EEG biomarkers of activation of the lymphatic drainage system of the brain during sleep and opening of the blood-brain barrier.

The lymphatic drainage system of the brain (LDSB) is the removal of metabolites and wastes from its tissues. A dysfunction of LDSB is an important sign of aging, brain oncology, the Alzheimer's and Parkinson's diseases. The development of new strategies for diagnosis of LDSB injuries can improve prevention of age-related cerebral amyloid angiopathy, neurodegenerative and cerebrovascular diseases. There are two conditions, such as deep sleep and opening of the blood-brain-barrier (OBBB) associated with the LDSB activation. A promising candidate for measurement of LDSB could be electroencephalography (EEG). In this pilot study on rats, we tested the hypothesis, whether deep sleep and OBBB can be an informative platform for an effective extracting of information about the LDSB functions. Using the nonlinear analysis of EEG dynamics and machine learning technology, we discovered that the LDSB activation during OBBB and sleep is associated with similar changes in the EEG θ-activity. The OBBB causes the higher LDSB activation vs. sleep that is accompanied by specific changes in the low frequency EEG activity extracted by the power spectra analysis of the EEG dynamics combined with the coherence function. Thus, our findings demonstrate a link between neural activity associated with the LDSB activation during sleep and OBBB that is an important informative platform for extraction of the EEG-biomarkers of the LDSB activity. These results open new perspectives for the development of technology for the LDSB diagnostics that would open a novel era in the prognosis of brain diseases caused by the LDSB disorders, including OBBB.

Improving the efficacy of potato clonal micropropagation by inoculation with the rhizosphere bacteria Azospirillum baldaniorum Sp245 and Ochrobactrum cytisi IPA7.2.

Sustainable development of agriculture depends on the provision of quality seeds to the market. Inoculation with plant-growth-promoting rhizobacteria in in vitro culture can be used to improve the growth eff icacy and performance of microplants. We examined the effect of in vitro inoculation of microplants of the cultivars Nevsky and Kondor with the strains Azospirillum baldaniorum Sp245 and Ochrobactrum cytisi IPA7.2 separately and in combination. We examined the morphological variables of plant growth in in vitro culture and under ex vitro adaptation conditions; we also investigated the growth and performance of the plants in the greenhouse. The dependence of the inoculation eff icacy on potato genotype, growth stage, and inoculum composition was ascertained throughout the experiment. In vitro, A. baldaniorum Sp245 alone and in combination with O. cytisi IPA7.2 promoted the formation of roots on the microplants of both cultivars and the growth of Nevsky shoots. During plant growth ex vitro, all growth variables of the Nevsky microplants were promoted by O. cytisi IPA7.2 alone and in combination with A. baldaniorum Sp245. In both cultivars grown in the greenhouse, shoot growth was promoted in most inoculation treatments. The survival ability of the Nevsky microplants in the greenhouse increased 1.7-fold under the effect of simultaneous inoculation. Inoculation of microplants with a combination of A. baldaniorum Sp245 and O. cytisi IPA7.2 increased the number of Nevsky minitubers 1.5-fold and the number of Kondor minitubers 3.5-fold. Inoculation with the tested strains can be used to promote the growth of microplants and increase the yield of minitubers in potato seed breeding for the production of healthy planting material.

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.

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.

[Threatened paradoxical embolism, massive occlusion of pulmonary artery: risk stratification, treatment policy]. / Ugrozhaiushchaia paradoksal'naia émboliia, massivnaia okkliuziia legochnoi arterii: stratifikatsiia riska, taktika lecheniia.

Described in the article is a clinical case report regarding a male patient presenting with pulmonary thromboembolism, with a floating thrombus in the common femoral vein, in the right atrium, prolapsing into the right ventricle and propagating through a patent foramen ovale to the left atrium, thus being a threat of paradoxical embolism. The echocardiography findings demonstrated the following: mean pressure in the pulmonary artery amounting to 56 mm Hg, dilatation of the right atrium and right ventricle. The patient was subjected to simultaneous thrombectomy from the common femoral artery, from the right, left atria and pulmonary artery in conditions of cardioplegia, as well as ligation of the superficial femoral artery. The postoperative period proved uneventful. The patient was discharged on postoperative day 15, with pressure in the pulmonary artery amounting to 38 mm Hg. Besides, analysed herein are the contemporary literature data, clinical guidelines, and opinions of experts concerning treatment policy in this complex pathology.

[Recipe and application of new oxygen cocktail with high protein content in nutrition of cardiological patients].

