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91.
92.
Oxidative stress conditions increase the frequency of de novo formation of the yeast [PSI+] prion
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Victoria A. Doronina Gemma L. Staniforth Shaun H. Speldewinde Mick F. Tuite Chris M. Grant 《Molecular microbiology》2015,96(1):163-174
Prions are self‐perpetuating amyloid protein aggregates which underlie various neurodegenerative diseases in mammals and heritable traits in yeast. The molecular basis of how yeast and mammalian prions form spontaneously into infectious amyloid‐like structures is poorly understood. We have explored the hypothesis that oxidative stress is a general trigger for prion formation using the yeast [PSI+] prion, which is the altered conformation of the Sup35 translation termination factor. We show that the frequency of [PSI+] prion formation is elevated under conditions of oxidative stress and in mutants lacking key antioxidants. We detect increased oxidation of Sup35 methionine residues in antioxidant mutants and show that overexpression of methionine sulphoxide reductase abrogates both the oxidation of Sup35 and its conversion to the [PSI+] prion. [PSI+] prion formation is particularly elevated in a mutant lacking the Sod1 Cu,Zn‐superoxide dismutase. We have used fluorescence microscopy to show that the de novo appearance of [PSI+] is both rapid and increased in frequency in this mutant. Finally, electron microscopy analysis of native Sup35 reveals that similar fibrillar structures are formed in both the wild‐type and antioxidant mutants. Together, our data indicate that oxidative stress is a general trigger of [PSI+] formation, which can be alleviated by antioxidant defenses. 相似文献
93.
Luke Thomas W. Jason Kennington Michael Stat Shaun P. Wilkinson Johnathan T. Kool Gary A. Kendrick 《Proceedings. Biological sciences / The Royal Society》2015,282(1812)
A detailed understanding of the genetic structure of populations and an accurate interpretation of processes driving contemporary patterns of gene flow are fundamental to successful spatial conservation management. The field of seascape genetics seeks to incorporate environmental variables and processes into analyses of population genetic data to improve our understanding of forces driving genetic divergence in the marine environment. Information about barriers to gene flow (such as ocean currents) is used to define a resistance surface to predict the spatial genetic structure of populations and explain deviations from the widely applied isolation-by-distance model. The majority of seascape approaches to date have been applied to linear coastal systems or at large spatial scales (more than 250 km), with very few applied to complex systems at regional spatial scales (less than 100 km). Here, we apply a seascape genetics approach to a peripheral population of the broadcast-spawning coral Acropora spicifera across the Houtman Abrolhos Islands, a high-latitude complex coral reef system off the central coast of Western Australia. We coupled population genetic data from a panel of microsatellite DNA markers with a biophysical dispersal model to test whether oceanographic processes could explain patterns of genetic divergence. We identified significant variation in allele frequencies over distances of less than 10 km, with significant differentiation occurring between adjacent sites but not between the most geographically distant ones. Recruitment probabilities between sites based on simulated larval dispersal were projected into a measure of resistance to connectivity that was significantly correlated with patterns of genetic divergence, demonstrating that patterns of spatial genetic structure are a function of restrictions to gene flow imposed by oceanographic currents. This study advances our understanding of the role of larval dispersal on the fine-scale genetic structure of coral populations across a complex island system and applies a methodological framework that can be tailored to suit a variety of marine organisms with a range of life-history characteristics. 相似文献
94.
Improved white spruce (Picea glauca) genome assemblies and annotation of large gene families of conifer terpenoid and phenolic defense metabolism
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René L. Warren Christopher I. Keeling Macaire Man Saint Yuen Anthony Raymond Greg A. Taylor Benjamin P. Vandervalk Hamid Mohamadi Daniel Paulino Readman Chiu Shaun D. Jackman Gordon Robertson Chen Yang Brian Boyle Margarete Hoffmann Detlef Weigel David R. Nelson Carol Ritland Nathalie Isabel Barry Jaquish Alvin Yanchuk Jean Bousquet Steven J. M. Jones John MacKay Inanc Birol Joerg Bohlmann 《The Plant journal : for cell and molecular biology》2015,83(2):189-212
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96.
