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Mitochondrial dysfunction and ubiquitin-proteasome system (UPS) failure contribute significantly to the development of Parkinson's disease (PD). The proteasome subunit Rpn13 located on the regulatory (19S) subparticle play an important role in the delivery of proteins, subjected to degradation, to the proteolytic (20S) part of proteasome. We have previously found several brain mitochondrial proteins specifically bound to Rpn13 (Buneeva et al. (2020) Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry, 14, 297-305). In this study we have investigated the effect of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and the neuroprotector isatin on the mitochondrial subproteome of Rpn13-binding proteins of the mouse brain. Administration of MPTP (30 mg/kg) to animals caused movement disorders typical of PD, while pretreatment with isatin (100 mg/kg, 30 min before MPTP) reduced their severity. At the same time, the injection of MPTP, isatin, or their combination (isatin + MPTP) had a significant impact on the total number and the composition of Rpn13-binding proteins. The injection of MPTP decreased the total number of Rpn13-binding proteins in comparison with control, and the injection of isatin prior to MPTP or without MPTP caused an essential increase in the number of Rpn13-binding proteins, mainly of the functional group of proteins participating in the protein metabolism regulation, gene expression, and differentiation. Selected biosensor validation confirmed the interaction of Rpn13 subunit of proteasome with some proteins (glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase, histones H2A and H2B) revealed while proteomic profiling. The results obtained testify that under the conditions of experimental MPTP-induced parkinsonism the neuroprotective effect of isatin may be aimed at the interaction of mitochondria with the components of UPS.Mitokhondrial'naia disfunktsiia i sboĭ v rabote ubikvitin-proteasomnoĭ sistemy (UPS) vnosiat sushchestvennyĭ vklad v razvitie bolezni Parkinsona (BP). Sub"edinitsa proteasomy Rpn13, raspolozhennaia na reguliatornoĭ subchastitse (19S), igraet vazhnuiu rol' v dostavke belkov, podlezhashchikh degradatsii, v proteoliticheskuiu chast' (20S) proteasomy. Ranee nami obnaruzhen riad mitokhondrial'nykh belkov mozga, spetsificheski sviazyvaiushchikhsia s Rpn13 (Buneeva i dr., Biomeditsinskaia khimiia, 2020, 66(2), 138-144). V dannoĭ rabote izucheno vliianie neĭrotoksina 1-metil-4-fenil-1,2,3,6-tetragidropiridina (MFTP) i neĭroprotektora izatina na mitokhondrial'nyĭ subproteom Rpn13-sviazyvaiushchikh belkov mozga myshi. Vvedenie MFTP (30 mg/kg) zhivotnym vyzyvalo razvitie dvigatel'nykh narusheniĭ, svoĭstvennykh dlia BP, a predvaritel'noe vvedenie izatina (100 mg/kg) oslablialo ikh vyrazhennost'. Pri étom vvedenie MFTP, izatina ili ikh kombinatsii (izatin + MFTP) privodilo k izmeneniiu obshchego chisla i sostava Rpn13-sviazyvaiushchikh belkov. Vvedenie MFTP snizhalo obshchee chislo Rpn13-sviazyvaiushchikh belkov po sravneniiu s kontrolem, a vvedenie izatina pered vvedeniem MFTP ili bez MFTP privodilo k sushchestvennomu uvelicheniiu chisla Rpn13-sviazyvaiushchikh belkov preimushchestvenno iz funktsional'noĭ gruppy belkov, uchastvuiushchikh v reguliatsii metabolizma belkov, a takzhe ékspressii genov, kletochnogo deleniia i differentsirovki. Vyborochnaia biosensornaia validatsiia podtverdila vzaimodeĭstvie riada belkov (glitseral'degid-3-fosfatdegidrogenaza, piruvatkinaza, gistony N2A i N2V), vyiavlennykh v khode proteomnogo profilirovaniia, s sub"edinitseĭ proteasomy Rpn13. Poluchennye rezul'taty svidetel'stvuiut o tom, chto v usloviiakh éksperimental'nogo MFTP-indutsirovannogo parkinsonizma neĭroprotektornoe deĭstvie izatina mozhet byt' napravleno na vzaimodeĭstvie mitokhondriĭ s komponentami UPS.

В статье рассмотрены методологические основы организации и проведения исследований постагрогенной трансформации экосистем Европейской части России. Комплексные исследования проведены в среднетаежной подзоне Карелии. Установлено, что изменение различных компонентов природной среды происходит в процессе ее восстановления после прекращения использования в агросфере. Сделан вывод о возможности использования полученных данных в мониторинге природной среды. Полученные данные могут быть основой при организации работ в данной области.

В статье рассмотрено распространение месторождения талько-хлоритов, приведен состав, свойства, использование горной породы. Отдельно рассмотрены вопросы изменения природной среды в условиях разработки тальккарбонатных месторождений. Приводятся данные модельных полевых и лабораторных экспериментов о влиянии талькохлоритов на свойства почв. Сделан вывод о возможном их использовании при мелиорации почв. Полученные данные можно использовать при разработке агроэкологических основ повышения плодородия почв при использовании отходов тальккарбонатных пород.

