TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal...TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.展开更多
[Objective] This paper aimed to explore the genetic relationships among different types of Prunus domestica L. in Xinjiang. [Method] The inter-simple se- quence repeat （ISSR） markers were applied to analyze the gene...[Objective] This paper aimed to explore the genetic relationships among different types of Prunus domestica L. in Xinjiang. [Method] The inter-simple se- quence repeat （ISSR） markers were applied to analyze the genetic diversity and relationships among 30 individual plants from 5 types of P. domestica germpiasm resources in Xinjiang. [Result] A total of 317 bands were amplified by 16 selected IS- SR primers. Among the amplified bands, there were 246 polymorphic bands, accounting for 77.60% of the total. The Nei＇s gene diversity index （H） of individuals was 0.266 6. The average Shannon＇s information index （I） of individuals was 0.399 1. And most of the genetic similarity coefficients ranged from 0.555 2 to 0.996 8. It is indicated that the P. domestica germplasm resources have a certain genetic diversity in Xinjiang. The cluster analysis showed that, at the genetic similarity coefficient of 0.719, the 30 individuals were divided into 3 major groups, including a group of introduced European plum varieties, a group of Tacheng Smoked Plum and Tacheng Binzi and a group of Jiashi Smoked Plum and Wild European Plum. While at the genetic similarity coefficient of 0.949, Jiashi Smoked Plum and Wild European Plum were divided into two small groups. [Conclusion] There are very close genetic relationships between Jiashi Smoked Plum and Wild European Plum, and among the introduced European plum varieties, Tacheng Smoked Plum and Tacheng Binzi.展开更多
[Objective] The aim of this study was to understand the flowering biological characteristics of different varieties Prunus domestica L. in Aksu Jiamu Experi- ment Station. [Method] Three varieties of plum as Prunus do...[Objective] The aim of this study was to understand the flowering biological characteristics of different varieties Prunus domestica L. in Aksu Jiamu Experi- ment Station. [Method] Three varieties of plum as Prunus domestica L. cv. ＇French＇, Prunus domestica L. cv. ＂Victoria＇ and Prunus domestica L. cv. ＂Stanley＇ were the research subjects. The phenophases of blooming, and the morphological and developmental characteristics of floral organs were observed. The amount and viability of pollen and the stigma receptivity were measured. [Result] Three varieties of plum all blossomed in early April, and the florescence had lasted for 9-10 d. The average number of anthers was 28.48%. The average number of pollen grains in each flower was 28 700.0. The pollen germination rate was 27.4%. 86.75% of the flowers were medium-styled or long-styled. There was no significant difference in the petal shape, color, anther number, calyx color, and flower ovary among the three varieties of plum. The stigma receptivity was strongest on the first day of flowering, and then dropped gradually. Therefore, the flowers of plum were manual pollinated on the first day of flowering. The duration time of stigma receptivity of Prunus domestica L. cv. ＇Victoria＇ was longer than the other cultivars, the duration time of stigma receptivity was about 5 d. [Conclusion] The pollen number and pollen germination rate of Prunus domestica L. cv. ＇Stanley＇ were higher than the other cultivars, which be considered the most suitable pollinizer for plum. In contrast, the complete flower rate of Prunus domestica L. cv. ＇French＇ and Prunus domestica L. cv. ＇Victoria＇ was relatively high, but the pollen number and pollen germination rate of Prunus domestica L. cv. ＇French＇ and Prunus domestica L. cv. ＇Victoria＇ were lower than Prunus domestica L. cv. ＇Stanley＇, which are not suitable to use as a pollinizer for plum.展开更多
