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Crystal structure of a PP2A B56-BubR1 complex and its implications for PP2A substrate recruitment and localization

Protein & Cell 2016年第7期7卷 516-526页

作者： Jiao Wang Zhizhi Wang Tingting Yu Huan Yang david M. Virshup Geert J. P. L. Kops Sang Hyun lee weihong Zhou Xin Li Wenqing Xu Zihe Rao College of Life Sciences Nankai University Tianjin 30071 China Department of Biological Structure University of Washington Seattle WA 98195 USA Program in Cancer and Stem Cell Biology Duke-NUS Graduate Medical School 8 College Road Singapore 169857 Singapore Department of Pediatrics Duke University Medical Center Durham NC 27710 USA Molecular Cancer Research and Cancer-Genomics Centre and Department of Medical Oncology UMC Utrecht Universiteitsweg 100 3584 CG Utrecht The Netherlands National Laboratory of Macromolecutes Institute of Biophysics Chinese Academy of Sciences Beijing 100010 China

Protein phosphatase 2A （PP2A） accounts for the majority of total Ser/Thr phosphatase activities in most cell types and regulates many biological processes. PP2A holoenzymes contain a scaffold A subunit, a cat- alytic C subunit, and one of the regulatory/targeting B subunits. How the B subunit controls PP2A localization and substrate specificity, which is a crucial aspect of PP2A regulation, remains poorly understood. The kine- tochore is a critical site for PP2A functioning, where PP2A orchestrates chromosome segregation through its interactions with BubR1. The PP2A-BubR1 interac- tion plays important roles in both spindle checkpoint silencing and stable microtubule-kinetochore attach- ment. Here we present the crystal structure of a PP2A B56-BubRI complex, which demonstrates that a con- served BubRl LxxlxE motif binds to the concave side of the B56 pseudo-HEAT repeats. The BubR1 motif binds to a groove formed between B56 HEAT repeats 3 and 4, which is quite distant from the B56 binding surface for PP2A catalytic C subunit and thus is unlikely to affect PP2A activity. In addition, the BubR1 binding site on B56 is far from the B56 binding site of shugoshin, another kinetochore PP2A-binding protein, and thus BubR1 and shugoshin can potentially interact with PP2A-B56 simultaneously. Our structural and biochemical analysis indicates that other proteins with the LxxlxE motif may also bind to the same PP2A B56 surface. Thus, our structure of the PP2A B56-BubR1 complex provides important insights into how the B56 subunit directs the recruitment of PP2A to specific targets.

关键词： PP2A BubR1 kinetochore cellulartargeting substrate recruitment

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通过研究解密大脑——脑健康的未来

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英国医学杂志中文版 2021年第1期24卷 29-32页

作者： david Z Wang lee H Schwamm 钱天翼戴琼海美国凤凰城Barrow Neurological Institute 美国哈佛麻省总医院卒中中心中国腾讯觅影/医疗技术委员会中国清华大学信息学院及脑与认知科学研究院

david Z Wang和同事们研究了大脑研究的最新进展,以及它们如何影响大脑疾病的治疗。整个世界都在积极地解决大脑之奥秘,人们已经在了解大脑对人类意识产生中发挥的基本作用以及发现脑疾病的治疗方法方面走了很长一段路。公元前430年希... 详细信息

david Z Wang和同事们研究了大脑研究的最新进展,以及它们如何影响大脑疾病的治疗。整个世界都在积极地解决大脑之奥秘,人们已经在了解大脑对人类意识产生中发挥的基本作用以及发现脑疾病的治疗方法方面走了很长一段路。公元前430年希波克拉底的《神圣疾病》(The Sacred Disease)中就有记载,大脑是用来容纳心室的,其主要目的是作为身体从外部呼吸空气的容器和转运点,从而为我们的生命带来喜怒哀乐。

关键词：希波克拉底人类意识脑健康转运点大脑喜怒哀乐

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Study on the “meta-Effect” Photochemical Reactions of Selected Benzophenone and Anthraquinone Compounds

Study on the “meta-Effect” Photochemical Reactions of Sele...

