Methionine sulfoxide reductase B from Corynebacterium diphtheriae catalyzes sulfoxide reduction via an intramolecular disulfide cascade

Corynebacterium diphtheriae is a human pathogen that causes diphtheria. In response to immune system–induced oxidative stress, C. diphtheriae expresses antioxidant enzymes, among which are methionine sulfoxide reductase (Msr) enzymes, which are critical for bacterial survival in the face of oxidative stress. Although some aspects of the catalytic mechanism of the Msr enzymes have been reported, several details still await full elucidation. Here, we solved the solution structure of C. diphtheriae MsrB (Cd-MsrB) and unraveled its catalytic and oxidation-protection mechanisms. Cd-MsrB catalyzes methionine sulfoxide reduction involving three redox-active cysteines. Using NMR heteronuclear single-quantum coherence (HSQC) spectra, kinetics, biochemical assays, and MS analyses, we show that the conserved nucleophilic residue Cys122 is S-sulfenylated after substrate reduction, which is then resolved by a conserved cysteine, Cys66, or by the non-conserved residue Cys127. We noted that the overall structural changes during the disulfide cascade expose the Cys122–Cys66 disulfide to recycling through thioredoxin (Trx). In the presence of hydrogen peroxide, Cd-MsrB formed reversible intra- and intermolecular disulfides without losing its Cys-coordinated Zn2+, and only the non-conserved Cys127 reacted with the low-molecular-weight (LMW) thiol mycothiol, protecting it from overoxidation. In summary, our structure–function analyses reveal critical details of the Cd-MsrB catalytic mechanism, including a major structural rearrangement that primes the Cys122–Cys66 disulfide for Trx reduction and a reversible protection against excessive oxidation of the catalytic cysteines in Cd-MsrB through intra- and intermolecular disulfide formation and S-mycothiolation

Развитие перспективных сетевых тренажерных комплексов на воздушном транспорте с применением нечетких моделей и помехоустойчивого кодирования

The article analyzes foreign experience and concludes that one of the ways to improve the efficiency of aviation security in the Russian Federation is to use modern network training complexes. A new approach to the assessment of the competence of the aviation security screeners was proposed and tested, that allows to take into account the parameters of the oculomotor activity and heart rate variability of the aviation security screeners being tested, different from the existing approaches using fuzzy classification models. The eye-tracking technology and the device of psychophysiological testing UPFT-1/30 "Psychophysiologist" were used as instruments of psychophysiological monitoring. The basics of automatic generation of fuzzy models such as Sugeno and Mamdani from experimental data are presented. Experimental studies were conducted on the basis of the Ulyanovsk Civil Aviation Institute. The results of the comparison of the generated models showed that the Sugeno model trained with the use of ANFIS-algorithm is more accurate than the Mamdani model and the linear regression model identifies the dependence being studied, according to the competence of aviation security screeners. As a criterion of quality of models on training and test data the average square error is used. The actual problem of choosing an effective concept of noise-resistant coding in the telecommunication component of advanced training complexes is substantiated. The ways of solving the important problem of increasing the reliability of actual digital data in network training complexes based on the use of noise-resistant coding are described. A model of permutation decoder of non-binary redundant code based on lexicographic cognitive map is presented. This model of redundant code decoder uses methods of cognitive data processing in the implementation of the procedure of permutation decoding to effectively protect remote control commands from the influence of destructive factors on the control process.В данной работе проведен анализ зарубежного опыта и сделан вывод, что один из путей повышения эффективности обеспечения авиационной безопасности в Российской Федерации заключается в применении современных сетевых тренажерных комплексов. Предложен и апробирован новый подход к оценке уровня компетентности операторов досмотра, позволяющий учитывать параметры глазодвигательной деятельности и вариабельности сердечного ритма испытуемых операторов, отличающийся от существующих подходов применением нечетких моделей классификации. В качестве аппаратурных средств психофизиологического мониторинга использованы технология Eye tracking и устройство психофизиологического тестирования УПФТ-1/30 «Психофизиолог». Представлены основы автоматической генерации нечетких моделей типа Сугено и Мамдани из экспериментальных данных. Проведены экспериментальные исследования на базе ФГБОУ ВО УИ ГА. Результаты сравнения сгенерированных моделей показали, что модель Сугено, обученная с применением ANFIS-алгоритма, точнее, чем модель Мамдани и модель линейной регрессии, идентифицирует исследуемую зависимость по оценке компетентности операторов досмотра. В качестве критерия качества моделей на обучающих и тестовых данных использована средняя квадратическая ошибка. Обоснована актуальная задача выбора эффективной концепции помехоустойчивого кодирования в телекоммуникационной составляющей перспективных тренажерных комплексов. Описаны пути решения важной задачи повышения достоверности актуальных цифровых данных в сетевых тренажерных комплексах на основе применения средств помехоустойчивого кодирования. Представлена модель перестановочного декодера недвоичного избыточного кода на базе лексикографической когнитивной карты. Данная модель декодера избыточного кода использует методы когнитивной обработки данных при реализации процедуры перестановочного декодирования для эффективной защиты команд дистанционного управления от влияния деструктивных факторов на процесс управления