We have isolated fractions of 26S and 20S proteasomes were from the rabbit liver and the brain. According to mass spectrometric (MS) analysis, the 26S proteasome fractions from these organs contained catalytic and regulatory subunits characteristic of the proteasome core and regulatory subunits. The 20S fractions of brain and liver proteasomes contained only catalytic proteasome subunits. In addition to proteasome subunits, the isolated fractions contained components of the ubiquitin-proteasome system, ubiquitinated proteins, enzymes that play an important role in metabolic processes, cytoskeletal components, signaling, regulatory, and protective proteins, as well as proteins regulating gene expression, cell division, and differentiation. The abundance of a number of proteasome-associated proteins was comparable or exceeded the abundance of intrinsic proteasome components. About a third of the proteins common to all studied fractions (26S and 20S of brain and liver proteasomes) belong to the group of multifunctional proteins. Selective biosensor validation confirmed the affinity binding of proteins (aldolase, phosphoglycerate kinase) identified during MS analysis to the brain 20S proteasome. Comparison of the subproteomes of the 26S and 20S brain proteasomes showed that removal of components of the regulatory (19S) subparticles caused almost two-fold increase in the total number of individual proteins associated with the core part of the proteasome (20S). In the liver, the number of proteins associated with the core part of the proteasome remained basically unchanged after the removal of the components of the regulatory (19S) subparticles. This indicates that in the brain and, possibly, in other organs, proteins of the regulatory (19S) subunit play an important role in the formation of the proteasome interactome.Iz pecheni i mozga krolika vydeleny fraktsii 26S i 20S proteasom. Po dannym mass-spektrometricheskogo (MS) analiza, fraktsii 26S proteasom iz étikh organov soderzhali kataliticheskie i reguliatornye sub"edinitsy, kharakternye dlia korovoĭ chasti proteasom i dlia reguliatornykh subchastits. Fraktsii 20S proteasom mozga i pecheni soderzhali tol'ko kataliticheskie sub"edinitsy proteasom. Pomimo sub"edinits proteasom, v poluchennykh fraktsiiakh obnaruzheny komponenty ubikvitin-proteasomnoĭ sistemy, ubikvitinirovannye belki, fermenty, igraiushchie vazhnuiu rol' v metabolicheskikh protsessakh, komponenty tsitoskeleta, signal'nye, reguliatornye i zashchitnye belki, a takzhe belki reguliatsii ékspressii genov, kletochnogo deleniia i differentsirovki. Predstavlennost' riada assotsiirovannykh s proteasomami belkov byla sopostavima ili prevyshala predstavlennost' sobstvennykh komponentov proteasom. Okolo treti belkov, obshchikh dlia vsekh issledovannykh fraktsiĭ (26S i 20S proteasom mozga i pecheni), otnosiatsia k gruppe mul'tifunktsional'nykh belkov. Vyborochnaia biosensornaia validatsiia podtverdila affinnoe sviazyvanie identifitsirovannykh v khode MS analiza belkov (al'dolaza, fosfoglitseratkinaza) s 20S proteasomoĭ mozga. Sopostavlenie subproteomov 26S i 20S proteasom mozga pokazalo, chto pri udalenii komponentov reguliatornykh (19S) subchastits kolichestvo individual'nykh belkov, assotsiirovannykh s korovoĭ chast'iu proteasomy (20S), prakticheski udvaivalos'. V pecheni kolichestvo belkov, assotsiirovannykh s korovoĭ chast'iu proteasomy, posle udaleniia komponentov reguliatornykh subchastits prakticheski ne izmenialos'. Éto svidetel'stvuet o tom, chto v mozge i, vozmozhno, v drugikh organakh belki reguliatornoĭ (19S) subchastitsy igraiut vazhnuiu rol' v formirovanii proteasomnogo interaktoma.

In this article, an original method is proposed for address and covalent immobilization of anti-E. coli antibodies on a screen-printed electrode (SPE). The method is based on a copper-catalyzed “click” reaction between a polyvinylbenzylazide (PVBA) film electrochemically deposited on the electrode surface and acetylene fragments of propargyl-N-hydroxysuccinimide ester. The products of electrochemical oxidation of copper particles incorporated in the polymer film on the electrode were first used for catalysis of the click reaction. This approach allowed us to reduce the immobilization time from a few hours for conventional methods to just 30 min, and to prevent denaturation of the immunoreceptor. The modified electrodes were characterized by scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS), and cyclic voltammetry (CV). Based on the results obtained, a label-free impedimetric immunosensor for E. coli detection was developed. The detection limit of the immunosensor was estimated as 6.3 CFU/ml, with a linear range of 103–106 CFU/ml. The immunosensor demonstrated good stability during 30 days of storage in phosphate buffer solution (PBS, pH 7) and selectivity toward excess Staphylococcus aureus bacteria.

