[Metabolome profiling in the study of aging processes]. / Metabolomnoe profilirovanie v izuchenii protsessov stareniia.

Aging of a living organism is closely related to systemic metabolic changes. But due to the multilevel and network nature of metabolic pathways, it is difficult to understand these connections. Today, this problem is solved using one of the main approaches of metabolomics - untargeted metabolome profiling. The purpose of this publication is to systematize the results of metabolomic studies based on such profiling, both in animal models and in humans.

[Ten years of the Russian metabolomics: history of development and achievements]. / Desiat' let rossiiskoi metabolomike: istoriia razvitiia i osnovnye rezul'taty.

Metabolomics is one of the omics sciences, the technologies of which are widely used today in many life sciences. Its application influenced the discovery of new biomarkers of diseases, the description of biochemical processes occurring in many organisms, laid the basis for a new generation of clinical laboratory diagnostics. The purpose of this review is to show how metabolomics is represented in the studies of Russian scientists, to demonstrate the main directions and achievements of the Russian science in this field. The review also highlights the history of metabolomics, existing problems and the place of Russian metabolomics in their solution.

[Blood metabolome analysis for creating a digital image of a healthy person]. / Metabolomnyi analiz krovi dlia sozdaniia tsifrovogo obraza zdorovogo cheloveka.

In the frame of the work, data on the implementation of metabolomics tests in medicine have been systematized. Based on the obtained data, a set of protocols was proposed, the sequential realization of which makes it possible to conduct a blood metabolome analysis for medical purposes. Using this analysis and the number of blood samples from healthy volunteers, a prototype of a healthy person's metabolomic image has been developed; it allows visually and digitally to assess the compliance of the human blood metabolome with the norm. At the same time, 99% of the metabolic processes reflected in the blood plasma are estimated. If abnormalities are detected, the metabolomic image allows to get the value of these deviations of metabolic processes in digital terms.

Observation of chiral surface excitons in a topological insulator Bi2Se3.

The protected electron states at the boundaries or on the surfaces of topological insulators (TIs) have been the subject of intense theoretical and experimental investigations. Such states are enforced by very strong spin-orbit interaction in solids composed of heavy elements. Here, we study the composite particles-chiral excitons-formed by the Coulomb attraction between electrons and holes residing on the surface of an archetypical 3D TI, [Formula: see text] Photoluminescence (PL) emission arising due to recombination of excitons in conventional semiconductors is usually unpolarized because of scattering by phonons and other degrees of freedom during exciton thermalization. On the contrary, we observe almost perfectly polarization-preserving PL emission from chiral excitons. We demonstrate that the chiral excitons can be optically oriented with circularly polarized light in a broad range of excitation energies, even when the latter deviate from the (apparent) optical band gap by hundreds of millielectronvolts, and that the orientation remains preserved even at room temperature. Based on the dependences of the PL spectra on the energy and polarization of incident photons, we propose that chiral excitons are made from massive holes and massless (Dirac) electrons, both with chiral spin textures enforced by strong spin-orbit coupling. A theoretical model based on this proposal describes quantitatively the experimental observations. The optical orientation of composite particles, the chiral excitons, emerges as a general result of strong spin-orbit coupling in a 2D electron system. Our findings can potentially expand applications of TIs in photonics and optoelectronics.

[Pharmacometabonomics - the novel way to personalized drug therapy]. / Farmakometabonomika ­ novyi podkhod k personalizatsii lekarstvennoi terapii.

The review is devoted to pharmacometabonomics - a new branch of science focused on personalization of drug therapy through the comprehensive analysis of metabolites of patient's biological fluids. It considers the history of pharmacometabonomic, positioning to other "-omic" sciences, and system approach, realized by this science, in determination of individual therapeutic dose of the drugs and also a technical implementation of pharmacometabonomic based on direct mass spectrometry of blood plasma metabolites. Special attention is paid to a comparative analysis of pharmacometabonomics and other main approaches to personalized therapy in the clinic, such as pharmacogenetics and therapeutic drug monitoring. Finally, prospects of pharmacometabonomics applications in clinical practice were also discussed.

Chiral Spin Mode on the Surface of a Topological Insulator.

Using polarization-resolved resonant Raman spectroscopy, we explore collective spin excitations of the chiral surface states in a three dimensional topological insulator, Bi_{2}Se_{3}. We observe a sharp peak at 150 meV in the pseudovector A_{2} symmetry channel of the Raman spectra. By comparing the data with calculations, we identify this peak as the transverse collective spin mode of surface Dirac fermions. This mode, unlike a Dirac plasmon or a surface plasmon in the charge sector of excitations, is analogous to a spin wave in a partially polarized Fermi liquid, with spin-orbit coupling playing the role of an effective magnetic field.

[Mass spectrometry analysis of blood plasma lipidome as method of disease diagnostics, evuation of effectiveness and optimization of drug therapy].

