664 research outputs found
ПРАВОВІ ТА ОРГАНІЗАЦІЙНІ ЗАСАДИ ЗАПОБІГАННЯ КОРУПЦІЇ У СФЕРІ ПУБЛІЧНОГО УПРАВЛІННЯ УКРАЇНИ
Стаття присвячена проблемі корупції в сфері публічного управління в сучасній Україні. Розглянуті основні причини існування корупції в органах державної влади і місцевого самоврядування. Визначені чинники інституціоналізації корупційних відносин та утворення мережі неформальних деструктивних інститутів в органах влади. Окреслені правові та організаційні засади запобігання та протидії корупції в сфері державного управління. Здійснено пошук ефективних інструментів протидії корупції в органах влади
A novel intermediate in transcription initiation by human mitochondrial RNA polymerase
The mitochondrial genome is transcribed by a single-subunit T7 phage-like RNA polymerase (mtRNAP),structurally unrelated to cellular RNAPs. In higher eukaryotes, mtRNAP requires two transcription factors for efficient initiation-TFAM, a major nucleoid protein, and TFB2M, a transient component of mtRNAP catalytic site. The mechanisms behind assembly of the mitochondrial transcription machinery and its regulation are poorly understood. We isolated and identified a previously unknown human mitochondrial transcription intermediate-a pre-initiation complex that includes mtRNAP, TFAM and promoter DNA. Using protein-protein cross-linking, we demonstrate that human TFAM binds to the N-terminal domain of mtRNAP, which results in bending of the promoter DNA around mtRNAP. The subsequent recruitment of TFB2M induces promoter melting and formation of an open initiation complex. Our data indicate that the pre-initiation complex is likely to be an important target for transcription regulation and provide basis for further structural, biochemical and biophysical studies of mitochondrial transcription
Mechanisms of mitochondrial promoter recognition in humans and other mammalian species
Recognition of mammalian mitochondrial promoters requires the concerted action of mitochondrial RNA polymerase (mtRNAP) and transcription initiation factors TFAM and TFB2M. In this work, we found that transcript slippage results in heterogeneity of the human mitochondrial transcripts in vivo and in vitro. This allowed us to correctly interpret the RNAseq data, identify the bona fide transcription start sites (TSS), and assign mitochondrial promoters for \u3e 50% of mammalian species and some other vertebrates. The divergent structure of the mammalian promoters reveals previously unappreciated aspects of mtDNA evolution. The correct assignment of TSS also enabled us to establish the precise register of the DNA in the initiation complex and permitted investigation of the sequence-specific protein-DNA interactions. We determined the molecular basis of promoter recognition by mtRNAP and TFB2M, which cooperatively recognize bases near TSS in a species-specific manner. Our findings reveal a role of mitochondrial transcription machinery in mitonuclear coevolution and speciation
Mechanism of Transcription Anti-termination in Human Mitochondria.
In human mitochondria, transcription termination events at a G-quadruplex region near the replication origin are thought to drive replication of mtDNA by generation of an RNA primer. This process is suppressed by a key regulator of mtDNA-the transcription factor TEFM. We determined the structure of an anti-termination complex in which TEFM is bound to transcribing mtRNAP. The structure reveals interactions of the dimeric pseudonuclease core of TEFM with mobile structural elements in mtRNAP and the nucleic acid components of the elongation complex (EC). Binding of TEFM to the DNA forms a downstream sliding clamp, providing high processivity to the EC. TEFM also binds near the RNA exit channel to prevent formation of the RNA G-quadruplex structure required for termination and thus synthesis of the replication primer. Our data provide insights into target specificity of TEFM and mechanisms by which it regulates the switch between transcription and replication of mtDNA
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ACHROMATIC LOW-BETA INTERACTION REGION DESIGN FOR AN ELECTRON-ION COLLIDER
An achromatic Interaction Region (IR) design concept is presented with an emphasis on its application at an electron-ion collider. A specially-designed symmetric Chromaticity Compensation Block (CCB) induces an angle spread in the passing beam such that it cancels the chromatic kick of the final focusing quadrupoles. Two such CCB's placed symmetrically around an interaction point (IP) allow simultaneous compensation of the 1st-order chromaticities and chromatic beam smear at the IP without inducing significant 2nd-order aberrations. Special attention is paid to the difference in the electron and ion IR design requirements. We discuss geometric matching of the electron and ion IR footprints. We investigate limitations on the momentum acceptance in this IR design
The main directions for optimizing traffic flows to increase their throughput
This paper analyzes various problems of mathematical modeling of traffic flows that are relevant for optimizing and reducing the congestion of road networks in large cities and metropolitan areas. Various types of relationships between traffic lights on a controlled section of the road have been studied, formulas have been proposed for calculating the optimal joint mode of operation and minimizing the formation of traffic jams in front of the intersection. A model for calculating the optimal traffic flow on a section of the road network and its implementation at the program level are proposed
Mathematical methods and models of traffic flow management
An overview of existing mathematical models of traffic flows is presented. Various macroscopic and microscopic mathematical models of traffic flows are considered, which make it possible to calculate the congestion of road transport networks. The basic principles of their application and significant differences between them are analyzed. Based on the considered mathematical models, a model of rebuilding vehicles between traffic lanes is proposed
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