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排序方式: 共有3158条查询结果,搜索用时 15 毫秒
131.
Violette Azzoni Julien Wicinski Manon Macario Martin Castagn Pascal Finetti Katerina Ambrosova Clia D. Rouault Arnaud Serg Anne Farina Emilie Agavnian Sergiu Coslet Emmanuelle Josselin Arnaud Guille Jos Adelaide Emmanouil Zacharioudakis Rmy Castellano Francois Bertucci Daniel Birnbaum Raphael Rodriguez Emmanuelle Charafe-Jauffret Christophe Ginestier 《Cell death & disease》2022,13(2)
Replication stress (RS) has a pivotal role in tumor initiation, progression, or therapeutic resistance. In this study, we depicted the mechanism of breast cancer stem cells’ (bCSCs) response to RS and its clinical implication. We demonstrated that bCSCs present a limited level of RS compared with non-bCSCs in patient samples. We described for the first time that the spatial nuclear location of BMI1 protein triggers RS response in breast cancers. Hence, in bCSCs, BMI1 is rapidly located to stalled replication forks to recruit RAD51 and activate homologous-recombination machinery, whereas in non-bCSCs BMI1 is trapped on demethylated 1q12 megasatellites precluding effective RS response. We further demonstrated that BMI1/RAD51 axis activation is necessary to prevent cisplatin-induced DNA damage and that treatment of patient-derived xenografts with a RAD51 inhibitor sensitizes tumor-initiating cells to cisplatin. The comprehensive view of replicative-stress response in bCSC has profound implications for understanding and improving therapeutic resistance.Subject terms: Breast cancer, Cancer stem cells 相似文献
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Nicholas Brousseau Laurianne Morin Manale Ouakki Patrice Savard Caroline Quach Yves Longtin Matthew P. Cheng Alex Carignan Simon F. Dufresne Jean-Michel Leduc Christian Lavalle Nicolas Gauthier Julie Bestman-Smith Maria-Jesus Arrieta Magued Ishak Simon Lvesque Philippe Martin Gaston De Serres 《CMAJ》2022,194(9):E350
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In order to obtain new insight into the control of balance during arm raising movements in bipedal stance, we performed a biomechanical analysis of kinematics and dynamical aspects of arm raising movements by combining experimental work, large-scale models of the body, and techniques simulating human behavior. A comparison between experimental and simulated joint kinematics showed that the minimum torque change model yielded realistic trajectories. We then performed an analysis based on computer simulations. Since keeping the center of pressure (CoP) and the projection of the center of mass (CoM) inside the support area is essential for equilibrium, we modeled an arm raising movement where displacement of one or the other variable is limited. For this optimization model, the effects of adding equilibrium constraints on movement trajectories were investigated. The results show that: (a) the choice of the regulated variable influences the strategy adopted by the system and (b) the system was not able to regulate the CoM for very fast movements without compromising its balance. Consequently, we suggest that the system is able to maintain balance while raising the arm by only controlling the CoP. This may be done mainly by using hip mechanisms and controlling net ankle torque. 相似文献
137.
Felber LM Cloutier SM Kündig C Kishi T Brossard V Jichlinski P Leisinger HJ Deperthes D 《BioTechniques》2004,36(5):878-885
A protease can be defined as an enzyme capable of hydrolyzing peptide bonds. Thus, characterization of a protease involves identification of target peptide sequences, measurement of activities toward these sequences, and determination of kinetic parameters. Biological protease substrates based on fluorescent protein pairs, which allow for use of fluorescence resonance energy transfer (FRET), have been recently developed for in vivo protease activity detection and represent a very interesting alternative to chemical substrates for in vitro protease characterization. Here, we analyze a FRET system consisting of cyan and yellow fluorescent proteins (CFP and YFP, respectively), which are fused by a peptide linker serving as protease substrate. Conditions for CFP-YFP fusion protein production in Escherichia coli and purification of proteins were optimized. FRET between CFP and YFP was found to be optimum at a pH between 5.5 and 10.0, at low concentrations of salt and a temperature superior to 25 degrees C. For efficient FRET to occur, the peptide linker between CFP and YFP can measure up to 25 amino acids. The CFP-substrate-YFP system demonstrated a high degree of resistance to nonspecific proteolysis, making it suitable for enzyme kinetic analysis. As with chemical substrates, substrate specificity of CFP-substrate-YFP proteins was tested towards different proteases and kcat/Km values were calculated. 相似文献
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ATG genes and macroautophagy 总被引:1,自引:0,他引:1
Codogno P 《Médecine sciences : M/S》2004,20(8-9):734-736
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