Pollution impact on microbial communities composition in natural and anthropogenically modified soils of Southern Russia.

Metagenomic studies of soil microbocenoses are extremely relevant nowadays. The study of pollution impact on soil microbiomes is of particular interest. The structure of microbial communities in soils with different levels of pollution by polycyclic aromatic hydrocarbons (PAHs) and potentially toxic elements (PTEs) was studied. High bacterial biodiversity was found in all the studied soil samples, but its lowest values are found in soil samples taken on the territory of technogenically polluted Lake Atamanskoye. Assessment of soil pollution showed the highest content of polycyclic aromatic hydrocarbons (PAHs) and potentially toxic elements (PTEs) for the soils Lake Atamanskoye. The high content of pollutants negatively affects the abundance of representatives of the phyla Actinobacteria, Planctomycetes, Verrucomicrobia, and Nitrospirae. Such phyla as Proteobacteria, Candidate Divisions TM7, OD1, WPS-2, Chlamydiae, Cyanobacteria are characterized by positive direct correlation with the content of pollutants, especially with PAHs. A cooperative effect of decrease in the number of Actinobacteria and Proteobacteria with an increase in Armatimonadetes probably corresponds to PTEs contamination. The proportion of Candidate Division OD1, Chlamydiae, Cyanobacteria, and Candidate Division WPS-2 was increased in the soil microbiome under the influence of severe combined pollution. Pollutants negatively affect the abundance of dominant unclassified_o__Gaiellales and unclassified_o__WD2101 genera. Iamia, Salinibacterium, Arthrobacter, Kaistobacter, Thiobacillus genera are characterized by a low abundance, but they are presumably the most resistant to soil pollution. It was revealed that the level of soil pollution largely determines the composition and diversity of bacterial communities in the soils of the studied territories. Operating taxonomic units have been established that have prognostic value for assessing the state, level of soil pollution, and their biological safety.

Transcranial Photobiomodulation of Clearance of Beta-Amyloid from the Mouse Brain: Effects on the Meningeal Lymphatic Drainage and Blood Oxygen Saturation of the Brain.

Here, we demonstrate the therapeutic effects of transcranial photobiomodulation (tPBM, 1267 nm, 32 J/cm2, a 9-day course) in mice with the injected model of Alzheimer's disease (AD) associated with accumulation of beta-amyloid (Aß) in the brain resulting in neurocognitive deficit vs. the control group (CG) (the neurological severity score (NNS), AD 3.67 ± 0.58 vs. CG 1.00 ± 0.26%, p < 0.05) and mild cerebral hypoxia (AD 72 ± 6% vs. CG 97 ± 2%, p < 0.001). The course of tPBM improved neurocognitive status of mice with AD (NNS, AD 2.03 ± 0.14 vs. CG 1.00 ± 0.26, vs. 2.03 ± 0.14, p < 0.05) due to stimulation of clearance of Aß from the brain via the meningeal lymphatic vessels (the immunohistochemical and confocal data) and an increase in blood oxygen saturation of the brain tissues (the pulse oximetry data) till 85 ± 2%, p < 0.05. These results open breakthrough strategies for non-pharmacological therapy of AD and clearly demonstrate that tPBM might be a promising therapeutic target for preventing or delaying AD based on stimulation of oxygenation of the brain tissues and activation of clearance of toxic molecules via the cerebral lymphatics.

Mechanisms of Sound-Induced Opening of the Blood-Brain Barrier.

The blood-brain barrier (BBB) poses a significant challenge for drug delivery to the brain. The limitations of our knowledge about the nature of BBB explain the slow progress in the therapy of brain diseases and absence of methods for drug delivery to the brain in clinical practice. Here, we show that the BBB opens for high-molecular-weight compounds after exposure to loud sound (100 dB 370 Hz) in rats. The role of stress induced by loud sound and the systemic and molecular mechanisms behind it are discussed in the framework of the BBB. This opens an informative platform for novel fundamental knowledge about the nature of BBB and for the development of a noninvasive brain drug delivery technology.

Polycyclic aromatic hydrocarbons, antibiotic resistance genes, toxicity in the exposed to anthropogenic pressure soils of the Southern Russia.

