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Purpose of the study: The purpose of the article is to substantiate the need for students’ value-semantic attitude formation towards the chosen occupation based on the University educational environment resources activation. This attitude, as practical experience proves, allows more successfully carry out occupational activities, strive for self-improvement of labor skills, and permanently extrapolates this attitude to the profession in one’s own life. Methodology: Research on testing models of value-semantic attitude’s formation to the profession among the students was conducted in the period from 2009 to 2018. Experimental research covered 395 people, including 339 students and 56 teachers. The following techniques and tests contributing to diagnostics were used for the study: the personality's strong-willed organization, the training motivation, educational achievements and need for them, valuable orientation-based unity of the group, the attitude to specific types of occupational activity. Results: The article clarifies the concept of value-semantic attitude to the profession, characterizes the educational environment of the University in the context of this problem, presents the functions and components of the axiological approach aimed at the development of the University educational environment; defines the pedagogical conditions under which students’ value-semantic attitude to the chosen profession will be qualitatively formed. The article reveals the possibilities of simulating such an educational environment. The article describes the results of the interrelated components’ implementation of the developed model for value-semantic relations’ formation, implemented for many years in educational institutions of higher education. Applications of this study: The possibility of educational courses, methods, forms and training technologies adaptation to the educational environment of universities, regardless of their profile orientation is described. Novelty/Originality of this study: The article proposes adapted and developed diagnostic methods; presents the developed criteria and levels to identify the formation of value-semantic attitude to the profession among the students.

At present, the problem of sustaining the law-abiding behavior of minors in educational institutions, identifying and eliminating the causes and conditions that contribute to the development of deviant behavior of students is becoming more and more topical. This paper presents the results of a monitoring study of the current state of the activities carried out by educational institutions to form the law-abiding behavior of minors in the territorial entities of the Russian Federation. It also presents the results of a theoretical study of the foreign experience of educational institutions in the framework of maintaining the law-abiding behavior of minors in the educational environment. The conclusions have been drawn that a system-activity approach should be the basis of an educational impact in educational institutions which will provide: the formation of students’ readiness for self-development; the design and construction of a social environment for the development of students based on moral principles, traditional Russian values, relevant scientific knowledge and skills, respect for the traditions of the multinational, multicultural and multiconfessional Russian society; active educational and cognitive activities of students; building educational and moral education activity, taking account of the individual age-related psychological and physiological characteristics of students and with a focus on educational results. The materials of the paper are part of a large-scale study within the framework of the "Conception for the development of a system for the prevention of neglect and juvenile delinquency for the period up to 2020", conducted by a team of scientists from 2017 to 2020, whose scientific interests lie in the study of the problem of deviant behavior of minors.

Non-steroidal anti-inflammatory drugs (NSAIDs) are most popular medications for the treatment of pain in common musculoskeletal diseases such as osteoarthritis (OA) and non-specific low back pain (LBP). However, the factors affecting the effectiveness of these drugs have not been determined fully. Aim: to identify factors affecting the effectiveness of NSAIDs in patients with OA and LBP. Materials and methods. An observational study was conducted to evaluate the effectiveness of a 2-week course of NSAIDs in OA and LBP in real clinical practice. The study group consisted of 3604 patients with OA and LBP (60.6% women and 39.4% men, mean age 55.0±13.4 years). According to the study design, aceclofenac (Airtal) and other NSAIDs used in the ratio 1:1. The main criterion of effectiveness was the frequency of complete pain relief after 2 weeks of therapy. In addition, the decrease of pain and general health were determined on a 10-point numerical rating scale (NRS). We compared the frequency of complete pain relief in patients who had and did not have the studied factors. The value of the studied factors was determined using OR (95% CI). Results and discussion. Most patients received aceclofenac (54.9%), as well as diclofenac (2.0%), ketoprofen (1.9%), lornoxicam (2.2%), meloxicam (13.7%), naproxen (2.1%), nimesulide (5.8%), celecoxib (5.9%), ethicoxib (7.1%) and other NSAIDs (4.4%); 56.2% of patients received muscle relaxants, mainly tolperisone (74.7%), vitamin B (10.4%), and proton pump inhibitors (42.8%). Complete pain relief was achieved in 54.8% of patients. The pain decrease and general health improvement were (for NRS) 63.9±13.4% and 61.7±14.8%, respectively. The efficacy of aceclofenac was slightly higher than in the whole group: complete pain relief was in 59.9% of patients. Adverse events in aceclofenac use were observed in 2.3% of patients, other NSAIDs-from 2.4 to 14.1%. The frequency of complete pain relief was higher in men: OR 1,239 (95% CI 1.08-1.418; p=0.002), who had the first episode of pain - OR 3.341 (95% CI 2.873-3.875; p=0.000), a good" response " to NSAIDs in history - OR 1.656 (95% CI 1.385-1.980; p=0.000) and received NSAIDs in combination with muscle relaxants - OR 1.218 (95% CI 1.067-1.390; p=0.004). The effect of therapy is lower in patients 65 years and older-OR 0,378 (95% CI 0.324-0.442; p=0,000), with body mass index >30 kg/m² - OR 0.619 (95% CI 0.529-0.723; p=0.000), with severe pain (≥7 points NRS) - OR 0.662 (95% CI 0.580-0.756; p=0.002), with pain at rest, - OR 0.515 (95% CI 0.450-0,589; p=0.000), pain at night - OR 0.581 (95% CI 0.501-0.672; p=0.000) and the presence of stiffness - OR 0.501 (95% CI 0.438-0,573; p=0.000). Treatment results are significantly worse in the cases of combination of LBP and joint pain, as well as pain in the trochanter major and pes anserinus area (p