Isotopic Scaling in Nuclear Reactions

A three parameter scaling relationship between isotopic distributions for elements with Z$\leq 8$ has been observed that allows a simple description of the dependence of such distributions on the overall isospin of the system. This scaling law (termed iso-scaling) applies for a variety of reaction mechanisms that are dominated by phase space, including evaporation, multifragmentation and deeply inelastic scattering. The origins of this scaling behavior for the various reaction mechanisms are explained. For multifragmentation processes, the systematics is influenced by the density dependence of the asymmetry term of the equation of state.Comment: 10 Pages, 2 Figure

Quivers, YBE and 3-manifolds

We study 4d superconformal indices for a large class of N=1 superconformal quiver gauge theories realized combinatorially as a bipartite graph or a set of "zig-zag paths" on a two-dimensional torus T^2. An exchange of loops, which we call a "double Yang-Baxter move", gives the Seiberg duality of the gauge theory, and the invariance of the index under the duality is translated into the Yang-Baxter-type equation of a spin system defined on a "Z-invariant" lattice on T^2. When we compactify the gauge theory to 3d, Higgs the theory and then compactify further to 2d, the superconformal index reduces to an integral of quantum/classical dilogarithm functions. The saddle point of this integral unexpectedly reproduces the hyperbolic volume of a hyperbolic 3-manifold. The 3-manifold is obtained by gluing hyperbolic ideal polyhedra in H^3, each of which could be thought of as a 3d lift of the faces of the 2d bipartite graph.The same quantity is also related with the thermodynamic limit of the BPS partition function, or equivalently the genus 0 topological string partition function, on a toric Calabi-Yau manifold dual to quiver gauge theories. We also comment on brane realization of our theories. This paper is a companion to another paper summarizing the results.Comment: 61 pages, 16 figures; v2: typos correcte

Upper atmospheres and ionospheres of planets and satellites

The upper atmospheres of the planets and their satellites are more directly exposed to sunlight and solar wind particles than the surface or the deeper atmospheric layers. At the altitudes where the associated energy is deposited, the atmospheres may become ionized and are referred to as ionospheres. The details of the photon and particle interactions with the upper atmosphere depend strongly on whether the object has anintrinsic magnetic field that may channel the precipitating particles into the atmosphere or drive the atmospheric gas out to space. Important implications of these interactions include atmospheric loss over diverse timescales, photochemistry and the formation of aerosols, which affect the evolution, composition and remote sensing of the planets (satellites). The upper atmosphere connects the planet (satellite) bulk composition to the near-planet (-satellite) environment. Understanding the relevant physics and chemistry provides insight to the past and future conditions of these objects, which is critical for understanding their evolution. This chapter introduces the basic concepts of upper atmospheres and ionospheres in our solar system, and discusses aspects of their neutral and ion composition, wind dynamics and energy budget. This knowledge is key to putting in context the observations of upper atmospheres and haze on exoplanets, and to devise a theory that explains exoplanet demographics.Comment: Invited Revie

Increased dynamics in the 40-57 Ω-loop of the G41S variant of human cytochrome c promote its pro-apoptotic conformation

Thrombocytopenia 4 is an inherited autosomal dominant thrombocytopenia, which occurs due to mutations in the human gene for cytochrome c that results in enhanced mitochondrial apoptotic activity. The Gly41Ser mutation was the first to be reported. Here we report stopped-flow kinetic studies of azide binding to human ferricytochrome c and its Gly41Ser variant, together with backbone amide H/D exchange and 15N-relaxation dynamics using NMR spectroscopy, to show that alternative conformations are kinetically and thermodynamically more readily accessible for the Gly41Ser variant than for the wild-type protein. Our work reveals a direct conformational link between the 40-57 Ω-loop in which residue 41 resides and the dynamical properties of the axial ligand to the heme iron, Met80, such that the replacement of glycine by serine promotes the dissociation of the Met80 ligand, thereby increasing the population of a peroxidase active state, which is a key non-native conformational state in apoptosis

Search for New Physics in e mu X Data at D0 Using Sleuth: A Quasi-Model-Independent Search Strategy for New Physics

We present a quasi-model-independent search for the physics responsible for electroweak symmetry breaking. We define final states to be studied, and construct a rule that identifies a set of relevant variables for any particular final state. A new algorithm ("Sleuth") searches for regions of excess in those variables and quantifies the significance of any detected excess. After demonstrating the sensitivity of the method, we apply it to the semi-inclusive channel e mu X collected in 108 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV at the D0 experiment during 1992-1996 at the Fermilab Tevatron. We find no evidence of new high p_T physics in this sample.Comment: 23 pages, 12 figures. Submitted to Physical Review

tau-->eta(eta')2pi nu, 3pi nu and WZW anomaly

The effects of the anomalous contact terms are taken into account in tau to eta(eta')2pi nu decay. tau to 3pi nu is computed. Theoretical result agrees with data. It is the first time the anomalous vertex eta aa is tested. An a_{1} resonance is predicted in the final state. The decay rate of tau to eta'3pi nu is predicted.Comment: 15 pages, one latex file for the paper and one p-script file for the figur