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排序方式: 共有354条查询结果,搜索用时 815 毫秒
81.
Flintoft L 《Nature reviews. Genetics》2010,11(12):816-817
82.
Dunlevy LP Burren KA Mills K Chitty LS Copp AJ Greene ND 《Birth defects research. Part A, Clinical and molecular teratology》2006,76(7):544-552
BACKGROUND: Closure of the cranial neural tube during embryogenesis is a crucial process in development of the brain. Failure of this event results in the severe neural tube defect (NTD) exencephaly, the developmental forerunner of anencephaly. METHODS: The requirement for methylation cycle function in cranial neural tube closure was tested by treatment of cultured mouse embryos with cycloleucine or ethionine, inhibitors of methionine adenosyl transferase. Embryonic phenotypes were investigated by histological analysis, and immunostaining was performed for markers of proliferation and apoptosis. Methylation cycle intermediates s-adenosylmethionine and s-adenosylhomocysteine were also quantitated by tandem mass spectrometry. RESULTS: Ethionine and cycloleucine treatments significantly reduced the ratio of abundance of s-adenosylmethionine to s-adenosylhomocysteine and are, therefore, predicted to suppress the methylation cycle. Exposure to these inhibitors during the period of cranial neurulation caused a high incidence of exencephaly, in the absence of generalized toxicity, growth retardation, or developmental delay. Reduced neuroepithelial thickness and reduced density of cranial mesenchyme were detected in ethionine-treated but not cycloleucine-treated embryos that developed exencephaly. Reduced mesenchymal density is a potential cause of ethionine-induced exencephaly, although we could not detect a causative alteration in proliferation or apoptosis prior to failure of neural tube closure. CONCLUSIONS: Adequate functioning of the methylation cycle is essential for cranial neural tube closure in the mouse, suggesting that suppression of the methylation cycle could also increase the risk of human NTDs. We hypothesize that inhibition of the methylation cycle causes NTDs due to disruption of crucial reactions involving methylation of DNA, proteins or other biomolecules. 相似文献
83.
Bordeleau ME Mori A Oberer M Lindqvist L Chard LS Higa T Belsham GJ Wagner G Tanaka J Pelletier J 《Nature chemical biology》2006,2(4):213-220
RNA helicases are molecular motors that are involved in virtually all aspects of RNA metabolism. Eukaryotic initiation factor (eIF) 4A is the prototypical member of the DEAD-box family of RNA helicases. It is thought to use energy from ATP hydrolysis to unwind mRNA structure and, in conjunction with other translation factors, it prepares mRNA templates for ribosome recruitment during translation initiation. In screening marine extracts for new eukaryotic translation initiation inhibitors, we identified the natural product hippuristanol. We show here that this compound is a selective and potent inhibitor of eIF4A RNA-binding activity that can be used to distinguish between eIF4A-dependent and -independent modes of translation initiation in vitro and in vivo. We also show that poliovirus replication is delayed when infected cells are exposed to hippuristanol. Our study demonstrates the feasibility of selectively targeting members of the DEAD-box helicase family with small-molecule inhibitors. 相似文献
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87.
