Analytical methodologies for sensing catechol-O-methyltransferase activity and their applications

Mammalian catechol-O-methyltransferases(COMT)are an important class of conjugative enzymes,which play a key role in the metabolism and inactivation of catechol neurotransmitters,catechol estrogens and a wide range of endobiotics and xenobiotics that bear the catechol group.Currently,COMT inhibitors are used in combination with levodopa for the treatment of Parkinson’s disease in clinical practice.The crucial role of COMT in human health has raised great interest in the development of more practical assays for highly selective and sensitive detection of COMT activity in real samples,as well as for rapid screening and characterization of COMT inhibitors as drug candidates.This review summarizes recent advances in analytical methodologies for sensing COMT activity and their applications.Several lists of biochemical assays for measuring COMT activity,including the probe substrates,along with their analytical conditions and kinetic parameters,are presented.Finally,the challenges and future perspectives in the field,such as visualization of COMT activity in vivo and in situ,are highlighted.Collectively,this review article overviews the practical assays for measuring COMT activities in complex biological samples,which will strongly facilitate the investigations on the relevance of COMT to human diseases and promote the discovery of COMT inhibitors via high-throughput screening.

Prospects for the detection rate of very-high-energyγ-ray emissions from shortγ-ray bursts with the HADAR experiment

The observation of short gamma ray bursts(SGRBs)in the TeV energy range plays an important role in understanding the radiation mechanism and probing potential new physics,such as Lorentz invariance violation(LIV).However,no SGRBs have been observed in this energy range owing to the short duration of SGRBs and the weakness of current experiments.New experiments with new technology are required to detect the very high energy(VHE)emission of SGRBs.In this study,we simulate the VHE γ-ray emissions from SGRBs and calculate the annu-al detection rate with the High Altitude Detection of Astronomical Radiation(HADAR)experiment.First,a set of pseudo-SGRB samples is generated and checked using the observations of the Fermi-GBM,Fermi-LAT,and Swift-BAT measurements.The annual detection rate is calculated from these SGRB samples based on the performance of the HADAR instrument.As a result,the HADAR experiment can detect 0.5 SGRBs per year if the spectral break-off of γ-rays caused by the internal absorption and Klein-Nishina(KN)effect is larger than 100 GeV.For a GRB090510-like GRB in HADAR's view,it should be possible to detect approximately 2000 photons considering the internal absorption and KN effect.With a time delay assumption due to LIV effects,a simulated light curve of GRB090510 has evident energy dependence.We hope that the HADAR experiment can perform SGRB observa-tions and test our calculations in the future.