[Treatment of patients with burns in surgical clinics of Leningrad hospitals in 1920-1930s]. / Lechenie bol'nykh s ozhogami v khirurgicheskikh klinikakh meditsinskikh institutov Leningrada v 1920­1930-kh godakh.

OBJECTIVE: To reconstruct the events of early period of Soviet school of combustiology (1920-1930s) via analysis and systematization of clinical and experimental studies devoted to burns and performed in the Leningrad medical institutes in 1920-1930s. MATERIAL AND METHODS: We analyzed various reports by employees of the Leningrad medical institutes devoted to practice and theory of burn treatment within the above-mentioned historical period. RESULTS: Analysis of Soviet and foreign reports for 1920-1930s made it possible to systematize data on the treatment of burns in the Leningrad medical institutes for the period from the mid-1920s to the beginning of the Great Patriotic War. We presented experimental data on local and general processes following burn injuries. CONCLUSION: We discovered and introduced into scientific circulation some reports of Leningrad scientists on clinical and theoretical aspects of burn injuries which fell out of the field of view of modern researchers for various reasons. These data emphasize diverse work carried out by the staff of surgical and theoretical departments regarding the treatment of burn injuries.

Fragments of the Fab-3 and Fab-4 Boundaries of the Drosophila melanogaster Bithorax Complex That Include CTCF Sites Are not Effective Insulators.

The segment-specific regulatory domains of the Bithorax complex (BX-C), which consists of three homeotic genes Ubx, abd-A and Abd-B, are separated by boundaries that function as insulators. Most of the boundaries contain binding sites for the architectural protein CTCF, which is conserved for higher eukaryotes. As was shown previously, the CTCF sites determine the insulator activity of the boundaries of the Abd-B regulatory region. In this study, it was shown that fragments of the Fab-3 and Fab-4 boundaries of the abd-A regulatory region, containing CTCF binding sites, are not effective insulators.

[The inhibitors of angiogenesis in therapy of diabetic macular edema: the modern experience and perspectives of application on the Russian Federation].

The article presents and analyzes functional results of intravitreal application of two angiogenesis inhibitors of Ranibizumab and Aflibercept in treatment of diabetic macular edema. The positive results were obtained after triple administration of preparation with monthly intervals.

The Piragua Gene Is not Essential for Drosophila Development.

Proteins with clusters of C2H2 zinc finger domains (C2H2-proteins) constitute the most abundant class of transcription factors in higher eukaryotes. N-terminal ZAD (zinc finger-associated domain) dimerization domain has been identified in a large group of C2H2-proteins mostly in insects. The piragua gene encodes one of these proteins, Fu2. We have generated CRISPR/Cas9-mediated deletion of the piragua gene that has no phenotype. We have used φC31-mediated attP/attB recombination to generate a transgenic line expressing Fu2 protein fused with HA epitope. This line will be useful for analysis of DNA binding profile and functions of Fu2 protein.

The variability of soils and vegetation of hydrothermal fields in the Valley of Geysers at Kamchatka Peninsula.

The picturesque and high conservation value thermal landscapes of the Valley of Geysers feature endothermal (heated by endogenous fluids) soils which support endangered and unique species. However, such soils have not been distinguished as a separate taxon within most classification systems. In this study, we described the soil morphology at macro-, meso- and micro-scales, chemistry, mineralogy and vegetation of these landscapes as they are affected by the steam-heated acid-sulfate waters. The studied catenary sequence from exothermal (non-heated) to endothermal soils was characterized by decreasing contents of soil organic carbon, sand fraction, essential nutrients (Ca, K, Mg, Mn and Si), increasing soil acidity, amounts of fine particle-size fractions and contents of trace elements (Al, As, Co, Cr, Cu, Fe, Pb, Ti and V) as well as the development of sodium-sulfate salinity, kaolinization and ferrugination. In phytocenoses supported by endothermal soils, species of order Rosales and Asparagales were overrepresented among obligate and facultative thermophytes respectively, and species of order Poales were underrepresented among facultative thermophytes in relation to the flora of the Valley of Geysers. Phytocenoses on the non-heated Andosols were enriched in Polypodiopsida species. The results of our comparative analysis of the thermally-induced variability in the soils and vegetation contribute to the general understanding of mineralogical, bio-abiotic and biological systems affected by steam-heated acid-sulfate waters. We hope that our findings will provide a basis for future transdisciplinary studies of the influence of steam-heated waters of a hot spring on the thermal landscapes.

