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The causes of POD are complex and
2019-08-24
The causes of POD are complex, and not entirely clear. Androsova et al, believed that the main molecular mechanism of POD is a central cholinergic deficiency caused by deregulation of cholinergic anti-inflammatory pathways leading to increased inflammation. The cholinergic anti-inflammatory pathway,
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What is the predominant mechanism underlying the benefits
2019-08-24
What is the predominant mechanism underlying the benefits of udenafil, i.e. the vascular vs. myocardial effect? Lewis et al. suggested that the benefit of sildenafil in HFrEF would be derived from augmented RV systolic function that mainly results from pulmonary vasodilation, suggestive of the ‘vasc
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While previously reported optimizations on compound
2019-08-24
While previously reported optimizations on prostaglandin endoperoxide synthase focused on the phenyl ring A () and substituents on isoxazole ring, other alternatives to replace isoxazole ring were never explored. Herein, we propose to replace the isoxazole with its bioisosteric substituted phenyl ri
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Drug resistance to both pathogens and cancer
2019-08-24
Drug resistance to both pathogens and cancer has been a big hindrance in healthcare. Integrated research undertakings are being pursued to find the exact causes of the lack of response towards drugs. Surprisingly, host pumps are the key factors in failure of most drugs. The pumps either do not allow
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The discoidin domain receptors DDR and DDR are receptor tyro
2019-08-24
The discoidin domain receptors, DDR1 and DDR2, are receptor tyrosine kinases (RTKs) that are stimulated by collagen in the extracellular matrix (ECM). Unlike most other RTKs, they form ligand-independent stable dimers that are non-covalently linked. This ECM activation induces receptor phosphorylati
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We also note that though
2019-08-24
We also note that though the pacritinib of the N-terminus in Ube2E1∆N46 or the mutations in Ube2E16KtoR enhanced their activity compared to the wild type, it failed to match Ube2D2 (Fig. 1). We concluded this difference to be multi-factorial as none of the Ube2E1∆N46 point mutants involving “Ub bac
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Current therapeutic interventions are directed both
2019-08-24
Current therapeutic interventions are directed both to prevent (primarily by proper glycemic control) and to treat the advanced stages of diabetic retinopathy, when vision has already been significantly affected. Although these therapies can be very effective in preventing, delaying or reducing visi
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Although many GPCR heteromers have been identified using
2019-08-24
Although many GPCR heteromers have been identified using heterologous cell lines, only very few fit all three criteria. This is mainly due to the difficulties to study these structures in native tissues because of the lack of sensitive and selective tools, not only capable of detecting in vivo evide
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The acid base properties of
2019-08-23
3. The acid-base properties of the IL are important issues to consider because protonation changes caused by Brønsted-acidic or basic ions may result in enzyme deactivation [29]. Thereby, the acid-base properties of the newly designed IL need proper control for enzymes by selection of appropriate ca
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The discoidin domain receptors DDR and DDR are receptor tyro
2019-08-23
The discoidin domain receptors, DDR1 and DDR2, are receptor tyrosine kinases (RTKs) that are stimulated by collagen in the extracellular matrix (ECM). Unlike most other RTKs, they form ligand-independent stable dimers that are non-covalently linked. This ECM activation induces receptor phosphorylati
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Expression of EBI and its function for migration
2019-08-23
Expression of EBI2 and its function for migration in vitro in T cells was recently reported (Chalmin et al., 2015, Hannedouche et al., 2011, Liu et al., 2011, Pereira et al., 2009). Pereira et al. (2009) used an EBI2 reporter mouse and found that most CD4+ T cells, but only approximately half of the
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Itch also known as astrophin interacting protein AIP
2019-08-23
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 differences between ground and transition state
2019-08-23
The differences between ground and transition state properties are exemplified by a comparison of our human–yeast results with those of a structural study of possible differences in ubiquitin-Uba-1 binding in yeast (known structure) with human (simulated in [12]). Their discussion focuses on Ubiquit
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Similarly synthetic analogs of Alogliptin by
2019-08-23
Similarly synthetic analogs of Alogliptin by replacing the cyanobenzyl group with the butynyl group have been synthesized and tested as selective DPP-4 inhibitors [7], [8]. Additionally, quinazolines [9], [10], pyridopyrimidinediones [11], pyrazolopyrimidinones [12] and pyrimidines [13] as DPP-IV in
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The totality of evidence from randomized clinical trials sup
2019-08-23
The totality of evidence from randomized clinical trials supports the premise that worsening K-252c failure is a class effect of DPP-4 inhibitors. A meta-analysis by Verma et al. (54) of 100 randomized controlled clinical trials reported that the use of DPP-4 inhibitors was accompanied a significan
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