Objective N6-methyladenosine(m^(6)A)is a common epigenetic modification in eukaryotes.In this study,we explore the potential impact of m^(6)A-associated single nucleotide polymorphisms(m^(6)A-SNPs)on heart failure(HF)...Objective N6-methyladenosine(m^(6)A)is a common epigenetic modification in eukaryotes.In this study,we explore the potential impact of m^(6)A-associated single nucleotide polymorphisms(m^(6)A-SNPs)on heart failure(HF).Methods Data from genome-wide association studies(GWAS)investigating HF in humans and from m^(6)A-SNPs datasets were used to identify HF-associated m^(6)A-SNPs.Their functions were explored using expression quantitative trait locus(eQTL),gene expression,and gene enrichment analyses.Mediation protein quantitative trait locus(pQTL)-Mendelian randomization(MR)was used to investigate the potential mechanism between critical protein levels and risk factors for HF.Results We screened 44 HF-associated m^(6)A-SNPs,including 10 m^(6)A-SNPs that showed eQTL signals and differential expressions in HF.The SNP rs1801270 in CDKN1A showed the strongest association with HF(P=7.75×10^(−6)).Additionally,MR verified the genetic association between the CDKN1A protein and HF,as well as the mediating effect of blood pressure(BP)in this pathway.Higher circulating level of CDKN1A was associated with a lower risk of HF(odds ratio[OR]=0.82,95%confidence interval[CI]:0.69 to 0.99).The proportions of hypertension,systolic BP,and diastolic BP were 48.10%,28.94%,and 18.02%,respectively.Associations of PDIA6(P=1.30×10^(−2))and SMAD3(P=4.80×10^(−2))with HF were also detected.Conclusion Multiple HF-related m^(6)A-SNPs were identified in this study.Genetic associations of CDKN1A and other proteins with HF and its risk factors were demonstrated,providing new ideas for further exploration of the molecular mechanisms of HF.展开更多
The goal of this study was to investigate the genetic stability of the C57BL/6J （B6） inbred mouse strain maintained in different breeders. Three populations of B6, Popl and Pop2 purchased from Beijing and Pop3 purch...The goal of this study was to investigate the genetic stability of the C57BL/6J （B6） inbred mouse strain maintained in different breeders. Three populations of B6, Popl and Pop2 purchased from Beijing and Pop3 purchased from Shanghai, were examined. Fifteen microsatellite loci reported to be polymorphic among inbred strains were amplified using FAM labeled primers and genotyped with ABI Prism 377 automated sequencer. Seven loci were found polymorphic, and all the loci were homozygous in all the three populations. The present study indicates that genetic variation occurs in different B6 populations although they are still inbred in each breeder. The mechanism of genetic variation is not well understood now, but it is very important to know the precise content of the B6 genome before use of this strain in research.展开更多
This study was undertaken to dissect quantitative trait loci （QTLs） controlling yield traits on the short arm of rice chromosome 6. A residual heterozygous line that carries a heterozygous segment extending from RM5...This study was undertaken to dissect quantitative trait loci （QTLs） controlling yield traits on the short arm of rice chromosome 6. A residual heterozygous line that carries a heterozygous segment extending from RM587 to RM19784 on the short arm of rice chromosome 6 was selected from an F7 population of the indica rice cross Zhenshan 97B/Milyang 46. An F2：3 population consisting of 221 lines was derived and grown in two trial sites. Six yield traits including number of panicles per plant, number of filled grains per panicle, total number of spikelets per panicle, spikelet fertility, 1 000-grain weight, and grain yield per plant were measured. An SSR marker linkage map was constructed and employed to determine QTLs for yield traits with Windows QTL Cartographer 2.5. QTLs were detected in the target interval for all the traits analyzed except NP, with phenotypic variance explained by a single QTL ranging between 6.3% and 35.2%. Most of the QTLs for yield components acted as additive QTLs, while the three QTLs for grain yield had dominance degrees of 1.65, 0.84, and -0.42, respectively. It was indicated that three or more QTLs for yield traits were located in the target region. The genetic action mode, the direction of the QTL effect, and the magnitude of the QTL effect varied among different QTLs for a given trait, and among QTLs for different traits that were located in the same interval.展开更多
