Streptomyces phaeochromogenes BV-204, K-1115A Anthraquinone-Producing Strain: A New Protein Biosynthesis Inhibitor.

In the search for new antibiotics, it is a common occurrence that already known molecules are "rediscovered" while new promising ones remain unnoticed. A possible solution to this problem may be the so-called "target-oriented" search, using special reporter microorganisms that combine increased antibiotic sensitivity with the ability to identify a molecule's damaging effect. The use of such test organisms makes it possible to discover new promising properties even in known metabolites. In this study, we used a high-throughput screening method based on the pDualrep2 dual reporter system, which combines high sensitivity through the use of modified strains of test organisms and makes it possible to easily and accurately identify the interaction mechanisms of a substance and a bacterial cell at the initial stages of screening. This reporter system is unknown in Russia and is significantly superior to its global analogues. In the system, translation inhibition induces the expression of the fluorescent protein Katushka2s, while DNA damage is induced by TurboRFP. Using pDualrep2, we have isolated and described BV-204, an S. phaeochromogenes strain producing K-1115A, the biologically active substance that we have previously described. In our study, K-1115A for the first time has demonstrated antibiotic activity and an ability to inhibit bacterial translation, which was confirmed in vitro in a cell-free translation system for FLuc mRNA. K-1115A's antibacterial activity was tested and confirmed for S. aureus (MRSA) and B. subtilis, its cytotoxicity measured against that for the HEK293 cell line. Its therapeutic index amounted to 2 and 8, respectively. The obtained results open up prospects for further study of K-1115A; so, this can be regarded as the basis for the production of semi-synthetic derivatives with improved therapeutic properties to be manufactured in dosage forms.

Characterization of oxidation of glutathione by cytochrome c.

Cytochrome c is a member of the respiratory chain of the mitochondria. Non-membrane-bound (free) cytochrome c can be reduced by gluthatione as well as ascorbic acid. We investigated the effect of pH, Ca2+, Mg2+ and anionic phospholipids on the reduction of cytochrome c by glutathione.The reduction of cytochrome c by thiols was measured using photometry. Mitochondrial oxygen consumption was detected by use of oxygen electrode. Glutathione does not reduce cytochrome c at pH = 7.0 in the absence of Ca2+ and Mg2+. The reduction of cytochrome c by glutathione is inhibited by anionic lipids, especially cardiolipin. The typical conditions of apoptosis-elevated pH, Ca2+ level and Mg2+-increases the reduction of cytochrome c. Glutathione (5 mM) causes increased mitochondrial O2 consumption at pH = 8.0, in the presence of ADP either 1 mM Mg2+ or 1 mM Ca2+. Our results suggest that membrane bound cyt c does not oxidize glutathione. Free (not membrane bound) cytochrome c can oxidize glutathione. In mitochondria, O2 is depleted only in the presence of ADP, so the O2 depletion observed in the presence of glutathione can be related to the respiratory chain. Decreased glutathione levels play a role in apoptosis. Therefore, membrane unbound cyt c can contribute to apoptosis by oxidation of glutathione.

Nanoparticles of water-soluble dyads based on amino acid fullerene C60 derivatives and pyropheophorbide: Synthesis, photophysical properties, and photodynamic activity.

Synthesis, spectral properties, and photodynamic activity of water-soluble amino acid fullerene C60 derivatives (AFD) and four original AFD-PPa dyads, obtained by covalent addition of dye pyropheophorbide (PPa) to AFD, were studied. In aqueous solution, these AFD-PPa dyads form nanoassociates as a result of self-assembly. In this case, a significant change in the absorption spectra and strong quenching of the dye fluorescence in the structure of the dyads were observed. A comparison of superoxide or singlet oxygen generation efficiency of the studied compounds in an aqueous solution showed the photodynamic mechanism switching from type II (singlet oxygen generation of the native dye) to I type (superoxide generation of dyads). All dyads have pronounced phototoxicity on cells Hela with IC50 9.2 µM, 9.2 µM, 12.2 µM for dyads Val-C60-PPa, Ala-C60-PPa and Pro-C60-PPa, respectively. Such facilitation of type I photodynamic mechanism could be perspective against hypoxic tumors.

