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.

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.

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).

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).

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.

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.

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.

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.

Polaribacter staleyi sp. nov., a polysaccharide-degrading marine bacterium isolated from the red alga Ahnfeltia tobuchiensis.

A Gram-stain-negative, rod-shaped, motile by gliding and yellow-pigmented bacterium, designated strain 10Alg 139T, was isolated from the Pacific red alga Ahnfeltiato buchiensis. The phylogenetic analysis based on 16S rRNA gene sequences showed that the novel strain belonged to the genus Polaribacter, a member of the family Flavobacteriaceae, the phylum Bacteroidetes, with highest sequence similarity to Polaribacter butkevichii KMM 3938T (99.3 %) and 93.3-98.6 % to other recognized Polaribacter species. The prevalent fatty acids of strain 10Alg 139T were iso-C15 : 0 3-OH, C15 : 0 3-OH, iso-C15:0, iso-C13 : 0, C15 : 0 and C15 : 1ω6c. The polar lipid profile consisted of the major lipids phosphatidylethanolamine, two unidentified aminolipids and four unidentified lipids. The main respiratory quinone was menaquinone 6. The DNA G+C content of the type strain is 31.8 mol%. The new isolate and the type strains of recognized species of the genus Polaribacter were readily distinguished based on a number of phenotypic characteristics. A combination of the genotypic and phenotypic data showed that the isolate from alga represents a novel species of the genus Polaribacter, for which the name Polaribacterstaleyi sp. nov. is proposed. The type strain is 10Alg 139T (=KCTC 52773T=KMM 6729T).

Aquimarina algiphila sp. nov., a chitin degrading bacterium isolated from the red alga Tichocarpus crinitus.

A strictly aerobic, Gram-stain-negative, rod-shaped, motile by gliding and yellow-orange pigmented flavobacterium, designated strain 9Alg 151T, was isolated from the Pacific red alga Tichocarpus crinitus. Phylogenetic analysis based on 16S rRNA gene sequences showed that the novel strain fell into the genus Aquimarina of the family Flavobacteriaceae with a 16S rRNA gene sequence similarity range of 94.2-98.2 % to the recognized species of the genus. Strain 9Alg 151T grew in the presence of 0.5-5 % NaCl and at 5-34 °C, and hydrolysed aesculin, agar, gelatin, starch, Tween 40, DNA and chitin. The predominant fatty acids were iso-C17 : 0 3-OH, iso-C15 : 0, iso-C15 : 1 G, iso-C15 : 0 3-OH, iso-C16 : 0, iso-C17 : 1ω8c and summed feature 3. The polar lipid profile comprised phosphatidylethanolamine, three unidentified aminolipids and three unidentified lipids. The major respiratory quinone was MK-6. The genomic DNA G+C content was 32.6 mol%. On the basis of 16S rRNA gene sequence data, and chemotaxonomic and phenotypic characteristics, strain 9Alg 151T represents a novel species of the genus Aquimarina, for which the name Aquimarina algiphila sp. nov. is proposed. The type strain is 9Alg 151T (=KCTC 23622T=KMM 6462T).

Polymorphisms of Catechol-O-Methyl Transferase (COMT) Gene in Vulnerability to Levodopa-Induced Dyskinesia.

