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Finally the results in this article indicate that atomistic
2022-05-13
Finally, the results in this article indicate that atomistic MD in conjunction with computational electrophysiology and ion-permeation simulations provide a useful tool for the functional annotation of ion-channel structures. In particular, they exemplify how MD simulations in native lipid membranes
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H together with T also forms
2022-05-13
H109, together with T112, also forms a binding site for H+ (Chen et al., 2004; Harvey et al., 1999). H+-binding at this site also inhibits GlyR-mediated currents. Notably, the vicinity of neurons experiences changes in pH, to a mild extent in physiological conditions such as when neurons fire (Chesl
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Glucose uptake a critical metabolic control point in glycoly
2022-05-13
Glucose uptake, a critical metabolic control point in glycolysis, is mediated by the GLUT (SLC2) family of integral membrane transporters (Mueckler and Thorens, 2013). GLUT1 (SLC2A1), one of the most well-studied members of the SLC2 family, exhibits a wide tissue distribution; cell surface expressio
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In order to test the influence of the initial depolarization
2022-05-13
In order to test the influence of the initial depolarization, experiments were performed, where the degree of chloride substitution was varied, either by adding n-Ringer to meclofenamate incubated in a sucrose Ringer or by suspending the cells directly in Ringers identical to the final composition i
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SCPNs and CPNs exhibit similar
2022-05-12
SCPNs and CPNs exhibit similar strength of electrical coupling (Maruoka et al., 2017) and had similar membrane properties (Experimental Procedures), and showed no significant difference in amplification and synchronization (Figs. 2E and 3C). However, a subset of CPNs exhibit very strong electrical c
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Next we were interested in replacing the ketobenzimidazole
2022-05-12
Next, we were interested in replacing the ketobenzimidazole fragment of our inhibitors with a noncarbonyl bearing heterocycle. We reasoned that if we could replace the carbonyl while maintaining comparable FAAH inhibition, it would provide evidence for a noncovalent mechanism of action. Thus, we eva
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We thus asked whether enhanced AEA levels
2022-05-12
We thus asked whether enhanced AEA levels in the Aripiprazole sale reduce the level of age-related inflammatory changes and slow down brain ageing. To answer this question we compared the morphology of microglia and level of pro-inflammatory cytokines in the hippocampus of young and old wild-type a
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Our data show that oxidative stress high levels of ROS
2022-05-12
Our data show that oxidative stress (high levels of ROS) suppresses the process of lysosomal exocytosis, which would be predicted to impair the expulsion of toxic compounds from cells. Therefore, we propose that ROS have a biphasic effect on the lysosomal clearance: consistent with their role as a s
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br Experimental br Acknowledgments We thank
2022-05-12
Experimental Acknowledgments We thank Mintek and Rhodes University for generous financial support and permission to publish these findings. T.O.O. gratefully acknowledges Obafemi Awolowo University, Ile-Ife, Nigeria for study leave. Introduction There are ∼35.3 million people living with H
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It is important to mention that the IC
2022-05-12
It is important to mention that the IC50 of cetirizine needed to achieve histamine H2 receptor desensitization was 0.43 µM or 170 ng/ml (Fig. 1B), becoming clinically relevant since pharmacokinetic studies after oral administration of the clinically used dose (10 mg/day) reported a maximal plasma co
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It has been demonstrated that HO inhibits the production
2022-05-12
It has been demonstrated that HO-1 inhibits the production of proinflammatory mediators including TNF-α and IL-6 in response to sepsis [35], and the expression of iNOS and COX-2 [36,37]. An inverse association between HO-1 and iNOS has previously been described: the NO levels decline with increases
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E E evolution at transmission has been
2022-05-12
E1E2 evolution at transmission has been explored in multiple previous studies. Vertical transmission selects for E1E2 variants with increased replication fitness due of CTL escape mutations (Honegger et al., 2013). Experimental infection of chimeric liver mice selects for E1E2 variants with increase
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Due to the high structural similarity between GlxI and FosA
2022-05-11
Due to the high structural similarity between GlxI and FosA, it is possible that GlxI directed evolution experiments could produce FosA enzymatic activity in a GlxI enzyme. Although the current investigation was unable to detect FosA activity by mutation of a key metal liganding residue in the activ
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br Materials and methods br Results br
2022-05-11
Materials and methods Results Discussion DNA repair pathways have evolved for a long time to act independently of one another. However, over the past decade several overlaps and crosstalks between these pathways were identified, showing that the DNA repair system is more complex than previo
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br Funding This work was supported by grants of the
2022-05-11
Funding This work was supported by grants of the National Academy of Sciences of Ukraine within the programs “Molecular and cellular biotechnologies for medicine, industry and agriculture” (#35-2018), “Scientific Space Research for 2018-2022” (#19-2018), “Smart sensory devices of a new generation
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