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Bidirectional effect of Wnt signaling antagonist DKK1 on the modulation of anthrax toxin uptake

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Science China(Life Sciences) 2014年第5期57卷 469-481页

作者： QIAn LiLi CAI ChangZu YUAn PengFei JEOnG Sun-Young YAnG XiaoZhou DEALMEIDA Venita ERnST James COSTA Michael cohen Stanley n. WEI WenSheng College of Life Sciences and State Key Laboratory of Protein and Plant Gene Research Peking University Department of Genetics Stanford University School of Medicine Department of Cancer Targets GenentechInc.South San Francisco Department of Protein Chemistry and Protein Engineering GenentechInc.South San Francisco Department of Medicine Stanford University School of Medicine

LRP6, a co-receptor for the morphogen Wnt, aids endocytosis of anthrax complexes. Here we report that Dickkopfl （DKK1） protein, a secreted LRP6 ligand and antagonist, is also a modulator of anthrax toxin sensitivity, shRnA-mediated gene silencing or TALEn-mediated gene knockout of DKK1 reduced sensitivity of cells to PA-dependent hybrid toxins. However, unlike the solely inhibitory effect on Wnt signaling, the effects of DKK1 overexpression on anthrax toxicity were bidirectional, depending on its endogenous expression and cell context. Fluorescence microscopy and biochemical analyses showed that DKK1 facilitates internalization of anthrax toxins and their receptors, an event mediated by DKK1-LRP6-Kremen2 complex. Monoclonal antibodies against DKK1 provided dose-dependent protection to macrophages from killing by anthrax lethal toxin （LT）. Our discovery that DKK1 forms ternary structure with LRP6 and Kremen2 in promoting PA-mediated toxin internalization provides a paradigm for bacterial exploitation of mechanisms that host cells use to internalize signaling proteins.

关键词： DKK1 anthrax toxin LRP6 TALEns internalization Kremen2 receptor Wnt

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自主式灵巧弹药的目标识别

飞航导弹 1990年第12期 53-56页

作者： MARVIn n cohen 郭福涛

介绍了灵巧弹药的作战概念,采用的探测器和信号处理技术。

关键词：灵巧弹药目标识别末制导自主式

A randomized controlled trial of Promoting Physical Activity in Regional and Remote Cancer Survivors(PPARCS)

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Journal of Sport and Health Science 2024年第1期13卷 81-89页

作者： Sarah J.Hardcastle Chloe Maxwell-Smith Vinicius Cavalheri Terry Boyle Marta Leyton Román Cameron Platell Michael Levitt Christobel Saunders Frank Sardelic Sophie nightingale Jacob McCormick Craig Lynch Paul A.cohen Max Bulsara Dana Hince Sport and Physical Activity Research Centre Sheffield Hallam UniversitySheffieldS102BPUK Institute for Health Research The University of Notre DameFremantleWA 6959Australia Curtin School of Population Health Curtin UniversityPerthWA 6845Australia Curtin School of Allied Health Curtin UniversityPerthWA 6845Australia Allied Health South Metropolitan Health ServiceMurdochWA 6150Australia Australian Centre for Precision Health University of South AustraliaAdelaideSA 5001Australia Department of Didactics of Musical Plastic and Body ExpressionUniversity of ExtremaduraCaceres 10071Spain St.John of God Subiaco Hospital PerthWA 6008Australia Department of Surgery University of MelbourneMelbourneVIC 3010Australia Tamara Private Hospital TamworthNSW 2340Australia Peter MacCallum Cancer Centre MelbourneVIC 3000Australia College of Health and Medicine Australian National UniversityCanberraACT 2600Australia Division of Obstetrics and Gynaecology Medical SchoolUniversity of Western AustraliaPerthWA 6009Australia

Background:Physical activity(PA)is important for cancer *** of remotely delivered interventions are needed to assist in reaching under-served non-metropolitan cancer *** objective of this study was to ascertain whether wearable technology,coupled with health coaching was effective in increasing PA in breast and colorectal cancer survivors living in regional and remote areas in ***:Cancer survivors from 5 states were randomized to intervention and control *** participants were given a Fitbit Charge 2TMand received up to 6 telephone health coaching *** participants received PA print *** assessments at baseline and 12 weeks measured moderate-to-vigorous PA(MVPA),light PA,and sedentary ***:Eighty-seven participants were recruited(age=63±11 years;74(85%)female).There was a significant net improvement in MVPA of 49.8 min/week,favoring the intervention group(95%confidence interval(95%CI):13.6-86.1,p=0.007).There was also a net increase in MVPA bouts of 39.5 min/week(95%CI:11.9-67.1,p=0.005),favoring the intervention *** groups improved light PA and sedentary behavior,but there were no between-group ***:This’s the first study to demonstrate that,when compared to standard practice(i.e.,PA education),a wearable technology intervention coupled with distance-based health coaching,improves MVPA in non-metropolitan cancer *** results display promise for the use of scalable interventions using smart wearable technology in conjunction with phone-based health coaching to foster increased PA in geographically disadvantaged cancer survivors.