The aims of this study was to develop recipe composition and to evaluate the use of new oxygen cocktail with high protein content in the dietary therapy of cardiological patients. Objects of the study were: the control sample - an oxygen-containing product prepared using dairy whey, fruit and berry juice, highly esterified pectin; experimental samples - oxygen-containing products, which differed from the control sample by additional introduction of whey protein hydrolysate. Experimental samples have been modified by adding to them whey protein hydrolysate in the amount of 1-3% from the total weight of composition. Technological scheme to produce protein-carbohydrate basis with high content of protein 3% has been developed, parameters of the production process were worked out. Analysis of product chemical composition has shown that 100 g contained 3.4-3.6 g of protein, 0.2-0.3 g of fat, 6.0-8.0 g of carbohydrates. Food value of the product made up 34-46 kcal (162-196 kJ). Assessment of effectiveness of new oxygen-containing product in the diet in conditions of cardiological hospital was carried out. 30 patients aged 60-75 years were included in local open prospective study, meeting the following criteria: patients with chronic heart failure I-IIА stage I-II functional classes, were hospitalized in the cardiology department, not having contraindications to enteral oxygen therapy and signed an informed consent form. In combination with standard therapy patients received new oxygenated product with high content of protein in the dose 250 ml (from 100 g of the basis) daily for 10 days during the second breakfast. By the end of the observation period, according to results of the survey, the psycho-emotional state of patients improved. It has been found that the developed oxygen-containing product with high protein content in combination with a standard diet and drug therapy of the disease was well tolerated by patients.

Erratum: Prediction for a Four-Neutron Resonance [Phys. Rev. Lett. 117, 182502 (2016)].

This corrects the article DOI: 10.1103/PhysRevLett.117.182502.

Prediction for a Four-Neutron Resonance.

We utilize various ab initio approaches to search for a low-lying resonance in the four-neutron (4n) system using the JISP16 realistic NN interaction. Our most accurate prediction is obtained using a J-matrix extension of the no-core shell model and suggests a 4n resonant state at an energy near E_{r}=0.8 MeV with a width of approximately Γ=1.4 MeV.

[Immunochemical Detection of Azospirilla in Soil with Genus-Specific Antibodies].

Immunoelectrophoresis and immunodiffusion analysis with antibodies to whole intact cells of the type strain of nitrogen-fixing soil bacteria Azospirillum brasilense Sp7 revealed at least three conservative surface immunogenic proteins of azospirilla. Cross-reactions with these proteins made it possible to use the above antibodies for detection of azospirilla as a genus-specific probe conjugated with horseradish peroxidase as an enzymatic label. Direct immune-enzyme analysis of soil suspensions (typical chernozem, Saratov oblast) confirmed applicability of the conjugates based on genus-specific antibodies to the surface proteins of azospirilla for direct detection of this bacterial genus in environmental samples. These results provide a basis for broad application of this method for analysis of Azospirillum occurrence in soil.

[Application of the group theory to description of biological objects pseudosymmetry].

The application of the group theory to description of biological objects pseudosymmetry is introduced and substantiated by the example of rotatory symmetry of actinomorphic and zygomorphic flowers. Problems of biosymmetrics terminology are considered; point symmetry elements are characterized as being applied to description of flower symmetry; central constructs of the group theory are stated. Application of the Curie principle to biological objects is outlined. Algorithms for quantitative assessment of flower pseudosymmetry are given; the description is made of flower pseudosymmetry in the terms of the group theory, including evolutionary aspect. The conclusion is made that adaptation of the group theory to description of biological objects symmetry (biosymmetrics) is important not only in fundamental respect but also as a tool of inter-disciplinary mutual understanding between biologists, physicists, crystallographers and other specialists whose communicative language is mathematics.

[The effect of mutations in the synthesis of lipopolysaccharides and calcofluor-binding polysaccharides on biofilm formation by Azospirillum brasilense].

The thickness and antigenic properties of biofilms produced by Azospirillum brasilense Sp245 and its mutants deficient in the synthesis of lipopolysaccharides (Lps) and calcofluor-binding polysaccharides (CBPS) at the interface between water and hydrophilic or hydrophobic solid surfaces were compared. The mutants deficient in acidic LpsI synthesis produce thicker biofilms on hydrophilic surfaces. Biofilms produced on hydrophobic surfaces by bacteria that are unable to synthesize CBPS are less pronounced. Defects in CBPS production in Azospirillum mutants with impaired flagellar motility can cause adverse effects on the cell ability to attach to hydrophobic and hydrophilic surfaces. The loss of the neutral LpsII antigen by the mutants capable of producing CBPS does not affect their behavior on hydrophobic surfaces, which is probably due to the compensatory increase in the total polysaccharide production. The fundamental change in the Lps structure correlates with the activation of biofilm formation by the relevant mutants on hydrophilic and hydrophobic surfaces.

