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Several lines of evidence suggest that thermosensation in AF
2021-11-25
Several lines of evidence suggest that thermosensation in AFD is unlikely to be mediated by thermosensitive ion channels. AFD exhibits a steep temperature dependence with a reported Q of >1015 for temperature-evoked current, implying a strong amplification step in the thermotransduction process (Ram
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As more genes were identified to cause IRDs a relatively
2021-11-25
As more genes were identified to cause IRDs, a relatively large proportion were found to either cause multiple phenotypes or multiple inheritance patterns. Out of the 112 autosomal genes that are listed in RETNET (as of July 22, 2016) that are known to cause non-syndromic IRDs (RP, LCA, and CRD), 16
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Furthermore the role of GSK in the
2021-11-24
Furthermore, the role of GSK-3 in the pathogenesis of inflammation has been widely documented as it accompanies inflammatory conditions such as diabetes mellitus, mood disorders, Alzheimer’s disease, cancer (Jope et al., 2007), and has been associated with atherothrombotic CVD events. However, anoth
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In summary we have designed
2021-11-24
In summary, we have designed and optimized a new series of 1,4-dioxycyclohexane GPR119 agonists. SAR studies led to the discovery of the preferred molecule that has potent and efficacious GPR119 activity across species. This lead compound exhibited an excellent ADME and safety profile, and demonstra
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The NVC response in the diseased or aging
2021-11-24
The NVC response in the diseased or aging Alrestatin may be altered, including changes in both the chemical mediators of NVC, ion channel behaviour, and the dynamics of the vascular system. For example, in Alzheimer’s disease the production of NO is shown to be inhibited (Lourenço et al., 2014), hyp
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br Conclusion br Acknowledgements br Introduction Aminobutyr
2021-11-24
Conclusion Acknowledgements Introduction γ- Aminobutyric BIBR 1532 (GABA) is the main inhibitory neurotransmitter in the adult central nervous system. GABA receptors are divided into two classes, GABAA and GABAB. GABAA is an ionotropic receptor that mediates fast GABA responses by opening
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According to the World Health
2021-11-24
According to the World Health Organization, the average global intake of fat has increased by 20 g per person over the last half-century [21]. However, not all fats are the same and it is now well established that saturated and unsaturated fats, as well as trans fats, can act in opposing ways to inf
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The G protein coupled receptor GPR also
2021-11-24
The G protein-coupled receptor, GPR40 (also called FFAR1) responds to medium and long chain unsaturated fatty acids, resulting in increase of insulin secretion during elevated glucose levels. The glucose dependency of insulin secretion makes this receptor a very good target for developing therapies
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Interestingly we have shown that OA required
2021-11-24
Interestingly, we have shown that OA required FFAR4 to induce osteoblast gene expression in MC3T3-E1 pre-osteoblasts, but not to inhibit osteoclastogenesis in RAW264.7 murine macrophages. As previously suggested, FFAR1 may mediate the effects of OA in osteoclasts. However, FFAR1 has also been shown
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br STAR Methods br Introduction
2021-11-24
STAR★Methods Introduction Arsenite is a well-recognized toxic metalloid that commonly presents in the natural environment. Chronic exposure to arsenite can lead to a wide range of adverse health effects to human, including cancers, cardiovascular diseases, diabetes, skin lesion and neurodegene
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DAMPs are endogenous danger signals that
2021-11-24
DAMPs are endogenous danger signals that can initiate and perpetuate a noninfectious salinomycin during cell death [23]. HMGB1 is a well-studied nuclear DAMP in various types of regulated necrosis and has been implicated in the pathogenesis of infection and sterile inflammation. Our current data in
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br Conclusions Osteoclcastogenesis is regulated
2021-11-24
Conclusions Osteoclcastogenesis is regulated by multiple signal transduction pathways. To maintain bone homeostasis, osteoclast cells must achieve a balance regulation of formation, function, and trafficking of its precursors. Here, we proposed a model in which crosstalk between Fas and S1P/S1P1
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Next we were interested in replacing the ketobenzimidazole f
2021-11-24
Next, we were interested in replacing the ketobenzimidazole fragment of our inhibitors with a noncarbonyl bearing heterocycle. We reasoned that if we could replace the carbonyl while maintaining comparable FAAH inhibition, it would provide evidence for a noncovalent mechanism of action. Thus, we eva
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At the molecular level AZ scaffold proteins including piccol
2021-11-24
At the molecular level AZ scaffold proteins including piccolo and bassoon have been shown to directly or indirectly associate with endocytic and actin-binding proteins such as ABP1 (Fenster et al., 2003), profilin, and GIT (Podufall et al., 2014) (Fig. 2B). ABP1 and profilin, via regulating F-actin,
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Histamine which was used as the
2021-11-24
Histamine, which was used as the agonist, had low potencies in our functional experiments when compared to its affinity from binding studies (e.g. Lim et al., 2005). This phenomenon is related to the fact that the coupling of the presynaptic receptor to the transduction machinery and the final funct
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