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Mimosine is an effective cell synchronization reagent used for arresting cells in late G1 phase. However, the mechanism underlying mimosine-induced G1 cell cycle arrest remains unclear. Using highly synchronous cell populations, we show here that mimosine blocks S phase entry through ATM activation. HeLa S3 cells are exposed to thymidine for 15 h, released for 9 h by washing out the thymidine, and subsequently treated with 1 mm mimosine for a further 15 h (thymidine → mimosine). In contrast to thymidine-induced S phase arrest, mimosine treatment synchronizes >90% of cells at the G1-S phase boundary by inhibiting the transition of the prereplication complex to the preinitiation complex. Mimosine treatment activates ataxia telangiectasia mutated (ATM)/ataxia telangiectasia and Rad3-related (ATR)-mediated checkpoint signaling without inducing DNA damage. Inhibition of ATM activity is found to induce mimosine-arrested cells to enter S phase. In addition, ATM activation by mimosine treatment is mediated by reactive oxygen species (ROS). These results suggest that, upon mimosine treatment, ATM blocks S phase entry in response to ROS, which prevents replication fork stalling-induced DNA damage.  相似文献   
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Making the decision between self-renewal and differentiation of adult stem cells is critical for tissue repair and homeostasis. Here we show that the apoptotic adaptor Fas-associated death domain (FADD) regulates the fate decisions of muscle satellite cells (SCs). FADD phosphorylation was specifically induced in cycling SCs, which was high in metaphase and declined in later anaphase. Furthermore, phosphorylated FADD at Ser-191 accumulated in the uncommitted cycling SCs and was asymmetrically localized in the self-renewing daughter SCs. SCs containing a phosphoryl-mimicking mutation at Ser-191 of FADD (FADD-D) expressed higher levels of stem-like markers and reduced commitment-associated markers. Moreover, a phosphoryl-mimicking mutation at Ser-191 of FADD suppressed SC activation and differentiation, which promoted the cycling SCs into a reversible quiescent state. Therefore, these data indicate that FADD regulates the fate determination of cycling SCs.  相似文献   
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Lipoate-protein ligases are used to scavenge lipoic acid from the environment and attach the coenzyme to its cognate proteins, which are generally the E2 components of the 2-oxoacid dehydrogenases. The enzymes use ATP to activate lipoate to its adenylate, lipoyl-AMP, which remains tightly bound in the active site. This mixed anhydride is attacked by the ϵ-amino group of a specific lysine present on a highly conserved acceptor protein domain, resulting in the amide-linked coenzyme. The Streptomyces coelicolor genome encodes only a single putative lipoate ligase. However, this protein had only low sequence identity (<25%) to the lipoate ligases of demonstrated activity and appears to be a circularly permuted version of the known lipoate ligase proteins in that the canonical C-terminal domain seems to have been transposed to the N terminus. We tested the activity of this protein both by in vivo complementation of an Escherichia coli ligase-deficient strain and by in vitro assays. Moreover, when the domains were rearranged into a protein that mimicked the arrangement found in the canonical lipoate ligases, the enzyme retained complementation activity. Finally, when the two domains were separated into two proteins, both domain-containing proteins were required for complementation and catalysis of the overall ligase reaction in vitro. However, only the large domain-containing protein was required for transfer of lipoate from the lipoyl-AMP intermediate to the acceptor proteins, whereas both domain-containing proteins were required to form lipoyl-AMP.  相似文献   
