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An alternative to the agonist or antagonist potential in
2024-08-31
An alternative to the agonist or antagonist potential in drug discovery is the positive allosteric modulator (PAM) approach, which can augment the normal processes of neurotransmission as opposed to directly replacing or antagonizing them. PAMs are thought to bind to sites that are distinct from the
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br Disclaimer br Conflicts of interest br
2024-08-31
Disclaimer Conflicts of interest Role of the Sponsor Acknowledgements Funding/support: This project was supported by a grant from the Department of Surgery (R5129), Western University and by the Institute for Clinical Evaluative Sciences (ICES) Western site. ICES is funded by an annual g
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Introduction Cancer which is responsible for a million
2024-08-31
Introduction Cancer, which is responsible for a million deaths each year, is universally feared, and approximately 50% of newly diagnosed cases can be cured [1]. The existing cancer treatments, including surgery, chemotherapy, radiotherapy or a combination of them, are quickly losing efficacy. The
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In our previous report we
2024-08-31
In our previous report, we synthesized derivatives with some straight chain residues on the 2-position of the 3-cyanopyridine ring of compound 1. In this time we tried to introduce aromatic ring on the chain of the 2-position. Namely, we replaced the hydroxyl-alkylamino group in the position 2 of t
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br ASK in Huntington s disease and other polyglutamine disea
2024-08-31
ASK1 in Huntington's disease and other polyglutamine diseases The polyglutamine (polyQ) diseases are a group of inherited neurodegenerative disorders caused by the expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats in the coding regions of specific genes, leading to the production
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Nicotinamide Despite these conflicting data about COX
2024-08-31
Despite these conflicting data about COX-2/ER correlations, a large body of evidence supports that elevated COX-2 expression in breast cancer is a constant feature of high stage disease and a predictor of worse outcome. Upregulation of COX-2 protein has been identified in approximately 40% of cases
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Given that neither case is derived from
2024-08-31
Given that neither case is derived from multiplex LOXO-101 with affected individuals, principles of Mendelian segregation cannot be applied to implicate the T201S mutation in causing familial CJD. In addition, like many rare gene variants, it is not possible to apply practice guidelines such as the
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br Removal of therapeutic doses of antibiotics from Marek s
2024-08-31
Removal of therapeutic doses of CCT245737 from Marek’s Disease Vaccines The impact of this change seems to vary widely among operations, probably dependent on the pre-existing quality of hatching egg production, hatchery sanitation, hatchery management, and brooding management. Increases in 7-day
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In our study we provide evidence for the existence of
2024-08-30
In our study we provide evidence for the existence of an endosome-lysosomal pathway for the proteolytic degradation of AR triggered by its interaction with the ESCRT-I component TSG101. The following findings of this study support this notion: (1) We showed that TS101 interacts with endogenous or ec
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Based on our findings in this
2024-08-30
Based on our findings in this work as well as the previous published data in the experimental mice model of RSV infection, we suggest that modulation of 12/15 LOX expression and/or blocking of LOX products such as 12(S)-HETE may represent potential pharmacological approaches to prevent or treat vira
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Another possible scenario is that the same pathologic
2024-08-30
Another possible scenario is that the same pathologic process has different effects in different people. It might be that the pathway outlined in Fig. 6A is operative in some individuals, but other individuals have a factor Q (which could be genetic or environmental) that blocks the effect of A on T
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CGP 53353 br Applications of ATN in clinical trials In
2024-08-30
Applications of ATN in clinical trials In pivotal trials, the use of biomarkers will also have to be considered in the context of regulatory risk and scrutiny. Although an important intended application of the framework is in research studies, its use will undoubtedly impact clinical development
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br Experimental procedures br Results
2024-08-30
Experimental procedures Results Discussion Acknowledgments Introduction β-Adrenergic receptors (β-ARs) belong to the superfamily of membrane proteins termed G protein-coupled receptors. β-ARs are distributed in the effector recombinant insulin of most of the sympathetic nerve fibers,
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br Introduction Nausea and vomiting are among the
2024-08-30
Introduction Nausea and vomiting are among the most distressing side effects associated with chemotherapy in cancer patients (Billio et al., 2010). Severe emesis can negatively affect a patient's nutritional state, ability to work and motivation, which can, in turn, interfere with the clinical co
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While A Rs communicate mainly with the D
2024-08-30
While A1Rs communicate mainly with the D1R subtype [36], A2AR and D2R interaction occurs mainly in basal ganglia. D2Rs colocalizes with A2ARs in this egfr pathway area where they are preferentially localized postsynaptically in the soma and dendrites of GABAergic striatopallidal neurons [69]. This
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