PURPOSE: Parkinson's disease (PD), a common neurodegenerative disorder, is usually treated with Levodopa (L-DOPA). The use of this drug, however, is severely limited by the development of side effects of the motor system: Levodopa-induced dyskinesia (LID). The aim of this study is to investigate the association between seven COMT gene single-nucleotide polymorphisms (SNPs) and the development of LID in patients with PD. METHODS: 232 Caucasian patients with PD were investigated. 212 patients with PD received Levodopa therapy. Dyskinesia was assessed with the use of the Abnormal Involuntary Movement Scale (AIMS).  Genotyping was carried out on seven SNPs of the COMT gene (rs4680, rs6269, rs4633, rs4818, rs769224, rs165774, rs174696) using a real-time PCR method, and blind to the clinical status of the subjects. RESULTS: We found association between four SNPs, rs165774, rs4818, rs4633, rs4680, and LID. When the duration of disease was added as a covariate in regression analysis, however, the results did not reach statistical significance. Only the additive model for rs165774 was found to be close to be statistical significance (OR = 1.627 [0.976-2.741], permutation p = 0.057). CONCLUSIONS: The results failed to clearly support a contribution of the studied polymorphisms; this may be related to a dominant relationship with the disease duration confounding the effect on the prevalence of LID.

Olleya algicola sp. nov., a marine bacterium isolated from the green alga Ulva fenestrata.

A strictly aerobic, Gram-stain-negative, rod-shaped, motile by gliding and yellow-pigmented bacterium, designated strain 3Alg 18T, was isolated from the Pacific green alga Ulva fenestrata. Phylogenetic analysis based on 16S rRNA gene sequences showed that the novel strain was affiliated to the family Flavobacteriaceae of the phylum Bacteroidetes, being most closely related to the type strains of recognized species of the genus Olleya, with 16S rRNA gene sequence similarity of 97.9-99.3 %. Strain 3Alg 18T grew in the presence of 0.5-5 % (w/v) NaCl and at 4-37 °C, and hydrolysed aesculin, casein, gelatin, starch and Tweens 20, 40 and 80. The prevalent fatty acids were iso-C15 : 0, iso-C15 : 1 G, iso-C15 : 0 3-OH, iso-C16:0 2-OH, iso-C17 : 0 3-OH, summed feature 3, iso-C16 : 0 3-OH, anteiso-C15 : 0 and C15 : 0. The polar lipid profile contained phosphatidylethanolamine, three unidentified aminolipids and four unidentified lipids. The major respiratory quinone was menaquinone MK-6. The genomic DNA G+C content was 34.6 mol%. On the basis of 16S rRNA gene sequence data, and chemotaxonomic and phenotypic characteristics, strain 3Alg 18T represents a novel species of the genus Olleya, for which the name Olleya algicola sp. nov. is proposed. The type strain is 3Alg 18T (=KCTC 22024T=KMM 6133T).

Amylibacter ulvae sp. nov., a new alphaproteobacterium isolated from the Pacific green alga Ulva fenestrata.

A strictly aerobic, Gram-stain-negative, rod-shaped and non-motile bacterium, designated strain 6Alg 255(T), was isolated from the green alga Ulva fenestrata. Phylogenetic analysis based on 16S rRNA gene sequencing revealed that the novel strain affiliated to the family Rhodobacteraceae of the class Alphaproteobacteria being most closely related to Amylibacter marinus LMG 28364(T) with 16S rRNA gene sequence similarity of 97.2 %. Strain 6Alg 255(T) grew with 0.5-6.0 % NaCl and at 4-33 °C, hydrolysed aesculin, casein, gelatin and urea. The DNA G + C content was 50.4 mol%. The prevalent fatty acids were C18:1 ω7c and C16:0. The polar lipid profile was characterized by the presence of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine and unidentified aminolipid. The major respiratory quinone was Q-10. The significant molecular distinctiveness between the novel isolate and its nearest neighbour was strongly supported by the differences in physiological and biochemical tests. Therefore, strain 6Alg 255(T) represents a novel species of the genus Amylibacter, for which the name Amylibacter ulvae sp. nov. is proposed. The type strain is 6Alg 255(T) (=KCTC 32465(T) = KMM 6515(T)).

Lacinutrix cladophorae sp. nov., a flavobacterium isolated from the green alga Cladophora stimpsonii, transfer of Flavirhabdus iliipiscaria Shakeela et al. 2015 to the genus Lacinutrix as Lacinutrix iliipiscaria comb. nov. and emended description of the genus Lacinutrix.

