The gene sod in Acidithiobacillusferrooxidans may play a crucial role in its tolerance to the extremely acidic, toxic and oxidative environment of bioleaching. For insight into the anti-toxic mechanism of the bacteria...The gene sod in Acidithiobacillusferrooxidans may play a crucial role in its tolerance to the extremely acidic, toxic and oxidative environment of bioleaching. For insight into the anti-toxic mechanism of the bacteria, a three-dimensional (3D) molecular structure of the protein encoded by this gene was built by homology modeling techniques, refined by molecular dynamics simulations, assessed by PROFILE-3D and PROSTAT programs and its key residues were further detected by evolutionary trace analysis. Through these procedures, some trace residues were identified and spatially clustered. Among them, the residues of Asn38, Glyl03 and Glul61 are randomly scattered throughout the mapped structure; interestingly, the other residues are all distinctly clustered in a subgroup near Fe atom. From these results, this gene can be confirmed at 3D level to encode the Fe-depending superoxide dismutase and subsequently play an anti-toxic role. Furthermore, the detected key residues around Fe binding site can be conjectured to be directly responsible for Fe binding and catalytic function.展开更多
OBJECTIVE Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative dis⁃ease characterized by progressive loss of upper and lower motor neurons that results in skeletal muscle atrophy,weakness and paralysis.Oxida...OBJECTIVE Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative dis⁃ease characterized by progressive loss of upper and lower motor neurons that results in skeletal muscle atrophy,weakness and paralysis.Oxida⁃tive stress plays a key role in the pathogenesis of ALS,including familial forms of the disease arising from mutation of the gene coding for superoxide dismutase 1(SOD1).Moreover,although the pathogenesis of ALS is unclear,the abnormal accumulation of TAR DNA-binding pro⁃tein of 43 ku(TDP-43)is a pathological feature that exists in almost all patients.Thus far,there is no drug that can cure ALS/FTLD.Tetramethyl⁃pyrazine nitrone(TBN)is a derivative of tetra⁃methylapyrazine,derived from the traditional Chinese medicine Ligusticum chuanxiong,which has been widely proven to have therapeutic effects on models of various neurodegenerative diseases.TBN is currently under clinical investi⁃gation for several indications including a phaseⅡtrial of ALS.Here,we explored the therapeutic effect of TBN in the SOD1G93A and TDP-43M337V ALS mouse model.METHODS In the SOD1G93A transgenic mouse model,TBN was administered to mice by intraperitoneal or intragastric injection after the onset of motor deficits.At the same time,we unilaterally and bilaterally injected the TDP-43M337V virus into the striatum of the WT mouse,and gave the TBN treatment after the mice developed a phenotype.After administering these two models for a period of time,we con⁃ducted behavioral tests,including rotarod test,balance beam test,climbing pole test,etc,to evaluate the efficacy of TBN on SOD1G93A and TDP-43M337V models.Furthermore,we explored the possible mechanism of action of TBN in the treatment of ALS through Western blotting and immunohistochemistry/immunofluorescence staining analysis.RESULTS In the SOD1G93A transgenic mouse model,TBN slowed the pro⁃gression of motor neuron disease as evidenced by improved motor performance,reduced spinal motor neuron loss and the associated glial response,and decreased skeletal muscle fiber denervation and fibrosis.TBN treatment activated mitochondrial antioxidant activity through the PGC-1α/Nrf2/HO-1 pathway and decreased the expression of human SOD1.What′s more,in the TDP-43M337V mice model,the results showed that in mice with unilateral injection of TDP-43M337V,TBN improved motor deficits and cognitive im⁃pairment in the early stages of disease progres⁃sion.In mice with bilateral injection of TDP-43M337V into the striatum,TBN not only improved motor function but also prolonged survival rate.Moreover,we show that its therapeutic effect may be through activation of the Akt/mTOR/GSK-3βand AMPK/PGC-1α/Nrf2 signaling pathways.In summary,TBN is a promising agent for the treat⁃ment of ALS/FTLD.CONCLUSION TBN has shown good efficacy in both SOD1 and TDP-43 ALS-related models,and it may act by activating the AMPK/PGC-1α/Nrf2 signaling pathway,which shows some light for the development of ALS therapeutic drugs.展开更多
Cotton production substantiated a crucial part in the escalating economic development of many countries.To realize the increasing global demand for cotton,the emphasis should be laid on to improve cotton fiber growth ...Cotton production substantiated a crucial part in the escalating economic development of many countries.To realize the increasing global demand for cotton,the emphasis should be laid on to improve cotton fiber growth and production.The bioengineered transgenic cotton proved expedient in resolving inadequacies of conventional cotton,but still required improvements to encounter heightened demand of textile industries.One possible solution pertaining to this has been provided by nanoscience in the form of metal or metal oxide nanoparticles.These metal oxide nanoparticles have easy access to the various parts of cotton plants through its transportation system,and thus significantly influence several parameters relative to the growth and production of cotton fiber.This review summarizes the distribution and accumulation of metal oxide nanoparticles in cotton plant and its impact on different plant growth-promoting factors,which resulted in the improved cotton yields.展开更多
基金Project(2004CB619201) supported by the National Basic Research Program of ChinaProject (50321402) supported by the National Natural Science Foundation of China
文摘The gene sod in Acidithiobacillusferrooxidans may play a crucial role in its tolerance to the extremely acidic, toxic and oxidative environment of bioleaching. For insight into the anti-toxic mechanism of the bacteria, a three-dimensional (3D) molecular structure of the protein encoded by this gene was built by homology modeling techniques, refined by molecular dynamics simulations, assessed by PROFILE-3D and PROSTAT programs and its key residues were further detected by evolutionary trace analysis. Through these procedures, some trace residues were identified and spatially clustered. Among them, the residues of Asn38, Glyl03 and Glul61 are randomly scattered throughout the mapped structure; interestingly, the other residues are all distinctly clustered in a subgroup near Fe atom. From these results, this gene can be confirmed at 3D level to encode the Fe-depending superoxide dismutase and subsequently play an anti-toxic role. Furthermore, the detected key residues around Fe binding site can be conjectured to be directly responsible for Fe binding and catalytic function.
