[Perifocal edema and glymphatic system dysfunction: quantitative assessment based on diffusion tensor magnetic resonance imaging]. / Peritumoroznyi otek i disfunktsiya glimfaticheskoi sistemy golovnogo mozga: kolichestvennaya otsenka na osnove diffuzionno-tenzornoi MRT.

BACKGROUND: Pathogenesis of peritumoral cerebral edema is unclear and potentially associated with glymphatic system dysfunction. Diffusion tensor MRI (DT-MRI) with analysis of ALPS (Analysis along the Perivascular Space) index may be valuable for assessment of edema. This approach visualizes fluid flow along perivascular spaces of deep cerebral veins. OBJECTIVE: To assess glymphatic system function in supratentorial tumors and healthy volunteers using DT-MRI. MATERIAL AND METHODS: There were 52 patients (59% men) aged 43 (28-64) years with supratentorial tumors (meningioma - 20, grade 3-4 glioma - 15, metastases - 9, lymphoma - 8). Tumors and perifocal edema did not involve deep cerebral veins. The control group included 6 healthy volunteers aged 34-66 years. MRI protocol (Signa HDxt, 3 T) contained standard T1, T2, T2FLAIR, DWI and post-contrast T1 (3D BRAVO). DT-MRI had the following parameters: TR=10 000 ms, TEmin=102 ms, FOV=240 mm, isotropic voxel size 3×3×3 mm3, 60 directions of diffusion gradients. Measurements were carried out at b-factor 0 and 1000 s/mm2. Analysis was carried out in the ReadyView software. RESULTS: Right- and left-sided ALPS indices were similar in the control group (p=0.917). Perifocal edema (regardless of histological type of tumor) in the ipsilateral hemisphere was accompanied by significantly lower ALPS index (p<0.005), while these values in contralateral (intact) hemisphere were similar in both groups (p=0.7). CONCLUSION: We found significantly lower ALPS index in deep parts of the affected hemisphere in patients with perifocal edema. These data can indicate the role of glymphatic system dysfunction in pathogenesis of this pathology.

Results from the Baksan Experiment on Sterile Transitions (BEST).

The Baksan Experiment on Sterile Transitions (BEST) was designed to investigate the deficit of electron neutrinos ν_{e} observed in previous gallium-based radiochemical measurements with high-intensity neutrino sources, commonly referred to as the "gallium anomaly," which could be interpreted as evidence for oscillations between ν_{e} and sterile neutrino (ν_{s}) states. A 3.414-MCi ^{51}Cr ν_{e} source was placed at the center of two nested Ga volumes and measurements were made of the production of ^{71}Ge through the charged current reaction, ^{71}Ga(ν_{e},e^{-})^{71}Ge, at two average distances. The measured production rates for the inner and the outer targets, respectively, are [54.9_{-2.4}^{+2.5}(stat)±1.4(syst)] and [55.6_{-2.6}^{+2.7}(stat)±1.4(syst)] atoms of ^{71}Ge/d. The ratio (R) of the measured rate of ^{71}Ge production at each distance to the expected rate from the known cross section and experimental efficiencies are R_{in}=0.79±0.05 and R_{out}=0.77±0.05. The ratio of the outer to the inner result is 0.97±0.07, which is consistent with unity within uncertainty. The rates at each distance were found to be similar, but 20%-24% lower than expected, thus reaffirming the anomaly. These results are consistent with ν_{e}→ν_{s} oscillations with a relatively large Δm^{2} (>0.5 eV^{2}) and mixing sin^{2}2θ (≈0.4).

A novel thermophilic Aeribacillus bacteriophage AP45 isolated from the Valley of Geysers, Kamchatka: genome analysis suggests the existence of a new genus within the Siphoviridae family.

A novel thermophilic bacteriophage AP45 and its host strain Aeribacillus sp. CEMTC656 were isolated from the Valley of Geysers, Kamchatka Peninsula, Russia. Bacteriophage AP45 was identified as a member of the Siphoviridae family by electron microscopy. It showed high thermostability and had a slow cycle of reproduction. The AP45 genome had 51,606 base pairs (bp) and contained 71 open reading frames (ORFs), 40 of them encoding proteins of predicted function. Genes encoding DNA and RNA polymerases were not identified, indicating that AP45 used host polymerases. Based on the ORF65 encoding putative endolysin, the recombinant protein rAP45Lys was developed and its peptidoglycan-hydrolyzing activity was demonstrated. The AP45 genome exhibited limited identity to other phage sequences; the highest identity, 36%, was with the genome of the thermophilic Geobacillus myovirus D6E. The majority of putative proteins encoded by the AP45 genome had higher similarity to proteins from bacteria belonging to the Bacillaceae family, than to bacteriophages. In addition, more than half of the putative ORFs in the AP45 genome were highly similar to prophage sequences of A. pallidus strain 8m3, which was isolated in north-east China. The AP45 phage and revealed prophages might be members of a new genus belonging to the Siphoviridae family.