A strictly aerobic, Gram-stain-negative, rod-shaped, motile by gliding and yellow-pigmented bacterium, designated strain 7Alg 4T, was isolated from the green alga Cladophora stimpsonii. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the novel strain was affiliated to the family Flavobacteriaceae of the phylum Bacteroidetes, and was most closely related to the recognized species of the genera Lacinutrixand Flavirhabdus, with 16S rRNA gene sequence similarities of 95.1-98.1 and 97.0 %, respectively. Strain 7Alg 4T grew in the presence of 1-5 % NaCl and at 4-32 °C, and hydrolysed aesculin, gelatin, starch and Tween 80. The prevalent fatty acids were iso-C15 : 1 G, iso-C15 : 0, iso-C17 : 0 3-OH, iso-C15 : 0 3-OH and C15 : 0. The polar lipid profile was characterized by the presence of phosphatidylethanolamine, three unidentified aminolipids and four unidentified lipids. The major respiratory quinone was MK-6. The DNA G+C content was 31.9 mol%. On the basis of the differences in 16S rRNA gene sequences, chemotaxonomic and phenotypic characteristics, it is suggested that strain 7Alg 4T represents a novel species of the genus Lacinutrix, for which the name Lacinutrixcladophorae sp. nov. is proposed. The type strain is 7Alg 4T (=KCTC 23036T=KMM 6381T). Reclassification of Flavirhabdus iliipiscaria as Lacinutrix iliipiscaria comb. nov. and an emend of the genus Lacinutrix are also proposed.

Thalassospira australica sp. nov. isolated from sea water.

Two Gram-negative, non-pigmented, motile bacteria were isolated from a sea water sample collected at St. Kilda Beach, Port Philip Bay, Victoria, Australia. The two strains were found to grow between 4 and 40 °C, pH 5-10 and tolerate up to 10 % NaCl. A phylogenetic study, based on a 16S rRNA gene sequence analysis indicated that strains NP 3b2(T) and H 94 belong to the genus Thalassospira. The sequence similarity of the 16S rRNA gene between the two new isolates is 99.8 % and between these strains and all validly named Thalassospira species was found to be in the range of 95-99.4 %. The DNA-DNA relatedness between the two strains was found to be 80.2 %, while relatedness with other validly named species of the genus Thalassospira was between 53 and 65 %. The average nucleotide identity (ANI) and the in silico genome-to-genome distance (GGD) between the two bacteria and T. profundimaris WP0211(T), T. xiamenensis M-5(T), 'T. permensis' NBRC 106175(T) and T. lucentensis QMT2(T) was 76-82 % and 21-25 %, respectively. The results of phylogenetic and genomic analysis, together with physiological and biochemical properties, indicated that the two strains represent a new species of the genus Thalassospira. Based on these data, a new species, Thalassospira australica, is proposed with strain NP 3b2(T) (=KMM 6365(T) = JCM 31222(T)) as the type strain.

Methylated arginine analogues: their potential role in atherosclerosis and cognition using the poloxamer-407-induced mouse model of dyslipidemia.

An experimental mouse model of dyslipidemia and atherosclerosis was utilized to study the generation of methylarginines in vivo, as well as any potential behavioral changes in mice associated with the production of excess methylarginines. Following 14 weeks of poloxamer 407 treatment, mice developed atherosclerosis and the plasma concentrations of monomethylarginine and asymmetric dimethylarginine were found to be significantly greater than corresponding concentrations in control mice. This finding may have contributed to the development of aortic atherosclerotic lesions in poloxamer-treated mice by interfering with nitric oxide availability and, hence, normal function of vascular endothelium. Poloxamer-407-treated mice also showed a significant decrease in locomotor and exploratory activity, together with signs of emotional stress and anxiety relative to controls. Passive avoidance testing to assess learning and memory provided suggestive evidence that poloxamer-treated mice could potentially be characterized as having undergone a disruption in the process of forgetting about an aversive event, specifically, a foot shock, when compared with control mice. Thus, it is also suggested that the increase in both plasma monomethylarginine and asymmetric dimethylarginine in poloxamer-407-treated mice may somehow influence learning and memory, because endothelial dysfunction caused by reduced nitric oxide availability has been hypothesized to negatively influence cognitive function.