A rice residual heterozygous line （RHL） carrying a heterozygous segment extending from RM111 to RM19784 on the short arm of rice chromosome 6 was selected from a RHL-derived population used previously. The resultant...A rice residual heterozygous line （RHL） carrying a heterozygous segment extending from RM111 to RM19784 on the short arm of rice chromosome 6 was selected from a RHL-derived population used previously. The resultant F2：3 population was used to detect quantitative trait loci （QTLs） for three yield traits, the number of spikelets per panicle （NSP）, the number of grains per panicle （NGP） and grain yield per plant （GY）. Two QTLs for NSP, one QTL for NGP and one QTL for GY were detected, all of which were partially dominant and had the enhancing alleles from the maternal line Zhenshan 97B. Analysis based on the genotypic groups of the markers closely linked to the two QTLs for NSP indicated that they did not interact with each other. Two F2 populations and two near isogenic line （NIL） sets segregating in two sub-regions of interval RM111-RM19784 were developed. The two QTLs for NSP were validated, of which one had major effect and was co-segregated with heading date gene Hdl, and the other had smaller effect and was located in an upper region linked to Hdl. The two regions also showed significant effects on the number of filled grain and grain yield, although the effect on the number of filled grain was less consistent.展开更多
Objective To investigate the changes in the firing activity of noradrenergic neurons in the locus coeruleus (LC) in a rat model of Parkinson disease (PD). Methods 2 and 4 weeks after unilateral lesion of the nigrostri...Objective To investigate the changes in the firing activity of noradrenergic neurons in the locus coeruleus (LC) in a rat model of Parkinson disease (PD). Methods 2 and 4 weeks after unilateral lesion of the nigrostriatal pathway in the rat by local injection of 6-hydroxydopamine (6-OHDA) into the right substantia nigra pars compacta (SNc), the firing activity of noradrenergic neurons in LC was recorded by extracellular single unit recording. Results The firing rate of LC noradrenergic neurons increased sig...展开更多
The biaxial tensile behavior of isotropic Ti-6Al-4 V is characterized in this paper.A novel cruciform specimen was designed and optimized to achieve uniform stress and strain distribution within the gauge area.Biaxial...The biaxial tensile behavior of isotropic Ti-6Al-4 V is characterized in this paper.A novel cruciform specimen was designed and optimized to achieve uniform stress and strain distribution within the gauge area.Biaxial tensile tests were conducted at three different loading ratios by the biaxial testing machine.The Digital Image Correlation(DIC)technique was applied to determine strain distribution,and a high-speed camera was employed to record the fracture process.An Inverse Analysis(IA)approach with a combined experimental and numerical method was proposed to determine the true stresses at the gauge section of the specimen during biaxial tensile tests.The results indicate that the initial yield locus can be described by the Cazacu criterion accurately,whereas the Mises criterion can predict better the strengthening behavior of Ti-6Al-4 V in the first quadrant in the principal stress space.展开更多
基金supported by the National Natural Science Foundation of China[82070473,82170480,82030102]Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences[2021-I2M-1-010].
文摘Objective N6-methyladenosine(m^(6)A)is a common epigenetic modification in eukaryotes.In this study,we explore the potential impact of m^(6)A-associated single nucleotide polymorphisms(m^(6)A-SNPs)on heart failure(HF).Methods Data from genome-wide association studies(GWAS)investigating HF in humans and from m^(6)A-SNPs datasets were used to identify HF-associated m^(6)A-SNPs.Their functions were explored using expression quantitative trait locus(eQTL),gene expression,and gene enrichment analyses.Mediation protein quantitative trait locus(pQTL)-Mendelian randomization(MR)was used to investigate the potential mechanism between critical protein levels and risk factors for HF.Results We screened 44 HF-associated m^(6)A-SNPs,including 10 m^(6)A-SNPs that showed eQTL signals and differential expressions in HF.The SNP rs1801270 in CDKN1A showed the strongest association with HF(P=7.75×10^(−6)).Additionally,MR verified the genetic association between the CDKN1A protein and HF,as well as the mediating effect of blood pressure(BP)in this pathway.Higher circulating level of CDKN1A was associated with a lower risk of HF(odds ratio[OR]=0.82,95%confidence interval[CI]:0.69 to 0.99).The proportions of hypertension,systolic BP,and diastolic BP were 48.10%,28.94%,and 18.02%,respectively.Associations of PDIA6(P=1.30×10^(−2))and SMAD3(P=4.80×10^(−2))with HF were also detected.Conclusion Multiple HF-related m^(6)A-SNPs were identified in this study.Genetic associations of CDKN1A and other proteins with HF and its risk factors were demonstrated,providing new ideas for further exploration of the molecular mechanisms of HF.