On a Possible Way to Increase the Efficiency of Photosynthesis.

The paper briefly describes the evolution of the key enzyme of photosynthesis, RuBisCO. Before the emergence of the reaction of carbon dioxide assimilation via photosynthesis, this protein was involved in the methionine metabolism chain. Possibly, for this reason, the carboxylation reaction catalyzed by enzyme proceeds very slowly. In addition to carboxylation, RuBisCO can simultaneously oxidize ribulose bisphosphate, a substrate to which the fixed CO2 is attached. This, in turn, also reduces the effectiveness of photosynthesis. In this regard, the literature discusses various options for increasing plant productivity by creating new forms of RuBisCO or fundamentally different pathways of carbon dioxide assimilation. In this work, we propose a modification of the carboxylation reaction that makes it possible to avoid photorespiration and thus increase the efficiency of photosynthesis.

[Choice of optimal treatment policy in patients with descending aortic dissection]. / Vybor optimal'noi taktiki lecheniia patsientov s rassloeniem niskhodiashchei aorty.

Contemporary approaches to treatment of patients with dissection of the descending aorta (DA), as well as the data of international registries and guidelines are contradictory. The endovascular method of treatment of patients with descending aortic dissection has been recognized to be revolutionary. However, there seems to be no commonly accepted concept concerning appropriate use of currently available techniques of treating patients with DA dissection. This study was aimed at analysing the experience gained in using various methods of treatment of patients with descending aortic dissection (DAD). We retrospectively examined the results of surgical treatment of 78 patients with DAD. Of these, 45 patients were found to have Stanford type B dissection and 33 patients had type A dissection, who underwent treatment during ten years from January 2008. The decision concerning the type of care for patients with DAD (conservative, surgical, endovascular or combined methods of treatment) directly depends on the patient's state stability, technical feasibility of the intended procedure, and the presence of concomitant pathology. The findings obtained in our study demonstrated better immediate outcomes of the endovascular approach compared with the hybrid and surgical ones. In order to achieve complete haemodynamic correction of the pathology, to minimize the risk of aortic remodelling and the development of aorta-related complications, the treatment should not be limited to endoprosthetic repair of the thoracic portion of the DA with a stent graft, but should rather be supplemented with stenting of more distal segments, including with uncoated stents at the level of the visceral branches. Only such staged approach may provide better conditions for obliteration of the aortic false lumen and formation of a 'neo-frame' of the aortic wall.

Design of a custom insertable probe platform for measurements of C-2W inner divertor plasma parameters.

A custom motor controlled probe system has been designed to make spatially resolved measurements of temperature, density, flow, and plasma potential in the C-2W inner divertors. Measurements in the inner divertors, which have a 1.7 m radius and are located on either end of the confinement vessel, are critical in order to gauge exactly how local settings affect the plasma conditions, confinement, and stability in the field-reversed configuration core. The inner Divertor Insertable Probe Platform (iDIPP) system consists of a custom motor controlled linear rack and pinion transporter that has a 1.9 m travel length in order to reach the center of the divertor. Mounted to the end of the transporter is a 1 m long segmented probe shaft made of individually floating stainless steel rings to prevent shorting out the electrode plates, which are biased up to 5 kV/m. A variety of interchangeable probe tips, including a triple Langmuir probe, a baffled probe, and a Gundestrup probe, can plug into the end of the probe shaft. Custom UHV coiled cabling comprised of 9 shielded conductors expands/retracts with the motion of the transporter in/out of the divertor. The physics motivating plasma parameter measurements in the inner divertors and the details of the design of the iDIPP system will be discussed.

Adsorption and photodynamic efficiency of meso-tetrakis(p-sulfonatophenyl)porphyrin on the surface of bilayer lipid membranes.

