Objective To compare the effects or ouabain and digoxin on both the systolic blood pressure and sodium pump a-subunit isoforms gene expression in the aortic smooth muscle of rats. Methods Normal Sprague- Dawley rats w...Objective To compare the effects or ouabain and digoxin on both the systolic blood pressure and sodium pump a-subunit isoforms gene expression in the aortic smooth muscle of rats. Methods Normal Sprague- Dawley rats were injected with ouabain (20μg·kg-1·d-l,i. p), digoxin (32 μg·kg-1·d-1, i. p)and normal saline once a day, respectively, and indirect systolic blood pressure was recorded once a week. Six weeks later,all the rats were killed and sodium pump α1-,α2-,and α3-subunit mRNA levels were detected in the aortic smooth muscle with reverse transcription polymerase chain reaction（RT-PCR） method. Results The systolic blood pressure of rats infused with ouabain increased significantly at the end of week 6 [l32. 6±9.0 mmHg （1 mmHg = 0. 133 kPa） vs 115. 7 ± 8. 2 mmHg, P <0.01],while no difference of blood pressure was found between digoxin group and NS group （P>0.05）. The expression or sodium pump α-subunit isoforms in aortic smooth muscle was regulated by either ouabain or digox- in:both ouabain and digoxin increased α1- and α3-subunit expression, α2-subunit decreased in digoxin group but un- changed in ouabain group. Conclusion These results suggest that both ouabain and digoxin could regulate sodium pump α-subunit isoform expression, which might be related to the physiological roles or endogenous ouabain and might be responsible for the difference between the pharmacological and toxicological effects or ouabain and digoxin, including their effects on blood pressure.展开更多
Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in viv...Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.展开更多
We demonstrate an all-solid quasi-continuous-wave （QCW） narrow-band source tunable to sodium D2a line at 589.159 nm. The source is based on sum-frequency mixing between lasers at 1064 nm and 1319 nm in a LBO crystal...We demonstrate an all-solid quasi-continuous-wave （QCW） narrow-band source tunable to sodium D2a line at 589.159 nm. The source is based on sum-frequency mixing between lasers at 1064 nm and 1319 nm in a LBO crystal. The 1064 nm and 1319 nm lasers are produced from two diode side-pumped Nd：YAG master oscillator power amplifier （MOPA） laser systems, respectively. A 33 W output of 589 nm laser is obtained with beam quality factor M^2 = 1.25, frequency stability better than ±0.2 GHz and linewidth less than 0.44 GHz. A prototype 589 nm laser system is assembled, and a sodium laser guided star has been successfully observed in the field test.展开更多
The Australian first working sodium guide star laser system has been designed and developed for various astronomical and space-related applications. A completely diode-pumped pulsed system was developed initially foll...The Australian first working sodium guide star laser system has been designed and developed for various astronomical and space-related applications. A completely diode-pumped pulsed system was developed initially followed by a largely fiber-based continuous wave (CW) system operating at 589 nm achieved through a unique wavelength conversion scheme by combining 1342 and 1050 nm through a sum frequency generation process. For the CW system, single-mode laser beams at both 1342 and 1050 nm are achieved from fiber-based seed oscillators and fiber amplifiers. The output power of ~25 W at 1342 nm is achieved from a single frequency fiber Raman amplifier. Output power up to 70 W at 1050 nm is achieved from a Yb-doped fiber pre-amplifier followed by a Yb-doped fiber power amplifier. For the sum frequency generation process, optimum focusing parameters are evaluated and determined. The CW system has generated more than 20 W output power at 589 nm, a circularly polarised beam with a good beam quality, spectral linewidth ≤ 2 MHz, and the laser output locked on the sodium D2 line at 589.159 nm. The system has been successfully demonstrated at EOS Space Research Centre, Mt Stromlo, Canberra, and become the Australian first working sodium guide star laser system.展开更多
基金This project supported by the National Natural Science Foundation of China(No. 39670325).
文摘Objective To compare the effects or ouabain and digoxin on both the systolic blood pressure and sodium pump a-subunit isoforms gene expression in the aortic smooth muscle of rats. Methods Normal Sprague- Dawley rats were injected with ouabain (20μg·kg-1·d-l,i. p), digoxin (32 μg·kg-1·d-1, i. p)and normal saline once a day, respectively, and indirect systolic blood pressure was recorded once a week. Six weeks later,all the rats were killed and sodium pump α1-,α2-,and α3-subunit mRNA levels were detected in the aortic smooth muscle with reverse transcription polymerase chain reaction（RT-PCR） method. Results The systolic blood pressure of rats infused with ouabain increased significantly at the end of week 6 [l32. 6±9.0 mmHg （1 mmHg = 0. 133 kPa） vs 115. 7 ± 8. 2 mmHg, P <0.01],while no difference of blood pressure was found between digoxin group and NS group （P>0.05）. The expression or sodium pump α-subunit isoforms in aortic smooth muscle was regulated by either ouabain or digox- in:both ouabain and digoxin increased α1- and α3-subunit expression, α2-subunit decreased in digoxin group but un- changed in ouabain group. Conclusion These results suggest that both ouabain and digoxin could regulate sodium pump α-subunit isoform expression, which might be related to the physiological roles or endogenous ouabain and might be responsible for the difference between the pharmacological and toxicological effects or ouabain and digoxin, including their effects on blood pressure.
基金supported by the Natural Science Foundation of Fujian Province,No.2020J02027the National Natural Science Foundation of China,No.31970461the Foundation of NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate,Fujian Maternity and Child Health Hospital,No.2022-NHP-05(all to WC).
文摘Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.
文摘We demonstrate an all-solid quasi-continuous-wave （QCW） narrow-band source tunable to sodium D2a line at 589.159 nm. The source is based on sum-frequency mixing between lasers at 1064 nm and 1319 nm in a LBO crystal. The 1064 nm and 1319 nm lasers are produced from two diode side-pumped Nd：YAG master oscillator power amplifier （MOPA） laser systems, respectively. A 33 W output of 589 nm laser is obtained with beam quality factor M^2 = 1.25, frequency stability better than ±0.2 GHz and linewidth less than 0.44 GHz. A prototype 589 nm laser system is assembled, and a sodium laser guided star has been successfully observed in the field test.
文摘The Australian first working sodium guide star laser system has been designed and developed for various astronomical and space-related applications. A completely diode-pumped pulsed system was developed initially followed by a largely fiber-based continuous wave (CW) system operating at 589 nm achieved through a unique wavelength conversion scheme by combining 1342 and 1050 nm through a sum frequency generation process. For the CW system, single-mode laser beams at both 1342 and 1050 nm are achieved from fiber-based seed oscillators and fiber amplifiers. The output power of ~25 W at 1342 nm is achieved from a single frequency fiber Raman amplifier. Output power up to 70 W at 1050 nm is achieved from a Yb-doped fiber pre-amplifier followed by a Yb-doped fiber power amplifier. For the sum frequency generation process, optimum focusing parameters are evaluated and determined. The CW system has generated more than 20 W output power at 589 nm, a circularly polarised beam with a good beam quality, spectral linewidth ≤ 2 MHz, and the laser output locked on the sodium D2 line at 589.159 nm. The system has been successfully demonstrated at EOS Space Research Centre, Mt Stromlo, Canberra, and become the Australian first working sodium guide star laser system.
