Drug-associated reward memories are conducive to intense craving and often trigger relapse.Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive proce...Drug-associated reward memories are conducive to intense craving and often trigger relapse.Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is elusive.Here,we used a mass spectrometry-based lipidomic method to evaluate the impact of simvastatin on the mouse brain in a cocaine-induced reinstatement paradigm.We found that simvastatin blocked the reinstatement of cocaine-induced conditioned place preference(CPP)without affecting CPP acquisition.Specifically,only simvastatin administered during extinction prevented cocaine-primed reinstatement.Global lipidome analysis showed that the nucleus accumbens was the region with the greatest degree of change caused by simvastatin.The metabolism of fatty-acids,phospholipids,and triacylglycerol was profoundly affected.Simvastatin reversed most of the effects on phospholipids induced by cocaine.The correlation matrix showed that cocaine and simvastatin significantly reshaped the lipid metabolic pathways in specific brain regions.Furthermore,simvastatin almost reversed all changes in the fatty acyl profile and unsaturation caused by cocaine.In summary,pre-extinction treatment with simvastatin facilitates cocaine extinction and prevents cocaine relapse with brain lipidome remodeling.展开更多
Using the radar reflectivity and intensive rainfall data, artificial seeding effects of convective clouds in Beijing on 8 August 2008, the opening day of the 29th Summer Olympics, were analyzed. The results indicate t...Using the radar reflectivity and intensive rainfall data, artificial seeding effects of convective clouds in Beijing on 8 August 2008, the opening day of the 29th Summer Olympics, were analyzed. The results indicate that, cloud seeding at single operation site for convective clouds invading from southwest direction may sharply mitigate the rainfall observed at leeward automatic weather stations within 5 - 10 min, while enhances the precipitation at a later stage about 10 - 20 min. Cloud seeding effects of operation sites Yuegezhuangxi, Changgouzhen, and Zhoukou, which are placed along the main moving routes or localized developing convective clouds in the west and center parts of Fangshan district, are very conspicuous. Combining the operation sites distribution and radar echoes, it is found that the site Changgouzhen, which is very close to the convective core, plays an essential role in suppressing the growth of convective cloud, reducing the coverage area of intense echoes classified as 45 - 60 dBZ, as well as mitigating the precipitation from neighboring automatic weather stations. Based on radar reflectivity and rainfall data, we find that the clouds over lots of operation sites in eastern Fangshan district are not cold enough to favor glaciogenic seeding with silver iodide, meanwhile, there is not too much precipitation observed.展开更多
The expression of linear DNA sequence is precisely regulated by the three-dimensional(3D)architecture of chromatin.Morphine-induced aberrant gene networks of neurons have been extensively investigated;however,how morp...The expression of linear DNA sequence is precisely regulated by the three-dimensional(3D)architecture of chromatin.Morphine-induced aberrant gene networks of neurons have been extensively investigated;however,how morphine impacts the 3D genomic architecture of neurons is still unknown.Here,we applied digestion-ligation-only high-throughput chromosome conformation capture(DLO Hi-C)technology to investigate the effects of morphine on the 3D chromatin architecture of primate cortical neurons.After receiving continuous morphine administration for 90 days on rhesus monkeys,we discovered that morphine re-arranged chromosome territories,with a total of 391 segmented compartments being switched.Morphine altered over half of the detected topologically associated domains(TADs),most of which exhibited a variety of shifts,followed by separating and fusing types.Analysis of the looping events at kilobase-scale resolution revealed that morphine increased not only the number but also the length of differential loops.Moreover,all identified differentially expressed genes from the RNA sequencing data were mapped to the specific TAD boundaries or differential loops,and were further validated for changed expression.Collectively,an altered 3D genomic architecture of cortical neurons may regulate the gene networks associated with morphine effects.Our finding provides critical hubs connecting chromosome spatial organization and gene networks associated with the morphine effects in humans.展开更多
基金the National Natural Science Foundation of China(81871043 and 82071494)the National Science and Technology Major Project of China(2018ZX09201017 and 2018ZX09201018)the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYGD18024).
