Glycogen Synthase Kinase 3-Dependent Phosphorylation of Mdm2 Regulates p53 Abundance

The Mdm2 oncoprotein regulates abundance and activity of the p53 tumor suppressor protein. For efficient degradation of p53, Mdm2 needs to be phosphorylated at several contiguous residues within the central conserved domain. We show that glycogen synthase kinase 3 (GSK-3) phosphorylated the Mdm2 protein in vitro and in vivo in the central domain. Inhibition of GSK-3 rescued p53 from degradation in an Mdm2-dependent manner while its association with Mdm2 was not affected. Likewise, inhibition of GSK-3 did not alter localization of p53 and Mdm2 or the interaction of Mdm2 and MdmX. Ionizing radiation, which leads to p53 accumulation, directed phosphorylation of GSK-3 at serine 9, which preceded and overlapped with the increase in p53 levels. Moreover, expression of a GSK-3 mutant where serine 9 was replaced with an alanine reduced the accumulation of p53 and induction of its target p21(WAF-1). We therefore conclude that inhibition of GSK-3 contributes to hypophosphorylation of Mdm2 in response to ionizing rays, and in consequence to p53 stabilization

Affect of the lubrication mode on the tribophysical properties of lubricants with innovative 2D nanoparticles of tungsten and molybdenum diselenide

LUBMAT-IBERTRIB, 18th-19th-20th June 2024, San Sebastián (Spain), Kursaal.This paper addresses affect of the lubrication mode on the tribophysical properties of lubricants with innovative 2H-MCh2. Regarding their use as effective solid lubricant additives to lubricants with significantly improved tribological properties for modern technology. The mentioned materials in this work are 2H-WSe2 or 2H-MoSe2 and some typical lubrication (industrial and aviation oil, hydraulic liquid) Tribology tests in the boundary lubrication mode of oils with graphene-like nanoparticles 2Н-MoSe2 or 2Н WSe2 showed that these additives significantly, but ambiguously, affect the tribological properties of lubricating compositions. The effectiveness of the applications, as shown below, essentially depends on the composition and lubricating (physico-chemical) properties of the base oil, as well as on the friction conditions.The study was partially supported by the grant from Spanish National Research Council (CSIC) - UCRAN20010 and SPS NATO (MYP G6128.)Peer reviewe

The Role of Stepwise Photoionization in Measurements of the Ionization Potentials in Dense Plasma

The interaction of high-contrast high-intensity laser radiation with solids allows us to create hot or warm plasma of solid or even over-solid density, such as in the case of inertial fusion particularly. The multicharged ions contained in it can no longer be considered isolated. As a result, this leads to a decrease in the ionization potentials and to the disappearance of a number of bound ionic states. To describe the ionization potential depression, two major approaches are now used predominantly, where the key parameter is either average interelectronic or interionic distance. Since neither of the approaches can be substantiated purely theoretically, their applicability can only be established by comparison with experimental results. In recent experiments with X-ray free-electron lasers, it was concluded that the ionization potential depression rather depends on the interelectronic distance. However, when measuring ionization potentials, it was assumed that the main role in ionization processes is played by the direct photoionization of the ion ground state. In the present paper, we show that stepwise photoionization processes should play a significant role in dense plasma, disrupting a straight correspondence between the threshold in direct photoionization by X-ray laser photons and the actual ionization potential of multicharged ions. It means that the measurement results mentioned above are not correct, and the main conclusion about the importance of the interelectronic distance for depression of the ionization potential is not correct

Unexpected Room Temperature Ferromagnetism of a Ball-Milled Graphene Oxide—Melamine Mixture

Nitrogen-doped carbon nanomaterial (NDCNM) was synthesized by grinding a mixture of graphene oxide and melamine in a planetary mill with both balls and milling chamber of zirconium dioxide. In the electron spin resonance spectrum of NDCNM, a broad signal with g = 2.08 was observed in addition to a narrow signal at g = 2.0034. In the study using a vibrating-sample magnetometer, the synthesized material is presumably a ferromagnet with a coercive force of 100 Oe. The specific magnetization at 10,000 Oe is approximately 0.020 and 0.055 emu/g at room temperature and liquid nitrogen temperature, respectively

Transcriptional Landscape of Staphylococcus aureus Kayvirus Bacteriophage vB_SauM-515A1

