• RSL3 A high throughput screening campaign led to

  2023-01-31

  

  A high-throughput screening campaign led to the discovery of the first series of both potent and selective ATR kinase inhibitors by Vertex Pharmaceuticals (Charrier et al., 2011). One of these compounds, VE-821, was shown to be a potent ATP-competitive inhibitor of ATR with minimal cross-reactivity

• br Antibiotic drug discovery approaches Traditionally novel

  2023-01-31

  

  Antibiotic drug discovery approaches Traditionally, novel Gemfibrozil were largely discovered by phenotypic screening approaches of various sources of compounds, such as natural products isolated from extracts of soil microbes and semi-synthetic or fully synthetic compound libraries derived from

• It has been proposed that angiotensin II

  2023-01-31

  

  It has been proposed that angiotensin II (Ang II) may upregulate COX-2 expression and the subsequent vasoconstrictor prostanoids production through the activation of AT-1 receptors in vascular smooth muscle cells (Hu et al., 2002). Additionally, this peptide is also able to stimulate the generation

• br Introduction Breast cancer is the second most lethal canc

  2023-01-31

  

  Introduction Breast cancer is the second most lethal cancer among women, accounting for approximately 40,000 deaths in the United States in 2015 [1]. The prognosis of breast cancer has improved significantly with the identification of immunohistochemical subtypes that predict response to therapy

• Some of previous immunohistochemical studies have compared t

  2023-01-31

  

  Some of previous immunohistochemical studies have compared the levels of AR expression in low-grade versus high-grade and/or non-muscle-invasive versus muscle-invasive tumors. There was a significant or marginal decrease (Boorjian et al., 2004, Miyamoto et al., 2012b, Rau et al., 2011, Shyr et al.,

• Y27632 receptor br Acknowledgements Dr Paul J Gasser is

  2023-01-31

  

  Acknowledgements Dr. Paul J. Gasser is supported by the National Institutes of Health (grant number R01DA032895), and the Charles E. Kubly Mental Health Research Center. Dr. Christopher A. Lowry is supported by the National Institutes of Health (grant number R21 MH116263), the Department of the N

• Medium spiny neurons MSNs in the striatum start from a

  2023-01-31

  

  Medium spiny neurons (MSNs) in the striatum start from a deeply hyperpolarized resting membrane potential, slowly depolarize and show a delayed start of firing during a current injection (Kawaguchi, 1993, Nisenbaum and Wilson, 1995, Planert et al., 2013). The firing pattern during the current inject

• pde inhibitors Active SI behavior was dose dependently affec

  2023-01-31

  

  Active SI behavior was dose-dependently affected by PACAP treatment (F3,25 = 14.42, p pde inhibitors 1 week later (F3,20 = 8.93, p hypothesis that PACAP causes disruptions in posterror adjustments that are similar to disruptions seen in humans with depression.

• br A Rs which were cloned and then

  2023-01-31

  

  A3Rs, which were cloned and then pharmacologically identified in the early 1990s, are expressed in multiple organs and peripheral tissues including ZJ 43 involved in inflammatory responses (Gessi et al., 2008, Borea et al., 2014). While low levels are expressed in the CNS, A3R agonists produce fun

• Diabetes or inflammation is associated with up

  2023-01-31

  

  Diabetes or inflammation is associated with up-regulation of A2AAR (Pang et al., 2010). High levels of A2AARs are found in macrophages and microglial cells that are poised, on activation, to abrogate the immune response (Trincavelli et al., 2008). In addition, hyperglycemia is associated with increa

• Adenosine is a ubiquitous homeostatic purine

  2023-01-31

  

  Adenosine is a ubiquitous homeostatic purine nucleoside that accumulates extracellularly in response to metabolic stresses such as hypoxia and inflammation. Activation of either G protein-coupled adenosine receptors (ARs; A1R, A2AR, A2BR, and A3R) by extracellular adenosine can modulate cell signali

• Double immunofluorescence staining of Gas and Axl with neuro

  2023-01-31

  

  Double immunofluorescence staining of Gas6 and Axl with neuronal specific nuclear protein (NeuN), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule 1 (Iba-1), demonstrated that Gas6 and Axl are expressed by neurons, astrocytes and microglia/macrophages (Fig. 2). In

• br Acknowledgements We thank Dr Stefan Schulte Merker

  2023-01-31

  

  Acknowledgements We thank Dr. Stefan Schulte-Merker and his group members at the Hubrecht Institute (Utrecht, the Netherlands) for their invaluable support of the zebrafish studies. Our work is supported by grants from the Dutch Cancer Society (KWF) and the Netherlands Organisation for Scientific

• Pompe disease is accompanied by the deficiency of the lysoso

  2023-01-31

  

  Pompe disease is accompanied by the deficiency of the lysosomal α-1,4-glucosidase that makes the TAK-285 unable to hydrolyze glycogen to glucose, thereby resulting in the accumulation of glycogen in lysosomes, especially in skeletal muscles and cardiac tissues. This accumulation results in the stru

• Our results suggest that plasma membrane and a

  2023-01-31

  

  Our results suggest that plasma membrane and a3-containing V-ATPases represent an important and novel target in the development of drugs to limit breast cancer metastasis. That knock-down of a3 has been shown to reduce metastasis of melanoma cells in an in vivo mouse model suggests that this role ma

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