High-Resolution Three-Dimensional NMR Structure Of The KRAS Proto-Oncogene Promoter Reveals Key Features Of A G-Quadruplex Involved In Transcriptional Regulation

Non-canonical base pairing within guanine-rich DNA and RNA sequences can produce G-quartets, whose stacking leads to the formation of a G-quadruplex (G4). G4s can coexist with canonical duplex DNA in the human genome and have been suggested to suppress gene transcription, and much attention has therefore focused on studying G4s in promotor regions of disease-related genes. For example, the human KRAS proto-oncogene contains a nuclease-hypersensitive element located upstream of the major transcription start site. The KRAS nuclease-hypersensitive element (NHE) region contains a G-rich element (22RT; 5′-AGGGCGGTGTGGGAATAGGGAA-3′) and encompasses a Myc-associated zinc finger-binding site that regulates KRAS transcription. The NEH region therefore has been proposed as a target for new drugs that control KRAS transcription, which requires detailed knowledge of the NHE structure. In this study, we report a high-resolution NMR structure of the G-rich element within the KRAS NHE. We found that the G-rich element forms a parallel structure with three G-quartets connected by a four-nucleotide loop and two short one-nucleotide double-chain reversal loops. In addition, a thymine bulge is found between G8 and G9. The loops of different lengths and the presence of a bulge between the G-quartets are structural elements that potentially can be targeted by small chemical ligands that would further stabilize the structure and interfere or block transcriptional regulators such as Myc-associated zinc finger from accessing their binding sites on the KRAS promoter. In conclusion, our work suggests a possible new route for the development of anticancer agents that could suppress KRAS expression

Development of personnel technologies in the customs system of the Russian Federation

In the paper, the authors study the main reasons for introducing economic sanctions against the Russian Federation and how to counteract them. At the same time, the current situation requires intensified development of the international business to modernize the Russian economy. For this, it has become imperative to understand the role and place of the customs of the Russian Federation in this process and to further improve the approaches to staffing a federal executive body – the Federal Customs Service (FCS of Russia) in terms of selecting highly skilled personnel. In the end, a unified methodology for evaluating candidates taking civil service postsin the customs bodies is propose

Research of component composition and catalitic reactivity of metallurgical industry slag

The article deals with the research of component composition and catalitic reactivity of metallurgical waste products. The slags component composition was investigated by X-ray fluorescence analysis. The slag stuff has been modified with alkali (NaOH) and mineral acids (HNO3, H2SO4, HCI and H3PO4), and their catalytic reactivity in the catalytic decomposition of ethyl alcohol and hydrogen peroxide has been determined for the first time. The revealed catalytic reactivity of the slag staff for the decomposition of ethyl alcohol and hydrogen peroxide indicates the need for a more detailed research and development of an industrial non-ferrous waste treatment technology

Improving the assay-gravimetric method for determining the content of noble metals

The study considers the current state and problems of analytical control as the most important component of all stages of technology and production of noble metals. Based on the analysis carried out, a universal method for measuring the mass fraction of gold and silver in ores, products of their enrichment and metallurgical processing by the assay-gravimetric method was improved, and the optimal parameters for determining gold and silver were determined

Cosmological scalar fields that mimic the ΛCDM\Lambda CDM cosmological model

We look for cosmologies with a scalar field (dark energy without cosmological constant), which mimic the standard $\Lambda CDM$ cosmological model yielding exactly the same large-scale geometry described by the evolution of the Hubble parameter (i.e. photometric distance and angular diameter distance as functions on $z$). Asymptotic behavior of the field solutions is studied in the case of spatially flat Universe with pressureless matter and separable scalar field Lagrangians (power-law kinetic term + power-law potential). Exact analytic solutions are found in some special cases. A number of models have the field solutions with infinite behavior in the past or even singular behavior at finite redshifts. We point out that introduction of the cosmological scalar field involves some degeneracy leading to lower precision in determination of $\Omega_m$. To remove this degeneracy additional information is needed beyond the data on large-scale geometry.Comment: VIII International Conference "Relativistic Astrophysics, Gravitation and Cosmology": May 21-23, 2008, Kyiv, Ukrain

Alternative Method of Surgical Treatment of Post-Infarction Left Ventricular Free Wall Rupture. Case Report

Acute myocardial infarction (AMI) is one of the causes of death in developed countries, despite the latest medical technologies. AMI is usually accompanied by numerous fatal complications. One of these complications is left ventricular free wall rupture (LVFWR). Myocardial rupture after AMI can occur from 1 day to 3 weeks after the infarction. Most ruptures occur 3-5 days after a heart attack. Left ventricular free wall rupture requires only emergency surgical intervention, which in most cases consists in applying U-shaped sutures or wrapping sutures using Teflon patch. The aim. To demonstrate an example of alternative surgical tactics and intraoperative management of a patient with myocardial infarction complicated by rupture of the free wall of the heart with the transition to cardiogenic shock. Case report. We presented the clinical case of patient V., 72 years old, who was delivered by ambulance on January 10, 2023 to the intensive care department of the National Amosov Institute of Cardiovascular Surgery (Kyiv, Ukraine). Main diagnosis: ischemic heart disease, acute coronary syndrome with ST-elevation myocardial infarction, cardiogenic shock. Conclusion. The only effective method of treatment of rupture of the free wall of the heart is surgical intervention. Using a sandwich patch with resection of necrotic areas of the myocardium and U-shaped sutures with Teflon patch passed from the side of the left ventricular cavity through the myocardium in the peri-infarct zone and through a patch from a vascular prosthesis allows hermetically sew up the LVFWR