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During the past three decades platinum
2020-10-05
During the past three decades, platinum-based DNA-alkylating agents have been employed in the treatment of various cancers [14]. Oxaliplatin is currently used as a first-line treatment for colorectal cancer (CRC) [15]. Unfortunately, a large portion of CRC patients receiving oxaliplatin-based chemot
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The only reported synthesis of the aminobicyclic core of
2020-10-05
The only reported synthesis of the aminobicyclic core of is based on bis-alkylation of a 4-amino-5,6-dihydroxypyrmidine with dibromoethane. The likelihood of poor regiocontrol/reactivity in utilizing such a transformation for the synthesis of compounds with a substituent on the dioxinyl ring led us
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Nuclear export mediated by CRM
2020-10-03
Nuclear export mediated by CRM1 is initiated by an interaction between RanGTP and the HEAT9 loop of CRM1, triggering a conformational change in the NES binding site that permits NES–cargo protein binding (Dong et al., 2009, Fung and Chook, 2014). Our docking simulation results predicted that DP2392-
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Current therapeutic protocols in OS
2020-10-01
Current therapeutic protocols in OS and ES consist of neoadjuvant chemotherapy and local surgical resection, followed by adjuvant chemotherapy. These treatments lead to a 70% overall survival for localized disease but can decrease to 15% in case of metastasis. With CS being resistant to conventional
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ERR is constitutively active in the absence
2020-10-01
ERRγ is constitutively active in the absence of endogenous ligand. However, several synthetic ligands that can repress or induce ERRγ function by disrupting ERRγ-coactivator interactions have been reported to date. The estrogen receptor modulators diethylstilbestrol (DES) and 4-hydroxytamoxifen (4-O
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br Materials and methods br Results br
2020-09-30
Materials and methods Results Discussion and conclusion The cardiac hypertrophy model can be established by two methods: drug induction and operation. The drug induction method is simple, while the operation method is closer to the real development of the disease. In this experiment, accord
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Enolase is an example of a moonlighting protein that
2020-09-30
Enolase is an example of a moonlighting protein that displays multiple biological actions, including plasminogen, laminin, fibronectin, mucin and cytokeratin binding properties. It has also been described as a complement-evasion protein and as a protein capable of inducing neutrophil trap formation.
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Crystallographic and NMR based analyses have revealed
2020-09-30
Crystallographic and NMR-based analyses have revealed that RINGs and U-boxes have a common mode of interaction with E2s (Fig. 2A). The key structural elements are two loop-like regions, which, in the case of RINGs, coordinate Zn. The loops surround a shallow groove formed by the central α-helix. Tog
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The pseudo DUBs KIAA and Abraxas are required
2020-09-30
The pseudo DUBs KIAA0157 and Abraxas are required for the catalytic function of BRCC36. Comparison of the BRCC36–KIAA0157 heterodimer structure with an inactive BRCC36 homodimer structure provides a model for understanding how this functional interplay is achieved. As shown in schematic form in Fig
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External factors such as protein
2020-09-30
External factors, such as protein partners, can also activate DUBs by either reinforcing the stimulatory effects of intramolecular factors or by other means. The intramolecular activation of the USP7 CD by its HUBL domain is allosterically potentiated by external factor GMP synthase (GMPS), which co
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br Materials and methods br Results br
2020-09-29
Materials and methods Results Discussion DNA-PKcs and the Ku heterodimer (Ku70 and Ku80) constitute the DNA-PK complex, which is a serine/threonine kinase. DNA-PK phosphorylates H2AX and other substrates, such as main NHEJ factors (Artemis, XRCC4, and DNA ligase IV) [4]. Therefore, DNA-PK d
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br Development of a liquid chromatography mass spectrometry
2020-09-29
Development of a liquid chromatography-mass spectrometry method to improve detection of PA species detection Liquid chromatography-mass spectrometry (LC-MS) is a powerful tool to detect different molecular species of phospholipids in D-Pantothenic acid receptor (Houjou et al., 2005, Pulfer and M
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Given the excellent in vitro
2020-09-29
Given the excellent in vitro pharmacology profiles of methyl ester 28 and primary amide 29 efforts were reengaged on neutral analogs of these leads, with a focus on non-amide replacements for the carboxylic MK-0457 functionality of 1. Acetonitrile 49 was found to have a good balance of DGAT-1 inhib
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Our western blotting results showed that phospho
2020-09-29
Our western blotting results showed that phospho-DDR1 levels continued to increase after I/R injury, and the overall activation trend between phospho-DDR1 and MMP-9 was the same. We found that phospho-DDR1 expression started to increase significantly at 12h after I/R injury, which may be related to
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Functionally all members of the IL family have been
2020-09-29
Functionally, all members of the IL-12 family have been annotated along major inflammatory signaling axes but their roles have often weighed on opposing sides of the immunological balance. For instance, IL-12 and IL-23 are classified as pro-inflammatory cytokines [10] as opposed to the rather protec
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