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As mentioned above variation of the A ring
2023-12-16
As mentioned above, variation of the A-ring was undertaken in order to improve microsomal stability and kinase selectivity relative to PI-3065 (). 1-Imidazole-2-carboxamides with substitution at the 4-position (–) were mostly tolerated with 4-cyano-imidazole-2-carboxamide () having comparable inhib
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Earlier studies showed that exposure of cells to IR caused
2023-12-16
Earlier studies showed that exposure of cells to IR caused ATM-dependent phosphorylation of 53BP1, as judged by electrophoretic mobility shift [24], [25], [26]. To date, the only known in vivo 53BP1 phosphorylation site(s) are Ser25 and possibly Ser29 [27]. In the course of our studies, we noticed t
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In addition to connecting high
2023-12-16
In addition to connecting high ARG1 levels with DNMT3A/TET2 mutations in MDS/CMML patient biopsies, we also wanted to address the cell type demonstrating elevated ARG1. Following our mouse work, we hypothesized that overexpression of this protein would be found in myelomonocytic cddo including macr
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br Experimental section br Acknowledgment S B T is
2023-12-16
Experimental section Acknowledgment S.B.T. is grateful to the Deutsche Forschungsgemeinschaft (DFG), the Wilhelm Sander-Stiftung and Interdisciplinary Center for Molecular Materials (ICMM) for generous research support. M.M. greatly acknowledges the experimental support and the scientific cont
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Consistent with the in vitro results memantine ameliorated A
2023-12-15
Consistent with the in vitro results, memantine ameliorated Aβ-induced cytotoxicity in rat primary cortical cultures. Studies reported that memantine protected neurons against the damage caused by aggregated Aβ40 or Aβ42 oligomers in vivo[26], [27]. These results suggest that, in addition to its neu
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At the organismal level skeletal muscle lung
2023-12-15
At the organismal level, skeletal muscle, lung and adipose tissues mediate net de novo synthesis and release of glutamine, whereas net glutamine catabolism occurs in the kidney [7]. The liver exhibits net glutamine consumption coupled to urea production in the post-absorptive state, and net glutamin
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Overexpression of AR in a
2023-12-15
Overexpression of AR in a transgenic mouse model leads to a capsular cataract phenotype involving proliferation and formation of a fibrotic plaque of cells reminiscent of cells at the posterior Beta-Lapachone in PCO [17]. To investigate the molecular mechanism that could link AR expression to this
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Nelfinavir br Results br Discussion Tapinarof
2023-12-15
Results Discussion Tapinarof (GSK2894512) is a naturally derived investigational topical medicine with demonstrated clinical efficacy for patients with AD and psoriasis (Bissonnette et al., 2010, Bissonnette et al., 2012a). The drug substance is a polyphenol produced by bacteria that is struct
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As an alternative to chronic receptor blockade we have
2023-12-15
As an alternative to chronic receptor blockade, we have been targeting adenosine kinase (ADK) – an astrocyte-based enzyme that catalyses the phosphorylation of adenosine, as a means to modify Cinchonidine synthesis adenosinergic signalling (Boison, 2006, Etherington et al., 2009). Up-regulating ADK
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br Results br Discussion Today enzymes play important roles
2023-12-15
Results Discussion Today, enzymes play important roles in various fields. A good assay for enzyme activity is of great value, especially when it has good specificity, sensitivity, reproducibility and economy. ADK is the first identified enzyme in the metabolic pathway of adenosine salvage [15,
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For comprehensive understanding of actin myosin XI
2023-12-15
For comprehensive understanding of actin-myosin XI as a control network, it will be necessary to determine the functions of all the myosin XI and NMS-1286937 receptor isoforms. However, it is difficult to reveal the function of individual myosin XI isoforms because most myosin XI single knockouts e
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Introduction Chronic inflammation is increasingly known
2023-12-15
Introduction Chronic inflammation is increasingly known as one of the most critical etiological factors in gastrointestinal (GI) cancers (Lee et al., 2016; Wang and Cho, 2015). Overexpression of 5-lipoxygenase (5-LOX), 5-LOX-activating protein (FLAP), as well as other leukotriene (LT) biosynthetic
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Five alternatively spliced isoforms of ATX have
2023-12-15
Five alternatively-spliced isoforms of ATX have been described and all are catalytically active [16], [17]. The original ATX described in 1992 is termed ATXα, whereas the most abundant isoform is ATXβ and is the same isoform responsible for plasma lysoPLD activity [18]. Full length ATX is synthesize
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Phagosomes acquire some hydrolases early during their journe
2023-12-15
Phagosomes acquire some hydrolases early during their journey from the cell surface to lysosomes. An example for such hydrolase is cathepsin H which is most concentrated in the early phagosome at a pH of approximately 6.3 (Claus et al., 1998), the pH optimum of enzyme activity (Schwartz and Barrett,
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In response to DSB the lesion
2023-12-15
In response to DSB, the lesion recognition factor Mre11-Rad50-Nbs1 (MRN) complex helps the recruitment of ATM to the damage site and its activation by phosphorylation [29]. However, whether UV-damage recognition factors directly influence ATR and ATM recruitment and their phosphorylation is not clea
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