In the regions polluted with industrial or agricultural toxicants, dysmetabolic nephropathy is detected in every 2 or 3 children and this rate increases with age. Exogenous intoxication is not the only cause of dysmetabolic nephropathy; of no less importance are endogenous toxicants, such as oxidative stress products, excess of usual metabolites or emergence of unusual products of abnormal metabolism. The toxicants are ascertained to be able to change the conformation of protein molecules to give rise to additional ligand loci ensuring the aggressive uptake of trace elements that fix changes in protein molecules, making them antigenically alien to the body. Low molecular weight proteins with their changed structure, which penetrate through the basement membrane, are unrecognized by the reabsorption systems of proximal tubules and excreted with urine, determining the appearance of the most steady and age-increasing sign of dysmetabolic nephropathy – microproteinuria or trace elementuria.

Background:Tofacitinib is an oral Janus Kinase inhibitor for the treatment of rheumatoid arthritis (RA).Objectives:To evaluate the three-year effectiveness of tofacitinib in RA conventional synthetic (cs) DMARDs non-responders.Methods:Data from 374 patients from Russian national register OREL of patients with RA treated with tofacitinib not less than 3 years after failure of conventional DMARDs were included in the statistical analysis. Clinical and laboratory data from 4 consecutive visits with an interval of 12 months between the visits (± 28 days) were analyzed. Treatment with any biologics ever was an exclusion criteria. Demographical (age, sex) and disease-related characteristics of RA (symptoms duration, RF- and ACCP positivity, presence of joint erosions, DAS28, CDAI, number of tender and swollen joints (NTJ, NSJ), erythrocytes sedimentation rate (ESR), C-reactive protein (CRP)) collected. Statistical analysis performed with statistical programs SPSS2017 and GraphPadPrizm. p-value < 0.05 considered as significant.Results:Baseline characteristics of RA patients, involved in the analysis are presented in table 1.Table 1.Baseline characteristics of the patients with RA (n=374).ParameterCharacteristicsMale, n (%)92 (24.5)Age, years (mean±SD)53.4±13.38Symptoms duration, month (mean±SD)140±137Positive rheumatoid factor (RF), n (%)123(32.8)Positive antibodies to cyclic citrullinated peptide (ACCP), n (%)329(87.9)Erosions of hand joints (X-rays), n (%)372 (99.4)BMI, kg/m2(mean ±SD)26.8 ± 6.14Smokers (current and in the past), n (%)54 (14.4)Changes in the diseases activity parameters in patients with RA, treated with tofacitinib not less than 3 years after cs DMARD failure are presented in table 2, figure 1, and figure 2.Figure 1.DAS28 of patients with RA, treated with tofacitinib (n=374) – 3-years follow-up (time-points are presented in years ± 28 days).Figure 2.DAS28 of patients with RA, treated with tofacitinib (n=374) – 3-years follow-up (time-points are presented in years ± 28 days).Table 2.Changes in RA parameters in patients treated with tofacitinib, n=374 (M±SE).Disease characteristicsBaselineYear 1#Year 2#Year 3#C-RP, mg/L30.1±35.08.3±12.87.6±10.79.4±13.5ESR, mm/h35.2±21.222.7±17.221.9±17.722.3±17.3NTJ from 2811.2±6.54.6±4.94.8±5.03.9±3.8NTJ from 287.6±5.12.4±3.21.7±3.11.4±2.8*difference with baseline is significant with p#- ±28 daysConclusion:According to the real world data treatment with tofacitinib may provide good response rates in RA patients, refractory to the previous csDMARDs treatment in long-term perspective.Acknowledgments :PfizerDisclosure of Interests: :Inna Gaydukova Grant/research support from: JSC BIOCAD, Speakers bureau: Pfizer, Novartis, AbbVie, JSC BIOCAD, Сelgene, MSD, Sanofi, V Mazurov: None declared, Alexander Lila: None declared, Andrey Baranov Grant/research support from: Bayer, Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Evgeniy Zhilyaev Speakers bureau: Novartis, UCB, Pfizer, Biocad, Abbvie, MSD, Roche, Ekaterina Koltsova: None declared, Evgeniya Shmidt Speakers bureau: MSD, Novartis, Pfizer, Oxana Fomina: None declared, Irina Bondareva: None declared, Olga Anoshenkova: None declared, Aleksey Vasilenko: None declared, Elizaveta Vasilenko: None declared, Natalya Yudina: None declared, Larisa Knyazeva: None declared, Vyacheslav Poncratov: None declared, Ekaterina Gaydukova: None declared, Evgeny Nasonov Speakers bureau: Lilly, AbbVie, Pfizer, Biocad, R-Pharm

