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| 1 | CRISPR/Cas9-mediated PINK1 deletion leads to neurodegeneration in rhesus monkeys显示文摘Dear Editor,PINK1 mutations cause autosomal recessive and early-onset Parkinson’s disease(PD)with selective neurodegeneration.Unfortunately,current PINK1 knockout(KO)mouse1,2 and pig models3,4 are unable to recapitulate the selective and overt neurodegeneration seen in PD patients.Furthermore,endogenous Pink1 in the mouse brain is expressed at very low levels and can only be detected via immunoprecipitation,5 meaning that PINK1’s function in the mammalian brain needs to be assessed using larger animals that are closer to humans.We previously used CRISPR/Cas9 to target the monkey gene in one-cell stage embryos.6 Using the same approach,we designed two gRNAs to target exon 2(T1)and exon 4(T2),which encode a kinase domain in the PINK1 gene of rhesus monkeys(Fig.1a).CRISPR/Cas9 and PINK1 gRNAs were injected into one-cell stage rhesus monkey embryos.A T7E1 assay and sequencing of PCR products from the injected embryos showed high efficiency(61.5%)in targeting PINK1(Fig.1b and Supplementary information,Fig.S1).Transfer of 87 embryos to 28 surrogate rhesus monkeys resulted in 11 pregnancies(39.2%)(Fig.1b).Eleven fetuses developed to term and were born naturally.Of these live monkeys,eight carried PINK1 mutations(M),and three were wild type(WT).However,three mutant monkeys(M1,M3 and M4)were newborn triplets that struggled to survive and died 3-4 days after birth.One WT newborn monkey also died after a difficult labor.Another mutant monkey(M2)died 7 days after birth without noticeable warning signs or symptoms.The other three mutant monkeys(M6,M7 and M8)have lived for three years;M5,however,reduced its food intake and showed weakness at the age of 1.5 years,and died 30 days after anesthesia for MRI examination. | Weili Yang Yunbo Liu Zhuchi Tu Chong Xiao Sen Yan Xishan Ma Xiangyu Guo Xiusheng Chen Peng Yin Zhengyi Yang Su Yang Tianzi Jiang Shihua Li Chuan Qin Xiao-Jiang Li | 2019 | Cell Research2019，29，4： | 12 |
| 2 | Imaging performance evaluation in depth-of-interaction PET with a new method of sinogram generation:A Monte Carlo simulation study显示文摘In conventional PET systems,the parallax error degrades image resolution and causes image distortion.To remedy this,a PET ring diameter has to be much larger than the required size of field of view(FOV),and therefore the cost goes up.Measurement of depth-of-interaction(DOI)information is effective to reduce the parallax error and improve the image quality.This study is aimed at developing a practical method to incorporate DOI information in PET sinogram generation and image reconstruction processes and evaluate its efficacy through Monte Carlo simulation.An animal PET system with 30-mm long LSO crystals and 2-mm DOI measurement accuracy was simulated and list-mode PET data were collected.A sinogram generation method was proposed to bin each coincidence event to the correct LOR location according to both incident crystal indices and DOI positions of the two annihilation photons.The sinograms were reconstructed with an iterative OSMAPEM(ordered subset maximum a posteriori expectation maximization)algorithm.Two phantoms(a rod source phantom and a Derenzo phantom)were simulated,and the benefits of DOI were investigated in terms of reconstructed source diameter(FWHM)and source positioning accuracy.The results demonstrate that the proposed method works well to incorporate DOI information in data processing,which not only overcomes the image distortion problem but also significantly improves image resolution and resolution uniformity and results in satisfactory image quality. | XIA Yan MA Tianyu LIU Yaqiang SUN Xishan WANG Shi SHAO Yiping | 2011 | Nuclear Science and Techniques2011，22，3： | 1 |
| 3 | Effects of Storage Temperature on the Effective Activity of Straw Frozen Semen after Thawing显示文摘The aim was to discuss the optimal storage environment and proper insemination time after thawing of 0. 25 m L straw frozen semen. Straw frozen semen was thawed at 40 ℃ for 20 s,and then stored at 0- 4 ℃,14- 16 ℃,25- 27 ℃ for 2,4,6,8 and 10 h,respectively. The sperm motility was detected. After thawing,semen was stored at 0- 4 ℃ and 14- 16 ℃ for 10 h. Their sperm motilities( 0. 434 ± 0. 016 7 and 0. 423 ± 0. 019 6) had no significant differences( P> 0. 05) with initial thawing motility( 0. 441 ± 0. 030). Sperm motility reduced as the storage time prolonged at 25- 27 ℃. Sperm motility after 6 h had significant differences with that of initial thawing motility( P < 0. 05),and sperm motilities after 8 and 10 h showed extremely significant differences( P < 0. 01).Thus,sperm motility after thawing was still very high after stored at 0- 4 ℃ and 14- 16 ℃ within 10 h,which met the requirements for insemination. Under this temperature and time ranges,sperm could be carried over long distances,which had small effects on sperm quality and reached the expected insemination effects.However,under the temperature of 25- 27 ℃,semen should be used for insemination within 6 h after thawing. | Qiao Limin Ma Jianmin Qiao Fuqiang Yao Hua Xiao Xishan Hou Yinxu Fu Jingtao Ren Kang | 2015 | Animal Husbandry and Feed Science2015，7，4： | 0 |
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