• Despite the importance of intratumor phenotypic heterogeneit

  2021-09-15

  

  Despite the importance of intratumor phenotypic heterogeneity for tumor progression and therapy resistance (Marusyk et al., 2012, Marusyk and Polyak, 2010), our understanding of regulators of this process and our ability to modulate them are very limited. Recent advances in genomic sequencing and si

• br Conflicts of interest br

  2021-09-15

  

  Conflicts of interest Significance p53 is required for the induction of cell senescence to limit the proliferation of polyploid cells. We found that Hippo signal deficiency or Yap activation in mouse livers result in polyploid formation and polyploid cell growth. The combined loss of Hippo sig

• The second approach to optimizing microsomal

  2021-09-15

  

  The second approach to optimizing microsomal stability in this series involved the strategic positioning of steric bulk along the tether as a means of encumbering the access of oxidative enzymes to the methylene bridge. This approach has been employed in other P2-P4 macrocyclic inhibitors of NS3/4A

• Chronic exposure of cells to cytotoxic drugs can

  2021-09-15

  

  Chronic exposure of cells to cytotoxic drugs can result in the selection of multiple phenotypic and genetic changes. Thus, the use of MCF7/VP cells, which were selected for resistance to VP-16, was potentially problematic. However, a thorough characterization of MCF7/VP cells demonstrated that they

• br Results br Discussion We have reported the crystal struct

  2021-09-14

  

  Results Discussion We have reported the crystal structures of VcmN, the high-resolution structures of this MATE transporter from a pathogenic bacterium. The structures display distinct conformations of TM1, as a consequence of their unique hydrogen-bonding networks. We interpret this result to

• We recently reported the first cyclopropene

  2021-09-14

  

  We recently reported the first cyclopropene-analog of the amino NIBR189 neurotransmitter glutamate (Fig. 2A) [27]. This first-generation cyclopropene-glutamate expanded the only other documented report of a cyclopropene-neurotransmitter (cyclopropene-GABA analog by Reissig and coworkers) [28]. We ob

• The caseins are a family of milk phosphoproteins

  2021-09-14

  

  The caseins are a family of milk phosphoproteins whose biological function is to provide supersaturating concentrations of calcium, phosphates, and essential Balaglitazone synthesis to the neonate (Vonderhaar and Ziska, 1989). α- and β-caseins, the most abundant of the milk caseins, are described a

• br Involvement of gap junctions

  2021-09-14

  

  Involvement of gap junctions and Panx1 in spinal cord processing of pain information Several studies indicated that GJs in the CNS contribute to pain. A common finding in such studies is that intrathecal administration of GJ blocker attenuates pain behavior. For example, intrathecal CBX attenuate

• Because of its role in the

  2021-09-14

  

  Because of its role in the cleavage of Aβ and the fact that many genetic forms of AD are caused by mutations in the enzyme, GS has long been a target for drug development, though previous clinical trials of Semagacestat, a GS inhibitor, have failed due to an increase in skin cancer, and a decrease i

• br Materials and methods br Results and

  2021-09-14

  

  Materials and methods Results and discussion Conclusions Acknowledgments The authors are grateful to Dr. N. Prevete for providing the human AGS shCTR and AGS shFPR2 cells. This work was supported by POR Campania FSE 2007-2013 Project CREME and Ministry of Health, Italy, RF-2011-02349269.

• br Conclusion In summary a series of novel GPR agonists

  2021-09-14

  

  Conclusion In summary, a series of novel GPR40 agonists bearing phenylpropiolic prolyl hydroxylase motif with favorable metabolic stability were prepared and evaluated for their activities as GPR40 agonists. Among them, compound 9 was identified as a structurally distinct GPR40 agonist possessing

• To identify genes with significant expression differences

  2021-09-14

  

  To identify genes with significant rotenone differences, we performed differential gene expression analysis between the two individuals with TRRAP variants (combined as biological replicates) and two unaffected controls. Gene ontology (GO) enrichment analysis of these genes with the GOrilla web app

• GGsTop receptor The transcription factor Nrf is a master

  2021-09-14

  

  The transcription factor Nrf2 is a master regulator of cytoprotective responses to endogenous and exogenous stresses caused by reactive oxygen species (ROS) and electrophiles [6]. Nrf2 promoter polymorphisms are significantly associated with the development of gastric mucosal inflammation, either in

• Additionally increased GLO gene expression protein expressio

  2021-09-14

  

  Additionally, increased GLO1 gene expression, protein expression, and activity have been reported in a variety of cancers, including breast,22, 23, 24 pancreatic, melanoma, and prostate.27, 28, 29 Vince and Daluge proposed that inhibitors of GLO1 could serve as anti-tumor agents, by increasing conce

• The structures of KDM A

  2021-09-13

  

  The structures of KDM4A revealed a Cys-His Zn(II) binding site that is close to the substrate binding spot, which bioinformatic analyses indicated was not present in any other histone demethylase subfamily. Therefore, an alternative method to inhibit the KDM4 family (95) would be to use compounds th

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