It becomes increasingly clear that ubiquitination of cellular proteins is not an indispensable prerequisite of their degradation in proteasomes. There are a number of proteins to be eliminated which are not pre-ubiquitinated for their recognition by regulatory subcomplex of 26S proteasome, but which directly interact with the 20S proteasome core particle (20S proteasome). The obligatory precondition for such interaction consists in existence of disordered (hydrophobic) fragments in the target protein. In this study we have investigated the interaction of a number of multifunctional (moonlighting) proteins (glyceraldehyde-3-phosphate dehydrogenase (GAPDH), aldolase, pyruvate kinase) and neurodegeneration-related proteins (a-synuclein, myelin basic protein) with 20S proteasome immobilized on the SPR-biosensor chip and stabilized by means of a bifunctional agent dimethyl pimelimidate (in order to prevent possible dissociation of this subcomplex). Only two of all investigated proteins (aldolase and pyruvate kinase) interacted with the immobilized 20S proteasome (Kd of 8.17´10-7 M and 5.56´10-7 M, respectively). In addition to earlier detected GAPDH ubiquitination, mass spectrometric analysis of the studied proteins revealed the presence of the ubiquitin signature (Lys-e-Gly-Gly) only in aldolase. Oxidation of aldolase and pyruvate kinase, which promotes elimination of proteins via their direct interaction with 20S proteasome, caused a 2-3-fold decrease in their Kd values as comparison with this parameter obtained for the intact proteins. The results of this study provide further evidence for direct interaction of both ubiquitinated proteins (aldolase), and non-ubiquitinated proteins (pyruvate kinase) with the 20S proteasome core particle (20S proteasome). The effectiveness of this interaction is basically equal for the ubiquitinated proteins and non-ubiquitinated proteins.Stanovitsia vse bolee ochevidnym, chto ubikvitinirovanie vnutrikletochnykh belkov ne iavliaetsia obiazatel'nym étapom, neobkhodimym dlia ikh degradatsii v proteasomakh. Izvestno nemalo podlezhashchikh éliminatsii belkov, kotorye ne podvergaiutsia predvaritel'nomu ubikvitinirovaniiu dlia uznavaniia reguliatornymi subchastitsami 26S proteasomy, a postupaiut neposredstvenno v ee korovuiu (proteoliticheskuiu) chast' – 20S proteasomu. Neobkhodimym usloviem dlia étogo iavliaetsia nalichie v belke nestrukturirovannykh uchastkov. V dannoĭ rabote issledovali sviazyvanie riada polifunktsional'nykh belkov (glitseral'degid-3-fosfatdegidrogenaza (GAFD), al'dolaza, piruvatkinaza), a takzhe belkov, uchastvuiushchikh v protsessakh neĭrodegeneratsii (a-sinuklein, osnovnoĭ belok mielina), s immobilizovannoĭ na chipe SPR-biosensora Biacore 20S proteasomoĭ. Dlia predotvrashcheniia vozmozhnoĭ dissotsiatsii 20S proteasomu v khode immobilizatsii stabilizirovali pri pomoshchi bifunktsional'nogo sshivaiushchego reagenta – dimetilpimelimidata. Iz vsekh issledovannykh belkov tol'ko al'dolaza i piruvatkinaza vzaimodeĭstvovali s 20S proteasomoĭ (Kd sootvetstvenno 8,17´10-7 M i 5,56´10-7 M). V dopolnenie k ranee obnaruzhennomu ubikvitinirovaniiu GAFD, mass-spektrometricheskiĭ analiz preparatov étikh belkov vyiavil nalichie tak nazyvaemoĭ ubikvitinovoĭ signatury Lys-e-Gly-Gly tol'ko v preparate al'dolazy. Okislenie piruvatkinazy i al'dolazy, sposobstvuiushchee éliminatsii belkov v rezul'tate ikh neposredstvennogo vzaimodeĭstviia s 20S proteasomoĭ, privodilo k snizheniiu Kd v 2-3 raza po sravneniiu s intaktnymi belkami. Poluchennye rezul'taty svidetel'stvuiut v pol'zu togo, chto s 20S proteasomoĭ odinakovo éffektivno sviazyvaiutsia kak ubikvitinirovannye (al'dolaza), tak i neubikvitinirovannye (piruvatkinaza) belki.

In this article, we have shown the results of E. coli bacteria determination in water using the enzyme free electrochemical immunosensor with covalent via click chemistry immobilized receptor layer in comparison with dropwise immobilized antibodies. Covalent immobilization was realized by creating precursors on the surface of the working electrode with the reaction of azide-alkyne copper-catalysed cycloaddition approach. The detection limit of the immunosensor with covalent and dropwise immobilization of antibodies was estimated as 6.6 CFU/ml and 11.2 CFU/ml, respectively, a linear range was 103-106 CFU/ml. Moreover, the sensor with "click"immobilized antibodies showed good stability for 30 days when stored in a phosphate buffer, while the sensor with dropwise immobilized receptor layer was stable for 3 days. © Published under licence by IOP Publishing Ltd. This work was supported by the Presidential Grants Fund of the Russian Federation (grant MK-567.2020.3).

