Cardiogenic shock is the leading cause of death among patients hospitalized with acute myocardial infarction （MI）. Understanding the mechanisms for acute pump failure is therefore important. The aim of this study is...Cardiogenic shock is the leading cause of death among patients hospitalized with acute myocardial infarction （MI）. Understanding the mechanisms for acute pump failure is therefore important. The aim of this study is to examine in an acute MI dog model whether mitochondrial bio-energetic function within non-ischemic wall regions are associated with pump failure. Anterior MI was produced in dogs via ligation of left anterior descending （LAD） coronary artery, that resulted in an infract size of about 30% of the left ventricular wall. Measurements ofhemodynamic status, mitochondrial function, free radical production and mitochondrial uncoupling protein 3 （UCP3） expression were determined over 24 h period. Hemodynamic measurements revealed a 〉 50% reduction in cardiac output at 24 h post infarction when compared to baseline. Biopsy samples were obtained from the posterior non-ischemic wall during acute infarction. ADP/O ratios for isolated mitochondria from non-ischemic myocardium at 6 h and 24 h were decreased when compared to the ADP/O ratios within the same samples with and without palmitic acid （PA）. GTP inhibition of （PA）-stimulated state 4 respiration in isolated mitochondria from the non-ischemic wall increased by 7% and 33% at 6 h and 24 h post-infarction respectively when compared to sham and pre-infarction samples. This would suggest that the mitochondria are uncoupled and this is supported by an associated increase in UCP3 expression observed on western blots from these same biopsy samples. Blood samples from the coronary sinus measured by electron paramagnetic resonance （EPR） methods showed an increase in reactive oxygen species （ROS） over baseline at 6 h and 24 h post-infarction. In conclusion, mitochondrial bio-energetic ADP/O ratios as a result of acute infarction are abnormal within the non-ischemic wall. Mitochondria appear to be energetically uncoupled and this is associated with declining pump function. Free radical production may be associated with the induction of uncoupling proteins in the mitochondria.展开更多
Pikas(Lagomorpha:Ochotonidae)are small mouselike lagomorphs.To investigate their adaptation to different ecological environments during their dispersal from the Qinghai-Xizang(Tibet)Plateau(QTP),we collected 226 pikas...Pikas(Lagomorpha:Ochotonidae)are small mouselike lagomorphs.To investigate their adaptation to different ecological environments during their dispersal from the Qinghai-Xizang(Tibet)Plateau(QTP),we collected 226 pikas and measured 20 morphological characteristics and recorded habitat information.We also sequenced the genome of 81specimens,representing 27 putative pika species.The genome-wide tree based on 4?090 coding genes identified five subgenera,i.e.,Alienauroa,Conothoa,Lagotona,Ochotona,and Pika,consistent with morphometric data.Morphologically,Alienauroa and Ochotona had similar traits,including smaller size and earlier divergence time compared to other pikas.Consistently,the habitats of Alienauroa and Ochotona differed from those of the remaining subgenera.Phylogenetic signal analysis detected 83 genes significantly related to morphological characteristics,including several visual and hearingrelated genes.Analysis of shared amino acid substitutions and positively selected genes(PSGs)in Alienauroa and Ochotona identified two genes,i.e.,mitochondrial function-related TSFM(p.Q155E)and low-light visual sensitivity-related PROM1(p.H419Y).Functional experiments demonstrated that TSFM-155E significantly enhanced mitochondrial function compared to TSFM-155Q in other pikas,and PROM1-419Y decreased the modeling of dynamic intracellular chloride efflux upon calcium uptake.Alienauroa and Ochotona individuals mostly inhabit different environments(e.g.,subtropical forests)than other pikas,suggesting that a shift from the larger ancestral type and changes in sensory acuity and energy enhancement may have been required in their new environments.This study increases our understanding of the evolutionary history of pikas.展开更多
