Structural basis of E2-25K/UBB+1 interaction leading to proteasome inhibition and neurotoxicity.

E2-25K/Hip2 is an unusual ubiquitin-conjugating enzyme that interacts with the frameshift mutant of ubiquitin B (UBB(+1)) and has been identified as a crucial factor regulating amyloid-ß neurotoxicity. To study the structural basis of the neurotoxicity mediated by the E2-25K-UBB(+1) interaction, we determined the three-dimensional structures of UBB(+1), E2-25K and the E2-25K/ubiquitin, and E2-25K/UBB(+1) complex. The structures revealed that ubiquitin or UBB(+1) is bound to E2-25K via the enzyme MGF motif and residues in α9 of the enzyme. Polyubiquitylation assays together with analyses of various E2-25K mutants showed that disrupting UBB(+1) binding markedly diminishes synthesis of neurotoxic UBB(+1)-anchored polyubiquitin. These results suggest that the interaction between E2-25K and UBB(+1) is critical for the synthesis and accumulation of UBB(+1)-anchored polyubiquitin, which results in proteasomal inhibition and neuronal cell death.

Roles of urology as assessed by an analysis of inpatients referred to urology.

PURPOSE: The purpose of this study was to identify the necessity for professional urology treatment and the roles of urology in the treatment of inpatients referred to the urology department. MATERIALS AND METHODS: The subjects were patients referred to the department of urology among the inpatients of Chosun University Hospital from January 1, 2009, to December 31, 2011. The patients' sex and age, the referring department, and the disease group were extracted from the patients' medical records. Disease groups were classified as urination disorder, infection, tumor, calculus, trauma, pediatrics, andrology, and others. The urination disorder group was classified into the subcategories of neurogenic bladder, benign prostatic hypertrophy, urinary retention, urinary incontinence, and overactive bladder. RESULTS: The total number of referrals was 3,261, and males made up 54.79%. In the age distribution, 2,321 patients (71.17%) were over 60 years of age and the largest population group was patients in their 70s (32.72%). According to the department referring the patients, internal medicine (34.06%) and orthopedic surgery (16.83%) made up a high percentage. Concerning the disease group, urination disorder was the highest, being 61.26%. In the subclassification of the urination disorder group, benign prostatic hypertrophy was the highest category at 32.23%. CONCLUSIONS: In this urology cooperative behavior analysis of our hospital over 3 years, a high percentage of older patients over 60 years of age and a high percentage of urination disorders were found. Urination disorder-related diseases in persons of advanced age are expected to increase as Korea becomes an aged society, and doctors in other departments should be aware that professional treatment and management by a urologist is needed for the treatment of these disorders.

Regulation of type II collagen expression by cyclin-dependent kinase 6, cyclin D1, and p21 in articular chondrocytes.

This study examined whether cell cycle regulatory proteins, such as cyclin-dependent kinases (CDKs), cyclins, and CDK inhibitors, regulate type II collagen expression and mediate interlukin-1 (IL-1beta)-induced suppression of type II collagen expression in articular chondrocytes. IL-1beta inhibited type II collagen expression, but activated CDK6. Ectopic expression of CDK2 did not alter type II collagen expression. However, overexpression of CDK6 inhibited type II collagen expression, whereas inhibition of CDK6 activity blocked IL-1beta-induced suppression of type II collagen expression. IL-1beta upregulated the expression of cyclin D1, which is known to activate CDK6. In turn, overexpression of cyclin D1 suppressed type II collagen expression. In contrast to cyclin D1, IL-1beta triggered down-regulation of the CDK inhibitor, p21. Overexpression of p21 blocked IL-1beta- or CDK6-induced suppression of type II collagen expression. Our results collectively indicate that CDK6/cyclin D1/p21 complex regulates type II collagen expression in articular chondrocytes.

Marinimicrobium koreense gen. nov., sp. nov. and Marinimicrobium agarilyticum sp. nov., novel moderately halotolerant bacteria isolated from tidal flat sediment in Korea.

Two moderately halotolerant Gram-negative bacteria were isolated from tidal flat sediment of the South Sea in Korea (the Korea Strait). The strains, designated M9T and M18T, were strictly aerobic, rod-shaped and non-spore-forming and motile with a flagellum and their major fatty acids were C(16:0) and C(19:0) cyclo omega8c. Strains M9T and M18T could grow in the presence of up to 13-15% (w/v) NaCl, but their optimum salt concentrations were relatively low (0-3%, w/v). The major predominant isoprenoid quinone was Q-8 and the G + C content of the genomic DNA was 57-58 mol%. Phylogenetic analyses and comparative 16S rRNA gene sequence studies revealed that strains M9T and M18T formed a phylogenetic lineage distinct from the genus Teredinibacter within the class Gammaproteobacteria and were most closely related to the genera Microbulbifer, Saccharophagus and Teredinibacter, with less than 92.5% 16S rRNA gene sequence similarity. The level of 16S rRNA gene sequence similarity between the two strains was 96.7%. On the basis of physiological and phylogenetic properties, strains M9T and M18T represent separate species within a novel genus of the class Gammaproteobacteria, for which the names Marinimicrobium koreense gen. nov., sp. nov. (type species) and Marinimicrobium agarilyticum sp. nov. are proposed. The type strains of Marinimicrobium koreense and Marinimicrobium agarilyticum are M9T (= KCTC 12356T = DSM 16974T) and M18T (= KCTC 12357T = DSM 16975T), respectively.

