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

Study on performance of compression engine operated by biodiesel fuel

The analysis of the performance of biofuel is aimed at evaluating the energy efficiency of operating the engine with the use of biodiesel fuel as function of the fuel’s composition and other physical-and-chemical parameters. The mathematical models and analysis techniques known to the authors do not take into account the effect that the use of different bio-diesel fuels has on the operation of the engine and, therefore, need refinement in terms of the mathematical expressions and empirical formulae that describe the physical processes taking place in the engine’s cylinders. The aim of the study is to improve the mathematical relations taking into consideration the physical-and-chemical parameters of different types of fuel. The research methods proposed in the article are based on step-by-step consideration of the mathematical models of processes that follow each other, with due account for their possible overlapping, which jointly have an effect on the engine’s output indices. The boundary conditions and parameter increments are pre-set in electronic work sheets. Thus, it becomes possible, using the refined mathematical model, to calculate the main performance indices of the diesel engine with due account for the changes in the physical-and-chemical parameters of the fuel. The novelty of the described approach is in the possibility, through the use of the refined model and taking into account the data on the composition of the fuel and the design and operation parameters of the engine, to calculate the indices that allow evaluating the efficiency of use of specific fuels in the internal combustion engine under consideration. In results, formulas for the calculation of the effective power of the engine, fresh air charge density, excess air factor, effective specific fuel consumption and combustion pressure have been developed. Combustion pressure modelling and experimental data is presented

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]

Factors predicting chronic pain after open inguinal hernia repair : a regression analysis of randomized trial comparing three different meshes with three fixation methods (FinnMesh Study)

Correction: Volume: 22 Issue: 5 Pages: 819-819 DOI: 10.1007/s10029-018-1788-y WOS:000446065400016Chronic pain after inguinal hernioplasty is the foremost side-effect up to 10-30% of patients. Mesh fixation may influence on the incidence of chronic pain after open anterior mesh repairs. Some 625 patients who underwent open anterior mesh repairs were randomized to receive one of the three meshes and fixations: cyanoacrylate glue with low-weight polypropylene mesh (n = 216), non-absorbable sutures with partially absorbable mesh (n = 207) or self-gripping polyesther mesh (n = 202). Factors related to chronic pain (visual analogue scores; VAS ae 30, range 0-100) at 1 year postoperatively were analyzed using logistic regression method. A second analysis using telephone interview and patient records was performed 2 years after the index surgery. At index operation, all patient characteristics were similar in the three study groups. After 1 year, chronic inguinal pain was found in 52 patients and after 2 years in only 16 patients with no difference between the study groups. During 2 years' follow-up, three (0.48%) patients with recurrences and five (0.8%) patients with chronic pain were re-operated. Multivariate regression analysis indicated that only new recurrent hernias and high pain scores at day 7 were predictive factors for longstanding groin pain (p = 0.001). Type of mesh or fixation, gender, pre-operative VAS, age, body mass index or duration of operation did not predict chronic pain. Only the presence of recurrent hernia and early severe pain after index operation seemed to predict longstanding inguinal pain.Peer reviewe

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

Digital Technologies in Jewelry design: Present and Future

В статье поднимаются вопросы виртуализации культуры и искусства на примере анализа возможностей проектирования и производства ювелирных украшений в эпоху цифровизации. Показано изменение роли дизайнера ювелирных украшений в связи с вовлечением в процесс разработки дизайна конечного потребителя. Описано влияние аддитивных технологий на дизайн ювелирных украшений и возможность получения украшений принципиально новой конструкции.The paper is devoted to the study of culture and art virtualization by analyzing the possibilities of jewelry designing and manufacturing in the digital era. The jewelry designer role is changed because the end user is involved in the design process more and more. The influence of additive technologies on the jewelry design and the possibility of obtaining fundamentally new design jewelry are described

Gd2O3, SiO2-Gd2O3 and SiO2-MnO2 nanoparticles as potential MRI contrast agents

Gd2O3, SiO2-Gd2O3 and SiO2-MnO2 nanoparticles were produced by the method of pulsed electron evaporation of oxide targets with condensation of the vapors in a vacuum. These materials are considered as probable contrast agents for magnetic resonance imaging (MRI). The Gd2O3 nanoparticles exhibit a rather high r1 and r2 relaxivities. These results point to the potential of using nanocrystals for MRI diagnosis. The mesoporous nanostructures SiO2-Gd2O3 and SiO2-MnO2 could be considered as multimodal theranostic agents. © 2020 IOP Publishing Ltd

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

Time course of changes in the development of gait disorders in multiple sclerosis

Objective: to estimate the time course of changes in foot biomechanical function as multiple sclerosis (MS) progresses in patients with different degrees of disability compared to a control group. Patients and methods. To estimate the time course of changes in gait disorders in MS, changes in foot biomechanical function were explored in 30 patients with relapsing-remitting MS. Their neurological status was evaluated using the expanded disability status scale (EDSS); pedographic examination was made applying a plantar pressure distribution system; all the patients were examined twice. During the first examination, the patients were divided into two groups: 1) minimal neurological disorders (EDSS scores of < 3.0) and 2) moderate ones (EDSS scores of ≥3.0). Results and discussion. The patients with a mild neurological deficit showed increases in foot load and its lateralization by elevating pressure on the heads of the fourth and fifth metatarsal bones, as evidenced by a significant rise in mean pressure, maximum force, and force-time integral. These changes occurred in the absence of the patients’ complaints of changes in movements. Pedographic examination revealed the changes indicating an enlarged anterior transverse arch and the lower role of the hallux in body weight transfer in the patients with a moderate neurological deficit despite the fact that there were no further visible negative changes in a motor process or progression in neurological deficit. The pedographic examination makes it possible to estimate the degree of gait disorders caused by pyramidal and/or cerebellar lesions and to identify a leading role of this or that functional system in their genesis. Pyramidal dysfunction has impact on the pressurization of the heads of the second and third metatarsal bones. Computed pedography can identify clinically subtle movement changes and estimate the time course of changes in movement disorders in MS patients, including those to evaluate the efficiency of therapy and rehabilitation measures