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As a possible back up to Sch we explored inhibitors
2022-05-31

As a possible back-up to Sch 503034 (), we explored inhibitors that contained alternative electrophiles to ketoamides. Boronic acids have been extensively investigated as possible electrophiles that could react with nucleophilic serine in the context of developing inhibitors of thrombin receptor and
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Stimulation of GC A by CNP was further corroborated by
2022-05-31

Stimulation of GC-A by CNP was further corroborated by using a cGMP enzyme immunoassay. We could show that CNP significantly stimulated cGMP synthesis in the GC-A reporter cell line. CNP stimulation resulted in similar maximal cGMP levels compared to stimulation by ANP and BNP. Therefore, by lumines
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While a role for YAP TAZ signaling in oligodendrocytes
2022-05-31

While a role for YAP/TAZ signaling in oligodendrocytes has not been described, these pregnane x receptor are also responsive to mechanical stimuli. OPC proliferation and migration can be altered by plating on substrates of varying stiffness [20], resulting in differentiation in a density-dependent
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As part of our discovery efforts searching
2022-05-31

As part of our discovery efforts searching for small molecule GPR119 agonists, we analyzed active pharmacophores of known agonists from the literature, and found that -methylsulfonylphenyl and substituted 4-hydroxyl piperidine are common fragments. In our initial efforts, we linked these two fragmen
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TAK 165 synthesis A subsequent modeling study by a different
2022-05-31

A subsequent modeling study by a different group was based on the bovine rhodopsin homology model using the 1L9H construct [38]. However, the site-directed mutagenesis data and docking suggested that the niacin-binding pocket is different to that described in the aforementioned report, but similar t
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The GlyR is pentameric with each
2022-05-31

The GlyR is pentameric, with each subunit consisting of an extracellular ligand binding domain (LBD), four transmembrane (TM) segments, and a large intracellular loop between TM3 and TM4. Binding of neurotransmitter produces conformational changes that are rapidly transmitted to the membrane-spannin
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Moreover we revealed that alanine and
2022-05-31

Moreover, we revealed that β-alanine and taurine, a structural analog of β-alanine, have different receptor affinity in the SG neurons of the spinal dorsal horn. Additionally, previous studies indicate that taurine regulates nociceptive information at the spinal cord level, and we have previously de
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br Introduction The alternative splicing of pre mRNA
2022-05-31

Introduction The alternative splicing of pre-mRNA is essential for generating multiple matured mRNAs from a single gene by selectively removing introns. Neural LY2409881 show many examples of regulated alternative splicing events, which produce structural changes in proteins important for the de
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Introduction Glucocorticoids are released in
2022-05-31

Introduction Glucocorticoids are released in response to stress and play an important role in inflammation, cellular growth, development, body fluid homeostasis, carbohydrate, lipid, and protein metabolism. However, circulating glucocorticoid excess has been associated with a classical phenotype of
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Heme activates the master regulator of the anti oxidant stre
2022-05-30

Heme activates the master regulator of the anti-oxidant stress response, NRF2, which mediates the up-regulation of a battery of phase II detoxifying genes [106]. Remarkably, HO-1 induction by NRF2 is regulated via an interplay with the transcriptional repressor BACH1 at the Maf recognition BMX-IN-1
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Others demonstrated that Paneth cells maintain
2022-05-30

Others demonstrated that Paneth cells maintain stem cell function and crypt homeostasis by providing metabolic lactate to sustain the enhanced mitochondrial oxidative phosphorylation in the Lgr5+ ISCs (Rodriguez-Colman et al., 2017), which substantially agrees with our findings in this study. Furthe
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The advent of next generation sequencing NGS has
2022-05-30

The advent of next-generation sequencing (NGS) has shown that considerable variation in human genome is still undiscovered and therefore a considerable number of rare variations that are related to disease susceptibility may still be unknown. NGS has allowed to strengthen the association between los
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In the FARM motifs of GGPPSs hydrophobic amino acids
2022-05-27

In the FARM motifs of GGPPSs, hydrophobic pkm2 are replaced by aliphatic amino acids, which are more flexible residues and allow the entrance of longer substrates into the pocket (Wang and Ohnuma, 2000). It has been reported that the lepidopteran Manduca sexta CA possesses GGPP synthase (GGPPS) acti
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Sperm exocytosis or acrosome reaction AR is a regulated secr
2022-05-27

Sperm exocytosis or acrosome reaction (AR) is a regulated secretion with special characteristics essential for fertilization. The AR relies on the same highly conserved molecules that drive intracellular membrane fusion and exocytosis in all other Luciferase Reporter Assay Kit (see [59] for a recen
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Since stroke and cerebrovascular diseases
2022-05-27

Since stroke and cerebrovascular diseases were considered serious AEs following vaccination, we performed manual chart review to confirm the diagnosis and symptom onset date for all stroke and cerebrovascular disease cases identified by ICD-9 codes. Chart review of 131 presumptive cases confirmed 82
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