In-Depth Genome Characterization and Pan-Genome Analysis of Strain KMM 296, a Producer of Highly Active Alkaline Phosphatase; Proposal for the Reclassification of Cobetia litoralis and Cobetia pacifica as the Later Heterotypic Synonyms of Cobetia amphilecti and Cobetia marina, and Emended Description of the Species Cobetia amphilecti and Cobetia marina.

A strictly aerobic, Gram-stain-negative, rod-shaped, and motile bacterium, designated strain KMM 296, isolated from the coelomic fluid of the mussel Crenomytilus grayanus, was investigated in detail due to its ability to produce a highly active alkaline phosphatase CmAP of the structural family PhoA. A previous taxonomic study allocated the strain to the species Cobetia marina, a member of the family Halomonadaceae of the class Gammaproteobacteria. However, 16S rRNA gene sequencing showed KMM 296's relatedness to Cobetia amphilecti NRIC 0815T. The isolate grew with 0.5-19% NaCl at 4-42 °C and hydrolyzed Tweens 20 and 40 and L-tyrosine. The DNA G+C content was 62.5 mol%. The prevalent fatty acids were C18:1 ω7c, C12:0 3-OH, C18:1 ω7c, C12:0, and C17:0 cyclo. The polar lipid profile was characterized by the presence of phosphatidylethanolamine, phosphatidylglycerol, phosphatidic acid, and also an unidentified aminolipid, phospholipid, and a few unidentified lipids. The major respiratory quinone was Q-8. According to phylogenomic and chemotaxonomic evidence, and the nearest neighbors, the strain KMM 296 represents a member of the species C. amphilecti. The genome-based analysis of C. amphilecti NRIC 0815T and C. litoralis NRIC 0814T showed their belonging to a single species. In addition, the high similarity between the C. pacifica NRIC 0813T and C. marina LMG 2217T genomes suggests their affiliation to one species. Based on the rules of priority, C. litoralis should be reclassified as a later heterotypic synonym of C. amphilecti, and C. pacifica is a later heterotypic synonym of C. marina. The emended descriptions of the species C. amphilecti and C. marina are also proposed.

Rhodoalgimonas zhirmunskyi gen. nov., sp. nov., a Marine Alphaproteobacterium Isolated from the Pacific Red Alga Ahnfeltia tobuchiensis: Phenotypic Characterization and Pan-Genome Analysis.

A novel Gram-staining negative, strictly aerobic, rod-shaped, and non-motile bacterium, designated strain 10Alg 79T, was isolated from the red alga Ahnfeltia tobuchiensis. A phylogenetic analysis based on 16S rRNA gene sequences placed the novel strain within the family Roseobacteraceae, class Alphaproteobacteria, phylum Pseudomonadota, where the nearest neighbor was Shimia sediminis ZQ172T (97.33% of identity). However, a phylogenomic study clearly showed that strain 10Alg 79T forms a distinct evolutionary lineage at the genus level within the family Roseobacteraceae combining with strains Aquicoccus porphyridii L1 8-17T, Marimonas arenosa KCTC 52189T, and Lentibacter algarum DSM 24677T. The ANI, AAI, and dDDH values between them were 75.63-78.15%, 67.41-73.08%, and 18.8-19.8%, respectively. The genome comprises 3,754,741 bp with a DNA GC content of 62.1 mol%. The prevalent fatty acids of strain 10Alg 79T were C18:1 ω7c and C16:0. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, an unidentified aminolipid, an unidentified phospholipid and an unidentified lipid. A pan-genome analysis showed that the unique part of the 10Alg 79T genome consists of 13 genus-specific clusters and 413 singletons. The annotated singletons were more often related to transport protein systems, transcriptional regulators, and enzymes. A functional annotation of the draft genome sequence revealed that this bacterium could be a source of a new phosphorylase, which may be used for phosphoglycoside synthesis. A combination of the genotypic and phenotypic data showed that the bacterial isolate represents a novel species and a novel genus, for which the name Rhodoalgimonas zhirmunskyi gen. nov., sp. nov. is proposed. The type strain is 10Alg 79T (=KCTC 72611T = KMM 6723T).

Terpene-Containing Analogues of Glitazars as Potential Therapeutic Agents for Metabolic Syndrome.