The work reveals the general social and technological prerequisites for integrating computer technologies into Russian education at various levels and profiles of educational institutions. The reasons for the basic contradictions in traditional and innovative pedagogical principles in professional training of performing musicians have been substantiated. Productive ways to solve the problem have been described based on the leading developments of education researchers in the computer and music technologies as well as in electronic music. The essence of the computer and music technologies concept as a specialized field of music pedagogy in Russia has been revealed. Features of hardware and software have been defined based on the digital interface of musical instruments and the prospects for their use in pedagogical activities. The methods, forms, and conditions for practical implementation of experimental training of pianist students from the Institute of Culture and Arts of the Moscow City University have been presented. The generalized results and conclusions of the experimental training in instrument performance of the pedagogical university students using the software and hardware components of the computer and music technologies have been analyzed and discussed.

Background: Rituximab (RTX) is successfully used in patients with active rheumatoid arthritis (RA) who previously received biological disease-modifying antirheumatic drugs (bDMARDs) at a dose of 1000 mg. Previous preclinical and clinical studies showed that BCD-020 is highly similar to innovator RTX. ALTERRA study demonstrated that first-line use of 600 mg BCD-020 is very effective in bDMARDs naive patients with RA. Objectives: The goal of ALTERRA study was to evaluate the efficacy and safety of the alternative dosing regimen (600 mg) of BCD-020 in bDMARDs naive patients with RA. Methods: ALTERRA study was conducted as multicenter randomized double-blind placebo-controlled phase 3 study. After the screening patients were stratified by age, anti-CCP level and DAS28 score, randomized (2:1) into 2 arms and received BCD-020 (in combination with methotrexate (MTX)) in a dose 600 mg IV or placebo (in combination with MTX) on day 1 and day 15, then, if the activity of arthritis persisted after 24 wks of study, a second course was provided. Patients were observed up to 52 wks. Results: A total of 159 patients were enrolled in ALTERRA study, 107 patients in BCD-020 arm and 52 patients in placebo arm. Efficacy: ACR20 at wk 24 was reached by 65.69% of patients in BCD-020 arm and 29.41% in placebo arm (p=0.00005, the difference in proportion of registration ACR20 with 95%CI was 29.41 [19.27%; 53.28%], margin 10.5%) in per protocol population, so hypothesis of superiority was confirmed. The performed analysis showed a much more pronounced decrease in the DAS28–4 (ESR) index in BCD-020 arm compared with placebo arm (p=0.0006) at wk 24. A much more significant decrease in change of the HAQ-DI index was also shown in the BCD-020 arm (p=0.008). Analysis of efficacy at wk 52 showed the preservation of the response after 2 courses of therapy with BCD-020, 600 mg (in combination with MTX): ACR20 reached by 84.5%, ACR50 – by 54.6%, ACR70 – by 29.9 % of patients. Safety: BCD-020 showed a favorable safety profile with no significant difference with placebo use (in combination with MTX). After 24 wks patients of both groups developed high similar level of related adverse events: 16.8% of patients in BCD-020 arm and 11.76% in placebo arm (p=0.555). There were only 3 cases of severe adverse events (2.8%) in BCD-020 arm and 2 cases (3.92%) in placebo group. From wk 24 to wk 52: 13.08% of patients (who received 2 courses of BCD-020) and 19.61% of patients (who received one course of BCD-020 after 