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In addition to narrowing a wide
2022-06-05
In addition to narrowing a wide knowledge gap in Hh developmental biology research, improved understanding of Disp structure and function is likely to also be relevant to cancer. A growing body of evidence supports that Shh facilitates tumor–stroma communication in a range of cancers to influence tu
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The therapeutic potential of acetate has been
2022-06-05
The therapeutic potential of acetate has been advocated by research on neurodegenerative disorders such as Canavan's disease (Arun et al., 2010, Mathew et al., 2005), where oral acetate improved motor function in a genetic model of the disorder, and in studies of behavioural phenotypes associated wi
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NPxY was recognized as the first short
2022-06-05
NPxY was recognized as the first short signal sequence motif in the cytoplasmic domain of membrane receptors and proteins with critical roles in internalization and trafficking of receptor molecules [130]. Including LDL receptor, beta-1 integrin, megalin, beta-amyloid precursor protein, EGF receptor
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br Next we explored the SAR around the aryl ring
2022-06-05
Next, we explored the SAR around the aryl ring attached to the pyrrole nitrogen in the presence of the 3-CF and the 2,6-difluorophenylpropionic Glycopyrrolate sidechain (). The EC value of the unsubstituted phenyl was about 100 nM. The 4-methyl was 2-fold more potent, however ethyl and bromo did
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Restless running behavior was first described in
2022-06-05
‘Restless running behavior’ was first described in mice after administration of 30mg/kg i.p. ALX-5407 and was thought to be due to an augmentation of NMDA-induced dopamine activity [27]. The motor impairments caused by ALX-5407 were confirmed by Perry et al. [10] and extended to another sarcosine-de
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Because AM had limited efficacy on rodent GPR
2022-06-05
Because (AM-3189) had limited efficacy on rodent GPR40, we used two rodent models expressing human GPR40 to demonstrate efficacy of (AM-3189). First, we used human islet transplanted nude mice. In this model, endogenous pancreatic β-cells were ablated using streptozotocin, and mice were rescued to e
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br Funding sources This work
2022-06-05
Funding sources This work was supported, in part, by NIH GM115388 to BGM. Acknowledgements Introduction Glucokinase (GCK) plays a central role in the regulation of glucose metabolism. Its activity is restricted to NSC228155 with important roles in whole-body glucose homeostasis [1]. In pa
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The classical genomic effects of GR come
2022-06-05
The classical genomic effects of GR come about through ligand-bound GR homodimerizing in the nucleus and via direct binding to GREs on the target genes, bringing about transcriptional activation or repression. Examples of target genes up-regulated by activated GR include genes encoding β2-adrenergic
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Moreover we examined inhibition of GLI mediated mRNA express
2022-06-05
Moreover, we examined inhibition of GLI-mediated mRNA expression by 1. Colubrinic BMH-21 mg (1) inhibited the mRNA production of PTCH in PANC1 cells in the dose-dependent manner. This result clearly shows 1 inhibits GLI-mediated transcription (Fig. 6). Discussion In this study, we identified th
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Because of its role in the cleavage of A
2022-06-05
Because of its role in the cleavage of Aβ and the fact that many genetic forms of AD are caused by mutations in the enzyme, GS has long been a target for drug development, though previous clinical trials of Semagacestat, a GS inhibitor, have failed due to an increase in skin cancer, and a decrease i
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Albumin is the major carrier of free fatty acids
2022-06-05
Albumin is the major carrier of free fatty acids (FFAs) in plasma [59], and harbours seven binding sites that are common to FFAs with a range of chain-lengths (C10-C18) across its three domains (Fig. 1a) [60,61]. In vitro, saturated, mono- and poly-unsaturated FFAs, with chain lengths ranging from C
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The subcellular redistribution of some metabolic enzymes is
2022-06-02
The subcellular redistribution of some metabolic enzymes is dynamic and responsive to metabolic conditions. In the absence of glucose, Glucokinase (GK) is bound to its regulatory protein in the nucleus of the hepatocyte and translocates to the cytoplasm when sugar levels increase [12]. Muscle glycog
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guanabenz The Ala to Leu substitution would reduce the size
2022-06-02
The Ala116 to Leu110 substitution would reduce the size of the active-site cavity disfavoring the production of longer allylic compounds as a result of steric hindrance, according to the observations of Poulter and co-workers [29], [30]. However, this explanation appears to be unlikely since several
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br Ethics statements br Introduction Hepatocellular carcinom
2022-06-02
Ethics statements Introduction Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor and the third leading cause of cancer-related mortality worldwide, with rapidly-increasing incidence in recent years [1,2]. Mounting evidence shows that viral hepatitis, toxin exposure, non-a
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Recent studies have also identified additional proteins that
2022-06-02
Recent studies have also identified additional proteins that could act as scaffolds and promote the interaction of core Hippo pathway components. APC, which is best known as a key component of the β-catenin destruction complex, was observed in mammalian BMS-626529 to have an additional function as a
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