Nuclear Factor Erythroid 2-Related Factor 2/Kelch-Like ECH-Associated Protein 1 as a Predictor of Prognosis and Radiotherapy Resistance in Patients With Locally Advanced Rectal Cancer: A Prospective Analysis.

BACKGROUND: The nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) signaling pathway is involved in the regulation of cellular responses to oxidative stress. Nrf2 acts as a cell protector from inflammation, cellular damage, and tumorigenesis, whereas Keap1 is a negative regulator of Nrf2. Dysregulation of the Nrf2/Keap1 pathway results in tumorigenesis and the active metabolism of tumor cells, leading to high resistance to radiotherapy. This study aimed to evaluate the predictive role of Nrf2 and Keap1 in the radiosensitivity and prognosis of locally advanced rectal cancer (LARC). METHODS: In total, 90 patients with LARC underwent surgery after preoperative chemoradiotherapy (CRT). Endoscopic biopsies from the tumors were obtained before radiation, and the Nrf2 and Keap1 expressions were assessed by immunohistochemistry. The response to therapy was evaluated after surgery following CRT according to the pathologic tumor regression grade. The disease-free survival (DFS) and overall survival rates were also documented. The association between the Nrf2 and Keap1 immunoreactivity and the clinicopathological parameters was analyzed. RESULTS: The overexpression of the nuclear Nrf2 before CRT showed a significant correlation with better DFS. The cytoplasmic Nrf2 expression was associated with more residual tumors after radiotherapy and a more unfavorable DFS, indicating lower radiosensitivity. CONCLUSION: CRT is an important issue in LARC and is a major aspect of treatment. Thus, the Nrf2/Keap1 expression may be a potential predictor of preoperative therapeutic resistance. The Nrf2-Keap1 modulators that interact with each other may also be effectively applicable to CRT effect in LARC.

Gender, reproductive output covariation and their role on gene diversity of Pinus koraiensis seed orchard crops.

BACKGROUND: Gender and fertility variation have an impact on mating dynamics in a population because they affect the gene exchange among parental members and the genetic composition of the resultant seed crops. Fertility is the proportional gametic contribution of parents to their progeny. An effective number of parents, derivative of effective population size, is the probability that two alleles randomly chosen from the gamete gene pool originated from the same parent. The effective number of parents is directly related to the fertility variation among parents, which should be monitored for manipulating gene diversity of seed crops. We formulated a fundamental equation of estimating the effective number of parents and applied it to a seed production population. RESULTS: Effective number of parents (Np) was derived from fertility variation (Ψ) considering covariance (correlation coefficient, r) between maternal and paternal fertility. The Ψ was calculated from the coefficient of variation in reproductive outputs and divided into female (ψf) and male (ψm) fertility variation in the population under study. The Np was estimated from the parental Ψ estimated by the fertility variation of maternal (ψf) and paternal (ψm) parents. The gene diversity of seed crops was monitored by Ψ and Np. in a 1.5 generation Pinus koraiensis seed orchard as a case of monoecious species. A large variation of female and male strobili production was observed among the studied 52 parents over four consecutive years, showing statistically significant differences across all studied years. Parental balance curve showed greater distortion in paternal than maternal parents. The Ψ ranged from 1.879 to 4.035 with greater ψm than ψf, and the Np varied from 14.8 to 36.8. When pooled, the relative effective number of parents was improved as 80.0% of the census number. CONCLUSIONS: We recommend the use of fertility variation (i.e., CV, Ψ), Person's product-moment correlation (r), and effective number of parents (Np) as tools for gauging gene diversity of seed crops in production populations. For increasing Np and gene diversity, additional management options such as mixing seed-lots, equal cone harvest and application of supplemental-mass-pollination are recommended.

Roseovarius ponticola sp. nov., a novel lipolytic bacterium of the family Rhodobacteraceae isolated from seawater.

