An experimental muon source(EMuS) will be built at the China Spallation Neutron Source(CSNS). In phase I of CSNS, it has been decided that EMuS will provide a proton beam of 5 kW and 1.6 GeV to generate muon beams. A ...An experimental muon source(EMuS) will be built at the China Spallation Neutron Source(CSNS). In phase I of CSNS, it has been decided that EMuS will provide a proton beam of 5 kW and 1.6 GeV to generate muon beams. A 128-channel muon spin rotation/relaxation/resonance(μSR) spectrometer is proposed as a prototype surface muon spectrometer in a sub-branch of EMuS. The prototype spectrometer includes a detection system, sample environment, and supporting mechanics. The current design has two rings located at the forward and backward directions of the muon spin with 64 detectors per ring. The simulation shows that the highest asymmetry of approximately 0.28 is achieved by utilizing two 10-mm-thick brass degraders. To obtain the optimal asymmetry, the two-ring structure is updated to a four-ring structure with 32 segments in each ring. An asymmetry of 0.42 is obtained through the simulation, which is higher than that of all the current μSR spectrometers in the world.展开更多
Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are inv...Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s disease.Therefore,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and neuroinflammation.To better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor UNC0642.We found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)mRNA.Accordingly,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control group.We also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a inhibitor.To confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative insult.In this setting,treatment with G9a inhibitor increases both cell survival and antioxidant enzymes.Moreover,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and apoptosis.In addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers expression.Finally,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a inhibition.Altogether,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.展开更多
基金supported by the National Natural Science Foundation of China(No.11527811)the Key Program of State Key Laboratory of Particle Detection and ElectronicsA part of the work performed in the UKRI ISIS Detector Group was sponsored by the China Scholarship Council
文摘An experimental muon source(EMuS) will be built at the China Spallation Neutron Source(CSNS). In phase I of CSNS, it has been decided that EMuS will provide a proton beam of 5 kW and 1.6 GeV to generate muon beams. A 128-channel muon spin rotation/relaxation/resonance(μSR) spectrometer is proposed as a prototype surface muon spectrometer in a sub-branch of EMuS. The prototype spectrometer includes a detection system, sample environment, and supporting mechanics. The current design has two rings located at the forward and backward directions of the muon spin with 64 detectors per ring. The simulation shows that the highest asymmetry of approximately 0.28 is achieved by utilizing two 10-mm-thick brass degraders. To obtain the optimal asymmetry, the two-ring structure is updated to a four-ring structure with 32 segments in each ring. An asymmetry of 0.42 is obtained through the simulation, which is higher than that of all the current μSR spectrometers in the world.
基金supported by the Ministerio de Economía,Industria y Competitividad(Agencia Estatal de Investigación,AEI,to CGF and MP)Fondo Europeo de Desarrollo Regional(MINECO-FEDER)(PID2022-139016OA-I00,PDC2022-133441-I00,to CGF and MP),Generalitat de Catalunya(2021 SGR 00357+3 种基金to CGF and MP)co-financed by Secretaria d’Universitats i Recerca del Departament d’Empresai Coneixement de la Generalitat de Catalunya 2021(Llavor 00086,to CGF)the recipient of an Alzheimer’s Association Research Fellowship(AARF-21-848511)the Agència de Gestiód’Ajuts Universitaris i de Recerca(AGAUR)for her FI-SDUR fellowship(2021FISDU 00182).
文摘Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s disease.Therefore,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and neuroinflammation.To better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor UNC0642.We found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)mRNA.Accordingly,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control group.We also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a inhibitor.To confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative insult.In this setting,treatment with G9a inhibitor increases both cell survival and antioxidant enzymes.Moreover,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and apoptosis.In addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers expression.Finally,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a inhibition.Altogether,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.
