• Suz is required for methyltransferase activity

  2022-01-24

  

  Suz12 is required for methyltransferase activity, silencing function, and PRC2 protein stabilization in somatic and human ESCs (Cao and Zhang, 2004, Pasini et al., 2004, Collinson et al., 2016). Our experiments indicate that, in addition to associating with the H3K27 demethylases KDM6A (UTX) (Wang e

• br Materials and methods br Results br Discussion Early

  2022-01-24

  

  Materials and methods Results Discussion Early studies in the mid 1980s tentatively identified cCMP in tissues using fast atom bombardment MS [3], [4], but specificity and sensitivity of the method are insufficient for unequivocal identification as compared to modern MS analytical methods.

• br Activation of soluble guanylate

  2022-01-24

  

  Activation of soluble guanylate cyclase The molecular steps involved in sGC activation have evolved significantly over the last several years. The key studies are outlined below, but here we provide an overall summary. The activation mechanism of sGC was initially proposed to be relatively simple

• Some biguanides can cross the

  2022-01-24

  

  Some biguanides can cross the mitochondrial membrane and increase L-lactate formation by inhibiting oxidative Potassium Canrenoate [34]. On the other hand, it has also been reported that levels of fasting plasma lactate in T2DM patients are similar regardless of whether or not metformin is administe

• br Surrogate ligands for GPR Although identification of endo

  2022-01-24

  

  Surrogate ligands for GPR35 Although identification of endogenously produced chemicals with agonist action at GPR35 is of considerable importance, the ligands described above are far from ideal to probe the roles of GPR35. Surrogate ligands are therefore required. Until recently, the key GPR35 ag

• For some agonists these stable GPR responses were resistant

  2022-01-24

  

  For some agonists, these stable GPR119 responses were resistant to washing. Thus, sustained activation could continue, for at least a number of hours, even after removal of free agonist. These data are consistent with reports for other GPCR systems that do not desensitize (Calebiro et al., 2009, Fer

• Neostigmine Bromide br Materials and methods br Results br

  2022-01-21

  

  Materials and methods Results Discussion Acknowledgments Introduction As we move into an aging society, there has been a growing interest in neurological disorders [1]. Neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s disease (AD) cause cognitive malfunction

• The following are the supplementary

  2022-01-21

  

  The following are the supplementary data related to this article. Conflict of interest Acknowledgements This work was supported by JSPS KAKENHI Grant Numbers 24770068 and 15K07152. Introduction Aminoacyl-tRNA synthetases (aaRSs) help maintain the genetic code by recognizing their cognate

• Optimization of the tetrahydroindazole series led to the

  2022-01-21

  

  Optimization of the tetrahydroindazole series led to the discovery of two moderately potent γ-secretase modulators, 2-cyclobutane and 2-hydroxy-2-methylpropane which were subsequently evaluated in a kinetic aqueous solubility assay. Unfortunately, neither analog demonstrated improved solubility ()

• The focused set of cyclopentapyrazoles produced

  2022-01-21

  

  The focused set of cyclopentapyrazoles produced six compounds with sufficient activity to warrant the evaluation of kinetic solubility. Despite the improved activity of the series, these compounds remain stalwartly insoluble (), indicating the need for additional chemical modifications which address

• In the upper part of the intestine a

  2022-01-21

  

  In the upper part of the intestine a small amount of conjugated BAs are reabsorbed via passive diffusion, whereas the part of BAs that escape enterohepatic circulation passes into the colon where they undergo bacterial conversions such as deconjugation, dehydroxylation or dehydrogenation, into secon

• Combretastatin A4 br Experimental br Results and discussion

  2022-01-21

  

  Experimental Results and discussion One of the major challenges of oral drug delivery via nanocarriers is the fairly low efficiency of crossing the intestinal barrier. While there is the possibility of a paracellular transport for polar substances below 1000 Dalton [26], the key mechanism of o

• In neurons and neuroendocrine cells the productive fusion

  2022-01-21

  

  In neurons and neuroendocrine cells, the productive fusion pathway is thought to initiate with the Munc18-1/Syx1 complex (Ma et al., 2013, Hughson, 2013, Lai et al., 2017). The Munc13-1 MUN domain is able to catalyze opening of Syx1 (the transition from the Munc18-1/Syx1 complex to the SNARE complex

• We have expanded these studies by doing

  2022-01-21

  

  We have expanded these studies by doing EEG recording in the ET-1 model. Using this technique, we demonstrated that activation of either the ETA CGS 21680 or the ETB receptor induces electrical seizures. ET-1 induced electrical seizures occurred in the presence of either the ETA receptor antagonist

• H R antagonism can prevent seizure development and improve w

  2022-01-21

  

  H3R antagonism can prevent seizure development and improve working memory through the activation of histaminergic neurons (Huang et al., 2004, Zhang et al., 2003). In addition, we have recently found that H3R antagonism protects against ischemia-reperfusion injury via histamine-independent mechanism

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