Structural stability of CuAl2O4under pressure.

Structural properties of CuAl2O4, which was recently argued to show unusual suppression of the Jahn-Teller distortions by the spin-orbit coupling, are investigated under pressures up to 6 GPa. Analysis of x-ray powder diffraction experiments shows that CuAl2O4gets unstable and decomposes onto CuO and Al2O3at pressures ∼6 GPa and temperature ∼1000 K. This finding is complemented by the density-functional theory +U+ spin-orbit coupling calculations, which demonstrate that this instability is partially driven by a (relatively) large compressibility of strongly Jahn-Teller distorted CuO.

Emergence of a Magnetostructural Dipolar Glass in the Quadruple Perovskite Dy_{1-δ}Mn_{7+δ}O_{12}.

We show that a polar, pseudo-Jahn-Teller instability exists for the underbonded rare-earth A-site cations in the quadruple perovskite Dy_{1-δ}Mn_{7+δ}O_{12}, which leads to the spontaneous formation of a dipolar glass. This observation alone expands the applicability of pseudo-Jahn-Teller physics in perovskite-derived materials, for which it is typically confined to B-site cations. We demonstrate that the dipolar glass order parameter is coupled to a ferrimagnetic order parameter via strain, leading to a first order magnetostructural phase transition that can be tuned by magnetic field. This phenomenology may emerge in a broad range of perovskite-derived materials in which A-site cation ordering and octahedral tilting are mutually tied to meet the criteria of structural stability.

Effects of Covalent Conjugates of Fullerene Derivatives with Xanthene Dyes on Activity of Ca2+-ATPase of the Sarcoplasmic Reticulum.

The effects of the newly synthesized covalent conjugates of water-soluble fullerene derivatives (WSFD) with xanthene dyes: polyanionic WSFD-fluorescein (1), polycationic WSFD-fluorescein (2), polyanionic WSFD-eosin (3), and polyanionic WSFD (4), polycationic WSFD (5), fluorescein (6) and eosin (7), on activity of the membrane-bound Ca2+-ATPase of the sarcoplasmic reticulum (SR Ca2+-ATPase) were studied. Compounds 1, 3, 4, 6, and 7 inhibit the hydrolytic function of the enzyme, the inhibition constants for these compounds are Ki=1.3×10-5 M (1), Ki=4.7×10-6 M (3), Ki=2.5×10-6 M (4), Ki=6.1×10-5 M (6), and Ki=5.8×10-6 M (7). The effects of compounds 3, 6, and 7 on the hydrolytic function of the enzyme is competitive; compounds 1 and 4 are noncompetitive. Polycationic WSFD fluorescein (2) and polycationic WSFD (5) do not affect ATP hydrolysis, but inhibit active Ca2+ transport in a concentration of 0.01 mM by 100±10 and 40±4%, respectively. Conjugates 1 and 3 completely inhibit the hydrolytic and transport functions of the enzyme in a concentration of 0.01 mM, and in a concentration of 0.001 mM inhibit active Ca2+ transport by 60±6 and 55±6% uncoupling the hydrolytic and transport functions of SR Ca2+-ATPases. The obtained results demonstrate a significant effect of the studied compounds on the active transmembrane transfer of Ca2+ and make it possible to predict the presence of antimetastatic and antiaggregatory activities of the studied compounds.

Spontaneous Rotation of Ferrimagnetism Driven by Antiferromagnetic Spin Canting.

Spin-reorientation phase transitions that involve the rotation of a crystal's magnetization have been well characterized in distorted-perovskite oxides such as orthoferrites. In these systems spin reorientation occurs due to competing rare-earth and transition metal anisotropies coupled via f-d exchange. Here, we demonstrate an alternative paradigm for spin reorientation in distorted perovskites. We show that the R_{2}CuMnMn_{4}O_{12} (R=Y or Dy) triple A-site columnar-ordered quadruple perovskites have three ordered magnetic phases and up to two spin-reorientation phase transitions. Unlike the spin-reorientation phenomena in other distorted perovskites, these transitions are independent of rare-earth magnetism, but are instead driven by an instability towards antiferromagnetic spin canting likely originating in frustrated Heisenberg exchange interactions, and the competition between Dzyaloshinskii-Moriya and single-ion anisotropies.

