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951.
The 6-deoxyerythronolide B synthase (DEBS) is a prototypical assembly line polyketide synthase produced by the actinomycete Saccharopolyspora erythraea that synthesizes the macrocyclic core of the antibiotic erythromycin 6-deoxyerythronolide B. The megasynthase is a 2-MDa trimeric complex composed of three unique homodimers assembled from the gene products DEBS1, DEBS2, and DEBS3, which are housed within the erythromycin biosynthetic gene cluster. Each homodimer contains two clusters of catalytically independent enzymatic domains, each referred to as a module, which catalyzes one round of polyketide chain extension and modification. Modules are named sequentially to indicate the order in which they are utilized during synthesis of 6-deoxyerythronolide B. We report small-angle X-ray scattering (SAXS) analyses of a whole module and a bimodule from DEBS, as well as a set of domains for which high-resolution structures are available. In all cases, the solution state was probed under previously established conditions ensuring that each protein is catalytically active. SAXS data are consistent with atomic-resolution structures of DEBS fragments. Therefore, we used the available high-resolution structures of DEBS domains to model the architectures of the larger protein assemblies using rigid-body refinement. Our data support a model in which the third module of DEBS forms a disc-shaped structure capable of caging the acyl carrier protein domain proximal to each active site. The molecular envelope of DEBS3 is a thin elongated ellipsoid, and the results of rigid-body modeling suggest that modules 5 and 6 stack collinearly along the 2-fold axis of symmetry. 相似文献
952.
Hiroyuki Matsui Naoto Fukuno Yoshiaki Kanda Yusuke Kantoh Toko Chida Yuko Nagaura Osamu Suzuki Hideki Nishitoh Kohsuke Takeda Hidenori Ichijo Yasuhiro Sawada Keiichi Sasaki Takayasu Kobayashi Shinri Tamura 《The Journal of biological chemistry》2014,289(10):6438-6450
Bone mass is maintained by the balance between the activities of bone-forming osteoblasts and bone-resorbing osteoclasts. It is well known that adequate mechanical stress is essential for the maintenance of bone mass, whereas excess mechanical stress induces bone resorption. However, it has not been clarified how osteoblasts respond to different magnitudes of mechanical stress. Here we report that large-magnitude (12%) cyclic stretch induced Ca2+ influx, which activated reactive oxygen species generation in MC3T3-E1 osteoblasts. Reactive oxygen species then activated the ASK1-JNK/p38 pathways. The activated JNK led to transiently enhanced expression of FGF-inducible 14 (Fn14, a member of the TNF receptor superfamily) gene. Cells with enhanced expression of Fn14 subsequently acquired sensitivity to the ligand of Fn14, TNF-related weak inducer of apoptosis, and underwent apoptosis. On the other hand, the ASK1-p38 pathway induced expression of the monocyte chemoattractant protein 3 (MCP-3) gene, which promoted chemotaxis of preosteoclasts. In contrast, the ERK pathway was activated by small-magnitude stretching (1%) and induced expression of two osteogenic genes, collagen Ia (Col1a) and osteopontin (OPN). Moreover, activated JNK suppressed Col1a and OPN induction in large-magnitude mechanical stretch-loaded cells. The enhanced expression of Fn14 and MCP-3 by 12% stretch and the enhanced expression of Col1a and OPN by 1% stretch were also observed in mouse primary osteoblasts. These results suggest that differences in the response of osteoblasts to varying magnitudes of mechanical stress play a key role in switching the mode of bone metabolism between formation and resorption. 相似文献
953.
954.
Yukimaru Sugiyama Hiroyuki Kurita Takeshi Matsui Satoshi Kimoto Junko Egawa 《Primates; journal of primatology》2014,55(2):303-311
From the late 1960s to the early 1970s, many congenitally malformed infants were born into provisioned Japanese macaque troops. Although the exact cause of this problem was not determined, the occurrence of malformations decreased thereafter. We examined possible factors such as total population size, number of adult females, birth rate, and volume of provisioned food. Agrichemicals attached to provisioned food are suspected as the main cause, as other factors were found to have no influence. Many more malformations were seen in males compared with females, in feet compared with hands, and in the fourth compared with other digits. We confirmed that the frequency of congenital malformation was high during the 1960s through to the mid-1970s when increased levels of provisioned food were given and that the incidence of congenital malformations was also elevated among wild macaques during this time. 相似文献
955.