A convenient transition-metal-free approach, based on nucleophilic substitution of hydrogen (SNH), for consecutive regioselective C–H functionalization of 1,3,7-triazapyrene scaffolds with carboranyllithium and phenyllithium is reported. The theoretical calculations disclosed highlight key features in the regioselectivity and mechanism of the investigated SNH transformations. The novel 1,3,7-triazapyrene-based ortho-carboranes obtained have large potential in the field of molecular electronics as organic luminophores, which are characterized by the aggregation-induced emission and dual-emission effects.

Background Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is one of the major targets of NO in cells, especially in neurodegenerative diseases. S-Nitrosylation of GAPDH is accompanied by its translocation into the nucleus with subsequent apoptosis. The product of GAPDH modification by NO is considered to be S-nitrosylated GAPDH (GAPDH-SNO). However, this has not been confirmed by direct methods. Methods Products of GAPDH modification in the presence of the NO donor diethylamine NONOate were analyzed by MALDI- and ESI- mass spectrometry methods. Results The adduct between GAPDH and dimedone was detected by MALDI-MS analysis after incubation of S-nitrosylated GAPDH with dimedone, which points to the formation of cysteine-sulfenic acid (GAPDH-SOH) in the protein. Analysis of the protein hydrolysate revealed the incorporation of dimedone into the catalytic residue Cys150. An additional peak that corresponded to GAPDH-SNO was detected by ESI-MS analysis in GAPDH after the incubation with the NO donor. The content of GAPDH-SNO and GAPDH-SOH in the modified GAPDH was evaluated by different approaches and constituted 2.3 and 0.7 mol per mol GAPDH, respectively. A small fraction of GAPDH was irreversibly inactivated after NO treatment, suggesting that a minor part of the products includes cysteine-sulfinic or cysteine-sulfonic acids. Conclusions The main products of GAPDH modification by NO are GAPDH-SNO and GAPDH-SOH that is presumably formed due to the hydrolysis of GAPDH-SNO. General significance The obtained results are important for understanding the molecular mechanism of redox regulation of cell functions and the role of GAPDH in the development of neurodegenerative disorders.

Soils of low-mountain landscapes in the northwest of Karelia have been studied. The soil cover of the studied area is mainly represented by Al–Fe-humus soils (Podzols); thin soils (Leptosols) are widespread. Characteristic morphological features of all the studied soils are relatively shallow profiles, high stone content, and underlying by hard bedrock with fine earth material in crevices between large boulders. The studied soils have the high carbon and low nitrogen content, which points to unfavorable conditions of organic matter transformation. The content of most macro- and microelements is not high, which is typical for soils of the region; the content of copper and zinc exceeds the regional background two–three times. Regularities of the vertical zonality in the properties of soils of mountain ecosystems manifest themselves in decreasing thickness of the soil profile at higher altitude above sea level in parallel to decreasing thickness of the layer of loose rocks, while the stone content increases. In soils of the forest-tundra zone, the organomineral horizon with the high organic matter content is formed immediately under the forest litter. The litter horizon is the soils of this zone is characterized by increased concentrations of calcium, magnesium, phosphorus, and zinc.

Mitochondria play an important role in molecular mechanisms of neuroplasticity, adaptive changes of the brain that occur in the structure and function of its cells in response to altered physiological conditions or development of pathological disorders. Mitochondria are a crucial target for actions of neurotoxins, causing symptoms of Parkinson's disease in various experimental animal models, and also neuroprotectors. Good evidence exists in the literature that mitochondrial dysfunction induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) influences functioning of the ubiquitin-proteasomal system (UPS) responsible for selective proteolytic degradation of proteins from various intracellular compartments (including mitochondria), and neuroprotective effects of certain antiparkinsonian agents (monoamine oxidase inhibitors) may be associated with their effects on UPS. The 19S proteasomal Rpn10 subunit is considered as a ubiquitin receptor responsible for delivery of ubiquitinated proteins to the proteasome proteolytic machinery. In this study, we investigated proteomic profiles of mouse brain mitochondrial Rpn10-binding proteins, brain monoamine oxidase B (MAO B) activity, and their changes induced by a single-dose administration of the neurotoxin MPTP and the neuroprotector isatin. Administration of isatin to mice prevented MPTP-induced inactivation of MAO B and influenced the profile of brain mitochondrial Rpn10-binding proteins, in which two pools of proteins were clearly recognized. The constitutive pool was insensitive to neurotoxic/neuroprotective treatments, while the variable pool was specifically influenced by MPTP and the neuroprotector isatin. Taking into consideration that the neuroprotective dose of isatin used in this study can result in brain isatin concentrations that are proapoptotic for cells in vitro, the altered repertoire of mitochondrial Rpn10-binding proteins may thus represent a part of a switch mechanism from targeted elimination of individual (damaged) proteins to more efficient ("global") elimination of damaged organelles and whole damaged cells.

