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br Regulation of GCK by intrinsic
2022-01-19
Regulation of GCK by intrinsic conformational dynamics GCK is a 465-residue, 52-kDa enzyme comprised of two domains, hereafter referred to as the large domain and the small domain, that are separated by a flexible hinge region. As with other proteins that adopt the hexokinase fold, substrates bin
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Consistent with recent independent studies we confirm that t
2022-01-19
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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While the apparent complexity of gap junction regulation
2022-01-19
While the apparent complexity of gap junction regulation presents challenges, new technologies continue to propel the field forward. Advances in microscopy are increasingly able to capture rapid dynamics at the plasma membrane (e.g., biosensors [67] and lattice light sheet microscopy [100]) and to d
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fura 2 Primarily because secretase was a therapeutic
2022-01-19
Primarily because γ-secretase was a therapeutic target in AD, a plethora of γ-secretase inhibitors (GSIs) have been developed that effectively inhibit γ-secretase cleavage in humans [16]. Indeed, “druggability” of γ-secretase has not been an issue even when the identity of the target was unknown in
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Moreover intestinal chronic inflammation is a
2022-01-19
Moreover, intestinal chronic inflammation is a promoting factor in the development of CRC in patients affected by inflammatory bowel disease (IBD), such as Crohn's disease and ulcerative colitis. We have previously shown that pharmacological FXR activation via its ligand obeticolic hcv protease inhi
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Importantly both genetic deletion and pharmacological inhibi
2022-01-19
Importantly, both genetic deletion and pharmacological inhibition of FAAH also reduced NTG-induced neuronal hyperactivity in the trigeminal nucleus, which receives sensory input from craniofacial deep tissues. NTG is known to evoke the robust neuronal activation, as evidenced by the induction of the
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Liposomes that are less than nm in
2022-01-19
Liposomes that are less than 200nm in diameter are necessary to optimize uptake of liposomes by c di gmp (Oesterling et al., 2014). The liposomes constructed in these experiments were found to be sufficiently small in diameter for use in in vivo and in vitro experiments. Even smaller diameters are
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Previous studies have shown that HER is also
2022-01-18
Previous studies have shown that HER2 is also involved in IL-6 expression and signaling. IL-6, HER2, and GP130, the beta-subunit of the IL-6 receptor (IL-6R), are physically associated and co-immunoprecipitate in response to IL-6 stimulation [1]. IL-6 induced HER2 clustering to the GP130 complex, le
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br Materials and methods br Results br Discussion Both
2022-01-18
Materials and methods Results Discussion Both EMT of the tubular epithelial WYE-132 australia and the activation of fibroblasts are critical factors in the pathogenesis and progression of renal interstitial fibrosis. Accumulating evidence implicates EMT in the onset and pathogenesis of ren
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Under increased drug pressure more protease variants
2022-01-18
Under increased drug pressure, more protease variants with more than one substitution will likely become clinically relevant. The accumulation of additional substitutions can allow RAS variants to emerge that alone are not viable, but in combination can rescue the viral fitness. We previously demons
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Limited efforts were made to exploit the naturally occurring
2022-01-18
Limited efforts were made to exploit the naturally-occurring antigen-specific Treg for ex vivo expansion. This study sets up a reproducible protocol for the expansion of insulin-specific Treg isolated from NOD mice. These 5 03 exhibited higher suppressive capacity compared to the polyclonal Treg and
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br The glyoxalase system has
2022-01-18
The glyoxalase system has not yet been studied in E. histolytica or G. lamblia. Searches in the G. lamblia genome (GiardiaDB.org) revealed two genes encoding hydroxyacylglutathione hydrolases (Morrison et al., 2007), but no glyoxalase I gene was found. The genome of E. histolytica does not have a
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br Conflict of interest statement br Acknowledgments This wo
2022-01-18
Conflict of interest statement Acknowledgments This work was funded in part by a grant from the National Institutes of Health, NIDDK award #DK61425 (to PWS). Introduction The efflux of toxic compounds from the cell by multidrug exporters is an important mechanism for cellular homeostasis a
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Whether or not SMO and SMO dependent HH signaling play
2022-01-18
Whether or not SMO and SMO-dependent HH signaling play a role in hematopoiesis is a subject of strong controversy. Obviously, the effects of SMO deletion are highly contextual and dependent on the timing of deletion. transplanted murine Smo−/− fetal liver BIIE 0246 australia into sublethally irrad
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Although the ramifications of non additive SAR are
2022-01-18
Although the ramifications of non-additive SAR are context-dependent, the knowledge that perturbations in one region of a chemical series are not synergistic with perturbations in another region of the same chemical series is clearly pertinent to any medicinal chemistry effort. In our experience, no
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