Isolation and characterization of a group of new Proteus bacteriophages.

Four lytic Proteus bacteriophages, PM75, PM85, PM93, and PM116, which are active against multi-drug-resistant strains of P. mirabilis, were isolated from cattle and poultry samples. According to electron microscopy data, all of the investigated phages belonged to the family Podoviridae. They all demonstrated lytic activity against sensitive strains of P. mirabilis, and three of the phages, PM85, PM93, and PM116, are potential candidates for use in antibacterial treatment. The genomes and putative proteins of bacteriophages PM85, PM93, and PM116 were similar to those of Proteus phage vB_PmiP_Pm5460 [KP890822], and the investigated phages formed a distinct clade within the genus Sp6virus, subfamily Autographivirinae. The genome sequence of phage PM75 was similar to that of a previously described Proteus phage, PM16 [KF319020], and both of them demonstrated low nucleotide sequence identity to the genomes of the other most similar phages, namely, Vibrio phage VP93, Pantoea phage LIMElight, and KP34-like bacteriophages. According to cluster analysis of the complete genome sequences and phylogenetic analysis of the proteins essential for their life cycle, phages PM75 and PM16 are distinct from other similar phages from the phiKMV supergroup and should be recognized as constituting a new genus, "Pm16virus", within the subfamily Autographivirinae.

Comparative Characteristics of Discrimination of S. enterica Isolates by Phagotyping Test and Dienes Test.

We propose an original methodological approach to discrimination of newly isolated Salmonella enterica strains with the use of Dienes test. Dienes test is used for identification of P. vulgaris and P. mirabilis strains. It consists in growth suppression by mobile bacterial strain cultures and the formation of a demarcation line (Dienes line) between the strains growing towards each other. Similarities and differences between salmonella phagotyping method and Dienes test-based discrimination of the strains are detected. The studied sample of salmonellas was divided into 12 phagotypes. Cluster analysis has shown that most of the salmonella strains could not be clusterized by both methods. Discrimination by different methods has shown that the largest clusters contain the same strains. Clusterization of salmonella strains by different methods shows moderate congruency. Rand index used for comparison of the results of the sample clusterization by different methods is 0.88. High heterogeneity of salmonella strains is presumably explained by heterogeneity of antagonism factors within the S. enterica species. Intraspecies antagonism is essential for limitation of the horizontal gene transfer in closely related strains and for increase of the genetic heterogeneity of salmonella population in the host.

[Female pelvic floor dysfunction from the perspectives of genetic studies].

Currently, despite the growing prevalence of female pelvic floor dysfunction, no consensus exists among researchers regarding its etiology and pathogenesis. There is no doubt, however, that this is a multifactorial disorder with a genetic predisposition. The risk for developing pelvic floor dysfunction is determined by the interaction of multiple additive genetic (mutations and/or polymorphic alleles) and environmental factors. This review of the world literature presents a rationale for searching specific molecular genetic factors shaping the structure of the genetic susceptibility to female pelvic floor dysfunction. The pelvic organ prolapse in women has been found to be associated with the rs1800012 polymorphism of the COL1A1 gene, genotype rs1800255-A/A of COL3A1 gene and the rs2228480 polymorphism of ESR1, although this data still controversial and need to be validated in the independent samples. The systematic accumulation of data, their reproduction in different populations and ethnic groups is necessary to further generalize the evidence on the pathogenesis and the functional significance of each gene variant.

[Association of polymorphism of 1800255 COL3A1 gene with pelvic organ prolapse and urinary incontinence in women: preliminary data].

RELEVANCE: Collagen type I and III have a significant role in the development of pelvic organ prolapse (POP) and urinary incontinence in women. The role of the COL3A1 gene polymorphism remains debatable. Some studies and meta-analyzes have found a direct correlation between genetic defects and POP, while other researchers have not confirmed this association. This study aimed to investigate the association of the 1800255 COL3A1 gene polymorphism with the development of POP and urinary incontinence in women. MATERIALS AND METHODS: The study group comprised 52 patients (mean age 64.4 years) with verified POP and stress urinary incontinence. The control group included 21 patients without pelvic floor dysfunction. Patients were comparable in age and had at least one or more risk factors for developing pelvic floor dysfunction. Exclusion criteria for both groups were Marfan and Ehlers-Danlos syndromes and a history of surgery for POP or incontinence (for the control group). In all women, saliva samples were collected to detect polymorphism at the rs1800255 locus of the COL3A1 gene. Genotyping was conducted by Sanger sequencing. RESULTS: In patients with isolated genital prolapse, homozygous polymorphism (AA) had a low sensitivity (0.06) but an extremely high specificity (0.95). Heterozygote (GA) had the sensitivity of 0.35, the specificity of 0.53, and the AUC of 0.44. For urinary incontinence by homozygote (AA), sensitivity was 0.08, specificity 0.96, and by heterozygote (GA) 0.45 and 0.63, respectively. For the combination of pelvic prolapse and urinary incontinence by homozygote (AA), sensitivity was 0.07, specificity 1.0, and heterozygote (GA) 0.41 and 0.62, respectively. CONCLUSION: Given the high specificity of the polymorphism at the rs1800255 locus of the COL3A1 gene, determined by the Sanger sequencing, it can be concluded that there is an association between this polymorphism and urinary incontinence and POP in women.