文摘Drug-associated reward memories are conducive to intense craving and often trigger relapse.Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is elusive.Here,we used a mass spectrometry-based lipidomic method to evaluate the impact of simvastatin on the mouse brain in a cocaine-induced reinstatement paradigm.We found that simvastatin blocked the reinstatement of cocaine-induced conditioned place preference(CPP)without affecting CPP acquisition.Specifically,only simvastatin administered during extinction prevented cocaine-primed reinstatement.Global lipidome analysis showed that the nucleus accumbens was the region with the greatest degree of change caused by simvastatin.The metabolism of fatty-acids,phospholipids,and triacylglycerol was profoundly affected.Simvastatin reversed most of the effects on phospholipids induced by cocaine.The correlation matrix showed that cocaine and simvastatin significantly reshaped the lipid metabolic pathways in specific brain regions.Furthermore,simvastatin almost reversed all changes in the fatty acyl profile and unsaturation caused by cocaine.In summary,pre-extinction treatment with simvastatin facilitates cocaine extinction and prevents cocaine relapse with brain lipidome remodeling.
文摘Using the radar reflectivity and intensive rainfall data, artificial seeding effects of convective clouds in Beijing on 8 August 2008, the opening day of the 29th Summer Olympics, were analyzed. The results indicate that, cloud seeding at single operation site for convective clouds invading from southwest direction may sharply mitigate the rainfall observed at leeward automatic weather stations within 5 - 10 min, while enhances the precipitation at a later stage about 10 - 20 min. Cloud seeding effects of operation sites Yuegezhuangxi, Changgouzhen, and Zhoukou, which are placed along the main moving routes or localized developing convective clouds in the west and center parts of Fangshan district, are very conspicuous. Combining the operation sites distribution and radar echoes, it is found that the site Changgouzhen, which is very close to the convective core, plays an essential role in suppressing the growth of convective cloud, reducing the coverage area of intense echoes classified as 45 - 60 dBZ, as well as mitigating the precipitation from neighboring automatic weather stations. Based on radar reflectivity and rainfall data, we find that the clouds over lots of operation sites in eastern Fangshan district are not cold enough to favor glaciogenic seeding with silver iodide, meanwhile, there is not too much precipitation observed.
基金supported by the grants from the National Natural Science Foundation of China(Grant Nos.82071494,81871043,32000719,and 81272459)the 1.3.5 Project for Disciplines of Excellence of West China Hospital of Sichuan University(Grant No.ZYGD23011)+3 种基金the China Postdoctoral Science Foundation(Grant No.2021M702362)the PostDoctor Research Project,West China Hospital,Sichuan University(Grant No.2020HXBH010)the Sichuan Science and Technology Program(Grant No.23NSFSC2884)the Science,Technology and Innovation Commission of Shenzhen Municipality(Grant No.ZDSYS20190902093601675),China.
文摘The expression of linear DNA sequence is precisely regulated by the three-dimensional(3D)architecture of chromatin.Morphine-induced aberrant gene networks of neurons have been extensively investigated;however,how morphine impacts the 3D genomic architecture of neurons is still unknown.Here,we applied digestion-ligation-only high-throughput chromosome conformation capture(DLO Hi-C)technology to investigate the effects of morphine on the 3D chromatin architecture of primate cortical neurons.After receiving continuous morphine administration for 90 days on rhesus monkeys,we discovered that morphine re-arranged chromosome territories,with a total of 391 segmented compartments being switched.Morphine altered over half of the detected topologically associated domains(TADs),most of which exhibited a variety of shifts,followed by separating and fusing types.Analysis of the looping events at kilobase-scale resolution revealed that morphine increased not only the number but also the length of differential loops.Moreover,all identified differentially expressed genes from the RNA sequencing data were mapped to the specific TAD boundaries or differential loops,and were further validated for changed expression.Collectively,an altered 3D genomic architecture of cortical neurons may regulate the gene networks associated with morphine effects.Our finding provides critical hubs connecting chromosome spatial organization and gene networks associated with the morphine effects in humans.
