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71.
Amyloid features and neuronal toxicity of mature prion fibrils are highly sensitive to high pressure 总被引:1,自引:0,他引:1
El Moustaine D Perrier V Acquatella-Tran Van Ba I Meersman F Ostapchenko VG Baskakov IV Lange R Torrent J 《The Journal of biological chemistry》2011,286(15):13448-13459
Prion proteins (PrP) can aggregate into toxic and possibly infectious amyloid fibrils. This particular macrostructure confers on them an extreme and still unexplained stability. To provide mechanistic insights into this self-assembly process, we used high pressure as a thermodynamic tool for perturbing the structure of mature amyloid fibrils that were prepared from recombinant full-length mouse PrP. Application of high pressure led to irreversible loss of several specific amyloid features, such as thioflavin T and 8-anilino-1-naphthalene sulfonate binding, alteration of the characteristic proteinase K digestion pattern, and a significant decrease in the β-sheet structure and cytotoxicity of amyloid fibrils. Partial disaggregation of the mature fibrils into monomeric soluble PrP was observed. The remaining amyloid fibrils underwent a change in secondary structure that led to morphologically different fibrils composed of a reduced number of proto-filaments. The kinetics of these reactions was studied by recording the pressure-induced dissociation of thioflavin T from the amyloid fibrils. Analysis of the pressure and temperature dependence of the relaxation rates revealed partly unstructured and hydrated kinetic transition states and highlighted the importance of collapsing and hydrating inter- and intramolecular cavities to overcome the high free energy barrier that stabilizes amyloid fibrils. 相似文献
72.
Lee CI Yang Q Perrier V Baskakov IV 《Protein science : a publication of the Protein Society》2007,16(10):2166-2173
Previous studies identified several single-point mutants of the prion protein that displayed dominant-negative effects on prion replication. The dominant-negative effect was assumed to be mediated by protein X, an as-yet-unknown cellular cofactor that is believed to be essential for prion replication. To gain insight into the mechanism that underlies the dominant-negative phenomena, we evaluated the effect of the Q218K variant of full-length recombinant prion protein (Q218K rPrP), one of the dominant-negative mutants, on cell-free polymerization of wild-type rPrP into amyloid fibrils. We found that both Q218K and wild-type (WT) rPrPs were incorporated into fibrils when incubated as a mixture; however, the yield of polymerization was substantially decreased in the presence of Q218K rPrP. Furthermore, in contrast to fibrils produced from WT rPrP, the fibrils generated in the mixture of WT and Q218K rPrPs did not acquire the proteinase K-resistant core of 16 kDa that was shown previously to encompass residues 97-230 and was similar to that of PrP(Sc). Our studies demonstrate that the Q218K variant exhibits the dominant-negative effect in cell-free conversion in the absence of protein X, and that this effect is, presumably, mediated by physical interaction between Q218K and WT rPrP during the polymerization process. 相似文献
73.
Helen C. Turner P. Sharma J. R. Perrier A. Bertucci L. Smilenov G. Johnson M. Taveras D. J. Brenner G. Garty 《Radiation and environmental biophysics》2014,53(2):265-272
At the Center for High-Throughput Minimally Invasive Radiation Biodosimetry, we have developed a rapid automated biodosimetry tool (RABiT); this is a completely automated, ultra-high-throughput robotically based biodosimetry workstation designed for use following a large-scale radiological event, to perform radiation biodosimetry measurements based on a fingerstick blood sample. High throughput is achieved through purpose built robotics, sample handling in filter-bottomed multi-well plates and innovations in high-speed imaging and analysis. Currently, we are adapting the RABiT technologies for use in laboratory settings, for applications in epidemiological and clinical studies. Our overall goal is to extend the RABiT system to directly measure the kinetics of DNA repair proteins. The design of the kinetic/time-dependent studies is based on repeated, automated sampling of lymphocytes from a central reservoir of cells housed in the RABiT incubator as a function of time after the irradiation challenge. In the present study, we have characterized the DNA repair kinetics of the following repair proteins: γ-H2AX, 53-BP1, ATM kinase, MDC1 at multiple times (0.5, 2, 4, 7 and 24 h) after irradiation with 4 Gy γ rays. In order to provide a consistent dose exposure at time zero, we have developed an automated capillary irradiator to introduce DNA DSBs into fingerstick-size blood samples within the RABiT. To demonstrate the scalability of the laboratory-based RABiT system, we have initiated a population study using γ-H2AX as a biomarker. 相似文献
74.