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中国化学会第十二届全国物理有机化学学术会议

作者：马佳妮 david lee Phillips 西北大学化学与材料科学学院香港大学化学系

Benzophenone(BP)and anthraquinone(AQ)derivatives have been studied under a variety of *** hydrogen abstraction reaction and electron transfer are commonly observed.A new kind of reaction only occurs for meta-substitut...

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Microporous Metal Organic Frameworks as Functional Materials for Gas Storage and Separation

Microporous Metal Organic Frameworks as Functional Materials...

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中国化学会第五届全国结构化学学术会议

作者： JeongYong lee david H.Olson Department of Chemistry and Chemical Biology Rutgers The State University of New Jersey PiscatawayNJ 08854USA Department of Chemistry and Chemical Biology Rutgers The State University of New Jersey PiscatawayNJ 08854USA

＜正＞Recent studies have uncovered many unique and interesting functionality of metal coordination compounds,in particular,those of microporous metal organic frameworks（MMOFs）having extended three-dimensional open ...

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Case Study of Middle East Respiratory Syndrome (MERS-CoV) Outbreak in South Korea and Future Implications

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Advances in Infectious Diseases 2020年第2期10卷 76-89页

作者： Woo Hyung lee david Ahn Kunmin Kim Peter S. Park Seog In Moon Hark Joon lee david Park Hyun Seung Shin Eunice Kang Daniel Choo david S. Chung Biotechnology School of Science Hong Kong University of Science of Technology Hong Kong China Department of Economics William & Mary Williamsburg VA USA Department of Chemistry and Biochemistry University of California San Diego CA USA Department of Biology College of Art and Science Biology Cornell University Ithaca NY USA Department of Biology Amherst College Amherst MA USA Department of Biology Washington University St. Louis MO USA College of Art and Science Biology Emory University Atlanta GA USA Division of Biomedical Informatics University of Virginia Charlottesville VA USA Youth with Talents Fairfax VA USA School of Medicine University of Virginia Charlottesville VA USA

The Middle East Respiratory Syndrome (MERS-CoV) is a potentially fatal respiratory viral infection that has had outbreaks in the Middle East and Asia region starting in 2012. As recent as 2015, MERS had outbreaks in South Korea, resulting in 36 deaths among 186 infected patients. The purpose of this thesis is to gain an in-depth understanding of how this viral infection behaves in outbreaks and how it is spread around the globe. To gain insight, real time analysis was performed under a case study methodology based on pooled data from the Ministry of Health & Welfare of South Korea. We calculated a striated mortality rate based on gender, age, and the presence of pre-existing health conditions ranging from heart, lung, and kidney diseases. We found that MERS outbreak follows the pattern of a point source outbreak, largely spurred by the patient-referral system under the universal healthcare system in South Korea. The purpose of this case is to discuss the benefits and challenges of such patient referral system, and to offer a possible solution in improving transparency between healthcare providers and the government under a universal healthcare system to prevent future outbreaks.

关键词： Infectious Diseases Respiratory Viral Infections Public Health Disease Prevention

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Novel strategy for disease risk prediction incorporating predicted gene expression and DNA methylation data:a multi-phased study of prostate cancer

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Cancer Communications 2021年第12期41卷 1387-1397页

