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br Discussion The regulation of
2020-04-09
Discussion The regulation of intracellular cholesterol levels is a biological process of vital importance for cellular function and integrity, and involves robust transcriptional and post-transcriptional mechanisms that are sensitive to metabolic feedback control. Amongst post-transcriptional mec
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In addition to cleaving ubiquitins off modified proteins
2020-04-09
In addition to cleaving ubiquitins off modified proteins, DUBs can also cleave between ubiquitin moieties within a polyubiquitin chain to edit the ubiquitin signal. DUBs employ different strategies to recognize polyubiquitin (Figure 1). DUBs that rely only on interactions on the S1 site tend to be 9
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Here we describe a novel series of arylazoderivatives develo
2020-04-09
Here, we describe a novel series of arylazoderivatives developed from CAN508, one of the first known selective CDK9 inhibitors. We focused on modification of both ends of parental molecule, CAN508, in order to improve cytotoxicity and CDK activity. We therefore analyzed how changes in molecules will
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br Methods br Results br Discussion On the other hand
2020-04-09
Methods Results Discussion On the other hand, surgical patients have to some extent stress during pre- and/or post-operative period. It is well known that CRF/CRF1 receptor is involved in the activation of HPA during acute and chronic stress (Papadimitriou and Priftis, 2009, Zelena et al.,
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Kinetic isotope effects KIEs inform on
2020-04-09
Kinetic isotope effects (KIEs) inform on bond vibrational changes between the ground state (GS) and TS of a chemical reaction and remain one of the most powerful experimental techniques for interrogating TS structure. KIEs on enzyme reactions measured by the internal Cytarabine mg of labeled substr
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Our results from neutropenic mice infected with both fungal
2020-04-09
Our results from neutropenic mice infected with both fungal strains revealed that the inflammatory process was more severe 72hours post-infection (Fig. 4). Angioinvasion was mainly observed 48hours after infection for both strains. Transformation of A. fumigatus conidia into hyphae in immunocompeten
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Crystallographic and NMR based analyses have revealed that R
2020-04-09
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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In our preliminary evaluation of this series we
2020-04-09
In our preliminary evaluation of this series, we were surprised to discover that TAK-875 was found to bind CSF-1R in a classical DFG-in binding mode (a). Dramatic conformational differences in the juxtamembrane domain and activation loops are apparent when this DFG-in structure is compared with prio
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br RING dimerization RING type domains are found
2020-04-08
RING dimerization RING-type domains are found in many different structural contexts. While many exist as single-chain ML 221 (Fig. 3A), a notable feature of RING-type E3s is their tendency to form homodimers and heterodimers (Fig. 3C–F). Homodimeric RING-type E3s include cIAP, RNF4, BIRC7 (shown
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During the host response to
2020-04-08
During the host response to inflammation, inflammatory mediators, including release of pro-inflammatory cytokines, have been associated with altered content, expression, and activity of CYP450 enzymes, consequently leading to alterations in the metabolism and elimination of certain drugs. The losses
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Moxifloxacin In general cellular senescence is considered a
2020-04-08
In general, cellular senescence is considered a programmed response to stress that can be activated by oxidative stress, irradiation or action of substances or drugs. These stressors cause DNA damage and, through the action of specific proteins (p53 and p21), lead to cell senescence (di Fagagna, 200
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Introduction Postoperative delirium POD is a potentially deb
2020-04-07
Introduction Postoperative delirium (POD) is a potentially debilitating disorder experienced by many elderly patients admitted to a surgical intensive care unit (ICU) after noncardiac surgery. Delirium is often defined as acute cognitive dysfunction that is characterized by an altered mental status
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The prospects of the use of this novel
2020-04-07
The prospects of the use of this novel approach for the selective local thermo-activation of enzymes include biomedical and biotechnological applications. As NPs could be engineered to gain access to dibromide receptor through the endosomal compartment [47] or through non-endocytotic pathways [48],
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At present there have been
2020-04-07
At present, there have been relatively few studies that evaluated potential correlations between pulmonary and pleura metastases, hilar and mediastinal 8-Bromo-cGMP, sodium salt nodes, and organs associated with distant metastasis and EGFR mutations [33,34,37]. Further research on these relationshi
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Several studies suggest that the beneficial metabolic effect
2020-04-07
Several studies suggest that the beneficial metabolic effects of adiponectin in humans are primarily mediated by its HMW isoform. Increases in the ratio of HMW to total adiponectin, but not the total adiponectin level, correlated well with improved DL-Dithiothreitol sensitivity during treatment wit
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