• Toxicity is the main reason for the failure

  2022-10-13

  

  Toxicity is the main reason for the failure at all stages of the new drug development process. The major part of safety-related attrition occurs at preclinical phases while predicting preclinical safety liabilities earlier in the drug development process. This strategy enables the design and/or sele

• br Introduction Over one million

  2022-10-13

  

  Introduction Over one million people are currently living with HIV in the United States (CDC, 2016). Through advances in HIV medications, the use of antiretroviral therapy has led to people living longer with HIV (Palella et al., 2006). In attempts to mitigate the effects of the psychological and

• A recent novel and important finding

  2022-10-12

  

  A recent novel and important finding is that YAP connects cellular growth with anabolism; YAP suppresses the transcriptional induction of genes which importantly regulate gluconeogenesis in the liver; namely glucose-6-phosphatase catalytic subunit (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1

• Due to the importance of gene regulation in cancers

  2022-10-12

  

  Due to the importance of gene regulation in cancers, HDAC inhibitors have been studied extensively in cancer biology and are in current clinical use as anti-tumor therapies [17]. The HDAC inhibitors vorinostat, romidepsin, and belinostat have been approved for certain T-cell lymphomas, and panobinos

• Interestingly myorelaxation and the stimulation of

  2022-10-12

  

  Interestingly, myorelaxation and the stimulation of cGMP production are properties also reported for sGC stimulators, such as YC-1 and BAY 41–2272 (i.e., indazole compounds that were discovered in the 1990s) [35]. They relax aortic ring contractions induced by phenylephrine, and their effects are si

• N-3-oxo-dodecanoyl-L-Homoserine lactone There are important

  2022-10-12

  

  There are important questions that remain to be answered. How does Rap2a protein affect NF-κB activation? Why do Rap2a silencing and overexpression results to the identical hampered NF-κB activation phenotype? Overexpression experiments have demonstrated that atypical κB-Ras GTPases could inhibit NF

• By combining the results of the melting curve analysis of

  2022-10-12

  

  By combining the results of the melting curve analysis of exon 5 and exon 6, the allelic setup of our 250 subjects was determined; the four allelic variants are shown in Table 1. However, GSTP1-1 *A/*C and GSTP1-1 *B/*D could not be distinguished from one another because both genotypes are character

• GPR is a G protein coupled receptor that

  2022-10-12

  

  GPR55 is a G protein-coupled receptor that has pro-oncogenic properties and whose expression correlates with tumor aggressiveness and increased activation of extracellular signal-regulated kinase (ERK) cascade [12]. Elevated expression of GPR55 has been linked to aggressiveness in human pancreatic,

• Several groups studied CTD mouse models which largely

  2022-10-12

  

  Several groups studied CTD mouse models, which largely mimicked the symptoms (i.e. impaired cognition and autistic-like behaviour) of the human disease (Kurosawa et al., 2012; Baroncelli et al., 2016; Stockebrand, 2018). The CRT-1 knockout mice showed a drastic deterioration in the GABAergic system,

• To evaluate SLC A abundance after transfection

  2022-10-12

  

  To evaluate SLC45A1 abundance after transfection, we performed western blots. Transfected COS-7 (-)-JQ1 synthesis were lysed and separated for membrane fraction. Equal amounts of proteins from membrane fractions were resolved by SDS-PAGE, transferred to a nitrocellulose filter, and immunoblotted wi

• Regulation of pancreatic and cell mass has

  2022-10-12

  

  Regulation of pancreatic α and β cell mass has been extensively studied and hotly debated, due to potential therapeutic implications. Early claims of Angptl8 as “betatrophin” and Angptl4 as a regulator of glucagon secretion and α cell proliferation (Yi et al., 2013, Ben-Zvi et al., 2015) have not st

• br STAR Methods br Acknowledgments We would like to

  2022-10-12

  

  STAR★Methods Acknowledgments We would like to thank Dr. Xiping Cheng for help with the immunohistochemistry staining, Qi Su for help with gene expression analysis, and Dr. Chaoying Liang at the UTSW Genomics Microarray Core facility for assistance on RNA-seq. W.-H.L. was supported by grant awa

• Besides its established insulinotropic actions

  2022-10-12

  

  Besides its established insulinotropic actions, GIP has been shown to possess other direct beneficial effects on the beta cell, including stimulation of growth, differentiation, proliferation and survival.21, 22, 23 It has also been shown to stimulate proinsulin gene transcription and translation. M

• br Presenilins and Wnt catenin signalling Several groups hav

  2022-10-11

  

  Presenilins and Wnt/β-catenin signalling Several groups have provided substantial data indicating that PS1 acts as a negative modulator of the transcriptional activity of the β-catenin/Tcf-4 complex (Fig. 4) [120], [121], [122]. β-Catenin is a multifunctional protein that was first described as a

• br FXR FGF in the control of BAs synthesis

  2022-10-11

  

  FXR–FGF15/19 in the control of BAs synthesis The nuclear receptor FXR is the master regulator of BAs homeostasis, modulating their synthesis, 7915 and uptake [15]. FXR decreases BA de novo hepatic biosynthesis by reducing the expression of CYP7A1. At the canalicular membrane, newly-synthesized B

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