To reveal the insecticidal mechanism of terpinen-4-ol, the activity of Na＋,K＋-ATPase in insects tested were determined in vivo and in vitro. The results showed that terpinen-4-ol and its ester derivatives had strong...To reveal the insecticidal mechanism of terpinen-4-ol, the activity of Na＋,K＋-ATPase in insects tested were determined in vivo and in vitro. The results showed that terpinen-4-ol and its ester derivatives had strong contact activity to housefly and the contact toxicities of its derivatives except Z3 were all superior or equivalent to terpinen-4-ol. All the 7 compounds had strong inhibition towards activity of Na＋,K＋-ATPase. With poisoning symptom exacerbating, the inhibition rates were gradually increased. In vitro, the IC50 of terpinen-4-ol, Z1, Z2, Z4, Z5, and Z6 was 155.89, 197.98, 96.02, 121.36, 124.85, and 153.74 μg mL% respectively. There was well correlation between the LDs0 of terpinen-4-ol derivatives to housefly and the IC50 of terpinen-4-ol derivatives to Na＋,K＋-ATPase in housefly. In conclusion, Na＋,K＋-ATPase was likely the target of terpinen-4-ol against insects.展开更多
An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(...An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(TCF/LEF)transcription factor family,interacts with the Wnt signaling pathway regulator β-catenin and acts as a DNA-specific binding protein.This study sought to elucidate the impact of the interaction between miR 3293p and TCF7L1 on.the growth and apoptosis of OS and analyze the regulatory expression relationship between miRNA and mRNA in osteosarcoma cells using a variety of approaches.MiR329-3p was significantly downregulated,while TCF7L1 was considerably up-regulated in all examined OS cell lines.Additionally,a clinical comparison study was performed using the TCGA database.Subsequently,the regulatory relationship between miR-329-3p and TCF7L1 on the proliferation and apoptosis of OS cells was verified through in vitro and in vivo experiments.When miR 329-3p was transfected into the OS cell line,the expression of TCF7L1 decreased,the proliferation of OS cells was inhibited,the cytoskeleton disintegrated,and the nucleus condensed to fom apoptotic bodies.The expression of proteins that indicate apoptosis increased simultaneously.The cell cycle was arrested in the G0/G1 phase,and the G1/S transition was blocked.The introduction of miR 3293p also inhibited downstream Cyclin D1 of the Wnt pathway.Xenograf experiments indicated that the overexpression of miR-329-3p signi ficanly inhibited the growth of OS xenografts in nude mice,and the expression of TCF7L1 and C-Myc in tumor tssues decreased.MiR 329-3p was significantly reduced in OS cells and played a suppressive role in tumorigenesis and proliferation by targeting TCF7L1 both in vitro and in vivo.Osteosarcoma cell cycle arrest and pathway inhibition were observed upon the regulation of TCF7LI by miR 3293p.Summarizing these results,it can be inferred that miR.3293p exerts anticancer efects in osteosarcoma by inhibiting TCF7L1.展开更多
基金supported by the Koeln Fortune Program/Faculty of Medicine,University of Cologne,the Alzheimer Forschung Initiative e.V.(grant#22039,to HZ)open-access funding from the DFG/GRC issued to the University of CologneAlzheimer Forschung Initiative e.V.for Open Access Publishing(a publication grant#P2401,to MAAK)。
文摘TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.
文摘[Objective] This paper aimed to explore the genetic relationships among different types of Prunus domestica L. in Xinjiang. [Method] The inter-simple se- quence repeat （ISSR） markers were applied to analyze the genetic diversity and relationships among 30 individual plants from 5 types of P. domestica germpiasm resources in Xinjiang. [Result] A total of 317 bands were amplified by 16 selected IS- SR primers. Among the amplified bands, there were 246 polymorphic bands, accounting for 77.60% of the total. The Nei＇s gene diversity index （H） of individuals was 0.266 6. The average Shannon＇s information index （I） of individuals was 0.399 1. And most of the genetic similarity coefficients ranged from 0.555 2 to 0.996 8. It is indicated that the P. domestica germplasm resources have a certain genetic diversity in Xinjiang. The cluster analysis showed that, at the genetic similarity coefficient of 0.719, the 30 individuals were divided into 3 major groups, including a group of introduced European plum varieties, a group of Tacheng Smoked Plum and Tacheng Binzi and a group of Jiashi Smoked Plum and Wild European Plum. While at the genetic similarity coefficient of 0.949, Jiashi Smoked Plum and Wild European Plum were divided into two small groups. [Conclusion] There are very close genetic relationships between Jiashi Smoked Plum and Wild European Plum, and among the introduced European plum varieties, Tacheng Smoked Plum and Tacheng Binzi.