A new method for the analysis of blood lipid based on direct mass spectrometry of lipophilic low molecular weight fraction of blood plasma has been considered. Such technique allows quantification of hundreds of various types of lipids and this changes existing concepts on diagnostics of lipid disorders and related diseases. The versatility and quickness of the method significantly simplify its wide use. This method is applicable for diagnostics of atherosclerosis, diabetes, cancer and other diseases. Detalization of plasma lipid composition at the molecular level by means of mass spectrometry allows to assess the effectiveness of therapy and to optimize the drug treatment of cardiovascular diseases by phospholipid preparations.

Pressure tuning the Fermi level through the Dirac point of giant Rashba semiconductor BiTeI.

We report measurements of Shubnikov-de Haas oscillations in the giant Rashba semiconductor BiTeI under applied pressures up to ∼2 GPa. We observe one high frequency oscillation at all pressures and one low frequency oscillation that emerges between ∼0.3-0.7 GPa indicating the appearance of a second small Fermi surface. BiTeI has a conduction band bottom that is split into two sub-bands due to the strong Rashba coupling, resulting in a 'Dirac point'. Our results suggest that the chemical potential starts below the Dirac point in the conduction band at ambient pressure and moves upward, crossing it as pressure is increased. The presence of the chemical potential above this Dirac point results in two Fermi surfaces. We present a simple model that captures this effect and can be used to understand the pressure dependence of our sample parameters. These extracted parameters are in quantitative agreement with first-principles calculations and other experiments. The parameters extracted via our model support the notion that pressure brings the system closer to the predicted topological quantum phase transition.

[Mass spectrometry of blood low-molecular fraction as a method for unification of therapeutic drug monitoring].

The article describes a new therapeutic drug monitoring (TDM) method based on direct infusion of low-molecular fraction of blood into electrospray ionization source of mass spectrometer. This technique allows performing TDM of almost all drugs used in clinic. In article, the universality and high-throughput of the method, that significantly simplifies its wide application, have been shown. Moreover, the possibility of method application in most cases of drug therapy has been argued as a tool of control of drug doses, rationality of drug therapy, and the quality of the drugs themselves. In conclusion, the prospects for application of the method as primary means of improving the quality and personalization of drug therapy have been discussed.

Transport and elastic scattering times as probes of the nature of impurity scattering in single-layer and bilayer graphene.

Transport and elastic scattering times, tau{tr} and tau{e}, are experimentally determined from the carrier density dependence of the magnetoconductance of monolayer and bilayer graphene. Both times and their dependences on carrier density are found to be very different in the monolayer and the bilayer. However, their ratio tau{tr}/tau{e} is found to be close to 1.8 in the two systems and nearly independent of the carrier density. These measurements give insight on the nature (neutral or charged) and range of the scatterers. Comparison with theoretical predictions suggests that the main scattering mechanism in our samples is due to strong (resonant) scatterers of a range shorter than the Fermi wavelength, likely candidates being vacancies, voids, adatoms or short-range ripples.

Nonanalytic spin susceptibility of a Fermi liquid: the case of Fe-based pnictides.

We propose an explanation of the peculiar linear temperature dependence of the uniform spin susceptibility chi(T) in ferropnictides. We argue that the linear in T term appears to be due to the nonanalytic temperature dependence of chi(T) in a two-dimensional Fermi liquid. We show that the prefactor of the T term is expressed via the square of the spin-density-wave (SDW) amplitude connecting nested hole and electron pockets. Because of an incipient SDW instability, this amplitude is large, which, along with a small value of the Fermi energy, makes the T dependence of chi(T) strong. We demonstrate that this mechanism is in quantitative agreement with the experiment.

Anomalous c-axis transport in layered metals.

Transport in metals with a strongly anisotropic single-particle spectrum is studied. Coherent band transport in all directions, described by the standard Boltzmann equation, is shown to withstand both elastic and inelastic scattering as long as EFtau >> 1. A model of phonon-assisted tunneling via resonant states located in between the layers is suggested to explain a nonmonotonic temperature dependence of the c-axis resistivity observed in experiments.

Quantum correction to conductivity close to a ferromagnetic quantum critical point in two dimensions.

We study the temperature dependence of the conductivity due to quantum interference processes for a two-dimensional disordered itinerant electron system close to a ferromagnetic quantum critical point. Near the quantum critical point, the crossover between diffusive and ballistic regimes of quantum interference effects occurs at a temperature T*=1/taugamma(E(F)tau)2, where gamma is the parameter associated with the Landau damping of the spin fluctuations, tau is the impurity scattering time, and E(F) is the Fermi energy. For a generic choice of parameters, T* is smaller than the nominal crossover scale 1/tau. In the ballistic quantum critical regime, the conductivity behaves as T1/3.

[Structural and functional characteristics of insulin and mechanism of its effect]. / Strukturno-funktsional'nye osobennosti insulina i mekhanizma ego deistviia.

