); and 3)-abundant extracellular vesicles of various sizes. Taken together, these ultrastructural features describe a novel intra-cytoplasmic connection among SARS-CoV-2 infected cells that may act as an alternative route of viral transmission, disengaged from the well-known extra-cytoplasmic ACE2 docking mechanism. Our findings may explain the elusiveness of SARS-CoV-2 to survive from the immune surveillance of the infected host.

Autonomous Docking of Hybrid-Wheeled Modular Robots with an Integrated Active Genderless Docking Mechanism

This paper presents a self-reconfigurable modular robot with an integrated 2-DOF active docking mechanism. Active docking in modular robotic systems has received a lot of interest recently as it allows small versatile robotic systems to coalesce and achieve the structural benefits of large systems. This feature enables reconfigurable modular robotic systems to bridge the gap between small agile systems and larger robotic systems. The proposed self-reconfigurable mobile robot design exhibits dual mobility using a tracked drive mechanism for longitudinal locomotion and a wheeled drive mechanism for lateral locomotion. The 2-DOF docking interface allows for efficient docking while tolerating misalignments. To aid autonomous docking, visual marker-based tracking is used to detect and re-position the source robot relative to the target robot. The tracked features are then used in Image-Based Visual Servoing to bring the robots close enough for the docking procedure. The hybrid-tracking algorithm allows eliminating external pixelated noise in the image plane resulting in higher tracking accuracy along with faster frame update on a low-cost onboard computational device. This paper presents the overall mechanical design and the integration details of the modular robotic module with the docking mechanism. An overview of the autonomous tracking and docking algorithm is presented along-with a proof-of-concept real world demonstration of the autonomous docking and self-reconfigurability. Experimental results to validate the robustness of the proposed tracking method, as well as the reliability of the autonomous docking procedure, are also presented.

Stress Granule-Mediated Oxidized RNA Decay in P-Body: Hypothetical Role of ADAR1, Tudor-SN, and STAU1

Reactive oxygen species (ROS) generated under oxidative stress (OS) cause oxidative damage to RNA. Recent studies have suggested a role for oxidized RNA in several human disorders. Under the conditions of oxidative stress, mRNAs released from polysome dissociation accumulate and initiate stress granule (SG) assembly. SGs are highly enriched in mRNAs, containing inverted repeat (IR) Alus in 3′ UTRs, AU-rich elements, and RNA-binding proteins. SGs and processing bodies (P-bodies) transiently interact through a docking mechanism to allow the exchange of RNA species. However, the types of RNA species exchanged, and the mechanisms and outcomes of exchange are still unknown. Specialized RNA-binding proteins, including adenosine deaminase acting on RNA (ADAR1-p150), with an affinity toward inverted repeat Alus, and Tudor staphylococcal nuclease (Tudor-SN) are specifically recruited to SGs under OS along with an RNA transport protein, Staufen1 (STAU1), but their precise biochemical roles in SGs and SG/P-body docking are uncertain. Here, we critically review relevant literature and propose a hypothetical mechanism for the processing and decay of oxidized-RNA in SGs/P-bodies, as well as the role of ADAR1-p150, Tudor-SN, and STAU1.

New Natural Compound Inhibitors of Checkpoint Kinase-1(CHK1) Based on Computational Study

As a malignant tumor of the ovary, the general treatment principle of ovarian cancer is surgical treatment, supplemented by chemotherapy, and some patients can use targeted drugs. Its treatment effect is relatively poor, so the prognosis is poor, the mortality rate is high. To contribute to drug design and refinement, ideal lead compounds with potential inhibitory effects on ATP-competitive CHK1 (Checkpoint kinase-1) inhibitors were downloaded from the drug library (ZINC15 database) and screened afterwards. The ATP-competitive CHK1 inhibitors were identified by using computer-aided virtual screening technology. We first calculated the LibDock score through the docking of proteins and molecules, and then analyzed the pharmacological and toxicological properties. Then, we performed precise docking of the small molecules selected in the above steps with CHK1 protein to analyze their docking mechanism and affinity. Next, we used molecular dynamics simulation to make a assessment if the ligand-CHK1 complex were stable in natural environment. As the result shown, ZINC000008214547 and ZINC000072103632 were proved to bind with CHK1 with a higher binding affinity and stability. Additionally, their toxicological analysis shows that they are less toxic and will not inhibit the activity of cytochrome P-450 2D6. In the simulation of molecular dynamics, we also found that ZINC000008214547-CHK1 and ZINC000072103632-CHK1 complexes’ potential energy were more favorable compared with reference ligand, Prexasertib. Not only that, the two complexes also showed better stability in the natural environment. So, all results elucidated that ZINC000008214547 and ZINC000072103632 were favorable lead inhibitors of CHK1 protein. ZINC000008214547 and ZINC000072103632 were safe and had the potential to inhibit CHK1 protein. They may contribute a solid foundation for the development of CHK1 target drug.

Minimum contact stress modification for profile curve design defects in the beam-spring-cone docking mechanism

A minimum contact stress modification method for profile curve design defects in a beam-spring-cone docking mechanism (BSCDM) based on genetic algorithm is presented in this paper, the profile curve and contact position of BSCDM are optimized. Under low-speed conditions, an improved elastic contact model of semi-space elastic bodies is established to modify and optimize the elliptic profile envelope curve based on Hertz contact theory and two kinds of complete elliptic integral, the improved contact model is used to solve elastic contact problems with the geometric characteristics of the ellipse surface, the optimal profile curve of the docking joint and the optimal docking contact point position are obtained. The results of numerical simulation and the experiment demonstrate the feasibility and validity of above models and methods.

A 6DOF Virtual Environment Space Docking Operation with Human Supervision

In this work, we present a synchronous co-simulation of a 6DOF (six degree of freedom) ball and plate platform and its 3D computer model. The co-simulation in the virtual environment is intended to mimic the rendezvous between a cargo vehicle such as the Falcon 9 from SpaceX and the ISS (International Space Station). The visual feedback sensing of the position of the 6DOF platform is implemented using a Kinect RGB-D device. The human in the loop acts as supervisory control for initiating the docking mechanism. This paper delivers an adaptive fractional order control solution which is easily tunable, implementable and validated on a laboratory benchmark. The results indicate that fractional order control can tackle large variability in the system dynamics and deliver specified performance at all times.