Amyloid-β peptide (1-42) (Aβ1-42) is a key player in the development and progression of Alzheimer's disease (AD) and related pathologies, determined by formation of protein aggregates in the central nervous system. Aβ1-42 binding to crucial intracellular targets (and their subsequent inactivation) obviously represents one of the earliest events preceding extracellular pathogenic oligomerization/aggregation of Aβ1-42. It is reasonable to expect that dissociation of the Aβ1-42 complexes with intracellular proteins by means of inhibitors followed by subsequent degradation of Aβ1-42 would not only protect critically important proteins but also prevent intracellular accumulation of Aβ1-42. The aim of this study was to investigate the effect of the neuroprotector isatin (100 mM) on interaction of known Aβ-binding proteins, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and pyruvate kinase, with Aβ1-42 and its fragments (Aβ1-28, Aβ12-28, Aβ25-35). Aβ1-42 and its fragments (Aβ1-28, Aβ12-28, Aβ25-35) immobilized on the Biacore optical biosensor chip interacted with GAPDH and pyruvate kinase. The lowest and basically equal Kd values were determined for GAPDH and pyruvate kinase complexes with immobilized Aβ1-42 and Aβ25-35. The presence of 100 mM isatin caused a significant (more than fivefold) increase in the Kd values for GAPDH complexes with all Aβ peptides except Aβ1-28. In contrast to GAPDH isatin increased dissociation of pyruvate kinase complexes only with Aβ1-42 (causing a 30-fold increase in Kd) and to a lesser extent with Aβ12-28 and Aβ25-35 (a 10-fold increase in Kd). It should be noted that in the presence of isatin the Kd values for GAPDH and pyruvate kinase complexes with all Aβ studied were in a narrower concentration range (10-7 M - 10-6 M) than in the absence of this neuroprotector (10-8 M - 10-6 M). Data obtained suggest existence of principal possibility of (pharmacological) protection of crucial intracellular targets against both Aβ1-42, and its aggressive truncated peptides (Aβ25-35).Beta-amiloidnyĭ peptid (1-42) (Aβ1-42) iavliaetsia odnim iz “kliuchevykh igrokov”, vovlechennykh v razvitie bolezni Al'tsgeĭmera (AD) i drugikh patologicheskikh sostoianiĭ, obuslovlennykh obrazovaniem i nakopleniem belkovykh agregatov v tsentral'noĭ nervnoĭ sisteme. Ego sviazyvanie s vazhnymi vnutrikletochnymi misheniami s posleduiushcheĭ ikh inaktivatsieĭ, po-vidimomu, mozhet predstavliat' soboĭ odno iz rannikh sobytiĭ, predshestvuiushchikh formirovaniiu vnekletochnoĭ patogennoĭ oligomerizatsii/agregatsii Aβ1-42. Mozhno ozhidat', chto dissotsiatsiia kompleksov Aβ1-42 s belkami-misheniami pod deĭstviem ingibitorov kompleksoobrazovaniia i posleduiushchaia degradatsiia Aβ1-42 budet ne tol'ko zashchishchat' kriticheski vazhnye vnutrikletochnye misheni, no takzhe prepiatstvovat' nakopleniiu Aβ1-42 vnutri kletok. Tsel'iu dannoĭ raboty bylo issledovanie vliianiia neĭroprotektora izatina (100 mkM) na vzaimodeĭstvie izvestnykh Ab-sviazyvaiushchikh belkov – glitseral'degid-3-fosfatdegidrogenazy (GAFD) i piruvatkinazy – s Aβ1-42 i ego fragmentami (Aβ1-28, Aβ12-28, Aβ25-35). Immobilizovannye na chipe opticheskogo biosensora Biacore Aβ1-42 i ego fragmenty (Aβ1-28, Aβ12-28, Aβ25-35) vzaimodeĭstvovali s GAFD i piruvatkinazoĭ. Naibolee nizkie i primerno ravnye znacheniia Kd byli polucheny dlia kompleksov étikh fermentov s Aβ1-42 i Aβ25-35. V prisutstvii 100 mkM izatina sushchestvennoe uvelichenie Kd v 5 i bolee raz otmecheno dlia kompleksov GAFD so vsemi issledovannymi Ab peptidami za iskliucheniem Aβ1-28. V otlichie ot GAFD, izatin sposobstvoval dissotsiatsii kompleksov piruvatkinazy tol'ko s polnorazmernym Aβ1-42 (vyzyvaia uvelichenie Kd bolee chem v tridtsat' raz) i v men'sheĭ stepeni s Aβ25-35 i Aβ1-28 (uvelichenie Kd primerno na odin poriadok). Pri étom znacheniia Kd dlia kompleksov piruvatkinazy i GAFD so vsemi issledovannymi Ab peptidami v prisutstvii 100 mkM izatina nakhodilis' v bolee uzkom diapazone (10-7 M – 10-6 M), chem v otsutstvie étogo neĭroprotektora (10-8 M – 10-6 M). Poluchennye dannye svidetel'stvuiut o sushchestvovanii printsipial'noĭ vozmozhnosti (farmakologicheskoĭ) zashchity vazhnykh vnutrikletochnykh misheneĭ ot deĭstviia kak Aβ1-42, tak i ego agressivnykh ukorochennykh peptidov (Aβ25-35).