T. Koeduka K. Sugimoto B. Watanabe N. Someya D. Kawanishi T. Gotoh R. Ozawa J. Takabayashi K. Matsui J. Hiratake 《Plant biology (Stuttgart, Germany)》2014,16(2):451-456
A variety of volatile phenylpropenes, C6‐C3 compounds are widely distributed in the plant kingdom, whereas prenylated phenylpropenes are limited to a few plant species. In this study, we analysed the volatile profiles from Illicium anisatum leaves and identified two O‐prenylated phenylpropenes, 4‐allyl‐2‐methoxy‐1‐[(3‐methylbut‐2‐en‐1‐yl)oxy]benzene [O‐dimethylallyleugenol ( 9 )] and 5‐allyl‐1,3‐dimethoxy‐2‐(3‐methylbut‐2‐en‐1‐yl)oxy]benzene [O‐dimethylallyl‐6‐methoxyeugenol ( 11 )] as major constituents. The structure–activity relationship of a series of eugenol derivatives showed that specific phenylpropenes, including eugenol ( 1 ), isoeugenol ( 2 ) and 6‐methoxyeugenol ( 6 ), with a phenolic hydroxy group had antifungal activity for a fungal pathogen, whereas guaiacol, a simple phenolic compound, and allylbenzene had no such activity. The eugenol derivatives that exhibited antifungal activity, in turn, had no significant toxicant property for mite oviposition. Interestingly, O‐dimethylallyleugenol ( 9 ) in which the phenolic oxygen was masked with a dimethylallyl group exhibited a specific, potent oviposition deterrent activity for mites. The sharp contrast in structural requirements of phenylpropenes suggested distinct mechanisms underlying the two biological activities and the importance of a phenolic hydroxy group and its dimethylallylation for the structure‐based design of new functional properties of phenylpropenes. 相似文献
956.
Kohmei Kadowaki Hirotoshi Sato Satoshi Yamamoto Akifumi S. Tanabe Amane Hidaka Hirokazu Toju 《Population Ecology》2014,56(2):301-310
Soil microbes are considered to be a key determinant of the aboveground plant community. They are not distributed uniformly in the environment, and their activity, abundance, and ecosystem functioning could vary across localities, characterized by high β-diversity. Investigating factors that contribute to high β-diversity can help infer the possible mechanisms of microbial community assembly, and predict the scale and extent of impacts that soil microbes have on the plant community. Because soil systems consist of multiple horizons (i.e., vertical stratification) associated with different soil properties, complete understanding of high β-diversity requires consideration of both horizontal and vertical spatial structures of soil microbial communities. We studied the community composition of soil fungi from the O- and A-horizons in a Castanopsis-dominated temperate forest, and compared horizontal spatial autocorrelation in species composition between the two soil horizons (O- versus A-horizons). Pyrosequencing analysis yielded 67,129 sequencing reads, summed across all the 48 forest soil samples. Clustering analysis resulted in 597 molecular operational taxonomic units (OTUs), 68 % of which were identified as fungi, represented by four phyla. The Mantel test revealed that the O-horizon communities are spatially clustered, and the observed high β-diversity was driven not only by changes in OTUs present, but also by high turnover in identities of OTUs in soil samples. Furthermore, Mantel correlogram analysis showed that the O-horizon communities resembled each other in composition within the range of 50 m, whereas the A-horizon communities lacked such horizontal autocorrelation. These differences in the scale patchiness could arise from two processes: (1) that environmental conditions could show higher heterogeneity in finer scale at the A-horizon than at the O-horizon; and/or (2) dispersal could be more frequent at the O-horizon than the A-horizon. The present study suggests that either environmental filtering (i.e., the niche-based process) or dispersal limitation (i.e., neutral process) could characterize the observed patterns of spatial clustering in the soil fungal community. 相似文献
957.
