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51.
The study of cell cycle control in plants is expected to contribute to the understanding of plants' unique developmental features. The principal regulators of the eukaryotic cell cycle, namely, cyclin-dependent kinases (CDKs) and cyclins, are also conserved in plants. This review is concerned with our present knowledge on cell cycle regulation in Arabidopsis thaliana, which is widely accepted as a model plant for the study of a broad range of biological questions. Up to the present, 2 CDKs and 11 cyclins have been identified in Arabidopsis. While the expression of one of these CDKs has been found to be positively correlated with the competence of cells to divide, cyc1A1 expression of the cyclin has been almost exclusively confined to dividing cells. Although much remains to be studied concerning upstream regulators of these genes, the successful introduction of mutant CDKs into plants demonstrates the potential of using such an approach to intentionally modulate the plant cell cycle and development. 相似文献
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The heterogeneous responses of clonal cancer cells to treatment is understood to be caused by several factors, including stochasticity, cell-cycle dynamics, and different micro-environments. In a tumor, cancer cells may encounter fluctuating conditions and transit from a stationary culture to a proliferating state, for example this may occur following treatment. Here, we undertake a quantitative evaluation of the response of single cancerous lymphoblasts (L1210 cells) to various treatments administered during this transition. Additionally, we developed an experimental system, a “Mammalian Mother Machine,” that tracks the fate of thousands of mammalian cells over several generations under transient exposure to chemotherapeutic drugs. Using our developed system, we were able to follow the same cell under repeated treatments and continuously track many generations. We found that the dynamics of the transition between stationary and proliferative states are highly variable and affect the response to drug treatment. Using cell-cycle markers, we were able to isolate a subpopulation of persister cells with distinctly higher than average survival probability. The higher survival rate encountered with cell-cycle phase specific drugs was associated with a significantly longer time-till-division, and was reduced by a non cell-cycle specific drug. Our results suggest that the variability of transition times from the stationary to the proliferating state may be an obstacle hampering the effectiveness of drugs and should be taken into account when designing treatment regimens. 相似文献
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Orit Jacobson Zhantong Wang Guocan Yu Ying Ma Xiaoyuan Chen Dale O. Kiesewetter 《Bioorganic & medicinal chemistry》2019,27(19):115041
The efficient radiosynthesis of biomolecules utilizing minute quantities of maleimide substrate is important for availability of novel peptide molecular imaging agents. We evaluated both 3-18F-fluoropropane-1-thiol and 2-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy)ethane-1-thiol (18F-fluoro-PEG4 thiol) as prosthetic groups for radiolabeling under physiological conditions. The precursor employed a benzoate for protection of the thiol and an arylsulfonate leaving group. The radiofluorination was fully automated on an Eckert & Ziegler synthesis system using standard Kryptofix222/K2CO3 conditions. In order to minimize the amount of biological molecule required for subsequent conjugation, the intermediates, S-(3-18F-fluoropropyl) benzothioate and 18F-fluoro-PEG4 benzothioate, were purified by HPLC. The intermediates were isolated from the HPLC in yields of 37–47% and 28–35%, respectively, and retrieved from eluate using solid phase extraction. Treatment of the benzothioates with sodium methoxide followed by acetic acid provided the free thiols. The desired maleimide substrate in acetonitrile or phosphate buffer was then added and incubated at room temperature for 15 min. The final radiolabeled bioconjugate was purified on a separate HPLC or NAP-5 column. Maleimides utilized for the coupling reaction included phenyl maleimide, an Evans Blue maleimide derivative, a dimeric RGDfK maleimide (E[c(RGDfK)]2), two aptamer maleimides, and PSMA maleimide derivative. Isolated radiochemical yields (non-decay corrected) of maleimide addition products based on starting 18F-fluoride ranged from 6 to 22% in a synthesis time of about 90 min.18F-thiol prosthetic groups were further tested in vivo by conjugation to E[c(RGDfK)]2 maleimide in a U87MG xenograft model. PET studies demonstrated similar tumor accumulation of both prosthetic groups. 18F-fluoro-PEG4-S-E[c(RGDfK)]2 displayed a somewhat favorable pharmacokinetics compared to 18F-fluoropropyl-S-E[c(RGDfK)]2. Bone uptake was low for both indicating in vivo stability. 相似文献
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Pinhas-Hamiel O Lerner-Geva L Copperman NM Jacobson MS 《Obesity (Silver Spring, Md.)》2007,15(11):2825-2831
Objective: The goal was to describe the lipid profile and insulin changes seen in obese children and adolescents at different stages of puberty. Research Methods and Procedures: A cross‐sectional study was conducted by chart review of 181 obese (BMI > 95th) children and adolescents 5 to 17 years of age, who were referred to the Center for Atherosclerosis Prevention for cardiovascular risk reduction from January 2003 through December 2003. Results: Eighty (44.2%) subjects were <12 years of age, and 101 (55.8%) were ≥12 years. Severity of obesity as expressed by BMI standard deviation score did not differ between these age groups. A significant difference with lower serum levels of total cholesterol, non‐high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol was seen with older age and with advancing sexual maturity rating. Triglycerides, very‐low‐density lipoprotein cholesterol, and lipoprotein(a) levels remained elevated across age and pubertal stages. Insulin levels and insulin resistance as expressed by homeostasis model assessment were significantly higher with older age. Similar trends were observed both in obese boys and obese girls during puberty. Discussion: The most striking findings of this study are that in the 5‐ to 17‐year‐old obese population, the combination of elevated triglycerides and very‐low‐density lipoprotein cholesterol and low high‐density lipoprotein cholesterol levels place them at greater cardiovascular risk than their non‐obese peers, even when the changing patterns of lipids and lipoproteins seen during pubertal maturation are accounted for. 相似文献
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Orit Uziel Einat Beery Vladimir Dronichev Katty Samocha Sergei Gryaznov Lola Weiss Shimon Slavin Michal Kushnir Yardena Nordenberg Claudette Rabinowitz Baruch Rinkevich Tania Zehavi Meir Lahav 《PloS one》2010,5(2)