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Our previous high throughput screening HTS campaign using au
2019-12-17
Our previous high-throughput screening (HTS) campaign using automated, robust, and sensitive fluorescence based Tolvaptan assay [10], [11] led to the identification of several EPAC specific inhibitors (ESIs), and was subsequently followed by extensive hit-to-lead optimizations [20], [21], [22], [23]
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Compounds and possessed relatively low clogP values and
2019-12-17
Compounds 11–13 and 15 possessed relatively low clogP values and tended to show relatively weak antagonist activity regardless of their potent EP1 receptor affinity. Compounds 2–4, which were selected based on their potent in vivo antagonist activity, were found to be effective in an animal model.
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As with all meta analysis this study certainly has
2019-12-17
As with all meta-analysis, this study certainly has some limitations. First, our results were derived from unadjusted analyses due to lack of raw data, and lack of further adjusted analyses for age, gender and co-morbidity conditions may impact the reliability of our findings [63]. Second, obvious h
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Celiac disease occurs in the
2019-12-17
Celiac disease occurs in the small intestine due to the ingestion of gluten and triggers an immune response by T-cells resulting in tissue remodelling and malnutrition [6]. Earlier studies by many researchers have shown that the prolamins of gluten are the toxic agent for celiac disease, since they
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Celiac disease occurs in the
2019-12-17
Celiac disease occurs in the small intestine due to the ingestion of gluten and triggers an immune response by T-cells resulting in tissue remodelling and malnutrition [6]. Earlier studies by many researchers have shown that the prolamins of gluten are the toxic agent for celiac disease, since they
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In this study we were able derive new insights into
2019-12-17
In this study, we were able derive new insights into the biology of DDR2 including the demonstration that cellular tyrosine phosphorylated proteins co-localise with DDR2 and exogenously added collagen I (Fig. 1G). This finding suggests that similar to the focal adhesion complexes associated with int
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CCR is another chemokine receptor that
2019-12-17
CCR7 is another chemokine receptor that is upregulated in CLL [3], [61], [71], [96] and is believed to play a role in enabling cell entry into lymph nodes [97]. Higher mRNA and protein expression of CCR7 has been observed in unmutated compared to mutated IGHV CLL [46] and increased expression has be
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Itch also known as astrophin interacting protein AIP
2019-12-17
Itch, also known as astrophin-1 interacting protein-4 (AIP4), is a HECT domain-E3 ligase. It was discovered in 1998 in mouse coat color genetic studies which displayed the disruption caused by the Itch gene inducing a lethal autoimmune inflammatory condition. The substrates of Itch are transmembrane
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The structure of the HOIP RBR LDD module
2019-12-17
The structure of the HOIP RBR–LDD module bound to UbcH5~Ub reveals insights into an activated HOIP component [47]. Contacts between the E2~Ub and the non-cognate RBR module in the crystal suggest how a structure in which the active sites of the E2 and the E3 are in close proximity might look. In thi
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Cellular immune responses such as phagocytosis and
2019-12-17
Cellular immune responses, such as phagocytosis and apoptosis, are very important processes to eradicate the invading pathogens and reduce concomitant host damage. And all of these processes are fine-tuned by the ubiquitin system (Li et al., 2016). Phagocytosis is a major mechanism of cellular immun
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Here we explored the relative contribution of D
2019-12-17
Here we explored the relative contribution of D1-like and D2-like receptor subtypes in the control of glutamate release, as well as their pharmacological properties and their interactions modulating the release. The pharmacological parameters (EC50 and Emax) of dopamine for the different types of re
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To our knowledge this is the first report of an
2019-12-16
To our knowledge, this is the first report of an oncocytoma expressing alpha-enolase or causing autoimmune retinopathy and optic neuropathy. Although generally considered benign, oncocytomas have rarely been associated with paraneoplastic syndromes, including tumor-induced hypertension, erythrocytos
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br Conflict of Interest br Statement
2019-12-16
Conflict of Interest Statement of Authorship Introduction Plant endopeptidases are involved in many important biological processes. Recent developments in molecular biological techniques have revealed trace amounts of endopeptidases play essential roles in plant development, turnover of pho
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br Molecular characterization of LEI L DNase II LEI like
2019-12-16
Molecular characterization of LEI/L-DNase II LEI, like most serpins, is a metastable protein and its anti-protease activity is related to its “stressed to relaxed transition”. So that, the inhibition of elastase by the well described suicide mechanism generates the cleaved form of LEI (see Padron
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A key inciting event in atherosclerosis is
2019-12-16
A key inciting event in atherosclerosis is the deposition of circulating low-density lipoprotein (LDL) in the subendothelial space of major arteries. In the subendothelium, native LDL is no longer protected by circulating antioxidants and is oxidatively modified to oxidized LDL (OxLDL) [5]. OxLDL is
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