Metabolic syndrome is a complex of abnormalities involving impaired glucose and lipid metabolism, which needs effective pharmacotherapy. One way to reduce lipid and glucose levels associated with this pathology is the simultaneous activation of nuclear PPAR-alpha and gamma. For this purpose, we synthesized a number of potential agonists based on the pharmacophore fragment of glitazars with the inclusion of mono- or diterpenic moiety in the molecular structure. The study of their pharmacological activity in mice with obesity and type 2 diabetes mellitus (C57Bl/6Ay) revealed one substance that was capable of reducing the triglyceride levels in the liver and adipose tissue of mice by enhancing their catabolism and expressing a hypoglycemic effect connected with the sensitization of mice tissue to insulin. It has also been shown to have no toxic effects on the liver.

Overall survival with first-line atezolizumab in combination with vemurafenib and cobimetinib in BRAFV600 mutation-positive advanced melanoma (IMspire150): second interim analysis of a multicentre, randomised, phase 3 study.

BACKGROUND: Primary analysis of the phase 3 IMspire150 study showed improved investigator-assessed progression-free survival with first-line atezolizumab, vemurafenib, and cobimetinib (atezolizumab group) versus placebo, vemurafenib, and cobimetinib (control group) in patients with BRAFV600 mutation-positive melanoma. With a median follow-up of 18·9 months (IQR 10·4-23·8) at the primary analysis, overall survival data were immature. Here, we report the results from the second, prespecified, interim overall survival analysis. METHODS: The multicentre, double-blind, placebo-controlled, randomised, phase 3 IMspire150 study was done at 108 academic and community hospitals in 20 countries. Patients aged 18 years or older with previously untreated unresectable stage IIIc or stage IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible for inclusion. Patients were randomly assigned (1:1) to receive either atezolizumab (840 mg intravenously on day 1 and 15) or placebo plus vemurafenib (960 mg or 720 mg twice daily orally) and cobimetinib (60 mg once daily orally; 21 days on and 7 days off) in 28-day cycles. Atezolizumab and placebo were added to treatment regimens from cycle two onwards. Randomisation was done centrally (Durham, NC, USA) based on a permuted block randomisation scheme (block size of 4) using an interactive web-based response system and was stratified by geographical region and baseline lactate dehydrogenase concentration. Overall survival was analysed in the intention-to-treat population and safety was analysed in all patients who received at least one dose of study drug according to actual treatment received. The primary endpoint was investigator-assessed progression-free survival, which was previously reported. Here, we report the second, prespecified, interim overall survival analysis, which was planned after about 270 overall survival events had occurred. The trial is ongoing, but is no longer enrolling patients, and it is registered with ClinicalTrials.gov, NCT02908672. FINDINGS: Between Jan 13, 2017, and April 26, 2018, 514 patients (median age 54 years [IQR 43-63]; 299 [58%] men and 215 [42%] women) were enrolled in the trial and randomly assigned to the atezolizumab group (256 [50%] patients) or the control group (258 [50%] patients). At the data cutoff (Sept 8, 2021), 273 patients had died (126 in the atezolizumab group and 147 in the control group). Median follow-up was 29·1 months (IQR 10·1-45·4) for the atezolizumab group versus 22·8 months (10·6-44·1) for the control group. Median overall survival was 39·0 months (95% CI 29·9-not estimable) in the atezolizumab group versus 25·8 months (22·0-34·6) in the control group (HR 0·84 [95% CI 0·66-1·06]; p=0·14). The most common adverse events of any grade in the atezolizumab group were blood creatine phosphokinase increased (123 [53%] of 231 patients), diarrhoea (116 [50%]), and pyrexia (115 [50%]). The most common adverse events of any grade in the control group were diarrhoea (157 [56%] of 280 patients), blood creatine phosphokinase increased (135 [48%]), and rash (119 [43%]). The most common grade 3-4 adverse events were increased lipase (54 [23%] of 231 patients in the atezolizumab group vs 62 [22%] of 280 patients in the control group), increased blood creatine phosphokinase (51 [22%] vs 50 [18%]), and increased alanine aminotransferase (32 [14%] vs 26 [9%]). Serious adverse events were reported in 112 (48%) patients in the atezolizumab group and 117 (42%) patients in the control group. Grade 5 adverse events were reported in eight (3%) patients in the atezolizumab group versus six (2%) patients in the control group. Two grade 5 adverse events (hepatitis fulminant and hepatic failure) in the atezolizumab group were considered to be associated with the triplet combination, and one event in the control group (pulmonary haemorrhage) was considered to be associated with cobimetinib. INTERPRETATION: Additional follow-up of the IMspire150 trial showed that overall survival was not significantly improved with atezolizumab, vemurafenib, and cobimetinib compared with placebo, vemurafenib, and cobimetinib in patients with BRAFV600 mutation-positive advanced melanoma. Results of the final analysis are awaited to establish whether a significant improvement in overall survival can be achieved with long-term treatment with this triplet combination versus vemurafenib plus cobimetinib. FUNDING: F Hoffmann-La Roche.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: First Described Complication after Gam-COVID-Vac Vaccine.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe, debilitating chronic disease characterized by marked tiredness and fatigue, cognitive dysfunction, sleep disturbances, pain, and autonomic, immunological, and metabolic dysfunctions, in which all symptoms are usually exacerbated by physical and/or psychological stress. SUBJECTS AND METHODS: We report a case of ME/CFS with severe myalgia and severe locomotor disorders in a 25-year-old female after Gam-COVID-Vac vaccine (Sputnik V) ten days before the manifestation of the symptoms. RESULTS: This is the first report of such a complication from the Gam-COVID-Vac vaccine.

