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Because of its role in the
2021-10-23
Because of its role in the cleavage of Aβ and the fact that many genetic forms of AD are caused by mutations in the enzyme, GS has long been a target for drug development, though previous clinical trials of Semagacestat, a GS inhibitor, have failed due to an increase in skin cancer, and a decrease i
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br Acknowledgements The authors have no ethical
2021-10-22
Acknowledgements The authors have no ethical conflicts to disclose. The authors have no conflicts of interest to declare. This work was funded by the Research Council of Lithuania. Introduction This paper studies whether there is a causal influence of the risk-taking incentives provided by op
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br Conclusion Our data allow pharmacological discrimination
2021-10-22
Conclusion Our data allow pharmacological discrimination of diverse of H3 CW069 antagonists that can be linked to their differential efficacy in preclinical and clinical disease settings (Fig. 6). Moreover, we identify the sigma-1 receptor as a common “off target” for H3 antagonists, and that di
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In recent years the Hippo signaling pathway has emerged as
2021-10-22
In recent years, the Hippo signaling pathway has emerged as an important regulator balancing cell proliferation and differentiation [[5], [6], [7]]. The pathway components, first described in the fruit fly Drosophila melanogaster, are highly conserved across different phyla [6]. The signaling pathwa
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Thus both in Drosophila and
2021-10-22
Thus, both in Drosophila and mammals, the Hippo pathway responds to cell–cell junctions via an apical NF2/Mer-containing complex. Indeed, Hippo signalling and NF2 are required for contact inhibition of growth in cell culture, which is thought to reflect an in vivo function as a sensor of tissue crow
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Sugar gliders and hedgehogs are
2021-10-22
Sugar gliders and hedgehogs are insectivores and actively seek arthropods in nightly forays. It is suspected that Triatoma were not feeding on the sugar gliders and hedgehogs, but rather were being eaten. The oral route of infection is often nonfatal and induces a carrier state in South American did
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The effects of opioids such as morphine are
2021-10-22
The effects of opioids such as morphine are mediated through the opioid receptors. Opioid receptors are widely expressed both peripherally and in the CNS (Chen et al., 1993, Evans et al., 1992). The opioid agonist morphine has been shown to amplify the effect of the tubular cell-gp120 interaction on
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br Materials and methods br
2021-10-22
Materials and methods Results and discussion Conclusion A new label-free targeted methodology using two-step fractionation coupled with conventional microflow LC-MS/MS was developed and validated to profile 54 selected clinically relevant human plasma glycoproteins. The developed method has
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br Materials animals and methods br Results br Discussion Th
2021-10-22
Materials, animals and methods Results Discussion This study presents mice with a missense point mutation in R258 of FFAR1 that has functional consequences. Firstly, in islets of Ffar1R258W/R258W mice, both the physiological agonist palmitate and the synthetic agonist TUG-469 were unable to
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br Materials and methods Rat forebrains were
2021-10-22
Materials and methods Rat forebrains were obtained from Sprague–Dawley rats at 2, 7, 14, 21, and 30–35 postnatal days and were homogenized in 1:5 volumes (w/v) of 0.32 M sucrose containing 1 mM EGTA, 1 mM EDTA, 1 μg/ml TPCK, 50 μM leupeptin, and 3 μM antipain with 10 strokes in a glass-teflon hom
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The development of metabolic stable
2021-10-22
The development of metabolic stable, non-peptidergic galanin agonists could be the basis to clinical diagnosis and treatment of tumors with high levels of galanin receptor expression like gliomas and pituitary tumors. As for gliomas, penetration of the blood brain barrier by the compounds might be p
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The mechanisms underlying the inhibitory effects of n FAs
2021-10-21
The mechanisms underlying the inhibitory effects of n-3 FAs on neoplasia have not been completely elucidated. Until recently, the emphasis has been on the ability of n-3 FAs to compete for the pathways that lead to the synthesis of pro-inflammatory eicosanoids from arachidonic acid, an n-6 FA, there
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Despite their undisputed importance however FPR
2021-10-21
Despite their undisputed importance, however, FPR receptors are not in the limelight of GPCR-related research (for review [12] and references therein). We, therefore, draw attention to this GPCR receptor family, in order to re-initiate FPR-related research, particularly in the light of biased agonis
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Herein we report the discovery of
2021-10-21
Herein, we report the discovery of AM-3189 (). AM-3189 maintains the in vivo efficacy of AMG 837 while displaying a superior pharmacokinetic profile and minimal CNS exposure. As we reported previously, activity on the GPR40 receptor varies significantly with substitution at the β-carbon relative to
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Although angiogenesis is crucial for cerebral ischemic rehab
2021-10-21
Although angiogenesis is crucial for cerebral ischemic rehabilitation, the mechanism underlying NGF promotion of angiogenesis is not clear. Previous studies showed that angiogenesis can be promoted by FAK, in a breast cancer model [19]. Recent studies showed that FAK phosphorylation participated in
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