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Previously we described that cadmium induces a more pronounc
2024-09-12
Previously, we described that cadmium induces a more pronounced, but not selective, cell death on primary cholinergic neurons from basal forebrain (Del Pino et al., 2014). Degeneration of septal cholinergic neurons from basal forebrain, as happens in AD, results in memory deficits (Scheiderer et al.
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br ACh and ER tests hereafter
2024-09-12
ACh and ER tests hereafter Spasm provocation tests have self-limitations to document coronary artery spasm during daily life. In the past reports, ST elevation was reproducible in some patients with variant GYY 4137 morpholine salt by the administration of ACh or ER. However, we now employ the E
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Since the localization of LO depends on phosphorylation we a
2024-09-12
Since the localization of 5-LO depends on phosphorylation, we also analyzed the phosphorylation profile of 5-LO-WT and all isoforms by Western blot using specific Phorbol 12,13-dibutyrate against the phosphorylation sites S271 and S523. Whereas phosphorylation at S271 activates the 5-LO, inhibits n
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The syntheses of a and b are
2024-09-12
The syntheses of 27a and 27b are shown in Scheme 5. Substituted naphthalene 21c was brominated using N-bromosuccinimide (NBS) and 2,2′-azobis(2-methylpropionitrile) (AIBN) to yield 25, which was subjected to lactam cyclization to form 26a and 26b, respectively. Deprotections of each L002 mg yielded
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Thirty six of the analogs synthesized showed ATX inhibition
2024-09-12
Thirty-six of the analogs synthesized showed ATX inhibition greater than 50% at 10μM with FS-3, twelve of which had improved potency over the lead (Fig. 5). Of these, 22 was sub-micromolar (IC50 670nM). The 3,5-dichlorophenoxy ring of 22 is reminiscent of the 3,5-dichlorophenylthiourea ring in Hoegl
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The original Aurora kinase was identified during
2024-09-12
The original Aurora kinase was identified during a phenotypic screen for defects in mitotic spindles in Drosophila mutants. Aurora mutants were so named because of the morphological defects at the mitotic spindle resembling the Aurora borealis, or the Northern light [4]. The structure of the Auroras
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At the outset of targeting the
2024-09-12
At the outset of targeting the two Gln756 side-chain rotamers, it was unclear which rotational isomer would lead to more potent ASK1 inhibitors. While such a preference might have been anticipated, the cohort of ASK1 inhibitors in Table 3 did not provide any guidance regarding which of the Gln756 am
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Hyperactivity of the hypothalamus pituitary adrenal HPA
2024-09-11
Hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis, which is well described in MDD (Pariante and Lightman, 2008, Marques et al., 2009), is also observed in AD and results in increased glucocorticoid (GC, cortisol in primates) levels in blood and CSF (Davis et al., 1986, Martignoni et al.
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Introduction Increasing environmental pollution caused by he
2024-09-11
Introduction Increasing environmental pollution caused by heavy metals, originating mainly from industrial processes and urban activities, as well as the widespread application of pesticides, fertilizers, manure and sewage sludge, has posed a serious problem for safe food production and become a po
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An important observation in our study is the lack of
2024-09-11
An important observation in our study is the lack of effect of paroxetine pretreatment alone on β2AR membrane expression, which suggests that paroxetine, and pharmacologic inhibition of GRK2 in general, does not directly induce changes in receptor dynamics. Rather, the decreased ligand-induced β-arr
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In the previous study we demonstrated the importance of
2024-09-11
In the previous study, we demonstrated the importance of the mPFC postsynaptic 5-HT1A receptor in the sustained antidepressant effects, because a sustained antidepressant effect was obtained with intra-mPFC injection, but not systemic injection of 8-OH-DPAT, a 5-HT1A receptor agonist (Fukumoto et al
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The obtained results indicate that even when the impairment
2024-09-11
The obtained results indicate that even when the impairment of the same forms of memory are present, amnesia can develop in different ways. Impairment of memory reconsolidation in the conditioned food aversion model through both the serotonin receptor antagonist and the antagonist of NMDA glutamate
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For comprehensive understanding of actin myosin XI
2024-09-11
For comprehensive understanding of actin-myosin XI as a control network, it will be necessary to determine the functions of all the myosin XI and utp biochemistry isoforms. However, it is difficult to reveal the function of individual myosin XI isoforms because most myosin XI single knockouts exhibi
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br Introduction Cell motility is fundamentally important in
2024-09-11
Introduction Cell motility is fundamentally important in morphogenesis, wound healing, and the immune response. One of the best-studied basic types of cell movement is lamellipodial motility [1, 2], characterized by a thin (∼0.1–0.2 μm), broad (∼10–40 μm) motile appendage containing a dynamic N1-
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Molecular docking simulations were carried
2024-09-11
Molecular docking simulations were carried out for ligands – in the ACE crystal structure (1O86) and DPP4 crystal structure (2G5P). Comparison of the binding mode of – () with enalaprilat (a) in ACE shows that the phenethyl group (–, enalaprilat) occupies the S1 pocket and the adjacent carboxylic ML
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