关键词： Behavior change Exercise Health disparities Oncology Wearable technology

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药物研究中如何合理设计新的先导化合物

世界临床药物 1985年第4期 196-198页

作者： cohen n C 万维勤

跳出对已知结构进行经典最佳化的框框药厂研究目标之一是创制新药。实际上现在药物化学主要还是在改进已知药物的疗效。即使目前的QSAR法也只是为了使已知化合物的类似物最佳化。而且愈是探索越难达到构效上的创新。跳出二度空间的化学... 详细信息

跳出对已知结构进行经典最佳化的框框药厂研究目标之一是创制新药。实际上现在药物化学主要还是在改进已知药物的疗效。即使目前的QSAR法也只是为了使已知化合物的类似物最佳化。而且愈是探索越难达到构效上的创新。跳出二度空间的化学结构设计药物目前只有寻找新的先导化合物才能开阔思路,而从三度空间(3-D)来考察分子似可达到这一目的。事实上经典的二度化学分子结构式与三度空间的分子相比,已不能满足新药设计的要求,后者更能为构效关系提供信息。对映异构体具有令人意外的不同生物作用和分子生物学的“锁与钥匙”概念,是说明分子三度空间性质很重要的两个良好证

关键词：先导化合物合理设计药物设计分子特征化学结构精神抑制药

非小细胞肺腺癌患者的复发性栓塞性卒中及瓣膜性心脏病

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世界核心医学期刊文摘（神经病学分册） 2006年第5期2卷 50-51页

作者： Royter V cohen S.n. 牛亚利 8631 W. 3rd Street Los Angeles CA 90048 United States

The etiology and mechanisms of stroke could differ in cancer compared to non- cancer patients due to altered blood coagulability and/or non-bacterial thrombotic endocarditis (nBTE). These conditions could be either missed by using inappropriate diagnostic methods or misinterpreted. For instance, certain techniques (transthoracic echocardiography, TTE)may provide false-negative results and delay appropriate therapy. On the other hand, these patients, by having atypical findings, may challenge the differential between bacterial and sterile valvular heart disease. Cerebrovascular disease in cancer patients is often aggressive with tendency to recurrent events and rapid neurological devastation. Timely diagnosis is crucial. Current treatment approach to nBTE includes anticoagulation. We report a case of multiple embolic strokes in a patient diagnosed with lung cancer. Primary and secondary stroke prevention is discussed with relevant review of the literature.

关键词：肺癌患者瓣膜性心脏病栓塞性卒中非小细胞非细菌性血栓性复发性非肿瘤患者经胸超声心动图肺腺

眼内压失控行睫状体冷冻疗法和透巩膜二极管激光睫状体光凝的比较

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世界核心医学期刊文摘（眼科学分册） 2005年第11期1卷 33-34页

作者： Goldenberg-cohen n. Bahar I. Ostashinski M. 韩静 Department of Ophthalmology RabinMedical Center Beilinson Campus Petah Tiqva 49100 IsraelDr.

BACKGROUnD AnD OBJECTIVE: To compare the use of cyclocryotherapy and diode laser cyclophotocoagulation for the treatment of uncontrolled intraocular pressure. P ATIEnTS AnD METHODS: Seventy consecutive patients (70 eyes)-treated for high, u nresponsive intraocular pressure during a 4-year period with cyclocryotherapy ( n=38) or diode laser cyclophotocoagulation (n=32) with a follow-up period of at least 3 months (mean follow-up=15.7 months) were compared for intraocular pres sure, visual acuity, and complication rate. RESULTS: Mean intraocular pressure w as reduced from 40.9 ±11.9 to 20.5 ±10.3 mm Hg in the cyclocryotherapy group, and from 35.9 ±9.3 to 21.3 ±10.7 mm Hg in the cyclophotocoagulation group. Int raocular pressure was controlled in 60.5%and 62.5%of eyes, respectively. Deter ioration in visual acuity occurred in 31.5%of the cyclocryotherapy group and 37 .5%of the cyclophotocoagulation group. Severe visual loss to no light perceptio n was noted in 6 eyes and 2 eyes, respectively, and phthisis bulbi in 2 eyes in the cyclocryotherapy group (5.2%) and 1 eye in the cyclophotocoagulation group (3.1%). COnCLUSIOnS: Cyclocryotherapy and diode laser cyclophotocoagulation are equally effective in decreasing intraocular pressure in patients with persisten t uncontrolled glaucoma, with a lower rate of complications associated with diod e laser cyclophotocoagulation.

关键词：睫状体冷冻疗法睫状体光凝二极管激光眼内压无光感眼球痨冷冻组持续性

链霉菌线型质粒pSLA2复制相关基因kilccc的鉴定及功能分析

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链霉菌线型质粒pSLA2复制相关基因kilccc的鉴定及功能分析

新大陆国家形成的生态学基础：一般和局部模型的构建

首届中国青年学者微生物遗传学学术研讨会

作者：覃重军沈美娟焦瑞身 Stanley n.cohen 中国科学院上海植物生理研究所美国斯坦福大学遗传系

细菌的染色体和质粒一般为环型结构,而属于革兰氏阳性细菌的链霉菌属的染色体为线型结构;此外,还发现大小为12 kb至1700 kb的线型质粒。pSLA2是从娄彻氏链霉菌(Stretpomyces rochei)中分离到的一个17 kb高拷贝的线型质粒。该质粒带有一...

