• Considering these reports and with the aim of

  2020-02-24

  

  Considering these reports, and with the aim of further investigating the mechanism by which the cAMP-Epac/PKA pathway activates eNOS, we have performed imaging experiments evaluating the effect of drugs that increase cAMP or modify its signalling pathways (PKA or Epac activators and inhibitors) on b

• The synthesis of the required substrates is

  2020-02-24

  

  The synthesis of the required substrates is shown in (see for experimental details). Treatment of heterocycle with Adenine HCl under basic conditions afforded a mixture of the mono-substituted product (22%) and the di-substituted compound (38%) which were separated by column chromatography. C

• Several effective strategies have been

  2020-02-24

  

  Several effective strategies have been developed to design activatable MR probes according to the Solomon, Bloembergen and Morgan (SBM) theory, including modulation of the number of inner-sphere water molecules (q), the rotational tumbling time (τ) and the residence lifetime of inner-sphere water mo

• br The classical ubiquitination pathway Ubiquitination is an

  2020-02-24

  

  The classical ubiquitination pathway Ubiquitination is an enzymatic process that involves the addition of an ubiquitin protein to a substrate that usually becomes inactivated followed by degradation in the proteasome; however, several other functions have also been described. For the discovery of

• br Conflicts of interest br Financial support

  2020-02-24

  

  Conflicts of interest Financial support NZ is an Established Investigator of the Dutch Heart Foundation (2013T111) and is supported by an ERC Consolidator grant (617376) from the European Research Council and by a Vici grant from the Netherlands Organization for Scientific Research (NWO; 91818

• br Results br Discussion The structures presented

  2020-02-24

  

  Results Discussion The structures presented here were solved at high A-366 and show in detail how DDR1 achieves high affinity for imatinib and ponatinib, respectively. Both type II inhibitors bind in their more potent extended conformations to the inactive DFG-out conformation of the kinase d

• GNE-317 The CysLT receptor antagonist BayCysLT

  2020-02-24

  

  The CysLT2 receptor antagonist BayCysLT2RA significantly suppressed multiple antigen challenge-induced infiltration of eosinophils and mononuclear GNE-317 into the lung, indicating that CysLT2 receptor activation is involved in leukocyte migration. In contrast to the present finding, Barret et al.

• In the preclinical evaluation of CRF receptor antagonists ef

  2020-02-24

  

  In the preclinical evaluation of CRF1 receptor antagonists, effects were mainly focused on the regulation of hyperactivated HPA axis and the modulation of anxiety or depressive-like behaviors in CRF challenge [16], [17], [18] or stress models [16], [19], [20]. However, it remains to be concluded whe

• There are some limitations to our study First the

  2020-02-24

  

  There are some limitations to our study. First, the small sample size, even if comparable or higher than most studies, did not offer the possibility to consider other variables, such as frequency of use or age of onset. Second, since most subjects did not report current use, we could not analyze sep

• CK comprises a family of serine threonine protein kinases th

  2020-02-24

  

  CK1 comprises a family of serine/threonine protein kinases, that includes different CK1 isoforms namely α, β, δ, ε and γ their various splice variants [56]. It was reported that the pharmacological inhibitor IC261 shows an order of magnitude of higher selectivity for CK1δ or CK1ε isoforms (IC50 of 1

• Since the aggregation of neurotoxic forms of A plays a

  2020-02-24

  

  Since the aggregation of neurotoxic forms of Aβ plays a pivotal role in AD pathogenesis, an approach that using small molecules to bind Aβ monomers and prevent their assembly into cytotoxic oligomers attracts great interest for the development of AD drugs. Therefore, the potential inhibitory activit

• LP a levels are lowered by combined oral

  2020-02-24

  

  LP(a) levels are lowered by combined oral hormone therapy [80], [81], [82], [83], [84], whereas for most studies using transdermal HRT little or no changes have been observed [85], [86], [87]. Oral versus transdermal administration In general most markers are influenced in a similar way by oral

• 77 The Ewing sarcoma breakpoint region gene EWSR is a partne

  2020-02-24

  

  The Ewing sarcoma breakpoint region 1 gene (EWSR1) is a partner in a large, diverse range of mesenchymal (and some nonmesenchymal) tumors (Tables 1 and 2). As the 5′ partner, EWSR1 is able to fuse with an array of genes. These fusions can generate genetically different but phenotypically identical n

• Since OH PGE is a

  2020-02-24

  

  Since 1-OH-PGE2 is a moderately selective EP4 agonist which could bind to mouse EP3 and EP4 with a relatively similar affinity (Kiriyama et al., 1997), we have used a highly selective EP4 agonist CAY10580 to evaluate the involvement of EP4 activation in PGE2-facilitated EP4 internalization and recyc

• Imeglimin hydrochloride It is also critical that APC

  2020-02-22

  

  It is also critical that APC/CCDC20 is inhibited by MCC during the spindle assembly checkpoint, prior to correct chromosome alignment on the mitotic spindle (Box 1, reviewed in 13, 34). As proposed in [13] and demonstrated in [82], human MCC is a heterotetrameric complex consisting of its own molecu

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