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141.
Ivan Barvík Jr. Josef Štěpánek Jiří Bok 《Journal of biomolecular structure & dynamics》2013,31(5):863-875
Abstract Impact of the internucleoside linkage modification by inserting a methylene group on the ability of the modified oligonucleotide to hybridize with a natural DNA strand was studied by fully solvated molecular dynamics (MD) simulations. Three undecamer complexes were analyzed: natural dT11.dA11 duplex as a reference and two its analogs with alternating modified and natural linkages in the deoxyadenosine chain. The isopolar, non-isosteric modified linkages were of 5′-O-PO2-CH2-O-3′ (5′PC3′) or 5′-O-CH2-PO2-O-3′ (5′CP3′) type. Simulations were performed by using the AMBER 5.0 software package with the force field completed by a set of parameters needed to model the modified segments. Both modifications were found to lead to double helical complexes, in which the thymidine strand as well as deoxyriboses and unmodified linkages in the adenosine strand adopted conformations typical for the B-type structure. For each of the two conformational richer modified linkages two stable conformations were found at 300 K: the -ggt and ggt for the 5′PC3′ and ggg, tgg for the 5′CP3′, respectively. Both modified chains adopted helical conformations with heightened values of the inclination parameter but without affecting the Watson-Crick hydrogen bonds. 相似文献
142.
143.
Isabelle Côté 《Ethnic and racial studies》2013,36(11):1855-1873
The tumultuous events of summer 2009 have brought Uighur protests and minority mobilization in the Xinjiang Uighur Autonomous Region (XUAR) to the forefront. But this focus overlooks similar protests organized by various groups of Han Chinese settlers over the years. This paper contributes to the body of literature on minority mobilization and ethnic relations in Xinjiang by illustrating how the political mobilization of a group that is simultaneously a national majority and a regional minority differs substantially from ‘traditional’ minority mobilization. Reviewing the main instances of Han Chinese political mobilization since the XUAR was created in 1955, I argue that two factors are particularly important in enabling their mobilization: the Han Chinese's subjective perception of discrimination and their close ethnic ties to the state. This paper concludes with a discussion on the presence of a cycle of protests between Han settlers and the Uighurs in Xinjiang. 相似文献
144.
Yashar Feyziyev Zsuzsanna Deák Stenbjörn Styring Gábor Bernát 《Journal of bioenergetics and biomembranes》2013,45(1-2):111-120
The Mn4CaO5 cluster of photosystem II (PSII) catalyzes the oxidation of water to molecular oxygen through the light-driven redox S-cycle. The water oxidizing complex (WOC) forms a triad with TyrosineZ and P680, which mediates electrons from water towards the acceptor side of PSII. Under certain conditions two other redox-active components, TyrosineD (YD) and Cytochrome b 559 (Cyt b 559) can also interact with the S-states. In the present work we investigate the electron transfer from Cyt b 559 and YD to the S2 and S3 states at 195 K. First, YD ? and Cyt b 559 were chemically reduced. The S2 and S3 states were then achieved by application of one or two laser flashes, respectively, on samples stabilized in the S1 state. EPR signals of the WOC (the S2-state multiline signal, ML-S2), YD ? and oxidized Cyt b 559 were simultaneously detected during a prolonged dark incubation at 195 K. During 163 days of incubation a large fraction of the S2 population decayed to S1 in the S2 samples by following a single exponential decay. Differently, S3 samples showed an initial increase in the ML-S2 intensity (due to S3 to S2 conversion) and a subsequent slow decay due to S2 to S1 conversion. In both cases, only a minor oxidation of YD was observed. In contrast, the signal intensity of the oxidized Cyt b 559 showed a two-fold increase in both the S2 and S3 samples. The electron donation from Cyt b 559 was much more efficient to the S2 state than to the S3 state. 相似文献
145.
Sally E. Thomas Elke Malzer Adriana Ordó?ez Lucy E. Dalton Emily F. A. van ′t Wout Elizabeth Liniker Damian C. Crowther David A. Lomas Stefan J. Marciniak 《The Journal of biological chemistry》2013,288(11):7606-7617
Cell cycle checkpoints ensure that proliferation occurs only under permissive conditions, but their role in linking nutrient availability to cell division is incompletely understood. Protein folding within the endoplasmic reticulum (ER) is exquisitely sensitive to energy supply and amino acid sources because deficiencies impair luminal protein folding and consequently trigger ER stress signaling. Following ER stress, many cell types arrest within the G1 phase, although recent studies have identified a novel ER stress G2 checkpoint. Here, we report that ER stress affects cell cycle progression via two classes of signal: an early inhibition of protein synthesis leading to G2 delay involving CHK1 and a later induction of G1 arrest associated both with the induction of p53 target genes and loss of cyclin D1. We show that substitution of p53/47 for p53 impairs the ER stress G1 checkpoint, attenuates the recovery of protein translation, and impairs induction of NOXA, a mediator of cell death. We propose that cell cycle regulation in response to ER stress comprises redundant pathways invoked sequentially first to impair G2 progression prior to ultimate G1 arrest. 相似文献
146.