作者： Chong Wu Jingjing Zhu Austin King Xiaoran Tong Qing Lu Jong Y.Park Liang Wang Guimin Gao Hong-Wen Deng Yaohua Yang Karen E.Knudsen Timothy R.Rebbeck Jirong Long wei Zheng wei Pan david V.Conti Christopher A Haiman Lang Wu Department of Statistics Florida State UniversityTallahasseeFL 32304USA Cancer Epidemiology Division Population Sciences in the Pacific ProgramUniversity of Hawaii Cancer CenterUniversity of Hawaii at ManoaHonoluluHI 96813USA Department of Epidemiology and Biostatistics Michigan State UniversityEast LansingMI 48824USA Department of Biostatistics University of FloridaGainesvilleFL 32603USA Department of Cancer Epidemiology H.Lee Moffitt Cancer Center and Research InstituteTampaFL 33612USA Department of Tumor Biology H.Lee Moffitt Cancer Center and Research InstituteTampaFL 33612USA Department of Public Health Sciences University of ChicagoChicagoIL 60637USA Center of Bioinformatics and Genomics Department of Global Biostatistics and Data ScienceTulane UniversityNew OrleansLA 70112USA Division of Epidemiology Department of MedicineVanderbilt Epidemiology CenterVanderbilt-Ingram Cancer CenterVanderbilt University Medical CenterNashvilleTN 37203USA Department of Cancer Biology Sidney Kimmel Cancer CenterThomas Jefferson UniversityPhiladelphiaPA 19107USA Department of Medical Oncology Dana-Farber Cancer InstituteBostonMA 02215USA Department of Epidemiology Harvard TH Chan School of Public HealthBostonMA 02115USA Division of Biostatistics University of MinnesotaMinneapolisMN 55455USA Department of Preventive Medicine Keck School of MedicineUniversity of Southern California/Norris Comprehensive Cancer CenterLos AngelesCA 90033USA

Background:DNA methylation and gene expression are known to play important roles in the etiology of human diseases such as prostate cancer(PCa).However,it has not yet been possible to incorporate information of DNA methylation and gene expression into polygenic risk scores(PRSs).Here,we aimed to develop and validate an improved PRS for PCa risk by incorporating genetically predicted gene expression and DNA methylation,and other genomic information using an integrative ***:Using data from the PRACTICAL consortium,we derived multiple sets of genetic scores,including those based on available single-nucleotide polymorphisms through widely used methods of pruning and thresholding,LDpred,LDpred-funt,AnnoPred,and EBPRS,as well as PRS constructed using the genetically predicted gene expression and DNA methylation through a revised pruning and thresholding *** the tuning step,using the UK Biobank data(1458 prevalent cases and 1467 controls),we selected PRSs with the best *** an independent set of data from the UK Biobank,we developed an integrative PRS combining information from individual ***,in the testing step,we tested the performance of the integrative PRS in another independent set of UK Biobank data of incident cases and ***:Our constructed PRS had improved performance(C statistics:76.1%)over PRSs constructed by individual benchmark methods(from 69.6%to 74.7%).Furthermore,our new PRS had much higher risk assessment power than family *** overall net reclassification improvement was 69.0%by adding PRS to the baseline model compared with 12.5%by adding family ***:We developed and validated a new PRS which may improve the utility in predicting the risk of developing *** innovative method can also be applied to other human diseases to improve risk prediction across multiple outcomes.

关键词： risk prediction polygenic risk scores predicted gene expression predicted DNA methylation integrative models prostate cancer

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The Effect of Fasting on PET Imaging of Hepatocellular Carcinoma

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Journal of Cancer Therapy 2013年第2期4卷 562-567页

作者： Nathan Tenley david J. Corn Lewis Yuan Zhenghong lee Department of Biomedical Engineering Case Western Reserve University Cleveland USA Department of Radiology University Hospitals Case Medical Center Cleveland USA.

