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To develop novel EPAC inhibitors Zhou
2021-04-01

To develop novel EPAC inhibitors, Zhou and co-workers optimized the HTS hit as the chemical lead. After modifications of the substituents on the phenyl ring or C6-position of compound , compound () was identified to be the more potent compound in this series with an IC value of 4.0µM (EPAC2). Dock
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The nitrophenols b d were prepared as described
2021-04-01

The nitrophenols 34b–d were prepared as described in Scheme 3b. Nitration of phenols 39b–d with 1equiv of sodium nitrate in the presence of hydrochloric 1 646 gave an inseparable mixture of 34b–d and 40b–d (1:1). This synthetic problem was successfully avoided as described below. Nitration of 39b–d
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br Materials and methods br Results and discussion br
2021-04-01

Materials and methods Results and discussion Conclusions Codon-optimized MGSK-Lys-C was expressed at a high level in an optimized expression system as inclusion bodies. The Lys-C activity reached its maximum with about 9340 nkat/Lculture under standard (chemical) refolding conditions. The r
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Despite the differences in the clustering abilities of
2021-04-01

Despite the differences in the clustering abilities of DDR1b versus DDR2 upon ligand administration, we also noted striking similarities in the spatial distribution and phosphorylation of DDR1b-YFP and DDR2-GFP. We show for the first time that in MC3T3-E1 cells, after 4 h of collagen administration,
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br Introduction Increasing investigations show
2021-04-01

Introduction Increasing investigations show that the earthworm extract has various beneficial pharmacological activities, including fibrinolytic [2] and anticoagulative activity [3], anti-inflammatory activity [4], anti-oxidative activity [5], [6], peripheral nerve regeneration [7], bone regenera
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In contrast to inflammatory cytokines TGF has immunosuppress
2021-04-01

In contrast to inflammatory cytokines, TGF-β has immunosuppressive properties yet is also important for tissue imprinting immune cell function during development [23]. Salivary gland (SG) ILCs, in addition to liver and intestinal intraepithelial ILC1, express markers denoting tissue residency and TG
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br Other pathways involved in
2021-03-30

Other pathways involved in the preventive and therapeutic potential of flavonoids in neurodegenerative diseases Rather than the induction of MAPK/ERK pathway, flavonoids actively modulate other critical intracellular neuronal survival and death protein kinases pathways, more importantly PI3K/Akt,
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As an endogenous negative modulator
2021-03-30

As an endogenous negative modulator, CRBN inhibits AMPK’s activation (phosphorylation of Thr172) by directly binding to the α-subunit of AMPK, disrupting γ-subunit recruitment to the AMPK complex (Lee et al., 2011, Lee et al., 2013). In our study, we did not focus on AMPK activation, since only a si
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br Acknowledgements The research leading to these results
2021-03-30

Acknowledgements The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7-PEOPLE-2013-COFUND) under grant agreement no 609020 − Scientia Fellows (JB) and the Research Council of Norway (NFR-grant 221444) (JB, JPM, OB). Introduction Hu
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br A brief introduction to DUBs
2021-03-29

A brief introduction to DUBs The reversal of ubiquitin conjugation of targeted proteins relies on deubiquitinating rq 1 synthesis (DUBs), which catalytically cleave single Ub or poly-ubiquitin chains from proteins. The human genome encodes approximately 100 potential DUBs which can be classified
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These data from developing brain are in contrast to
2021-03-29

These data from developing SirReal2 are in contrast to noradrenergic receptor regulation in the adult brain. In adult animals, a persistent increase in the α2-AR high affinity state is elicited as a result of DSP-4 lesion or reserpinization, as measured by [3H]clonidine binding to membrane preparat
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br Materials and method br Results and discussion We
2021-03-29

Materials and method Results and discussion We carried out DNA ligation using free and immobilized T4 DNA ligase in the absence of a magnetic field at 16°C, where the enzyme concentration (final concentration after mixing the solutions for the reaction) in both cases was 0.40μg/mL, and found t
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br Competing interests br Acknowledgements br
2021-03-29

Competing interests Acknowledgements Introduction Diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DG) in biomembranes to produce phosphatidic 85 8 (PA) [1], [2], [3], [4], [5], [6]. To date, ten mammalian DGK isozymes (α, β, γ, δ, ε, ζ, η, θ, ι and κ) have been identified. These
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DDR distribution in healthy fibrotic
2021-03-29

DDR1 distribution in healthy, fibrotic and inflamed tissues Whereas we can easily mine publicly available databases to infer DDR1 expression profile in different tissues (as reported in Fig. 1), fine comprehension of DDR1 biology has been hampered by the absence of a commercially available specific
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RNA sequencing RNA seq is a particularly effective technolog
2021-03-29

RNA-sequencing (RNA-seq) is a particularly effective technology for gene discovery in a given process, especially in non-model species for which reference genome sequences are not available. Although the major application of RNA-seq analyses is the identification of differentially expressed genes (D
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