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76 result(s) for "Lebedinsky, A. S."
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Perspectives of treatment of anemias with cells of fetal liver, immobilized in macroporous alginate-gelatin carriers
Aim of the work was to study possibility of erythropoiesis stimulation by transplantation of fetal liver cells, seeded into macro­porous carriers to the rats with post-hemorrhargic anemia, induced by 70% hepatectomy. Fetal liver cells (FLC) were isolated from fetuses of rats with 15 days’ gestation and were cryopreserved. Decryopreserved FLC were seeded into macroporous spongy alginate-gelatin scaffolds, which were covered by alginate capsule and implanted into omentum of rats with modeled liver insufficiency. It was shown that fetal liver cells, immobilized in macroporous scaffolds after implantation have positive effect on red blood count and hemoglobin content, indicating that this approach is promising for the development of new methods of anemia treatment.
Form III RubisCO-mediated transaldolase variant of the Calvin cycle in a chemolithoautotrophic bacterium
The Calvin–Benson–Bassham (CBB) cycle assimilates CO₂ for the primary production of organic matter in all plants and algae, as well as in some autotrophic bacteria. The key enzyme of the CBB cycle, ribulose-bisphosphate carboxylase/oxygenase (RubisCO), is a main determinant of de novo organic matter production on Earth. Of the three carboxylating forms of RubisCO, forms I and II participate in autotrophy, and form III so far has been associated only with nucleotide and nucleoside metabolism. Here, we report that form III RubisCO functions in the CBB cycle in the thermophilic chemolithoautotrophic bacterium Thermodesulfobium acidiphilum, a phylum-level lineage representative. We further show that autotrophic CO₂ fixation in T. acidiphilum is accomplished via the transaldolase variant of the CBB cycle, which has not been previously demonstrated experimentally and has been considered unlikely to occur. Thus, this work reveals a distinct form of the key pathway of CO₂ fixation.
Diversity and ecophysiological features of thermophilic carboxydotrophic anaerobes
Both natural and anthropogenic hot environments contain appreciable levels of carbon monoxide (CO). Anaerobic microbial communities play an important role in CO conversion in such environments. CO is involved in a number of redox reactions. It is biotransformed by thermophilic methanogens, acetogens, hydrogenogens, sulfate reducers, and ferric iron reducers. Most thermophilic CO-oxidizing anaerobes have diverse metabolic capacities, but two hydrogenogenic species are obligate carboxydotrophs. Among known thermophilic carboxydotrophic anaerobes, hydrogenogens are most numerous, and based on available data they are most important in CO biotransformation in hot environments.
A phase 2 randomized dose-ranging study of the JAK2-selective inhibitor fedratinib (SAR302503) in patients with myelofibrosis
In this phase 2 open-label randomized study, 31 patients with intermediate-2 or high-risk myelofibrosis received fedratinib 300, 400 or 500 mg once daily in consecutive 4-week cycles. Mean spleen volume reductions at 12 weeks (primary end point) were 30.3% (300 mg), 33.1% (400 mg) and 43.3% (500 mg). Spleen response rates (patients achieving ⩾35% spleen reduction) at 12/24 weeks were 30%/30% (300 mg), 50%/60% (400 mg) and 64%/55% (500 mg), respectively. By 4 weeks, improvements in myelofibrosis (MF)-associated symptoms were observed. At 48 weeks, 68% of patients remained on fedratinib and 16% had discontinued because of adverse events (AEs). Common grade 3/4 AEs were anemia (58%), fatigue (13%), diarrhea (13%), vomiting (10%) and nausea (6%). Serious AEs included one case of reversible hepatic failure and one case of Wernicke’s encephalopathy (after analysis cutoff). Fedratinib treatment led to reduced STAT3 phosphorylation but no meaningful change in JAK2 V617F allele burden. Significant modulation ( P< 0.05, adjusted for multiple comparisons) of 28 cytokines was observed, many of which correlated with spleen reduction. These data confirm the clinical activity of fedratinib in MF. After the analysis cutoff date, additional reports of Wernicke's encephalopathy in other fedratinib trials led to discontinuation of the sponsored clinical development program.
