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br Conformational Activation of APC C Enables Binding to
2019-10-18

Conformational Activation of APC/C Enables Binding to the Coactivator CDC20 APC/C comes to life by binding a coactivator. This is controlled in part by phosphorylation and APC/C conformational changes that expose the Methyllycaconitine citrate mass for the C box and IR tail of the coactivator. I
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In addition to G coupling it is important
2019-10-18

In addition to Gα coupling, it is important to consider that the transition from goal-directed to habitual drug taking also relies on striatal D2R-A2AR heterodimers. Following cocaine self-administration, D2R-A2AR density is increased in the NAc, leading to greater antagonism of the inhibitory (anti
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As mentioned above there are
2019-10-18

As mentioned above, there are two major pathways for the DSB repair in mammalian cells, NHEJ and HR/HDR (homology-directed repair) [13], [51]. NHEJ is active throughout the cell cycle, predominately during the G0 and G1 phases and is considered the major pathway for the DSB repair in human cells [52
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In the case of high
2019-10-18

In the case of high-fidelity polymerases, we propose that water is used to achieve negative selection against nucleotide binding. With specialized DNA polymerases, we propose that nucleobase desolvation plays a different yet important role in allowing these enzymes to replicate damaged DNA. In this
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AMD-070 To determine direct DDR binding partners and to
2019-10-18

To determine direct DDR1-binding partners and to further connect to Akt and mTOR signaling, we performed mass spectrometry on DDR1 immunoprecipitates and found various candidates of the Akt and mTOR pathway such as LARP1 (La-related protein 1) and RPS6 (40S ribosomal protein S6/ S6). Most intriguing
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Each of the CYP enzymes
2019-10-18

Each of the CYP450 enzymes alluded to above are highly selective catalysts, in that, the three aryl coupling reactions en route the biosynthesis of 1 are catalyzed by three different CYP450 enzymes in a sequential manner (Fig. 1). In sharp mtor pathway is the recently described marine bacterial CYP4
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The requisite extended benzyl alcohols and and final
2019-10-18

The requisite extended benzyl alcohols –, , and and final potential DFG-out binding hybrid inhibitors – and – were prepared as shown in , . Benzaldehyde was alkylated with -methoxybenzyl chloride and then reduced with sodium borohydride to give benzyl alcohol . Pyridine derivative was prepared by O-
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br Materials and methods br Results br
2019-10-18

Materials and methods Results Discussion We confirmed the published cDNA and protein sequence of feline CSF-1R and stably cloned the cat receptor into the Ba/F3 cell line. Activation of feline CSF-1R by recombinant human CSF-1 was previously tested by Woolford et al. [14]. Expression of onc
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We also identified a role for the transcription factor
2019-10-18

We also identified a role for the transcription factor p53 in the regulation of the Crm1 promoter. p53 can activate or repress the transcription of target genes. While activation generally occurs through binding of p53 to its consensus binding site in the promoter region of target genes, for example
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Several extragenic cot ts suppressors have
2019-10-18

Several extragenic cot-1 (ts) suppressors have been identified. Among them, cytoplasmic dynein, dynactin, and nuclear distribution mutants of N. crassa, as well as an additional gene gul-1 (NCU01197), have been shown to have genetic interactions with cot-1 (Bruno et al., 1996, Seiler et al., 2006, T
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The swelling independent activation of chloride channels
2019-10-18

The swelling-independent activation of chloride channels by glycerol is proved by our further experiments. When glycerol concentration in the isoosmotic solution was reduced to the micromolar scale or even lower concentration, a Cl− current was still induced. The cathepsin inhibitor were not swollen
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br Dienogest DNG Dienogest is a nortestosterone derivative w
2019-10-18

Dienogest (DNG) Dienogest is a 19-nortestosterone derivative with two special structural changes [Fig. 1a]: [a] At the cabon-17 position there is a cyanomethyl group instead of an ethinyl group; [b] A double bond is present between carbons 9 and 10. DNG is the only progestogen that combines prope
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In summary we have identified a
2019-10-18

In summary, we have identified a series of amides as ERRγ agonists with suitable potency for further development. Our SAR studies of this chemotype identified SR19881 as the most potent full agonist of ERRγ with an EC=0.39 μM in a binding assay and an EC=4.7 μM in a cell-based assay. SR19881 was als
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br Results and discussion br
2019-10-18

Results and discussion Conclusions In conclusion, we have developed rational strategies that allowed us to successfully identify a series of novel analogs structurally related to to modulate the activity of estrogen-related receptors (ERRγ and ERRβ), which are constitutively active. All of th
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In bone PGE exerts both anabolic and
2019-10-18

In bone, PGE2 exerts both anabolic and catabolic effects [6], [7], [8], [9]. Administration of PGE2 to mice lacking each of the four prostanoid receptors identified EP4 as the primary mediator of PGE2-induced bone formation [10]. While the role of EP1 in osteoblastic differentiation and bone metabol
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