24 wk) developed related adverse events. Figure 1 ACR 20/50/70 in bDMARDs naive patients with RA after 24-wk treatment of BCD-020/placebo (in combination with MTX). Conclusions: ALTERRA study showed high efficacy and favorable safety profile of RTX biosimilar BCD-020 at a dose of 600 mg in combination with MTX in bDMARDs naive patients with RA. Disclosure of Interest: V. Mazurov: None declared, L. Denisov: None declared, I. Gordeev: None declared, O. Nesmeyanova: None declared, T. Plaksina: None declared, E. Ilivanova: None declared, D. Krechikova: None declared, E. Zonova: None declared, L. Knyazeva: None declared, A. Artemeva Employee of: JSC BIOCAD, E. Dokukina Employee of: JSC BIOCAD, E. Chernyaeva Employee of: JSC BIOCAD, R. Ivanov Employee of: JSC BIOCAD

The effect of alpha-N-acetylation (Nt-acetylation) on the properties of parvalbumin (PA), a Ca2+-binding relaxing factor of skeletal muscles and major food allergen, has been explored. Intact PA contains an N-terminal acetyl group which is absent in the protein expressed in Escherichia coli (rWT), as confirmed by mass spectrometry. Compared to intact pike α-PA, its rWT form exhibits essentially altered profile of thermal unfolding, lowered α-helicity, and decreased affinities to Ca2+ and Mg2+. The structural destabilization of the rWT protein results in lowered resistance to chymotryptic digestion and increased propensity to oligomerization. The rate constants of Ca2+ dissociation from the rWT PA are markedly increased, which indicates that Nt-acetylation modifies functional status of the protein. Rat α-PA demonstrates similar properties for intact and rWT forms. The drastic difference in the effects induced by Nt-acetylation in the PA orthologs can be rationalized by higher disorder level of AB domain in pike PA. Though evolution of PA's genes resulted in the protein sequences with highly divergent properties, Nt-acetylation unifies their functional properties. The structural stability conferred to PA by Nt-acetylation may contribute to its allergenicity. Overall, Nt-acetylation is shown to be a prerequisite for maintenance of structural and functional status of some parvalbumins.

Some natural proteins induce tumor-selective apoptosis. α-Lactalbumin (α-LA), a milk calcium-binding protein, is converted into an antitumor form, called HAMLET/BAMLET, via partial unfolding and association with oleic acid (OA). Besides triggering multiple cell death mechanisms in tumor cells, HAMLET exhibits bactericidal activity against Streptococcus pneumoniae. The existing methods for preparation of active complexes of α-LA with OA employ neutral pH solutions, which greatly limit water solubility of OA. Therefore these methods suffer from low scalability and/or heterogeneity of the resulting α-LA – OA samples. In this study we present a novel method for preparation of α-LA – OA complexes using alkaline conditions that favor aqueous solubility of OA. The unbound OA is removed by precipitation under acidic conditions. The resulting sample, bLA–OA-45, bears 11 OA molecules and exhibits physico-chemical properties similar to those of BAMLET. Cytotoxic activities of bLA–OA-45 against human epidermoid larynx carcinoma and S. pneumoniae D39 cells are close to those of HAMLET. Treatment of S. pneumoniae with bLA–OA-45 or HAMLET induces depolarization and rupture of the membrane. The cells are markedly rescued from death upon pretreatment with an inhibitor of Ca2+ transport. Hence, the activation mechanisms of S. pneumoniae death are analogous for these two complexes. The developed express method for preparation of active α-LA – OA complex is high-throughput and suited for development of other protein complexes with low-molecular-weight amphiphilic substances possessing valuable cytotoxic properties.

