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Toxicity is the main reason for the failure
2023-12-16
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
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br Oxidative microbe killing and V ATPase Oxidative killing
2023-12-16
Oxidative microbe killing and V-ATPase Oxidative killing of phagocytosed microorganisms is predominately achieved through the uptake of large quantities of molecular oxygen by the infected cell and the activity particularly of the NADPH oxidase complex on phagosomes (Savina et al., 2006) and the
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ATM dependent initiation of radiation induced
2023-12-16
ATM-dependent initiation of radiation-induced G2/M checkpoint arrest is well established [11], [34], [35]. However, the ATR pathway may also be involved [36], [37]. Brown and Baltimore generated Cre/lox-conditional cell lines or GSK 1120212 with a kinase inactive allele of ATR (ATRkd) to evaluate t
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The interaction of ATR ATRIP with
2023-12-16
The interaction of ATR-ATRIP with RPA-coated ssDNA is sufficient for ATR-ATRIP recruitment to DNA lesions, but it is not sufficient to fully activate ATR. In response to DNA damage, the heterotrimeric ring-shaped complex 9-1-1 (RAD9-RAD1-HUS1 in humans; Ddc1-Rad17-Mec3 in S. cerevisiae) is loaded at
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Somatostatin analogs also bind to somatostatin receptors It
2023-12-16
Somatostatin analogs also bind to somatostatin receptors. It has been reported that octreotide has a high affinity for hSSTR2, moderate affinity for hSSTR3 and hSSTR5, and does not bind to hSSTR1 or hSSTR4 (Ben-Shlomo and Melmed 2008). Compared to octreotide, pasireotide displays 40-, 30-, and 5-fol
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br Conclusions br Author declaration br
2023-12-16
Conclusions Author declaration Acknowledgements Introduction ASK1 scaffolding proteins ASK1 adaptor proteins Conclusions Scaffolding and adaptor proteins can coordinate the specific activation of a MAP3K-MAP2K-MAPK pathway in response to various stimuli. For example, both AM966
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Mechanistically it was soon realized that in undead
2023-12-16
Mechanistically, it was soon realized that in undead cells, Dronc promotes the activation of Jun-N-terminal kinase (JNK) signaling as the major inducer of AiP [25], [28] (Fig. 2B,C). However, it has been unknown for a long time how active Dronc promotes JNK signaling. Recently, it was reported that
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The chronic induction of skeletal muscle AMPK
2023-12-15
The chronic induction of skeletal muscle AMPK activity is an attractive therapeutic approach for DMD, as it addresses multiple cellular pathways needed for powerful phenotypic plasticity, including activation of the slow oxidative myofiber program, corrective autophagic signaling, as well as regulat
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Taken together the results reveal
2023-12-15
Taken together, the results reveal a complex feedback and feedforward signaling network between the tryptophan metabolic enzymes IDO1/TDO2, the KP metabolite KYN, and the ligand-activated transcription factor AhR (Figure 2). Cancer Genistein highjack this signaling circuitry to deregulate immunologi
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br Functions essentially consisting in transport
2023-12-15
Functions essentially consisting in transport of substrates across plasma membranes Direct activation of neurotransmitter transporters elicits responses in neurons As previously mentioned (Section 2.1), nerve terminals handling classical transmitters possess transporters able to (re)capture se
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br Methods br Results br Discussion Adiponectin is naturally
2023-12-15
Methods Results Discussion Adiponectin is naturally expressed and secreted exclusively from adipocytes, and adiponectin levels and its isoforms in circulation have recently been reported to highly associate with human coronary artery disease (CAD) [46], [47], [48], [49], these studies clear
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Amsacrine Introduction hydroxytryptamine HT is found through
2023-12-15
Introduction 5-hydroxytryptamine (5-HT) is found throughout the body and influences smooth muscle activity in various tissues including the intestine, vasculature and urinary Amsacrine (Kim and Camilleri, 2000, Klarskov and Horby-Petersen, 1986, Mohammad-Zadeh et al., 2008). The current classifica
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Although our data failed to reproduce the robust enhancement
2023-12-15
Although our data failed to reproduce the robust enhancement of LTP in the rat dentate with nicotine that was previously reported, our results with NS6740 suggest a more fundamental role for α7 receptor signaling in modulation of synaptic tone in the LTP pathway. The discovery of the cholinergic ant
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The effect of capital deductions on equilibrium prices
2023-12-15
The effect of capital deductions on equilibrium prices is given by the following comparative statics Thus, equilibrium prices are strictly decreasing in the share of capital cost deduction. The reason is that a higher share of capital cost deduction reduces the effective marginal costs, which makes
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Among steroid saponins ginsenosides are the active component
2023-12-14
Among steroid saponins, ginsenosides are the active components of ginseng, a well-known chinese medicinal plant. More than hundreds of different ginsenosides have been isolated from ginseng and have shown in the past to be membrane active substances and to influence the membrane by modulating lipid
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