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ER redox imbalance leads to the accumulation
2020-03-12
ER redox imbalance leads to the accumulation of misfolded proteins, which might trigger the unfolded protein response (UPR) [17]. In the initiation of UPR, GRP78 preferentially binds to unfolded proteins, shifting the binding equilibrium away from IRE-1, PERK, and ATF-6, the initiators of UPR [18].
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br Coactivator Binding Sets APC C Catalytic Core
2020-03-12
Coactivator Binding Sets APC/C Catalytic Core in Motion A coactivator not only recruits substrates to APC/C [18] (Figure 3B), but also stimulates repositioning of the catalytic core 19, 24. High-resolution cryo-EM maps of apo forms of APC/C without a coactivator show the catalytic core and platfo
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The potential off target activity of
2020-03-12
The potential off-target activity of against other ATP-dependent enzymes, such as kinases, was also investigated. Encouragingly, there was no significant inhibition of ATP binding to 97 human kinases, when was evaluated at 10μM within a DiscoveRx scanEDGE® kinome screen (, ). All together, these d
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Group B phytocystatins are also expressed in caryopses
2020-03-11
Group B phytocystatins are also expressed in caryopses. Although their expression patterns during germination are similar to those of the group A inhibitors, their expression patterns during seed development vary, indicating that they play different roles in the latter process. The highest levels of
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In humans CYP A major isoforms of CYP As
2020-03-11
In humans, CYP3A4/5, major isoforms of CYP3As in the liver, have variants that reduce the enzyme activities [33], [34]. In addition, Werk et al. recently reported the first case of a complete failure of CYP3A enzyme activity due to homozygous loss-of-function mutation of CYP3A4 combined with nonfunc
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a-MSH, amide It should be noted that the long
2020-03-11
It should be noted that the long-lifetime binding-responsive luminescence of ARC-1528 and ARC-1530 becomes evident only upon illumination with radiation at near-UV range where the excitation of ATB or ASB moiety is possible. At higher wavelength range (visible light), the fluorophore (5-TAMRA) can b
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To determine whether the same concentration of humic acid ca
2020-03-11
To determine whether the same concentration of humic CGS 35066 causes changes in PCR efficiency, we performed another experiment in which the humic acid was added to the PCR mix after bisulfite conversion. All samples that were amplified in the presence of humic acid (thick lines) show a decrease i
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br Effects of estradiol outside the nucleus are
2020-03-11
Effects of estradiol outside the nucleus are often mediated by classical estrogen receptors Today, it is widely accepted that steroid hormones can signal in ways that do not rely on receptors acting in the nucleus, including activation of receptors localized to the cellular membrane. Rapid effect
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br Nuclear estrogen receptors Indirect genomic
2020-03-11
Nuclear estrogen receptors: Indirect genomic signaling As mentioned earlier, the transcription of several genes that do not contain EREs in their promoter regions can also be regulated by estradiol, without direct binding of the estrogen receptors to the DNA. According to the most recent reports,
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Importantly our in vivo data fit to the in
2020-03-11
Importantly, our in vivo data fit to the in vitro data, further confirming the synergistic effect of XJD and gefitinib on the inhibition of lung cancer and the regulation of SP1, HOTAIR, and EP4 LUF6000 levels. The doses of XJD used were based on our previous in vivo study (Zhao et al., 2016). We b
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Future advances in the in vivo molecular imaging of enzyme
2020-03-11
Future advances in the in vivo molecular imaging of enzyme activity will greatly benefit from the progress towards the quantitative detection of enzymes. Quantitative imaging requires knowledge of both the location and concentration of a specific enzyme, which is dependent on the simultaneous measur
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Crystallographic and NMR based analyses have revealed that R
2020-03-10
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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Another example of negative regulation is
2020-03-10
Another example of negative regulation is the inhibition of the yeast endosome-associated DUB Doa4 by Rfu1 (free ubiquitin chains 1). In a yeast genetics screen, deletion of Rfu1 was serendipitously found to alter global ubiquitin levels [69]. DUBs can regulate these levels by liberating conjugated
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L-690,330 Cancer has been linked to both genetic and
2020-03-10
Cancer has been linked to both genetic and epigenetic changes. Epigenetic modifications, mainly DNA methylation at CpG dinucleotides, affect the regulation of gene transcription without altering the gene\'s sequence. Short sequences rich in CpG dinucleotides (i.e., CpG islands) are often found in th
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4-IPP australia This study demonstrates that GUL affects mul
2020-03-10
This study demonstrates that GUL-1 affects multiple pathways/processes. As GUL-1 is likely to function as an RNA-binding protein, it is conceivable that the mRNAs involved are bound to GUL-1 as part of the regulatory function of the protein. In fact, in S. cerevisiae Ssd1 was shown to bind multiple
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