A specific state of the human milk Ca(2+) binding protein alpha-lactalbumin (hLA) complexed with oleic acid (OA) prepared using an OA-pretreated ion-exchange column (HAMLET) triggers several cell death pathways in various tumor cells. The possibility of preparing a hLA-OA complex with structural and cytotoxic properties similar to those of the HAMLET but under solution conditions has been explored. The complex was formed by titration of hLA by OA at pH 8.3 up to OA critical micelle concentration. We have shown that complex formation strongly depends on calcium, ionic strength, and temperature; the optimal conditions were established. The spectrofluorimetrically estimated number of OA molecules irreversibly bound per hLA molecule (after dialysis of the OA-loaded preparation against water followed by lyophilization) depends upon temperature: 2.9 at 17 degrees C (native apo-hLA; resulting complex referred to as LA-OA-17 state) and 9 at 45 degrees C (thermally unfolded apo-hLA; LA-OA-45). Intrinsic tryptophan fluorescence measurements revealed substantially decreased thermal stability of Ca(2+)-free forms of HAMLET, LA-OA-45, and OA-saturated protein. The irreversibly bound OA does not affect the Ca(2+) association constant of the protein. Phase plot analysis of fluorimetric and CD data indicates that the OA binding process involves several hLA intermediates. The effective pseudoequilibrium OA association constants for Ca(2+)-free hLA were estimated. The far-UV CD spectra of Ca(2+)-free hLA show that all OA-bound forms of the protein are characterized by elevated content of alpha-helical structure. The various hLA-OA complexes possess similar cytotoxic activities against human epidermoid larynx carcinoma cells. Overall, the LA-OA-45 complex possesses physicochemical, structural, and cytotoxic properties closely resembling those of HAMLET. The fact that the HAMLET-like complex can be formed in aqueous solution makes the process of its preparation more transparent and controllable, opening up opportunities for formation of active complexes with specific properties.

Background BCD-020 is the first Russian rituximab (RTX) biosimilar which was approved for medical use in lymphoma patients in Russia and some CIS countries. Previous preclinical and clinical studies showed that BCD-020 is highly similar to innovator RTX. Since there are several differences in mechanism of action of RTX in NHL and RA it is recommended to conduct separate clinical studies in oncology and autoimmune indications to prove similar efficacy and safety of biosimilar and original medicine. Objectives The primary objective was to evaluate the efficacy and safety of BCD-020 used in combination with MTX in patients with RA with inadequate response or intolerance to other DMARDs including 1 or more TNF inhibitor. The secondary objectives included direct comparison of safety, efficacy, pharmacokinetics, pharmacodynamics and immunogenicity of RTX biosimilar and innovator RTX. Methods This international multicenter randomized double-blind phase 3 clinical study was conducted in patients with active RA despite DMARD therapy, which included 1 or more TNF inhibitor. After completion of screening all eligible patients were stratified by age ( Results A total of 160 patients were enrolled; 159 patients had data eligible for efficacy analysis. ACR20 at Week 24 was reported in 84.14% patients in BCD-020 arm and 87.01% in reference arm. The 95% CI for the difference in proportion of ACR20 between groups was [-13.95; 8.74%], where the limits of 95% CI lie within the pre-specified equivalence margin. Both drugs caused deep and sustained depletion of B-cells from peripheral blood without any toxicity to other cell populations. Favorable safety profiles were demonstrated in both groups without any significant differences: AEs have been reported in 59.34% patients from BCD-020 arm and 54.12% patients from reference arm. Treatment discontinuation caused by AE/SAE was reported only for 3 (3.30%) patients in BCD-020 arm and 4 (3.53%) patients in the reference arm (p=1.00). SAEs occurred only in the reference group (2.35%). Binding antibodies were revealed in 3 patients from BCD-020 arm and in 7 patients from reference arm (p=0.209). There were 2 events of neutralizing antibodies against RTX, both in the reference arm (p=0.232). Conclusions Equivalent efficacy of BCD-020 compared to innovator RTX in patients with active RA has been confirmed. Further clinical evaluation of BCD-020 is planned to confirm long-term efficacy and safety. References interim study report. Disclosure of Interest A. Eremeeva Employee of: CJSC BIOCAD, E. Chernyaeva Employee of: CJSC BIOCAD, R. Ivanov Employee of: CJSC BIOCAD, E. Nasonov: None declared, L. Knyazeva: None declared

