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A has been reported to
2022-11-03

Aβ has been reported to decrease insulin receptors and impair insulin signaling in neurons, preventing phosphorylation of Akt and glycogen synthase kinase 3β (GSK-3β), downstream of insulin signaling, and to increase phosphorylation of tau protein causing neurofibrillary tangles (Tokutake et al., 20
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The SMN and SMN promoters
2022-11-03

The SMN1 and SMN2 promoters are regulated by transcription factors such as E26 transformation-specific domain containing protein (ELK-1) and cAMP response element-binding protein (CREB) 58, 59. Compared with WT animals, mice with SMA exhibit increased and decreased ELK-1 and CREB phosphorylation, re
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br Materials and methods br Conflict of interest br Acknowle
2022-11-03

Materials and methods Conflict of interest Acknowledgments We thank Christine Heiner (Department of Surgery, University of Pittsburgh) for her critical reading of the manuscript. This work was supported by grants from the US National Institutes of Health (R01GM115366, R01CA160417, and R01CA
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For hippocampal asymmetry two SNPs rs and
2022-11-03

For hippocampal asymmetry, two SNPs (rs1476679 and rs4147929) showed significant interaction with diagnosis. They have an inverse effect on asymmetry, which is consistent with their different roles as preventative or risk loci in AD. rs1476679 is intronic in the ZCWPW1 gene, is a histone modificatio
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In AD and possibly other forms of dementia it
2022-11-03

In AD, and possibly other forms of dementia, it has been suggested that tau mislocalization to dendritic spines anticipates neurodegeneration [48]. Accumulation of hyperphosphorylated tau in dendritic spies would cause a derangement of synaptic function, thereby impairing excitatory synaptic transmi
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The present study determined the effect of DCA on VSMC
2022-11-03

The present study determined the effect of DCA on VSMC calcification in vitro and in atherosclerotic ApoE-/- mice in vivo. We found that igf ir non-toxic concentrations of DCA, did not affect VSMC viability, induced calcification of VSMC in culture and increased atherosclerotic vascular calcificati
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To understand the kinase selectivity
2022-11-03

To understand the kinase selectivity profile of this series, ESI-09 , as a representative analog from this series, was profiled against 216 purified protein kinases representing the tyrosine and serine/threonine kinase families using an in-house Caliper EZ Reader mobility shift assay. Assays were c
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The hippocampus is the primary brain structure involved in
2022-11-03

The hippocampus is the primary brain structure involved in learning and memory. The role of hippocampal synaptic plasticity in neurological processes in cognition and depression has been extensively demonstrated. Synaptophysin is a critical substance in synaptogenesis, which is necessary for learnin
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br Role of LPA in tumor
2022-11-03

Role of LPA in tumor angiogenesis and skeletal metastasis The angiogenesis switch is essential for tumor expansion and escape of tumor SYN-117 from the primary site and forming distant metastases. Evidence for the role of LPA2 and LPA3 in the mobility of endothelial cells and the formation of ne
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Having taken a step back from affinity to gain better
2022-11-03

Having taken a step back from affinity to gain better exposure and solubility, we started work to replace the unstable oxazolinone, and address the selectivity over the hERG channel. Keeping in mind the binding mode of the series from crystal structures, triazole was identified as another mildly aci
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Aurora A or B selective and
2022-11-03

Aurora -A or -B selective and pan-aurora inhibitors have demonstrated different preclinical and clinical therapeutic efficacies [2,[19], [20], [21], [22], [23]]. For example, clinical trials for a pan-Aurora inhibitor VX-680 (developed by Vertex) were halted at phase II for toxicity reasons (one cas
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To test the compounds metabolic stability we measured the
2022-11-03

To test the compounds metabolic stability, we measured the half-life of compounds and in mouse hepatic microsomes (1mg/mL) and found them to have modest stability, with half-lives of 7.5 and 2.9min respectively, indicating these compounds may be unsuitable for studies. In order to gain structura
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Previously we have detected the expression of APJ
2022-11-03

Previously, we have detected the expression of APJ receptor on stomach projecting GDC-0994 in DMV, in addition, icv administration of apelin-13 induced a remarkable c-Fos activation in those cells which were previously marked by a retrograde neuronal tracer fast blue (Birsen et al., 2016). Moreover
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br Introduction Heart Failure HF
2022-11-02

Introduction Heart Failure (HF) is a major and growing health challenge in India and the developing countries. It is one of the most important causes of morbidity and mortality in the industrialized world. The incidence and prevalence estimates of HF are unreliable in India because of the lack of
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br Duality of interest br Contribution statement br Acknowle
2022-11-02

Duality of interest Contribution statement Acknowledgments Introduction Rapid, cell surface-initiated steroid actions have been reported for all major groups of steroid hormones and our understanding of membrane-mediated steroid actions has progressed rapidly over the last two decades. M
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