• Interestingly transgenic mice that constitutively express ac

  2021-12-20

  

  Interestingly, transgenic mice that constitutively express active FXR in the intestine (iVP16FXR) are protected from chemically-induced and genetically-induced cholestasis. This protective effect is attributed to the induction of intestinal FGF15 and repression of hepatic Cyp7a1 expression, downregu

• From a cell signaling perspective given the

  2021-12-20

  

  From a cell signaling perspective, given the importance of agonist-directed signaling and biased agonism, one goal of this research update was to review the known contributions of G protein-dependent versus β-arrestin-dependent signals toward promotion of beneficial functions that FFA4 facilitates.

• The pharmacokinetic properties of were amenable to oral

  2021-12-20

  

  The pharmacokinetic properties of 12 were amenable to oral dosing allowing in vivo comparison to 6. Compared to a maximum efficacious dose of 6 (60mg/kg), 12 demonstrated improved glycemic control during OGTT in high-fat fed/STZ treated (HF/STZ) and BDF/diet-induced obesity (DIO) mouse models of typ

• br Results br Discussion In this

  2021-12-20

  

  Results Discussion In this study, six new T30695 variants were synthesized with the acyclic R or S glycerol linker instead of GDC-0084 unit at 4, 8 or 12 T residue. Based on our previous studies on TBA-GQ, this type of modification should provoke local changes in GQ conformations in the final

• br Acknowledgement The authors would like

  2021-12-20

  

  Acknowledgement The authors would like to thank the University of Johannesburg and the National Research Foundation for the financial support. Mr. D Harris and Dr. R Meyer from Shimadzu South Africa are thanked for their technical support. Prof Ian Dubery is thanked for access to the LC-MS instru

• In the present study we investigated the mechanisms underlyi

  2021-12-20

  

  In the present study, we investigated the mechanisms underlying the ability of 5-FU to modify histone acetylation. Our results suggested that 5-FU induces global histone de-acetylation in CRC by promoting the degradation of p300 and CBP, two important homologous HATs catalyzing acetylation at multip

• Noticeably aminopyrimidine analogs are the most widely publi

  2021-12-20

  

  Noticeably, aminopyrimidine analogs are the most widely published H4R antagonists and it was Bayer who first disclosed two series of 2-aminopyrimidine compounds possessing significant H4R functional activity. Subsequently, further 2-aminopyrimidine H4R antagonists were published by Pfizer (ZPL-38937

• Fmoc-Gln(Trt)-OH Reactivation of memory engram neurons under

  2021-12-20

  

  Reactivation of memory engram neurons underlies memory retrieval. Neurons activated during memory formation are reactivated during the memory test 24, 25, 32. The reactivation is observed in the cerebral cortex as well as in the hippocampus and amygdala 33, 34. The ratio of the reactivation correlat

• br Conflict of interest br Funding This work

  2021-12-20

  

  Conflict of interest Funding This work was supported by the National Institutes of Health MSK Cancer Center Support Grant/Core Grant [P30 CA008748]. The funding source had no involvement in the study design; in the collection, analysis and interpretation of data; in the writing of the report;

• HDAC enzymes oppose the effects of HATs by

  2021-12-18

  

  HDAC enzymes oppose the effects of HATs by reversing lysine acetylation, an action that restores the positive charge of the lysine thus stabilizing the local chromatin structure. By removing acetyl groups from ε-amino lysines of proteins, HDACs not only alter transcription, but also promote either t

• NGS substitution linkage analysis and haplotype reconstructi

  2021-12-18

  

  NGS substitution linkage analysis and haplotype reconstruction was previously only used for short genome segments and not in the context of antiviral resistance. We optimized this approach to cover a complete viral protein and major DAA target, enabling us to investigate resistance associated NS3P h

• Several compounds have been described in the literature as i

  2021-12-18

  

  Several compounds have been described in the literature as inhibitors of the sGC. Among them, methylene blue and LY83583 () are not direct sGC inhibitors, but rather block cGMP formation by generating superoxide anion radicals that deactivate NO. Despite their extensive use in plethora of research s

• We have shown previously that

  2021-12-18

  

  We have shown previously that activation of the TGFβ/Smad signaling pathway in keratinocytes regulates 5-ht2 cytoskeleton organization via non-genomic and genomic mechanisms and that RhoB gene is a target of Smad proteins [12,13]. Although the role of RhoB in early non-genomic TGFβ-induced cell resp

• Subcellular domains where Rac is

  2021-12-18

  

  Subcellular domains where Rac is active show limited Rho activity and vice versa (Fig. 4). This distinctive patterning in Rho activity is achieved via the downstream Rac effector Par6, an important part of the so-called Par polarity complex. In primary epithelium, the cytoskeleton and associated Rho

• The ability of FFA to elevate

  2021-12-18

  

  The ability of FFA4 to elevate intracellular levels of Ca2+5, 38, 39, 40 provided early predictions of a key role of the phosphoinositidase C-linked G proteins Gq and/or G11 in transduction of signals from this receptor, while later studies that examined production of inositol phosphates [41] provid

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