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Questions about NgAgo

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Protein & Cell 2016年第12期7卷 913-915页

作者： shawn burgess Linzhao Cheng Feng Gu Zhiwei Huang Shuo Lin Jinsong Li Wei Li Wei Qin Yujie Sun Zhou Songyang Wensheng Wei Qiang Wu Haoyi Wang Xiaoqun Wang Jing-Wei Xiong Jianzhong Xi Hui Yang Bin Zhou Bo Zhang Junjiu Huang National Human Genome Research Institute NIH Bethesda MD 20892 USA Division of Hematology in Department of Medicine Johns HopkinsUniversity School of Medicine Baltimore MD 21205 USA Stem Cell Program in the Institute for Cell Engineering Johns Hopkins University School of Medicine Baltimore MD 21205 USA Center for Vision Research Eye Hospital Wenzhou Medical University Wenzhou 325035 China Stem Cell and Functional Genomics Laboratory School of LifeSciences Sun Yat-sen University Guangzhou 510275 China HIT Center of Life Sciences Harbin Institute of Technology Harbin 150080 China Department of Molecular Cell and Developmental Biology University of California Los Angeles Los Angeles CA 90095 USA Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China State Key Laboratory of Stem cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China College of Chemical Biology and Biotechnology Peking Univer- sity Shenzhen Graduate School Shenzhen 518055 China PKU BIOPIC Beijing 100871 China BIOPIC ICG CLS and School of Life Sciences Peking Univer-sity Beijing 100871 China Center for Comparative Biomedicine Institute of SystemsBiomedicine Shanghai Jiao Tong University Shanghai 200240China Institute of Biophysics Chinese Academy of Sciences Beijing100101 China Institute of Molecular Medicine Peking University Beijing100871 China College of Engineering Peking University Beiiing 100871 China Laboratory of Disease Models in Non-Human Primates Instituteof Neuroscience Shanghai Chinese Academy of SciencesShanghai 200031 China College of Life Sciences Peking University Beijing 100871 China

Dear Editor： Gao et al. published data in Nature Biotechnology （Nat Biotechnol. 2016 May 2） showing that DNA-guided genome editing using the Natronobacterium gregoryi Argonaute （NgAgo） protein targeted 47 mammalian genomic loci with a 100% success rate and an efficiency of 21.3%-41.3% at various targets. This report led us to test NgAgo＇s utility in various cells and organisms such as mouse and zebrafish for gene editing.

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Erratum to： Questions about NgAgo

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Protein & Cell 2017年第1期8卷 77-77页

作者： shawn burgess Linzhao Cheng Feng Gu Junjiu Huang Zhiwei Huang Shuo Lin Jinsong Li Wei Li Wei Qin Yujie Sun Zhou Songyang wensheng Wei Qiang Wu Haoyi Wang Xiaoqun Wang Jing-Wei Xiong Jianzhong Xi Hui Yang Bin Zhou Bo Zhang National Human Genome Research Institute NIH Bethesda MD USA Division of Hematology in Department of Medicine Johns Hopkins University School of Medicine Baltimore MD 21205 USA Stem Cell Program in the Institute for Cell Engineering Johns Hopkins University School of Medicine Baltimore MD 21205 USA Center for Vision Research Eye Hospital Wenzhou Medical University Wenzhou 325035 China Stem Cell and Functional Genomics Laboratory School of Life Sciences Sun Yat-sen University Guangzhou 510275 China HIT Center of Life Sciences Harbin Institute of Technology Harbin 150080 China Department of Molecular Cell and Developmental Biology University of California Los Angeles Los Angeles CA 90095 USA Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China State Key Laboratory of Stem cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China College of Chemical Biology and Biotechnology Peking University Shenzhen Graduate School Shenzhen 518055 China PKU BIOPIC Beijing 100871 China BIOPIC ICG CLS and School of Life Sciences Peking University Beijing 100871 China Center for Comparative Biomedicine Institute of Systems Biomedicine Shanghai Jiao Tong University Shanghai 200240 China Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China Institute of Molecular Medicine Peking University Beijing 100871 China College of Engineering Peking University Beijing 106871 China Laboratory of Disease Models in Non-Human Primates Institute of Neuroscience Shanghai Chinese Academy of Sciences Shanghai 200031 China College of Life Sciences Peking University Beijing 100871 China

In the original publication of this article the Figure 1E legend has been incorrectly published.

