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br Acknowledgements This work was
2021-09-02
Acknowledgements This work was supported by the National Institutes of Health [grant number GM024417]. Introduction In mammals, glucose is the major energy substrate supporting conceptus development after positive people formation [1,2]. While the equine morula uses similar amounts of pyruva
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br Materials and methods br Results br Discussion In this
2021-09-02
Materials and methods Results Discussion In this study, we demonstrated, for the first time, that manipulation of AKR1D1 expression and activity is able to regulate glucocorticoid availability in liver and non-liver cell lines. AKR1D1 over-expression leads to increased glucocorticoid cleara
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Consistent with recent independent studies
2021-09-02
Consistent with recent independent studies, we confirm that the GCG-induced increase in oxygen consumption is only partially blunted in Fgf21−/− mice [32], implicating additional GCGR-dependent mechanisms contributing to the acute GCG-dependent enhancement of energy expenditure. Notably, glucagon ad
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In patients with type diabetes glucagon receptor antagonism
2021-09-02
In patients with type 2 diabetes glucagon receptor antagonism led lowered fasting glucose however not postprandial glucose levels [9], which may reflect that glucagon may not be of particular importance for the diabetic hyperglycemia upon a meal. Current glucagon receptor antagonists have however be
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Inhibitors against the proteasome a component
2021-09-02
Inhibitors against the proteasome, a component of the ubiquitin-proteasome pathway that degrades cellular proteins, provide a new strategy for targeting the 26S proteasome [25]. Proteasome inhibitors can exhibit potent anti-cancer effects against different tumor GSK1070916 and were shown to induce
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Among sensitizers tested in the previous
2021-09-02
Among 22 sensitizers tested in the previous study, six test chemicals were pre- or pro-haptens (Nepal et al., 2018a). Among 6 chemicals, hydroquinone and 2-aminophenol, strong sensitizers, were falsely classified as non-sensitizers due to the lack of metabolic activation (Nepal et al., 2018a). Liter
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OCA has recently been approved for the treatment of
2021-09-02
OCA has recently been approved for the treatment of patients with PBC and is under study for diseases such as NASH, PSC and biliary atresia [30], [49]. Up to now, the beneficial effects of OCA have been related to its anti-cholestatic, anti-inflammatory and anti-fibrotic properties. We have here rep
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br Results and discussion br Conclusion In
2021-09-02
Results and discussion Conclusion In summary, we designed and discovered a series of novel GPR40 agonists containing 3,5-dimethylisoxazole with improved tPSA and ideal cLog P. Most of these compounds were confirmed as excellent GPR40 agonists in vitro. Especially, compound 11k exhibited robust
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br Acknowledgements We thank Dr Bhushan Nagar and Dr Albert
2021-09-02
Acknowledgements We thank Dr. Bhushan Nagar and Dr. Albert Berghuis for access to the X-ray diffraction machine at McGill University. We also thank Dr. Manon Couture and Dr. Steve Charette at Université Laval for access to scientific equipment. Funding for this research was provided by Discovery
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We sought to deduce the role
2021-09-02
We sought to deduce the role of membrane lipid determinants on endo- and exocytosis by applying a combination of metabolic (lipid) engineering approaches and biophysical methods, e.g. classical optical imaging technologies and high-resolution time-resolved patch-clamp/capacitance measurements. The l
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br Experimental Procedures br Author Contributions br Acknow
2021-09-02
Experimental Procedures Author Contributions Acknowledgments We acknowledge Géraldine Le Goff and Mathieu Canales for blood sampling, Cécile Gameiro and Jean-Pierre Aubry for flow cytometry technical assistance, Giuseppe Pantaleo for support, and Britta Engelhardt, Gisella Puga-Young, Nicol
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Generally glycines and other small residues such as alanine
2021-09-02
Generally, glycines (and other small residues such as alanine) present in a helical GxxxG-motif that are facing the same side of the helix form a uniform surface that enables direct contact with a second helix. Crystal structures of multipass membrane proteins have demonstrated that GxxxG-motifs are
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Mulan is a mitochondrial protein and is
2021-09-02
Mulan is a mitochondrial protein and is exclusively localized in the OMM with its RING domain facing the cytosol [14]. Based on this topology, Mulan can provide a link between molecular events in the mitochondria and cytoplasm. Mulan has been implicated in various processes including: mitochondrial
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Autophagy alterations are frequently reported as
2021-09-01
Autophagy alterations are frequently reported as one of the pathological mechanisms contributing to neurodegenerative diseases, due to incomplete removal of protein leukotriene receptor antagonists in the brain [30,41]. It was over a decade ago when mutations in PARK8 encoding for the LRRK2 protein
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On the other hand the IL promoter activity
2021-09-01
On the other hand, the IL-8 promoter activity induced by the signalling cascade of the CysLT1-G300S receptor is higher than that of the WT receptor. The chemokine IL-8 is mainly involved in the recruitment and activation of neutrophils and we have previously shown that this chemokine gene is a targe
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