A general and elementary protein folding step was described in a previous article. Energy conservation during this folding step yielded an equation with remarkable solutions over the field of rational numbers. Sets of...A general and elementary protein folding step was described in a previous article. Energy conservation during this folding step yielded an equation with remarkable solutions over the field of rational numbers. Sets of sequences optimized for folding were derived. In this work, a geometrical analysis of protein beta-sheet backbone structures allows the definition of positions of topological interest. They correspond to amino acids’ alpha carbons located on a unique axis crossing all beta-sheet’s strands or at proximity of this axis defined here. These positions of topological interest are shown to be highly correlated with the absence of sequences optimized for folding. Applications in protein structure prediction for the quality assessment of structural models are envisioned.展开更多
Objective To investigate activation of brown adipose tissue （BAT） stimulated by medium-chain triglyceride （MCT）. Methods 30 Male C57BL/6J obese mice induced by fed high fat diet （HFD） were divided into 2 groups,...Objective To investigate activation of brown adipose tissue （BAT） stimulated by medium-chain triglyceride （MCT）. Methods 30 Male C57BL/6J obese mice induced by fed high fat diet （HFD） were divided into 2 groups, and fed another HFD with 2% MCT or long-chain triglyceride （LCT） respectively for 12 weeks. Body weight, blood biochemical variables, interscapular brown fat tissue （IBAT） mass, expressions of mRNA and protein of beta 3-adrenergic receptors （β3-AR）, uncoupling protein-1 （UCP1）, hormone sensitive lipase （HSL）, protein kinase A （PKA）, and adipose triglyceride lipase （ATGL） in IBAT were measured. Results Significant decrease in body weight and body fat mass was observed in MCT group as compared with LCT group （P〈O.05） after 12 weeks. Greater increases in IBAT mass was observed in MCT group than in LCT group （P〈O.05）. Blood TG, TC, LDL-C in MCT group were decreased significantly, meanwhile blood HDL-C, ratio of HDL-C/LDL-C and norepinephrine were increased markedly. Expressions of mRNA and protein of β3-AR, UCP1, PKA, HSL, ATGL in BAT were greater in MCT group than in LCT group （P〈O.05）. Conclusion Our results suggest that MCT stimulated the activation of BAT, possible via norepinephrine pathway, which might partially contribute to reduction of the body fat mass in obese mice fed high fat diet.展开更多
多系统萎缩(multiple system atrophy,MSA)是一类神经系统退行性疾病,其病理特征是胶质细胞中出现含有不溶性α突触核蛋白(α-synuclein)的胞质包涵体.研究显示,α-synuclein在多系统萎缩的发病机制中有重要作用,但其毒性的分子机制目...多系统萎缩(multiple system atrophy,MSA)是一类神经系统退行性疾病,其病理特征是胶质细胞中出现含有不溶性α突触核蛋白(α-synuclein)的胞质包涵体.研究显示,α-synuclein在多系统萎缩的发病机制中有重要作用,但其毒性的分子机制目前还不清楚.本文在前期研究氧化应激条件下α-synuclein引起细胞内钙稳态失衡,提出了以氧化应激为连接的多系统萎缩中,胶质细胞死亡的新假说的基础上,深入分析了α-synuclein过表达导致U251细胞变性死亡的分子机制.首先证明过表达α-synuclein的U251细胞出现生长速度减慢、氧化应激水平增加和钙离子瞬时受体电位通道蛋白(transient receptor potential channel-1,TRPC1)表达量升高,而且细胞存活率的变化可通过下调TRPC1的表达得以恢复,说明TRPC1在α-synuclein过表达细胞死亡中发挥了重要作用;其次,研究发现α-synuclein稳转U251细胞中出现了明显的自噬水平增加和细胞凋亡的特征,表明α-synuclein通过作用于内质网钙泵以及细胞膜上的瞬时受体电位钙通道TRPC1,破坏了细胞内的钙稳态,进而影响自噬和凋亡,增加了U251细胞对于过氧化氢的敏感性,这可能是导致多系统萎缩病人脑内胶质细胞死亡的原因.展开更多
AIM: To evaluate the association of complement factor H(CFH) and microtubule-associated protein 1 light chain 3 beta(MAP1LC3B) gene polymorphisms with the risk of age-related macular degeneration(AMD) in a high-altitu...AIM: To evaluate the association of complement factor H(CFH) and microtubule-associated protein 1 light chain 3 beta(MAP1LC3B) gene polymorphisms with the risk of age-related macular degeneration(AMD) in a high-altitude population. METHODS: The study group consisted of 172 participants with symptoms of AMD who were examined and diagnosed between January 2019 and June 2020. The control group was composed of 120 healthy individuals. Each participant was required to provide two milliliters of peripheral blood for DNA extraction. Two single nucleotide polymorphisms(SNPs) of CFH(rs1061170 and rs800292) and two SNPs of MAP1LC3B(rs8044820 and rs9903) were genotyped. The genotypes and allele frequencies of the SNPs in the study and control groups were further compared using Chi-square and Fisher’s exact tests. RESULTS: In a high-altitude population, the nominally significant differences of rs800292 and rs9903’s genotype AG frequencies were observed in the AMD group(P=0.034 and 0.004, respectively). The frequencies of allele G of rs800292 and allele A of rs9903 were also significantly dif ferent in the AMD group compared to the control [(P=0.034, OR=0.70, 95%CI: 0.50-0.98) and(P=0.004, OR=1.60, 95%CI: 1.15-2.22), respectively]. No significant differences in the genotype distributions(P=0.16 and 0.40, respectively) and allele frequencies(P>0.05) of rs1061170 and rs8044820 were observed in the AMD group.CONCLUSION: Genotype AG of rs800292 may be a protective factor for AMD. Conversely, rs9903 seems to be a risk factor for AMD. Therefore, allele G of rs800292 may be a protective factor, and allele A of rs9903, a risk factor for AMD in Qinghai high-altitude population.展开更多
