Identification of Mfn2-S249 as a Phosphoregulatory Switch of Mitochondrial Fusion Dynamics

Mitochondrial remodeling is a fundamental process underlying cellular respiration and metabolism. Here we report TAK1 as a direct regulator of mitochondrial fusion. TAK1 is activated by a variety of mitogenic factors, cytokines and environmental stimuli, which we find induces rapid fragmentation through Mfn2 inactivation. TAK1 phosphorylates Mfn2 at Ser249, which inhibits the binding of GTP required for Mfn trans-dimerization and mitochondrial membrane fusion. Accordingly, expression of Mfn2-S249 phosphomimetics (Mfn2-E/D) constitutively promote fission whereas alanine mutant (Mfn2-A) yields hyperfused mitochondria and increased bioenergetics in cells. In mice, Mfn2-E knock-in yields embryonic lethality in homozygotes whereas heterozygotes are viable but exhibit increased visceral fat accumulation despite normal body weight and cognitive/motor functions compared to wildtype and Mfn2-A mice. Mature white adipocytes isolated from mutant mice reveal cell-autonomous TAK1-related effects on mitochondrial remodeling and lipid metabolism. These results identify Mfn2-S249 as a dynamic phosphoregulatory switch of mitochondrial fusion during development and energy homeostasis.

Within and Beyond the Nucleotide Addition Cycle of Viral RNA-dependent RNA Polymerases

Nucleotide addition cycle (NAC) is a fundamental process utilized by nucleic acid polymerases when carrying out nucleic acid biosynthesis. An induced-fit mechanism is usually taken by these polymerases upon NTP/dNTP substrate binding, leading to active site closure and formation of a phosphodiester bond. In viral RNA-dependent RNA polymerases, the post-chemistry translocation is stringently controlled by a structurally conserved motif, resulting in asymmetric movement of the template-product duplex. This perspective focuses on viral RdRP NAC and related mechanisms that have not been structurally clarified to date. Firstly, RdRP movement along the template strand in the absence of catalytic events may be relevant to catalytic complex dissociation or proofreading. Secondly, pyrophosphate or non-cognate NTP-mediated cleavage of the product strand 3′-nucleotide can also play a role in reactivating paused or arrested catalytic complexes. Furthermore, non-cognate NTP substrates, including NTP analog inhibitors, can not only alter NAC when being misincorporated, but also impact on subsequent NACs. Complications and challenges related to these topics are also discussed.

Localized X-Ray Photoelectron Impedance Spectroscopy (LoXPIS) for Tapping into Charge-Dynamics of Ionic-Liquid Electrolytes within Energy Storage Devices

Many electrochemical devices are based on the fundamental process of ion migration and accumulation on surfaces. Complex interplay of molecular properties of ions and device dimensions control the entire process...

Key Function of the Bank of Russia: Contradictions and Problems

The article examines the most important categories, mechanisms, and instruments of the monetary policy of the Bank of Russia from the point of view of both its development and its implementation. The essence, origins and driving forces of the main contradiction of Russia's monetary policy are revealed. It is shown that monetary policy, along with the economic policy of the state, should act as a regulator of important meanings of human existence, such as the growth of real incomes of the population, directly affecting the redistribution of money – this market form of universal requirement for part of the national wealth. The author's position is presented, according to which inflation is not so much a macroeconomic indicator, as it is often customary to treat this phenomenon, as a fundamental process of a market economy that determines the redistribution of national wealth between economic entities through money. The authors identified and described the main problems and local contradictions in the development and implementation of a unified state monetary policy, presented a detailed description of these phenomena. The methodology of dialectical-systemic and logical analysis, which was used by the authors as a research tool, allowed for the first time to formulate the main contradiction of the unified state monetary policy. The presented formulation reflects the essential principles of the poles of contradiction – the contradiction between form and content. In order to solve the problems identified and existing for a long time, the authors justify the need to take priority organizational and legal measures, first of all, changing the statute, reforming functions, strengthening operational capabilities and staffing of the National Financial Council.

Trans-Translation Is an Appealing Target for the Development of New Antimicrobial Compounds

Because of the ever-increasing multidrug resistance in microorganisms, it is crucial that we find and develop new antibiotics, especially molecules with different targets and mechanisms of action than those of the antibiotics in use today. Translation is a fundamental process that uses a large portion of the cell’s energy, and the ribosome is already the target of more than half of the antibiotics in clinical use. However, this process is highly regulated, and its quality control machinery is actively studied as a possible target for new inhibitors. In bacteria, ribosomal stalling is a frequent event that jeopardizes bacterial wellness, and the most severe form occurs when ribosomes stall at the 3′-end of mRNA molecules devoid of a stop codon. Trans-translation is the principal and most sophisticated quality control mechanism for solving this problem, which would otherwise result in inefficient or even toxic protein synthesis. It is based on the complex made by tmRNA and SmpB, and because trans-translation is absent in eukaryotes, but necessary for bacterial fitness or survival, it is an exciting and realistic target for new antibiotics. Here, we describe the current and future prospects for developing what we hope will be a novel generation of trans-translation inhibitors.