Mechanisms of Control by Pseudomonas Fluorescens of Barley Root Rot Caused by Fusarium culmorum
In this paper, we determined the reason that the intensity of barley fusarium root rot caused by Fusarium culmorum 30 decreases in the presence of the rhizobacterium Pseudomonas fluorescens 2137, if there is no obvious decrease in the amount of fungus in the roots in the presence of the bacterium. It has been suggested that (1) the presence of rhizobacterium stimulates the defense reactions in barley and (2) rhizobacterium reduces the production of trichothecene toxins by F. culmorum 30, a known factor of aggressiveness of the fungus. The responses of barley to the colonization of its roots by fungus and bacteria were studied in sterile vermiculite for 11 days according to the intensity of expression of the LOX, PAL, PR4 , and PR1 genes. The production of F. culmorum 30 trichothecene toxins was evaluated by the expression level of the TRI13 gene. As a result, it was found that P. fluorescens 2137 induced the expression of all studied defense genes in diurnal barley roots, but only in the presence of F. culmorum 30. In the presence of the bacterium, the expression level of the TRI13 gene did not decrease; however, a decrease in the number of diseased plants suggests that P. fluorescens 2137 is capable of detoxifying trichothecene toxins produced by the fungus or inducing this ability in barley.
Analysis of three genomes within the thermophilic bacterial species Caldanaerobacter subterraneus with a focus on carbon monoxide dehydrogenase evolution and hydrolase diversity
Background The Caldanaerobacter subterraneus species includes thermophilic fermentative bacteria able to grow on carbohydrates substrates with acetate and L-alanine as the main products. In this study, comprehensive analysis of three genomes of C. subterraneus s ubspecies was carried in order to identify genes encoding key metabolic enzymes and to document the genomic basis for the evolution of these organisms. Methods Average nucleotide identity and in silico DNA relatedness were estimated for the studied C. subterraneus genomes. Genome synteny was evaluated using R2CAT software. Protein conservation was analyzed using mGenome Subtractor. Horizontal gene transfer was predicted through the GOHTAM pipeline (using tetranucleotide composition) and phylogenetic analyses (by maximum likelihood). Hydrolases were identified through the MEROPS and CAZy platforms. Results The three genomes of C. subterraneus showed high similarity, although there are substantial differences in their gene composition and organization. Each subspecies possesses a gene cluster encoding a carbon monoxide dehydrogenase (CODH) and an energy converting hydrogenase (ECH). The CODH gene is associated with an operon that resembles the Escherichia coli hydrogenase hyc / hyf operons, a novel genetic context distinct from that found in archetypical hydrogenogenic carboxydotrophs. Apart from the CODH-associated hydrogenase, these bacteria also contain other hydrogenases, encoded by ech and hyd genes. An Mbx ferredoxin:NADP oxidoreductase homolog similar to that originally described in the archaeon Pyrococcus furiosus was uniquely encoded in the C. subterraneus subsp. yonseiensis genome. Compositional analysis demonstrated that some genes of the CODH-ECH and mbx operons present distinct sequence patterns in relation to the majority of the other genes of each genome. Phylogenetic reconstructions of the genes from these operons and those from the ech operon are incongruent to the species tree. Notably, the cooS gene of C. subterraneus subsp. pacificus and its homologs in C. subterraneus subsp. tengcongensis and C. subterraneus subsp. yonseiensis form distinct clades. The strains have diverse hydrolytic enzymes and they appear to be proteolytic and glycolytic. Divergent glycosidases from 14 families, among them amylases, chitinases, alpha-glucosidases, beta-glucosidases, and cellulases, were identified. Each of the three genomes also contains around 100 proteases from 50 subfamilies, as well about ten different esterases. Conclusions Genomic information suggests that multiple horizontal gene transfers conferred the adaptation of C. subterraneus subspecies to extreme niches throughout the carbon monoxide utilization and hydrogen production. The variety of hydrolases found in their genomes indicate the versatility of the species in obtaining energy and carbon from diverse substrates, therefore these organisms constitute a remarkable resource of enzymes with biotechnological potential.
