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Numerous small molecule CRF receptor antagonists
2020-12-23
Numerous small molecule CRF receptor antagonists have been reported in the literature. Some representative examples are shown in . In preclinical studies (DMP696), , was found to be efficacious in preclinical behavioral models for anxiety and depression. In an open label clinical trial with (R121
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Mild cognitive impairment MCI is a clinical transitional sta
2020-12-23
Mild cognitive impairment (MCI) is a clinical transitional stage between normal aging and Alzheimer disease (AD) [1]. Approximate 15–30% MCI patients convert to AD annually. Although many efforts have been taken to prevent the conversion from MCI to AD [2], [3], there are few biomarkers to predict t
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While we are taking full
2020-12-23
While we are taking full responsibility for any remaining errors and shortcomings of the paper, we would like to thank Dr. Jong-Hyeon Jeong, Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, for offering us insight and literature pointers useful in our quest to
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Located on the fore tarsals of the front pair of
2020-12-22
Located on the fore-tarsals of the front pair of legs, the Haller’s organ is presumed central to tick chemosensation. Recent genomic, transcriptomic and proteomic investigations have identified several families of transmembrane proteins in the forelegs of ticks that are likely involved in olfactory
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Nanocomposite films with a GNP
2020-12-22
Nanocomposite films with a GNP-DNA filler concentration of 20 wt%, 30 wt%, and 40 wt% were investigated by electrical impedance spectroscopy before and after UV-C irradiation (Fig. 2). EIS data were fitted to a RC-circuit model and surface resistivity values were calculated from the fitted resistanc
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What does this mean for cancer therapy We found
2020-12-22
What does this mean for cancer therapy? We found that components of the de novo pyrimidine synthesis pathway rarely mutate in cancer, clearly showing its importance. In our experimental models, the pathway, including DHODH itself, was primed to respond when the block in CoQ redox-cycling was removed
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br Introduction Our understanding of how ligands interact
2020-12-22
Introduction Our understanding of how ligands interact with G protein coupled receptors is evolving, particularly the recognition that some have the ability to preferentially activate a subset of intracellular signalling cascades – so called pathway biased ligands [1]. Additionally, it is now acc
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br Materials and methods br
2020-12-22
Materials and methods Results Discussion A reporter of FGF signaling activity has long been sought to facilitate the quantitative real-time analysis of pathway activity at single-cell resolution. Here we report the generation of a Spry4 reporter allele in ESCs and mice that recapitulates kn
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br Acknowledgements br Introduction Ischemic retinopathy is
2020-12-22
Acknowledgements Introduction Ischemic retinopathy is common to the major causes of blindness, including proliferative diabetic retinopathy, venous occlusion, and retinopathy of prematurity. The hypoxia that follows retinal capillary obliteration drives deregulated growth of new blood vessels
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Constitutive activity of Ras Raf MEK ERK
2020-12-22
Constitutive activity of Ras/Raf/MEK/ERK pathway plays a critical role on melanoma growth, thus inhibition of activity of Ras, Raf and MEK can reduce ERK activity, leading to a decrease in melanoma cell proliferation, survival and invasion (Burotto et al., 2014; Paluncic et al., 2016). Our results a
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To provide a brief critical evaluation
2020-12-22
To provide a brief critical evaluation of this technology and an outlook, we note that performance of SMEPT is critically dependent on each of the components making up this platform, namely the substrate, the enzyme, and the prodrug. With regards to the latter, SMEPT is built on the experience and s
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Upon further evaluation of the
2020-12-22
Upon further evaluation of the phage obtained from phage display, we compared the capture of each of the 4th round phage to a phage possessing the wild-type arylsulfatase A sequence (LCTPSR) using ELISA. Each phage was equivalently exposed to FGE and to the beads for capture; however, we found that
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In view of the hypotensive effect
2020-12-22
In view of the hypotensive effect of endothelial-specific overexpression of eNOS [17], [19], [28] we correlated skeletal muscle eNOS expression with sBP including data on colony 5 of eNOS-Tg [17] which was used to generate eNOS-Tg/KO (Fig. 4D). We found a highly significant one phase exponential dec
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The hepatic constitutive levels of CYP A were minimal
2020-12-22
The hepatic constitutive levels of CYP1A2 were minimal and were below detectable limits in the kidney, indicating an organ-specific trend which has been reported by other groups (Hawke and Welch, 1985, Paolini et al., 1997, Parkinson, 1996, Villard et al., 1998). Retinol administration did not have
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Mouse Cyp a is a homologous
2020-12-22
Mouse Cyp3a11 is a homologous isoform of the human CYP3A4 gene, and both are highly expressed in the liver (Hart, Cui, Klaassen, & Zhong, 2009). CYP3A4 is the most abundant CYP450 in hepatic microsomes responsible for drug and xenobiotic metabolism (Zanger & Schwab, 2013), and it is the most active
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