NCS (neuronal Ca2+ sensor) proteins belong to a family of calmodulin-related EF-hand Ca2+-binding proteins which, in spite of a high degree of structural similarity, are able to selectively recognize and regulate individual effector enzymes in a Ca2+-dependent manner. NCS proteins vary at their C-termini, which could therefore serve as structural control elements providing specific functions such as target recognition or Ca2+ sensitivity. Recoverin, an NCS protein operating in vision, regulates the activity of rhodopsin kinase, GRK1, in a Ca2+-dependent manner. In the present study, we investigated a series of recoverin forms that were mutated at the C-terminus. Using pull-down assays, surface plasmon resonance spectroscopy and rhodopsin phosphorylation assays, we demonstrated that truncation of recoverin at the C-terminus significantly reduced the affinity of recoverin for rhodopsin kinase. Site-directed mutagenesis of single amino acids in combination with structural analysis and computational modelling of the recoverin–kinase complex provided insight into the protein–protein interface between the kinase and the C-terminus of recoverin. Based on these results we suggest that Phe3 from the N-terminal helix of rhodopsin kinase and Lys192 from the C-terminal segment of recoverin form a cation–π interaction pair which is essential for target recognition by recoverin. Taken together, the results of the present study reveal a novel rhodopsin-kinase-binding site within the C-terminal region of recoverin, and highlights its significance for target recognition and regulation.

Recoverin belongs to the family of intracellular Ca(2+)-binding proteins containing EF-hand domains, neuronal calcium sensors (NCS). In photoreceptor outer segments, recoverin is involved into the recovery of visual cycle via Ca(2+)-dependent interaction with disk membranes and inhibition of rhodopsin kinase. The function of a conservative within NCS family Cys residue in the inactive EF-loop 1 remains unclear, but previous study has shown its vulnerability to oxidation under mild oxidizing conditions. To elucidate the influence of oxidation of the conservative Cys39 in recoverin the properties of its C39D mutant, mimicking oxidative conversion of Cys39 into sulfenic, sulfinic or sulfonic acids have been studied using intrinsic fluorescence, circular dichroism, and equilibrium centrifugation methods. The C39D substitution results in essential changes in structural, physico-chemical and physiological properties of the protein: it reduces α-helical content, decreases thermal stability and suppresses protein affinity for photoreceptor membranes. The latter effect precludes proper functioning of the Ca(2+)-myristoyl switch in recoverin. The revealed significance of oxidation state of Cys39 for maintaining the protein functional status shows that it may serve as redox sensor in vision and suggests an explanation of the available data on localization and light-dependent translocation of recoverin in rod photoreceptors.

The specific complexes of human alpha-lactalbumin (alpha-LA) with oleic acid (OA), HAMLET and LA-OA-17 (OA-complexes), possess cytotoxic activity against tumor cells but the mechanism of their cell penetration remains unclear. To explore the molecular mechanisms underlying interaction of the OA-complexes with the cell membrane, their interactions with small unilamellar dipalmitoylphosphatidylcholine (DPPC) vesicles and electroexcitable plasma membrane of internodal native and perfused cells of the green alga Chara corallina have been studied. The fractionation (Sephadex G-200) of mixtures of the OA-complexes with the vesicles shows that OA-binding increases the affinity of alpha-LA to DPPC vesicles. Calcium association decreases protein affinity to the vesicles; the effect being less pronounced for LA-OA-17. The voltage clamp technique studies show that LA-OA-17, HAMLET, and their constituents produce different modifying effects on the plasmalemmal ionic channels of the Chara corallina cells. The irreversible binding of OA-complexes to the plasmalemma is accompanied by changes in the activation-inactivation kinetics of developing integral transmembrane currents, suppression of the Ca(2+) current and Ca(2+)-activated Cl(-) current, and by increase in the nonspecific K(+) leakage currents. The latter reflects development of nonselective permeability of the plasma membrane. The HAMLET-induced effects on the plasmalemmal currents are less pronounced and potentiated by LA-OA-17. The control experiments with OA and intact alpha-LA show their qualitatively different and much less pronounced effects on the transmembrane ionic currents. Thus, the modification of alpha-LA by OA results in an increase in the protein association with the model lipid bilayer and in drastic irreversible changes in permeability of several types of the plasmalemmal ionic channels.