A lipolytic, Gram-negative, aerobic, non-motile and pleomorphic bacterial strain, designated W-SW3T, was isolated from seawater around Wando, an island of South Korea, and its taxonomic position was determined using a polyphasic approach. Its optimal growth occurred at 30 °C, pH 7.0-8.0 and 2.0-4.0% (w/v) NaCl. Neighbour-joining phylogenetic tree of 16S rRNA gene sequences showed that strain W-SW3T belonged to the genus Roseovarius of the family Rhodobacteraceae, by showing the highest 16S rRNA gene sequence similarity value (97.3%) to the type strain of Roseovarius nanhaiticus. Strain W-SW3T exhibited 16S rRNA gene sequence similarities of 93.2-95.6% to the type strains of the other Roseovarius species. Ubiquinone-10 was found as the predominant ubiquinone and C18:1ω7c and C16:0 were found as the major fatty acids. Phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified lipid and one unidentified aminolipid were major polar lipids detected. The DNA G + C content of strain W-SW3T was 63.9 mol%. Mean DNA-DNA relatedness values of strain W-SW3T with the type strains of R. nanhaiticus and R. antarcticus were 18 and 9%, respectively. The phenotypic properties, together with the phylogenetic and genetic data, made it possible strain W-SW3T to be separated from other recognized species of the genus Roseovarius. On the basis of the data presented, strain W-SW3T represents a novel species of the genus Roseovarius, for which the name Roseovarius ponticola sp. nov. is proposed. The type strain is W-SW3T (= KCTC 62424T = KACC 19615T = NBRC 113186T).

Colwellia ponticola sp. nov., isolated from seawater.

A Gram-stain-negative, aerobic, motile and rod-shaped bacterial strain, designated OISW-25T, was isolated from seawater in Republic of Korea. Strain OISW-25T grew optimally at 25 °C and in the presence of 2.0 % (w/v) NaCl. The phylogenetic trees based on 16S rRNA gene sequences showed that strain OISW-25T fell within the clade comprising the type strains of Colwellia species. Strain OISW-25T exhibited 16S rRNA gene sequence similarity values of 97.5, 97.2 and 97.1 % to the type strains of C. piezophila, C. maris and C. psychrerythraea, respectively, and of 93.6-96.6 % to the type strains of the other Colwellia species. The average nucleotide identity values between strain OISW-25T and C. piezophila ATCC BAA-637T and two non-type strains of C. psychrerythraea were 78.16-79.35 % and DNA-DNA relatedness value of strain OISW-25T with the type strain of C. maris was 17 %. The DNA G+C content of strain OISW-25T was 39.2 mol% (HPLC) or 38.7 mol% (genome data). Strain OISW-25T contained Q-8 as the predominant ubiquinone and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) and C16 : 0 as the major fatty acids. The major polar lipids of strain OISW-25T were phosphatidylethanolamine and phosphatidylglycerol. Distinguished phenotypic properties, along with the phylogenetic and genetic distinctiveness, revealed that strain OISW-25T is distinct from Colwellia species. On the basis of the data presented, strain OISW-25T is considered to represent a novel species of the genus Colwellia, for which the name Colwellia ponticola sp. nov. is proposed. The type strain is OISW-25T (=KCTC 62426T=NBRC 113187T).

Altererythrobacter insulae sp. nov., a lipolytic bacterium isolated from a tidal flat.

A lipolytic, Gram-stain-negative, aerobic, non-motile and coccoid, ovoid or rod-shaped bacterial strain, designated BPTF-M16T, was isolated from tidal flat sediment on the Yellow Sea in the Republic of Korea. Strain BPTF-M16T grew optimally at 30 °C and in the presence of 2.0-3.0 % (w/v) NaCl. A phylogenetic tree of 16S rRNA gene sequences showed that strain BPTF-M16T fell within the clade comprising the type strains of Altererythrobacter species. Strain BPTF-M16T exhibited 16S rRNA gene sequence similarity values of 98.0 and 97.1 % to the type strains of Altererythrobacterishigakiensis and Altererythrobactermarinus, respectively, and of less than 97.0 % to the type strains of the other recognized species. Strain BPTF-M16T contained Q-10 as the predominant ubiquinone and C18 : 1ω7c as the major fatty acid. The major polar lipids detected in strain BPTF-M16T were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, sphingoglycolipid and one unidentified glycolipid. Mean DNA-DNA relatedness values of strain BPTF-M16T with the type strains of A. ishigakiensis and A. marinus were 22 and 13 %, respectively. The average nucleotide identity value between strain BPTF-M16T and the type strain of A. ishigakiensis was 76.80 %. Differential phenotypic properties, together with the phylogenetic and genetic data, revealed that strain BPTF-M16T is separated from recognized Altererythrobacter species. On the basis of the data presented here, strain BPTF-M16T is considered to represent a novel species of the genus Altererythrobacter, for which the name Altererythrobacter insulae sp. nov. is proposed. The type strain is BPTF-M16T (=KCTC 62421T=KACC 19609T=NBRC 113190T).

