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Fatty acids have been repeatedly
2022-06-09
Fatty acids have been repeatedly shown to increase the responsiveness of pancreatic islets to glucose both in vitro and in vivo[6]. The recent identification of GPR40 as a receptor for free fatty acids that is localized to the pancreatic islet cells has therefore stimulated interest in obtaining sma
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An important difference between glucokinase and the
2022-06-09
An important difference between glucokinase and the other hexokinases is that it has a much lower affinity for glucose, such that it is not saturated at physiological blood glucose concentrations (Wilson, 1995, Wilson, 1997, Wilson, 2003, Wilson, 2004, Cárdenas et al., 1998). In addition, glucokina
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Herein in consider of the high similarity
2022-06-09
Herein, in consider of the high similarity between GR HBP site and AR HBP site, we applied rational drug design strategy to develop AR/GR antagonists based on the chemical structures of antiandrogens and crystal structure of GR. The following bioassay identified Z19 as a dual AR/GR antagonist. Z19 i
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A pooled overall survival analysis at year showed no differe
2022-06-09
A pooled overall survival analysis at 1year showed no difference in survival between the two study arms, although these studies were not designed or powered to demonstrate a survival benefit. Among the 979 total patients in both ROMANA 1 and 2, about 55% continued on to the ROMANA 3 trial. That tria
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br Introduction Connexins are transmembrane proteins
2022-06-09
Introduction Connexins are transmembrane proteins that allow the exchange of molecules with the extracellular environment or adjacent GSK343 via channels in the plasma membrane. Intercellular communication and exchange of biologically active molecules, salts, and nutrients to the extracellular e
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With rare exceptions the biological role of secretase cleava
2022-06-09
With rare exceptions, the biological role of γ-secretase cleavage of substrates other than Notch 1 has been ignored during proof of concept preclinical repurposing studies. For example, in the GSI AD trial, many individuals noted changes in hair color, apparently due to inhibition of tyrosinase, an
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Further insight in how exactly
2022-06-09
Further insight in how exactly galanin might inhibit seizures was obtained from galanin transgenic mice. It occurred that the altered susceptibility to seizures was in direct correlation with glutamate release from hippocampal slices obtained from these animals (Fig. 2(b)). While no differences were
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Introduction Osteoclasts are large multinuclear cells that a
2022-06-09
Introduction Osteoclasts are large, multinuclear Belinostat that are responsible for the resorption (breakdown) of bone [1]. Together with osteoblasts, the bone forming cell, they maintain the integrity of the skeleton through constant resorption and repair of bone. Osteoclast precursors of monocy
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In enzyme assays it is convenient to
2022-06-09
In enzyme assays, it is convenient to quantify the product formed in the enzyme reaction, where a decrease in the concentration of product indicates enzyme inhibition [35], [36], [37], [38]. In the present study, substrates were carefully chosen so that they are specific to each enzyme. Known natura
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Enhancer of Zeste Homolog EZH is a core
2022-06-09
Enhancer of Zeste Homolog 2 (EZH2) is a core component of the Polycomb Repressive Complex2 (PRC2) which also includes SUZ12 and EED. PRC2 represses gene transcription through trimethylation of Lys27 of histone H3 (H3K27), and contribute to the maintenance of cell identity, DZNep regulation and onco
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Tyr phosphorylation of AnxA was first reported to be
2022-06-09
Tyr23 phosphorylation of AnxA2 was first reported to be involved in endocytosis, particularly in the internalisation of the insulin receptor [20]. Phosphorylated Tyr23 seems to be necessary for the stable association of AnxA2 with endosomes, and for their early-stage transport [14]. The role of Anx
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A more quantitative view of
2022-06-08
A more quantitative view of kinase specificity suggests a continuum of phosphorylation rates for the various substrates of a particular kinase (Figure 4A). Such differences in ‘substrate quality’ can arise from variations in phosphorylation site or docking sequences and may explain why the timing or
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Molecular modeling of the sGC H NOX domain has placed
2022-06-08
Molecular modeling of the sGC H-NOX domain has placed the β1-domain Cys, β1-C78 and β1-C122, close to the heme binding pocket; specifically, the β1-C78 is placed diametrically opposite to β1-H105, the residue responsible for coordinating the heme iron [42,43]. β1-C78 is enclosed in a highly Pregneno
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Entinostat The rapid actions of glucocorticoids range from t
2022-06-08
The rapid actions of glucocorticoids range from the production of endocannabinoid as a retrograde messenger [9], to regulation of ion channels [10], [11], to inhibitory effects on immune Entinostat [12], [13], [14]. Many different kinase signaling pathways have been implicated in the rapid actions o
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The second experiment investigated the possible neuronal
2022-06-07
The second experiment investigated the possible neuronal mechanism underlying the effect of acupuncture. The baseline level of methamphetamine consumption in each group was similar, as in the first experiment (Fig. 2A). Acupuncture at HT7 also significantly inhibited the methamphetamine self-adminis
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