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Under conditions of energy scarcity or nutritional restricti
2020-03-04
Under conditions of energy scarcity or nutritional restriction, AMPK, a critical energy sensor, is activated in response to the increased ratio of AMP to ATP. Various kinases may phosphorylate AMPK, leading to its activation. For example, AMPK phosphorylation by liver kinase B 1 (LKB1) at Thr172 res
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The mechanism by which these
2020-03-04
The mechanism by which these HIV-PIs impair skeletal muscle palmitate transport and oxidation has been partially elucidated. CD36 (also referred to as fatty Ranolazine australia translocase; FAT) is a transmembrane protein involved in the transport of long-chain fatty acids (LCFA) across cellular me
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Given a disruption of membrane internalization and an increa
2020-03-04
Given a disruption of membrane internalization and an increase in synaptic glutamate receptors in CPG2 knockdown neurons, one might expect an increase in dendritic spine size as membrane continues to be inserted into the spines during receptor exocytosis. However, we observed the opposite phenotype,
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Potential break through technology poised to overcome
2020-03-03
Potential break-through technology poised to overcome these above-mentioned limitations is that of the “substrate mediated enzyme prodrug therapy”, SMEPT (Fig. 1). Learning from the previously established enzyme prodrug therapies (EPT) and specifically the antibody-directed EPT (ADEPT) [12], develop
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We first confirmed LPS induction
2020-03-03
We first confirmed LPS-induction of markers known to induce NF-κB signaling in Caco2BB cells, as established for numerous other cell types [31]. We initially selected this approach to monitor NF-κB activation instead of directly monitoring p65 as it is technically straightforward and provides both u
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Here we discuss implications of several major families of RI
2020-03-03
Here, we discuss implications of several major families of RING-type E3 ubiquitin ligases (MDM, Cullin, GRAIL, TRAF, TRIM) as targets in inflammation and immunity, and provide insights into potential small molecule interventions to mediate the cellular responses (summarized in Table 1). We briefly c
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It was hypothesized that if modafinil acts primarily via a
2020-03-03
It was hypothesized that if modafinil acts primarily via a noradrenergic mechanism, Dbh −/− mice should be non-responsive since they completely lack NE. In contrast, if modafinil acts mainly through DA systems, these mice should be hypersensitive. Modafinil was tested in Dbh −/− mice using both loco
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br Conclusions There is significant interest in understandin
2020-03-03
Conclusions There is significant interest in understanding the contribution of biological mechanisms to the non-linear/bilinear dose–response curves for DNA-reactive agents. Model monofunctional alkylating agents have datasets amenable to PoD determination for genotoxic effects in both in vitro a
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ICV injection of UCN or UCN performed
2020-03-03
ICV injection of UCN2 or UCN 3 performed in the morning of the 8th day (12h after the last IP administration) seems to increase further the time spent in the open arms of mice exposed to saline or nicotine treatment. Interestingly, in mice exposed to saline treatment ICV injection of UCN 2 or UCN 3
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Two additional hydrogen bonds are
2020-03-03
Two additional hydrogen-bonds are formed by the -substituted methoxy-group with Ser and Asp. Ser exerts the role of a gate keeper in CK1: Entry of the ATP in the binding-site causes a conformational change into the closed form by Ser, which locks the binding-site and prevents ATP-diffusion out of th
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It was reported that IVM modulates various
2020-03-03
It was reported that IVM modulates various ion channels, such as type-A GABACls, α7 acetylcholine-gated cation channels, P2X4 ATP-gated cation channels, and glycine-gated chloride Imatinib in vertebrates (Adelsberger et al., 2000, Khakh et al., 1999, Krause et al., 1998, Krůšek and Zemková, 1994, S
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The Fontan circulation When first described in the
2020-03-03
The Fontan circulation When first described in 1971, the Fontan operation ushered in a new paradigm in the care of children born with the varied forms of complex congenital fdps disease (CHD) characterized by a single effective pumping chamber.1., 2. This procedure, which creates a total cavopulmo
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Since anti MMP Therapy anti
2020-03-03
Since, anti-MMP Therapy [9], anti-iNOS therapy [10], TNF-α and IL-1β inhibitor (Diacerhein) [11] etc. are some of the disease modifying anti-osteoarthritis drugs have been used. But their action based on the evidence from the clinical trial and scientific literature suggesting the therapeutic effica
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Introduction Enzymes have higher selectivity specificity and
2020-03-03
Introduction Enzymes have higher selectivity, specificity and efficiency than chemical catalysts. Due to their properties and their green chemistry, biocatalysts are widely used in food, textile and pharmaceutical industry [1], [2]. A high efficient biocatalyst for industrial applications must be s
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In vitro studies in NSCLC
2020-03-03
In vitro studies in NSCLC cell lines expressing EGFR mutants (T790M mutation, exon 19 deletion E746-A750, L858R/T790M double mutation), demonstrated that Rociletinib potently inhibits proliferation in the mutant EGFR NSCLC Fmoc-Cl with Growth inhibition (GI50) values ranging from 7 to 32 nmol/L. In
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