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Jeremy W. K. Ng Dilraj Lama Suryani Lukman David P. Lane Chandra S. Verma Adelene Y. L. Sim 《Proteins》2015,83(12):2240-2250
R248 in the DNA binding domain (DBD) of p53 interacts directly with the minor groove of DNA. Earlier nuclear magnetic resonance (NMR) studies indicated that the R248Q mutation resulted in conformation changes in parts of DBD far from the mutation site. However, how information propagates from the mutation site to the rest of the DBD is still not well understood. We performed a series of all‐atom molecular dynamics (MD) simulations to dissect sterics and charge effects of R248 on p53‐DBD conformation: (i) wild‐type p53 DBD; (ii) p53 DBD with an electrically neutral arginine side‐chain; (iii) p53 DBD with R248A; (iv) p53 DBD with R248W; and (v) p53 DBD with R248Q. Our results agree well with experimental observations of global conformational changes induced by the R248Q mutation. Our simulations suggest that both charge‐ and sterics are important in the dynamics of the loop (L3) where the mutation resides. We show that helix 2 (H2) dynamics is altered as a result of a change in the hydrogen bonding partner of D281. In turn, neighboring L1 dynamics is altered: in mutants, L1 predominantly adopts the recessed conformation and is unable to interact with the major groove of DNA. We focused our attention the R248Q mutant that is commonly found in a wide range of cancer and observed changes at the zinc‐binding pocket that might account for the dominant negative effects of R248Q. Furthermore, in our simulations, the S6/S7 turn was more frequently solvent exposed in R248Q, suggesting that there is a greater tendency of R248Q to partially unfold and possibly lead to an increased aggregation propensity. Finally, based on the observations made in our simulations, we propose strategies for the rescue of R248Q mutants. Proteins 2015; 83:2240–2250. © 2015 Wiley Periodicals, Inc. 相似文献
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Infant-directed speech (IDS) provides an environment that appears to play a significant role in the origins of language in the human infant. Differences have been reported in the use of IDS across cultures, suggesting different styles of infant language-learning. Importantly, both cross-cultural and intra-cultural research suggest there may be a positive relationship between the use of IDS and rates of language development, underscoring the need to investigate cultural differences more deeply. The majority of studies, however, have conceptualized IDS monolithically, granting little attention to a potentially key distinction in how IDS manifests across cultures during the first two years. This study examines and quantifies for the first time differences within IDS in the use of baby register (IDS/BR), an acoustically identifiable type of IDS that includes features such as high pitch, long duration, and smooth intonation (the register that is usually assumed to occur in IDS), and adult register (IDS/AR), the type of IDS that does not include such features and thus sounds as if it could have been addressed to an adult. We studied IDS across 19 American and 19 Lebanese mother-infant dyads, with particular focus on the differential use of registers within IDS as mothers interacted with their infants ages 0–24 months. Our results showed considerable usage of IDS/AR (>30% of utterances) and a tendency for Lebanese mothers to use more IDS than American mothers. Implications for future research on IDS and its role in elucidating how language evolves across cultures are explored. 相似文献
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The observation of two distinct, well-defined oviposition areas in nests of the primitively eusocial wasp Polistes versicolor suggests the presence of multiple egg-layers and territorial behaviors. Electrophoretic analysis of enzyme loci in pupae from 35 colonies revealed an average observed heterozygosity of 0.10 and the existence of private polymorphisms, thereby indicating a low dispersion in this species. No evidence of diploid males was found. Phenotypic segregation analysis revealed the presence of more than one egg-laying female in 15 out of 35 colonies, as well as spatially preferential oviposition in 2 out of 13 nests, with distinct oviposition areas. Genetic relatedness estimates for brood were lower than expected for haplodiploid species under monogynous conditions (r = 0.75 for female broods and r = 0.5 for male) in 4 of those 13 nests, thereby inferring complex sociogenetic structuring in Polistes versicolor colonies. 相似文献
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Ida Romano Laura Dipasquale Pierangelo Orlando Licia Lama Giuliana d’Ippolito Javier Pascual Agata Gambacorta 《Extremophiles : life under extreme conditions》2010,14(2):233-240
A novel thermophilic, anaerobic, rod-shaped bacterium strain, designated Buff, was isolated from buffalo-dung samples collected
from a buffalo-farm located in Caserta (Campania, south of Italy). Strain Buff was Gram-positive, motile and no spore-forming.
The growth temperature range was 40–65°C with an optimum at 60°C, while pH growth range at 60°C was 5.5–8.0 with an optimum
at about pH 6.5. NaCl growth concentration ranged from 0 to 2.0% with an optimum at 0.5% (w/v); no growth was observed with
the presence of NaCl 3.0% (w/v). The strain produced ethanol, acetate, lactate, H2, H2S and CO2 by glucose fermentation. The DNA G + C content was 34.4 mol%. As determined by 16S rRNA sequence analysis, this organism
belonged to the genus Thermoanaerobacterium. On the basis of the physiological and molecular properties, we propose for strain Buff the new species designation Thermoanaerobacterium thermostercus sp. nov. This novel organism represents the first species of the genus Thermoanaerobacterium isolated from buffalo-dung. The type strain is Buff (=DSM 22141 = ATCC BAA-1776). 相似文献
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Romano I Lama L Nicolaus B Poli A Gambacorta A Giordano A 《The Journal of General and Applied Microbiology》2006,52(6):339-348
A halotolerant and alkaliphilic Gram-negative bacterium, strain 18bAG(T), that grows aerobically at the optimum temperature of 37 degrees C, and at pH 7.5-10 (optimum 9.0), was isolated from a salt pool located in Montefredane in Campania Region (South of Italy). The isolate tolerated high concentration of NaCl up to 20%. Strain 18bAG(T) accumulated osmolytes and polyhydroxybutyrate, produced exopolysaccharide and possessed alpha-glucosidase activity. The predominant respiratory quinones were ubiquinones, Q8 and Q6(6H); phosphoethanolamine, phosphatidylglycerol and diphosphatidylglycerol were the predominant polar lipids. Major fatty acids were C16 : 1, C16 : 0, and C18 : 0. On the basis of 16S rRNA gene sequence similarity, 18bAG(T) was shown to belong to Halomonas genus. Analysis of 16S rRNA gene revealed a high similarity of strain 18bAG(T) to Halomonas venusta (DSM 4743(T)) and Halomonas hydrothermalis (DSM 15725(T)). Level of DNA-DNA relatedness between strain 18bAG(T) and the most related species Halomonas venusta and Halomonas hydrothermalis was 56.0% and 41.2%, respectively. The G+C content (mol%) of DNA was 53.0. The RiboPrinting patterns of Halomonas venusta and 18AG(T) showed a pattern similarity of 0.50. On the basis of genomic information and phenotypic characteristics strain 18bAG(T) represents a new species, for which the name Halomonas alkaliphila sp. nov. is proposed. The type strain is 18bAG(T) (=DSM 16354T =ATCC BAA-953T). 相似文献