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21.
Nadine Reichhart Vladimir M. Milenkovic Christian H. Wetzel Olaf Strauß 《International journal of molecular sciences》2021,22(5)
The anoctamin (TMEM16) family of transmembrane protein consists of ten members in vertebrates, which act as Ca2+-dependent ion channels and/or Ca2+-dependent scramblases. ANO4 which is primarily expressed in the CNS and certain endocrine glands, has been associated with various neuronal disorders. Therefore, we focused our study on prioritizing missense mutations that are assumed to alter the structure and stability of ANO4 protein. We employed a wide array of evolution and structure based in silico prediction methods to identify potentially deleterious missense mutations in the ANO4 gene. Identified pathogenic mutations were then mapped to the modeled human ANO4 structure and the effects of missense mutations were studied on the atomic level using molecular dynamics simulations. Our data show that the G80A and A500T mutations significantly alter the stability of the mutant proteins, thus providing new perspective on the role of missense mutations in ANO4 gene. Results obtained in this study may help to identify disease associated mutations which affect ANO4 protein structure and function and might facilitate future functional characterization of ANO4. 相似文献
22.
Xin Shen Rui Zhang Shuhao Wang Xiang Chen Chuan Zhao Elena Kuzmina Elena Karaseva Vladimir Kolosnitsyn Qiang Zhang 《中国化学工程学报》2021,37(9):137-143
Lithium (Li) metal anodes promise an ultrahigh theoretical energy density and low redox potential,thus being the critical energy material for next-generation batteries.Unfortunately,the formation of Li den-drites in Li metal anodes remarkably hinders the practical applications of Li metal anodes.Herein,the dynamic evolution of discrete Li dendrites and aggregated Li dendrites with increasing current densities is visualized by in-situ optical microscopy in conjunction with ex-situ scanning electron microscopy.As revealed by the phase field simulations,the formation of aggregated Li dendrites under high current den-sity is attributed to the locally concentrated electric field rather than the depletion of Li ions.More specif-ically,the locally concentrated electric field stems from the spatial inhomogeneity on the Li metal surface and will be further enhanced with increasing current densities.Adjusting the above two factors with the help of the constructed phase field model is able to regulate the electrodeposited morphology from aggregated Li dendrites to discrete Li dendrites,and ultimately columnar Li morphology.The methodol-ogy and mechanistic understanding established herein give a significant step toward the practical appli-cations of Li metal anodes. 相似文献
23.
Svetlana V. Klinova Boris A. Katsnelson Ilzira A. Minigalieva Oksana P. Gerzen Alexander A. Balakin Ruslan V. Lisin Ksenia A. Butova Salavat R. Nabiev Oleg N. Lookin Leonid B. Katsnelson Larisa I. Privalova Daniil A. Kuznetsov Vladimir Ya. Shur Ekaterina V. Shishkina Oleg H. Makeev Irene E. Valamina Vladimir G. Panov Marina P. Sutunkova Larisa V. Nikitina Yuri L. Protsenko 《International journal of molecular sciences》2021,22(7)
Subchronic intoxication was induced in outbred male rats by repeated intraperitoneal injections with lead oxide (PbO) and/or cadmium oxide (CdO) nanoparticles (NPs) 3 times a week during 6 weeks for the purpose of examining its effects on the contractile characteristics of isolated right ventricle trabeculae and papillary muscles in isometric and afterload contractions. Isolated and combined intoxication with these NPs was observed to reduce the mechanical work produced by both types of myocardial preparation. Using the in vitro motility assay, we showed that the sliding velocity of regulated thin filaments drops under both isolated and combined intoxication with CdO–NP and PbO–NP. These results correlate with a shift in the expression of myosin heavy chain (MHC) isoforms towards slowly cycling β–MHC. The type of CdO–NP + PbO–NP combined cardiotoxicity depends on the effect of the toxic impact, the extent of this effect, the ratio of toxicant doses, and the degree of stretching of cardiomyocytes and muscle type studied. Some indices of combined Pb–NP and CdO–NP cardiotoxicity and general toxicity (genotoxicity included) became fully or partly normalized if intoxication developed against background administration of a bioprotective complex. 相似文献
24.
Alsu Z. Malikova Anastasia S. Shcherbakova Konstantin A. Konduktorov Anastasia S. Zemskaya Alexandra A. Dalina Vladimir I. Popenko Olga G. Leonova Alexei V. Morozov Nikolay N. Kurochkin Olga A. Smirnova Sergey N. Kochetkov Maxim V. Kozlov 《International journal of molecular sciences》2021,22(9)
Recent evidence suggests that fibrotic liver injury in patients with chronic hepatitis C correlates with cellular senescence in damaged liver tissue. However, it is still unclear how senescence can affect replication of the hepatitis C virus (HCV). In this work, we report that an inhibitor of cyclin-dependent kinases 4/6, palbociclib, not only induced in hepatoma cells a pre-senescent cellular phenotype, including G1 arrest in the cell cycle, but also accelerated viral replicon multiplication. Importantly, suppression of HCV replication by direct acting antivirals (DAAs) was barely affected by pre-senescence induction, and vice versa, the antiviral activities of host-targeting agents (HTAs), such as inhibitors of human histone deacetylases (HDACi), produced a wide range of reactions—from a dramatic reduction to a noticeable increase. It is very likely that under conditions of the G1 arrest in the cell cycle, HDACi exhibit their actual antiviral potency, since their inherent anticancer activity that complicates the interpretation of test results is minimized. 相似文献
25.