Pathophysiological Mechanisms of Antipsychotic-Induced Parkinsonism.

Among neurological adverse reactions in patients with schizophrenia treated with antipsychotics (APs), drug-induced parkinsonism (DIP) is the most common motility disorder caused by drugs affecting dopamine receptors. One of the causes of DIP is the disruption of neurotransmitter interactions that regulate the signaling pathways of the dopaminergic, cholinergic, GABAergic, adenosinergic, endocannabinoid, and other neurotransmitter systems. Presently, the development mechanisms remain poorly understood despite the presence of the considered theories of DIP pathogenesis.

The predictive potential of autoimmune-inflammatory syndrome induced by adjuvants (ASIA) criteria to assess the risk of adverse events and efficacy of immune checkpoint inhibitor therapy.

At the moment, there are no approved predictive markers of immune adverse events (irAES) induced by immune checkpoint inhibitors (ICIs) and the treatment efficacy. The early stages of irAES have some similarities with adjuvant-induced autoimmune/pro-inflammatory syndrome (ASIA). This study aims to assess the predictive possibility of using the "ASIA questionnaire" in patients on immune checkpoint inhibitor therapy in comparison with determination of PD-L1 expression to predict the risk of irAES development and therapy efficacy. We examined patients (n = 91) being treated for solid tumors. The signs of ASIA were found in 74% (66/91), while ASIA syndrome was diagnosed in 54% of cases (49/91). No statistically significant difference in the frequency of ICI-dependent complication development regarding the presence of previous ASIA clinical manifestations, hereditary factors, sex, different trigger factors was found. Index based on combination of PD-L1 determination and ASIA index was created. With reference > 2.5 units, the disease control rate (DCR) could be predicted with sensitivity 100.0% and specificity 70.00%, p = 0.007. The study did not reveal the diagnostic value of ASIA questionnaire to assess the risk of adverse events; however, in early stages, the development of ASIA symptoms diagnosed with the questionnaire in complex with PD-L1 expression allowed to predict a treatment efficacy.

Algicella marina gen. nov., sp. nov., a novel marine bacterium isolated from a Pacific red alga.

A novel Gram-staining negative, strictly aerobic, rod-shaped, and non-motile bacterium, designated strain 9Alg 56T, was isolated from the red alga Tichocarpus crinitus. The phylogenetic analysis based on 16S rRNA gene sequences placed the novel strain within the family Rhodobacteraceae, the order Rhodobacterales, the class Alphaproteobacteria, the phylum Pseudomonadota. The nearest neighbors of the new strain were Pontivivens insulae KCTC 42458T, Oceanibium sediminis KCTC 62076T, Halovulum dunhuangense YYQ-30T and Monaibacterium marinum C7T with 16S rRNA gene sequence similarity of 94.7, 94.4%, 93.1 and 92.7%, respectively. The AAI/ANI/dDDH values between 9Alg 56T and the five species of the closest genera (Pontivivens, Oceanibium, Halovulum, Monaibacterium, and 'Oceanomicrobium') were 58.63-63.91%/ 75.91-77.37%/ 19.3-20.4%. The prevalent fatty acids of strain 9Alg 56T were C18:1 ω7c, C18:0 and C14:0 3-OH. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, phosphatidic acid, phosphatidylcholine, and two unidentified lipids. The DNA G+C content of strain 9Alg 56T was 61.5 mol%. A combination of the genotypic and phenotypic data showed that the algal isolate represents a novel genus and species, for which the name Algicella marina gen. nov., sp. nov. is proposed. The type strain is 9Alg 56T (= KCTC 72005T = KMM 6775T).

