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排序方式: 共有102条查询结果,搜索用时 140 毫秒
1.
Gaelle Jan Violaine Delorme Nehm Saksouk Marie Abrivard Virginie Gonzalez Xavier Cayla Mohamed-Ali Hakimi Isabelle Tardieux 《Microbes and infection / Institut Pasteur》2009,11(12):935-945
Toxoplasma gondii is a human protozoan parasite that belongs to the phylum of Apicomplexa and causes toxoplasmosis. As the other members of this phylum, T. gondii obligatory multiplies within a host cell by a peculiar type of mitosis that leads to daughter cell assembly within a mother cell. Although parasite growth and virulence have been linked for years, few molecules controlling mitosis have been yet identified and they include a couple of kinases but not the counteracting phosphatases. Here, we report that in contrast to other animal cells, type 2C is by far the major type of serine threonine phosphatase activity both in extracellular and in intracellular dividing parasites. Using wild type and transgenic parasites, we characterized the 37 kDa TgPP2C molecule as an abundant cytoplasmic and nuclear enzyme with activity being under tight regulation. In addition, we showed that the increase in TgPP2C activity significantly affected parasite growth by impairing cytokinesis while nuclear division still occurred. This study supports for the first time that type 2C protein phosphatase is an important regulator of cell growth in T. gondii. 相似文献
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Mirbolook Atena Rasouli-Sadaghiani MirHassan Sepehr Ebrahim Lakzian Amir Hakimi Mohammad 《Journal of Plant Growth Regulation》2021,40(2):831-847
Journal of Plant Growth Regulation - Plants require optimum amounts of nutrients for suitable growth and yield production. Accordingly, the most efficient methods of fertilization, including the... 相似文献
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Mehrabi Fatemeh Shamspur Tayebeh Sheibani Hassan Mostafavi Ali Mohamadi Maryam Hakimi Hamid Bahramabadi Reza Salari Elham 《Biometals》2021,34(6):1237-1246
BioMetals - Trimethoprim and sulfamethoxazole are prescribed for a broad spectrum of bacteria. However, the use of these medicines is restricted due to the risk of microbial resistance in the body.... 相似文献
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Xiwen Cheng Shuang Guo Yu Liu Hao Chu Parvin Hakimi Nathan A. Berger Richard W. Hanson Hung-Ying Kao 《The Journal of biological chemistry》2013,288(41):29746-29759
The promyelocytic leukemia protein is a well known tumor suppressor, but its role in metabolism is largely unknown. Mice with a deletion in the gene for PML (KO mice) exhibit altered gene expression in liver, adipose tissue, and skeletal muscle, an accelerated rate of fatty acid metabolism, abnormal glucose metabolism, constitutive AMP-activating kinase (AMPK) activation, and insulin resistance in skeletal muscle. Last, an increased rate of energy expenditure protects PML KO mice from the effects of obesity induced by a Western diet. Collectively, our study uncovers a previously unappreciated role of PML in the regulation of metabolism and energy balance in mice. 相似文献
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Yogavel Manickam Nipun Malhotra Siddhartha Mishra Palak Babbar Abhishek Dusane Benoît Laleu Valeria Bellini Mohamed-Ali Hakimi Alexandre Bougdour Amit Sharma 《PLoS pathogens》2022,18(3)
Toxoplasmosis is caused by Toxoplasma gondii and in immunocompromised patients it may lead to seizures, encephalitis or death. The conserved enzyme prolyl-tRNA synthetase (PRS) is a validated druggable target in Toxoplasma gondii but the traditional ‘single target–single drug’ approach has its caveats. Here, we describe two potent inhibitors namely halofuginone (HFG) and a novel ATP mimetic (L95) that bind to Toxoplasma gondii PRS simultaneously at different neighbouring sites to cover all three of the enzyme substrate subsites. HFG and L95 act as one triple-site inhibitor in tandem and form an unusual ternary complex wherein HFG occupies the 3’-end of tRNA and the L-proline (L-pro) binding sites while L95 occupies the ATP pocket. These inhibitors exhibit nanomolar IC50 and EC50 values independently, and when given together reveal an additive mode of action in parasite inhibition assays. This work validates a novel approach and lays a structural framework for further drug development based on simultaneous targeting of multiple pockets to inhibit druggable proteins. 相似文献
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Dong Y Hakimi MA Chen X Kumaraswamy E Cooch NS Godwin AK Shiekhattar R 《Molecular cell》2003,12(5):1087-1099
We have isolated a holoenzyme complex termed BRCC containing BRCA1, BRCA2, and RAD51. BRCC not only displays increased association with p53 following DNA damage but also ubiquitinates p53 in vitro. BRCC36 and BRCC45 are novel components of the complex with sequence homology to a subunit of the signalosome and proteasome complexes. Reconstitution of a recombinant four-subunit complex containing BRCA1/BARD1/BRCC45/BRCC36 revealed an enhanced E3 ligase activity compared to that of BRCA1/BARD1 heterodimer. In vivo, depletion of BRCC36 and BRCC45 by the small interfering RNAs (siRNAs) resulted in increased sensitivity to ionizing radiation and defects in G2/M checkpoint. BRCC36 shows aberrant expression in sporadic breast tumors. These findings identify BRCC as a ubiquitin E3 ligase complex that enhances cellular survival following DNA damage. 相似文献
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This study was conducted to identify environmental and human health risks caused by Balarood Dam, in construction phrase. The first step, all risk-generating factors were identified using a Delphi Questionnaire. Afterwards, the identified criteria were prioritized once using the Analytical Hierarchy Process (AHP) method and then by the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS). Due to the complex and uncertain nature of decision-making in times of risk, it was necessary to use more than one weighting method to ensure accuracy of weights. The results from AHP and TOPSIS revealed a mismatch in priorities; therefore, an integration method was presented blending Mean-Rank, Borda, and Copeland methods. According to the TOPSIS results, factors including cut and fill, explosion, and transportation, were first to third highest-priority risk-generating factors, respectively. Considering the results from the AHP method, factors cut and fill, drilling, and explosion were identified as first to third top-priority risk-generating factors, respectively. The results obtained from the integration method suggested that cut and fill, explosion, and drilling are the most important environmental risks at construction phase. As a general conclusion, different weighting methods can lead to different results by which the fate of a decision may be changed and it is essential to control final scores by applying more than one weighting method. 相似文献
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