57Fe Mössbauer study of unusual magnetic structure of multiferroic 3R-AgFeO2.

We report new results of a 57Fe Mössbauer study of hyperfine magnetic interactions in the layered multiferroic 3R-AgFeO2 demonstrating two magnetic phase transitions at T N1 and T N2. The asymptotic value ß * ≈ 0.34 for the critical exponent obtained from the temperature dependence of the hyperfine field H hf(T) at 57Fe the nuclei below T N1 ≈ 14 K indicates that 3R-AgFeO2 shows quasi-3D critical behavior. The spectra just above T N1 (T N1 < T < T * ≈ 41 K) demonstrate a relaxation behavior due to critical spin fluctuations which indicates the occurrence of short-range correlations. At the intermediate temperature range, T N2 < T < T N1, the 57Fe Mössbauer spectra are described in terms of collinear spin-density-waves (SDW) with the inclusion of many high-order harmonics, indicating that the real magnetic structure of the ferrite appears to be more complicated than a pure sinusoidally modulated SDW. Below T < T N2 ≈ 9 K, the hyperfine field H hf reveals a large spatial anisotropy (ΔH anis ≈ 30 kOe) which is related with a local intra-cluster (FeO6) spin-dipole term that implies a conventional contribution of the polarized oxygen ions. We proposed a simple two-parametric formula to describe the dependence of H anis on the distortions of the (FeO6) clusters. Analysis of different mechanisms of spin and hyperfine interactions in 3R-AgFeO2 and its structural analogue CuFeO2 points to a specific role played by the topology of the exchange coupling and the oxygen polarization in the delafossite-like structures.

Catalytic properties and amino acid sequence of endo-1→3-ß-D-glucanase from the marine mollusk Tapes literata.

A specific 1→3-ß-D-glucanase with molecular mass 37 kDa was isolated in homogeneous state from crystalline style of the commercial marine mollusk Tapes literata. It exhibits maximal activity within the pH range from 4.5 to 7.5 at 45°C. The 1→3-ß-D-glucanase catalyzes hydrolysis of ß-1→3 bonds in glucans as an endoenzyme with retention of bond configuration, and it has transglycosylating activity. The K(m) for hydrolysis of laminaran is 0.25 mg/ml. The enzyme is classified as a glucan endo-(1→3)-ß-D-glucosidase (EC 3.2.1.39). The cDNA encoding this 1→3-ß-D-glucanase from T. literata was sequenced, and the amino acid sequence of the enzyme was determined. The endo-1→3-ß-D-glucanase from T. literata was assigned to the 16th structural family (GHF 16) of O-glycoside hydrolases.

[Activation of the bioluminescence of the sensor Escherichia coli strains used for detecting N-acyl-homoserine lactones in the presence of nitrofurans and NO generators].

Nitrofurans (nitrofurazone, nitrofurantoin, furazidin, nifuroxazide), and nitric oxide generators (sodium nitroprusside and isosorbide mononitrate) in subinhibitory concentrations were shown to significantly increase the bioluminescence of the sensor Escherichia coli strains used for detecting N-acyl-homoserine lactones, signaling molecules of Quorum Sensing (QS) regulatory systems. The highest activation of bioluminescence (up to 250-400 fold) was observed in the presence of nitrofurazone on E. coli DH5alpha biosensors containing lux-reporter plasmids pSB401 or pSB536. However, this activation was not specifically associated with the functioning of QS systems. We suggest that the effect observed results from a direct action of nitrofurans and NO donors on the process of bioluminescence. The data indicate the necessity of using the biosensors that make it possible to detect specific effects of substances tested on QS regulation.

[Influence of mutations at genes of global transcriptional regulators on production of autoinducer AI-2 Quorum Sensing in the system of Escherichia coli].