S. Graziani D. Christin S. Daulon P. Breton N. Perrier L. Taysse 《Neurochemical research》2014,39(5):911-921
In a previous report, alterations of the serotonin metabolism were previously reported in mice intoxicated with repeated low doses of soman. In order to better understand the effects induced by repeated low-dose exposure to organophosphorus compounds on physiological and behavioural functions, the levels of endogenous monoamines (serotonin and dopamine) in different brain areas in mice intoxicated with sublethal dose of (O-ethyl-S-[2(di-isopropylamino) ethyl] methyl phosphonothioate) (VX) were analysed by HPLC method with electrochemical detection. Animals were injected once a day for three consecutive days with 0.10 LD50 of VX (5 μg/kg, i.p). Neither severe signs of cholinergic toxicity nor pathological changes in brain tissue of exposed animals were observed. Cholinesterase (ChE) activity was only inhibited in plasma (a maximum of 30 % inhibition 24 h after the last injection of VX), but remained unchanged in the brain. Serotonin and dopamine (DA) metabolism appeared significantly modified. During the entire period of investigation, at least one of the three parameters investigated (i.e. DA and DOPAC levels and DOPAC/DA ratio) was modified. During the toxic challenge, an increase of the serotonin metabolism was noted in hippocampus (HPC), hypothalamus/thalamus, pons medulla and cerebellum (CER). This increase was maintained 4 weeks after exposure in HPC, pons medulla and CER whereas a decrease in cortex 3 weeks after the toxic challenge was observed. The lack of correlation between brain ChE activity and neurochemical outcomes points out to independent mechanisms. The involvement in possibly long-lasting behavioural disorders is discussed. 相似文献
75.
Nathalie Pross Agnès Demazières Nicolas Girard Romain Barnouin Déborah Metzger Alexis Klein Erica Perrier Isabelle Guelinckx 《PloS one》2014,9(4)
Objective
To evaluate the effects of a change in water intake on mood and sensation in 22 habitual high-volume (HIGH; 2-4 L/d) and 30 low-volume (LOW; <1.2 L/d) drinkers who were asked to respectively decrease and increase their daily water intake.Method
During baseline HIGH consumed 2.5 L and LOW 1 L of water/day. During 3 controlled intervention days HIGH''s water intake was restricted to 1 L/day whereas LOW''s was increased to 2.5 L water/day. Several mood scales (Bond & Lader Visual Analog Scale (VAS), Profile of Mood States, Karolinska Sleepiness Scale, Thirst & Emotional VAS) were administered at different time points during the study. ANOVA including intervention, time point and intervention by time point as fixed effects on mean values (i.e.; baseline data vs. mean of 3 intervention days) for each mood scale was performed.Results
At baseline HIGH and LOW were comparable in mood state, except for thirst scores (estimate = 17.16, p<0.001) and POMS depression-dejection scores (estimate = 0.55, p<0.05) which were both higher in the HIGH vs. LOW. In HIGH the restricted water intake resulted in a significant increase in thirst (p<0.001) and a decrease in contentedness (p<0.05), calmness (p<0.01), positive emotions (p<0.05) and vigor/activity (p<0.001). In LOW, increased water consumption resulted in a significant decrease in fatigue/inertia (p<0.001), confusion/bewilderment (p = 0.05) and thirst (p<0.001) and a trend to lower sleepiness (p = 0.07) compared to baseline.Conclusion
Increasing water intake has beneficial effects in LOW, especially sleep/wake feelings, whereas decreasing water intake has detrimental effects on HIGH''s mood. These deleterious effects in HIGH were observed in some sleep/wake moods as well as calmness, satisfaction and positive emotions. 相似文献76.
Pluripotent stem cell (PSC) technologies are becoming a key asset for deciphering pathological cascades and for developing new treatments against many neurodegenerative disorders, including Huntington's disease (HD). This perspective discusses the challenges and opportunities facing the use of PSCs for treating HD, focusing on four major applications: namely, the use of PSCs as a substitute source of human striatal cells for current HD cell therapy, as a cellular model of HD for the validation of human-specific gene therapies, for deciphering molecular mechanisms underlying HD, and in drug discovery. 相似文献
77.
