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131.
Katharine Holloway M McGaughey GB Coburn CA Stachel SJ Jones KG Stanton EL Gregro AR Lai MT Crouthamel MC Pietrak BL Munshi SK 《Bioorganic & medicinal chemistry letters》2007,17(3):823-827
Several simple scoring methods were examined for 2 series of beta-secretase (BACE-1) inhibitors to identify a docking/scoring protocol which could be used to design BACE-1 inhibitors in a drug discovery program. Both the PLP1 score and MMFFs interaction energy (E(inter)) performed as well or better than more computationally intensive methods for a set of substrate-based inhibitors, while the latter performed well for both sets of inhibitors. 相似文献
132.
Elizabeth D. Hughes Yun Yan Qu Suzanne J. Genik Robert H. Lyons Christopher D. Pacheco Andrew P. Lieberman Linda C. Samuelson Igor O. Nasonkin Sally A. Camper Margaret L. Van Keuren Thomas L. Saunders 《Mammalian genome》2007,18(8):549-558
Genetically modified mouse strains derived from embryonic stem (ES) cells are powerful tools for gene function analysis. ES
cells from the C57BL/6 mouse strain are not widely used to generate mouse models despite the advantage of a defined genetic
background. We assessed genetic variation in six such ES cell lines with 275 SSLP markers. Compared to C57BL/6, Bruce4 differed
at 34 SSLP markers and had significant heterozygosity on three chromosomes. BL/6#3 and Dale1 ES cell lines differed at only
3 SSLP makers. The C2 and WB6d ES cell lines differed at 6 SSLP markers. It is important to compare the efficiency of producing
mouse models with available C57BL/6 ES cells relative to standard 129 mouse strain ES cells. We assessed genetic stability
(the tendency of cells to become aneuploid) in 110 gene-targeted ES cell clones from the most widely used C57BL/6 ES cell
line, Bruce4, and 710 targeted 129 ES cell clones. Bruce4 clones were more likely to be aneuploid and unsuitable for ES cell-mouse
chimera production. Despite their tendency to aneuploidy and consequent inefficiency, use of Bruce4 ES cells can be valuable
for models requiring behavioral studies and other mouse models that benefit from a defined C57BL/6 background.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
133.
Piccinini Alexandre Oliveira Mariana Pacheco Silva Mariella Reinol Bett Gabriela Souza Becker Isabel Borges Mendes Talita Farias Salla Daniéle Hendler Silva Larissa Espindola Vilela Thais Ceresér Moraes Fernanda Mendes Moterle Diego Damiani Adriani Paganini Dagostin Lígia Salvan Tietbohl Lariani Tamires Bittencourt João Vitor Silvano Biehl Erica Denicol Tais Luise Bonfante Sandra Regina Andrade Vanessa Moraes Silveira Paulo Cesar Lock Prophiro Josiane Somariva Ferreira Gabriela Kozuchovski Petronilho Fabricia Kanis Luiz Alberto Rezin Gislaine Tezza 《Neurochemical research》2022,47(7):1888-1903
Neurochemical Research - This study aimed to evaluate the effect of Cynara cardunculus leaf ethanol extract on inflammatory and oxidative stress parameters in the hypothalamus, prefrontal cortex,... 相似文献
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136.
Gomez R Jolly S Williams T Tucker T Tynebor R Vacca J McGaughey G Lai MT Felock P Munshi V DeStefano D Touch S Miller M Yan Y Sanchez R Liang Y Paton B Wan BL Anthony N 《Bioorganic & medicinal chemistry letters》2011,21(24):7344-7350
Next generation NNRTIs are sought which possess both broad spectrum antiviral activity against key mutant strains and a high genetic barrier to the selection of new mutant viral strains. Pyridones were evaluated as an acyclic conformational constraint to replace the aryl ether core of MK-4965 (1) and the more rigid indazole constraint of MK-6186 (2). The resulting pyridone compounds are potent inhibitors of HIV RT and have antiviral activity in cell culture that is superior to other next generation NNRTI’s. 相似文献
137.
Reger TS Yang ZQ Schlegel KA Shu Y Mattern C Cube R Rittle KE McGaughey GB Hartman GD Tang C Ballard J Kuo Y Prueksaritanont T Nuss CE Doran SM Fox SV Garson SL Li Y Kraus RL Uebele VN Renger JJ Barrow JC 《Bioorganic & medicinal chemistry letters》2011,21(6):1692-1696
A novel series of amide T-type calcium channel antagonists were prepared and evaluated using in vitro and in vivo assays. Optimization of the screening hit 3 led to identification of the potent and selective T-type antagonist 37 that displayed in vivo efficacy in rodent models of epilepsy and sleep. 相似文献
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139.
Advances in technologies associated with mass spectrometry-based proteomic techniques have added a new dimension to the field of biomedical research. Most of the existing research on human gestation has focused on the application of these high-throughput methodologies in the study of amniotic fluid. In cases of fetal aneuploidies, the use of proteomic platforms has contributed to the identification of relevant protein biomarkers that could potentially change early diagnosis and treatment. The current article focuses on studies of normal amniotic fluid using proteomic technologies and describes alterations noted in the amniotic fluid proteome in the presence of fetal aneuploidies. 相似文献
140.
Adult pancreatic β cells can replicate during growth and after injury to maintain glucose homeostasis. Here, we report that β cells deficient in Dnmt1, an enzyme that propagates DNA methylation patterns during cell division, were converted to α cells. We identified the lineage determination gene aristaless-related homeobox (Arx), as methylated and repressed in β cells, and hypomethylated and expressed in α cells and Dnmt1-deficient β cells. We show that the methylated region of the Arx locus in β cells was bound by methyl-binding protein MeCP2, which recruited PRMT6, an enzyme that methylates histone H3R2 resulting in repression of Arx. This suggests that propagation of DNA methylation during cell division also ensures recruitment of enzymatic machinery capable of modifying and transmitting histone marks. Our results reveal that propagation of DNA methylation during cell division is essential for repression of α cell lineage determination genes to maintain pancreatic β cell identity. 相似文献