关键词： Erratum Questions NgAgo

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反转录病毒介导的斑马鱼全基因组高效突变

反转录病毒介导的斑马鱼全基因组高效突变

A genome-wide association analysis implicates SOX6 as a candidate gene for wrist bone mass

中国遗传学会第八次代表大会暨学术讨论会

作者：郑乃中王冬梅 Li-En Jao Kyle Dolan Jessica Ivey Seth Zonies Xiaolin Wu 邬康迈杨红波孟庆超朱作言 shawn M．burgess 林硕张博细胞增殖与分化教育部重点实验室北京大学生命科学学院

我们发展了一套高效的斑马鱼反转录病毒插入突变技术。通过在斑马鱼胚胎中注射源于鼠莫勒氏白血病病毒的假型反转录病毒和 LM-PCR 技术定位病毒插入的位点等方法,我们可以得到大量携带有反转录病毒插入的斑马鱼。通过对～3000个携带反... 详细信息

我们发展了一套高效的斑马鱼反转录病毒插入突变技术。通过在斑马鱼胚胎中注射源于鼠莫勒氏白血病病毒的假型反转录病毒和 LM-PCR 技术定位病毒插入的位点等方法,我们可以得到大量携带有反转录病毒插入的斑马鱼。通过对～3000个携带反转录病毒插入的 F成鱼的病毒插入位点附近的基因组进行高通量测序,我们得到了～4000个不同的反转录病毒插入旁侧序列。其中的1857个序列可以在斑马鱼基因组数据中得到定位,有687个插入位于基因附近,并且插入更偏好于第一个内含子区域。我们对25个病毒插入在基因内的斑马鱼进行内交。检测其后代胚胎的 mRNA 水平,结果表明对于约50%的"基因插入",mRNA 水平会有大于70%的降低,并且最有可能发生突变的插入位点为外显子和第一个内含子。基于上述结果,反转录病毒在基因内插入造成突变的几率大约为1/5。在19个导致 mRNA 水平降低的插入中观察到3个在胚胎发育过程中出现突变表型。这样,按照我们的策略,大约测定30个 F的序列可以找到一个突变体:这是用 TILLING 的方法鉴定突变体的效率的20-30倍。如果与斑马鱼的精子冻存技术相结合,将 F斑马鱼的精子冻存,那么将可能对斑马鱼全部基因进行突变。

关键词：斑马鱼插入诱变反转录病毒

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Science China(Life Sciences) 2010年第9期53卷 1065-1072页

作者： shawn LEVY Vanderbilt Microarray Shared Resource Vanderbilt University

Osteoporosis is a highly heritable common bone disease leading to fractures that severely impair the life quality of *** fractures caused by osteoporosis are largely due to the scarcity of wrist bone *** we report the results of a genome-wide association study (GWAS) of wrist bone mineral density (BMD).We examined ～500000 SNP markers in 1000 unrelated homogeneous Caucasian subjects and found a novel allelic association with wrist BMD at rs11023787 in the SOX6 (SRY (sex determining region Y)-box 6) gene (P=9.00×10-5).Subjects carrying the C allele of rs11023787 in SOX6 had significantly higher mean wrist BMD values than those with the T allele (0.485:0.462 g cm-2 for C allele vs.T allele carriers).For validation,we performed SOX6 association for BMD in an independent Chinese sample and found that SNP rs11023787 was significantly associated with wrist BMD in the Chinese sample (P=6.41×10-3).Meta-analyses of the GWAS scan and the replication studies yielded P-values of 5.20×10-6 for *** of this study,together with the functional relevance of SOX6 in cartilage formation,support the SOX6 gene as an important gene for BMD variation.

关键词： osteoporosis GWAS SOX6 SNPs wrist BMD

MicroRNA expression and function in prostate cancer： a review of current knowledge and opportunities for discovery

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Asian Journal of Andrology 2016年第4期18卷 559-567页

作者： Binod Kumar shawn E Lupold The James Buchanan Brady Urological Institute Department of Urology Johns Hopkins School of Medicine Baltimore MD USA.

MicroRNAs （miRNAs） are well-conserved noncoding RNAs that broadly regulate gene expression through posttranscriptional silencing of coding genes. Dysregulated miRNA expression in prostate and other cancers implicates their role in cancer biology. Moreover, functional studies provide support for the contribution of miRNAs to several key pathways in cancer initiation and progression. Comparative analyses of miRNA gene expression between malignant and nonmalignant prostate tissues, healthy controls and prostate cancer （PCa） patients, as well as less aggressive versus more aggressive disease indicate that miRNAs may be future diagnostic or prognostic biomarkers in tumor tissue, blood, or urine. Further, miRNAs may be future therapeutics or therapeutic targets. In this review, we examine the miRNAs most commonly observed to be de-regulated in PCa gene expression analyses and review the potential contribution of these miRNAs to important pathways in PCa initiation and progression.