Ancylomarina salipaludis sp. nov., isolated from a salt marsh.

A Gram-stain-negative, aerobic, non-motile and rod-shaped or filamentous bacterial strain, designated SHSM-M15T, was isolated from a salt marsh at Siheung in Republic of Korea and identified by polyphasic taxonomic study. Strain SHSM-M15T grew optimally at 25 °C, at pH 7.0-8.0 and in the presence of 1.0-2.0 % (w/v) NaCl. Phylogenetic trees based on 16S rRNA gene sequences showed that strain SHSM-M15T clusters with the type strain of Ancylomarina subtilis, showing 16S rRNA gene sequence similarity of 97.8 %. Strain SHSM-M15T had 16S rRNA gene sequence similarities of less than 93.7 % with the type strains of other recognised species. Strain SHSM-M15T contained MK-7 as the predominant menaquinone and iso-C15 : 0, iso-C15 : 0 3-OH and anteiso-C15 : 0 as the major fatty acids. The major polar lipid detected in strain SHSM-M15T was phosphatidylethanolamine. The DNA G+C content of strain SHSM-M15T from genomic sequence was 36.6 %. Mean DNA-DNA relatedness value between strain SHSM-M15T and the type strain of A. subtilis was 18 % and the average nucleotide identity value between strain SHSM-M15T and the type strain of A. subtilis was 87.98 %. The phylogenetic and genetic data and differential phenotypic properties indicated that strain SHSM-M15T is separated from A. subtilis. On the basis of the polyphasic data presented, strain SHSM-M15T is considered to represent a novel species of the genus Ancylomarina, for which the name Ancylomarina salipaludis sp. nov. is proposed. The type strain is SHSM-M15T (=KACC 19862T=NBRC 113749T).

Altererythrobacter aquimixticola sp. nov., isolated from sediment sampled at the junction between the ocean and a freshwater spring.

A Gram-stain-negative, aerobic, non-motile and coccoid-, ovoid- or rod-shaped bacterial strain, designated SSKS-13T, was isolated from sediment sampled at the junction between the ocean and a freshwater spring at Jeju island, Republic of Korea. Strain SSKS-13T grew optimally at 37 °C and in the presence of 2.0 % (w/v) NaCl. A neighbour-joining phylogenetic tree of 16S rRNA gene sequences showed that strain SSKS-13T fell within the clade comprising the type strains of Altererythrobacter species, clustering with the type strains of Altererythrobacter lauratis, Altererythrobacter palmitatis and Altererythrobacter buctensis having 16S rRNA gene sequence similarities of 97.2-97.6 %. Strain SSKS-13T exhibited 16S rRNA gene sequence similarities of less than 97.0 % to the type strains of the other recognized species. Strain SSKS-13T contained Q-10 as the predominant ubiquinone and C18 : 1 ω7c as the major fatty acid. The major polar lipids detected in strain SSKS-13T were phosphatidylethanolamine, phosphatidylglycerol and sphingoglycolipid. The DNA G+C content of strain SSKS-13T was 64.6 mol%. The mean DNA-DNA relatedness values of strain SSKS-13T with the type strains of A. lauratis, A. palmitatis and A. buctensis were 11.7-25.3 %. Differential phenotypic properties, together with the phylogenetic and genetic data, proved that strain SSKS-13T is distinct from recognized Altererythrobacter species. On the basis of the data presented here, strain SSKS-13T is considered to represent a novel species of the genus Altererythrobacter, for which the name Altererythrobacter aquimixticola sp. nov. is proposed. The type strain is SSKS-13T (=KACC 19863T=KCTC 62900T=NBRC 113545T).

Pharmacokinetics and bioequivalence of two fenofibrate choline formulations in healthy subjects under fed and fasted condition
.