Hypothesis for the development of immune-related adverse events in immune checkpoint inhibitors therapy.

There are no explanations for the diversity in the development of certain immune-related adverse events (irAEs) with immune checkpoint inhibitors (ICI). The goal of this study is to search for possible predisposing factors that contribute to the development of certain autoimmune complications during anti-CTLA4 and anti-PD1/PD-L1 therapy. According to the keywords "checkpoint inhibitors, anti-CTLA4, anti-PD1/PD-L1, immune adverse events, paraneoplastic syndrome" the review and original articles published in the international databases to 2021were selected and studied. According to the analysis of the published papers, we consider that a key role in the difference in the types of irAEs lies in the specificity of the drug. The high prevalence of skin and gastrointestinal autoimmune complications can be explained by the presence of gut dysbacteriosis in patients before treatment and developed during the treatment. For the development of specific types of irAEs, a complex of predisposing factors is required, such as HLA-genotype, paraneoplastic syndromes, and the expression of PD-L1 in the thyroid gland in the case of anti-PD1 therapy.

Aureibaculum algae sp. nov. isolated from the Pacific red alga Ahnfeltia tobuchiensis.

A Gram stain-negative, aerobic, rod-shaped, motile by gliding and yellow-orange-pigmented bacterium, designated strain 10Alg 115T, was isolated from the red alga Ahnfeltia tobuchiensis. The phylogenetic analysis based on 16S rRNA gene sequences placed the novel strain within the family Flavobacteriaceae, phylum Bacteroidetes. The nearest neighbor of the new isolate was Aureibaculum marinum KCTC 62204T with sequence similarity of 98.1%. The average nucleotide similarity and digital DNA-DNA hybridization values between the novel strain and Aureibaculum marinum KCTC 62204T were 80% and 22.3%, respectively. The prevalent fatty acids of strain 10Alg 115T were iso-C15:0, iso-C15:1 G, iso-C17:0 3-OH, iso-C16:0 3-OH and C15:0. The polar lipid profile consisted of phosphatidylethanolamine, two unidentified aminolipids and two unidentified lipids. The DNA G + C content of the type strain calculated from the whole-genome sequence was 32.2 mol%. A combination of the genotypic and phenotypic data showed that the algal isolate represents a novel species of the of genus Aureibaculum, for which the name Aureibaculum algae sp. nov. is proposed. The type strain is 10Alg 115T (= KCTC 62086T = KMM 6764T).

Multiple bacterial partners in symbiosis with the nudibranch mollusk Rostanga alisae.

The discovery of symbiotic associations extends our understanding of the biological diversity in the aquatic environment and their impact on the host's ecology. Of particular interest are nudibranchs that unprotected by a shell and feed mainly on sponges. The symbiotic association of the nudibranch Rostanga alisae with bacteria was supported by ample evidence, including an analysis of cloned bacterial 16S rRNA genes and a fluorescent in situ hybridization analysis, and microscopic observations. A total of 74 clones belonging to the phyla α-, ß-, γ-Proteobacteria, Actinobacteria, and Cyanobacteria were identified. FISH confirmed that bacteriocytes were packed with Bradyrhizobium, Maritalea, Labrenzia, Bulkholderia, Achromobacter, and Stenotrophomonas mainly in the foot and notum epidermis, and also an abundance of Synechococcus cyanobacteria in the intestinal epithelium. An ultrastructural analysis showed several bacterial morphotypes of bacteria in epidermal cells, intestine epithelium, and in mucus layer covering the mollusk body. The high proportion of typical bacterial fatty acids in R. alisae indicated that symbiotic bacteria make a substantial contribution to its nutrition. Thus, the nudibranch harbors a high diversity of specific endo- and extracellular bacteria, which previously unknown as symbionts of marine invertebrates that provide the mollusk with essential nutrients. They can provide chemical defense against predators.