Oxygen Requirement and Inhibition of C4
Photosynthesis
: An Analysis of C4 Plants Deficient in the
C3 and C4 Cycles 总被引:2,自引:0,他引:2
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Jo?o P. Maroco Maurice S.B. Ku Peter J. Lea Louisa V. Dever Richard C. Leegood Robert T. Furbank Gerald E. Edwards 《Plant physiology》1998,116(2):823-832
The basis for O2 sensitivity of C4 photosynthesis was evaluated using a C4-cycle-limited mutant of Amaranthus edulis (a phosphoenolpyruvate carboxylase-deficient mutant), and a C3-cycle-limited transformant of Flaveria bidentis (an antisense ribulose-1,5-bisphosphate carboxylase/oxygenase [Rubisco] small subunit transformant). Data obtained with the C4-cycle-limited mutant showed that atmospheric levels of O2 (20 kPa) caused increased inhibition of photosynthesis as a result of higher levels of photorespiration. The optimal O2 partial pressure for photosynthesis was reduced from approximately 5 kPa O2 to 1 to 2 kPa O2, becoming similar to that of C3 plants. Therefore, the higher O2 requirement for optimal C4 photosynthesis is specifically associated with the C4 function. With the Rubisco-limited F. bidentis, there was less inhibition of photosynthesis by supraoptimal levels of O2 than in the wild type. When CO2 fixation by Rubisco is limited, an increase in the CO2 concentration in bundle-sheath cells via the C4 cycle may further reduce the oxygenase activity of Rubisco and decrease the inhibition of photosynthesis by high partial pressures of O2 while increasing CO2 leakage and overcycling of the C4 pathway. These results indicate that in C4 plants the investment in the C3 and C4 cycles must be balanced for maximum efficiency. 相似文献
88.
Louisa V. Dever Mark Pearson Robert J. Ireland Richard C. Leegood Peter J. Lea 《Planta》1998,206(4):649-656
A mutant of Amaranthus edulis (Speg.) lacking activity of the C4 leaf form of NAD-malic enzyme (ME; EC 1.1.1.39) has been isolated. Homozygous mutant (5% wild-type ME activity) and heterozygous
(50% wild-type ME activity) F2 plants were shown to contain both the α and β NAD-ME subunits in similar amounts to those detected in the wild-type leaves.
The rate of photosynthetic CO2 assimilation was reduced in the homozygous mutant to 5% of that observed for the wild-type leaves. Other C4 enzymes were not down-regulated in the mutant plants. There was little difference in photosynthetic rate of the heterozygous
plants compared to the wild-type, suggesting that NAD-ME exerts little control over the rate of C4 photosynthesis, and that in the wild-type the enzyme has a very low control coefficient. The activity loss in the heterozygote
may therefore be compensated by regulatory mechanisms that increase the activity of the enzyme in vivo. Data for bundle-sheath
strands indicated that although the homozygous mutants were able to oxidise malate via the Krebs cycle, they were unable to
convert malate to pyruvate and alanine via NAD-ME.
Received: 2 April 1998 / Accepted: 7 May 1998 相似文献
89.
Daniel Bronder Anthony Tighe Darawalee Wangsa Dali Zong Thomas J. Meyer Ren Wardenaar Paul Minshall Daniela Hirsch Kerstin Heselmeyer-Haddad Louisa Nelson Diana Spierings Joanne C. McGrail Maggie Cam Andr Nussenzweig Floris Foijer Thomas Ried Stephen S. Taylor 《Disease models & mechanisms》2021,14(11)
90.
Sajad Sofi Louisa Williamson Gabrielle L. Turvey Charlotte Scoynes Claire Hirst Jonathan Godwin Neil Brockdorff Justin Ainscough Dawn Coverley 《The Journal of cell biology》2022,221(4)
CIZ1 forms large assemblies at the inactive X chromosome (Xi) in female fibroblasts in an Xist lncRNA-dependent manner and is required for accurate maintenance of polycomb targets genome-wide. Here we address requirements for assembly formation and show that CIZ1 undergoes two direct interactions with Xist, via independent N- and C-terminal domains. Interaction with Xist, assembly at Xi, and complexity of self-assemblies formed in vitro are modulated by two alternatively spliced glutamine-rich prion-like domains (PLD1 and 2). PLD2 is dispensable for accumulation at existing CIZ1–Xi assemblies in wild-type cells but is required in CIZ1-null cells where targeting, assembly, and enrichment for H3K27me3 and H2AK119ub occur de novo. In contrast, PLD1 is required for both de novo assembly and accumulation at preexisting assemblies and, in vitro, drives formation of a stable fibrillar network. Together they impart affinity for RNA and a complex relationship with repeat E of Xist. These data show that alternative splicing of two PLDs modulates CIZ1’s ability to build large RNA–protein assemblies. 相似文献