Yurii S. Borovikov Daria D. Andreeva Stanislava V. Avrova Vladimir V. Sirenko Armen O. Simonyan Charles S. Redwood Olga E. Karpicheva 《International journal of molecular sciences》2021,22(12)
Point mutations in the genes encoding the skeletal muscle isoforms of tropomyosin can cause a range of muscle diseases. The amino acid substitution of Arg for Pro residue in the 90th position (R90P) in γ-tropomyosin (Tpm3.12) is associated with congenital fiber type disproportion and muscle weakness. The molecular mechanisms underlying muscle dysfunction in this disease remain unclear. Here, we observed that this mutation causes an abnormally high Ca2+-sensitivity of myofilaments in vitro and in muscle fibers. To determine the critical conformational changes that myosin, actin, and tropomyosin undergo during the ATPase cycle and the alterations in these changes caused by R90P replacement in Tpm3.12, we used polarized fluorimetry. It was shown that the R90P mutation inhibits the ability of tropomyosin to shift towards the outer domains of actin, which is accompanied by the almost complete depression of troponin’s ability to switch actin monomers off and to reduce the amount of the myosin heads weakly bound to F-actin at a low Ca2+. These changes in the behavior of tropomyosin and the troponin–tropomyosin complex, as well as in the balance of strongly and weakly bound myosin heads in the ATPase cycle may underlie the occurrence of both abnormally high Ca2+-sensitivity and muscle weakness. BDM, an inhibitor of myosin ATPase activity, and W7, a troponin C antagonist, restore the ability of tropomyosin for Ca2+-dependent movement and the ability of the troponin–tropomyosin complex to switch actin monomers off, demonstrating a weakening of the damaging effect of the R90P mutation on muscle contractility. 相似文献
26.
Electrical discharge machining is an attractive machining technique which requires electrically conductive ceramic materials. Silicon nitride based composites with 35–40% of TiN possess electrical conductivity high enough to use this machining technique. The composite powder was prepared by combustion synthesis and densified by pressure sintering (sintering aids 6 wt% of Y2 O3 and 4 wt% of A1,03 ). High fracture toughness, K c 10.5 MPa. m1/2 , is typical for the composite. It can be expected that this material can compete with pure silicon nitride in applications requiring complex machining. 相似文献
27.
28.
Valerii S. Kozlov Elena P. Yausheva Svetlana A. Terpugova Mikhail V. Panchenko Dmitriy G. Chernov Vladimir P. Shmargunov 《International journal of remote sensing》2014,35(15):5722-5741
A comprehensive experiment on the study of dynamics of optical and microphysical characteristics of submicron aerosols in the near-ground air layer was carried out in June–August of 2012 under conditions of extremely strong smoke haze originating from vast forest fires in Siberia. Variations of the spectral angular scattering coefficients and the degree of linear polarization in the visible wavelength range are studied, as well as the mass concentrations of dry fractions of aerosol and black carbon, relative content of black carbon (BC fraction), single scattering albedo, particle size distribution function, complex refractive index of the particulate matter, and parameter of condensation activity of aerosol. Peculiarities of differences between optical and microphysical characteristics of near-ground aerosol in smoke haze and under smokeless conditions are revealed. This study is important for validation of results of remote sensing of the composition of smoke haze and background atmosphere obtained from satellite data and sun photometric measurements at the Aerosol Robotic Network (AERONET). 相似文献
29.
Vladimir Ćurić Joakim Lindblad Nataša Sladoje Hamid Sarve Gunilla Borgefors 《Pattern Analysis & Applications》2014,17(1):141-152
We propose a new distance measure, called Complement weighted sum of minimal distances, between finite sets in ${\mathbb Z }^n$ and evaluate its usefulness for shape registration and matching. In this set distance the contribution of each point of each set is weighted according to its distance to the complement of the set. In this way, outliers and noise contribute less to the new similarity measure. We evaluate the performance of the new set distance for registration of shapes in binary images and compare it to a number of often used set distances found in the literature. The most extensive evaluation uses a set of synthetic 2D images. We also show three examples of real problems: registering a set of 2D images extracted from synchrotron radiation micro-computed tomography (SR $\upmu $ CT) volumes depicting bone implants; the difficult multi-modal registration task of finding the exact location of a 2D slice of a bone implant, as imaged by a light microscope, within a 3D SR $\upmu $ CT volume of the same implant; and finally recognition of handwritten characters. The evaluation shows that our new set distance performs well for all tasks and outperforms the other observed distance measures in most cases. It is therefore useful in many image registration and shape comparison tasks. 相似文献
30.
Gregory B. Furman Shaul D. Goren Victor M. Meerovich Vladimir L. Sokolovsky 《Quantum Information Processing》2014,13(12):2759-2768
We study behavior of quantum discord, a kind of quantum correlation, in systems of dipole–dipole interacting spins in an external magnetic field in the whole temperature range ( \(-\infty ). It was shown that negative temperatures, which are introduced to describe inversions in the population in a finite level system, provide more favorable conditions for emergence of quantum correlations including entanglement. We show that at negative temperature, the correlations become more intense and discord exists between remote spins being in separated states. 相似文献