The Twort-like myoviruses (Kayvirus genus) of S. aureus are promising agents for bacteriophage therapy due to a broad host range and high killing activity against clinical isolates. This work improves the current understanding of the phage infection physiology by transcriptome analysis. The expression profiles of a typical member of the Kayvirus genus (vB_SauM-515A1) were obtained at three time-points post-infection using RNA sequencing. A total of 35 transcription units comprising 238 ORFs were established. The sequences for 58 early and 12 late promoters were identified in the phage genome. The early promoters represent the strong sigma-70 promoters consensus sequence and control the host-dependent expression of 26 transcription units (81% of genes). The late promoters exclusively controlled the expression of four transcription units, while the transcription of the other five units was directed by both types of promoters. The characteristic features of late promoters were long -10 box of TGTTATATTA consensus sequence and the absence of -35 boxes. The data obtained are also of general interest, demonstrating a strategy of the phage genome expression with a broad overlap of the early and late transcription phases without any middle transcription, which is unusual for the large phage genomes (>100 kbp)

Application of Fuzzy Logic and SNA Tools to Assessment of Communication Quality between Construction Project Participants

The purpose of this research is to study the communication network among the participants in a construction project. The proposed approach contains the solving of the following tasks: identification of the key factors that affect the communication quality; calculation of the “communication quality” indicator between each pair of participants using fuzzy logic; and evaluation of the key measures of centrality using the tools of a Social Network Analysis. Solving the set tasks can help break the problem of the low level of efficiency of construction project deliveries. This study was conducted when the design stage was already complete and the construction project had 17 participants. We used the following factors influencing communication quality: timeliness, understanding, bidirectionality, use of IT tools in communication acts and adequacy. The use of fuzzy logic tools can minimise the subjectivity of the qualitative data obtained from the questionnaires. The analysis of five centrality measures showed that “Project manager”, “Chief engineer”, “Construction site manager”, “Construction works manager” and “Architect” had the greatest values in comparison with other network participants. On the one hand, this organisational structure of communication can be considered correct because the main information flows through the project managers, who make the decisions. On the other hand, this indicates a significant dependence of the construction project on these participants and, in the event of certain risk events, may lead to a decrease in the efficiency of its implementation. The methods presented in this article can be used in project management to analyse a real communication network

A Facile Synthesis of Noble-Metal-Free Catalyst Based on Nitrogen Doped Graphene Oxide for Oxygen Reduction Reaction

A simple method for the mechanochemical synthesis of an effective metal-free electrocatalyst for the oxygen reduction reaction was demonstrated. A nitrogen-doped carbon material was obtained by grinding a mixture of graphene oxide and melamine in a planetary ball mill. The resulting material was characterized by XPS, EPR, and Raman and IR spectroscopy. The nitrogen concentration on the N-bmGO surface was 5.5 at.%. The nitrogen-enriched graphene material (NbmGO has half-wave potential of −0.175/−0.09 V and was shown to possess high activity as an electrocatalyst for oxygen reduction reaction. The electrocatalytic activity of NbmGO can be associated with a high concentration of active sites for the adsorption of oxygen molecules on its surface. The high current retention (93% for 12 h) after continuous polarization demonstrates the excellent long-term stability of NbmGO

Incoherent Optical Fluctuation Flowmetry: A New Method for the Assessment of Foot Perfusion in Patients with Diabetes-Related Lower-Extremity Complications

(1) Background: To date, there are no studies evaluating the ability of the incoherent optical fluctuation flowmetry (IOFF) method to assess foot tissue perfusion. The aim of this study was to evaluate the correlation between perfusion values measured by IOFF and TcPO2 in patients with diabetes-related lower-extremity complications. (2) Methods: This was an observational, cross-sectional, two-center study. Diabetic patients with peripheral artery disease and/or diabetic foot ulcers were studied (n = 27, examinations were carried out on 54 legs). Perfusion in the foot tissues was assessed using TcPO2 (reference standard for this study) and the IOFF method. (3) Results: High correlation coefficients of all perfusion parameters measured by IOFF with TcPO2 (Rs 0.7 to 0.76) were shown. The study demonstrated that the IOFF method allows, with a sensitivity of 85.7% and a specificity of 90.0%, the identification of patients with a critical decrease in TcPO2 2 and the moderately high sensitivity and specificity in detecting patients with severe ischemia of foot tissues shows the promise of the method for assessing a tissue perfusion in patients with diabetes-related lower-extremity complications