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971.
Exposure to estrogens is a risk factor for breast and other human cancers. Initiation of breast, prostate and other cancers
has been hypothesized to result from reaction of specific estrogen metabolites, catechol estrogen-3,4-quinones, with DNA to
form depurinating adducts at the N-7 of guanine and N-3 of adenine by 1,4-Michael addition. The catechol of the carcinogenic
synthetic estrogen hexestrol, a hydrogenated derivative of diethylstilbestrol, is metabolized to its quinone, which reacts
with DNA to form depurinating adducts at the N-7 of guanine and N-3 of adenine. The catecholamine dopamine and the metabolite
catechol (1,2-dihydroxybenzene) of the leukemogen benzene can also be oxidized to their quinones, which react with DNA to
form predominantly analogous depurinating adducts. Apurinic sites formed by depurinating adducts are converted into tumor-initiating
mutations by error-prone repair. These mutations could initiate cancer by estrogens and benzene, and Parkinson's disease by
the neurotransmitter dopamine. These data suggest a unifying molecular mechanism of initiation for many cancers and neurodegenerative
diseases and lay the groundwork for designing strategies to assess risk and prevent these diseases.
Received 4 September 2001; received after revision 28 November 2001; accepted 2 December 2001 相似文献
972.
973.
YidC mediates membrane protein insertion in bacteria 总被引:13,自引:0,他引:13
Samuelson JC Chen M Jiang F Möller I Wiedmann M Kuhn A Phillips GJ Dalbey RE 《Nature》2000,406(6796):637-641
The basic machinery for the translocation of proteins into or across membranes is remarkably conserved from Escherichia coli to humans. In eukaryotes, proteins are inserted into the endoplasmic reticulum using the signal recognition particle (SRP) and the SRP receptor, as well as the integral membrane Sec61 trimeric complex (composed of alpha, beta and gamma subunits). In bacteria, most proteins are inserted by a related pathway that includes the SRP homologue Ffh, the SRP receptor FtsY, and the SecYEG trimeric complex, where Y and E are related to the Sec61 alpha and gamma subunits, respectively. Proteins in bacteria that exhibit no dependence on the Sec translocase were previously thought to insert into the membrane directly without the aid of a protein machinery. Here we show that membrane insertion of two Sec-independent proteins requires YidC. YidC is essential for E. coli viability and homologues are present in mitochondria and chloroplasts. Depletion of YidC also interferes with insertion of Sec-dependent membrane proteins, but it has only a minor effect on the export of secretory proteins. These results provide evidence for an additional component of the translocation machinery that is specialized for the integration of membrane proteins. 相似文献
974.
Alteration of mitochondrial bioenergetics due to intravenous injection of a perfluorocarbon emulsion
D. Branca S. M. Chiarelli E. Vincenti C. Tortorella G. Scutari 《Cellular and molecular life sciences : CMLS》1994,50(7):660-663
Wistar albino rats were intravenously injected with 1 ml of an oxyphoretic emulsion of perfluorobutylfurane and killed 3, 7 or 30 days later. Mitochondria isolated from the liver and kidneys of treated rats showed a small decrease in the transmembrane electrical potential and a substantial depression of the rates of both ATP synthesis and ADP-stimulated respiration. These alterations in mitochondrial oxidative phosphorylation appear to be induced by perfluorocarbon and/or tensioactive molecules interacting with hydrophobic cell structures. 相似文献
975.
onc sequences (v-fes) of Snyder-Theilen feline sarcoma virus are derived from noncontiguous regions of a cat cellular gene (c-fes) 总被引:24,自引:0,他引:24
Type C sarcoma viruses are genetic recombinants containing portions of replication-competent helper viruses linked to sarcoma virus-specific sequences (generically designated onc genes) which are thought to be required for acute fibroblast transformation. The onc elements of different avian and mammalian sarcoma viral isolates are each homologous to subsets of cellular DNA sequences which have no well-defined role in normal cells. Because of the lack of significant homology between helper viral genes and cellular onc sequences, the recombinational mechanisms which facilitate the formation of sarcoma viral genomes remain unclear. In Moloney murine sarcoma virus, viral onc (or v-mos) and cellular onc (or c-mos) sequences exhibit complete and uninterrupted homology as determined by heteroduplex and restriction enzyme analyses of molecularly cloned DNA. By contrast, the cellular counterparts of the onc elements of Rous sarcoma virus (G. Cooper and R. Parker, personal communication), avian erythroblastosis virus (B. Vennstrom, personal communication), Abelson leukaemia virus (D. Baltimore, personal communication), Harvey sarcoma virus (E. Scolnick, personal communication) and simian sarcoma virus (R. Gallo, personal communication) are now known to contain intervening sequences which do not appear in the respective viral genomes. Here we report the use of the Southern blot technique to examine cat cellular DNA sequences (c-fes) homologous to the onc gene (v-fes) of Snyder-Theilen feline sarcoma virus (ST-FeSV). We used cloned DNA 'probes' containing defined portions of the ST-FeSV genome to show that v-fes sequences originate from at least four noncontiguous sequences in cat cellular DNA, separated from each other by intervening sequences. 相似文献
976.