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We developed an isotopic technique to assess mitochondrial acetyl-CoA turnover (≈citric acid flux) in perfused rat hearts. Hearts are perfused with buffer containing tracer [13C2,2H3]acetate, which forms M5 + M4 + M3 acetyl-CoA. The buffer may also contain one or two labeled substrates, which generate M2 acetyl-CoA (e.g. [13C6]glucose or [1,2-13C2]palmitate) or/and M1 acetyl-CoA (e.g. [1-13C]octanoate). The total acetyl-CoA turnover and the contributions of fuels to acetyl-CoA are calculated from the uptake of the acetate tracer and the mass isotopomer distribution of acetyl-CoA. The method was applied to measurements of acetyl-CoA turnover under different conditions (glucose ± palmitate ± insulin ± dichloroacetate). The data revealed (i) substrate cycling between glycogen and glucose-6-P and between glucose-6-P and triose phosphates, (ii) the release of small excess acetyl groups as acetylcarnitine and ketone bodies, and (iii) the channeling of mitochondrial acetyl-CoA from pyruvate dehydrogenase to carnitine acetyltransferase. Because of this channeling, the labeling of acetylcarnitine and ketone bodies released by the heart are not proxies of the labeling of mitochondrial acetyl-CoA.  相似文献   
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Recently, we have shown that an untrained respiratory system does limit the endurance of submaximal exercise (64% peak oxygen consumption) in normal sedentary subjects. These subjects were able to increase breathing endurance by almost 300% and cycle endurance by 50% after isolated respiratory training. The aim of the present study was to find out if normal, endurance trained subjects would also benefit from respiratory training. Breathing and cycle endurance as well as maximal oxygen consumption (VO2max) and anaerobic threshold were measured in eight subjects. Subsequently, the subjects trained their respiratory muscles for 4 weeks by breathing 85-160 l.min-1 for 30 min daily. Otherwise they continued their habitual endurance training. After respiratory training, the performance tests made at the beginning of the study were repeated. Respiratory training increased breathing endurance from 6.1 (SD 1.8) min to about 40 min. Cycle endurance at the anaerobic threshold [77 (SD 6) %VO2max] was improved from 22.8 (SD 8.3) min to 31.5 (SD 12.6) min while VO2max and the anaerobic threshold remained essentially the same. Therefore, the endurance of respiratory muscles can be improved remarkably even in trained subjects. Respiratory muscle fatigue induced hyperventilation which limited cycle performance at the anaerobic threshold. After respiratory training, minute ventilation for a given exercise intensity was reduced and cycle performance at the anaerobic threshold was prolonged. These results would indicate the respiratory system to be an exercise limiting factor in normal, endurance trained subjects.  相似文献   
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The tumor suppressor gene p53 was shown to directly regulate the expression of microRNA-34a (miR-34a). miR-34a regulates a plethora of target proteins, which are involved in cell cycle, apoptosis, differentiation, and cellular development.miR-34a resides in the region of chromosome 1p36.23, which is commonly deleted in many tumor types, while it results in the loss expression of miR-34a. The promoters of the miR-34a gene subject to inactivation by CpG methylation also induce the loss expression of miR-34a. Ectopic miR-34a expression induces apoptosis, cell cycle arrest, and differentiation or reduces migration. This review summarizes the progress regarding the role of miR-34a in cell cycle, differentiation, and apoptosis.  相似文献   
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刘晶茹  刘瑞权  姚亮 《生态学报》2012,32(20):6553-6557
生产和消费是产生诸多环境问题的根本原因,而可持续生产和消费则是实现可持续发展的根本途径。基于产业生态学视角,界定了可持续消费的定义及内涵,认为可持续消费首先须符合代内公平、代际公平和资源能源永续合理利用等可持续理念;其次辨识了可持续消费研究依次经历关注消费者行为直接环境影响、关注产品和服务生命周期环境影响到关注消费者责任3个阶段;最后结合我国城市化、工业化背景,提出我国可持续消费研究应该以城市居民为重点、加强生命周期数据库建设和内注重可持续生产等建议。  相似文献   
10.
The shortage of data for emissions from agricultural tractors contributes to LCA results on environmental load from modern crop production possibly having high error levels and high uncertainties. The first part of this work describes measurements and calculations made in order to obtain operation-specific agricultural emission data. Calculations are based on emission data measured on a standard 70 kW tractor of a widely available make. In the second part, results from an LCI on wheat production based on traditionally used emission data are calculated and compared with results obtained when using the emission data for specific working operations derived in part one. One conclusion of the study is that the emission values, when related to the energy in the used fuel, show very large variations between different driving operations. Another conclusion is that the use of the new data results in a marked reduction of the total air emissions produced in the wheat production chain, especially for CO and HC, but also for NOx and SO2.  相似文献   
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