Microbial life in Bourlyashchy, the hottest thermal pool of Uzon Caldera, Kamchatka
Bourlyashchy is the largest and hottest pool in the Uzon Caldera, located in the territory of Kronotsky Nature Reserve, Kamchatka, Russia, with sediment surface temperatures at the margins ranging from 86 to 97 °C, and pH from 6.0 to 7.0. The microbial communities of the pool water and sediments were studied comprehensively from 2005 to 2014. Radioisotopic tracer studies revealed the processes of inorganic carbon assimilation, sulfate reduction, lithotrophic methanogenesis and potentially very active process of acetate oxidation to CO 2 . The total number of microbial cells in water was different in different years ranging from 5.2 to 7.0 × 10 6 ; in sediments, it changed from year to year between 6.3 × 10 6 and 1.75 × 10 8 , increasing with a decrease in temperature. FISH with Archaea - and Bacteria -specific probes showed that the share of Bacteria differed with year, changing from 34 to 71 %. According to 16S rRNA gene pyrosequencing data, lithoautotrophs ( Aquificales and Thermoproteales ) predominated in water samples, while in sediments they shared the niche with organotrophic Crenarchaeota, Korarchaeota , and bacteria of the genus Caldimicrobium (phylum Thermodesulfobacteria ). The majority of organisms in water belonged to cultivated orders of prokaryotes; the only large uncultured group was that representing a novel order in class Thermoprotei . In sediments, unclassified Aquificeae comprised a significant part of the bacterial population. Thus, we showed that the hottest of the terrestrial hot pools studied contains numerous and active microbial populations where Bacteria represent a significant part of the microbial community, and planktonic and sediment populations differ in both composition and function.
Dissimilatory sulfate reduction in the archaeon ‘Candidatus Vulcanisaeta moutnovskia’ sheds light on the evolution of sulfur metabolism
Dissimilatory sulfate reduction (DSR)—an important reaction in the biogeochemical sulfur cycle—has been dated to the Palaeoarchaean using geological evidence, but its evolutionary history is poorly understood. Several lineages of bacteria carry out DSR, but in archaea only Archaeoglobus , which acquired DSR genes from bacteria, has been proven to catalyse this reaction. We investigated substantial rates of sulfate reduction in acidic hyperthermal terrestrial springs of the Kamchatka Peninsula and attributed DSR in this environment to Crenarchaeota in the Vulcanisaeta genus. Community profiling, coupled with radioisotope and growth experiments and proteomics, confirmed DSR by ‘ Candidatus Vulcanisaeta moutnovskia’, which has all of the required genes. Other cultivated Thermoproteaceae were briefly reported to use sulfate for respiration but we were unable to detect DSR in these isolates. Phylogenetic studies suggest that DSR is rare in archaea and that it originated in Vulcanisaeta , independent of Archaeoglobus , by separate acquisition of qmoABC genes phylogenetically related to bacterial hdrA genes. Dissimilatory sulfate reduction in archaeon ‘ Candidatus Vulcanisaeta moutnovskia’ is distinct from bacterial sulfate reduction and sheds light on the evolution of sulfur metabolism.
Relation of threshold levels fatigue crack development in low-alloy steel under harmonic and operational loading
The results of experimental studies of the patterns fatigue crack development in samples made of 20GFL steel cut from the cargo over-spring beam are analyzed. The relatio of the threshold stress intensity coefficient Kth, determined from the kinetic diagram of fatigue failure, and the parameters of the threshold level and the operational loading process is estimated.
A case of extraskeletal chondroma in the left inguinal region
Extraskeletal chondromas are rare benign neoplasms comprising mature hyaline cartilage. A distinctive feature of these tumors is that they develop in soft tissues away from bone and cartilage. Extraskeletal chondromas account for 1.5% of benign soft tissue tumors. They occur predominantly at 30-60, in males, and in the hand or foot. In only 4% of cases, the tumor is located not on the extremities. Patients predominantly complain of increased mass, rarely on pain or a pulling sensation. The literature on the chondromas of the anterior abdominal wall is scarce. We present a rare case of a large extraskeletal left inguinal chondroma in a 71-year-old patient. The mass was over 6 cm large, and this is the only case of inguinal chondroma described in the literature. The mass was resected with surrounding tissues (a surgical margin of 1 cm) under combined endotracheal anesthesia and the histology confirmed the tumor to be a chondroma.