Fatty Acids of Echinoderms: Diversity, Current Applications and Future Opportunities.

The phylum Echinodermata comprising the classes Asteroidea, Ophiuroidea, Echinoidea, Holothuroidea, and Crinodeia, is one of the important invertebrate groups. Members of this phylum live exclusively in marine habitats and are distributed in almost all depths and latitudes. Some of them, such as sea urchins and sea cucumbers, are commercially valuable and constitute a major fishery resource. Echinoderms are increasingly recognized as a unique source of various metabolites with a wide range of biological activities. The importance of dietary polyunsaturated fatty acids, such as eicosapentaenoic acid, in human health has drawn attention to echinoderms as a promising source of essential fatty acids (FAs). Extensive information on the FAs of the phylum has been accumulated to date. The biosynthetic capabilities and feeding habits of echinoderms explain the findings of the unusual FAs in them. Certain common and unusual FAs may serve as chemotaxonomic markers of the classes. The main goal of the review was to gather the relevant information on the distribution of FAs among the echinoderm classes, describe the structures, distribution, biosynthetic pathways, and bioactivity, with an emphasis on the FAs specific for echinoderms. A large part of the review is devoted to the FAs derived from echinoderms that exhibit various biological activities promising for potential therapeutic applications.

Nutrient Effects on Motor Neurons and the Risk of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is an incurable chronic progressive neurodegenerative disease with the progressive degeneration of motor neurons in the motor cortex and lower motor neurons in the spinal cord and the brain stem. The etiology and pathogenesis of ALS are being actively studied, but there is still no single concept. The study of ALS risk factors can help to understand the mechanism of this disease development and, possibly, slow down the rate of its progression in patients and also reduce the risk of its development in people with a predisposition toward familial ALS. The interest of researchers and clinicians in the protective role of nutrients in the development of ALS has been increasing in recent years. However, the role of some of them is not well-understood or disputed. The objective of this review is to analyze studies on the role of nutrients as environmental factors affecting the risk of developing ALS and the rate of motor neuron degeneration progression. METHODS: We searched the PubMed, Springer, Clinical keys, Google Scholar, and E-Library databases for publications using keywords and their combinations. We analyzed all the available studies published in 2010-2020. DISCUSSION: We analyzed 39 studies, including randomized clinical trials, clinical cases, and meta-analyses, involving ALS patients and studies on animal models of ALS. This review demonstrated that the following vitamins are the most significant protectors of ALS development: vitamin B12, vitamin E > vitamin C > vitamin B1, vitamin B9 > vitamin D > vitamin B2, vitamin B6 > vitamin A, and vitamin B7. In addition, this review indicates that the role of foods with a high content of cholesterol, polyunsaturated fatty acids, urates, and purines plays a big part in ALS development. CONCLUSION: The inclusion of vitamins and a ketogenic diet in disease-modifying ALS therapy can reduce the progression rate of motor neuron degeneration and slow the rate of disease progression, but the approach to nutrient selection must be personalized. The roles of vitamins C, D, and B7 as ALS protectors need further study.

Association and Gene-Gene Interactions Study of Late-Onset Alzheimer's Disease in the Russian Population.

Alzheimer's disease (AD) is a neurodegenerative disorder, and represents the most common cause of dementia. In this study, we performed several different analyses to detect loci involved in development of the late onset AD in the Russian population. DNA samples from 472 unrelated subjects were genotyped for 63 SNPs using iPLEX Assay and real-time PCR. We identified five genetic loci that were significantly associated with LOAD risk for the Russian population (TOMM40 rs2075650, APOE rs429358 and rs769449, NECTIN rs6857, APOE ε4). The results of the analysis based on comparison of the haplotype frequencies showed two risk haplotypes and one protective haplotype. The GMDR analysis demonstrated three significant models as a result: a one-factor, a two-factor and a three-factor model. A protein-protein interaction network with three subnetworks was formed for the 24 proteins. Eight proteins with a large number of interactions are identified: APOE, SORL1, APOC1, CD33, CLU, TOMM40, CNTNAP2 and CACNA1C. The present study confirms the importance of the APOE-TOMM40 locus as the main risk locus of development and progress of LOAD in the Russian population. Association analysis and bioinformatics approaches detected interactions both at the association level of single SNPs and at the level of genes and proteins.

