Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1-MCM2-7 bound to DNA

In eukaryotes, the Cdt1-bound replicative helicase core MCM2-7 is loaded onto DNA by the ORC-Cdc6 ATPase to form a prereplicative complex (pre-RC) with an MCM2-7 double hexamer encircling DNA. Using purified components in the presence of ATP-γS, we have captured in vitro an intermediate in pre-RC assembly that contains a complex between the ORC-Cdc6 and Cdt1-MCM2-7 heteroheptamers called the OCCM. Cryo-EM studies of this 14-subunit complex reveal that the two separate heptameric complexes are engaged extensively, with the ORC-Cdc6 N-terminal AAA+ domains latching onto the C-terminal AAA+ motor domains of the MCM2-7 hexamer. The conformation of ORC-Cdc6 undergoes a concerted change into a right-handed spiral with helical symmetry that is identical to that of the DNA double helix. The resulting ORC-Cdc6 helicase loader shows a notable structural similarity to the replication factor C clamp loader, suggesting a conserved mechanism of action

The use of manganese-doped mesoporous silica nanopowder for targeted drug delivery

The researched manganese-doped mesoporous silica nanopowder (SiO 2 -MnO 2 NP) was produced using evaporation caused by a pulsed electron beam in a vacuum. The synthesized material demonstrated high porosity, amorphous structure and magnetic properties increased with the addition of dopant. The evaluation of the sedimentation stability of NP suspensions showed the need for the additional stabilization. It was established that increasing the sonication time, as the way to increase stability, leads to changes in the structure of the NP. PEG stabilized suspensions showed the highest stability. Experimental results indicated that for different drugs individual methods of loading and release are required. Drug loaded NP demonstrated a high drug loading capacity of 0.09 mg Amoxicillin per mg NP, 0.075 mg Doxorubicin per mg NP that is five times higher than loading capacity of chemically synthesized NP. © Published under licence by IOP Publishing Ltd.This work was performed within a support of the Russian Science Foundation No. 16-16-04038)

CUL-2^LRR-1 and UBXN-3 drive replisome disassembly during DNA replication termination and mitosis

Replisome disassembly is the final step of DNA replication in eukaryotes, involving the ubiquitylation and CDC48-dependent dissolution of the CMG helicase (CDC45-MCM-GINS). Using Caenorhabditis elegans early embryos and Xenopus laevis egg extracts, we show that the E3 ligase CUL-2(LRR-1) associates with the replisome and drives ubiquitylation and disassembly of CMG, together with the CDC-48 cofactors UFD-1 and NPL-4. Removal of CMG from chromatin in frog egg extracts requires CUL2 neddylation, and our data identify chromatin recruitment of CUL2(LRR1) as a key regulated step during DNA replication termination. Interestingly, however, CMG persists on chromatin until prophase in worms that lack CUL-2(LRR-1), but is then removed by a mitotic pathway that requires the CDC-48 cofactor UBXN-3, orthologous to the human tumour suppressor FAF1. Partial inactivation of lrr-1 and ubxn-3 leads to synthetic lethality, suggesting future approaches by which a deeper understanding of CMG disassembly in metazoa could be exploited therapeutically

Physicochemical characterization and antioxidant properties of cerium oxide nanoparticles

Studies of the biological activity of cerium oxide nanoparticles (CONPs) show that this compound exhibits antioxidant, antitumor, antibacterial and antiviral properties. The CONPs were obtained by pulsed electron evaporation in a low-pressure gas with a specific surface area of ∼ 190 m 2 /g. Strongly-noequilibrium conditions of synthesis led to the formation of high defect structures, which makes it possible to change the Ce 3+ /Ce 4+ ions ratio and, consequently, to enhance the level of their biological activity. To analyze the content of cerium with different valences, X-ray photoelectron spectroscopy was performed. To determine the enzyme-like activity of CONPs, a chemical analysis of the interaction with hydrogen peroxide was carried out on a spectrophotometer. The results show a significant presence of Ce 3+ in CONPs and the inhibition of reactive oxygen species (ROS). The valence of the cerium atoms determines the chemical activity of CONPs; thus, in a more alkaline medium, the CONPs decrease the ROS concentration, while in the acidic medium its activity diminishes. By varying the parameters of the nanopowders obtained and achieving the optimum Ce 3+ /Ce 4+ ratio, one can produce CONPs having properties which enable the creation of pharmaceuticals for protection against ROS or for combating tumors, viruses and bacteria. © Published under licence by IOP Publishing Ltd.This work was performed within a support of the Russian Science Foundation project [16-16-04038]