977.
Rasmussen SG Choi HJ Fung JJ Pardon E Casarosa P Chae PS Devree BT Rosenbaum DM Thian FS Kobilka TS Schnapp A Konetzki I Sunahara RK Gellman SH Pautsch A Steyaert J Weis WI Kobilka BK 《Nature》2011,469(7329):175-180
G protein coupled receptors (GPCRs) exhibit a spectrum of functional behaviours in response to natural and synthetic ligands. Recent crystal structures provide insights into inactive states of several GPCRs. Efforts to obtain an agonist-bound active-state GPCR structure have proven difficult due to the inherent instability of this state in the absence of a G protein. We generated a camelid antibody fragment (nanobody) to the human β(2) adrenergic receptor (β(2)AR) that exhibits G protein-like behaviour, and obtained an agonist-bound, active-state crystal structure of the receptor-nanobody complex. Comparison with the inactive β(2)AR structure reveals subtle changes in the binding pocket; however, these small changes are associated with an 11?? outward movement of the cytoplasmic end of transmembrane segment 6, and rearrangements of transmembrane segments 5 and 7 that are remarkably similar to those observed in opsin, an active form of rhodopsin. This structure provides insights into the process of agonist binding and activation. 相似文献
978.
长期施肥条件下土壤钾素固定影响因素分析 总被引:13,自引:0,他引:13
为探索长期不同施肥对土壤钾素固定的影响, 采用室内模拟试验对中国主要农田土壤, 即红壤、水稻土、灰漠土、塿土、潮土、黑土和紫色土对外源钾固定能力的差异性进行了研究, 并对长期施肥条件下土壤钾素固定的影响因素进行了因子分析和逐步回归分析. 结果表明, 施肥15年后, 不同土壤固钾能力大小顺序为: 黑土>紫色土>塿土>潮土>水稻土>灰漠土>红壤. 土壤主要黏土矿物类型明显影响其固钾能力, 此外, 对以2:1型黏土矿物为主的土壤而言, 其固钾能力还受两个主要因子的影响: 因子1包括土壤速效钾、缓效钾和K+饱和度3个因素, 因子2包括土壤阳离子交换量(CEC)、土壤有机质(SOM)和<0.002 mm黏粒含量3个因素. 在外源钾加入浓度较低(0.4~ 1.6 g•L?1)时, 因子1和因子2分别主要通过土壤K+饱和度和CEC的变化影响土壤的固钾能力; 在外源钾加入浓度较高(2.4~4.0 g•L?1)时, 因子1和因子2分别主要通过土壤K+饱和度和<0.002 mm黏粒含量的变化影响土壤的固钾能力. 相似文献
979.
Huber D Gutnisky DA Peron S O'Connor DH Wiegert JS Tian L Oertner TG Looger LL Svoboda K 《Nature》2012,484(7395):473-478
The mechanisms linking sensation and action during learning are poorly understood. Layer 2/3 neurons in the motor cortex might participate in sensorimotor integration and learning; they receive input from sensory cortex and excite deep layer neurons, which control movement. Here we imaged activity in the same set of layer 2/3 neurons in the motor cortex over weeks, while mice learned to detect objects with their whiskers and report detection with licking. Spatially intermingled neurons represented sensory (touch) and motor behaviours (whisker movements and licking). With learning, the population-level representation of task-related licking strengthened. In trained mice, population-level representations were redundant and stable, despite dynamism of single-neuron representations. The activity of a subpopulation of neurons was consistent with touch driving licking behaviour. Our results suggest that ensembles of motor cortex neurons couple sensory input to multiple, related motor programs during learning. 相似文献
980.
D Fuchs A Hausen G Reibnegger D Schoenitzer E R Werner M P Dierich H Wachter 《Nature》1987,330(6150):702-703