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Among RAS mutant tumors analyzed we found
2021-05-26
Among RAS mutant tumors analyzed, we found that the efficacy of either the SHP2 inhibitor SHP099, or combined MEK and SHP2 inhibition was best in those expressing RAS mutations at G12 (Figure 7B). Recent studies revealed that cellular RAS(G12C) activity depends on RTK-mediated nucleotide exchange, a
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br Conclusions br Conflicts of interest br Research funding
2021-05-26
Conclusions Conflicts of interest Research funding This work was financially supported by Shanghai Committee of Science and Technology (No. 16431903800). Main Text Developmental processes make usage of a surprisingly limited number of morphogens and signaling components to control a ple
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Several studies have demonstrated that
2021-05-26
Several studies have demonstrated that αSyn specifically associates with lipid rafts (Cole et al., 2002), raising the possibility that the perturbation of rafts can affect the aggregation and phosphorylation of αSyn (Fortin et al., 2004). Schneider et al. (2010) described the potential involvement o
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How does an increase in E affinity
2021-05-26
How does an increase in E2 affinity for the RING domain favor higher activity and polyubiquitination by the E2? Binding of the RING domain to the E2 positions the donor Ub in the E2~Ub conjugate in a closed complex [16], [17], [18] that increases the reactivity of the thioester [60]. A higher affini
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br Conflicts of interest br Introduction G protein coupled r
2021-05-25
Conflicts of interest Introduction G protein-coupled receptors (GPCRs), form the largest human membrane protein family, with 800 members overall. Many druggable targets for treatment of common diseases involve GPCRs that mediate therapeutic effects of 34% of all marketed drugs (Hauser, Attwood
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Our data supports the conclusion that the
2021-05-25
Our data supports the conclusion that the exonuclease activity thought to be intrinsic to Artemis is not a component of the Artemis polypeptide. Many possibilities exist to explain the presence of the exonuclease activity in less-pure fractions of Artemis. It is possible that the exonuclease is simp
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br The central role of DNA
2021-05-25
The central role of DNA-PK in the NHEJ NHEJ can be divided in several steps (Fig. 1A): 1) recognition and binding of Ku at each ends of the DSB following by the assembly of the DNA-PK at the break points and bridging; 2) phosphorylation of the DNA ends by DNA-PKcs; 3) ligation of the ends by DNA
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br Material and methods br Results br Discussion Ligase
2021-05-25
Material and methods Results Discussion Ligase IV is essential for the final ligation of DSBs through the NHEJ pathway. Its co-factor, XRCC4, has been shown to be important for increasing its activity and stability. Interaction between these two factors have been mapped to the linker region
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IMD 0354 australia br Materials and methods br Results Becau
2021-05-25
Materials and methods Results Because of the specific binding of DGKε to an arachidonoyl group, there was a particular interest to evaluate the behavior of 2-AG with this isoform of DGK. The substrate specificity and kinetic constants for DGKε has been recently reported [13]. Using the preferr
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br Introduction Diacylglycerol kinase DGK is a
2021-05-25
Introduction Diacylglycerol kinase (DGK) is a lipid-metabolizing enzyme that phosphorylates diacylglycerol (DG) to produce phosphatidic angiotensin ii synthesis (PA) [[1], [2], [3], [4]]. DG and PA act as lipid second messengers in a wide variety of biological processes. Ten DGK isozymes (α, β,
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In a cell based functional assay the antagonist properties o
2021-05-25
In a cell-based functional assay, the antagonist properties of were assessed by measuring inhibition of CRF-stimulated cyclic adenosine monophosphate (cAMP) production in human Y-79 retinoblastoma cells. produced a concentration-dependent inhibition of CRF (1nM)-induced cAMP production with an IC
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rotenone Organ fibrosis is thought to
2021-05-25
Organ fibrosis is thought to be initiated by repeated or chronic epithelial injury. The current belief is that damaged epithelial rotenone induce an aberrant and unresolved wound repair process by activating fibroblasts via various profibrotic cues. Upon injury, epithelial cells activate the profib
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Currently phosphodiesterase type PDE inhibitors are used wid
2021-05-25
Currently, phosphodiesterase type 5 (PDE-5) inhibitors are used widely as the first- line oral treatment for erectile dysfunction of varying causes. Radical prostatectomy for the treatment of prostate cancer is frequently associated with erectile dysfunction, and this type of erectile dysfunction is
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The mitogen activated protein kinase MAPK family which consi
2021-05-25
The mitogen-activated protein kinase (MAPK) family, which consists of extracellular signal-regulated protein kinase 1/2 (ERK1/2), p38 MAPK, and c-Jun N-terminal kinase (JNK), is involved in the development of NP (Hung et al., 2012, Ji et al., 2009). Recently, Zhuang et al. (2005) demonstrated that t
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Among the different factors that
2021-05-25
Among the different factors that modulate Schwann cell biology, several studies pointed out the role played by neuroactive steroids, in particular progesterone (P4) and its derivatives dihydroprogesterone (DHP) and allopregnanolone (ALLO). Schwann GDC-0994 australia are steroidogenic, possessing th
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