A series of novel D–A and D–π–A push-pull systems based on a pyrazine and quinoxaline acceptor, bearing various electron-donating triphenylamine and carbazole moieties, are compared. A significant difference in electrochemical and photophysical properties was found depending on molecular structure. The compounds have strong solvatochromic properties. Quinoxaline-containing systems exhibit delayed fluorescence (DF) in thermal vacuum deposition films. Despite the low quantum yield of fluorescence in the solid state (less than 10%), organic light-emitting diodes with sufficiently high efficiency (4.2 cd/A) have been fabricated on the basis of this push-pull systems. The best results were obtained for compounds exhibiting DF. The possible channel for increasing the efficiency of OLED can be associated with the “hot excitons” mechanism.

The amyloid-beta peptide 1-42 formed during proteolytic processing of the amyloid precursor protein (APP) plays a key role in the development or progression of Alzheimer's disease (AD) and other pathologies associated with formation of protein aggregates in the central nervous system. Recent proteomic profiling of mouse and rat brain preparations by means of beta-amyloid peptide immobilized on Affigel-10 revealed a large group of amyloid-binding proteins (n80). Many (about 25%) of these proteins were previously identified as isatin-binding proteins. The aim of this study was to validate direct interaction between beta-amyloid peptide and highly purified intact and oxidized peroxiredoxin, M-type pyruvate kinase, alpha-enolase, and the effect of isatin on this interaction. The study performed using SPR-based Biacore 3000 and Biacore X100 biosensors has shown that all the proteins form molecular complexes with immobilized beta-amyloid peptide. The Kd values for these complexes varied from 8.36х10-8 M (peroxiredoxin) to 1.97х10-6 M (alpha-enolase). Oxidative modification of investigated proteins caused opposite effects on complexes of these peptides with beta-amyloid. The endogenous neuroprotector isatin increased dissociation of complexes formed by beta-amyloid peptide with both intact proteins (peroxiredoxin, glyceraldehyde-3-phosphate dehydrogenase) and/or oxidized proteins (peroxiredoxin, pyruvate kinase) used in this study.Beta-amiloidnyĭ peptid (1-42), obrazuiushchiĭsia v rezul'tate proteoliticheskogo protsessinga transmembrannogo belka-predshestvennika amiloida, rassmatrivaetsia v kachestve "kliuchevogo igroka" v razvitii bolezni Al'tsgeĭmera (AD) i drugikh patologicheskikh sostoianiĭ, obuslovlennykh obrazovaniem i nakopleniem belkovykh agregatov v tsentral'noĭ nervnoĭ sisteme. V khode proteomnogo profilirovaniia preparatov mozga intaktnykh krys i mysheĭ, provedennogo ranee s ispol'zovaniem v kachestve affinnogo sorbenta affigelia-10 s immobilizovannym beta-amiloidnym peptidom, bylo identifitsirovano bolee 80 individual'nykh belkov, spetsificheski sviazyvaiushchikhsia s étim ligandom. Mnogie iz nikh byli obnaruzheny ranee kak belki, sviazyvaiushchiesia s éndogennym neĭroprotektorom izatinom. Tsel'iu dannogo issledovaniia byla priamaia éksperimental'naia proverka vzaimodeĭstviia vysokoochishchennykh intaktnykh i okislennykh preparatov peroksiredoksina, piruvatkinazy myshechnogo tipa i al'fa-enolazy s immobilizovannym beta-amiloidnym peptidom i vliianie izatina na étot protsess. Po dannym biosensornogo analiza s ispol'zovaniem opticheskikh SPR-biosensorov Biacore 3000 i Biacore X100 vse issledovannye belki obrazovyvali molekuliarnye kompleksy s immobilizovannym beta-amiloidnym peptidom. Znacheniia Kd étikh kompleksov var'irovali ot 8,36kh10-8 M (u peroksiredoksina) do 1,97kh10-6 M (u al'fa-enolazy). Okislitel'naia modifikatsiia issledovannykh belkov okazyvala raznonapravlennoe vliianie na prochnost' kompleksov s beta-amiloidnym peptidom, a éndogennyĭ neĭroprotektor izatin povyshal dissotsiatsiiu kompleksov beta-amiloidnogo peptida s riadom intaktnykh (peroksiredoksin, GAFD) i/ili podvergnutykh okislitel'noĭ modifikatsii (peroksiredoksin, piruvatkinaza) model'nykh belkov.