The adsorption and photodynamic efficiency of 5,10,15,20-tetrakis(p-sulfonatophenyl)porphyrin (H2TPPS4) on bilayer lipid membranes (BLM) have been studied. The adsorption of H2TPPS4 on BLM leads to rising of the potential drop on the membrane/water interface which has been detected either by the intramembrane field compensation (IFC) method, or as ζ-potential of liposomes measured by the dynamic light scattering method. The dependence of this potential on the concentration of H2TPPS4 and KCl in the solution can be described in the frame of Gouy-Chapman model of diffuse double layer assuming that the molecules of H2TPPS4 adsorb on the surface of BLM as an anions with four charged groups. The potential disappeared when the pH of solution decreased from 6 to 3 allowing the conclusion that the protonated forms of H2TPPS4 can not adsorb on the BLM probably due to change of conformation or aggregation of the molecules. The photodynamic efficiency of H2TPPS4 was evaluated by measuring the rate of damage of the targets - molecules of styryl dye (di-4-ANEPPS) by singlet oxygen generated under illumination on the surface of BLM. This rate was proportional to the surface density of H2TPPS4 molecules on the membrane which was determined from the change of surface charge of the membrane due to adsorption of the H2TPPS4. These results indicate that the di-4-ANEPPS molecules are damaged by singlet oxygen generated by monomers of H2TPPS4 molecules adsorbed on the membrane. The rate of oxidation of di-4-ANEPPS molecules adsorbed on the same (cis) side of the membrane together with the H2TPPS4 molecules was either the same or higher than that when di-4-ANEPPS molecules were adsorbed on opposite (trans) side. It indicates that the quenching of singlet oxygen by the di-4-ANEPPS molecules at cis side of the membrane was negligible, in contrast to our earlier study when singlet oxygen was generated by aluminum(III) phthalocyanines with one or two peripheral sulfo groups. The difference between these phthalocyanines and H2TPPS4 was explained by their different adsorption depth in the membrane.

Residence time of singlet oxygen in membranes.

Photodynamic therapy uses photosensitizers (PS) to kill cancer cells by generating reactive oxygen species - like singlet oxygen (SO) - upon illumination with visible light. PS membrane anchoring augments local SO concentration, which in turn increases photodynamic efficiency. The latter may suffer from SO's escape into the aqueous solution or premature quenching. Here we determined the time constants of SO escape and quenching by target molecules to be in the nanosecond range, the former being threefold longer. We confined PS and dipolar target molecules either to different membrane monolayers or to the same leaflet and assessed their abundance by fluorescence correlation spectroscopy or membrane surface potential measurements. The rate at which the contribution of the dipolar target molecules to membrane dipole potential vanished, served as a measure of the photo-oxidation rate. The solution of the reaction-diffusion equations did not indicate diffusional rate limitations. Nevertheless, reducing the PS-target distance increased photodynamic efficiency by preventing other SO susceptible moieties from protecting the target. Importantly, our analytical model revealed a fourfold difference between SO generation rates per molecule of the two used PSs. Such analysis of PS quantum yield in a membrane environment may help in designing better PSs.

Asynchronous rhythms of circulating conjugated and unconjugated bile acids in the modulation of human metabolism.

BACKGROUND AND OBJECTIVES: Bile acids (BAs) traversing the enterohepatic circulation (EHC) influence important metabolic pathways. By determining individual serum BAs in relation to markers of metabolic activity, we explored how diurnal variations in their EHC relate to hepatic metabolism in normal humans. METHODS: Serum BAs, fibroblast growth factor 19 (FGF19), lipoproteins, glucose/insulin and markers of cholesterol and BA syntheses were monitored for 32 h in 8 healthy males. Studies were conducted at basal state and during initiation of cholestyramine treatment, with and without atorvastatin pretreatment. Time series cross-correlation analysis, Bayesian structural model and Granger causality test were applied. RESULTS: Bile acids synthesis dominated daytime, and cholesterol production at night. Conjugated BAs peaked after food intake, with subsequent FGF19 elevations. BA synthesis was reduced following conjugated BA and FGF19 peaks. Cholestyramine reduced conjugated BAs and FGF19, and increased BA and cholesterol production; the latter effects attenuated by atorvastatin. The relative importance of FGF19 vs. conjugated BAs in this feedback inhibition could not be discriminated. Unconjugated BAs displayed one major peak late at night/early morning that was unrelated to FGF19 and BA synthesis, and abolished by cholestyramine. The normal suppression of serum triglycerides, glucose and insulin observed at night was attenuated by cholestyramine. CONCLUSIONS: Conjugated and unconjugated BAs have asynchronous rhythms of EHC in humans. Postprandial transintestinal flux of conjugated BAs increases circulating FGF19 levels and suppresses BA synthesis. Unconjugated BAs peak late at night, indicating a non-postprandial diurnal change in human gut microflora, the physiological implications of which warrants further study.