Shaun H. Speldewinde Victoria A. Doronina Chris M. Grant 《Molecular biology of the cell》2015,26(25):4541-4551
Prions are self-propagating, infectious proteins that underlie several neurodegenerative diseases. The molecular basis underlying their sporadic formation is poorly understood. We show that autophagy protects against de novo formation of [PSI+], which is the prion form of the yeast Sup35 translation termination factor. Autophagy is a cellular degradation system, and preventing autophagy by mutating its core components elevates the frequency of spontaneous [PSI+] formation. Conversely, increasing autophagic flux by treating cells with the polyamine spermidine suppresses prion formation in mutants that normally show a high frequency of de novo prion formation. Autophagy also protects against the de novo formation of another prion, namely the Rnq1/[PIN+] prion, which is not related in sequence to the Sup35/[PSI+] prion. We show that growth under anaerobic conditions in the absence of molecular oxygen abrogates Sup35 protein damage and suppresses the high frequency of [PSI+] formation in an autophagy mutant. Autophagy therefore normally functions to remove oxidatively damaged Sup35, which accumulates in cells grown under aerobic conditions, but in the absence of autophagy, damaged/misfolded Sup35 undergoes structural transitions favoring its conversion to the propagatable [PSI+] form. 相似文献
97.
Singhvi A Teuliere J Talavera K Cordes S Ou G Vale RD Prasad BC Clark SG Garriga G 《Current biology : CB》2011,21(11):948-954
During development, all cells make the decision to live or die. Although the molecular mechanisms that execute the apoptotic program are well defined, less is known about how cells decide whether to live or die. In C.?elegans, this decision is linked to how cells divide asymmetrically [1, 2]. Several classes of molecules are known to regulate asymmetric cell divisions in metazoans, yet these molecules do not appear to control C.?elegans divisions that produce apoptotic cells [3]. We identified CNT-2, an Arf GTPase-activating protein (GAP) of the AGAP family, as a novel regulator of this type of neuroblast division. Loss of CNT-2 alters daughter cell size and causes the apoptotic cell to adopt the fate of its sister cell, resulting in extra neurons. CNT-2's Arf GAP activity is essential for its function in these divisions. The N terminus of CNT-2, which contains?a GTPase-like domain that defines the AGAP class of Arf GAPs, negatively regulates CNT-2's function. We provide evidence that CNT-2 regulates receptor-mediated endocytosis and consider the implications of its role in asymmetric cell divisions. 相似文献
98.
Neale BM Rivas MA Voight BF Altshuler D Devlin B Orho-Melander M Kathiresan S Purcell SM Roeder K Daly MJ 《PLoS genetics》2011,7(3):e1001322
Technological advances make it possible to use high-throughput sequencing as a primary discovery tool of medical genetics, specifically for assaying rare variation. Still this approach faces the analytic challenge that the influence of very rare variants can only be evaluated effectively as a group. A further complication is that any given rare variant could have no effect, could increase risk, or could be protective. We propose here the C-alpha test statistic as a novel approach for testing for the presence of this mixture of effects across a set of rare variants. Unlike existing burden tests, C-alpha, by testing the variance rather than the mean, maintains consistent power when the target set contains both risk and protective variants. Through simulations and analysis of case/control data, we demonstrate good power relative to existing methods that assess the burden of rare variants in individuals. 相似文献
99.
Winterton SL 《ZooKeys》2011,(120):55-63
The endemic Australian genus Actenomeros Winterton & Irwin, 1999b is reviewed. Three species are transferred from Nanexila Winterton & Irwin, 1999a: Actenomeros aureilineata (Winterton & Irwin, 1999a) comb. n., Actenomeros intermedia (Winterton & Irwin, 1999a) comb. n. and Actenomeros paradoxa (Winterton & Irwin, 1999a) comb. n. A new species (Actenomeros budawangsp. n.) is described and figured from New South Wales. A key to species is presented. 相似文献
100.