Hippolyte I Jenny C Gardes L Bakry F Rivallan R Pomies V Cubry P Tomekpe K Risterucci AM Roux N Rouard M Arnaud E Kolesnikova-Allen M Perrier X 《Annals of botany》2012,109(5):937-951
Background and Aims
The production of triploid banana and plantain (Musa spp.) cultivars with improved characteristics (e.g. greater disease resistance or higher yield), while still preserving the main features of current popular cultivars (e.g. taste and cooking quality), remains a major challenge for Musa breeders. In this regard, breeders require a sound knowledge of the lineage of the current sterile triploid cultivars, to select diploid parents that are able to transmit desirable traits, together with a breeding strategy ensuring final triploidization and sterility. Highly polymorphic single sequence repeats (SSRs) are valuable markers for investigating phylogenetic relationships.Methods
Here, the allelic distribution of each of 22 SSR loci across 561 Musa accessions is analysed.Key Results and Conclusions
We determine the closest diploid progenitors of the triploid ‘Cavendish’ and ‘Gros Michel’ subgroups, valuable information for breeding programmes. Nevertheless, in establishing the likely monoclonal origin of the main edible triploid banana subgroups (i.e. ‘Cavendish’, ‘Plantain’ and ‘Mutika-Lujugira’), we postulated that the huge phenotypic diversity observed within these subgroups did not result from gamete recombination, but rather from epigenetic regulations. This emphasizes the need to investigate the regulatory mechanisms of genome expression on a unique model in the plant kingdom. We also propose experimental standards to compare additional and independent genotyping data for reference. 相似文献78.
Mouna Jeridi Xavier Perrier Marguerite Rodier-Goud Ali Ferchichi Angélique D'Hont Frédéric Bakry 《Annals of botany》2012,110(8):1593-1606
Background and Aims
Edible bananas originated mainly from two wild species, Musa acuminata Colla (AA) and Musa balbisiana Colla (BB), and triploid cultivars with an AAA, AAB or ABB genome are the most widely used. In the present study, chromosome pairing affinities are investigated in a sterile AB Indian variety and in its fertile colchicine-induced allotetraploid (AABB) derivative to determine the inheritance pattern of the tetraploid genotype. The potential implications of interspecific recombination and chromosomal composition of diploid gametes for Musa improvement are presented.Methods
The pairing of different chromosome sets at diploid and tetraploid levels was investigated through a combination of conventional cytogenetic and genomic in-situ hybridization (GISH) analyses of meiotic chromosomes, leading to a likelihood model of the pairing behaviour. GISH analysis of mitotic chromosomes was also conducted to reveal the chromosome constitution of hybrids derived from crosses involving the allotetraploid genotype.Key Results
Analysis of chromosome associations at both ploidy levels suggested that the newly formed allotetraploid behaves as a ‘segmental allotetraploid’ with three chromosome sets in a tetrasomic pattern, three sets in a likely disomic pattern and the five remaining sets in an intermediate pattern. Balanced and unbalanced diploid gametes were detected in progenies, with the chromosome constitution appearing to be more homogenous in pollen than in ovules.Conclusions
Colchicine-induced allotetraploids in Musa provide access to the genetic background of natural AB varieties. The segmental inheritance pattern exhibited by the AABB allotetraploid genotype implies chromosome exchanges between M. acuminata and M. balbisiana species and opens new horizons for reciprocal transfer of valuable alleles. 相似文献79.
80.
Olivier Schoefs Lucie Jean Andree Ellert Michel Perrier Réjean Samson 《Soil & Sediment Contamination》2005,14(2):171-182
The fate of contaminant carbon was monitored during aerobic biodegradation in the presence of a mixed indigenous microbial consortium in order to calibrate a microbial-growth-based biokinetic model. The methodology simultaneously monitored mineralization, substrate depletion and microbial population evolution in biomass extract spiked with14C-labeled hexadecane. Hexadecane depletion and hexadecane-degrader population were monitored using sacrificed microcosms by centrifuging the extract so that the supernatant and the residue contained residual hexadecane and microbial population, respectively. This methodology allowed verification of the carbon mass balance (average14C-carbon recovery of 90.33 ± 1.62% for biotic microcosms) and calibration of a biokinetic model. Four biokinetic parameters and three yield coefficients were identified (Haldane kinetic parameters:μS = 1.3639 d-1, Ks = 0.4295 mg-C, KI = 6.6457 mg-C; decay kinetic parameter:μd = 1.3.102 d-1; substrate/biomass, carbon dioxide/ biomass during growth and carbon dioxide/biomass during decay yield coefficients: Ys = 1.5948 mg-C/mg-C, YP g = 0.4554 mg-C/mg-C, YP d = 1.3263 mg-C/mg-C) and compared with the literature data. The methodology can facilitate the identification of biodegradation models by decoupling the intrinsic ability of microorganisms to degrade contaminant from restrictions imposed by limiting conditions. 相似文献