DEAR EDITOR,Big cats,such as Amur tigers(Panthera tigris altaica)and Amur leopards(P.pardus orientalis),are apex predator and have evolved specialized traits for hunting and carnivory(Moya et al.,2022),thus playing a ...DEAR EDITOR,Big cats,such as Amur tigers(Panthera tigris altaica)and Amur leopards(P.pardus orientalis),are apex predator and have evolved specialized traits for hunting and carnivory(Moya et al.,2022),thus playing a crucial role in maintaining biodiversity and ecosystem integrity by regulating prey-predator dynamics.However,human-induced pressures,habitat fragmentation,and environmental alterations have restricted these species in small and isolated populations.Currently,all extant big cats are categorized as endangered or threatened according to their conservation status.Amur tigers and Amur leopards share overlapping geographic ranges,habitats,and certain prey species in the forests of Northeast Asia(Jiang et al.,2015).To reduce interspecies conflict,these carnivores exhibit differentiated dietary and temporal niches.Amur tigers predominantly prey on large ungulates,while Amur leopards hunt small to medium-sized animals(Sugimoto et al.,2016).Additionally,they occupy different temporal niches,with tigers being active at night and leopards more active during the day.Despite spatial and temporal niche partitioning,interspecific competition between these two species is inevitable.Tigers,benefiting from their greater size,have a competitive advantage over leopards,which can manifest in occasional leopard predation by tigers and declines in leopard populations with increasing tiger density(Jiang et al.,2015).Tigers also displace leopards from marginal habitats in nature reserves where they coexist.展开更多
The high-fidelity(HiFi)long-read sequencing technology developed by PacBio has greatly improved the base-level accuracy of genome assemblies.However,these assemblies still contain base-level errors,particularly within...The high-fidelity(HiFi)long-read sequencing technology developed by PacBio has greatly improved the base-level accuracy of genome assemblies.However,these assemblies still contain base-level errors,particularly within the error-prone regions of HiFi long reads.Existing genome polishing tools usually introduce overcorrections and haplotype switch errors when correcting errors in genomes assembled from HiFi long reads.Here,we describe an upgraded genome polishing tool-NextPolish2,which can fix base errors remaining in those“highly accurate”genomes assembled from HiFi long reads without introducing excessive overcorrections and haplotype switch errors.We believe that NextPolish2 has a great significance to further improve the accuracy of telomere-to-telomere(T2T)genomes.NextPolish2 is freely available at https://github.com/Nextomics/NextPolish2.展开更多
文摘Cardiogenic shock is the leading cause of death among patients hospitalized with acute myocardial infarction （MI）. Understanding the mechanisms for acute pump failure is therefore important. The aim of this study is to examine in an acute MI dog model whether mitochondrial bio-energetic function within non-ischemic wall regions are associated with pump failure. Anterior MI was produced in dogs via ligation of left anterior descending （LAD） coronary artery, that resulted in an infract size of about 30% of the left ventricular wall. Measurements ofhemodynamic status, mitochondrial function, free radical production and mitochondrial uncoupling protein 3 （UCP3） expression were determined over 24 h period. Hemodynamic measurements revealed a 〉 50% reduction in cardiac output at 24 h post infarction when compared to baseline. Biopsy samples were obtained from the posterior non-ischemic wall during acute infarction. ADP/O ratios for isolated mitochondria from non-ischemic myocardium at 6 h and 24 h were decreased when compared to the ADP/O ratios within the same samples with and without palmitic acid （PA）. GTP inhibition of （PA）-stimulated state 4 respiration in isolated mitochondria from the non-ischemic wall increased by 7% and 33% at 6 h and 24 h post-infarction respectively when compared to sham and pre-infarction samples. This would suggest that the mitochondria are uncoupled and this is supported by an associated increase in UCP3 expression observed on western blots from these same biopsy samples. Blood samples from the coronary sinus measured by electron paramagnetic resonance （EPR） methods showed an increase in reactive oxygen species （ROS） over baseline at 6 h and 24 h post-infarction. In conclusion, mitochondrial bio-energetic ADP/O ratios as a result of acute infarction are abnormal within the non-ischemic wall. Mitochondria appear to be energetically uncoupled and this is associated with declining pump function. Free radical production may be associated with the induction of uncoupling proteins in the mitochondria.
