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In addition unconventional mechanisms of internalization can
2024-11-20

In addition, unconventional mechanisms of internalization cannot be ignored. It is generally believed that the conventional homologous internalization of a GPCR depends on the activation of G proteins, since GRK activation requires the pre-activation of G proteins (Fig. 2). Feng et al. demonstrated
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That increased longevity was not the exclusive result of
2024-11-20

That increased longevity was not the exclusive result of blood pressure reduction. This was demonstrated by analysis of life-long, whole body deletion of AT1A receptors in normotensive mice. These animals exhibited a very significant increase in lifespan when compared to wild- type mice [159], [160]
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While there is much in vivo work on prion
2024-11-20

While there is much in vivo work on prion-like Aβ, it has not been shown that one can induce inclusions of Aβ in cultured cells as has been shown for tau and α-synuclein. One reason is practical; Aβ is a low molecular weight metabolite cleaved from within the larger amyloid precursor protein (APP) a
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Flavonoids protein interactions studies play a substantial
2024-11-20

Flavonoids-protein interactions studies play a substantial part in the hunt for novel molecules which are to interact with a selected disease-relevant target [35]. The mode of potential interaction gives information about the flavonoid effectiveness and selectivity. Lately, possible target molecules
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br Discussion Here we show opposing effects of iontophoretic
2024-11-19

Discussion Here, we show opposing effects of iontophoretically administered phenylephrine,aselective α1-AR agonist, on firing of putatively DAergic and non-DAergic neurons recorded in vivo in the VTA of urethane anaesthetized rats. Phenylephrine application caused a relatively weak decrease in fi
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br Acknowledgments This work was supported by
2024-11-19

Acknowledgments This work was supported by Grant-in-aid for Scientific Research (S) (20229008) (to T.K.), Targeted Proteins Research Program (to T.K.), the Global COE Research Program (to T.K.) and Translational Systems Biology and Medicine Initiative (to T.K.) from the Ministry of Education, Cul
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NLX a k a F or befiradol
2024-11-19

NLX-112 (a.k.a. F13640 or befiradol), exhibits nanomolar affinity at 5-HT1A receptors, and, in TAK 165 synthesis to the 5-HT1A receptor agonists listed above, it presents exceptional selectivity and high efficacy at these receptors (Colpaert et al., 2002, Newman-Tancredi et al., 2017). Additionally,
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Introduction The lysosomal storage disorder Gaucher disease
2024-11-19

Introduction The lysosomal storage disorder Gaucher disease (Mendelian Inheritance in Man, OMIM #230800) results from the recessively inherited deficiency of lysosomal glucocerebrosidase (GCase, EC 3.2.1.45), caused by mutations in the gene GBA1 (MIM# 606463) located on chromosome 1q21. The enzymat
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The relatively high concentration of HT used in this study
2024-11-19

The relatively high concentration of 5-HT used in this study (100 µM) is consistent with the concentrations used in other published ex vivo studies (Ropert and Guy, 1991, Passani et al., 1994, Shen and Andrade, 1998). In our paradigm 5-HT was focally applied at the surface of the slice via a fast pe
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Because of its role in tumor growth
2024-11-19

Because of its role in tumor growth, proliferation and metastasis, Axl is considered a therapeutic target. Several Axl inhibitors, including low-molecular-weight agents and antibodies, have been reported. Axl inhibition, using low-molecular-weight inhibitors or shRNA knockdown, resulted in reduced t
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Another important question concerns the mechanism by which a
2024-11-19

Another important question concerns the mechanism by which a polyubiquitinated substrate is released from the Cdc48 complex and passed on to downstream components, such as the proteasome. There are at least three proposed models. In the first, a ubiquitinated substrate is transferred by ubiquitin-bi
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br Introduction Increasing number of
2024-11-19

Introduction Increasing number of mycosis infections has been reported during the past several years because of the rise in the number of immuno-compromised individuals in subtropical and tropical countries with high mortality and morbidity [1], [2]. Trichophyton mentagrophytes, Trichophyton rubr
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br Under normal physiological conditions the agonist binds t
2024-11-19

Under normal physiological conditions, the agonist binds to AT1R on the surface of the plasma membrane and activates the receptor, mediating downstream signaling. Then, activated AT1R is phosphorylated by protein kinase C (PKC) [13] or G protein coupled receptor kinases (GPKs, such as GRK2 [13], G
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Since all the above vascular and glomerular effects contribu
2024-11-18

Since all the above vascular and glomerular effects contribute to blood pressure regulation, it is expected for 12/15-LOX pathway to play a role in pathogenesis of hypertension (Fig. 6). Indeed, there is evidence for alterations of the 12- and 15LOX enzymes and metabolites both in humans with essent
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br Discussion Elevated blood BCAA
2024-11-18

Discussion Elevated blood BCAA levels are a common feature of a developed pathophysiological state characterized by obesity and IR [4]. It has been suggested that this profile is part of a panel of biomarkers able to predict the onset of more severe complications like diabetes in humans [14]. In
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