基金Supported by High-quality and Highly-efficient Cultivation Technology Promotion of Prunus simonii~~
文摘[Objective] The aim of this study was to understand the flowering biological characteristics of different varieties Prunus domestica L. in Aksu Jiamu Experi- ment Station. [Method] Three varieties of plum as Prunus domestica L. cv. ＇French＇, Prunus domestica L. cv. ＂Victoria＇ and Prunus domestica L. cv. ＂Stanley＇ were the research subjects. The phenophases of blooming, and the morphological and developmental characteristics of floral organs were observed. The amount and viability of pollen and the stigma receptivity were measured. [Result] Three varieties of plum all blossomed in early April, and the florescence had lasted for 9-10 d. The average number of anthers was 28.48%. The average number of pollen grains in each flower was 28 700.0. The pollen germination rate was 27.4%. 86.75% of the flowers were medium-styled or long-styled. There was no significant difference in the petal shape, color, anther number, calyx color, and flower ovary among the three varieties of plum. The stigma receptivity was strongest on the first day of flowering, and then dropped gradually. Therefore, the flowers of plum were manual pollinated on the first day of flowering. The duration time of stigma receptivity of Prunus domestica L. cv. ＇Victoria＇ was longer than the other cultivars, the duration time of stigma receptivity was about 5 d. [Conclusion] The pollen number and pollen germination rate of Prunus domestica L. cv. ＇Stanley＇ were higher than the other cultivars, which be considered the most suitable pollinizer for plum. In contrast, the complete flower rate of Prunus domestica L. cv. ＇French＇ and Prunus domestica L. cv. ＇Victoria＇ was relatively high, but the pollen number and pollen germination rate of Prunus domestica L. cv. ＇French＇ and Prunus domestica L. cv. ＇Victoria＇ were lower than Prunus domestica L. cv. ＇Stanley＇, which are not suitable to use as a pollinizer for plum.
基金supported by the National Natural Science Foundation of China (30600404)
文摘To reveal the insecticidal mechanism of terpinen-4-ol, the activity of Na＋,K＋-ATPase in insects tested were determined in vivo and in vitro. The results showed that terpinen-4-ol and its ester derivatives had strong contact activity to housefly and the contact toxicities of its derivatives except Z3 were all superior or equivalent to terpinen-4-ol. All the 7 compounds had strong inhibition towards activity of Na＋,K＋-ATPase. With poisoning symptom exacerbating, the inhibition rates were gradually increased. In vitro, the IC50 of terpinen-4-ol, Z1, Z2, Z4, Z5, and Z6 was 155.89, 197.98, 96.02, 121.36, 124.85, and 153.74 μg mL% respectively. There was well correlation between the LDs0 of terpinen-4-ol derivatives to housefly and the IC50 of terpinen-4-ol derivatives to Na＋,K＋-ATPase in housefly. In conclusion, Na＋,K＋-ATPase was likely the target of terpinen-4-ol against insects.
基金The Fund of National Cancer Center Research and Development(26-A-4),The Grants-in-Aid for Scientific Research(Grant Nos.15K10451,16K10866 and 16K20063)from Japan Society for the Promotion of Science.
文摘An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(TCF/LEF)transcription factor family,interacts with the Wnt signaling pathway regulator β-catenin and acts as a DNA-specific binding protein.This study sought to elucidate the impact of the interaction between miR 3293p and TCF7L1 on.the growth and apoptosis of OS and analyze the regulatory expression relationship between miRNA and mRNA in osteosarcoma cells using a variety of approaches.MiR329-3p was significantly downregulated,while TCF7L1 was considerably up-regulated in all examined OS cell lines.Additionally,a clinical comparison study was performed using the TCGA database.Subsequently,the regulatory relationship between miR-329-3p and TCF7L1 on the proliferation and apoptosis of OS cells was verified through in vitro and in vivo experiments.When miR 329-3p was transfected into the OS cell line,the expression of TCF7L1 decreased,the proliferation of OS cells was inhibited,the cytoskeleton disintegrated,and the nucleus condensed to fom apoptotic bodies.The expression of proteins that indicate apoptosis increased simultaneously.The cell cycle was arrested in the G0/G1 phase,and the G1/S transition was blocked.The introduction of miR 3293p also inhibited downstream Cyclin D1 of the Wnt pathway.Xenograf experiments indicated that the overexpression of miR-329-3p signi ficanly inhibited the growth of OS xenografts in nude mice,and the expression of TCF7L1 and C-Myc in tumor tssues decreased.MiR 329-3p was significantly reduced in OS cells and played a suppressive role in tumorigenesis and proliferation by targeting TCF7L1 both in vitro and in vivo.Osteosarcoma cell cycle arrest and pathway inhibition were observed upon the regulation of TCF7LI by miR 3293p.Summarizing these results,it can be inferred that miR.3293p exerts anticancer efects in osteosarcoma by inhibiting TCF7L1.
基金Supported by the National Natural Science Foundation of China(11871452,12071052the Natural Science Foundation of Henan(202300410338)the Nanhu Scholar Program for Young Scholars of XYNU。
