Encephalomyocarditis virus (EMCV) infection leads to many diseases including encephalitis,myocarditis and diabetes in its natural host,the mouse.In this study,we generated four cDNA clones with a point mutation at pos...Encephalomyocarditis virus (EMCV) infection leads to many diseases including encephalitis,myocarditis and diabetes in its natural host,the mouse.In this study,we generated four cDNA clones with a point mutation at position 100 of VP1.The amino acids isoleucine,alanine,serine and proline were substituted with threonine in the four different clones of EMCV strain BJC3 by site-specific mutagenesis,and viable viruses were rescued.Although all mutants and wild-type viruses display different plaque morphologies,they replicate comparably in BHK-21 cells.The pathogenicity of the mutated viruses was systematically analyzed to investigate the importance of this amino acid in the viral pathogenicity and disease phenotype of EMCV infection in mice.The results showed that the isoleucine(T1100I) and proline-mutated viruses (T1100P) exhibited a reduced mortality,lower cerebral virus loads and alleviated brain damage while the viruses with serine (T1100S) and alanine (T1100A) substitutions displayed similar properties as the wild-type virus.These findings indicate that the amino acid at position 100 of VP1 is important for EMCV in vivo infection,and its mutation alters the pathogenicity of viral infection in mice.展开更多
OBJECTIVE: To investigate metabolic signatures in plasma of cancer patients with abnormal Savda using plasma-free amino acid profiles, and to evaluate the diagnostic potential of these profiles for the detection and e...OBJECTIVE: To investigate metabolic signatures in plasma of cancer patients with abnormal Savda using plasma-free amino acid profiles, and to evaluate the diagnostic potential of these profiles for the detection and explanation of the mechanisms of different symptoms in traditional Uyghur medicine.METHODS: Plasma samples from cancer patients with abnormal Savda(n=85) or non-abnormal Savda(n=105) and a healthy control group(n=65)were analyzed using high-performance liquid chromatography(HPLC). Orthogonal projection to latent structures with discriminant analysis was used for the classification and prediction of abnormal Savda, and spectral profiles were subjected to Student's t-tests to assess statistical significance.RESULTS: Compared with the healthy group, the levels of aspartic acid, glutamate, glycine, histidine,arginine, threonine, alanine, proline, methionine,isoleucine, leucine and phenylalanine decreased significantly in plasma of cancer patients with abnormal Savda(all P<0.05). Serine, cystine, tyrosine,valine and lysine levels showed no significant differences(all P>0.05). Compared with non-abnormal Savda syndrome patients, abnormal Savda syndrome patients showed high concentrations of glutamate, serine, valine, isoleucine, leucine and phenylalanine(all P<0.05). The remaining plasma amino acids showed no significant differences(all P>0.05).CONCLUSION: Plasma-free amino acid profiling has the potential to assist in understanding and determining abnormal Savda. A HPLC-based metabonomic platform could be a powerful tool for the classification of symptoms in traditional medicine.展开更多
基金supported by the National Natural Science Foundation of China (Grant No. 30530550)the Program for Innovative Research Team in University of China (Grant No. IRT0866)
文摘Encephalomyocarditis virus (EMCV) infection leads to many diseases including encephalitis,myocarditis and diabetes in its natural host,the mouse.In this study,we generated four cDNA clones with a point mutation at position 100 of VP1.The amino acids isoleucine,alanine,serine and proline were substituted with threonine in the four different clones of EMCV strain BJC3 by site-specific mutagenesis,and viable viruses were rescued.Although all mutants and wild-type viruses display different plaque morphologies,they replicate comparably in BHK-21 cells.The pathogenicity of the mutated viruses was systematically analyzed to investigate the importance of this amino acid in the viral pathogenicity and disease phenotype of EMCV infection in mice.The results showed that the isoleucine(T1100I) and proline-mutated viruses (T1100P) exhibited a reduced mortality,lower cerebral virus loads and alleviated brain damage while the viruses with serine (T1100S) and alanine (T1100A) substitutions displayed similar properties as the wild-type virus.These findings indicate that the amino acid at position 100 of VP1 is important for EMCV in vivo infection,and its mutation alters the pathogenicity of viral infection in mice.
基金Supported by the China National Natural Science Foundation Program of Comparative Study of Abnormal Savda and Stasis-Phlegm Syndrome Tumor Patients Based on Metabonomics(No.81160459)the Postdoctoral Foundation of Xinjiang Medical University of Metabonomic Study of Abnormal Savda Tumor Patients(No.2012-27)
文摘OBJECTIVE: To investigate metabolic signatures in plasma of cancer patients with abnormal Savda using plasma-free amino acid profiles, and to evaluate the diagnostic potential of these profiles for the detection and explanation of the mechanisms of different symptoms in traditional Uyghur medicine.METHODS: Plasma samples from cancer patients with abnormal Savda(n=85) or non-abnormal Savda(n=105) and a healthy control group(n=65)were analyzed using high-performance liquid chromatography(HPLC). Orthogonal projection to latent structures with discriminant analysis was used for the classification and prediction of abnormal Savda, and spectral profiles were subjected to Student's t-tests to assess statistical significance.RESULTS: Compared with the healthy group, the levels of aspartic acid, glutamate, glycine, histidine,arginine, threonine, alanine, proline, methionine,isoleucine, leucine and phenylalanine decreased significantly in plasma of cancer patients with abnormal Savda(all P<0.05). Serine, cystine, tyrosine,valine and lysine levels showed no significant differences(all P>0.05). Compared with non-abnormal Savda syndrome patients, abnormal Savda syndrome patients showed high concentrations of glutamate, serine, valine, isoleucine, leucine and phenylalanine(all P<0.05). The remaining plasma amino acids showed no significant differences(all P>0.05).CONCLUSION: Plasma-free amino acid profiling has the potential to assist in understanding and determining abnormal Savda. A HPLC-based metabonomic platform could be a powerful tool for the classification of symptoms in traditional medicine.
