Human Immunodeficiency Virus Type 1 exists in vivo as quasispecies, and one of the genome's characteristics is its diversity. During the antiretroviral therapy, drug resistance is the main obstacle to effective vi...Human Immunodeficiency Virus Type 1 exists in vivo as quasispecies, and one of the genome's characteristics is its diversity. During the antiretroviral therapy, drug resistance is the main obstacle to effective viral prevention. Understanding the molecular evolution process is fundamental to analyze the mechanism of drug resistance and develop a strategy to minimize resistance. Objective: The molecular evolution of drug resistance of one patient who had received reverse transcriptase inhibitors for a long time and had treatment which replaced Nevirapine with Indinavir was analyzed, with the aim of observing the drug resistance evolution pathway. Methods: The patient, XLF, was followed-up for six successive times. The viral populations were amplified and sequenced by single-genome amplification. All the sequences were submitted to the Stanford HIV Drug Resistance Database for the analysis of genotypic drug resistance. Results: 149 entire protease and 171 entire reverse transcriptase sequences were obtained from these samples, and all sequences were identified as subtype B. Before the patient received Indinavir, the viral population only had some polymorphisms in the protease sequences. After the patient began Indinavir treatment, the variants carrying polymorphisms declined while variants carrying the secondary mutation G73S gained the advantage. As therapy was prolonged, G73S was combined with M46I/L90M to form a resistance pattern M46I/G73S/L90M, which then became the dominant population. 97.9% of variants had the M46I/G73S/L90M pattern at XLF6. During the emergence of protease inhibitors resistance, reverse transcriptase inhibitors resistance maintained high levels. Conclusion: Indinavirresistance evolution was observed by single-genome amplification. During the course of changing the regimen to incorporate Indinavir, the G73S mutation occurred and was combined with M46I/L90M.展开更多
Plants employ multifaceted mechanisms to fight with numerous pathogens in nature.Resistance(R)genes are the most effective weapons against pathogen invasion since they can specifically recognize the corresponding path...Plants employ multifaceted mechanisms to fight with numerous pathogens in nature.Resistance(R)genes are the most effective weapons against pathogen invasion since they can specifically recognize the corresponding pathogen effectors or associated protein(s)to activate plant immune responses at the site of infection.Up to date,over 70 R genes have been isolated from various plant species.Most R proteins contain conserved motifs such as nucleotide-binding site(NBS),leucine-rich repeat(LRR),Toll-interleukin-1 receptor domain(TIR,homologous to cytoplasmic domains of the Drosophila Toll protein and the manamalian intefleukin-1 receptor),coiled-coil(CC)or leucine zipper(LZ)structure and protein kinase domain(PK).Recent results indicate that these domains play significant roles in R protein interactions with effector proteins from pathogens and in activating signal transduction pathways involved in innate immunity.This review highlights an overview of the recent progress in elucidating the structure,function and evolution of the isolated R genes in different plant-pathogen interaction systems.展开更多
The surface morphology, cross-sections, and joint break force（JBF） of joints welded under different electrode forces were studied. The defects, such as electrode sticking, notch, and excessive expulsions, were obser...The surface morphology, cross-sections, and joint break force（JBF） of joints welded under different electrode forces were studied. The defects, such as electrode sticking, notch, and excessive expulsions, were observed in the joints. No desirable joints were achieved with the consideration of weld geometries and joint performances. From the cross-sectional morphology, the joint evolution during the RMW of Pt alloy and 316 LVM SS wires was developed, which involved cold collapse and heat promoted set-down of Pt alloy wire, unbalanced heating at interface, molten phase squeezed out, and defect formation. Finally, the defect formation was also discussed.展开更多
The increase in bacterial antibiotic resistance poses a significant threat to the effectiveness of antibiotics,and there is growing evidence suggesting that global warming may speed up this process.However,the direct ...The increase in bacterial antibiotic resistance poses a significant threat to the effectiveness of antibiotics,and there is growing evidence suggesting that global warming may speed up this process.However,the direct influence of temperature on the development of antibiotic resistance and the underlying mechanisms is not yet fully understood.Here we show that antibiotic resistance exhibits a nonlinear response to elevated temperatures under the combined stress of temperatures and antibiotics.We find that the effectiveness of gatifloxacin against Escherichia coli significantly diminishes at 42℃,while resistance increases 256-fold at 27℃.Additionally,the increased transcription levels of genes such as marA,ygfA,and ibpB with rising temperatures,along with gene mutations at different sites,explain the observed variability in resistance patterns.These findings highlight the complexity of antibiotic resistance evolution and the urgent need for comprehensive studies to understand and mitigate the effects of global warming on antibiotic resistance.展开更多