Low light acclimation strategy of the brown macroalga Undaria pinnatifida: Significance of lipid and fatty acid remodeling for photosynthetic competence.

Brown macroalgae, being important components of benthic communities in temperate regions, are frequently subjected to light limitation. To extend our understanding of their low light acclimation strategies to the regulation of membrane lipid environment, photosynthetic characteristics, lipid class, fatty acid profiles and chloroplast ultrastructure were compared in Undaria pinnatifida (Phaeophyceae, Ochrophyta) after long-term exposure to low and moderate light intensities (LL, 100 and ML, 280 µmol photons · m-2 · s-1 ). We show that light limitation significantly increased PSII quantum efficiency and photosynthetic electron transport rate, enhanced pigment contents and concentration of thylakoid membranes in chloroplasts but decreased the distance between the thylakoid stacks. These physiological alterations at LL were accompanied by a selective remodeling of thylakoid membrane lipids driven by increases in monogalactosyldiacylglycerol (MGDG) and phosphatidylglycerol (PG) contents. Light limitation also induced active production of PG specific trans-Δ3 -hexadecenoic acid and accumulation of n-3 polyunsaturated fatty acids (PUFA) mostly in PG and MGDG at the expense of the rise in 18:3n-3 and 20:5n-3, 18:4n-3, respectively. These changes in lipid and FA profiles are apparently responsible for supporting thylakoid biogenesis and efficient photosynthesis at light limitation, thus contributing to photoacclimation strategies in brown algae. The content of triacylglycerols (TAG) and the level of their PUFA were decreased at LL, suggesting the consumption of TAG as a source of PUFA and energy reserves. Thus, U. pinnatifida is able to successfully overcome periods of low irradiance through the effective light harvesting and utilization that are provided by high flexibility of lipid biosynthesis.

Real-World Experience with Targeted Therapy in BRAF Mutant Advanced Melanoma Patients: Results from a Multicenter Retrospective Observational Study Advanced Melanoma in Russia (Experience) (ADMIRE).

Clinical trials of targeted therapy (TT) and immunotherapy (IT) for highly aggressive advanced melanoma have shown marked improvements in response and survival rates. However, real-world data on treatment patterns and clinical outcomes for patients with advanced BRAF V600 mutant melanoma are ultimately scarce. The study was designed as an observational retrospective chart review study, which included 382 patients with advanced BRAF V600 mutant melanoma, who received TT in a real-world setting and were not involved in clinical trials. The data were collected from twelve medical centers in Russia. The objective response rates (ORRs) to combined BRAFi plus MEKi and to BRAFi mono-therapy were 57.4% and 39.8%, respectively. The median progression-free survival (PFS) and median overall survival (OS) were 9.2 months and 22.6 months, respectively, for the combined first-line therapy; 9.4 months and 16.1 months, respectively, for the combined second-line therapy; and 7.4 months and 17.1 months, respectively, for the combined third- or higher-line therapy. Analysis of treatment patterns demonstrated the effectiveness of the combined TT with BRAF plus MEK inhibitors in patients with brain metastases, rare types of BRAF mutations, and across lines of therapy, as well as a well-tolerated and manageable safety profile.

Genome-Based Classification of Strain 16-SW-7, a Marine Bacterium Capable of Converting B Red Blood Cells, as Pseudoalteromonas distincta and Proposal to Reclassify Pseudoalteromonas paragorgicola as a Later Heterotypic Synonym of Pseudoalteromonas distincta.

