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Results indicated that superfusion of orexin
2022-04-11

Results indicated that superfusion of orexin alone, glutamate alone or orexin-glutamate co-administration significantly increases the spontaneous discharge rate of LC neurons in both morphine dependent and non-dependent rats (Fig. 2, Fig. 3). However, co-application of orexin and glutamate resulted
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Apoptosis a form of programmed cell
2022-04-09

Apoptosis, a form of programmed cell death, is a critical component in maintaining homeostasis and growth in all tissues and plays a significant role in immunity and cytotoxicity [54,55]. Although GR are expressed in all immune cells, the physiological outcomes of GR activation are highly cell type-
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Insulin de sensitization has been
2022-04-09

Insulin de-sensitization has been observed in the brains of people with AD [51], [52], [53] and we previously demonstrated that the GLP-1 analogue liraglutide was able to reverse this [54]. Importantly, Amodiaquine dihydrochloride dihydrate receptor insulin de-sensitization correlates well with cog
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Various strategies have been pursued in the
2022-04-09

Various strategies have been pursued in the search for GIPR antagonists. Antibodies raised against both GIP(1–42) [14], [15] or the GIPR [16], [17], a small molecule antagonist [18], amino Naringin substitutions of GIP(1–42) [19], and various GIP(1–42) truncations and modifications such as e.g. Pro3
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The molecular nature of these putative Ca channels is at
2022-04-09

The molecular nature of these putative Ca2+ Epidermal Growth Factor (EGF), human recombinant is at present unknown. Apart from the NSVDC channel, which is permeable to Ca2+ [27], [15] functional Ca2+ channels have been identified in patch clamp experiments [28]. These channels, which were character
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libraries br Electron crystallographic structures of connexi
2022-04-09

Electron crystallographic structures of connexins The structures of gap junctions are good targets for electron microscopy because they exhibit the characteristic features of self-assembly. Early studies examined the three-dimensional (3D) structures of native gap junction libraries from rodents
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br Structures of human secretase Before
2022-04-09

Structures of human γ-secretase Before the near-atomic resolution structures, the highest resolutions achieved for γ-secretase were 15 and 12Å [19, 21]. The 15-Å structure revealed a dig this chamber in the transmembrane domain and two pores at the top and bottom of γ-secretase, which were specul
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With rare exceptions the biological role
2022-04-09

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, ano
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As shown in Table the results of
2022-04-09

As shown in Table 3, the results of individual prediction modeling with chemicals at 0.4 mM, 0.6 mM, and 0.8 mM would lead to lesser sensitivity of 60.0%, 65.0%, and 65.0%, respectively, in microsome-unused group, and 85.0%, 85.0%, and 90.0%, in microsome-used group. If we consider only the results
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Prior to proceeding to the main tests
2022-04-09

Prior to proceeding to the main tests, essential conditions were optimized. At first, we tested whether the parameters that were successful in inducing LacZ gene for the production of β-galactosidase enzymes in E. coli culture system in our previous study would be sufficient to induce LacZ gene in t
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Analysis of the i motif structures during biased unfolding
2022-04-09

Analysis of the i-motif structures during biased unfolding of G-quadruplexes leads to the conclusion that at acidic pH the i-motif is absolutely unaffected by that process. The hydrogen bonds within the i-motif are intact (Fig. 3D) and they only fluctuate around mean values. On the other hand, the i
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The normal function of the FBPase
2022-04-09

The normal function of the FBPase enzyme is to catalyze the hydrolysis of F1,6BP to F6P. This activity is induced by diabetes and starvation and is increased in diabetic rats. The level of FBPase can be normalized by insulin, however, similar information is not available from diabetic patients. FBPa
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br Declarations of interest br
2022-04-09

Declarations of interest Founding information This work was partially supported by the New Energy and Industrial Technology Development Organization (NEDO) Japan [grant number P03043]; and Grants-in-Aid for Scientific Research [grant number 16H00738 to H.M.] from the Japan Society for the Prom
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br Ethics statements br Introduction Hepatocellular carcinom
2022-04-09

Ethics statements Introduction Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor and the third leading cause of cancer-related mortality worldwide, with rapidly-increasing incidence in recent years [1,2]. Mounting evidence shows that viral hepatitis, toxin exposure, non-a
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The suboptimal trypsin selectivity profile of DPC p http www
2022-04-09

The suboptimal trypsin selectivity profile of DPC423 prompted us to investigate additional P moieties for potency and selectivity. Glycinamide P () showed low nanomolar binding affinity against fXa which suggested that this P moiety sits deeper into the S pocket of fXa. To further elaborate on this
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