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SB 415286 All DGKs have at least two cysteine rich regions
2019-10-21
All DGKs have at least two cysteine-rich regions homologous to the C1A and C1B motifs of PKCs [26]. In theory, these domains may bind DAG, perhaps localizing DGKs to where DAG accumulates. However, no DGK C1 domain has so far been conclusively shown to bind DAG. In fact, structural predictions sugge
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Given the excellent in vitro pharmacology
2019-10-21
Given the excellent in vitro pharmacology profiles of methyl ester 28 and primary amide 29 efforts were reengaged on neutral analogs of these leads, with a focus on non-amide replacements for the carboxylic CRT 0066101 functionality of 1. Acetonitrile 49 was found to have a good balance of DGAT-1 in
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It is well established that Shp
2019-10-21
It is well established that Shp-2 can function as a substrate for several RTK, such as PDGF or EGFR [23], [36]. To test whether DDR1 recognizes Shp-2 as its substrate, we overexpressed a catalytically inactive Shp-2 mutant together with DDR1b in 293 cells [31]. Immunoprecipitation of Shp-2 followed
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During DNA replication p protein binds PCNA in its role
2019-10-21
During DNA replication p21 protein binds PCNA, in its role as processivity factor, to stop replication when there is DNA damage, and apparently p21 also binds PCNA when this is in complex with Cyc/CDKs [11]. In plants, KRPs (functional analogs of p21), inhibit kinase activity in CycD/CDKs complexes
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A growing body of data indicates that endothelial NOS eNOS
2019-10-21
A growing body of data indicates that endothelial NOS (eNOS) is a rate-limiting enzyme for the synthesis of nitric oxide (NO), its downstream gpr40 agonist molecule. High pathological concentrations of NO produced from inducible NO synthase (iNOS) induce apoptosis, whereas a reduction in the concen
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br ET Antagonist for the Future
2019-10-21
ET Antagonist for the Future: Macitentan and Atresentan Macitentan is an insurmountable antagonist, resulting from structure-activity studies to improve the efficacy and tolerability of bosentan, and gained approval in the United States in 2013 for the treatment of PAH. Actelion describes the com
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From a mechanistic standpoint the BCL RD domain represses th
2019-10-21
From a mechanistic standpoint, the BCL6 RD2 domain represses the GPR183 and S1PR1 loci by recruiting HDAC2, but not MTA3-NuRD, to suppress the enhancer activation mark H3K27ac at their distal regulatory elements. However, these data do not exclude the possibility that other as yet unknown corepresso
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br Conflicts of interest br Acknowledgements br
2019-10-21
Conflicts of interest Acknowledgements Introduction Atherosclerosis is the number one cause of death in the United States and among the leading causes of morbidity and mortality globally [1]. Inflammation is critical in all stages of atherosclerosis from the formation of a plaque in the ves
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br Acknowledgments The authors thank Dr Tai Sheng
2019-10-21
Acknowledgments The authors thank Dr. Tai-Sheng Cheng, Yu-Wen Huang and Ting-Wei Gau for technical assistance. This work was supported by the National Science Council of TaiwanNSC 98-2320-B-024-002-MY3 and National University of TainanAB102-216. This information is available free of charge via th
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Most enzymes involved in the
2019-10-21
Most A-1331852 involved in the addition and removal of ubiquitin bind weakly to an overlapping surface on ubiquitin. Previously, Sidhu and colleagues diversified this surface and then used phage display to screen these libraries of ubiquitin variants (UbVs) for binding to DUBs and E3 ligases (Ernst
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Total synthesis requires the two key
2019-10-21
Total synthesis requires the two key intermediates 3 and 7, which were synthesized using the route described in below. Phenylethylamine 3 was readily synthesized from vanillin or isovanillin; the overall yield was 50–52%. To prepare the intermediates 7, bromination of 2-(4-hydroxyphenyl) acetate wit
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Compounds that interact with MDR can do so
2019-10-21
Compounds that interact with MDR1 can do so by different mechanisms. Verapamil is known to modulate drug resistance by acting as a competitive MDR1 substrate [36]. Interestingly, NU7441 has similar growth inhibitory activity in the sensitive and resistant Tranexamic Acid synthesis and there was no o
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Compounds were prepared via the routes shown in varying the
2019-10-19
Compounds were prepared via the routes shown in , varying the sequence of reactions to install the thiazole or the phenyl ring at the end of the synthesis (pyridyl examples were prepared using similar chemistry). The aminothiazole building blocks were prepared as shown in . 5-Aminothiazole was prep
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We then explored the potential roles of vigilin along
2019-10-19
We then explored the potential roles of vigilin, along with other proteins which have affinity for the 69 nt CSF-1R element, in breast cancer cells. The sequestration of these proteins by excess 69 nt pyrimidine-rich element increases CSF-1R levels (Figures 2 and 4), and as a result, increases the d
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br Discussion We are reporting a cryptic insertion of chromo
2019-10-19
Discussion We are reporting a cryptic insertion of chromosome 22 material (EWS) to the long arm of chromosome 11 (11q24, FLI-1) recognizable by FISH in Pam3CSK4 Biotin clinical exhibiting trisomy 8 as the sole cytogenetic anomaly. In ES and PNET tumors, trisomy 8 is the most common secondary abno
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