A strictly aerobic, Gram-stain-negative, rod-shaped, and motile bacterium, designated strain 16-SW-7, isolated from a seawater sample, was investigated in detail due to its ability to produce a unique α-galactosidase converting B red blood cells into the universal type blood cells. The phylogenetic analysis based on 16S rRNA gene sequences revealed that the strain 16-SW-7 is a member of the Gammaproteobacteria genus Pseudoalteromonas. The closest relatives of the environmental isolate were Pseudoalteromonas distincta KMM 638T and Pseudoalteromonas paragorgicola KMM 3548T, with the plural paralogous 16S rRNA genes of 99.87-100% similarity. The strain 16-SW-7 grew with 1-10% NaCl and at 4-34°C, and hydrolyzed casein, gelatin, tyrosine, and DNA. The genomic DNA G+C content was 39.3 mol%. The prevalent fatty acids were C16:1 ω7c, C16:0, C17:1 ω8c, C18:1 ω7c, C17:0, and C12:0 3-OH. The polar lipid profile was characterized by the presence of phosphatidylethanolamine, phosphatidylglycerol, two unidentified amino lipids, and three unidentified lipids. The major respiratory quinone was Q-8. The finished genome of the strain 16-SW-7 (GenBank assembly accession number: GCA_005877035.1) has a size of 4,531,445 bp and comprises two circular chromosomes L1 and S1, deposited in the GenBank under the accession numbers CP040558 and CP040559, respectively. The strain 16-SW-7 has the ANI values of 98.2% with KMM 638T and KMM 3548T and the DDH values of 84.4 and 83.5%, respectively, indicating clearly that the three strains belonged to a single species. According to phylogenetic evidence and similarity for the chemotaxonomic and genotypic properties, the strain 16-SW-7 (= KCTC 52772 = KMM 701) represents a novel member of the species Pseudoalteromonas distincta. Also, we have proposed to reclassify Pseudoalteromonas paragorgicola as a later heterotypic synonym of P. distincta based on the rules of priority with the emendation of the species.

An ontology-based approach to the analysis of the acid-base state of patients at operative measures.

Researchers working in various domains are focusing on extracting information from data sets by data mining techniques. However, data mining is a complicated task, including multiple complex processes, so that it is unfriendly to non-computer researchers. Due to the lack of experience, they cannot design suitable workflows that lead to satisfactory results. This article proposes an ontology-based approach to help users choose appropriate data mining techniques for analyzing domain data. By merging with domain ontology and extracting the corresponding sub-ontology based on the task requirements, an ontology oriented to a specific domain is generated that can be used for algorithm selection. Users can query for suitable algorithms according to the current data characteristics and task requirements step by step. We build a workflow to analyze the Acid-Base State of patients at operative measures based on the proposed approach and obtain appropriate conclusions.

Treatment of Cognitive Impairment and the Role of Demographic Factors in Disease Progression: The Final Results of the Russian Observational Program "DIAMANT".

BACKGROUND: Chronic cerebral ischemia (CCI) is a form of cerebrovascular disease manifested as a vascular cognitive impairment (VCI). The management of the patients with CCI is determined by a healthy lifestyle and early therapy aimed at correcting and preventing this disease. Divaza is a drug with endothelial protective and nootropic effects. We present the final efficacy and safety analysis of all-Russian, open-label, prospective, observational, multicenter study of Divaza and emphasize the role of demographic and socioeconomic factors in cognitive disorder (CD) progression. METHODS: CCI patients (n = 2,583) with or without CD were enrolled. Patients received Divaza (2 tablets 3 times per day for 12 weeks). Montreal Cognitive Assessment (MoCA) testing was required. The change in the mean MoCA score post-treatment was used as the primary endpoint. As the secondary endpoints, the number of patients with a MoCA <26 and ≤17 (dementia); the percentage of patients with a MoCA score improvement in different age groups; the dynamics of mean MoCA score in age groups; and the relationship between CD and sex or regional social/economic factors were assessed. RESULTS: Divaza therapy led to a significant improvement: the mean MoCA score was up to 20% higher post-treatment (Wilcoxon test, p < 0.0001 vs. baseline). The number of participants with MoCA ≥26 increased by 33.6%. The number of patients with dementia was 4.1 times less after therapy (p < 0.00001 vs. baseline). Divaza improved cognitive functions of patients in each age group. Findings demonstrate that regional socioeconomic factors contribute to CD development and severity. The observed divergence between sexes was a result of a larger number of women enrolled. The study confirmed the safety of Divaza. CONCLUSIONS: In the study, we observed the efficacy of Divaza for the treatment of CD: a therapy contributed to an increase in the mean MoCA score and the positive dynamics in the number of patients with cognitive improvement.

Reconfigurable monitoring for telecommunication networks.

This article addresses the monitoring problem of the telecommunication networks. We consider these networks as multilevel dynamic objects. It shows that reconfigurable systems are necessary for their monitoring process in real life. We implement the reconfiguration abilities of the systems through the synthesis of monitoring programs and their execution in the monitoring systems and on the end-user devices. This article presents a new method for the synthesis of monitoring programs and develops a new language to describe the monitoring programs. The programs are translated into binary format and executed by the virtual machines installed on the elements of the networks. We present an example of the program synthesis for real distributed networks monitoring at last.