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排序方式: 共有697条查询结果,搜索用时 11 毫秒
1.
CHIP-mediated hyperubiquitylation of tau promotes its self-assembly into the insoluble tau filaments
Ji Hyeon Kim Jeeyoung Lee Won Hoon Choi Seoyoung Park Seo Hyeong Park Jung Hoon Lee Sang Min Lim Ji Young Mun Hyun-Soo Cho Dohyun Han Young Ho Suh Min Jae Lee 《Chemical science》2021,12(15):5599
The tau protein is a highly soluble and natively unfolded protein. Under pathological conditions, tau undergoes multiple post-translational modifications (PTMs) and conformational changes to form insoluble filaments, which are the proteinaceous signatures of tauopathies. To dissect the crosstalk among tau PTMs during the aggregation process, we phosphorylated and ubiquitylated recombinant tau in vitro using GSK3β and CHIP, respectively. The resulting phospho–ub-tau contained conventional polyubiquitin chains with lysine 48 linkages, sufficient for proteasomal degradation, whereas unphosphorylated ub-tau species retained only one–three ubiquitin moieties. Mass-spectrometric analysis of in vitro reconstituted phospho–ub-tau revealed seven additional ubiquitylation sites, some of which are known to stabilize tau protofilament stacking in the human brain with tauopathy. When the ubiquitylation reaction was prolonged, phospho–ub-tau transformed into insoluble hyperubiquitylated tau species featuring fibrillar morphology and in vitro seeding activity. We developed a small-molecule inhibitor of CHIP through biophysical screening; this effectively suppressed tau ubiquitylation in vitro and delayed its aggregation in cultured cells including primary cultured neurons. Our biochemical findings point to a “multiple-hit model,” where sequential events of tau phosphorylation and hyperubiquitylation function as a key driver of the fibrillization process, thus indicating that targeting tau ubiquitylation may be an effective strategy to alleviate the course of tauopathies.Multiple-hit model for tau aggregation, where sequential events of tau phosphorylation and hyperubiquitylation function as a key driver of the fibrillization process. 相似文献
2.
R. Veeraraghavan N. S. Hon A. G. Page 《Journal of Radioanalytical and Nuclear Chemistry》2004,261(1):69-72
A method based on synergic extraction has been evolved for the recovery of tens of milligrams of americium from analytical
wastes in 7-8M HNO3 medium containing excess uranium as a two step procedure viz., (1) separation of uranium by contacting with TBP in dodecane
and (2) recovery of americium by an extraction-cum-strip cycle using a synergic mixture of PMBP-TBP in dodecane after decreasing
the acidity of the solution. Other transition metals such as iron found in significant proportion were separated from Am by
using the difference in the kinetics of extraction of iron and americium into HPMBP-TBP-dodecane mixture by short duration
contacts. About 99% of Am could be recovered into about 20% of its initial volume.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
3.
K. W. Cheah L. C. Ho J. B. Xia J. Li W. H. Zheng W. R. Zhuang Q. M. Wang 《Applied Physics A: Materials Science & Processing》1995,60(6):601-606
Photoluminescence studies on porous silicon show that there are luminescence centers present in the surface states. By taking photoluminescence spectra of porous silicon with respect to temperature, a distinct peak can be observed in the temperature range 100–150 K. Both linear and nonlinear relationships were observed between excitation laser power and the photoluminescence intensity within this temperature range. In addition, there was a tendency for the photoluminescence peak to red shift at low temperature as well as at low excitation power. This is interpreted as indicating that the lower energy transition becomes dominant at low temperature and excitation power. The presence of these luminescence centers can be explained in terms of porous silicon as a mixture of silicon clusters and wires in which quantum confinement along with surface passivation would cause a mixing of andX band structure between the surface states and the bulk. This mixing would allow the formation of luminescence centers. 相似文献
4.
Zauresh S. Nurkeeva Al-Sayed Abdel Aal Vitaliy V. Khutoryanskiy Grigoriy A. Mun Aida G. Beksyrgaeva 《Radiation Physics and Chemistry》2003,67(6):717-722
Gamma-radiation grafting of vinyl ether of monoethanolamine and vinyl ether of ethyleneglycol (VEEG) on polyethylene films has been studied from binary monomer mixtures. The effect of co-monomer composition and total exposure radiation dose on the grafting process is investigated. A combination of potentiometric and gravimetric techniques is applied to determine the grafting degree of each monomer in the final graft copolymer. The presence of more active monomer VEEG in the mixture was found to enhance the grafting of both monomers because the increasing of copolymerization rate which in turn increases the total grafting degree. The modification of the hydrophilic properties of the graft copolymer is studied by examining the grafted films for water- and copper (II) ions uptake. 相似文献
5.