Analytic data on the status of Karelian soils at different stages of artificial reforestation (newly logged lands and 7-, 20-, and 40-year-old pine plantations) are discussed. Chemical (pH, saturation with bases, Ctotal, and Ntotal), biochemical (composition of carbohydrates), and microbiological (number of microorganisms of the most important ecological–trophic groups) soil properties have been investigated. It has been revealed that the forest litter is modified to the greatest rate after complete forest cutting. In soils formed under young 7-year-old pine plantations, organic-matter destruction becomes more intensive, and mortmass is transformed to a greater rate. The type and intensity of the input of plant debris to the soil vary with tree growth and affect the rate and tendency of organic-matter transformation. It is concluded that the studied soils are regenerated within a 40-year-long period after complete forest cutting.

Recent proteomic profiling of mouse brain preparations using the ubiquitin receptor, Rpn10 proteasome subunit, as an affinity ligand revealed a representative group of proteins bound to this sorbent (Medvedev, A. E., et al. (2017) Biochemistry (Moscow), 82, 330-339). In the present study, we investigated interaction of the Rpn10 subunit of proteasomes with some of these identified proteins: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase, and histones H2A and H2B. The study revealed: (i) quantitative affinity interaction of the proteasome subunit immobilized on a Biacore-3000 optical biosensor cuvette with both the GAPDH (K d = 2.4·10–6 M) and pyruvate kinase (K d = 2.8·10–5 M); (ii) quantitative high-affinity interaction of immobilized histones H2A and H2B with the Rpn10 subunit (Kd values of 6.5·10–8 and 3.2·10–9 M, respectively). Mass spectrometric analysis revealed the presence of the ubiquitin signature (GG) only in a highly purified preparation of GAPDH. We suggest that binding (especially high-affinity binding) of non-ubiquitinated proteins to the Rpn10 proteasome subunit can both regulate the functioning of this proteasomal ubiquitin receptor (by competing with ubiquitinated substrates) and promote activation of other pathways for proteolytic degradation of proteins destined to the proteasome.

Anodic-corrosion behavior of a number of chromium-nickel steels in a 80% H2SO4 solution was studied in order to replace platinum with less expensive electrodes in electrochemical synthesis of graphite bisulfite and corrosion parameters were determined.

Applicability of in vitro biotinylated ubiquitin for evaluation of endogenous ubiquitin conjugation and analysis of ubiquitin-associated protein-protein interactions has been investigated. Incubation of rat brain mitochondria with biotinylated ubiquitin followed by affinity chromatography on avidin-agarose, intensive washing, tryptic digestion of proteins bound to the affinity sorbent and their mass spectrometry analysis resulted in reliable identification of 50 proteins belonging to mitochondrial and extramitochondrial compartments. Since all these proteins were bound to avidin-agarose only after preincubation of the mitochondrial fraction with biotinylated ubiquitin, they could therefore be referred to as specifically bound proteins. A search for specific ubiquitination signature masses revealed several extramitochondrial and intramitochondrial ubiquitinated proteins representing about 20% of total number of proteins bound to avidin-agarose. The interactome analysis suggests that the identified non-ubiquitinated proteins obviously form tight complexes either with ubiquitinated proteins or with their partners and/or mitochondrial membrane components. Results of the present study demonstrate that the use of biotinylated ubiquitin may be considered as the method of choice for in vitro evaluation of endogenous ubiquitin-conjugating machinery in particular subcellular organelles and changes in ubiquitin/organelle associated interactomes. This may be useful for evaluation of changes in interactomes induced by protein ubiquitination under norm and various brain pathologies.

Special soil studies in the impact zone of the Kostomuksha Ore-Dressing enterprise were performed for the first time. The influence of the aerial pollution on the contents and composition of the free amino acids in the organic (forest litter) and mineral (podzolic) soil horizons was examined. An increase in the content of free amino acids in the soils near the pollution source was revealed. The content of amino acids in the organic soil horizons varied in dependence on the distance from the enterprise. The results obtained in this study may be used for the purposes of the biological diagnostics and monitoring of soils in the anthropogenically disturbed ecosystems of eastern Fennoscandia.

The glycolytic enzyme, pyruvate kinase, exhibits moderate affinity [3H]isatin binding (KD approximately 10 microM), which is inhibited by ATP (IC50 25 microM) and deprenyl (IC50 5 microM). Interaction of pyruvate kinase with isatin and its inhibition by ATP and deprenyl has also been confirmed using an independent biosensor technique and immobilized isatin analogue, aminoisatin. This effect has some specificity because the enzyme, creatine phosphokinase, does not exhibit specific isatin-binding. It is suggested that interaction of pyruvate kinase with isatin may reflect some non-glycolytic functions of this enzyme.

