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To confirm that these were bona fide interactions we investi
2022-06-17
To confirm that these were bona fide interactions, we investigated whether the potassium channel subunits or Tmem263 formed complexes with GLT-1 or DAT after immunoprecipitation. Lysates of HEK-293 cells previously cotransfected with HA-GLT-1 or HA-DAT, and either YFP-Kv7.3, YFP-Kv7.2 or YFP-Kv7.5 w
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SNL in rats led to
2022-06-17
SNL in rats led to upregulated Panx1 mRNA and protein level in DRG but not in spinal cord, and immunostaining revealed increased Panx1 in DRG neurons [50]. Although it was not emphasized, Panx1 labeling in SGCs was also increased in this pain model. Intrathecal injection of Panx1 blockers or Panx1-s
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D appears to be important for receptor function as a
2022-06-17
D83 appears to be important for receptor function as a mutation to an alanine produced a non-functional channel. Interestingly, maintaining the charge as in D83E produced only a small reduction in GABA sensitivity. Other mutations at this position which included residues capable of hydrogen bonding
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One effective approach to fine tuning the
2022-06-17
One effective approach to fine-tuning the lipophilicity profile of FFA1 agonists is to ‘decorate’ the 3-phenylpropahoic arn-509 receptor scaffold with polar heterocyclic moieties. Alternatively, this scaffold could be replaced with heterocyclic isosteres (as in Takeda’s compounds 1,2 and 3 as well
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In summary the SAR of a series of phenylpropanoic acid
2022-06-17
In summary, the SAR of a series of phenylpropanoic acid-free fatty DNQX disodium salt australia receptor agonists is described which resulted in the identification of potent FFA4 agonists. The superior pharmacokinetic properties of compound led to its selection as an in vivo tool compound which affo
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The C terminal regions in both FGF and
2022-06-17
The C-terminal regions in both FGF19 and FGF21 define their KLB interaction [15], [16], [23], [25]. However, less than 40% identity in comparative alignment of C-terminal sequences for these two proteins (Table 1) suggests that their interaction with KLB may require higher-order association with oth
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Fmoc-Asp-OAll The precise mechanism by which erastin inhibit
2022-06-17
The precise mechanism by which erastin inhibits SLC7A11-mediated cystine import it still unknown. The initially proposed mechanism, by which erastin binds a related transport protein, SLC7A5, and inhibits SLC7A11 in trans [25], was revised soon after, and it was suggested that erastin inhibits SLC7A
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FSLLRY-NH2 Several other assay parameters were also explored
2022-06-17
Several other assay parameters were also explored. First, the thermal dependence of the assay was investigated by measuring the specific activity at different temperatures (Fig. 7). That data show that enzymatic activity increases with increasing temperature. Interestingly, the observed rate increas
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br Conflict of interests br Acknowledgements This work was s
2022-06-17
Conflict of interests Acknowledgements This work was supported by the National Institutes of Health grants HD058577 and ES01678 to Kirill Kiselyov. We thank Sreeram Ravi for technical support. We also thank Mike Myers at the University of Pittsburgh Cancer Institute Flow Cytometry Facility.
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Introduction Histone is the core component
2022-06-16
Introduction Histone is the core component of chromatin and histone modification is one of the key mechanisms of epigenetic regulation (Bannister and Kouzarides, 2011). Amino NVP 231 residues on histone tails can be modified under different mechanisms including acetylation, methylation, phosphoryl
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Recent studies in our laboratory demonstrated that several h
2022-06-16
Recent studies in our laboratory demonstrated that several histamine H1 receptor antagonists induce apo A-I gene expression while histamine itself represses it [20]. In humans, there are three histamine receptor genes (H1, H2, and H3) that code for G-protein-coupled receptors (GPCR's) which bind his
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Another important outcome of reducing hypothalamic HIF in
2022-06-16
Another important outcome of reducing hypothalamic HIF in DIO was the increase in gliosis and hypothalamic inflammation. Both experimental and human studies have shown that hypothalamic inflammation plays an important role in obesity by inducing resistance to anorexigenic signals, such as insulin an
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Carbon monoxide another key product from the breakdown
2022-06-16
Carbon monoxide, another key product from the breakdown of heme by HO-1, also plays an important role in the vasculature. Like NO, CO is endogenously derived from the endothelium [68] and can weakly activate sGC by binding to its heme moiety [69]. CO was found to have vasodepressor activity in rats
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Fibronectin protein level was not affected by DIF although
2022-06-16
Fibronectin protein level was not affected by DIF-1, although fibronectin has also been considered a canonical Wnt signaling pathway target gene product [39]. Thus, the canonical Wnt signaling pathway may not be critical for the regulation of the expression of fibronectin in malignant melanoma cells
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br Acknowledgments This work was financially supported by
2022-06-16
Acknowledgments This work was financially supported by the National Natural Science Foundation of China (No. 81703451) and the China Postdoctoral Science Foundation Grant (No. 2017M611269). Introduction According to the International League Against Epilepsy (ILAE), epilepsy is generally defin
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