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GSK is a critical component of the Wnt signaling pathway
2021-09-22
GSK-3 is a critical component of the Wnt signaling pathway. The Wnt/beta-catenin signal transduction pathway is important in normal growth and development and is also frequently dysregulated in cancer and other diseases. The Wnt/beta-catenin pathway is finely tuned by both positive and negative inte
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br Conclusions br Conflicts of Interest br Introduction
2021-09-22
Conclusions Conflicts of Interest Introduction Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic multisystem illness of unconfirmed cause. ME/CFS has largely been diagnosed from Fukuda CFS criteria and/or the Canadian ME/CFS criteria. The Institute of Medicine in 2015
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During pain signal transmission glutamate is released into t
2021-09-22
During pain signal transmission, glutamate is released into the synaptic cleft, which, in turn, causes activation of N-methyl-d-aspartate (NMDA) receptors and hence neurotransmission across the synapse occurs. The synaptic concentration and resultant activity of glutamate are controlled by excitator
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P 22077 br Acknowledgments br Introduction Postmenopausal
2021-09-22
Acknowledgments Introduction Postmenopausal osteoporosis, which is primarily caused by P 22077 deficiency, has been a worldwide health problem and threatens postmenopausal women of all races. An estimated 80% of osteoporosis patients in the United States are women, and approximately 30% of po
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In addition to FAK P MAPK
2021-09-18
In addition to FAK, P-38 MAPK (38 kDa polypeptide) serves as cross-talk effector for signal transduction, enabling this factor to play a vital role in numerous biological processes (Cuenda and Rousseau, 2007). Pharmacologically modulation of P-38 has shown to be an effective approach in the orientat
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br Introduction Thrombosis is one of the leading
2021-09-18
Introduction Thrombosis is one of the leading causes of deaths in the cardiovascular diseases such as myocardial infarction (MI), unstable dizocilpine and acute coronary syndrome (ACS) in developed countries [1], [2]. It is estimated that venous thromboembolism (VTE) afflicts about 1 million (1–2
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In addition to Rabs several proteins
2021-09-18
In addition to Rabs, several proteins have been shown to interact with Rabphilin3a, for instance the GluN2A subunit of the NMDA receptor, PSD-95 ([56,57] and references therein), Rabaptin-5, α-actinin [16] and SNAP-25 [21,23,41,61]. Only the latter has been reported to participate in the AR. Explori
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Biliary tract cancers BTC are categorized into intrahepatic
2021-09-18
Biliary tract cancers (BTC) are categorized into intrahepatic, perihilar, extrahepatic BTC (or cholangiocarcinoma) as well as gallbladder cancer (GBC). Although the incidence of BTC is low in developed countries (3% of gastrointestinal cancers), BTC is the second most common primary liver tumor afte
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The overall characteristic of RNA profile of Leydig cell is
2021-09-18
The overall characteristic of RNA profile of Leydig cell is still a mystery. Variation in total RNA will cause subsequent difference in protein expression and phenotypic modulation [16]. In this study, we used a murine nicotine exposure model coupled with next generation RNA sequencing (NGS) and fou
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br Conflict of interest br
2021-09-18
Conflict of interest Author contributions Introduction 2-Quinolones [quinoline-2(1H)-ones], while less prominent than the isomeric 4-quinolones, nevertheless enjoy significant attention as scaffolds in compounds exhibiting a variety of biological activities. These include: 4-aryl-6-chloroq
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Integrase inhibitors have been licensed for use in
2021-09-18
Integrase inhibitors have been licensed for use in the UK since 2008. BHIVA now recommend starting all treatment naïve patients on a regimen containing two NRTIs, plus one of the following: a ritonavir boosted PI, an NNRTI, or an integrase inhibitor. They make further recommendations for patients wi
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br Results br Discussion A
2021-09-18
Results Discussion A key step in the regulation of gene LRRK2-IN-1 receptor is the methylation on H3K4, which is added by the multi-component MLL/COMPASS-like histone methyltransferases. Many studies have shown the requirement of shared core subunits for optimal methylation activity of cataly
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Materials and methods br Results and
2021-09-18
Materials and methods Results and discussion Acknowledgments This work was supported in part by the Japan Society for the Promotion of Science KAKENHI Grants JP21300174 and JP25282144 (H.K.). Introduction Epigenetic modifications of histones, such a lysine acetylation, play a key role in
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It should be noted that one
2021-09-18
It should be noted that one of the two phenyl groups of 15 is found in the main western pocket and the second phenyl group occupies the western secondary pocket (Ser53, Leu54, and Leu213). The nitrogen of the amide bond is involved in a hydrogen bonding interaction with Asp140. The alcoholic functio
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The second approach to optimizing microsomal stability in th
2021-09-18
The second approach to optimizing microsomal stability in this series involved the strategic positioning of steric bulk along the tether as a means of encumbering the access of oxidative enzymes to the methylene bridge. This approach has been employed in other P2-P4 macrocyclic inhibitors of NS3/4A
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