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br Acknowledgements We thank Jeffrey
2020-06-18
Acknowledgements We thank Jeffrey D. Konowalchuk and John Sony Robbins for their technical assistance. This work was supported by Natural Sciences and Engineering Research Council of Canada (NSERC) grants to DRB (RGPIN-2013-355303) and MB (RGPIN-2014-96395). AMR was supported by NSERC Vanier Doct
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Nitric oxide synthase NOS is a predominant enzyme
2020-06-18
Nitric oxide synthase (NOS) is a predominant enzyme of immune system, which elaborates nitric oxide (NO) from the amino antimalaria medication arginine (Arg). NO mediates vasodilatation, blood pressure regulation, neurotransmission, host defense, and macrophage-mediated immunity, among an array of
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Tacrine amino tetrahydroacridine I Fig was the first AChEI t
2020-06-18
Tacrine (9-amino-1,2,3,4-tetrahydroacridine) (I, Fig. 1) was the first AChEI to be approved by the Food and Drug Administration (FDA) for the treatment of AD [25], [26], [27], [28]. However, despite its good AChE inhibitory activity, tacrine was far from ideal due to its low bioavailability and shor
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The rate of protein degradation
2020-06-18
The rate of protein degradation is often affected by N-starvation [12], therefore, we examined the influence of N-starvation against the appearance of CEPs. N-starved cucumber cotyledons contained less amounts of protein and Rubisco, but the temporal changes in protein and Rubisco contents were simi
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Inflammation is critical in the pathobiology
2020-06-17
Inflammation is critical in the pathobiology of atherosclerosis. The inflammatory mediators impacted by FBXO3 described herein i.e. NF-κB, IL-1β, and TNF-α, and IL-8 have purported causal roles in atherosclerosis. For example, NF-κB activation is increased in mononuclear cells in human plaques [29]
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The modification of proteins with
2020-06-17
The modification of proteins with the small 76-amino L-AP5 protein ubiquitin (Ub) plays a central role in many key cellular processes. Ubiquitylation of a target protein requires the concerted action of a cascade of three enzymes (Figure 1). The ubiquitin-activating enzyme (E1) catalyzes the formati
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As for antiviral activity eight
2020-06-17
As for antiviral activity, eight out of 23 synthesized compounds were active against influenza B virus with EC50 values in the range of 0.19–39 μM. Four of the eight influenza B hits were active against influenza A and two were also active against RSV (4 and 6, EC50 = 0.40 and 1.8 μM, respectively).
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The present findings suggested that nsEP inhibited
2020-06-17
The present findings suggested that nsEP inhibited CPG2 via deprivation of zinc ions, with no effect on apoenzyme integrity. Zinc may be removed from CPG2 by the electric forces. Within CPG2, each zinc ion was coordinated by one histidine, one glutamate and one aspartate [6]. The nsEP field can alte
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These findings further extend our knowledge of
2020-06-17
These findings further extend our knowledge of how P4 and/or E2 can mediate anxiety and fear responses. Female rats in behavioral estrous and ovx rats administered systemic P4 and/or E2 demonstrated significantly less anxiety in the open field and/or elevated plus maze, compared to diestrous rats, a
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The mitogen activated protein kinase MAPK
2020-06-17
The mitogen-activated protein kinase (MAPK) pathway is a highly conserved module that mediates the transduction of signals from the cell surface to the nucleus (M. Köbel et al., 2005), meanwhile, it is known to be activated by a wide array of signals ranging from growth and differentiation factors t
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The majority of serpins inhibit serine proteases
2020-06-17
The majority of serpins inhibit serine proteases, but serpins that inhibit caspases or papain-like cysteine proteases have also been identified [4], [5]. Inhibitory serpins are ‘suicide’ or ‘single use’ inhibitors that use a unique conformational change to inhibit proteases. This conformational tran
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br Experimental procedures br Acknowledgments br
2020-06-17
Experimental procedures Acknowledgments Introduction Receptor tyrosine kinases (RTKs) control many fundamental cellular processes, such as cell proliferation, differentiation, migration, and metabolism (Lemmon and Schlessinger, 2010). RTK activity is normally tightly controlled, and dysregu
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br Future perspectives Understanding how peptides are degrad
2020-06-17
Future perspectives Understanding how peptides are degraded, particularly those which may be therapeutically useful, such as GLP-1, has proved to be invaluable in providing a rationale for the development of a novel class of therapeutic agents. However, while DPP-4 plays an important role in the
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For the first time we
2020-06-16
For the first time, we provide evidence for COMT Val158Met modulation of long-term fear extinction in humans, evident both in cortical (LPP) and autonomic (fear bradycardia) components of the conditioned fear response. We further found that the initial acquisition of fear is related to dispositional
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Nociceptive and hyperalgesic actions of ET are
2020-06-16
Nociceptive and hyperalgesic actions of ET-1 are produced through ETA and ETB receptors. Previous reports indicate that ETA receptor antagonists in peripheral tissues are effective in inhibiting ET-1 induced hyperalgesia, and attenuation of neuropathic pain in rats [16]. Studies have also shown that
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