基金National Natural Science Foundation of China (30830088 and 30800938)The National Key and Special Projects on Major Infectious Disease Grant (2008 ZX10001-004)
文摘Human Immunodeficiency Virus Type 1 exists in vivo as quasispecies, and one of the genome's characteristics is its diversity. During the antiretroviral therapy, drug resistance is the main obstacle to effective viral prevention. Understanding the molecular evolution process is fundamental to analyze the mechanism of drug resistance and develop a strategy to minimize resistance. Objective: The molecular evolution of drug resistance of one patient who had received reverse transcriptase inhibitors for a long time and had treatment which replaced Nevirapine with Indinavir was analyzed, with the aim of observing the drug resistance evolution pathway. Methods: The patient, XLF, was followed-up for six successive times. The viral populations were amplified and sequenced by single-genome amplification. All the sequences were submitted to the Stanford HIV Drug Resistance Database for the analysis of genotypic drug resistance. Results: 149 entire protease and 171 entire reverse transcriptase sequences were obtained from these samples, and all sequences were identified as subtype B. Before the patient received Indinavir, the viral population only had some polymorphisms in the protease sequences. After the patient began Indinavir treatment, the variants carrying polymorphisms declined while variants carrying the secondary mutation G73S gained the advantage. As therapy was prolonged, G73S was combined with M46I/L90M to form a resistance pattern M46I/G73S/L90M, which then became the dominant population. 97.9% of variants had the M46I/G73S/L90M pattern at XLF6. During the emergence of protease inhibitors resistance, reverse transcriptase inhibitors resistance maintained high levels. Conclusion: Indinavirresistance evolution was observed by single-genome amplification. During the course of changing the regimen to incorporate Indinavir, the G73S mutation occurred and was combined with M46I/L90M.
基金This work was supported by grants from the Natural Science Foundation of China(No.30470990,No.30571063)the"948"Project from the Minister of Agriculture in China,the"973"Project from the Minister of Science and Technology(No.2006CB101904)+1 种基金Hunan Natural Science Foundation(No.06JJ10006)Scientific Research Fund of Hunan Provincial Education department(No.04A024).
文摘Plants employ multifaceted mechanisms to fight with numerous pathogens in nature.Resistance(R)genes are the most effective weapons against pathogen invasion since they can specifically recognize the corresponding pathogen effectors or associated protein(s)to activate plant immune responses at the site of infection.Up to date,over 70 R genes have been isolated from various plant species.Most R proteins contain conserved motifs such as nucleotide-binding site(NBS),leucine-rich repeat(LRR),Toll-interleukin-1 receptor domain(TIR,homologous to cytoplasmic domains of the Drosophila Toll protein and the manamalian intefleukin-1 receptor),coiled-coil(CC)or leucine zipper(LZ)structure and protein kinase domain(PK).Recent results indicate that these domains play significant roles in R protein interactions with effector proteins from pathogens and in activating signal transduction pathways involved in innate immunity.This review highlights an overview of the recent progress in elucidating the structure,function and evolution of the isolated R genes in different plant-pathogen interaction systems.
基金Funded by the National Natural Science Foundation of China(No.51365044)the State Key Laboratory for Mechanical Behavior of Materials(No.20111203)the State Key Laboratory of Advanced Welding and Joining,Harbin Institute of Technology(No.AWJ-M13-09)
文摘The surface morphology, cross-sections, and joint break force（JBF） of joints welded under different electrode forces were studied. The defects, such as electrode sticking, notch, and excessive expulsions, were observed in the joints. No desirable joints were achieved with the consideration of weld geometries and joint performances. From the cross-sectional morphology, the joint evolution during the RMW of Pt alloy and 316 LVM SS wires was developed, which involved cold collapse and heat promoted set-down of Pt alloy wire, unbalanced heating at interface, molten phase squeezed out, and defect formation. Finally, the defect formation was also discussed.
基金National Natural Science Foundation of China(U2005206)National Key R&D Program of China(2023YFE0112100).
文摘The increase in bacterial antibiotic resistance poses a significant threat to the effectiveness of antibiotics,and there is growing evidence suggesting that global warming may speed up this process.However,the direct influence of temperature on the development of antibiotic resistance and the underlying mechanisms is not yet fully understood.Here we show that antibiotic resistance exhibits a nonlinear response to elevated temperatures under the combined stress of temperatures and antibiotics.We find that the effectiveness of gatifloxacin against Escherichia coli significantly diminishes at 42℃,while resistance increases 256-fold at 27℃.Additionally,the increased transcription levels of genes such as marA,ygfA,and ibpB with rising temperatures,along with gene mutations at different sites,explain the observed variability in resistance patterns.These findings highlight the complexity of antibiotic resistance evolution and the urgent need for comprehensive studies to understand and mitigate the effects of global warming on antibiotic resistance.