基金supported by the National Natural Science Foundation of China(31470110,31970399)China National GeneBank(CNGB)。
文摘Pikas(Lagomorpha:Ochotonidae)are small mouselike lagomorphs.To investigate their adaptation to different ecological environments during their dispersal from the Qinghai-Xizang(Tibet)Plateau(QTP),we collected 226 pikas and measured 20 morphological characteristics and recorded habitat information.We also sequenced the genome of 81specimens,representing 27 putative pika species.The genome-wide tree based on 4?090 coding genes identified five subgenera,i.e.,Alienauroa,Conothoa,Lagotona,Ochotona,and Pika,consistent with morphometric data.Morphologically,Alienauroa and Ochotona had similar traits,including smaller size and earlier divergence time compared to other pikas.Consistently,the habitats of Alienauroa and Ochotona differed from those of the remaining subgenera.Phylogenetic signal analysis detected 83 genes significantly related to morphological characteristics,including several visual and hearingrelated genes.Analysis of shared amino acid substitutions and positively selected genes(PSGs)in Alienauroa and Ochotona identified two genes,i.e.,mitochondrial function-related TSFM(p.Q155E)and low-light visual sensitivity-related PROM1(p.H419Y).Functional experiments demonstrated that TSFM-155E significantly enhanced mitochondrial function compared to TSFM-155Q in other pikas,and PROM1-419Y decreased the modeling of dynamic intracellular chloride efflux upon calcium uptake.Alienauroa and Ochotona individuals mostly inhabit different environments(e.g.,subtropical forests)than other pikas,suggesting that a shift from the larger ancestral type and changes in sensory acuity and energy enhancement may have been required in their new environments.This study increases our understanding of the evolutionary history of pikas.
基金supported by the Fundamental Research Funds for the Central Universities of China(2572022DQ03)National Natural Science Foundation of China(32170517)+1 种基金Guangdong Provincial Key Laboratory of Genome Read and Write(2017B030301011)supported by China National GeneBank(CNGB)。
文摘DEAR EDITOR,Big cats,such as Amur tigers(Panthera tigris altaica)and Amur leopards(P.pardus orientalis),are apex predator and have evolved specialized traits for hunting and carnivory(Moya et al.,2022),thus playing a crucial role in maintaining biodiversity and ecosystem integrity by regulating prey-predator dynamics.However,human-induced pressures,habitat fragmentation,and environmental alterations have restricted these species in small and isolated populations.Currently,all extant big cats are categorized as endangered or threatened according to their conservation status.Amur tigers and Amur leopards share overlapping geographic ranges,habitats,and certain prey species in the forests of Northeast Asia(Jiang et al.,2015).To reduce interspecies conflict,these carnivores exhibit differentiated dietary and temporal niches.Amur tigers predominantly prey on large ungulates,while Amur leopards hunt small to medium-sized animals(Sugimoto et al.,2016).Additionally,they occupy different temporal niches,with tigers being active at night and leopards more active during the day.Despite spatial and temporal niche partitioning,interspecific competition between these two species is inevitable.Tigers,benefiting from their greater size,have a competitive advantage over leopards,which can manifest in occasional leopard predation by tigers and declines in leopard populations with increasing tiger density(Jiang et al.,2015).Tigers also displace leopards from marginal habitats in nature reserves where they coexist.
基金supported by the National Key R&D Program of China(Grant No.2022YFC3400300)the National Natural Science Foundation of China(Grant Nos.32125009 and 32070663).
文摘The high-fidelity(HiFi)long-read sequencing technology developed by PacBio has greatly improved the base-level accuracy of genome assemblies.However,these assemblies still contain base-level errors,particularly within the error-prone regions of HiFi long reads.Existing genome polishing tools usually introduce overcorrections and haplotype switch errors when correcting errors in genomes assembled from HiFi long reads.Here,we describe an upgraded genome polishing tool-NextPolish2,which can fix base errors remaining in those“highly accurate”genomes assembled from HiFi long reads without introducing excessive overcorrections and haplotype switch errors.We believe that NextPolish2 has a great significance to further improve the accuracy of telomere-to-telomere(T2T)genomes.NextPolish2 is freely available at https://github.com/Nextomics/NextPolish2.