The control of gene expression in response to an increase in the bacterial population density (Quorum Sensing) involves low-molecular-weight signal molecules (autoinducers, AI). AI-2 and synthase LuxS mediating its synthesis are widely distributed in Gram-negative and Gram-positive bacteria. In this work, the data were obtained on the role of global regulators of gene expression in AI-2 synthesis in Escherichia coli cells. The mutation inactivating gene rpoS (encodes sigma S subunit of RNA polymerase) was shown to drastically decrease an amount of active AI-2 in the culture medium. Mutations at gene rpoN that encodes sigma N subunit of RNA polymerase and also at gene lon, which encodes Lon proteinase, on the contrary, increase an amount of active AI-2 in supernatants of cultures. Mutant strains lacking histone-like proteins H-NS and StpA accumulate a slightly higher amount of AI-2 than the isogenic wild-type strain: however, an amount of AI-2 decreased in the culture medium of the double mutant devoid of both these proteins.

[Regulation of biofilm formation in Escherichia coli K12: effect of mutations in HNS, StpA, lon, and rpoN genes].

More than 99% of bacteria exist in natural ecosystems as specifically organized biofilms adhering to solid surfaces. Biofilms have a typical architecture and are enclosed in exopolymeric matrix. Bacteria living in biofilms are extremely resistant to antibacterial factors. In this work we studied the role of some global regulators of gene expression on biofilm formation by Escherichia coli K12. The Histone-like proteins H-NS and StpA were shown to play an essential role in the regulation of biofilm formation. Mutant strains deficient in HNS or StpA had lower levels of biofilm formation than the wild-type isogenic strain. A double mutant deficient in the two proteins was virtually incapable of forming the biofilms. The mutations in the rpoN gene encoding for the sigma N subunit of RNA-polymerase and in lon gene encoding for Lon-proteinase induced a 40-60% increase in the biofilm formation.

[The endoscopic diagnosis and differential treatment of the complications of shunting operations in children]. / Endoskopicheskaia diagnostika i differentsirovannoe lechenie oslozhnenii shuntiruiushchikh operatsii u detei.

The authors present their experience with endoscopic diagnosis and differential treatment of children with complications after bypass surgery. They show the present-day potentialities, spectrum of surgical interventions and role of video-assisted neuroendoscopic surgery in determining a treatment policy and choosing its method. A principle of multiportality was defined and substantiated, a diagnosis and treatment algorithm for children with this pathology was proposed by using the new minimum invasive technique video-assisted surgery.

[Shunting operations in the hypertensive hydrocephalic syndrome in children with developmental defects of the central nervous system]. / Shuntiruiushchie operatsii pri gipertenzionno-gidrotsefal'nom sindrome u detei s porokami razvitiia tsentral'noi nervnoi sistemy.

By analyzing the outcomes of surgical treatment of 105 children with hypertensive syndrome of various genesis, the authors present their data on the detection, diagnosis, and treatment of children with malformations of the central nervous system (CNS). The paper defines the present feasibilities of neurosonography, magnetic resonance imaging, neuroendoscopic verification of CNS malformations and their place in determining the policy and choice of a surgical treatment. The rationale for and the efficiency of cerebrospinal fluid corrective operations in children with these abnormalities are defined. Less good prognosis and a higher risk of surgery for hydrocephalic complications have been revealed and statistically evidenced.

[Correlation between structure and radioprotective activity (RPA) in thiazole derivatives]. / Vzaimosvaz struktura-radiozashchitnaia aktivnost (RZA) v riadu proizvodnykh tiazola.

The method of potential functions was used to predict adequately the radioprotective efficacy of thiazole derivative series, the geometrical indexes (1n A2 and A6) and anti-ion mass being applied as descriptors for organic and inorganic molecule parts respectively.

[Prediction of the acute toxicity of benzimidazole compounds by the electron structure of their molecules]. / Prognozirovanie ostroi toksichnosti soedinenii riada benzimidazola po élektronnoi strukture ikh molekul.

The relationship between acute toxicity of benzimidazole series compounds and electron structure of molecules was followed by using the method of potential functions, the method of basic components and the CHARM programme. The principal possibility of predicting toxicity of various derivatives of this class by electron structure of their molecules was shown. The fragment method of the assessment of characteristics in the range of CNDO/2 approximation permitting the quality of prognosis of 86-93% is proposed.