文摘OBJECTIVE Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative dis⁃ease characterized by progressive loss of upper and lower motor neurons that results in skeletal muscle atrophy,weakness and paralysis.Oxida⁃tive stress plays a key role in the pathogenesis of ALS,including familial forms of the disease arising from mutation of the gene coding for superoxide dismutase 1(SOD1).Moreover,although the pathogenesis of ALS is unclear,the abnormal accumulation of TAR DNA-binding pro⁃tein of 43 ku(TDP-43)is a pathological feature that exists in almost all patients.Thus far,there is no drug that can cure ALS/FTLD.Tetramethyl⁃pyrazine nitrone(TBN)is a derivative of tetra⁃methylapyrazine,derived from the traditional Chinese medicine Ligusticum chuanxiong,which has been widely proven to have therapeutic effects on models of various neurodegenerative diseases.TBN is currently under clinical investi⁃gation for several indications including a phaseⅡtrial of ALS.Here,we explored the therapeutic effect of TBN in the SOD1G93A and TDP-43M337V ALS mouse model.METHODS In the SOD1G93A transgenic mouse model,TBN was administered to mice by intraperitoneal or intragastric injection after the onset of motor deficits.At the same time,we unilaterally and bilaterally injected the TDP-43M337V virus into the striatum of the WT mouse,and gave the TBN treatment after the mice developed a phenotype.After administering these two models for a period of time,we con⁃ducted behavioral tests,including rotarod test,balance beam test,climbing pole test,etc,to evaluate the efficacy of TBN on SOD1G93A and TDP-43M337V models.Furthermore,we explored the possible mechanism of action of TBN in the treatment of ALS through Western blotting and immunohistochemistry/immunofluorescence staining analysis.RESULTS In the SOD1G93A transgenic mouse model,TBN slowed the pro⁃gression of motor neuron disease as evidenced by improved motor performance,reduced spinal motor neuron loss and the associated glial response,and decreased skeletal muscle fiber denervation and fibrosis.TBN treatment activated mitochondrial antioxidant activity through the PGC-1α/Nrf2/HO-1 pathway and decreased the expression of human SOD1.What′s more,in the TDP-43M337V mice model,the results showed that in mice with unilateral injection of TDP-43M337V,TBN improved motor deficits and cognitive im⁃pairment in the early stages of disease progres⁃sion.In mice with bilateral injection of TDP-43M337V into the striatum,TBN not only improved motor function but also prolonged survival rate.Moreover,we show that its therapeutic effect may be through activation of the Akt/mTOR/GSK-3βand AMPK/PGC-1α/Nrf2 signaling pathways.In summary,TBN is a promising agent for the treat⁃ment of ALS/FTLD.CONCLUSION TBN has shown good efficacy in both SOD1 and TDP-43 ALS-related models,and it may act by activating the AMPK/PGC-1α/Nrf2 signaling pathway,which shows some light for the development of ALS therapeutic drugs.
文摘Cotton production substantiated a crucial part in the escalating economic development of many countries.To realize the increasing global demand for cotton,the emphasis should be laid on to improve cotton fiber growth and production.The bioengineered transgenic cotton proved expedient in resolving inadequacies of conventional cotton,but still required improvements to encounter heightened demand of textile industries.One possible solution pertaining to this has been provided by nanoscience in the form of metal or metal oxide nanoparticles.These metal oxide nanoparticles have easy access to the various parts of cotton plants through its transportation system,and thus significantly influence several parameters relative to the growth and production of cotton fiber.This review summarizes the distribution and accumulation of metal oxide nanoparticles in cotton plant and its impact on different plant growth-promoting factors,which resulted in the improved cotton yields.