A diastereoselective total synthesis of (±)-canadensolide is described. The key step is to introduce the α-methylene group by the ozonolysis of mono-substituted alkenes followed by reaction with a preheated mixture of CH2Br2-Et2NH. 相似文献
6.
Jong Min Oh Hyun-Jae Jang Myung-Gyun Kang Seul-Ki Mun Daeui Park Su-Jin Hong Min Ha Kim Soo-Young Kim Sung-Tae Yee Hoon Kim 《Molecules (Basel, Switzerland)》2023,28(1)
Thirteen compounds were isolated from the Canavalia lineata pods and their inhibitory activities against human monoamine oxidase-A (hMAO-A) and -B (hMAO-B) were evaluated. Among them, compounds 8 (medicarpin) and 13 (homopterocarpin) showed potent inhibitory activity against hMAO-B (IC50 = 0.45 and 0.72 µM, respectively) with selectivity index (SI) values of 44.2 and 2.07, respectively. Most of the compounds weakly inhibited MAO-A, except 9 (prunetin) and 13. Compounds 8 and 13 were reversible competitive inhibitors against hMAO-B (Ki = 0.27 and 0.21 µM, respectively). Structurally, the 3-OH group at A-ring of 8 showed higher hMAO-B inhibitory activity than 3-OCH3 group at the A-ring of 13. However, the 9-OCH3 group at B-ring of 13 showed higher hMAO-B inhibitory activity than 8,9-methylenedioxygroup at the B-ring of 12 (pterocarpin). In cytotoxicity study, 8 and 13 showed non-toxicity to the normal (MDCK) and cancer (HL-60) cells and moderate toxicity to neuroblastoma (SH-SY5Y) cell. Molecular docking simulation revealed that the binding affinities of 8 and 13 for hMAO-B (−8.7 and −7.7 kcal/mol, respectively) were higher than those for hMAO-A (−3.4 and −7.1 kcal/mol, respectively). These findings suggest that compounds 8 and 13 be considered potent reversible hMAO-B inhibitors to be used for the treatment of neurological disorders. 相似文献
7.
Seungyeon Lee Sora Mun You-Rim Lee Jiyeong Lee Hee-Gyoo Kang 《Molecules (Basel, Switzerland)》2022,27(24)
Ergothioneine, which is a naturally occurring metabolite, generally accumulates in tissues and cells subjected to oxidative stress, owing to its structural stability at physiological pH; therefore, it has been attracting attention in various biomedical fields. Ergothioneine has also been suggested as a potential forensic marker, but its applicability has not yet been quantitatively validated. In this study, quantitative analysis of ergothioneine in bloodstains was conducted to estimate the age of bloodstains and that of bloodstain donors. Blood from youth and elderly participants was used to generate bloodstains. After extracting metabolites from the bloodstains under prevalent age conditions, ergothioneine levels were quantified by mass spectrometry via multiple reaction monitoring. The concentration of ergothioneine in day 0 bloodstains (fresh blood), was significantly higher in the elderly group than in the youth group, but it did not differ by sex. Statistically significant differences were observed between the samples from the two age groups on days 0, 5 and 7, and on days 2 and 3 compared with day 0. The findings suggest that ergothioneine can be used to estimate the age of bloodstains and of the donor; it could be useful as a potential marker in reconstructing crime scenes. 相似文献
8.
Mun BS Watanabe M Rossi M Stamenkovic V Markovic NM Ross PN 《The Journal of chemical physics》2005,123(20):204717
The surface valence-band densities of states (DOS) of Pt(3)M (M=Ti,V,Cr,Fe,Co,Ni) polycrystalline alloys were investigated with ultraviolet photoemission spectroscopy. Upon annealing the ion-sputter-cleaned alloys at high temperatures, the observed valence-band DOS spectra clearly show the modified electronic structures on the surfaces suggesting the surface segregation of Pt as predicted in thermodynamic models. The measured d-band centers and widths for the annealed alloy surfaces show qualitatively the same trend as predicted by density-functional-theory calculations based on the model of a Pt "skin" on the topmost surface layer and a subsurface layer enriched in the 3d transition metal. 相似文献
9.
V. C. Adya M. Mohapatra Nimai Pathak Mithlesh Kumar N. S. Hon S. K. Thulasidas M. J. Kulkarni V. Natarajan 《Journal of Radioanalytical and Nuclear Chemistry》2016,307(1):341-346
This work presents the investigation of some commercially available and commonly used Si3N4 foils prepared with LPCVD technique. The density and the stoichiometry of these films were determined by Rutherford backscattering spectroscopy and profilometry, while the study of impurities was achieved with particle induced X-ray emission method. It was found that the density of the studied Si3N4 films is significantly less (~2.71 g cm?3), while the stoichiometry is close to the values of the bulk material. The results were verified by measuring the ion energy loss through the films by scanning transmission ion microscopy. 相似文献
10.