The clinical utility of positron emission tomography (PET) imaging for liver cancer applications is not clearly defined either for diagnosis or treatment assessment. Previous clinical studies demonstrated that fluorodeoxyglucose (FDG) did not show uptake in some hepatocellular carcinoma (HCC) while acetate showed uptake. Pre-imaging fasting is required for clinical PET imaging with FDG. No studies were done to confirm the effect of fasting on acetate uptake in HCC for PET imaging. We investigated this situation with a woodchuck model of viral infection-induced HCC. Methods: Four tumor-bearing and one control woodchucks were involved in this study. They were first imaged by PET in fed state followed by another imaging session one week later when they were fasted over-night. Some animals also had FDG- PET scan that was acquired later on the same day. After imaging studies, animals were sacrificed, and their liver excised for histology. Standardized Uptake Value (SUV) was calculated using a region of interest (ROI) placed on each tumor with focal uptake. Results: Acetate showed uptake in each HCC lesion when the animals were either fasted or fed with no significant difference in SUV values (p = 0.177);some of the tumors were histologically confirmed as well-differentiated HCC while others were confirmed as moderately- or poorly-differentiated HCC;no focal uptake was found in the control animal. For the accompanying FDG scans, the uptake was detected only in animals that were fasted although the uptake pattern was different from that with acetate. Conclusion: This study provided a hint that fasting or not has little impact on PET imaging of HCC with acetate. It also confirmed prior finding regarding tumor heterogeneity that led to different tracer uptake pattern in the same tumor. Human studies are needed to validate the findings from this pre-clinical investigation.

关键词： Acetate FDG Hepatocellular Carcinoma Woodchuck Positron Emission Tomography

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A cluster-randomized trial comparing two SWITCH implementation support strategies for school wellness intervention effectiveness

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Journal of Sport and Health Science 2023年第1期12卷 87-96页

作者： Richard R.Rosenkranz Philip M.Dixon david A.Dzewaltowski Gabriella M.McLoughlin Joey A.lee Senlin Chen Spyridoula Vazou Lorraine M.Lanningham-Foster Doug A.Gentile Gregory J.Welk Department of Food NutritionDietetics&HealthKansas State UniversityManhattanKS 66506USA Department of Statistics Snedecor HallIowa State UniversityAmesIA 50011-1210USA Department of Health Promotion University of NebraskaOmahaNE 68198-4365USA Implementation Science Center for Cancer Control and Prevention Research Center Brown SchoolWashington University in St.LouisSt.LouisMO 63130USA Division of Public Health Sciences(Department of Surgery) Washington University School of MedicineWashington University in St.LouisSt.LouisMO 63130USA Department of Health Sciences University of Colorado Colorado SpringsColorado SpringsCO 80918USA Department of Kinesiology Iowa State UniversityAmesIA 50011-4008USA Department of Food Science&Human Nutrition Iowa State UniversityAmesIA 50011USA Department of Psychology Iowa State UniversityAmesIA 50011-1041USA

Background:The School Wellness Integration Targeting Child Health(SWITCH)intervention has demonstrated feasibility as an implementation approach to help schools facilitate changes in students’physical activity(PA),sedentary screen time(SST),and dietary intake(DI).This study evaluated the comparative effectiveness of enhanced(individualized)implementation and standard(group-based)***:Twenty-two Iowa elementary schools participated,with each receiving standardized training(wellness conference and webinars).Schools were matched within region and randomized to receive either individualized or group implementation *** PA,SST,and DI outcomes of 1097 students were assessed at pre-and post-intervention periods using the Youth Activity *** mixed models evaluated differential change in outcomes by condition,for comparative effectiveness,and by ***:Both implementation conditions led to significant improvements in PA and SST over time(p<0.01),but DI did not improve commensurately(p value range:0.02‒0.05).There were no differential changes between the group and individualized conditions for PA(p=0.51),SST(p=0.19),or DI(p=0.73).There were no differential effects by gender(i.e.,non-significant condition-by-gender interactions)for PA(p_(for interaction)=0.86),SST(p_(for interaction)=0.46),or DI(p_(for interaction)=0.15).Effect sizes for both conditions equated to approximately 6 min more PA per day and approximately 3 min less sedentary ***:The observed lack of difference in outcomes suggests that group implementation of SWITCH is equally effective as individualized implementation for building capacity in school wellness ***,the lack of interaction by gender suggests that SWITCH can be beneficial for both boys and *** research is needed to understand the school-level factors that influence implementation(and outcomes)of SWITCH.

