Phosphorylation-induced conformation of beta(2)-adrenoceptor related to arrestin recruitment revealed by NMR

The C-terminal region of G-protein-coupled receptors (GPCRs), stimulated by agonist binding, is phosphorylated by GPCR kinases, and the phosphorylated GPCRs bind to arrestin, leading to the cellular responses. To understand the mechanism underlying the formation of the phosphorylated GPCR-arrestin complex, we performed NMR analyses of the phosphorylated beta(2)-adrenoceptor (beta(2)AR) and the phosphorylated beta(2)AR-beta-arrestin 1 complex, in the lipid bilayers of nanodisc. Here we show that the phosphorylated C-terminal region adheres to either the intracellular side of the transmembrane region or lipids, and that the phosphorylation of the C-terminal region allosterically alters the conformation around M215(5.54) and M279(6.41), located on transemembrane helices 5 and 6, respectively. In addition, we found that the conformation induced by the phosphorylation is similar to that corresponding to the beta-arrestin-bound state. The phosphorylation-induced structures revealed in this study propose a conserved structural motif of GPCRs that enables beta-arrestin to recognize dozens of GPCRs.Peer reviewe

(-)-Epigallocatechin Gallate Reduces Platelet-Derived Growth Factor-BB-Stimulated Interleukin-6 Synthesis in Osteoblasts: Suppression of SAPK/JNK

We previously showed that the mitogen-activated protein (MAP) kinase superfamily, p44/p42 MAP kinase, p38 MAP kinase, and stress-activated protein kinase (SAPK)/c-Jun N-terminal (JNK), positively plays a part in the platelet-derived growth factor-BB- (PDGF-BB-) stimulated synthesis of interleukin-6 (IL-6), a potent bone resorptive agent, in osteoblast-like MC3T3-E1 cells while Akt and p70 S6 kinase negatively regulates the synthesis. In the present study, we investigated whether (-)-epigallocatechin gallate (EGCG), one of the major green tea flavonoids, affects the synthesis of IL-6 in these cells and the mechanism. EGCG significantly reduced the IL-6 synthesis and IL-6 mRNA expression stimulated by PDGF-BB, EGCG reduced the PDGF-BB-stimulated IL-6 synthesis also in primary-cultured osteoblasts. EGCG had no effect on the levels of osteocalcin and osteoprotegerin in MC3T3-E1 cells. The PDGF-BB-induced autophosphorylation of PDGF receptor β was not suppressed by EGCG. The PDGF-BB-induced phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was not affected by EGCG. On the other hand, EGCG markedly suppressed the PDGF-BB-induced phosphorylation of SAPK/JNK. Finally, the PDGF-BB-induced phosphorylation of Akt and p70 S6 kinase was not affected by EGCG. These results strongly suggest that EGCG inhibits the PDGF-BB-stimulated synthesis of IL-6 via suppression of SAPK/JNK pathway in osteoblasts

Identification of candidate flowering and sex genes in white Guinea yam (D. rotundata Poir.) by SuperSAGE transcriptome profiling

Open Access JournalDioecy (distinct male and female individuals) combined with scarce to non-flowering are common features of cultivated yam (Dioscorea spp.). However, the molecular mechanisms underlying flowering and sex determination in Dioscorea are unknown. We conducted SuperSAGE transcriptome profiling of male, female and monoecious individuals to identify flowering and sex-related genes in white Guinea yam (D. rotundata). SuperSAGE analysis generated a total of 20,236 unique tags, of which 13,901 were represented by a minimum of 10 tags. Of these, 88 tags were significantly differentially expressed in male, female and monoecious plants. Of the 88 differentially expressed SuperSAGE tags, 18 corresponded to genes previously implicated in flower development and sex determination in multiple plant species. We validated the SuperSAGE data with quantitative real-time PCR (qRT-PCR)-based analysis of the expression of four candidate genes. Our findings suggest that mechanisms of flowering and sex determination are likely conserved in Dioscorea. We further investigated the flowering patterns of 1938 D. rotundata accessions representing diverse geographical origins over two years, revealing that over 85% of the accessions are either male or non-flowering, and that less than 15% are female, while monoecious plants are rare. Intensity of flowering appeared to be a function of sex, with male plants flowering more abundantly than female ones. Candidate genes identified in this study can be targeted with the aim to induce regular flowering in poor to non-flowering cultivars. Findings of the study provide important inputs for further studies aiming to overcome the challenge of flowering in yams and to improve the efficiency of yam breeding

経尿道的手術患者における留置カテーテルによる尿路感染症

経尿道手術を受け, 術後無菌的な閉鎖式ドレナージによる比較的短期間の尿道カテーテル留置が行なわれた75人の患者について検討した.これらのうち, 72%がカテーテル抜去後尿培養陰性を示した.カテーテル留置に伴う細菌尿をさらに効果的に予防するためには, 予防的な抗生剤の使用と, 標準化されたカテーテル管理体制の併用の必要性が示唆されるA study of 75 patients undergoing transurethral surgery with relatively short-term urethral catheterization with a sterile closed gravity drainage system revealed a 72% over-all incidence of negative urine cultures after catheter removal. The combination of prophylactic use of antimicrobials and a standardized catheter care system is valuable for preventing catheter-associated bacteriuria

急性虫垂炎における異常尿所見について

急性虫垂炎に罹患した32人の患者(成人20人, 子供12人)を対象に, 異常尿所見と手術所見との関連性について検討した.これらのうち尿所見が異常を呈した例は成人10例, 子供5例であった.すべての尿は清潔に採取された.異常尿所見は女性により多く認められた.尿所見が異常を呈した患者の大部分において, 尿路系の近傍で破裂した, あるいは炎症をともなった虫垂を認めたIn a retrospective review of 32 consecutive patients (20 adults and 12 children) with acute appendicitis, we correlated abnormal urinalysis with the operative findings. Abnormal results on urinalysis were noted in 10 adults and 5 children. All urine specimens were collected by the clean-catch method. Abnormal findings were found more frequently in female patients. The majority of the patients with abnormal urinalysis had a ruptured or inflamed appendix in proximity to the urinary tract

クローン氏病による膀胱腫瘍を思わせた膀胱腸瘻の1例

Enterovesical fistula as a complication of Crohn's disease is a rare condition. A case of Crohn's disease with ileovesical and rectovesical fistulas manifesting as bladder tumor is presented

精巣上体原発癌の1例

We present a rare case of primary carcinoma of the left epididymis in a 32-year-old man. Pathological diagnosis was anaplastic carcinoma of epididymis. The patient is alive and free of metastases 2 years after orchidectomy. Clinical and pathological aspects of epididymal carcinomas are discussed with reference to previously reported cases