Lytic bacteriophage PM16 specific for Proteus mirabilis: a novel member of the genus Phikmvvirus.

Lytic Proteus phage PM16, isolated from human faeces, is a novel virus that is specific for Proteus mirabilis cells. Bacteriophage PM16 is characterized by high stability, a short latency period, large burst size and the occurrence of low phage resistance. Phage PM16 was classified as a member of the genus Phikmvvirus on the basis of genome organization, gene synteny, and protein sequences similarities. Within the genus Phikmvvirus, phage PM16 is grouped with Vibrio phage VP93, Pantoea phage LIMElight, Acinetobacter phage Petty, Enterobacter phage phiKDA1, and KP34-like bacteriophages. An investigation of the phage-cell interaction demonstrated that phage PM16 attached to the cell surface, not to the bacterial flagella. The study of P. mirabilis mutant cells obtained during the phage-resistant bacterial cell assay that were resistant to phage PM16 re-infection revealed a non-swarming phenotype, changes in membrane characteristics, and the absence of flagella. Presumably, the resistance of non-swarming P. mirabilis cells to phage PM16 re-infection is determined by changes in membrane macromolecular composition and is associated with the absence of flagella and a non-swarming phenotype.

[PHARMACOLOGICAL CORRECTION OF APOPTOSIS LEVEL OF CORTICAL NEURONS IN AGED HER2/NEU TRANSGENIC MICE].

Neurodegenerative changes and neuronal death are the basis for development of the nervous system aging. We investigated the mechanism of apoptosis of the sensorimotor cortex neurons of transgenic mice HER2/neu during aging, changes in the cortex function and the participation of exogenous neurometabolites (cytoflavin, piracetam) in regulation of neuronal death and locomotor and psycho-emotional status of mice. The level of apoptosis and expression of apoptosis markers (TUNEL, immunohistochemistry, Western blotting) in HER2/neu transgenic mice as compared to wild type mice (FBV line) were determined. In aging FBV mice the basal activity was shown to decrease and anxiety to increase correlating with the high level of neuronal apoptosis. We identified behavioral characteristics of transgenic HER2/neu mice and found that their low basal activity does not change with aging. Previously we have shown that in this strain of mice the apoptosis level is low, without any age-related changes, due to the suppression, first of all, of the p53-dependent pathway by HER2 (tyrosine kinase receptor) overexpression. Cytoflavin and piracetam were revealed to possess a marked neuroprotective effect, preserving and restoring functions of the nervous system (improving locomotion and psychological status) in both strains of mice. The effect of neurometabolites studied on neuronal apoptosis is ambiguous. In case of its low level it is a moderate stumulation of apoptosis via the external p53-dependent pathways with activation of caspase-3 in transgenic HER2/neu mice with high carcinogenesis level that can possibly prevent tumor development. On the contrary, in old wild-type animals we observed a significant decrease of age-dependent apoptosis level (by stimulating expression of the anti-apoptotic protein Mcl-1), which prevents neurodegeneration.

Teichulosonic acid, an anionic polymer of a new class from the cell wall of Actinoplanes utahensis VKM Ac-674(T).

The cell wall of Actinoplanes utahensis VKM Ac-674(T) contains two anionic polymers: teichoic acid 1,3-poly(glycerol phosphate) that is widespread in cell walls of Gram-positive bacteria; and a unique teichulosonic acid belonging to a new class of bioglycans described only in microorganisms of the Actinomycetales order. The latter polymer contains residues of di-N-acyl derivative of sialic acid-like monosaccharide - 5,7-diamino-3,5,7,9-tetradeoxy-L-glycero-ß-L-manno-non-2-ulosonic or pseudaminic acid (Pse) which bears the N-(3,4-dihydroxybutanoyl) group (Dhb) at C7. This polymer has irregular structure and consists of fragments of two types, which differ in substitution of the Dhb residues at O4 either with ß-D-glucopyranose or with ß-Pse residues. Most of the ß-Pse residues (~80%) are glycosylated at position 4 with α-D-galactopyranose residues in both types of fragments. The glucose, galactose, and Dhb residues are partly O-acetylated. The structures of the polymers were established by chemical and NMR spectroscopy methods.