Production of Nanopowder of Cerium (III) Fluoride Obtained by Pulsed Electron Beam Evaporation in Vacuum

The method of pulsed electron beam evaporation in vacuum was first used to obtain CeF3 nanopowder (NP). During NP production, a high evaporation rate of the target (~ 7 g/h) and a higher percentage of NP collection (> 72%) were observed, both for fluoride and the previously obtained CeO2 oxide. It was found that the produced NP contains two crystalline phases: hexagonal CeF3 (95 wt.%, coherent scattering region ≈ 8 nm and [Ce-O-F] or [Ce-F]. The magnetic susceptibility of CeF3 nanoparticles (NPles) coincides with the susceptibility of micron particles, indicating the potential for using such NPles as a contrast agent for tomography. High specific surface area (CeO2-270 m2/g, CeF3 – 62 m2/g), large pore volume (0.35-0.11 cm3/g) allow the use of NPles as nanocontainers for drug delivery. © 2021 Institute of Physics Publishing. All rights reserved.The reported study was funded by RFBR and GACR, project number 20-58-26002

Production of Nanopowders of Bismuth Oxide Doped with Silver by Pulsed Electron Beam Evaporation in Vacuum

Various bismuth containing compounds are promising in many applications, including for creating photocatalysts based on them using a visible range of light. However, strong polymorphism (9 polymophic phases of Bi2O3), thermal instability and changes in the properties of bismuth oxide during long-term storage significantly complicate work with it. One way to increase stability and improve photocatalytic properties is by doping Bi2O3 with various metals. Ag doped Bi2O3 nanoparticles (NPs) are typically produced using chemical techniques often associated with the presence of toxic chemicals. The present paper used an environmentally friendly method of producing NPs using the method of pulsed electron beam evaporation in vacuum. The evaporation target was obtained by solid phase synthesis in an electric furnace on air using silver nitrate additives (1 and 5 wt.%).Textural, thermal and magnetic properties of the obtained NPs have been studied. Was found that the Ag-Bi2O3 NPs have a specific surface area (SSA) of 23.7 m2/g, which was almost 2 times bigger than the SSA of the pure Bi2O3 (13.2 m2/g) obtained previously. The thermal stability of the Ag-doped Bi2O3 samples was maintained to the temperature 350°C. While further heating on air took place the phase transition β → α. © 2021 Institute of Physics Publishing. All rights reserved.Authors are grateful to the research scientist of IMF UB RAS, to PhD Gaviko V.S. for XRD NPs. The reported study was funded by RFBR and GACR, project number 20-58-26002

Formation of Droplets in a Heterophasic Amorphocrystalline Nanopowder Bi2O3 Produced by Pulsed Electron Beam Evaporation in Vacuum

In the present work, a mesoporous multiphase amorphous crystal nanopowder Bi2O3 with a specific surface area of up to 23 m2/g was produced by pulsed electron beam evaporation in vacuum. Influence of thermal annealing (200-500 C) of powders in air is investigated. The formation of droplets with a size of 3-5 nm on the surface of all large nanoparticles constituting the framework 3D nanopowder agglomerates was found due to extrusion of liquid bismuth from the volume during cooling. © Published under licence by IOP Publishing Ltd.The study was carried out with the financial support of RFFI and the Czech Science Foundation as part of scientific project No. 20-58-26002

Photon-noise-tolerant dispersive readout of a superconducting qubit using a nonlinear Purcell filter

Residual noise photons in a readout resonator become a major source of dephasing for a superconducting qubit when the resonator is optimized for a fast, high-fidelity dispersive readout. Here, we propose and demonstrate a nonlinear Purcell filter that suppresses such an undesired dephasing process without sacrificing the readout performance. When a readout pulse is applied, the filter automatically reduces the effective linewidth of the readout resonator, increasing the sensitivity of the qubit to the input field. The noise tolerance of the device we fabricated is shown to be enhanced by a factor of three relative to a device with a linear filter. The measurement rate is enhanced by another factor of three by utilizing the bifurcation of the nonlinear filter. A readout fidelity of 99.4% and a QND fidelity of 99.2% are achieved using a 40-ns readout pulse. The nonlinear Purcell filter will be an effective tool for realizing a fast, high-fidelity readout without compromising the coherence time of the qubit.Comment: 13 pages, 9 figure

Modifying the Surface of Cerium Oxide Nanopowders Produced by Physical Method

The work was supported by Russian Science Foundation project № 18-72-00041. The authors are grateful to A. N. Kiryakov (Ural Federal University) for assistance in luminescence measurements