Protein ubiquitination is considered as an important mechanism that is responsible not only for specific labeling of proteins for their subsequent degradation but also for localization of proteins in the cell and regulation of protein-protein interactions. In the context of protein-protein interactions binding of (mono/poly)ubiquitinated molecules to proteins containing specific ubiquitin binding domains appear to play the decisive role. Although formation of the ubiquitin interactome has been demonstrated for cytosol, involvement of mitochondria and associated extramitochondrial proteins into such interactions still requires detailed investigation. In this study using an optical biosensor we have demonstrated binding of proteins of mouse brain mitochondrial lysates to immobilized monomeric ubiquitin. Model purified proteins, which are known to be associated with the outer mitochondrial compartment (glyceraldehyde-3-phosphate dehydorgenase, creatine phosphokinase), interacted with immobilized ubiquitin as well as with each other. This suggests that (poly)ubiquitinated chains may be involved in protein-protein interactions between ubiquitinated and non-ubiquitinated proteins and thus may contribute to formation of (mitochondrial) ubiquitin subinteractome.Ubikvitinirovanie belkov iavliaetsia vazhnym mekhanizmom, kotoryĭ ne tol'ko obespechivaet spetsificheskoe mechenie dlia posleduiushcheĭ degradatsii, no i vo mnogom opredeliaet lokalizatsiiu belkov v kletke i reguliatsiiu belok-belkovykh vzaimodeĭstviĭ. V kontekste belok-belkovykh vzaimodeĭstviĭ reshaiushchuiu rol' igraet prisoedinenie (mono/poli)ubikvitinovykh molekul k belkam, soderzhashchim spetsificheskie ubikvitin-sviazyvaiushchie domeny. Formirovanie ubikvitinovogo interaktoma pokazano dlia tsitozolia. Vovlechenie v takogo roda vzaimodeĭstviia mitokhondriĭ i assotsiirovannykh s nimi ékstramitokhondrial'nykh belkov izucheno znachitel'no khuzhe. V nastoiashchem issledovanii s ispol'zovaniem opticheskogo biosensora pokazano sviazyvanie belkov lizata mitokhondrial'noĭ fraktsii mozga mysheĭ s immobilizovannym monomernym ubikvitinom. Model'nye ochishchennye belki (glitseral'degid-3-fosfatdegidrogenaza, kreatinkinaza), assotsiirovannye s vneshnim kompartmentom mitokhondriĭ, vzaimodeĭstvovali kak s immobilizovannym ubikvitinom, tak i mezhdu soboĭ. Éto svidetel'stvuet v pol'zu togo, chto (poli)ubikvitinovye tsepi mogut uchastvovat' v belok-belkovykh vzaimodeĭstviiakh mezhdu ubikvitinirovannymi i neubikvitinirovannymi belkami i vnosit' opredelennyĭ vklad v formirovanie (mitokhondrial'nogo) ubikvitinovogo subinteraktoma.

The data on the microbial communities and biochemical properties of forest soils obtained in the course of long-term studies in the region of the Kostomuksha ore mining and processing enterprise are presented. The changes in the parameters investigated caused by the anthropogenic impact were revealed. It was concluded that the microbial-biochemical characteristics may be used as an indicator of the state of soils exposed to aerial pollution.

The amyloid-β peptide is considered as a key player in the development and progression of Alzheimer’s disease (AD). Although good evidence exists that amyloid-β accumulates inside cells, intracellular brain amyloid-binding proteins remain poorly characterized. Proteomic profiling of rat brain homogenates, performed in this study, resulted in identification of 89 individual intracellular amyloid-binding proteins, and approximately 25% of them were proteins that we had previously identified as specifically binding to isatin, an endogenous neuroprotector molecule. A significant proportion of the amyloid-binding proteins (more than 30%) are differentially expressed or altered/oxidatively modified in AD patients. Incubation of brain homogenates with 70 µM hydrogen peroxide significantly influenced the profile of amyloid-β binding proteins and 0.1 mM isatin decreased the number of identified amyloid-β binding proteins both in control and hydrogen peroxide treated brain homogenates. The effects of hydrogen peroxide and isatin have been confirmed in optical biosensor experiments with purified glyceraldehyde-3-phosphate dehydrogenase, one of the known crucial amyloid-β binding proteins (also identified in this study). Data obtained suggest that isatin protects crucial intracellular protein targets against amyloid binding, and possibly favors intracellular degradation of this protein via preventing formation of amyloid-β oligomers described in the literature for some isatin derivatives.

A mathematical model and results of numerical calculation of the process of interaction between a swirling jet and drift flow are presented in the paper. The structure of flow and the process of chemical reactions are investigated under conditions of transverse injection of a swirling jet of combustion products into a flow of fuel-air mixture. Inferences are made of the possibility of using a transversely injected jet to provide for a gasdynamic stabilization of flame in combustors of gas-turbine engines.