Teichuronic and teichulosonic acids of actinomycetes.

The subject of the present review is the structural diversity and abundance of cell wall teichuronic and teichulosonic acids of representatives of the order Actinomycetales. Recently found teichulosonic acids are a new class of natural glycopolymers with ald-2-ulosonic acid residues: Kdn (3-deoxy-D-glycero-D-galacto-non-2-ulosonic acid) or di-N-acyl derivatives of Pse (5,7-diamino-3,5,7,9-tetradeoxy-L-glycero-L-manno-non-2-ulosonic or pseudaminic acid) as the obligatory component. The structures of teichuronic and teichulosonic acids are presented. Data are summarized on the occurrence of the glycopolymers of different nature in the cell wall of the studied actinomycetes. The biological role of the glycopolymers and their possible taxonomic implication are discussed. The comprehensive tables given in the Supplement show (13)C NMR spectroscopic data of teichuronic and teichulosonic acids obtained by the authors.

Phosphate-containing cell wall polymers of bacilli.

Anionic phosphate-containing cell wall polymers of bacilli are represented by teichoic acids and poly(glycosyl 1-phosphates). Different locations of phosphodiester bonds in the main chain of teichoic acids as well as the nature and combination of the constituent structural elements underlie their structural diversity. Currently, the structures of teichoic acids of bacilli can be classified into three types, viz. poly(polyol phosphates) with glycerol or ribitol as the polyol; poly(glycosylpolyol phosphates), mainly glycerol-containing polymers; and poly(acylglycosylglycerol phosphate), in which the components are covalently linked through glycosidic, phosphodiester, and amide bonds. In addition to teichoic acids, poly(glycosyl 1-phosphates) with mono- and disaccharide residues in the repeating units have been detected in cell walls of several Bacillus subtilis and Bacillus pumilus strains. The known structures of teichoic acids and poly(glycosyl 1-phosphates) of B. subtilis, B. atrophaeus, B. licheniformis, B. pumilus, B. stearothermophilus, B. coagulans, B. cereus as well as oligomers that link the polymers to peptidoglycan are surveyed. The reported data on the structures of phosphate-containing polymers of different strains of B. subtilis suggest heterogeneity of the species and may be of interest for the taxonomy of bacilli to allow differentiation of closely related organisms according to the "structures and composition of cell wall polymers" criterion.

Heterogeneous set of cell wall teichoic acids in strains of Bacillus subtilis VKM B-760 and VKM B-764.

Cell walls of Bacillus subtilis VKM B-760 and VKM B-764 are characterized by heterogeneous composition of teichoic acids. Polymer I with structure -6)-beta-D-Galp-(1-->1)-sn-Gro-(3-P-, polymer II with structure -6)-alpha-D-Glcp-(1-->1)-sn-Gro-(3-P-, and a small amount of unsubstituted 1,3-poly(glycerol phosphate) were detected in strain VKM B-760. Strain VKM B-764 contains an analogous set of teichoic acids, but a characteristic feature of polymer II is the presence of disubstituted glycerol residue with alpha-glucopyranose localization in the integral chain at C-1 hydroxyl and beta-glucopyranose as a side branch at C-2 hydroxyl (polymer III): -6)-alpha-D-Glcp-(1-->1)-[beta-D-Glcp-(1-->2)]-sn-Gro-(3-P-. The structures of polymer I in bacilli and polymer III in Gram-positive bacteria are described for the first time. Teichoic acids were studied by chemical methods and on the basis of combined analysis of one-dimensional 1H-, 13C-, and (31)P-NMR spectra, homonuclear two-dimensional (1)H/(1)H COSY, TOCSY, and ROESY, and heteronuclear two-dimensional (1)H/(13)C gHSQC- and HMQC-TOCSY experiments. Simultaneous presence of several different structure teichoic acids in the bacillus cell walls as well as chemotaxonomical perspectives of the application of these polymers as species-specific markers for members of the Bacillus genus is discussed.

Carbohydrate-containing polymers of the cell wall of the thermophilic streptomycete Streptomyces thermoviolaceus subsp. thermoviolaceus VKM Ac-1857T.

Anionic polymers of the cell surface of a thermophilic streptomycete were investigated. The cell wall of Streptomyces thermoviolaceus subsp. thermoviolaceus VKM Ac-1857(T) was found to contain polymers with different structure: teichoic acid--1,3-poly(glycerol phosphate), disaccharide-1-phosphate polymer with repeating unit -6)-alpha-Galp-(1-->6)-alpha-GlcpNAc-P-, and polysaccharide without phosphate with repeating unit -->6)-alpha-GalpNAc-(1-->3)-beta-GalpNAc-(1-->. Disaccharide-1-phosphate and polysaccharide without phosphate have not been described earlier in prokaryotic cell walls.