Early-stage atherosclerosis in poloxamer 407-induced hyperlipidemic mice: pathological features and changes in the lipid composition of serum lipoprotein fractions and subfractions.

BACKGROUND: The aims of this study were to evaluate the effect of poloxamer 407 administration on atherogenic serum lipoprotein fractions and subfractions associated with cholesterol, triglycerides and phospholipids, as well as the onset of early atherosclerosis, in mice. METHODS: Mice were administered either sterile saline or poloxamer 407 (to induce a dose-controlled hyperlipidemia) for 1 month and then sacrificed at 1, 4 and 10 days after the last dose of poloxamer 407. Systolic and diastolic blood pressure, the activity of a cysteine protease (cathepsin B) in cardiac and liver tissue, and histological/morphological examination of heart and liver specimens was performed for each group of mice at each time point. Lastly, small angle X-ray scattering was utilized to analyze the lipoprotein fractions and subfractions associated with cholesterol, triglycerides and phospholipids for both groups of mice at each time point. Statistical analysis was performed using one-way, analysis-of-variance with post hoc analysis to determine significantly different mean values, while correlation analysis employed the Spearman test. RESULTS: Poloxamer 407-treated mice revealed significant hyperlipidemia, moderately elevated blood pressure, general lipidosis in liver cells, increased cysteine protease activity in heart tissue, and contractile-type changes in cardiomyocytes. Similar to humans, the onset of atherosclerosis in poloxamer 407-treated mice was characterized by a steady increase in serum low-density, intermediate-density and very-low-density lipoprotein fractions, as well as very-low-density lipoprotein subfractions. CONCLUSIONS: We would propose that the sustained elevation of serum atherogenic lipoprotein fractions and subfractions induced by the administration of poloxamer 407 to mice resulted in the morphological changes we observed in both heart and liver cells, which are suggested to precede atherosclerosis, since this is a well-established mouse model of atherosclerosis. Since most of the cellular, biochemical and physiological changes documented in the present study using poloxamer 407-treated mice are related to the symptoms of early atherosclerosis in humans, it is suggested that the poloxamer 407-induced mouse model of hyperlipidemia and atherosclerosis might prove beneficial as an experimental animal model with which to evaluate the pathological features observed in early-stage atherosclerosis.

Lutibacter holmesii sp. nov., a marine bacterium of the family Flavobacteriaceae isolated from the sea urchin Strongylocentrotus intermedius, and emended description of the genus Lutibacter.

Seven Gram-staining-negative, strictly aerobic, pale-yellow-pigmented, rod-shaped and non-motile strains were isolated from the sea urchin Strongylocentrotus intermedius collected from Troitsa Bay, Sea of Japan. Phylogenetic analyses based on 16S rRNA gene sequences showed that these isolates were affiliated with the family Flavobacteriaceae. The novel isolates showed 99.9-100 % 16S rRNA gene sequence similarity to each other and were closely related to the type strains of the recognized members of the genus Lutibacter with sequence similarities of 95.8-98.4 %. The G+C content of the genomic DNA was 35-36 mol%. DNA-DNA relatedness among the sea urchin isolates was 95-99 % and between strain KMM 6277T and its most closely related type strains, Lutibacter agarilyticus KCTC 23842T and Lutibacter litoralis JCM 13034T, was 38 and 27 %, respectively. The prevalent fatty acids were iso-C15 : 0, anteiso-C15 : 0, summed feature 3 (comprising iso-C15 : 0 2-OH and/or C16 : 1 ω7c fatty acids), iso-C15 : 1 and C15 : 0. The polar lipid profile was composed of the phosphatidylethanolamine, one unknown aminolipid and one unknown lipid. The main respiratory isoprenoid quinone was MK-6.The results of phylogenetic, phenotypic and genotypic analyses indicated that the novel strains represent a novel species within the genus Lutibacter, for which the name Lutibacter holmesii sp. nov. is proposed. The type strain is KMM 6277T ( = CCUG 62221T = LMG 26737T).