[The study of mycolytic properties of aerobic spore-forming bacteria producing extracellular chitinases].

The mycolytic activity of 27 strains of antagonistic bacilli belonging to two taxonomic groups (18 strains of Bacillus subtilis and 9 strains of Paenibacillus ehimensis) capable of induced synthesis of chitinolytic enzymes was studied. Most of the B. subtilis strains neither displayed visible mycolytic effects on the phytopathogenic fungus Bipolaris sorokiniana in vitro, nor produced chitinases in the presence of an auto-claved mycelium. On the contrary, P. ehimensis strains grown under conditions favorable for induction of chitinases and other hydrolases exhibited a pronounced lytic effect on B. sorokiniana and actively grew by utilizing mycelium as the sole source of carbon and nitrogen. Comparison of the mycolytic activities of extracellular hydrolases in the studied strains demonstrated low correlation between chitinase production and the ability of the strains to degrade the cell walls of B. sorokiniana. Characterization of enzyme profiles in the studied strains revealed that beta-1,3-glucanase was a more significant factor than chitinase for determining the mycolytic potential of bacteria and their ability to utilize the mycelium of phytopathogenic fungi as a growth substrate.

[Detection of a surface sheath on Azospirillum brasilense polar flagellum].

The presence of a polysaccharide sheath on the surface of the polar flagellum of Azospirillum brasilense was revealed by immunoelectron microscopy and immunodiffusion analysis with strain-specific antibodies to lipopolysaccharides (LPS). The antigenic identity of A. brasilense Sp245 sheath material and one of the two O-specific polysaccharides of its somatic LPS was demonstrated. The screening effect of the sheath in respect to flagellin was determined by agglutination tests and by the inhibition of azospirilla motility in liquid and semisolid agarized media caused by strain-specific antibodies to LPS; no pronounced effect of genus-specific antibodies to flagellin was observed.

[Isolation and characterisation of chitosanase from Bacillus sp. 739 strain]. / Vydelenie i svoistva khitozanazy shtamma Bacillus sp. 739.

The specific nature of the chitosanase activity of the strain Bacillus sp. 739 has been determined. Maximum enzyme activity was observed in a medium containing the biomass of the fruiting bodies of the fungus Macrolepiota procera. The chitosanase was purified to homogeneity using chromatography on DEAE-Sephadex A-50 and Toyopearl HW-50. The molecular weight of the enzyme, assessed by electrophoresis (the Laemmli procedure) approximated 46 kDa. Temperature and pH optima of the purified chitosanase were in the ranges 45-55 degrees C and 6.0-6.5, respectively. Time to half-maximum inactivation of the enzyme at 50 degrees C was equal to 1 h. With colloidal chitosan as the substrate, the value of K(M) of the purified chitosanase was equal to 25 mg/ml. The enzyme also exhibited a weak ability to hydrolyze colloidal chitin.

[Chitinolytic activity of Bacillus Cohn.--phytopathogenic fungus antagonist]. / Khitinoliticheskaia aktivnost' bakterii Bacillus Cohn.-- antagonistov fitopatogennykh gribov.

Among the 70 tested Bacillus spp. strains antagonistic to phytopathogenic fungi, 19 were found to possess chitinolytic activity when grown on solid media with 0.5% colloidal chitin. The chitinolytic activity of almost all of these 19 strains grown in liquid cultures ranged from 0.1 to 0.3 U/ml. One of the 19 strains exhibited exochitinase activity. In addition to chitinase, two strains also produced chitosanase and one strain, beta-1,3-glucanase. No correlation was found between the antifungal activity of the bacillar strains studied and their ability to synthesize extracellular chitinase. Among the 19 chitinolytic strains, the correlation between these parameters was also low (r x,y = 0.45), although the enzymatic preparations of most of these strains inhibited the growth of the phytopathogenic fungus Helminthosporium sativum.

[Protein and peptide factors from Bacillus sp.739 inhibit the growth of phytopathogenic fungi]. / Belkovye i peptidnye factory Bacillus sp.739--ingibitory rosta fitopatogennykh gribov.

Thermolabile peptides inhibiting the growth of Helminthosporium sativum, a facultative phytopathogen, have been isolated from the low-molecular-weight fraction of extracellular metabolites of the strain Bacillus sp. 739. Paper chromatography of the fraction, followed by bioautography, revealed the presence of three components exhibiting antifungal activity. These components were separated by gel chromatography on Toyopearl HW-40. SDS-PAGE (the Laemmli procedure) demonstrated that only one component was a protein (MW, approximately 14 kDa). The other two substances were polypeptides with molecular weights less than 6 kDa each. The protein factor inhibited the growth of H. sativum with a minimum effective concentration of 0.1 to 0.2 mg/ml.