The influence of anthropogenic pollution, particularly with polycyclic aromatic hydrocarbons (PAHs) on soil toxicity and spread of antibiotic resistance genes (ARGs) is extremely important nowadays. We studied 20 soil samples from a technogenically polluted site, municipal solid wastes (MSW) landfills, and rural settlements in the southwestern part of the Rostov Region of Russia. A close correlation was established between the results of biosensor testing for integral toxicity, the content of genes for the biodegradation of hydrocarbons, and the concentration of PAHs in soils. The relation between the quantitative content of ARGs and the qualitative and quantitative composition of PAHs has not been registered. Soils subjected to different types of the anthropogenic pressure differed in PAHs composition. The technogenic soils are the most polluted ones. These soils are enriched with 5 ring PAHs and carry the maximum variety of assayed ARGs, despite the fact that they do not receive household or medical waste.

Phenomenon of music-induced opening of the blood-brain barrier in healthy mice.

Music plays a more important role in our life than just being an entertainment. For example, it can be used as an anti-anxiety therapy of human and animals. However, the unsafe listening of loud music triggers hearing loss in millions of young people and professional musicians (rock, jazz and symphony orchestra) owing to exposure to damaging sound levels using personal audio devices or at noisy entertainment venues including nightclubs, discotheques, bars and concerts. Therefore, it is important to understand how loud music affects us. In this pioneering study on healthy mice, we discover that loud rock music below the safety threshold causes opening of the blood-brain barrier (OBBB), which plays a vital role in protecting the brain from viruses, bacteria and toxins. We clearly demonstrate that listening to loud music during 2 h in an intermittent adaptive regime is accompanied by delayed (1 h after music exposure) and short-lasting to (during 1-4 h) OBBB to low and high molecular weight compounds without cochlear and brain impairments. We present the systemic and molecular mechanisms responsible for music-induced OBBB. Finally, a revision of our traditional knowledge about the BBB nature and the novel strategies in optimizing of sound-mediated methods for brain drug delivery are discussed.

Meningeal Lymphatic Pathway of Brain Clearing From the Blood After Haemorrhagic Injuries.

This seems to be the time to gain new knowledge about the meningeal lymphatic system and a deeper understanding of its anatomy and physiology. Although it is known that the meningeal lymphatics present in the layers of the brain, limited information is available about the role of this system in brain function. Here, for the first time we clearly demonstrate that the meningeal lymphatic pathway is involved in brain clearing from the blood after intracranial hemorrhage associated with hypoxia and forms a connective bridge between interstitial, cerebral spinal fluid and peripheral lymphatics. We also show that the development of methods to stimulate meningeal lymph flow after hemorrhagic evidence in the brain might be a neuroprotective strategy for effective recovery of the brain after a cerebrovascular catastrophe.

EF-G-induced ribosome sliding along the noncoding mRNA.

Translational bypassing is a recoding event during which ribosomes slide over a noncoding region of the messenger RNA (mRNA) to synthesize one protein from two discontinuous reading frames. Structures in the mRNA orchestrate forward movement of the ribosome, but what causes ribosomes to start sliding remains unclear. Here, we show that elongation factor G (EF-G) triggers ribosome take-off by a pseudotranslocation event using a small mRNA stem-loop as an A-site transfer RNA mimic and requires hydrolysis of about two molecules of guanosine 5'-triphosphate per nucleotide of the noncoding gap. Bypassing ribosomes adopt a hyper-rotated conformation, also observed with ribosomes stalled by the SecM sequence, suggesting common ribosome dynamics during translation stalling. Our results demonstrate a new function of EF-G in promoting ribosome sliding along the mRNA, in contrast to codon-wise ribosome movement during canonical translation, and suggest a mechanism by which ribosomes could traverse untranslated parts of mRNAs.

Features of structural organization and expression regulation of malate dehydrogenase isoforms from Rhodobacter sphaeroides strain 2R.

Two isoforms of malate dehydrogenase (MDH), dimeric and tetrameric, have been found in the purple non-sulfur bacterium Rhodobacter sphaeroides strain 2R, devoid of the glyoxylate shunt, which assimilate acetate via the citramalate cycle. Inhibitory analysis showed that the 74-kDa protein is involved in tricarboxylic acid cycle, while the 148-kDa MDH takes part in the citramalate pathway. A single gene encoding synthesis of the isologous subunits of the MDH isoforms was found during molecular-biological investigations. The appearance in the studied bacterium of the tetrameric MDH isoform during growth in the presence of acetate is probably due to the increased level of mdh gene expression, revealed by the real-time PCR, the product of which in cooperation with the citramalate cycle enzymes plays an important role in acetate assimilation.

[Regulation of carbon flows in the tricarboxylic acid cycle-glyoxylate bypass system in Rhodopseudomonas palustris under different growth conditions].