Winogradskyella litoriviva sp. nov., isolated from coastal seawater.

A Gram-stain-negative, facultatively anaerobic, moderately halophilic and gliding bacterium, designated KMM 6491T, was isolated from coastal seawater collected from Troitsa Bay, the Sea of Japan. Comparative analysis of 16S rRNA gene sequences revealed that strain KMM 6491T was a member of the genus Winogradskyella, with 94.5­97.9 % sequence similarity to recognized species of the genus Winogradskyella. The DNA G+C content of strain KMM 6491T was 31.3 mol% and DNA­DNA relatedness values with the type strains of Winogradskyella echinorum, Winogradskyella damuponensis, Winogradskyella eximia and Winogradskyella pulchriflava were in range of 10­26 %. Strain KMM 6491T contained menaquinone 6 (MK-6) as the single quinone and iso-C15 : 0, iso-C15 : 1, iso-C15 : 0 3-OH, iso-C17 : 0 3-OH, C15 : 0 and summed feature 3 (comprising iso-C15 : 0 2-OH and/or C16 : 1ω7c) anteiso-C15 : 0, as the prevalent fatty acids. The major polar lipids of strain KMM 6491T were phosphatidylethanolamine, two unknown aminolipids and two unknown lipids. Strain KMM 6491T was able to grow with 0.5­7 % NaCl and at 4­34 °C. The novel strain decomposed gelatin and starch and produced acid from d-glucose, maltose, mannose, rhamnose, sucrose, fructose and glycerol. On the basis of the results of the phylogenetic and phenotypic analyses it is suggested that strain KMM 6491T represents a novel species of the genus Winogradskyella, for which the name Winogradskyella litoriviva sp. nov. is proposed. The type strain is KMM 6491T ( = KCTC 23972T = LMG 26984T).

Flavobacterium ahnfeltiae sp. nov., a new marine polysaccharide-degrading bacterium isolated from a Pacific red alga.

A Gram-negative, aerobic, rod-shaped, motile by gliding and yellow-pigmented bacterium, designated strain 10Alg 130(T), that displayed the ability to destroy polysaccharides of red and brown algae, was isolated from the red alga Ahnfeltia tobuchiensis. The phylogenetic analysis based on 16S rRNA gene sequence placed the novel strain within the genus Flavobacterium, the type genus of the family Flavobacteriaceae, the phylum Bacteroidetes, with sequence similarities of 96.2 and 95.7 % to Flavobacterium jumunjiense KCTC 23618(T) and Flavobacterium ponti CCUG 58402(T), and 95.3-92.5 % to other recognized Flavobacterium species. The prevalent fatty acids of strain 10Alg 130(T) were iso-C15:0, iso-C15:0 3-OH, iso-C17:0 3-OH, C15:0 and iso-C17:1ω9c. The polar lipid profile consisted of phosphatidylethanolamine, two unknown aminolipids and three unknown lipids. The DNA G+C content of the type strain was 34.3 mol%. The new isolate and the type strains of recognized species of the genus Flavobacterium could strongly be distinguished by a number of phenotypic characteristics. A combination of the genotypic and phenotypic data showed that the algal isolate represents a novel species of the genus Flavobacterium, for which the name Flavobacterium ahnfeltiae sp. nov. is proposed. The type strain is 10Alg 130(T) (=KCTC 32467(T) = KMM 6686(T)).