[Predicting the probability of development and progression of primary open angle glaucoma by regression modeling]. / Prognozirovanie veroiatnosti razvitiia i progressirovaniia pervichnoi otkrytougol'noi glaukomy metodom regressionnogo modelirovaniia.

Prediction of the clinical course of primary open-angle glaucoma (POAG) is one of the main directions in solving the problem of vision loss prevention and stabilization of the pathological process. Simple statistical methods of correlation analysis show the extent of each risk factor's impact, but do not indicate the total impact of these factors in personalized combinations. The relationships between the risk factors is subject to correlation and regression analysis. The regression equation represents the dependence of the mathematical expectation of the resulting sign on the combination of factor signs. PURPOSE: To develop a technique for predicting the probability of development and progression of primary open-angle glaucoma based on a personalized combination of risk factors by linear multivariate regression analysis. MATERIAL AND METHODS: The study included 66 patients (23 female and 43 male; 132 eyes) with newly diagnosed primary open-angle glaucoma. The control group consisted of 14 patients (8 male and 6 female). Standard ophthalmic examination was supplemented with biochemical study of lacrimal fluid. Concentration of matrix metalloproteinase MMP-2 and MMP-9 in tear fluid in both eyes was determined using 'sandwich' enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The study resulted in the development of regression equations and step-by-step multivariate logistic models that can help calculate the risk of development and progression of POAG. Those models are based on expert evaluation of clinical and instrumental indicators of hydrodynamic disturbances (coefficient of outflow ease - C, volume of intraocular fluid secretion - F, fluctuation of intraocular pressure), as well as personalized morphometric parameters of the retina (central retinal thickness in the macular area) and concentration of MMP-2 and MMP-9 in the tear film. CONCLUSION: The newly developed regression equations are highly informative and can be a reliable tool for studying of the influence vector and assessment of pathogenic potential of the independent risk factors in specific personalized combinations.

[Prediction of Bacterial and Archaeal Allergenicity with AllPred Program].

Nowadays, allergic disorders have become one of the most important social problems in the world. This can be related to the advent of new allergenic agents in the environment, as well as an increasing density of human contact with known allergens, including various proteins. Thus, the development of computer programs designed for the prediction of allergenic properties of proteins becomes one of the urgent tasks of mo dern bioinformatics. Previously we developed a web accessible Allpred Program (http://www-bionet.sscc.ru/ psd/cgi-bin/programs/Allpred/allpred.cgi) that allows users to assess the allergenicity of proteins by taking into account the characteristics of their spatial structure. In this paper, using AllPred, we predicted the allergenicity of proteins from 462 archaea and bacteria species for which a complete genome was available. The segregation of considered proteins on archaea and bacteria has shown that allergens are predicted more often among archaea than among bacteria. The division of these proteins into groups according to their intracellular localization has revealed that the majority of allergenic proteins were among the secreted proteins. The application of methods for predicting the level of gene expression of microorganisms based on DNA sequence analysis showed a statistically significant relationship between the expression level of the proteins and their allergenicity. This analysis has revealed that potentially allergenic proteins were more common among highly expressed proteins. Sorting microorganisms into the pathogenic and nonpathogenic groups has shown that pathogens can potentially be more allergenic because of a statistically significant greater number of allergens predicted among their proteins.