Visualizing translation dynamics at atomic detail inside a bacterial cell

Translation is the fundamental process of protein synthesis and is catalysed by the ribosome in all living cells. Here, we use cryo-electron tomography and sub-tomogram analysis to visualize the dynamics of translation inside the prokaryote Mycoplasma pneumoniae. We first obtain an in-cell atomic model for the M. pneumoniae ribosome that reveals distinct extensions of ribosomal proteins. Classification then resolves thirteen ribosome states that differ in conformation and composition and reflect intermediates during translation. Based on these states, we animate translation elongation and demonstrate how antibiotics reshape the translation landscape inside cells. During translation elongation, ribosomes often arrange in a defined manner to form polysomes. By mapping the intracellular three-dimensional organization of translating ribosomes, we show that their association into polysomes exerts a local coordination mechanism that is mediated by the ribosomal protein L9. Our work demonstrates the feasibility of visualizing molecular processes at atomic detail inside cells.

The Revolution is Over, Forget It: To the 30th Anniversary of the Russian Federation

After the collapse of the Soviet Union, the power in post-Soviet Russia was seized by the leaders of the democratic movement - first wave democrats, and the more progressive Soviet nomenclature. As a result of the miscalculations made by the leaders of the democratic movement, the representatives of the Soviet nomenclature soon started displacing the first wave democrats and the reformers of the Gaidar call from the Russian governmental bodies in order to gain full control over the governance in the country. This appeared to be a manifestation of the more general and fundamental process, where the Russian nomenclature separated from the democratic movement, emerging as a new ruling stratum - the immediate heir to the Soviet nomenclature. The turning point, which accelerated the separation and the retreat of the Russian nomenclature from liberal and democratic principles of the countrys modernization, was the beginning of the Chechen tragedy in 1994. Not only did the Chechen events separate the Russian nomenclature and the democratic movement but also split the democratic movement itself. The goal of the article is to examine the transformation of the relationship between the democratic movement and the soviet and, later on, Russian nomenclature during the revolutionary changes of the early 1990s.

Special Issue “Interaction of Ionizing Photons with Atomic and Molecular Ions”

The interaction of ionizing photons with atoms or ions is a fundamental process in nature, with laboratory, atmospheric and astrophysical implications [...]

Test particle acceleration in resistive torsional fan magnetic reconnection using laboratory plasma parameters

Particle acceleration via magnetic reconnection is a fundamental process in astrophysical plasmas. Experimental architectures are able to confirm a wide variety of particle dynamics following the two-dimensional Sweet–Parker model, but are limited in their reproduction of the fan-spine magnetic field topology about three-dimensional (3-D) null points. Specifically, there is not yet an experiment featuring driven 3-D torsional magnetic reconnection. To move in this direction, this paper expands on recent work toward the design of an experimental infrastructure for inducing 3-D torsional fan reconnection by predicting feasible particle acceleration profiles. Solutions to the steady-state, kinematic, resistive magnetohydrodynamic equations are used to numerically calculate particle trajectories from a localized resistivity profile using well-understood laboratory plasma parameters. We confine a thin, 10 eV helium sheath following the snowplough model into the region of this localized resistivity and find that it is accelerated to energies of ${\approx }2$ keV. This sheath is rapidly accelerated and focused along the spine axis propagating a few centimetres from the reconnection region. These dynamics suggest a novel architecture that may hold promise for future experiments studying solar coronal particle acceleration and for technology applications such as spacecraft propulsion.

Food chain information systems in medium- and smallsized slaughterhouses of central Italy and organ and carcass condemnations: A five-year survey

The flow of information between farms and slaughterhouses about animal health, is a fundamental process for modern meat inspection. The information provided by Food Chain Information (FCI) systems in medium-small sized slaughterhouses in central Italy, focusing on the data provided on the animal’s health status, was performed through a five-year survey together with the number of organ and carcass condemnation for bovine, swine and ovine. The annual prevalence of condemnation was higher in bovine (from 10.49% in 2015 to 17.16% in 2019) than swine (from 6.39% in 2015 to 12.64% in 2019) and ovine (from 8.05% in 2019 to 8.98% in 2017), and an overall prevalence increase was observed in bovine and swine, throughout the years. The frequent lack of Food Chain Information (FCI) from farms to slaughterhouses should be emphasised, taking into consideration that a poor implementation of the system by farmers, could lead to a persistent risk of disease at farm level for these two species.