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Our previous high throughput screening HTS campaign using
2020-01-11
Our previous high-throughput screening (HTS) campaign using automated, robust, and sensitive fluorescence based 5 alpha reductase inhibitor assay [10], [11] led to the identification of several EPAC specific inhibitors (ESIs), and was subsequently followed by extensive hit-to-lead optimizations [20
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br Significance Ubl post translational
2020-01-11
Significance Ubl post-translational modifications are potential targets for developing novel therapeutics for life-threatening diseases, such as c-Myc- and KRas-driven cancers that lack targeted therapy. However, only a few drugs are available to target these modifications. This lack of drugs hig
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br Author contribution br Acknowledgements We want to thank
2020-01-11
Author contribution Acknowledgements We want to thank Dr. Manuel Rodriguez, Dr. Ch. Blattner, Dr. Jorge Moscat, Dr. Erwin Knecht and Dr. Peter Tontonoz for materials. This work has been supported by grants from the Spanish Ministry of Education and ScienceSAF2011-27442 and a grant from General
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Our finding that VEGF A induced
2020-01-10
Our finding that VEGF-A induced downregulation of EphB4 is VEGFR2 dependent (Fig. 4A) is not surprising because VEGFR2 is the primary signaling receptor of VEGF-A in EC [34]. However, our finding that VEGF-A induced upregulation of dll4 psoralen sale is not inhibited by VEGFR2 inhibition suggests t
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The question remains however as to the downstream signaling
2020-01-10
The question remains, however as to the downstream signaling by Epacs that contributes to persistent sensitization of sensory neurons. Activation of the Ras family of GTPases by Epac1 (RapGEF3) or Epac2 (RapGEF4) (Bos, 2003, de Rooij et al., 1998) is linked to a number of downstream signaling effect
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We postulate that OT contained in milk during early
2020-01-10
We postulate that OT contained in milk during early postnatal development causes a mild enteroprotective preconditioning of the ER (Fig 9). This is perhaps akin to a mechanism shown by others [50], [51], [52], which is characterized by selective activation of the IRE1a/XBP1/eIF2a (via PKR) UPR pathw
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PF-3758309 The four other mutations S T V I T
2020-01-10
The four other mutations (S281T, V317I, T328A and A329S) were not detected in the absence of the A286S. This could suggest that when all of them are present, there would be a tri-dimensional structural modification that would interfere with the binding of the insecticide and produce different levels
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An Emerging Role for the EphrinB EphB RASA Signaling Axis
2020-01-10
An Emerging Role for the EphrinB2-EphB4-RASA1 Signaling Axis in Human Congenital Cerebrovascular Disorders Normal vascular development includes de novo blood vessel formation from endothelial cells (ECs) (vasculogenesis) 1, 2, expansion of the network through vessel sprouting, splitting, and remode
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To compare the phage of the th round results we
2020-01-10
To compare the phage of the 4th round results, we conducted isolated single rounds of FGE screening as described above for the 4 individual phage 4(1), 4(2), 4(3), and NC then determined the number of colony forming units afforded by cleavage from the support. Interestingly, we found that the 4(2) s
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Some antioxidants including N acetylcysteine and SOD have be
2020-01-10
Some antioxidants, including N-acetylcysteine and SOD, have been shown to decrease collagen deposition and protect the lungs in various animal models and even in clinical trials (Chan et al., 2013, Loomis-King et al., 2013, Rafii et al., 2013, Teixeira et al., 2008, Wang et al., 2013). Bleomycin-ind
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br Discussion Nowadays data of
2020-01-10
Discussion Nowadays, data of uncommon EGFR mutations are limited, considering that patients carrying these rare alterations are usually excluded from clinical trials. Available survival data of activity of EGFR TKIs on this class of mutations, coming from a small number of usually retrospective s
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Introduction Innate lymphoid cells ILCs are recently
2020-01-10
Introduction Innate lymphoid Verteporfin (ILCs) are recently described immune cells of lymphoid origin and include cytotoxic natural killer (NK) cells and interleukin-7 receptor alpha (also known as CD127)+ subsets, which, similar to T helper (Th) lymphocytes, can be distinguished on the basis of
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Other GPCRs notable for changes in expression
2020-01-09
Other GPCRs notable for changes in expression on CLL cells include upregulation of the thromboxane A2 receptor TBXA2R mRNA [61] and up and downregulation of mRNA and protein from the neurotensin receptors NTSR2 and NTSR1, respectively [62]. The Eμ-TCL1 mouse model of CLL has been used to study mult
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The RING domain was previously considered
2020-01-09
The RING domain was previously considered sufficient to confer ubiquitination by RING-type E3 ligases. However, recent reports have shown that sequences closest to the RING domain are also important in E3 ligase function. Residues like Tyr193 in RNF4 [40], Phe296 and Arg294 in BIRC7 [31], and Lys65
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GLP also showed cardioprotective effects i e infarct size
2020-01-09
GLP-1 also showed cardioprotective effects (i.e., infarct size reduction and ejection fraction improvement) in experimental models of myocardial ischemia-reperfusion injury by suppressing caspase-3 activation and preventing apoptosis of cardiomyocytes [[50], [51]]. Of note, such a cardioprotection w
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