OBJECTIVE: The objective of this study was to evaluate the pharmacokinetics and bioequivalence of two formulations (the original capsule ("reference") and the new tablet ("test") formulations) of 135-mg choline fenofibrate under fed and fasted conditions. MATERIALS AND METHODS: This was an open-label, randomized, single-dose, crossover bioequivalence study in healthy Korean males. A total of 40 individuals were separately enrolled in the high-fat fed and the fasting study, respectively, and were randomized in a 1:1 ratio into two sequences. Serial blood samples were collected over 72 hours after drug administration. Plasma concentrations of fenofibric acid were determined by a validated LC-MS/MS method. Pharmacokinetic (PK) parameters were estimated using noncompartmental methods. RESULTS: Overall, 37 and 35 individuals completed the fed and the fasting study, respectively, as planned. The estimated Cmax, AUC0-∞, and AUC0-last were comparable between the test and the reference formulations in both fed and fasting studies (p > 0.05). The 90% confidence intervals for the geometric mean ratios of Cmax, AUC0-∞, and AUC0-last were 0.92 - 1.06, 0.95 - 1.01, and 0.95 - 1.01 in the fed study; and 0.94 - 1.12, 0.94 - 1.00, and 0.94 - 1.00 in the fasting study, respectively. For both formulations, tmax was significantly prolonged under fed condition compared to fasting condition (p < 0.0001); all other PK parameters were comparable between the fed and the fasting studies (p > 0.05). CONCLUSION: The reference and the test formulations of 135 mg choline fenofibrate show comparable pharmacokinetic profiles of fenofibric acid under both fed and fasted conditions and are considered bioequivalent.
.

Zhongshania ponticola sp. nov., a novel lipolytic bacterium of the class Gammaproteobacteria isolated from seawater.

A bacterial strain, designated GM-8T, which was isolated from seawater around Pohang in Republic of Korea, was subjected to a polyphasic taxonomic study. It was lipolytic, Gram-stain-negative, aerobic, non-motile and coccoid, ovoid, or rod-shaped. Strain GM-8T grew optimally at 30 °C and in the presence of 2.0-3.0% (w/v) NaCl. The phylogenetic trees of 16S rRNA gene sequences based on three algorithms showed that strain GM-8T joined the clade comprising the type strains of Zhongshania species. The novel strain exhibited the highest 16S rRNA gene sequence similarity value (98.6%) to Zhongshania borealis CL-AS9T and sequence similarities of 97.7-98.3% to the type strains of three other Zhongshania species. Strain GM-8T contained Q-8 as the predominant ubiquinone and C17:1 ω8c, summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), and C18:1 ω7c as the major fatty acids. Phosphatidylglycerol and phosphatidylethanolamine were major polar lipids found in strain GM-8T and the type strain of Zhongshania antarctica. The DNA G + C content of strain GM-8T was 50.9 mol%. Mean DNA-DNA relatedness values between strain GM-8T and the type strains of four other Zhongshania species were 13.3-20.3%. Its differential phenotypic traits, together with the phylogenetic and genetic evidences, revealed that strain GM-8T is distinct from recognized species of the genus Zhongshania. On the basis of the data presented, strain GM-8T represents a novel species of the genus Zhongshania, for which the name Zhongshania ponticola sp. nov. is proposed. The type strain is GM-8T (= KCTC 62425T = KACC 19616T = NBRC 113193T).

Pseudoruegeria litorisediminis sp. nov., a novel lipolytic bacterium of the family Rhodobacteraceae isolated from a tidal flat.

A lipolytic bacterial strain, designated BPTF-M5T, was isolated from a tidal flat sediment of the Yellow Sea in Republic of Korea, and identified by a polyphasic taxonomic approach. It was Gram negative, aerobic, non-motile and rod shaped. Strain BPTF-M5T grew optimally at 30 °C and in the presence of 2.0-3.0% (w/v) NaCl. A neighbour-joining phylogenetic tree of 16S rRNA gene sequences showed that strain BPTF-M5T fell within the clade comprising the type strains of Pseudoruegeria species. The novel strain exhibited the highest 16S rRNA gene sequence similarity value (98.6%) to Pseudoruegeria marinistellae SF-16T. Strain BPTF-M5T exhibited sequence similarities of 97.0-98.5% to the type strains of five other Pseudoruegeria species and of less than 96.1% to other recognized species. Strain BPTF-M5T contained Q-10 as the predominant ubiquinone and C18:1 ω7c as the major fatty acid. Phosphatidylglycerol, one unidentified aminolipid, one unidentified lipid and one unidentified glycolipid were detected as major polar lipids in the novel strain. The DNA G + C content of strain BPTF-M5T was 63.3 mol%. DNA-DNA relatedness values between strain BPTF-M5T and the type strains of the six Pseudoruegeria species were 11.0-24.3%. The phenotypic properties of strain BPTF-M5T were clearly distinguished from those of the type strains of the six Pseudoruegeria species. Based on the polyphasic data presented, strain BPTF-M5T represents a novel species of the genus Pseudoruegeria, for which the name Pseudoruegeria litorisediminis sp. nov. is proposed. The type strain is BPTF-M5T (= KCTC 62420T = KACC 19613T = NBRC 113189T).