[Modern approaches to the diagnosis of precancerous pathology and early lung cancer]. / Sovremennye podkhody k diagnostike predopukholevoi patologii i rannego raka legkogo.

AIM: To assess the possibilities of modern diagnostic techniques to diagnose precancerous pathology and early central lung cancer. MATERIAL AND METHODS: Analysis of Russian and foreign publications for precancerous pathology and early lung cancer, results and comparison of various diagnostic techniques. RESULTS: Central lung cancer has a stepwise development with transformation of normal bronchial epithelium to hyperplastic followed by focal metaplasia, dysplasia, cancer in situ (CIS) and microinvasive cancer. Fluorography, chest X-ray, computed tomography, magnetic resonance imaging and sputum cytology examination are used to diagnose lung cancer. However, endoscopy plays a leading role in diagnosis of early central lung cancer which rapidly and effectively detects changes of tracheobronchial tree mucosa at the initial stages of carcinogenesis thanks to the use of modern techniques (spectral, autofluorescent and ZOOM - endoscopy).

Effect of New Derivatives of 2-Aminothiophene-3-Carboxylic Acid on Calcium-Activated Chloride Currents in Rat Neurons.

Using the patch-clamp method in the whole-cell configuration, we showed that the new derivatives of 2-aminothiophene-3-carboxylic acid, which were synthesized by us earlier, can both block (compound 1) and potentiate (compound 2) calcium-activated chloride currents in single rat cerebellar Purkinje cells.

DNA METHYLATION ANALYSIS DURING THE OPTIMIZATION OF Agrobacterium-MEDIATED TRANSFORMATION OF SOYBEAN.

Soybean is recognized as one of the plants which are very difficult to be transformed. Considering the low transformation efficiency of soybean, we aimed to determine the effect of 6-benzylaminopurine (6-BA), shoot induction time, and infection time of Agrobacterium on the clonal propagation of Glycine max. Results showed that 1.6 mg/L 6-BA could be optimal to promote the induction of adventitious shoots. An induction time of 15 d was considered optimal for the actual experiment involving soybean shoot induction. Agrobacterium was cultured until an OD600 = 0.8 was reached for an infection time of 30 min; this infection time may be optimal to promote soybean transformation. Whole genome DNA methylation was analyzed by high-performance liquid chromatography (HPLC)-assisted quantification, and DNA methylation result is consistent with the phenotypic data of shoot development. In addition, two methylation-related genes (Decrease in DNA methylation 1 and DNA methyltransferases chromomethylase 2) were analyzed to determine expression differences by qRT-PCR in the shoots that were developed under different experimental conditions. In general, the expression values of these genes were normally downregulated under the recommended experimental conditions of soybean regeneration. This study showed the overall methylation changes in the in vitro culture of soybean, as affected by several variable parameters, which is useful to promote the transformation efficiency of soybean.

Voltage-sensitive styryl dyes as singlet oxygen targets on the surface of bilayer lipid membrane.

Photosensitizers are widely used as photodynamic therapeutic agents killing cancer cells by photooxidation of their components. Development of new effective photosensitive molecules requires profound knowledge of possible targets for reactive oxygen species, especially for its singlet form. Here we studied photooxidation of voltage-sensitive styryl dyes (di-4-ANEPPS, di-8-ANEPPS, RH-421 and RH-237) by singlet oxygen on the surface of bilayer lipid membranes commonly used as cell membrane models. Oxidation was induced by irradiation of a photosensitizer (aluminum phthalocyanine tetrasulfonate) and monitored by the change of dipole potential on the surface of the membrane. We studied the drop of the dipole potential both in the case when the dye molecules were adsorbed on the same side of the lipid bilayer as the photosensitizer (cis-configuration) and in the case when they were adsorbed on the opposite side (trans-configuration). Based on a simple model, we determined the rate of oxidation of the dyes from the kinetics of change of the potential during and after irradiation. This rate is proportional to steady-state concentration of singlet oxygen in the membrane under irradiation. Comparison of the oxidation rates of various dyes reveals that compounds of ANEPPS series are more sensitive to singlet oxygen than RH type dyes, indicating that naphthalene group is primarily responsible for their oxidation.