On the basis of analysis of own and literature data on insulin-receptor interaction two centers responsible for receptor binding were identified on 3D-structure of insulin with receptor. Two extracellular domains of insulin receptor interact with these centers on insulin molecule. The comparative analysis of primary structures of the protein disulfide isomerase thioredoxine domains and C-terminal domain of the receptor suggests existence of the thioredoxine domain in the insulin receptor. In this connection the role of the thiol disulfide an exchange reaction is discussed in terms of insulin interaction with receptor followed by subsequent conformational changes in the receptor molecule and activation of the intercellular tyrosine kinase domain. It is supposed, that besides known mechanism of receptor mediated insulin signal transduction and tyrosine kinase activation, there is other mechanism of insulin intracellular signal transduction realised via cytosolic insulin-binding proteins. Major components of intercellular insulin signal transduction include: protein disulfide isomerase and insulin degrading enzyme. The importance of change of the intracellular insulin degradation rate for insulin signal transduction is discussed.

[Hypoglycemic effect of an extract from Aronia melanocarpa leaves]. / Issledovanie gipoglikemicheskogo deistviia ékstrakta iz list'ev Aronia melanocarpa.

The action of extract from Aronia melanocarpa leaves to blood glucose level was investigated. It was shown that incorporated into drinking water and administrated intraperitoneally, the extract significantly reduce the blood glucose level of streptozotocin (STZ)-diabetic and normal rats.

[Stimulation of glucose uptake in PC 12 and L 929 cells by extracts from Aronia melanocarpa leaves]. / Stimuliatsiia pogloshcheniia gliukozy kletkami PC 12 i L 929 ékstraktom iz list'iev Aronia melanocarpa.

The ability of extract from Aronia melanocarpa leaves to increase glucose uptake was investigated. It was shown, that the extract stimulated glucose uptake by cells PC12 and L 929 at the concentration close to native insulin.

New peptidomimetics of insulin.

New peptidomimetics that have been obtained in the course of our experimental work show distinct insulin-like activity both in vitro and in vivo. The first peptidomimetic (PM 1) is essentially a decapeptide in which sites of A (20-21) and B (19-26) chains of insulin are linked by the peptides bond (Cys-Gly-Glu-Arg-Gly-Phe-Phe-Tyr-Cys-Asn). The second peptidomimetic (PM 2) has similar set of amino acid residues, except that two aromatic amino acids corresponding to the residues of B chain of insulin (B24 and B26) have been replaced with their D optical isomers (Cys-Gly-Glu-Arg-Gly-DPhe-Phe-DTyr-Cys-Asn). The third peptidomimetic (PM 3) has been obtained through acylation of N-terminal of PM 1 by the use of palmitic acid. The peptidomimetic incorporating D aromatic amino acids (PM 2) was demonstrated to exhibit more pronounced hypoglycemic impact, while the acylation of decapeptide tends to prolong the effective time of peptidomimetic influence in vivo.

Magnetization in the ultraquantum limit.

The magnetization below and far above the quantum limit for small Fermi surface orbits has been measured in the metallic compound LaRhIn(5). The magnetization due to a pocket of Fermi surface that comprises less than 1 part in 10(4) of the total Brillouin zone volume, and for which the quantum limit is approximately 7 T, leads to the appearance of an overall sample magnetic moment at fields between 7 and 32 T. This moment arises from diamagnetic currents produced by electrons in the ultraquantum limit. A model calculation of the origin and magnitude of the effect is in excellent agreement with the measured field dependence of the induced magnetization.

[The prolonged action of an insulin peptidomimetic by the substitution of L-amino acid for its D-isomer]. / Uvelichenie vremeni deistviia peptidomimetika insulina putem zameny L-aminokislotnykh ostatkov ikh D-opticheskimi izomerami.

The synthesized decapeptide represents functionally important site for binding to the insulin receptor. Amino acid residues at position, 1-8 correlate with B-chain of insulin at position B19-B26, and the residues at position 9-10 correlate with A-chain at position A20-A21. The new peptide was obtained by substitution of two aromatic L-amino acid residues (B24 and B26) for their D-optical isomers. These peptides were tested with cell cultures L929 and PC12 (glucose uptake). Increased concentration of peptides correlated with stimulation of glucose uptake by cells. Studies carried out on animals with streptosotocine-caused diabetes showed that, synthesized peptides were able to decrease glucose level in blood, but decapeptide with D amino acid showed a more pronounced effect compared to the decapeptide with L amino acid.

[Specific interaction of liposomes coated by insulin synthetic fragments with PC 12 cells]. / Issledovanie sposobnosti liposom, modifitsirovannykh sinteticheskimi fragmentami insulina, spetsificheski vzaimodeistvovat' s kletkami PC 12.

The synthesized peptides represent the functionally important site for binding to insulin receptor. Amino acids of peptide I correlate with B-chain of insulin at the position B19-B26 and A-chain at the position A20-A21. Amino acids of peptide II correlate with B-chain of insulin at position B23-B26 and A-chain at the position A20-A21. It was shown, that the these peptides increased liposomal binding followed by receptor-mediated endocytosis by cells PC12.