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101.
Chase D Serafinas C Ashcroft N Kosinski M Longo D Ferris DK Golden A 《Genesis (New York, N.Y. : 2000)》2000,26(1):26-41
The Polo-like kinases are key regulatory molecules required during the cell cycle for the successful completion of mitosis. We have cloned a C. elegans homolog of the Drosophila melanogaster polo gene (designated plk-1 for C. elegans polo-like kinase-1) and present the subcellular localization of the PLK-1 protein during the meiotic and mitotic cell cycles in C. elegans oocytes and embryos, respectively. Disruption of PLK-1 expression by RNA-mediated interference (RNAi) disrupts normal oocyte and embryonic development. Inspection of oocytes revealed a defect in nuclear envelope breakdown (NEBD) before ovulation. This defect in NEBD was also observed in oocytes that were depleted of the cyclin-dependent kinase NCC-1 (C. elegans homolog of Cdc2). The plk-1 RNAi oocytes were fertilized; however the resulting embryos were unable to separate their meiotic chromosomes or form and extrude polar bodies. These defects led to embryonic arrest as single cells. genesis 26:26-41, 2000. Published 2000 Wiley-Liss, Inc. 相似文献
102.
Background
Discovering sequence patterns with variation can unveil functions of a protein family that are important for drug discovery. Exploring protein families using existing methods such as multiple sequence alignment is computationally expensive, thus pattern search, called motif finding in Bioinformatics, is used. However, at present, combinatorial algorithms result in large sets of solutions, and probabilistic models require a richer representation of the amino acid associations. To overcome these shortcomings, we present a method for ranking and compacting these solutions in a new representation referred to as Aligned Pattern Clusters (APCs). To tackle the problem of a large solution set, our method reveals a reduced set of candidate solutions without losing any information. To address the problem of representation, our method captures the amino acid associations and conservations of the aligned patterns. Our algorithm renders a set of APCs in which a set of patterns is discovered, pruned, aligned, and synthesized from the input sequences of a protein family.Results
Our algorithm identifies the binding or other functional segments and their embedded residues which are important drug targets from the cytochrome c and the ubiquitin protein families taken from Unitprot. The results are independently confirmed by pFam's multiple sequence alignment. For cytochrome c protein the number of resulting patterns with variations are reduced by 76.62% from the number of original patterns without variations. Furthermore, all of the top four candidate APCs correspond to the binding segments with one of each of their conserved amino acid as the binding residue. The discovered proximal APCs agree with pFam and PROSITE results. Surprisingly, the distal binding site discovered by our algorithm is not discovered by pFam nor PROSITE, but confirmed by the three-dimensional cytochrome c structure. When applied to the ubiquitin protein family, our results agree with pFam and reveals six of the seven Lysine binding residues as conserved aligned columns with entropy redundancy measure of 1.0.Conclusion
The discovery, ranking, reduction, and representation of a set of patterns is important to avert time-consuming and expensive simulations and experimentations during proteomic study and drug discovery.103.
Shijie Liao Wenyu Feng Yun Liu Ziyi Wang Xiaofei Ding Fangming Song Xixi Lin Huijie Song Anil KC Yuangang Su Jiamin Liang Jiake Xu Qian Liu Jinmin Zhao 《Journal of cellular physiology》2021,236(2):1432-1444
Revision operations have become a new issue after successful artificial joint replacements, and periprosthetic osteolysis leading to prosthetic loosening is the main cause of why the overactivation of osteoclasts (OCs) plays an important role. The effect of biochanin A (BCA) has been examined in osteoporosis, but no study on the role of BCA in prosthetic loosening osteolysis has been conducted yet. In this study, we utilised enzyme‐linked immunosorbent assay, computed tomography imaging, and histological analysis. Results showed that BCA downregulated the secretion levels of tumor necrosis factor‐α, interleukin‐1α (IL‐1α), and IL‐1β to suppress inflammatory responses. The secretion levels of receptor‐activated nuclear factor‐κB ligand, CTX‐1, and osteoclast‐associated receptor as well as Ti‐induced osteolysis were also reduced. BCA effectively inhibited osteoclastogenesis and suppressed hydroxyapatite resorption by downregulating OC‐related genes in vitro. Analysis of mechanisms indicated that BCA inhibited the signalling pathways of mitogen‐activated protein kinase (P38, extracellular signal‐regulated kinase, and c‐JUN N‐terminal kinase) and nuclear factor‐κB (inhibitor κB‐α and P65), thereby downregulating the expression of nuclear factor of activated T cell 1 and c‐Fos. In conclusion, BCA may be an alternative choice for the prevention of prosthetic loosening caused by OCs. 相似文献
104.
Wensheng Yu Ling Tong Seong Heon Kim Michael K.C. Wong Lei Chen De-Yi Yang Bandarpalle B. Shankar Brian J. Lavey Guowei Zhou Aneta Kosinski Razia Rizvi Dansu Li Robert J. Feltz John J. Piwinski Kristin E. Rosner Neng-Yang Shih M. Arshad Siddiqui Zhuyan Guo Peter Orth Himanshu Shah Joseph A. Kozlowski 《Bioorganic & medicinal chemistry letters》2010,20(17):5286-5289
We disclose further optimization of hydantoin TNF-α convertase enzyme (TACE) inhibitors. SAR with respect to the non-prime region of TACE active site was explored. A series of biaryl substituted hydantoin compounds was shown to have sub-nanomolar Ki, good rat PK, and good selectivity versus MMP-1, -2, -3, -7, -9, and -13. 相似文献
105.
Bakhtiarova A Taslimi P Elliman SJ Kosinski PA Hubbard B Kavana M Kemp DM 《Biochemical and biophysical research communications》2006,351(2):481-484
The potential therapeutic value of resveratrol in age-related disease settings including cancer, diabetes, and Alzheimer's has emerged from a rapidly growing body of experimental evidence. Protection from oxidative stress appears to be a common feature of resveratrol that may be mediated through SirT1, though more specific molecular mechanisms by which resveratrol mediates its effects remain unclear. This has prompted an upsurge in cell-based mechanistic studies, often incorporating reporter assays for pathway elucidation in response to resveratrol treatment. Here, we report that resveratrol potently inhibits firefly luciferase with a K(i) value of 2microM, and caution that this confounding element may lead to compromised data interpretation. 相似文献
106.
IMMUNOCHEMICAL STUDIES OF RAT BRAIN 总被引:1,自引:0,他引:1
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Henry J. Sutton Racheal Aye Azza H. Idris Rachel Vistein Eunice Nduati Oscar Kai Jedida Mwacharo Xi Li Xin Gao T. Daniel Andrews Marios Koutsakos Thi H.O. Nguyen Maxim Nekrasov Peter Milburn Auda Eltahla Andrea A. Berry Natasha KC Sumana Chakravarty Ian A. Cockburn 《Cell reports》2021,34(6):108684
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