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All components of the UPP were predicted to be
2020-01-25
All components of the UPP were predicted to be susceptible to oxidative stress due to the cysteine residues in their active sites [36]. Curcusone D inhibits DUBs but has no significant effect on the action of E1, E2s, E3s, or the proteasome, which indicates that the targets of the ROS induced by cur
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GLP signaling mediates important renal functions
2020-01-25
GLP-1 signaling mediates important renal functions [101], as suggested by the expression of both DPP-4 and GLP-1R in the kidney of several species, including humans [102]. However, controversial data exists on the specific expression pattern of these proteins, based on the specificity and sensitivit
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One of the hallmarks of the terminal stages
2020-01-25
One of the hallmarks of the terminal stages of apoptosis is the fragmentation of chromosomal DNA that proceeds in a two-step manner: the DNA is initially cleaved into 50–300kb fragments and eventually into oligonucleosomal pieces [12], [13]. The two major apoptotic nucleases are DNA fragmentation fa
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Arsenic is an endocrine disruptor with estrogenic
2020-01-25
Arsenic is an endocrine disruptor with estrogenic activity. Further study has shown that arsenic exposure can significantly increase the expression of estrogen receptor-related genes, steroid metabolism-related enzymes and lung cancer-related genes in the lung tissues of female mice on the occurrenc
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br Conflict of interest br Acknowledgements This work was su
2020-01-25
Conflict of interest Acknowledgements This work was supported by the Basic Science Research Program through the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning (2013R1A1A1076117) and also by the Priority Research Centers Program through the NRF funde
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Given its high frequency it is not surprising that
2020-01-25
Given its high frequency, it is not surprising that different strategies have been developed to restore the sensitivity of EGFR T790M-mutant amitriptyline hydrochloride receptor to EGFR inhibition. To date, several different strategies have been evaluated in both preclinical and clinical models, bu
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br Phylogenetic analysis KSTDs have
2020-01-25
Phylogenetic analysis — Δ1-KSTDs have rather diverse amino Cy3 hydrazide sale sequences. A sequence distance analysis using the program MEGA6 [75] of all currently biochemically characterized Δ1-KSTDs yielded a largest p-distance [76] of 0.67 (on a scale of 0-1) for the Δ1-KSTDs from the actinoba
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Another enzyme class that has emerged as a potential alterna
2020-01-23
Another enzyme class that has emerged as a potential alternative to P450s are the so-called ‘unspecific peroxygenases’ (UPOs). They also contain a heme but are extracellularly expressed fungal enzymes that are often more stable than P450 monooxygenases. Importantly, UPOs use H2O2 instead of O2 as th
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br Acknowledgments br Introduction Ubiquitin ligases limit t
2020-01-23
Acknowledgments Introduction Ubiquitin ligases limit the stability and activity of substrates by targeting them for proteasomal-dependent degradation. Siah is a two-member family of ubiquitin ligases implicated in control of key cellular processes. Among those, Siah ligases control prolyl hydr
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TC-I 15 receptor br Materials and methods br Results br Disc
2020-01-23
Materials and methods Results Discussion UPP components including the proteasome, E1s, E2s, E3s and DUBs may become one the most important TC-I 15 receptor of therapeutic targets for the pharmaceutical industry in the near future and supersede those which are involved in the phosphorylatio
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Determination of relative potency EC by dose
2020-01-22
Determination of relative potency (EC50) by dose response assays in vitro is subject to the same sources of variability as determination of affinity, since the EC50 and Hill slope of the dose response curve are highly dependent on the binding of ligand to a competing receptor that may be present, an
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The objective of the present work
2020-01-22
The objective of the present work is to search for the optimum blend when 12.5–50% metakaolin is substituted by RHA and reacted with 10 M sodium hydroxide solution to produce geopolymers. It was hypothesized that the amorphous mtor inhibitor from RHA will increase the Si/Al ratio of the mix and in
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br Marginal zone lymphoma Marginal zone lymphoma MZL
2020-01-22
Marginal zone lymphoma Marginal zone lymphoma (MZL) comprises three lymphoma entities that arise from the marginal zone surrounding the germinal center: extranodal MZL or mucosa-associated lymphoid tissue (MALT), splenic MZL, and nodal MZL. Deep sequencing of nodal MZL patients found that 5/35 (1
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In the context of E ligase drug discovery it
2020-01-22
In the context of E3 ligase drug discovery, it is critical to identify the appropriate E2/E3 substrate pairing to ensure the development and use of the most physiologically relevant screening assay. There have been many reports of limited E2/E3 activity profiling with a small number of E2 and E3 Hal
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br Results br Discussion Many
2020-01-22
Results Discussion Many assays in the literature for DBH require the use of catalase to protect the active site from hydrogen peroxide, which is a by-product in the initial step of the reaction. For the non-immobilized enzyme there was a visible increase in the rate with increasing amounts of
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