基金Supported by Peking University People's Hospital Research and Development Foundation(RDB2007-03)~~
文摘The goal of this study was to investigate the genetic stability of the C57BL/6J （B6） inbred mouse strain maintained in different breeders. Three populations of B6, Popl and Pop2 purchased from Beijing and Pop3 purchased from Shanghai, were examined. Fifteen microsatellite loci reported to be polymorphic among inbred strains were amplified using FAM labeled primers and genotyped with ABI Prism 377 automated sequencer. Seven loci were found polymorphic, and all the loci were homozygous in all the three populations. The present study indicates that genetic variation occurs in different B6 populations although they are still inbred in each breeder. The mechanism of genetic variation is not well understood now, but it is very important to know the precise content of the B6 genome before use of this strain in research.
基金supported by the Zhejiang Natural Science Foundation(Y304446)the National 863 Program of China(2006AA10Z1E8)the Chinese Super Rice Breeding Program(200606).
文摘This study was undertaken to dissect quantitative trait loci （QTLs） controlling yield traits on the short arm of rice chromosome 6. A residual heterozygous line that carries a heterozygous segment extending from RM587 to RM19784 on the short arm of rice chromosome 6 was selected from an F7 population of the indica rice cross Zhenshan 97B/Milyang 46. An F2：3 population consisting of 221 lines was derived and grown in two trial sites. Six yield traits including number of panicles per plant, number of filled grains per panicle, total number of spikelets per panicle, spikelet fertility, 1 000-grain weight, and grain yield per plant were measured. An SSR marker linkage map was constructed and employed to determine QTLs for yield traits with Windows QTL Cartographer 2.5. QTLs were detected in the target interval for all the traits analyzed except NP, with phenotypic variance explained by a single QTL ranging between 6.3% and 35.2%. Most of the QTLs for yield components acted as additive QTLs, while the three QTLs for grain yield had dominance degrees of 1.65, 0.84, and -0.42, respectively. It was indicated that three or more QTLs for yield traits were located in the target region. The genetic action mode, the direction of the QTL effect, and the magnitude of the QTL effect varied among different QTLs for a given trait, and among QTLs for different traits that were located in the same interval.
基金supported by the Chinese Super Rice Research Program(200906)the High-Yielding Transgenic Program,China(2008ZX08001-004)the National Natural Science Foundation of China(30571062)
文摘A rice residual heterozygous line （RHL） carrying a heterozygous segment extending from RM111 to RM19784 on the short arm of rice chromosome 6 was selected from a RHL-derived population used previously. The resultant F2：3 population was used to detect quantitative trait loci （QTLs） for three yield traits, the number of spikelets per panicle （NSP）, the number of grains per panicle （NGP） and grain yield per plant （GY）. Two QTLs for NSP, one QTL for NGP and one QTL for GY were detected, all of which were partially dominant and had the enhancing alleles from the maternal line Zhenshan 97B. Analysis based on the genotypic groups of the markers closely linked to the two QTLs for NSP indicated that they did not interact with each other. Two F2 populations and two near isogenic line （NIL） sets segregating in two sub-regions of interval RM111-RM19784 were developed. The two QTLs for NSP were validated, of which one had major effect and was co-segregated with heading date gene Hdl, and the other had smaller effect and was located in an upper region linked to Hdl. The two regions also showed significant effects on the number of filled grain and grain yield, although the effect on the number of filled grain was less consistent.
基金supported by the Foundation of Science and Technological Program of Shaanxi Province,China (No. 2007K15-G1).
文摘Objective To investigate the changes in the firing activity of noradrenergic neurons in the locus coeruleus (LC) in a rat model of Parkinson disease (PD). Methods 2 and 4 weeks after unilateral lesion of the nigrostriatal pathway in the rat by local injection of 6-hydroxydopamine (6-OHDA) into the right substantia nigra pars compacta (SNc), the firing activity of noradrenergic neurons in LC was recorded by extracellular single unit recording. Results The firing rate of LC noradrenergic neurons increased sig...
基金the financial support from National Natural Science Foundation of China(Nos.11922211,11832015,11527803)the 111 Project,China(No.BP0719007)Science Challenge Project,China(No.TZ2018001).
文摘The biaxial tensile behavior of isotropic Ti-6Al-4 V is characterized in this paper.A novel cruciform specimen was designed and optimized to achieve uniform stress and strain distribution within the gauge area.Biaxial tensile tests were conducted at three different loading ratios by the biaxial testing machine.The Digital Image Correlation(DIC)technique was applied to determine strain distribution,and a high-speed camera was employed to record the fracture process.An Inverse Analysis(IA)approach with a combined experimental and numerical method was proposed to determine the true stresses at the gauge section of the specimen during biaxial tensile tests.The results indicate that the initial yield locus can be described by the Cazacu criterion accurately,whereas the Mises criterion can predict better the strengthening behavior of Ti-6Al-4 V in the first quadrant in the principal stress space.