Pseudoruegeria insulae sp. nov., isolated from a tidal flat.

A Gram-stain-negative, aerobic, non-motile and ovoid or rod-shaped bacterial strain, designated BPTF-M20T, was isolated from tidal flat sediment in the Yellow Sea, Republic of Korea. Strain BPTF-M20T grew optimally at 30 °C, at pH 7.0-8.0 and in the presence of 2.0-3.0 % (w/v) NaCl. A neighbour-joining phylogenetic tree of 16S rRNA gene sequences showed that strain BPTF-M20T fell within the clade comprising the type strains of Pseudoruegeria species. Strain BPTF-M20T exhibited 16S rRNA gene sequence similarity values of 97.4-98.3 % to the type strains of Pseudoruegeria haliotis, Pseudoruegeria lutimaris, 'Pseudoruegeria litorisediminis' and Pseudoruegeria sabulilitoris and 96.4-96.9 % to the type strains of the other Pseudoruegeria species. Strain BPTF-M20T contained Q-10 as the predominant ubiquinone and C18 : 1ω7c as the major fatty acid. The major polar lipids detected in strain BPTF-M20T were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, one unidentified aminolipid and one unidentified glycolipid. The DNA G+C content of strain BPTF-M20T was 63.2 mol%. Mean DNA-DNA relatedness values of strain BPTF-M20T with the type strains of P. haliotis, P. lutimaris, P. sabulilitoris and 'P. litorisediminis' were 18-27 %. Differential phenotypic properties, together with the phylogenetic and genetic data, revealed that strain BPTF-M20T was separated from recognized Pseudoruegeria species. On the basis of the data presented here, strain BPTF-M20T is considered to represent a novel species of the genus Pseudoruegeria, for which the name Pseudoruegeriainsulae sp. nov. is proposed. The type strain is BPTF-M20T (=KACC 19614T=KCTC 62422T=NBRC 113188T).

Aestuariimonas insulae gen. nov., sp. nov., isolated from a tidal flat.

A Gram-stain-negative, aerobic, non-motile and ovoid or rod-shaped bacterial strain, designated OITF-44T, was isolated from a tidal flat in Oido, an island of the Republic of Korea. Strain OITF-44T grew optimally at 25 °C and in the presence of 2.0 % (w/v) NaCl. The phylogenetic trees based on 16S rRNA gene sequences revealed that strain OITF-44T formed an independent lineage within the clade comprising the genera Lutimonas, Taeania, Actibacter and Namhaeicola. The novel strain exhibited 16S rRNA gene sequence similarity values of 93.9-95.7 % to the type strains of the species of the genera Lutimonas, Taeania, Actibacter and Namhaeicola, and of less than 93.5 % to the type strains of other recognized species. Strain OITF-44T contained MK-6 as the predominant menaquinone and iso-C15 : 0, iso-C15 : 1 G, iso-C16 : 1 H and iso-C16 : 0 3-OH as the major fatty acids. The major polar lipids of strain OITF-44T were phosphatidylethanolamine, one unidentified lipid and one unidentified phospholipid. The DNA G+C content of strain OITF-44T was 33.9 mol%. The chemotaxonomic data and other differential phenotypic properties made it reasonable to distinguish strain OITF-44T from the type strains of the type species of the genera Lutimonas, Taeania, Actibacter and Namhaeicola. On the basis of the data presented here, strain OITF-44T is considered to constitute a new genus and species within the family Flavobacteriaceae, for which the name Aestuariimonas insulae gen. nov., sp. nov. is proposed. The type strain of Aestuariimonas insulae is OITF-44T (=KACC 19569T=KCTC 62197T=DSM 105891T=NBRC 113118T).