The functional roles of the malate dehydrogenase (MDH) tetrameric and dimeric isoforms in the metabolism of the purple nonsulfur phototrophic bacterium Rhodopseudomonas palustris, strain f-8pt, was studied with the use of specific inhibitors. It was shown that the enzyme tetrameric form allows the functioning of the glyoxylate cycle and the dimeric form provides for the operation of the tricarboxylic acid cycle.

[Isolation and purification of malate dehydrogenase isoforms from phototrophic purple bacteria Rhodobacter sphaeroides and Rhodopseudomonas palustris].

A five-step procedure was used to obtain electrophoretically pure preparations of malate dehydrogenase (EC 1.1.1.37) from Rhodobacter sphaeroides and Rhodopseudomonas palustris. The procedure included extraction, ammonium sulfate fractionation, gel filtration, and ion exchange and gel permeation chromatography. The enzyme was found to exist in two isoforms, dimeric and tetrameric, formed by the oligomerization of identical subunits. The isoforms are assumed to be involved in different metabolic processes.

[Isolation and properties of malate dehydrogenase from meso- and thermophilic bacteria].

A scheme of purification of malate dehydrogenase from Macromonas bipunctata strain D-405 and Vulcanithermus medioatlanticus DSM 14978T was developed. This scheme was used to obtain electrophoretically homogeneous enzyme preparations of the mesophilic bacterium M. bipunctata (specific activity, 26.9 +/- 0.8 U/mg protein; yield, 10.9%) and the thermophilic bacterium V. medioatlanticus (specific activity, 5.0 +/- 0.2 U/mg protein; yield, 19.2%). Using these high-purity enzymatic preparations, the physicochemical and regulatory properties of malate dehydrogenase were studied and the differences in kinetic characteristics and thermal stability of the preparations were determined.

Physicochemical properties of malate dehydrogenase from the bacterium Rhodopseudomonas palustris strain f8pt.

Electrophoretically homogenous isoforms of malate dehydrogenase with different quaternary structure were prepared from Rhodopseudomonas palustris strain f8pt cultured photolithoheterotrophically on malate and acetate. By selective inhibition of the tricarboxylic acid cycle or glyoxylate cycle, it was shown that the dimeric isoform of the enzyme is responsible for Krebs cycle functioning and the tetrameric isoform is involved in functioning of the glyoxylate cycle.

[Catalytic autoantibodies--a new molecular instrument in cardiology and ophthalmology].

AIM: To develop a conceptual model of using catalytic autoantibodies as diagnostic and monitoring tools in organ-specific autoimmune disorders. MATERIAL AND METHODS: A total of 99 patients (56 males and 43 females aged 21-52 years) with autoimmune myocarditis (AM) and 198 patients (77 males and 121 females aged 8-79 years) with autoimmune uveitis (A U) participated in the study. AM patients were examined for anticardiomyosin and anti-DNA autoantibodies (ACM, ADNAab), AU patients - for autoantibodies to S-antigen, IRBP, redopsin, phosphocine, autoDNA. RESULTS: AM patients had double level of DNA-binding autoantibodies. In 1/3 of them there was hydrolysing DNA and cytotoxic activity. In AU patients maximal titers were in Behcet's disease, sympathic ophthalmia, generalized uveitis and viral uveitis. CONCLUSION: Autoantibodies with different specificity and function including DNA-abzymes can be additional diagnostic and prognostic markers.

[Prevalence of ischemic heart disease, basic risk factors, and efficacy of long-term multifactorial prophylaxis at work in some regions of Russia]. / Rasprostranennost' ishemicheskoi bolezni serdtsa, osnovnykh faktorov riska ee razvitiia i éffektivnost' mnogoletnei mnogofaktornoi profilaktiki na predpriiatiiakh v riade regionov Rossii.

AIM: To study prevalence of ischemic heart disease (IHD) and its various clinical forms depending on sex, age, profession including risk factors (RF) and their combination and efficiency of long-term multifactorial active prevention programs at enterprises in several regions of the Russian Federation. MATERIAL AND METHODS: 14,000 male and 20,969 female volunteers were observed in organized groups in three Russian cities (Cheboksary, Pskov, St-Petersburg). 8984 males and 14,515 females entered seven groups of outpatient follow-up and active long-term multifactorial prevention during 5-10 years. RESULTS: Risk factor correction produced a significant decrease in mean systolic and diastolic blood pressure, frequency and intensity of smoking, overweight, improved ECG parameters, increased number of the examinees free of risk factors; state of IHD patients improved. Overall mortality, IHD and stroke mortality, number of temporary disability days were significantly less in the prevention group. CONCLUSION: Active multifactorial "in office" prevention for 5 to 10 years reduced RF prevalence and intensity, quantity of days at sick-leave fell by 48.5%. The presence of IHD and risk factors in both groups increased overall mortality rates and cardiovascular (IHD and stroke) mortality rates at the beginning of the study. The multifactorial prevention of IHD and risk factors resulted in a significant reduction of overall mortality rates as well as cardiovascular mortality rates in groups of active prevention.

