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br Funding This work was partly supported by the grant
2019-07-10

Funding This work was partly supported by the grant ‘Maria Grazia Cuccoli’ from Fondazione Cassa di Risparmio di Bologna. Declarations of interest Acknowledgements Introduction The main strategy of oncolytic viral therapy is based on the fact that naturally occurring or engineered virus
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Overall the DDR kinase domain has a
2019-07-10

Overall, the DDR1 kinase domain has a typical kinase domain structure and adequate sequence and/or structure similarity with other kinase domains, as shown in Fig. 2, which allow homology modeling of the active and inactive conformations. In addition to conformational changes to the activation loop
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Here we describe a novel series of
2019-07-10

Here, we describe a novel series of arylazoderivatives developed from CAN508, one of the first known selective CDK9 inhibitors. We focused on modification of both ends of parental molecule, CAN508, in order to improve cytotoxicity and CDK activity. We therefore analyzed how changes in molecules will
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Exon encodes a section of the extracellular ligand binding
2019-07-10

Exon 3 encodes a section of the extracellular ligand-binding domain and two variants in the 5′ region were first identified in Drosophila melanogaster (Semenov and Pak, 1999). These variants were initially termed modules 1 and 2 and correspond to exons 3a and 3b, respectively. To date, exon 3 alter
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br Experimental Procedures br Author Contributions M M and M
2019-07-10

Experimental Procedures Author Contributions M.M. and M.T. designed and supervised the study. S.I. conducted the analysis on NOG-rd mice. H.-Y.T., M.F., and T.M. conducted and analyzed MEA. S.I., H.-Y.T., and M.M. performed 3D image analysis. N.K., T.K., M.G., and R.T. planned and established
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br Introduction Cell transplantation therapies using embryon
2019-07-10

Introduction Cell transplantation therapies using embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC)-derived retinal tissue (ESC/iPSC retina) or Sorbitol have emerged as therapeutic options for retinal degeneration following recent breakthroughs. A number of groups have shown tha
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br Materials and methods br
2019-07-09

Materials and methods Results Discussion In this study, we employed a liquid chromatography mass spectrometry (LC–MS)-based metabolomic approach to profile GEF metabolism and bioactivation in human and mouse liver microsomes. Metabolomic approaches rendered us readily screen out the GEF-rel
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The two most important biological machineries controlling pr
2019-07-09

The two most important biological machineries controlling proteostasis, PQC, and degradation are autophagy and the ubiquitin-proteasome system (UPS) (). Autophagy is a lysosome-dependent, tightly regulated catabolic process that degrades unwanted cell organelles and cytoplasmic constituents in lysos
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There have been two reports of tumor
2019-07-09

There have been two reports of tumor shrinkage in response to dasatinib treatment in lung SCC patients harboring the DDR2 kinase domain S768R mutation., In the first case described by Hammerman et al. a combination of erlotinib (an epithelial growth factor receptor inhibitor) and dasatinib was admin
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One possible explanation for differences in the binding abil
2019-07-09

One possible explanation for differences in the binding ability of monomeric versus dimeric forms of DDR2 ECD to collagen could be that the monomeric form only binds to the primary GVMGFO site, whereas dimeric (and oligomeric) DDR2 ECD binds to additional sites on the collagen triple-helical molecul
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Cabazitaxel of We found that E and GEN each
2019-07-09

We found that E2 and GEN each has mostly similar effects on recruitment of the epigenetic modulators to the MB-COMT distal promoter (summarized in Table 2). These effects are associated with increased promoter methylation and gene suppression of COMT. It is noted that the array of epigenetic modulat
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We did not observe inhibition of vCPH by any of
2019-07-09

We did not observe inhibition of vCPH by any of the TCA cycle intermediates (apart from the metal chelators citrate and isocitrate), nor by the factor inhibiting HIF (FIH; a 2OG-dependent asparaginyl hydroxylase) inhibitor N-oxalyl d-phenylalanine (NOF) or the γ-butyrobetaine dioxygenase inhibitor m
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Another layer of CK regulation in the Hh and
2019-07-09

Another layer of CK1 regulation in the Hh and Wnt pathways is to employ different CK1 isoforms to phosphorylate distinct pathway components or even distinct sites on the same substrates. In this regard, it has been shown recently that the membrane-associated CK1 isoform CK1γ, but not the cytosolic i
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There is a considerable molecular genetic
2019-07-09

There is a considerable molecular genetic heterogeneity within ES/PNET. As mentioned above, either or can rearrange with in these gene fusions. Furthermore, for either gene fusion, additional heterogeneity stems from the location of the genomic breakpoints of the translocation, resulting in differen
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Another milestone in the field is the
2019-07-09

Another milestone in the field is the de novo discovery of EPAC2 and EPAC1 specific inhibitors through fluorescence-based HTS assays. Due to the excellent EPAC/PKA selectivity of LB42708 , it has been widely applied as a useful chemical probe to discriminate EPAC related signaling pathways and biol
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