Aestuariibius insulae gen. nov., sp. nov., isolated from a tidal flat sediment.

A Gram-stain-negative, non-motile and ovoid or rod-shaped bacterial strain, DBTF-13T, which was isolated from a tidal flat sediment of the Yellow Sea in South Korea, was characterized taxonomically. Strain DBTF-13T grew optimally at 25-30 °C and pH 7.0-8.0, and in the presence of 2.0 % (w/v) NaCl. The phylogenetic trees based on 16S rRNA gene sequences revealed that strain DBTF-13T formed an evolutionary lineage independent of other genera, including the genera Pseudooctadecabacter and Octadecabacter. Strain DBTF-13T exhibited 16S rRNA gene sequence similarity values of 96.9 % to the type strain of Pseudooctadecabacter jejudonensis, and of 95.8-96.5 % to the type strains of Octadecabacter species. Strain DBTF-13T contained Q-10 as the predominant ubiquinone and C18 : 1ω7c and C16 : 0 as the major fatty acids. The major polar lipids of strain DBTF-13T were phosphatidylcholine, phosphatidylglycerol, one unidentified aminolipid and one unidentified lipid. The DNA G+C content of strain DBTF-13T was 61.6 mol%. The chemotaxonomic data and other differential phenotypic properties made it reasonable to differentiate strain DBTF-13T from the genera Pseudooctadecabacter and Octadecabacter. On the basis of the data presented, strain DBTF-13T constitutes a new genus and species within the class Alphaproteobacteria, for which the name Aestuariibius insulae gen. nov., sp. nov. is proposed. The type strain is DBTF-13T (=KACC 19432T=NBRC 113038T).

Pseudomaribius aestuariivivens gen. nov., sp. nov., isolated from a tidal flat sediment.

A Gram-stain-negative, non-motile and ovoid or rod-shaped bacterial strain, DBTF-15T, was isolated from a tidal flat sediment on the Yellow Sea in South Korea. Strain DBTF-15T grew optimally at 25-30 °C, at pH 7.0-8.0 and in the presence of 2.0 % (w/v) NaCl. The phylogenetic trees based on 16S rRNA gene sequences revealed that strain DBTF-15T joined the cluster comprising the type strains of species of the genus Palleronia. Strain DBTF-15T exhibited higher 16S rRNA gene sequence similarity values to the type strains (96.5-96.7 %) of Maribius pelagius and Maribius salinus than to those (94.6-96.1 %) of the three species of the genus Palleronia. It exhibited 16S rRNA gene sequence similarity values of less than 93.9 % to the type strains of the other recognized species. Strain DBTF-15T contained Q-10 as the predominant ubiquinone and C18 : 1ω7c as the major fatty acid. The major polar lipids of strain DBTF-15T were phosphatidylcholine, phosphatidylglycerol and one unidentified aminolipid. The DNA G+C content of strain DBTF-15T was 68.7 mol%. The chemotaxonomic data and other differential phenotypic properties made it possible to distinguish strain DBTF-15T from the genera Maribius and Palleronia. On the basis of the data presented, strain DBTF-15T constitutes a novel genus and species within the class Alphaproteobacteria, for which the name Pseudomaribius aestuariivivens gen. nov., sp. nov. is proposed. The type strain is DBTF-15T (=KACC 19431T=NBRC 113039T).

Vitellibacter todarodis sp. nov., isolated from intestinal tract of a squid (Todarodes pacificus).