Caroline Richard Patrick Couture Sophie Desroches Alice H. Lichtenstein Beno?t Lamarche 《Journal of lipid research》2013,54(1):232-237
We investigated the effect of weight loss, independent of change in diet composition, on HDL and apoAI metabolism in men with metabolic syndrome (MetS). Subjects (19 men with MetS [NCEP-ATPIII]) were fed an isoenergetic Mediterranean-style diet for 5 weeks (all foods provided). Participants then underwent a 20-week free-living period during which they were counseled to restrict energy intake, after which they were again fed an isoenergetic Mediterranean-style diet for 5 weeks. At the end of the two controlled diets, participants received a single bolus of [5,5,5-2H3] L-leucine, and fasting blood samples were collected over a 96 h period. ApoAI kinetic was assessed using multicompartmental modeling of the tracer enrichment data. Participants achieved a 9.1 ± 2.8% reduction in body weight (P < 0.001). Weight loss resulted in an increase in plasma HDL-cholesterol (HDL-C) concentrations of 6.0% (P = 0.059) and HDL3-C of 7.9% (P = 0.045), attributable to a reduction in apoAI fractional catabolic rate (−7.8%; P = 0.046) with no change in apoAI production rate (2.2%; P = 0.58). These data indicate that weight loss, independent of variation in diet composition, increases plasma HDL primarily by delaying the catabolism of apoAI. 相似文献
147.
Jeff A. O'Meara Christopher T. Lemke Cédrickx Godbout George Kukolj Lisette Lagacé Beno?t Moreau Diane Thibeault Peter W. White Montse Llinàs-Brunet 《The Journal of biological chemistry》2013,288(8):5673-5681
Although optimizing the resistance profile of an inhibitor can be challenging, it is potentially important for improving the long term effectiveness of antiviral therapy. This work describes our rational approach toward the identification of a macrocyclic acylsulfonamide that is a potent inhibitor of the NS3-NS4A proteases of all hepatitis C virus genotypes and of a panel of genotype 1-resistant variants. The enhanced potency of this compound versus variants D168V and R155K facilitated x-ray determination of the inhibitor-variant complexes. In turn, these structural studies revealed a complex molecular basis of resistance and rationalized how such compounds are able to circumvent these mechanisms. 相似文献
148.
149.
Johann B?hm Frédéric Chevessier André?Maues De?Paula Catherine Koch Shahram Attarian Claire Feger Daniel Hanta? Pascal Laforêt Karima Ghorab Jean-Michel Vallat Michel Fardeau Dominique Figarella-Branger Jean Pouget Norma?B. Romero Marc Koch Claudine Ebel Nicolas Levy Martin Krahn Bruno Eymard Marc Bartoli Jocelyn Laporte 《American journal of human genetics》2013,92(2):271-278
Tubular aggregates are regular arrays of membrane tubules accumulating in muscle with age. They are found as secondary features in several muscle disorders, including alcohol- and drug-induced myopathies, exercise-induced cramps, and inherited myasthenia, but also exist as a pure genetic form characterized by slowly progressive muscle weakness. We identified dominant STIM1 mutations as a genetic cause of tubular-aggregate myopathy (TAM). Stromal interaction molecule 1 (STIM1) is the main Ca2+ sensor in the endoplasmic reticulum, and all mutations were found in the highly conserved intraluminal Ca2+-binding EF hands. Ca2+ stores are refilled through a process called store-operated Ca2+ entry (SOCE). Upon Ca2+-store depletion, wild-type STIM1 oligomerizes and thereby triggers extracellular Ca2+ entry. In contrast, the missense mutations found in our four TAM-affected families induced constitutive STIM1 clustering, indicating that Ca2+ sensing was impaired. By monitoring the calcium response of TAM myoblasts to SOCE, we found a significantly higher basal Ca2+ level in TAM cells and a dysregulation of intracellular Ca2+ homeostasis. Because recessive STIM1 loss-of-function mutations were associated with immunodeficiency, we conclude that the tissue-specific impact of STIM1 loss or constitutive activation is different and that a tight regulation of STIM1-dependent SOCE is fundamental for normal skeletal-muscle structure and function. 相似文献
150.
We characterize lichen flora of Slovakia based on the review of recent studies published since 1998, point at selected lichen taxa described for science from this territory and outline main geographical elements and other important groups. We annex critically revised and updated checklist of lichens of Slovakia, which includes 1,628 species. As a result of intensive field work the number of species increased by 142 new species since the last version of checklist published 15 years ago, 26 species were excluded. 相似文献