[Composition of lipid components of dry mixtures for doughnuts during the storage process]. / Sostoianie lipidnoi komponenty sukhikh smesei dlia ponchikov v protsesse khraneniia.

Changes in various indices of lipid components of dried doughnut mixtures during their joint or separate 3-month storage were studied. Methyl oleate oxidation model was used to determine the prooxidant properties of the initial mixture. The antioxidant activity, inhibition of oxidation, and inhibitory properties of lipids were shown to be enhanced during storage. The composition of phospholipids varied considerably due to changes in the degree of unsaturation of lipids in the mixture during storage. Joint storage of components resulted in a greater stability and better preservation of lipid components (as compared to their separate storage).

[Mechanism of chromosome loss after irradiation of mature Drosophila sperm]. / Mekhanizm poter' khromosom pri obluchenii zrelykh spermiev Drozofily

The frequency of radiation-induced chromosome losses is not connected with heterochromatic content but depends on the total chromosomal DNA content. This dependence is of the selective nature and appears as a result of the effect of dominant lethality of non-repaired euchromatic breaks. Simultaneous losses of the two chromosomes in one nucleus are not independent, because of the interaction of the heterochromatic breaks underlying these losses. The conclusion is made that the chromosome losses are involved in the exchange events accompanied by the centromere deletion.

[Number of chromosome breaks and the probability of break reunion during irradiation of mature Drosophila sperm]. / Chislo razryvov khromosom i veroiatnost' ikh vossoedineniia pri obluchenii zrelykh spermiev drozofily.

The dose-effect curves for half and full translocations induced in mature sperm with the break points within the same chromosomal region were obtained. Probability of reunion q and the number of breaks N that could be calculated from these curves varies within the range 0.83-0.69 and 0.011-0.078, respectively. The half and full translocations were induced under maternal effect of mus 104D1. In this case, q = 0.86 (for normal genotype 0.79) and N = 0.114 (for normal genotype 0.048). These figures show that the dose increase and the introduction of the mus 104 cause increase in the breaks number and only weak change in break reunion occurs. The method developed can be used for the search for mutations that interfere with break reunion.

[Sensitivity of bone marrow cells damaged by antitumor drugs to cytotoxic action of effectors of a normal spleen]. / Chuvstvitel'nost' povrezhdennykh tsitostatikami kletok kostnogo mozga k tsitotoksicheskomu deistviiu éffektorov normal'noi selezenki.

Different cytogenetic effects in bone marrow cells induced by antitumor drugs with different mechanisms of action was studied. The treatment of adriablastine causes the appearance of chromatid deletion, vinblastine-polyploid cells, cyclophosphamide-chromosomal and chromatid aberration in mice. It was shown that bone marrow cells with cytogenetic damage have altered susceptibility to normal spleen cells-effectors cytotoxic action.

[Early and late effects of the cytogenetic action of doxorubicin]. / Rannie i otdelannye éffekty tsitogeneticheskogo deistviia doksorubitsina.

Cytogenetic disorders in hemopoietic cells of the bone marrow were studied on mice CBA at early and late periods after exposure to MIDs of doxorubicin, an anthracycline antibiotic. It was shown that at the early period doxorubicin induced aberrations, mainly of the chromatid type, in the hemopoietic cells of the bone marrow. Instability of the genetic apparatus of the hemopoietic cells observed for 3 months of the experiment was likely to be the immediate cause of the disorders in hemopoiesis at the late periods after exposure to doxorubicin.

[Long-term consequences of the damaging effect of cytostatic drugs on hematopoiesis and lymphoid tissue]. / Problemy otdalennykh posledstvii povrezhdaiushchego deistviia tsitostaticheskikh preparatov na krovetvorenie i limfoidnuiu tkan'.

The evidence on the changes detectable in remote periods (at 1, 3, and 6 months) is presented. It shows that the quantitative and functional defects are retained in the hemopoietic and lymphoid tissues within 3-6 months after exposure to the effects of various cytostatic agents. These defects may be corrected by means of immunomodulators.