细菌的染色体和质粒一般为环型结构,而属于革兰氏阳性细菌的链霉菌属的染色体为线型结构;此外,还发现大小为12 kb至1700 kb的线型质粒。pSLA2是从娄彻氏链霉菌(Stretpomyces rochei)中分离到的一个17 kb高拷贝的线型质粒。该质粒带有一个位于分

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南方文物 2008年第1期 133-140页

作者：马克·科恩(M．n．cohen)[美] 陈洪波(译) 陈淳(校) 不详复旦大学文博系

1965年丹麦经济学家埃斯特·博塞罗普出版了《农业起源的条件》一书,对马尔萨斯经典的人口/资源平衡理论进行了修正,认为人口的增长和资源的短缺会刺激人类在经济上作出变革。她认为栽培和强化农业是社会面对人口压力所促成的进步。博... 详细信息

1965年丹麦经济学家埃斯特·博塞罗普出版了《农业起源的条件》一书,对马尔萨斯经典的人口/资源平衡理论进行了修正,认为人口的增长和资源的短缺会刺激人类在经济上作出变革。她认为栽培和强化农业是社会面对人口压力所促成的进步。博塞罗普的理论受到了学界的极大关注,本文作者马克·科恩于1977年出版了《史前期的粮食危机》一书,对博塞罗普的理论作了全面的论证和阐述,并首创骨骼古病理学和营养分析的方法来检验农业起源前存在人口压力的假设,最终使古病理学研究成为当代考古学一个前沿探索领域。人口压力理论也激励了卡内罗等学者提出冲突论来解释国家起源的动力机制,并使科恩将其延伸到国家起源动因的阐释上。科恩认为,更新世末和全新世初的人口压力和野生资源短缺,迫使人类社会发展出农业来应对粮食危机,而随后发生的早期国家和集权政府起源也是同一过程的合理结果。当农业人口增长接近土地载能的时候,人类社会就发展出国家机构来应付这种危机。虽然文章从生态学基础来讨论早期国家的起源,但是并没有落入一种环境决定论的窠臼。由于国家起源的一个最基本条件是大量的人口聚集,因此促使人口聚集的生态环境条件是必须考虑的先决条件。科恩在文章中提出,既要肯定国家起源动因应该有通则性的认识,但是也需要对局部状况作具体的分析。因为世界上几大文明中心的环境差异很大,因此这些早期国家的诞生很可能是不同区域中的社会在应对特定环境条件时所做的相似反应,从而表现为具体过程差异较大,但在集权政府形成上有一种趋同的发展趋势。因此,对早期国家起源的通则性认识和具体个案的特殊性分析都不可偏废。

关键词：国家形成生态学新大陆模型和局阐释模式文化演变解释方法

皮肤非神经性粒细胞瘤伴复发性ALK融合基因

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临床与实验病理学杂志 2019年第7期35卷 837-837页

作者： cohen J n Yeh I Jordan R C 张曲霞许春伟福建省肿瘤医院病理科

非神经源性颗粒细胞瘤(nnGCT)临床罕见,由大卵圆形细胞组成,具有丰富的颗粒状细胞质、多变核以及区域淋巴结扩散潜力。与常见的颗粒细胞瘤(GCT)相反,nnGCT缺乏S-100表达,可表现为更显著的核异型性和有丝分裂活性。作者调查12例nnGCT的... 详细信息

非神经源性颗粒细胞瘤(nnGCT)临床罕见,由大卵圆形细胞组成,具有丰富的颗粒状细胞质、多变核以及区域淋巴结扩散潜力。与常见的颗粒细胞瘤(GCT)相反,nnGCT缺乏S-100表达,可表现为更显著的核异型性和有丝分裂活性。作者调查12例nnGCT的临床病理特征,并使用新一代测序识别在nnGCT和6个GCT的子集中潜在驱动事件。nnGCT显示轻至中度的核异型性,可变的有丝分裂。5例皮肤nnGCT的遗传分析显示3例(60%)有ALK基因融合,具体表现为2例2号染色体中间缺失,导致DCTn1与ALK框内融合;1例染色体易位导致5号染色体上的SQSTM1与ALK融合。6例GCT中2例显示7号染色体增加。在nnGCT和GCT中未发现其他分子或染色体改变。ALK免疫组化显示4例(4/9)皮肤nnCGT呈弱-中度阳性,包括3例伴ALK融合的肿瘤。ALK免疫染色阳性的nnGCT与ALK染色阴性的nnGCT形态学特征无区别。

关键词：颗粒细胞瘤 ALK 融合基因皮肤复发性神经性临床病理特征 2号染色体