Pontibacillus chungwhensis gen. nov., sp. nov., a moderately halophilic Gram-positive bacterium from a solar saltern in Korea.

Three moderately halophilic, spore-forming strains, designated BH030062T, BH030049 and BH030080, were isolated from a solar saltern in Korea. Phylogenetic analyses and comparative 16S rRNA gene sequence studies revealed that the isolates represent a novel distinct monophyletic lineage within the phyletic group classically defined as the genus Bacillus and are most closely related to members of the genera Gracilibacillus (93.7-95.1 % similarity), Virgibacillus (93.5-94.8 %), Halobacillus (94.8-95.9 %), Filobacillus (94.4-94.8 %) and Lentibacillus (93.3-93.7 %). Strain BH030062T was strictly aerobic, rod-shaped, Gram-positive and motile by means of peritrichous flagella. It grew in the presence of 1-15 % (w/v) NaCl and at temperatures of 15-45 degrees C. The cell wall peptidoglycan contained A1gamma-meso-diaminopimelic acid as the diagnostic diamino acid. The predominant cellular fatty acids were iso-C(15 : 0), anteiso-C(15 : 0) and iso-C(16 : 0). DNA G+C content was about 41 mol% and the major isoprenoid quinone was MK-7. On the basis of their physiological and molecular properties, the isolates represent a new genus, Pontibacillus gen. nov., and novel species, Pontibacillus chungwhensis sp. nov. The type strain is BH030062T (=KCTC 3890T=DSM 16287T).

Lentibacillus lacisalsi sp. nov., a moderately halophilic bacterium isolated from a saline lake in China.

An aerobic, spore-forming, moderately halophilic bacterium, strain BH260(T), was isolated from a salt lake in China. Cells of this strain were found to be motile rods with flagella. The organism grew optimally at 30-32 degrees C and pH 8.0 in the presence of 12-15% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that the isolate formed a clade with the type strains of the genus Lentibacillus. The levels of 16S rRNA gene sequence similarity for strain BH260(T) with respect to Lentibacillus salsus KCTC 3911(T), Lentibacillus juripiscarius JCM 12147(T) and Lentibacillus salicampi KCCM 41560(T) were 96.0, 95.5 and 95.3%, respectively. Chemotaxonomic data (a DNA G+C content of 44 mol%; MK-7 as the major isoprenoid quinone; A1gamma-meso-diaminopimelic acid as the cell-wall type; phosphatidylglycerol and diphosphatidylglycerol as the major polar lipids; anteiso-C(15:0), anteiso-C(17:0) and iso-C(16:0) as the major fatty acids) also supported assignment of the isolate to the genus Lentibacillus. On the basis of physiological and molecular properties, the isolate represents a novel species within the genus Lentibacillus, for which the name Lentibacillus lacisalsi sp. nov. is proposed. The type strain is BH260(T) (=KCTC 3915(T)=DSM 16462(T)).

Halomonas taeanensis sp. nov., a novel moderately halophilic bacterium isolated from a solar saltern in Korea.

A moderately halophilic, Gram-negative bacterium, strain BH539(T), which was isolated from a solar saltern at Taean in Korea, was considered to be a member of the genus Halomonas. Strain BH539(T) grew at salinities of 1-25% (w/v) and at temperatures of 10-45 degrees C. Cells were short rods that were motile by means of several flagella. Their major fatty acids were C(18:1)omega7c, C(16:0) and C(19:0) cyclo omega8c. The genomic DNA G+C content was about 65 mol% and the predominant ubiquinone was Q-9. Phylogenetic analyses based on 16S rRNA gene sequences indicated that the isolate formed a branch of the species Cobetia marina. However, 23S and 16S rRNA gene sequence similarities revealed that strain BH539(T) was related more closely to the type strains of the genus Halomonas. Phylogenetic analyses based on 23S rRNA gene sequences also indicated that the strain formed a phyletic line within the genus Halomonas. Therefore, it was concluded that strain BH539(T) should be classified within the genus Halomonas, rather than Cobetia. On the basis of physiological and molecular properties, strain BH539(T) represents a novel species of the genus Halomonas, for which the name Halomonas taeanensis sp. nov. is proposed. The type strain is BH539(T) (=KCTC 12284(T)=DSM 16463(T)).