Recently defined family of intrinsically disordered proteins (IDP) includes proteins lacking rigid tertiary structure meanwhile fulfilling essential biological functions. Here we show that apo-state of pike parvalbumin (alpha- and beta-isoforms, pI 5.0 and 4.2, respectively) belongs to the family of IDP, which is in accord with theoretical predictions. Parvalbumin (PA) is a 12-kDa calcium-binding protein involved into regulation of relaxation of fast muscles. Differential scanning calorimetry measurements of metal-depleted form of PA revealed the absence of any thermally induced transitions with measurable denaturation enthalpy along with elevated specific heat capacity, implying the lack of rigid tertiary structure and exposure of hydrophobic protein groups to the solvent. Calcium removal from the PAs causes more than 10-fold increase in fluorescence intensity of hydrophobic probe bis-ANS and is accompanied by a decrease in alpha-helical content and a marked increase in mobility of aromatic residues environment, as judged by circular dichroism spectroscopy (CD). Guanidinium chloride-induced unfolding of the apo-parvalbumins monitored by CD showed the lack of fixed tertiary structure. Theoretical estimation of energetics of the charge-charge interactions in the PAs indicated their pronounced destabilization upon calcium removal, which is in line with sequence-based predictions of disordered protein chain regions. Far-UV CD studies of apo-alpha-PA revealed hallmarks of cold denaturation of the protein at temperatures below 20 degrees C. Moreover, a cooperative thermal denaturation transition with mid-temperature at 10-15 degrees C is revealed by near-UV CD for both PAs. The absence of detectable enthalpy change in this temperature region suggests continuous nature of the transition. Overall, the theoretical and experimental data obtained show that PA in apo-state is essentially disordered nevertheless demonstrates complex denaturation behavior. The native rigid tertiary structure of PA is attained upon association of one (alpha-PA) or two (beta-PA) calcium ions per protein molecule, as follows from calorimetric and calcium titration data.

1. The rhodium carbonyl hydride complex RhH(CO) (PPh3)3 is an active catalyst for the synthesis of phenyl isocyanate, the o-, m-, and p-tolyl isocyanates, and mesityl isocyanate from the corresponding aromatic nitro compounds by carbonylation with CO. The optimum reaction conditions were determined (pressure, temperature, time, substrate/catalyst ratio). 2. The use of MoCl5 as a cocatalyst increases the conversion of the nitro compound, the yield of the isocyanate, and the selectivity of the process. 3. Methyl substituents in the o-position activate the nitro group when nitro compounds are carbonylated with CO.

1. Anionic carbonyl halide complexes of rhodium and palladium are active homogeneous catalysts for the synthesis of aryl isocyanates by carbonylation of nitro compounds. 2. By introducing BU4NCl into the catalytic system based on palladium complexes in an amount of 1 to 2 moles per g-atom of palladium, nitrobenzene and o-nitrotoluene can be carbonylated to give a 20–25% yield of the corresponding isocyanates under carbon monoxide at atmospheric pressure.

1. Shielded phenols containing silicon and/or germanium have been found to rearrange to phenoxysilanes or phenoxygermanes under the influence of complex formation with oxygen. 2. The silicon- and germanium-containing phenols form π complexes with oxygen in which the oxygen acts as an acceptor. The constants of complex formation have been determined. 3. Silicon- and germanium-containing shielded phenols, when exposed to elevated temperatures or the action of bases, rearrange to phenoxysilanes or phenoxygermanes. The germanium-containing phenols are more stable at high temperatures than are the silicon-containing phenols, but are rearranged more readily under the influence of organic bases. The p isomers are more stable than the o isomers.

The Ph3P complexes of Rh and Ir are active homogeneous catalysts for the synthesis of methyl N-phenylcarbamate by the carbonylation of PhNO2 in MeOH.