A Gram-stain-negative, non-motile, aerobic and rod-shaped or ovoid bacterial strain, designated MYP2-2T, was isolated from the intestinal tract of a squid (Todarodes pacificus) collected from the East Sea, South Korea, and subjected to a polyphasic taxonomic study. Strain MYP2-2T grew optimally at 30-35 °C and in the presence of 2.0 % (w/v) NaCl. A neighbour-joining phylogenetic tree based on 16S rRNA gene sequences revealed that strain MYP2-2T belonged to the genus Vitellibacter. Strain MYP2-2T exhibited 16S rRNA gene sequence similarities of 95.4-96.6 % to the type strains of Vitellibacter species and of less than 94.5 % to the type strains of other recognized species examined. Strain MYP2-2T contained menaquinone MK-6 as the predominant respiratory quinone and iso-C15 : 0 and iso-C17 : 0 3-OH as the major fatty acids. The major polar lipids detected in strain MYP2-2T were phosphatidylethanolamine and one unidentified lipid. The DNA G+C content of strain MYP2-2T was 41.6 mol%. Differential phenotypic properties, together with its phylogenetic distinctiveness, revealed that strain MYP2-2T is separated from recognized species of the genus Vitellibacter. On the basis of the data presented, strain MYP2-2T is considered to represent a novel species of the genus Vitellibacter, for which the name Vitellibacter todarodis sp. nov. is proposed. The type strain is MYP2-2T (=KCTC 62141T=NBRC 113025T).

Pseudopontivivens aestuariicola gen. nov., sp. nov., a Novel Bacterium of the Class Alphaproteobacteria Isolated from a Tidal Flat.

A Gram-stain-negative, non-motile and coccoid, ovoid or rod-shaped bacterial strain, OITF-57T, which was isolated from a tidal flat sediment in South Korea, was characterized taxonomically. Strain OITF-57T grew optimally at 25 °C, at pH 7.0-8.0 and in the presence of 2.0% (w/v) NaCl. Strain OITF-57T exhibited the highest 16S rRNA gene sequence similarity value (94.2%) to the type strain of Pontivivens insulae forming a cluster in the neighbour-joining phylogenetic tree. In the maximum-likelihood and maximum-parsimony phylogenetic trees based on 16S rRNA gene sequences and the phylogenetic tress based on gyrB sequences, strain OITF-57T formed evolutionary lineages independent of those of other taxa. Strain OITF-57T contained Q-10 as the predominant ubiquinone and C18:1 ω7c as the major fatty acid. The major polar lipids of strain OITF-57T were phosphatidylcholine and phosphatidylglycerol. The DNA G + C content of strain OITF-57T was 66.0 mol%. The chemotaxonomic data and other differential phenotypic properties made it possible to distinguish strain OITF-57T from the genus Pontivivens and other phylogenetically related genera. On the basis of the data presented, strain OITF-57T constitutes a new genus and species within the class Alphaproteobacteria, for which the name Pseudopontivivens aestuariicola gen. nov., sp. nov. is proposed. The type strain is OITF-57T (= KACC 19570T = CGMCC 1.13481T).

Endogenous N-terminal Domain Cleavage Modulates α1D-Adrenergic Receptor Pharmacodynamics.

The α1D-adrenergic receptor (ADRA1D) is a key regulator of cardiovascular, prostate, and central nervous system functions. This clinically relevant G protein-coupled receptor has proven difficult to study, as it must form an obligate modular homodimer containing the PDZ proteins scribble and syntrophin or become retained in the endoplasmic reticulum as non-functional protein. We previously determined that targeted removal of the N-terminal (NT) 79 amino acids facilitates ADRA1D plasma membrane expression and agonist-stimulated functional responses. However, whether such an event occurs in physiological contexts was unknown. Herein, we report the ADRA1D is subjected to innate NT processing in cultured human cells. SNAP near-infrared imaging and tandem-affinity purification revealed the ADRA1D is expressed as both full-length and NT truncated forms in multiple human cell lines. Serial truncation mapping identified the cleavage site as Leu(90)/Val(91) in the 95-amino acid ADRA1D NT domain, suggesting human cells express a Δ1-91 ADRA1D species. Tandem-affinity purification MS/MS and co-immunoprecipitation analysis indicate NT processing of ADRA1D is not required to form scribble-syntrophin macromolecular complexes. Yet, label-free dynamic mass redistribution signaling assays demonstrate that Δ1-91 ADRA1D agonist responses were greater than WT ADRA1D. Mutagenesis of the cleavage site nullified the processing event, resulting in ADRA1D agonist responses less than the WT receptor. Thus, we propose that processing of the ADRA1D NT domain is a physiological mechanism employed by cells to generate a functional ADRA1D isoform with optimal pharmacodynamic properties.

PINK1 positively regulates HDAC3 to suppress dopaminergic neuronal cell death.

