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Shenhav Cohen Donghoon Lee Bo Zhai Steven P. Gygi Alfred L. Goldberg 《The Journal of cell biology》2014,204(5):747-758
Activation of the PI3K–Akt–FoxO pathway induces cell growth, whereas its inhibition reduces cell survival and, in muscle, causes atrophy. Here, we report a novel mechanism that suppresses PI3K–Akt–FoxO signaling. Although skeletal muscle lacks desmosomes, it contains multiple desmosomal components, including plakoglobin. In normal muscle plakoglobin binds the insulin receptor and PI3K subunit p85 and promotes PI3K–Akt–FoxO signaling. During atrophy, however, its interaction with PI3K–p85 is reduced by the ubiquitin ligase Trim32 (tripartite motif containing protein 32). Inhibition of Trim32 enhanced plakoglobin binding to PI3K–p85 and promoted PI3K–Akt–FoxO signaling. Surprisingly, plakoglobin overexpression alone enhanced PI3K–Akt–FoxO signaling. Furthermore, Trim32 inhibition in normal muscle increased PI3K–Akt–FoxO signaling, enhanced glucose uptake, and induced fiber growth, whereas plakoglobin down-regulation reduced PI3K–Akt–FoxO signaling, decreased glucose uptake, and caused atrophy. Thus, by promoting plakoglobin–PI3K dissociation, Trim32 reduces PI3K–Akt–FoxO signaling in normal and atrophying muscle. This mechanism probably contributes to insulin resistance during fasting and catabolic diseases and perhaps to the myopathies and cardiomyopathies seen with Trim32 and plakoglobin mutations. 相似文献
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Characterization of two mannose-binding protein cDNAs from rhesus monkey (Macaca mulatta): structure and evolutionary implications 总被引:3,自引:0,他引:3
Mannose-binding proteins (MBPs), members of the collectin family,have been implicated as lectin opsonins for various virusesand bacteria. Two distinct but related MBPs, MBP-A and MBP-C,with -55% identity at the amino acid level, have been previouslycharacterized from rodents. In humans, however, only one formof MBP has been characterized. In this paper we report studieselucidating the evolution of primate MBPs. ELISA and Westernblot analyses indicated that rhesus and cynomolgus monkeys havetwo forms of MBP in their sera, while chimpanzees have onlyone form, similar to humans. Two distinct MBP cDNA clones wereisolated and characterized from a rhesus monkey liver cDNA library.Rhesus MBP-A is closely related to the mouse and rat MBP-A,showing 77% and 75% identity at the amino acid level, respectively.Rhesus MBP-A also has three cysteines at the N-terminus, similarto mouse and rat MBP-A and human MBP. Rhesus MBP-C shares 90%identity with the human MBP at the amino acid level and hasthree cysteines at the N-terminus, in contrast to two cysteineresidues found in rodent MBP-C. A stretch of nine amino acidsclose to the N-terminus, absent in both mouse and rat MBP-A,but present in rodent MBP-C, chicken and human MBPs, is alsofound in the rhesus MBP-A. The phylogenetic analysis of rhesusand other mammalian MBPs, coupled with the serological datasuggest that at least two distinct MBP genes existed prior tomammalian radiation and the hominoid ancestor apparently lostone of these genes or failed to express it. collectin rhesus monkey mannose-binding protein MBP cDNA mannan-binding protein 相似文献
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Fill Factor Losses in Cu2ZnSn(SxSe1−x)4 Solar Cells: Insights from Physical and Electrical Characterization of Devices and Exfoliated Films 下载免费PDF全文
Kong Fai Tai Oki Gunawan Masaru Kuwahara Shi Chen Subodh Gautam Mhaisalkar Cheng Hon Alfred Huan David B. Mitzi 《Liver Transplantation》2016,6(3)
Besides the open circuit voltage (VOC) deficit, fill factor (FF) is the second most significant parameter deficit for earth‐abundant kesterite solar cell technology. Here, various pathways for FF loss are discussed, with focus on the series resistance issue and its various contributing factors. Electrical and physical characterizations of the full range of bandgap (Eg = 1.0–1.5 eV) Cu2ZnSn(SxSe1?x)4 (CZTSSe) devices, as well as bare and exfoliated films with various S/(S + Se) ratios, are performed. High intensity Suns‐VOC measurement indicates a nonohmic junction developing in high bandgap CZTSSe. Grazing incidence X‐ray diffraction, Raman mapping, field emission scanning electron microscopy, and X‐ray photoelectron spectroscopy indicate the formation of Sn(S,Se)2, Mo(S,Se)2, and Zn(S,Se) at the high bandgap CZTSSe/Mo interface, contributing to the increased series resistance (RS) and nonohmic back contact characteristics. This study offers some clues as to why the record‐CZTSSe solar cells occur within a bandgap range centered around 1.15 eV and offers some direction for further optimization. 相似文献
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Using radioimmunoassay, blood platelet aggregation studies and GC-MS the existence of prostaglandins in the endomycetalean yeastDipodascopsis uninucleata was confirmed by our group. These findings triggered the search for similar eicosanoids in the rest of the Endomycetales. We commenced by scanning for the easily detectable precursors of eicosanoids, linoleic- and linolenic acid. We selected two families (i.e. Lipomycetaceae and Dipodascaceae), both producing these precursors, for further investigation.Representative strains of the two families were tested for their ability to grow in the presence of 1mM aspirin, a specific inhibitor of prostaglandin biosynthesis. In contrast to the lipomycetaceous species the dipodascaceous species were insensitive to this drug. These results were verified when representative strains of both families were investigated for their ability to produce eicosanoids from externally fed radio-labeled arachidonic acid along an aspirin sensitive pathway. Thin layer chromatography of culture extracts, followed by autoradiography, showed that while none of the Dipodascaceae produced aspirin sensitive arachidonic acid metabolites, the members of the Lipomycetaceae tested positive for these metabolites. These findings supported the separation of the lipomycetaceous yeastDipodascopsis from the Dipodascaceae. The findings also correlate with the delimitation of these yeasts in two families (i.e. Dipodascaceae and Lipomycetaceae).Further investigation indicated that prostaglandin production by the genusDipodascopsis is mainly associated with ascosporogenesis. Thin layer chromatography of cell extracts fromDipodascopsis tóthii, followed by scintillation counting, indicated the presence of PGF2 and PGE2 during ascosporogenesis. 相似文献
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Purified chloroplast DNA ( cp DNA) extracts from 31 species of Picea and two species of Pinus (P. sylvestris and P. cembra ) were digested with eight restriction endo-nucleases, separated by electrophoresis and scored for restriction fragment length polymorphisms. The resulting data was analyzed phenetically and cladistically. The phenetic analysis indicated lower levels of cpDNA differentiation within Picea than within Pinus and lower levels of differentiation among Eurasian than among North-American Picea species. The cladistic analysis, using Pinus sylvestris as an outgroup, suggested monophyly for Picea and resolved several monophyletic groups among the 31 species of Picea . An assessment of biogeographic events, based on the cladogram, suggests that Picea originated in North-America and that the colonization of Eurasia occurred through separate, intercontinental migrations. 相似文献
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