关键词： miRNA prostate cancer noncoding RNA

Experimental investigation of sediment transport in partially ice-covered channels

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International Journal of Sediment Research 2023年第5期38卷 769-779页

作者： Mina Rouzegar shawn P.Clark Department of Civil Engineering University of Manitoba

It is important to understand the effects of ice cover on sediment transport in cold climates, where subfreezing temperatures affect water bodies for a significant part of the year. The literature contains many studies on sediment transport in open channel flow, and several studies on sediment transport in completely ice-covered flow. There has been little or no research on sediment transport in partially icecovered channels. In the current study, laboratory experiments were done in a rectangular flume to quantify the impact of border ice presence on the sediment transport rate. The effects of ice cover extent and changing flow strengths on sediment transport distribution also were investigated, and the results were compared to those for fully ice-covered and open channel flow. The ice coverage ratios considered were 0(representing the open water condition), 0.25, 0.50, 0.67, and 1(representing fully ice-covered flow). The partial ice cover was found to impact the sediment transport distribution within the channel. The effect of ice coverage extent on sediment transport distribution was more significant at lower flow strengths and became negligible at higher flow strengths. The conventional equations for sediment transport in open channel flow and fully ice-covered flow that relate the dimensionless bedload transport rate to the flow strength were found to be applicable to estimate the total cross-section-averaged bedload transport for partially ice-covered flow when modified appropriately. Empirical coefficients for these equations were determined using the experimental data.

关键词： Sediment transport Bedload Ice-covered channel Border ice

Measurement of bullet impact conditions using automated in-flight photography system

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Defence Technology（防务技术） 2017年第4期13卷 288-294页

作者： Ryan Decker Marco Duca shawn Spickert-Fulton Armament Research Design and Engineering Center 94 Ramsey Avenue Picatinny Arsenal NJ 07806 USA

Knowledge of impact conditions is critical to evaluating the terminal impact performance of a *** a small caliber bullet,in-flight velocity has been precisely measured for decades using detection screens,but accurately quantifying the orientation of the bullet on a target has been more *** report introduces the Automated Small-Arms Photogrammetry(ASAP)analysis method used to measure,model,and predict the orientation of a small caliber bullet before reaching an impact *** uses advanced hardware developed by Sydor Technologies to record a series of infrared digital *** images(four orthogonal pairs)are processed using computer vision algorithms to quantify the orientation of the projectile and re-project its precise position and orientation into a three-dimensional muzzle-fixed coordinate *** epicyclic motion model is fit to the measured data,and the epicyclic motion is extrapolated to the target *** results are fairly immediate and may be reviewed during ***-out demonstrations have shown that the impact-angle prediction capability is less than six hundredths of a degree for the 5.56 mm ball round ***:Yaw,Terminal ballistics,Exterior ballistics,Test&evaluation,Computer vision,Image processing,Angle of

关键词： Terminal ballistics Exterior ballistics Test & evaluation Computer vision Image processing Angle of attack

The substrates of Plk1, beyond the functions in mitosis

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Protein & Cell 2010年第11期1卷 999-1010页

作者： X.shawn Liu Bing Song Xiaoqi Liu Department of Biochemistry Purdue UniversityWest LafayetteIndiana 47907USA Department of Biological Sciences Purdue UniversityWest LafayetteIndiana 47907USA Center for Cancer Research Purdue UniversityWest LafayetteIndiana 47907USA

Polo-like kinase 1(Plk1)is a key regulator of cell division in eukaryotic *** this short review,we briefly summarized the well-established functions modulated by Plk1 during *** mitosis,we focused mainly on the unexpected processes in which Plk1 emerges as a critical player,including microtubule dynamics,DNA replication,chromosome dynamics,p53 regulation,and recovery from the G2 DNA-damage *** discussion is mainly based on the critical substrates targeted by Plk1 during these cellular events and the functional significance associated with each phosphorylation event.

关键词： Polo-like kinase 1 phosphorylation substrates

Predicting the Thermal Behavior in Functional Textile Fibers Having Embedded Electronics

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Advanced Fiber Materials 2022年第6期4卷 1609-1619页

作者： Shaun Berry shawn Redmond Tairan Wang Mordechai Rothschild MIT Lincoln Laboratory 244 Wood StreetLexingtonMA 02421USA

In this paper,both steady-state and transient thermal simulations were performed on functional fibers having an embedded electronic chip acting as a heat *** were conducted for a range of different fiber materials and arbitrary fiber cross-sectional *** show that under steady-state heating conditions,the thermal response for any arbitrary fiber shape and fiber material system was convection dominated regardless of the effective thermal conductivity of the fiber,and that the corresponding temperature rise within the fiber can be predicted analytically allowing for the maximum temperature to be estimated for any known heat load and fiber *** the case of transient heating,we show that for pulsed power operation of the embedded electronic device,the maximum temperature reached in the fiber is always greater than the maximum temperature of the equivalent steady-state average ***,high peak powers can be safely achieved if the power-on pulse time and duty cycle are selected to limit the maximum temperature reached in the *** on the results from the transient simulations,a set of criteria was developed to determine whether the operating conditions would be:(1)allowable for the fiber system,thus requiring no transient simulations,(2)requiring a transient simulation to verify that the maximum temperature is acceptable,and(3)the operating conditions are too severe and device operation at these conditions are not practical.

关键词： Functional fibers Smart fibers Thermal modeling Fabrics MOEMS