Ichiro Mizushima Dai Inoue Motohisa Yamamoto Kazunori Yamada Takako Saeki Yoshifumi Ubara Shoko Matsui Yasufumi Masaki Takashi Wada Satomi Kasashima Kenichi Harada Hiroki Takahashi Kenji Notohara Yasuni Nakanuma Hisanori Umehara Masakazu Yamagishi Mitsuhiro Kawano 《Arthritis research & therapy》2014,16(4)
Introduction
Immunoglobulin G4 (IgG4)–related aortitis/periaortitis and periarteritis are vascular manifestations of IgG4-related disease. In this disease, the affected aneurysmal lesion has been suspected to be at risk of rupture. In this study, we aimed to clarify the clinical course after corticosteroid therapy in IgG4-related aortitis/periaortitis and periarteritis.Methods
We retrospectively evaluated clinical features, including laboratory data, imaging findings and the course after corticosteroid therapy, in 40 patients diagnosed with IgG4-related aortitis/periaortitis and periarteritis on the basis of periaortic/periarterial radiological findings, satisfaction of the comprehensive diagnostic criteria or each organ-specific diagnostic criteria, and exclusion of other diseases.Results
The patients were mainly elderly, with an average age of 66.4 years and with a marked male predominance and extensive other organ involvement. Subjective symptoms were scanty, and only a small proportion had elevated serum C-reactive protein levels. The affected aorta/artery were the abdominal aortas or the iliac arteries in most cases. Thirty-six patients were treated with prednisolone, and the periaortic/periarterial lesions improved in most of them during the follow-up period. Two (50.0%) of four patients with luminal dilatation of the affected lesions before corticosteroid therapy had exacerbations of luminal dilatation after therapy, whereas none of the twenty-six patients without it had a new appearance of luminal dilatation after therapy.Conclusions
The results of this retrospective multicenter study highlight three important points: (1) the possibility of latent existence and progression of periaortic/periarterial lesions, (2) the efficacy of corticosteroid therapy in preventing new aneurysm formation in patients without luminal dilatation of periaortic/periarterial lesions and (3) the possibility that a small proportion of patients may actually develop luminal dilatation of periaortic/periarterial lesions in IgG4-related aortitis/periaortitis and periarteritis. A larger-scale prospective study is required to confirm the efficacy and safety of corticosteroid therapy in patients with versus those without luminal dilatation and to devise a more useful and safe treatment strategy, including administration of other immunosuppressants. 相似文献958.
Seung Joong Kim Javier Fernandez-Martinez Parthasarathy Sampathkumar Anne Martel Tsutomu Matsui Hiro Tsuruta Thomas M. Weiss Yi Shi Ane Markina-Inarrairaegui Jeffery B. Bonanno J. Michael Sauder Stephen K. Burley Brian T. Chait Steven C. Almo Michael P. Rout Andrej Sali 《Molecular & cellular proteomics : MCP》2014,13(11):2911-2926
959.
Yohei Mikami Shinta Mizuno Nobuhiro Nakamoto Atsushi Hayashi Tomohisa Sujino Toshiro Sato Nobuhiko Kamada Katsuyoshi Matsuoka Tadakazu Hisamatsu Hirotoshi Ebinuma Toshifumi Hibi Akihiko Yoshimura Takanori Kanai 《PloS one》2014,9(1)
The liver is a physiological site of immune tolerance, the breakdown of which induces immunity. Liver antigen-presenting cells may be involved in both immune tolerance and activation. Although inflammatory diseases of the liver are frequently associated with inflammatory bowel diseases, the underlying immunological mechanisms remain to be elucidated. Here we report two murine models of inflammatory bowel disease: RAG-2−/− mice adoptively transferred with CD4+CD45RBhigh T cells; and IL-10−/− mice, accompanied by the infiltration of mononuclear cells in the liver. Notably, CD11b−CD11clowPDCA-1+ plasmacytoid dendritic cells (DCs) abundantly residing in the liver of normal wild-type mice disappeared in colitic CD4+CD45RBhigh T cell-transferred RAG-2−/− mice and IL-10−/− mice in parallel with the emergence of macrophages (Mφs) and conventional DCs (cDCs). Furthermore, liver Mφ/cDCs emerging during intestinal inflammation not only promote the proliferation of naïve CD4+ T cells, but also instruct them to differentiate into IFN-γ-producing Th1 cells in vitro. The emergence of pathological Mφ/cDCs in the liver also occurred in a model of acute dextran sulfate sodium (DSS)-induced colitis under specific pathogen-free conditions, but was canceled in germ-free conditions. Last, the Mφ/cDCs that emerged in acute DSS colitis significantly exacerbated Fas-mediated hepatitis. Collectively, intestinal inflammation skews the composition of antigen-presenting cells in the liver through signaling from commensal bacteria and predisposes the liver to inflammation. 相似文献
960.
Yoshitsugu Matsui Hisashi Matsubara Shinji Ueno Yasuki Ito Hiroko Terasaki Mineo Kondo 《PloS one》2014,9(10)