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serine threonine protein kinase VS strategies have been buil
2022-05-26
VS strategies have been building momentum in G4 drug discovery both as a low-cost enrichment step and as a lead development step in the discovery pipeline, which our laboratory has previously discussed [31]. Whereas traditional HTS methods rely on obtaining and screening hundreds or thousands of com
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Further research should indeed focus
2022-05-26
Further research should indeed focus on understanding the nutritional value of food and its effect on metabolism, overall activation of metabolic NRs network. Moreover, given the prominent role of microbiota in the modulation of the FXR signalling (Degirolamo et al., 2014), there is enough impetus t
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Herein we describe the design and optimization of fused ring
2022-05-26
Herein, we describe the design and optimization of fused-ring phenyl propanoic acids as novel GPR40 agonists, leading to the discovery of compound 40a which exhibits excellent pharmacokinetic properties, improved hepatobiliary transporter inhibition, and significant glucose-lowering efficacy during
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Here we dissect X chromosome
2022-05-26
Here, we dissect X chromosome dosage compensation (DC) in C. elegans to determine the effect of chromatin modifications on higher-order chromosome structure during long-range gene regulation. DC is exemplary because it controls hundreds of genes simultaneously, it distinguishes X chromosomes from au
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The stable association of Hat complexes with histones
2022-05-26
The stable association of Hat1 complexes with histones H3 and H4 raises a number of interesting issues. The first is the question of how Hat1 remains stably associated with histones H3 and H4. While the simple answer is that Hat1 remains bound to histones because of its association with histone chap
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Several recent studies have linked clock function with
2022-05-25
Several recent studies have linked clock function with the cell cycle and reported that clock components, such as PER1, PER2, BMAL1, and CRY1/2 decrease cell proliferation or improve the action of anti-cancer drugs in different cancer cell lines. Moreover, certain types of human cancer show an alter
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br Acknowledgments Authors are thankful to
2022-05-25
Acknowledgments Authors are thankful to the participants of the study for their cooperation. Financial support from Higher Education Commission (HEC) of Pakistan is highly acknowledged. AZ is supported by indigenous PhD fellowship from HEC. Indigenous PhD Fellowship for 5k Scholars batch 2 PIN NO
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In contrast the sGC activator BAY relaxed the
2022-05-25
In contrast, the sGC activator BAY 58-2667 relaxed the CC in a concentration-dependent manner (Figure 4B), a response that was significantly increased in the CC of sGCβ1ki/ki mice compared with WT mice. The finding that BAY 58-2667 also possessed a corporal relaxing effect in WT mice is suggestive b
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br The SRP SR Heterodimer
2022-05-25
The SRP/SR Heterodimer: GTPase Tangos Drive Co-Translational Protein Targeting SRP and SR mediate a universally conserved protein targeting pathway responsible for the delivery of 25–30% of newly synthesized proteome to the eukaryotic endoplasmic reticulum (ER) or the bacterial plasma membrane 11
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br Animal models of NASH The
2022-05-25
Animal models of NASH The human NAS system (see above) is largely reproducible in NAFLD mouse models [37] and, therefore, has been increasingly applied in the preclinical assessment of liver histological responses to test compounds. In general, the NAS system is well suited for this purpose, alth
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A considerable body of evidence suggests that alcohols volat
2022-05-25
A considerable body of evidence suggests that alcohols, volatile anesthetics and inhaled drugs of abuse act at discrete sites on glycine and GABAA receptors, specifically within circumscribed protein pockets (Mascia et al., 2000, Mihic et al., 1997, Beckstead et al., 2000). An amino opioid receptor
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br Recent insights into EAAT structure
2022-05-25
Recent insights into EAAT structure/function aspects The EAATs are secondary-active transporters coupling the movement of one Glu with the symport of three Na+ and one proton and the counter-transport of one K+ [3, 4]. The transporters are trimeric assemblies of protomers that function independen
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br Introduction As is now
2022-05-25
Introduction As is now well known, obesity is major risk factor for various diseases such as nonalcoholic fatty liver disease, cardiovascular disease, some cancers (McWilliams and Petersen, 2009), type-2 diabetes mellitus (Jakobsen et al., 2007), and hypertension (Aneja et al., 2004), among other
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Therefore we investigated the acute and
2022-05-25
Therefore, we investigated the acute and delayed response of 92 human mono- and dizygous twins to an acute shift from low fat to high fat diet with respect to serum levels of VEGF and the expression of SLC2A1 in subcutaneous adipose tissue (AT). By comparing the degree of concordance of basal and di
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The mechanism underlying the anorectic effect of OXM is
2022-05-25
The mechanism underlying the anorectic effect of OXM is well established. It is centrally mediated via GLP-1 receptor activation, confirmed by both pharmacological blockade of the GLP-1 receptor, and using GLP-1 receptor knock-out mice [2], [11], [12]. However, the mechanism by which it increases en
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