关键词： Children Implementation science Obesity prevention Physical activity School health

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Network Engineering 2000

Network Engineering 2000

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2000 2nd International Conference on Microwave and Millimeter Wave Technology

作者： david J.Y.lee William C.Y.lee Global Technology Vodafone AirTouch Plc

＜正＞Introduction of location technology shifts the paradigm of network *** opens the door for providing revolutionary approach for network *** is discussed in this paper on a revolutionary way of combining parameters made available through location technology and currently available system parameters for future network engineering and operation. The "continuous" snapshots of the network can be parsed and intelligently stored into the network performance data warehouse as *** images can be analyzed off-line to select certain "troubled" instances of the network（this can be site specific）.These instances can,then,be analyzed through simulation and/or engineer *** optimized solution can be *** "troubled" instance and associated solutions can be feedback into the "virtual network engineer" simulated by the Al engine to increase its knowledge ***,the intelligent pseudo "network engineer" can identify "troubled" network instance and compare with the existing images and associated solution in the data *** existing solution then can be applied to perform real time automated network *** is done through image processing by selecting the most similar network instance and associated solution. By saving more and more "troubled" instances and developed associated solutions,the "virtual network engineer" increases its knowledge bases and becomes more and more "intelligent" and can handle future "troubled" instance based on the "experience". For example,the dynamic power allocation and individual specific dedicated dynamic SHO thresholds for each mobile can be combined to efficiently engineer the network performance once the mobile location and associated network characteristics can be identified.

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Evaluation of spatial and temporal patterns of insect damage and aflatoxin level in the pre-harvest corn fields to improve management tactics

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Insect Science 2014年第5期21卷 572-583页

作者： Xinzhi Ni Jeffrey P. Wilson Michael D. Toews G. david Buntin R. Dewey lee Xin Li Zhongren Lei Kanglai He Wenwei Xu Xianchun Li Alisa Huffaker Eric A. Schmelz USDA-ARS Crop Genetics and Breeding Research Unit Department of Entomology University of Georgia Tifton Department of Entomology University of Georgia Griffin Department of Crop and Soil Sciences University of Georgia Tifton Georgia USA Collegeof Plant Protection Northwest A&F University Yangling Shaanxi State Key Laboratory for Biology of Plant Diseases and Insect Pests Institute of Plant Protection Chinese Academy of Agricultural Sciences Beijing China Texas A&M University Texas AgriLife LubbockTexas Department of Entomology University of Arizona Tucson Arizona USDA-ARS Center for Medical Agricultural and Veterinary Entomology Gainesviile Florida USA

Spatial and temporal patterns of insect damage in relation to aflatoxin contamination in a corn field with plants of uniform genetic background are not well understood. After previous examination of spatial patterns of insect damage and aflatoxin in pre-harvest corn fields, we further examined both spatial and temporal patterns of cob- and kernel- feeding insect damage, and aflatoxin level with two samplings at pre-harvest in 2008 and 2009. The feeding damage by each of the ear/kernel-feeding insects （i.e., corn earworm/fall armyworm damage on the silk/cob, and discoloration of corn kernels by stink bugs） and maize weevil population were assessed at each grid point with five ears. Sampling data showed a field edge effect in both insect damage and aflatoxin contamination in both years. Maize weevils tended toward an aggregated distribution more frequently than either corn earworm or stink bug damage in both years. The frequency of detecting aggregated distribution for aflatoxin level was less than any of the insect damage assessments. Stink bug damage and maize weevil number were more closely associated with aflatoxin level than was corn earworm damage. In addition, the indices of spatial-temporal association （χ） demonstrated that the number of maize weevils was associated between the first （4 weeks pre-harvest） and second （1 week pre-harvest） samplings in both years on all fields. In contrast, corn earworm damage between the first and second samplings from the field on the Belflower Farm, and aflatoxin level and corn earworm damage from the field on the Lang Farm were dissociated in 2009.

关键词： aflatoxin level corn earworm damage maize weevil population SADIE analysis spatial pattern spatio-temporal association stink bug damage

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