[CFH gene polymorphism in primary open-angle glaucoma patients]. / Otsenka polimorfizma gena CFH u bol'nykh c pervichnoi otkrytougol'noi glaukomoi.

AIM: to study the CFH T402H polymorphism in glaucoma patients and controls. MATERIAL AND METHODS: Genetic analysis was performed in 68 patients with primary open-angle glaucoma (POAG) of various severity. The control group consisted of 30 participants. Venous whole blood samples were obtained. From them, leukocytes were isolated and human genomic DNA extracted for further PCR. RESULTS: None of the patients from either group was homozygous for the 402H allele. With ganglion cells death (i.e. at later stages of the disease), the percentage of homozygotes that carry no CFH polymorphism increases up to 65%, while that of heterozygotes decreases down to 35%. CONCLUSION: As shown, most of early and advanced POAG patients are heterozygotes. At these stages of the disease own ganglion cells are very likely to be damaged. Further progression, however, is associated with a gradual decrease in heterozygotes (down to 35%) due to a substantial loss of neuroepithelial cells and suppression of the autoimmune response which has lost its target.

Psychotropic Activity of New Fluorinated Derivatives of Tetrahydrocarbasoles.

Psychotropic properties of CA-7043× and CA-7050×, new fluorinated derivatives of tetrahydrocarbasoles, were examined on outbred CD1 mice and transgenic 5×FAD mice with Alzheimer disease. Both agents exerted cognitive-stimulating and anxiolytic effects in a dose of 5 mg/kg. In the new cage test, they retarded extinction of orientation and exploratory behavior. CA-7043× produced an anxiolytic effect on CD1 mice assessed in the open-field test and exerted cognitive-stimulating action in the new location test. In the same tests, CA-7050× demonstrated the cognitive-stimulating and anxiolytic effects on transgenic 5×FAD mice.

pH-Dependent Formation and Disintegration of the Influenza A Virus Protein Scaffold To Provide Tension for Membrane Fusion.

UNLABELLED: Influenza virus is taken up from a pH-neutral extracellular milieu into an endosome, whose contents then acidify, causing changes in the viral matrix protein (M1) that coats the inner monolayer of the viral lipid envelope. At a pH of ~6, M1 interacts with the viral ribonucleoprotein (RNP) in a putative priming stage; at this stage, the interactions of the M1 scaffold coating the lipid envelope are intact. The M1 coat disintegrates as acidification continues to a pH of ~5 to clear a physical path for the viral genome to transit from the viral interior to the cytoplasm. Here we investigated the physicochemical mechanism of M1's pH-dependent disintegration. In neutral media, the adsorption of M1 protein on the lipid bilayer was electrostatic in nature and reversible. The energy of the interaction of M1 molecules with each other in M1 dimers was about 10 times as weak as that of the interaction of M1 molecules with the lipid bilayer. Acidification drives conformational changes in M1 molecules due to changes in the M1 charge, leading to alterations in their electrostatic interactions. Dropping the pH from 7.1 to 6.0 did not disturb the M1 layer; dropping it lower partially desorbed M1 because of increased repulsion between M1 monomers still stuck to the membrane. Lipid vesicles coated with M1 demonstrated pH-dependent rupture of the vesicle membrane, presumably because of the tension generated by this repulsive force. Thus, the disruption of the vesicles coincident with M1 protein scaffold disintegration at pH 5 likely stretches the lipid membrane to the point of rupture, promoting fusion pore widening for RNP release. IMPORTANCE: Influenza remains a top killer of human beings throughout the world, in part because of the influenza virus's rapid binding to cells and its uptake into compartments hidden from the immune system. To attack the influenza virus during this time of hiding, we need to understand the physical forces that allow the internalized virus to infect the cell. In particular, we need to know how the protective coat of protein inside the viral surface reacts to the changes in acid that come soon after internalization. We found that acid makes the molecules of the protein coat push each other while they are still stuck to the virus, so that they would like to rip the membrane apart. This ripping force is known to promote membrane fusion, the process by which infection actually occurs.