Huntington＇s disease （HD） is caused by abnormal CAG repeat expansion in the 5＇-end of the Huntingtin （HTT） gene. In addition to the canonical C-terminal full-length huntingtin （htt） nuclear export signal, a cy...Huntington＇s disease （HD） is caused by abnormal CAG repeat expansion in the 5＇-end of the Huntingtin （HTT） gene. In addition to the canonical C-terminal full-length huntingtin （htt） nuclear export signal, a cytoplasmic localization-related domain （CLRD） in the N-terminus of htt has recently been reported. Here, we analyzed this domain by introducing deletion and substitution mutations in a truncated N-terminal htt protein and subsequently monitored htt expression, aggregation and subcellular localization by immunocytochemistry and Western blot analysis. We demonstrated that Htt1-17 was the essential sequence for htt cytoplasmic localization. We also found that the subcellular distribution of htt was altered when Htt1_17 was mutated to contain amino acids of different charges, suggesting a structural requirement of Htt1-17 for the cytoplasmic localization of htt. Deletion of the first three amino acids did not affect its association with mitochondria. We observed that defective cytoplasmic localization resulted in a reduction of total htt aggregates and increased nuclear aggregates, indicating that the subcellular distribution of the protein might influence the aggregation process. These studies provide new insight into the molecular mechanism of htt aggregation in HD.展开更多
Based on the Overlapped Multiplexing Principle[12],a frequency domain OVFDM(Overlapped Frequency Domain Multiplexing) Coding is proposed.By the data weighted shift overlapped version of any band-limited Multiplexing T...Based on the Overlapped Multiplexing Principle[12],a frequency domain OVFDM(Overlapped Frequency Domain Multiplexing) Coding is proposed.By the data weighted shift overlapped version of any band-limited Multiplexing Transfer Function H(f) the coding gain and spectral efficiency are both achieved.The heavier the overlap of the data weighted Multiplexing Transfer Function H(f),the higher the coding gain and spectral efficiency as well as the closer the output to the optimum complex Gaussian distribution.The bit error probability performance is estimated.The time domain OVTDM(Overlapped Time Domain Multiplexing) Coding,the dual of OVFDM in time domain is incidentally proposed as well.Both theoretical analysis and testified simulations show that OVFDM(OVTDM) is suitable for high spectral efficiency application and its spectral efficiency is only roughly linear to SNR rather than the well-known logarithm to SNR.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.30770761 and 30971000)
文摘Huntington＇s disease （HD） is caused by abnormal CAG repeat expansion in the 5＇-end of the Huntingtin （HTT） gene. In addition to the canonical C-terminal full-length huntingtin （htt） nuclear export signal, a cytoplasmic localization-related domain （CLRD） in the N-terminus of htt has recently been reported. Here, we analyzed this domain by introducing deletion and substitution mutations in a truncated N-terminal htt protein and subsequently monitored htt expression, aggregation and subcellular localization by immunocytochemistry and Western blot analysis. We demonstrated that Htt1-17 was the essential sequence for htt cytoplasmic localization. We also found that the subcellular distribution of htt was altered when Htt1_17 was mutated to contain amino acids of different charges, suggesting a structural requirement of Htt1-17 for the cytoplasmic localization of htt. Deletion of the first three amino acids did not affect its association with mitochondria. We observed that defective cytoplasmic localization resulted in a reduction of total htt aggregates and increased nuclear aggregates, indicating that the subcellular distribution of the protein might influence the aggregation process. These studies provide new insight into the molecular mechanism of htt aggregation in HD.
基金The NNSF(National Nature Science Foundation)of China for their continuously long term support by key projects
文摘Based on the Overlapped Multiplexing Principle[12],a frequency domain OVFDM(Overlapped Frequency Domain Multiplexing) Coding is proposed.By the data weighted shift overlapped version of any band-limited Multiplexing Transfer Function H(f) the coding gain and spectral efficiency are both achieved.The heavier the overlap of the data weighted Multiplexing Transfer Function H(f),the higher the coding gain and spectral efficiency as well as the closer the output to the optimum complex Gaussian distribution.The bit error probability performance is estimated.The time domain OVTDM(Overlapped Time Domain Multiplexing) Coding,the dual of OVFDM in time domain is incidentally proposed as well.Both theoretical analysis and testified simulations show that OVFDM(OVTDM) is suitable for high spectral efficiency application and its spectral efficiency is only roughly linear to SNR rather than the well-known logarithm to SNR.
