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The increased occurrence of ARIA E in
2024-09-21
The increased occurrence of ARIA-E in APOE ε4 carriers in phase 2 studies resulted in separate protocols for carriers and noncarriers in the subsequent phase 3 studies. Two 18-month trials comprising 1121 carriers and 1331 noncarriers with mild to moderate AD tested doses of bapineuzumab that varied
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Inhibition of autophagy has been shown to
2024-09-21
Inhibition of autophagy has been shown to alleviate neuronal damage after cerebral ischemia, both in cell culture and rodent models (Koike et al., 2008, Li et al., 2015, Wang et al., 2016, Zhang et al., 2014, Zheng et al., 2014). Therefore, blockage of autophagy is a potential target for prevention
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XEN445 br Concluding remarks Enhanced membrane binding upon
2024-09-21
Concluding remarks Enhanced membrane binding upon calcium stimulation in XEN445 suggests a pre-requisite step that involves a conformational change in LOX. This might facilitate it to tether to the membrane and regulate enzyme activity. The calcium binding loops and the putative active site entra
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br Conclusion br Acknowledgement This work was supported by
2024-09-21
Conclusion Acknowledgement This work was supported by JSPS KAKENHI (Grant Number 15K18770). Introduction Neural crest Bacitracin synthesis are multipotent progenitors in the vertebrate embryo that give rise to a vast array of different cell types including pigment cells, craniofacial skel
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agonists simulate norepinephrine NE in binding to presynapti
2024-09-21
α2 agonists simulate norepinephrine (NE) in binding to presynaptic surface autoreceptors, which in turn mediates feedback inhibition of NE release. Another major control mechanism for noradrenergic neurotransmission is termination of signaling by presynaptic NE transporter (NET)-mediated NE reuptake
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In the vasculature it is known that A
2024-09-21
In the vasculature, it is known that A2A and A2B adenosine receptors are stimulatory for adenylyl-cyclase, leading to cyclic-AMP (cAMP) production and vasodilation, while the A1 and A3 adenosine receptors are linked to the inhibitory Gi, suppressing adenylyl-cyclase and favoring contraction. However
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br Methods br Results br Discussion
2024-09-21
Methods Results Discussion Acknowledgements This work was supported by the National Institutes of Health [Grant R21 NS081429], a Pilot Grant from the Vanderbilt Conte Center supported by the National Institutes of Health [Grant P50 M096972], and by the Department of Anesthesiology at V
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The reductase activity in patients with OHD as
2024-09-21
The 5α-reductase activity in patients with 21-OHD, as assessed by the 5α-THF to 5β-THF (ratio 3) and by the 5α-17HP to 17HP (ratio 4) ratios, showed a similar pattern of activities (Fig. 2A–C) and significant correlations (ratio 1 vs. ratio 3; rs=0.67; pNHS-12-Biotin to the 5α-reducase activity, th
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ONX-0912 The evidence points toward a role for LO activity
2024-09-20
The evidence points toward a role for 12/15-LO activity in WAT in modulating chronic local inflammation and subsequent systemic metabolic decline in the obese state. However, little is known as to the role of 12- and 15-LOs in BAT. Indeed, in addition to WAT, platelet- and leukocyte-type 12-LO are e
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br Materials and Methods br Results br Discussion HETE is
2024-09-20
Materials and Methods Results Discussion 15-HETE is a predominant eicosanoid in pulmonary vascular remodeling, and it could promote hypoxia-induced PAH via its involvement in the regulation of proliferation and cell cycle progression in PASMCs. To understand its role in HPH, we have previou
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Why do glutamate and glycine bind to the
2024-09-20
Why do glutamate and glycine bind to the glucagon receptor in such different ways? Given the overall structural similarity between the GluN2A and GluN1 LBDs, one might conclude that the LBDs also bind ligands via similar processes. NMDA receptors with engineered disulfide linkages that lock the Glu
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Then Autodock was employed for site directed docking on
2024-09-20
Then, Autodock4.2 was employed for site directed docking on AD with the ligands of the cluster(s) having high binding affinities in VS II experiment (Morris et al., 2009). Docking protocols were followed as per our earlier report with 200 GA (genetic algorithm) run (Kalani et al., 2015). Likewise, l
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br Results br Discussion br Conclusions In summary
2024-09-20
Results Discussion Conclusions In summary, this study provides novel report of pericardial adipose aromatase expression – in both human and rodent. We show that aromatase expression is remarkably upregulated with aging (Fig. 1C), and that total aromatase PYR-41 conversion capacity is signi
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Ala a branched chain amino acid
2024-09-20
Ala, a branched chain amino acid, has been reported to play a functional role in intracellular pH regulation, and it typically accumulates in response to various stresses (Limami et al., 2008, Rocha et al., 2010). Our data demonstrated that increasing Cd concentrations at lower Cd doses resulted in
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The lactam emerged as lead candidate
2024-09-20
The lactam (6) emerged as lead candidate due to its high selectivity, outstanding potency (against ALK or in clinically known ALK mutants), low in vitro clearance, and low efflux potential. The lactam (6) was selected for further profiling against the resistant ALK mutants. Preclinical rat pharmacok
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