文摘A general and elementary protein folding step was described in a previous article. Energy conservation during this folding step yielded an equation with remarkable solutions over the field of rational numbers. Sets of sequences optimized for folding were derived. In this work, a geometrical analysis of protein beta-sheet backbone structures allows the definition of positions of topological interest. They correspond to amino acids’ alpha carbons located on a unique axis crossing all beta-sheet’s strands or at proximity of this axis defined here. These positions of topological interest are shown to be highly correlated with the absence of sequences optimized for folding. Applications in protein structure prediction for the quality assessment of structural models are envisioned.
基金supported by the National Natural Science Foundation of China(No.81172667 and No.81202203)
文摘Objective To investigate activation of brown adipose tissue （BAT） stimulated by medium-chain triglyceride （MCT）. Methods 30 Male C57BL/6J obese mice induced by fed high fat diet （HFD） were divided into 2 groups, and fed another HFD with 2% MCT or long-chain triglyceride （LCT） respectively for 12 weeks. Body weight, blood biochemical variables, interscapular brown fat tissue （IBAT） mass, expressions of mRNA and protein of beta 3-adrenergic receptors （β3-AR）, uncoupling protein-1 （UCP1）, hormone sensitive lipase （HSL）, protein kinase A （PKA）, and adipose triglyceride lipase （ATGL） in IBAT were measured. Results Significant decrease in body weight and body fat mass was observed in MCT group as compared with LCT group （P〈O.05） after 12 weeks. Greater increases in IBAT mass was observed in MCT group than in LCT group （P〈O.05）. Blood TG, TC, LDL-C in MCT group were decreased significantly, meanwhile blood HDL-C, ratio of HDL-C/LDL-C and norepinephrine were increased markedly. Expressions of mRNA and protein of β3-AR, UCP1, PKA, HSL, ATGL in BAT were greater in MCT group than in LCT group （P〈O.05）. Conclusion Our results suggest that MCT stimulated the activation of BAT, possible via norepinephrine pathway, which might partially contribute to reduction of the body fat mass in obese mice fed high fat diet.
文摘AIM: To evaluate the association of complement factor H(CFH) and microtubule-associated protein 1 light chain 3 beta(MAP1LC3B) gene polymorphisms with the risk of age-related macular degeneration(AMD) in a high-altitude population. METHODS: The study group consisted of 172 participants with symptoms of AMD who were examined and diagnosed between January 2019 and June 2020. The control group was composed of 120 healthy individuals. Each participant was required to provide two milliliters of peripheral blood for DNA extraction. Two single nucleotide polymorphisms(SNPs) of CFH(rs1061170 and rs800292) and two SNPs of MAP1LC3B(rs8044820 and rs9903) were genotyped. The genotypes and allele frequencies of the SNPs in the study and control groups were further compared using Chi-square and Fisher’s exact tests. RESULTS: In a high-altitude population, the nominally significant differences of rs800292 and rs9903’s genotype AG frequencies were observed in the AMD group(P=0.034 and 0.004, respectively). The frequencies of allele G of rs800292 and allele A of rs9903 were also significantly dif ferent in the AMD group compared to the control [(P=0.034, OR=0.70, 95%CI: 0.50-0.98) and(P=0.004, OR=1.60, 95%CI: 1.15-2.22), respectively]. No significant differences in the genotype distributions(P=0.16 and 0.40, respectively) and allele frequencies(P>0.05) of rs1061170 and rs8044820 were observed in the AMD group.CONCLUSION: Genotype AG of rs800292 may be a protective factor for AMD. Conversely, rs9903 seems to be a risk factor for AMD. Therefore, allele G of rs800292 may be a protective factor, and allele A of rs9903, a risk factor for AMD in Qinghai high-altitude population.