Deciphering the molecular basis of neuronal cell death is a central issue in the etiology of neurodegenerative diseases, such as Parkinson's and Alzheimer's. Dysregulation of p53 levels has been implicated in neuronal apoptosis. The role of histone deacetylase 3 (HDAC3) in suppressing p53-dependent apoptosis has been recently emphasized; however, the molecular basis of modulation of p53 function by HDAC3 remains unclear. Here we show that PTEN-induced putative kinase 1 (PINK1), which is linked to autosomal recessive early-onset familial Parkinson's disease, phosphorylates HDAC3 at Ser-424 to enhance its HDAC activity in a neural cell-specific manner. PINK1 prevents H2O2-induced C-terminal cleavage of HDAC3 via phosphorylation of HDAC3 at Ser-424, which is reversed by protein phosphatase 4c. PINK1-mediated phosphorylation of HDAC3 enhances its direct association with p53 and causes subsequent hypoacetylation of p53. Genetic deletion of PINK1 partly impaired the suppressive role of HDAC3 in regulating p53 acetylation and transcriptional activity. However, depletion of HDAC3 fully abolished the PINK1-mediated p53 inhibitory loop. Finally, ectopic expression of phosphomometic-HDAC3(S424E) substantially overcomes the defective action of PINK1 against oxidative stress in dopaminergic neuronal cells. Together, our results uncovered a mechanism by which PINK1-HDAC3 network mediates p53 inhibitory loop in response to oxidative stress-induced damage.

Label-Free Dynamic Mass Redistribution Reveals Low-Density, Prosurvival α1B-Adrenergic Receptors in Human SW480 Colon Carcinoma Cells.

Small molecules that target the adrenergic family of G protein-coupled receptors (GPCRs) show promising therapeutic efficacy for the treatment of various cancers. In this study, we report that human colon cancer cell line SW480 expresses low-density functional α1B-adrenergic receptors (ARs) as revealed by label-free dynamic mass redistribution (DMR) signaling technology and confirmed by quantitative reverse-transcriptase polymerase chain reaction analysis. Remarkably, although endogenous α1B-ARs are not detectable via either [3H]-prazosin-binding analysis or phosphoinositol hydrolysis assays, their activation leads to robust DMR and enhanced cell viability. We provide pharmacological evidence that stimulation of α1B-ARs enhances SW480 cell viability without affecting proliferation, whereas stimulating ß-ARs diminishes both viability and proliferation of SW480 cells. Our study illustrates the power of label-free DMR technology for identifying and characterizing low-density GPCRs in cells and suggests that drugs targeting both α1B- and ß-ARs may represent valuable small-molecule therapeutics for the treatment of colon cancer.

Puniceibacterium confluentis sp. nov., isolated from the junction between the ocean and a freshwater spring, and emended description of the genus Puniceibacterium.

A Gram-stain-negative, non-motile, aerobic and ovoid or rod-shaped bacterium, designated JSSK-17T, was isolated from the place where the ocean and a freshwater spring meet at Jeju island, South Korea. Strain JSSK-17T grew optimally at 30 °C, at pH 7.0-8.0 and in the presence of 1.0-2.0 % (w/v) NaCl. Phylogenetic trees, based on 16S rRNA gene sequences, showed that strain JSSK-17T clustered with the type strains of Puniceibacterium antarcticum and Puniceibacterium sediminis, exhibiting sequence similarities of 98.1-98.2 %. Strain JSSK-17T and the type strains of P. antarcticum and P. sediminis contained Q-10 as the predominant ubiquinone and C18 : 1ω7c as the major fatty acid. The predominant polar lipids detected in strain JSSK-17T and the type strains of P. antarcticum and P. sediminis were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminolipid, one unidentified glycolipid and one unidentified phospholipid. The DNA G+C content of strain JSSK-17T was 64.4 mol% and its DNA-DNA relatedness values with the type strains of P. antarcticum and P. sediminis were 24 and 15 %, respectively. The differential phenotypic properties, together with the phylogenetic and genetic distinctiveness, revealed that strain JSSK-17T is separated from the two reference species of the genus Puniceibacteriumwith validly published names. On the basis of the data presented, strain JSSK-17T is considered to represent a novel species of the genus Puniceibacterium, for which the name Puniceibacterium confluentis sp. nov. is proposed. The type strain is JSSK-17T (=KCTC 52765T=NBRC 112766T).