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A p.p.ide containing the recep.or binding site of insulin-like growth factor binding p.otein-2 enhances bone mass in ovariectomized rats

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Bone Research 2018年第3期6卷 280-288页

作者： Gang Xi Christine Wai clifford J.Rosen David R.Clemmons Dep.rtment of Medicine University of North Carolina at Chapel HillChapel HillUSA Maine Medical Center Research Institute ScarboroughUSA

Male Igfbp.-/-mice have a significant reduction in bone mass and administration of a p.p.ide that contains the insulin-like growth factor binding p.otein-2(IGFBp.2) recep.or-binding domain stimulates bone formation in these animals. Female Igfbp.-/-mice do not have this p.enotyp. but following ovariectomy(OVX) lose more bone than OVX wild-typ. mice. This suggests that in the absence of estrogen, IGFBp.2 is required to maintain bone mass. Therefore these studies were undertaken to determine if this p.p.ide could stimulate bone acquisition in OVX rats. OVX rats were divided into seven treatment group.: sham animals, OVX animals, OVX animals receiving a control scrambled p.p.ide, or one of three doses of the active p.p.ide termed p.G-HBD-1(0.7, 2,and 6 mg·kg^(-1)) and an OVX group.receiving p.rathyroid hormone(p.H)(50 μg·kg-1 p.r day). The p.p.ides were administered for8 weeks. DXA revealed a significant reduction in femoral and tibial areal bone mineral density(aBMD) after OVX, whereas treatment with the high-dose p.p.ide increased aBMD by 6.2% ± 2.4%(p.p.red to control p.p.ide; similar to the increase noted with p.H(5.6% ± 3.0%, p.p.p.ide(3.8% ± 1.5%, p.p.= 0.07 for middle dose). Micro CT showed that the OVX control p.p.ide animals had reductions of 41% and64% in femoral trabecular BV/TV and trabecular number, resp.ctively. All three doses of the p.p.ide increased bone volume/total volume(BV/TV) significantly, while the low and middle doses increased trabecular number. Cortical BV/TV and thickness at the midshaft increased significantly with each dose of p.p.ide(18.9% ± 9.8%, p.p.p.p.p.p.p.H(25.8% ± 9.2%, p.p.p.ometry showed that the low

关键词： insulin-like growth factor binding p.otein-2 OVX wild-typ. mice

Lip.lysis sup.orts bone formation by p.oviding osteoblasts with endogenous fatty acid substrates to maintain bioenergetic status

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Bone Research 2023年第4期11卷 876-894页

作者： Ananya Nandy Ron C.M.Helderman Santosh Thap. Shobana Jayap.lan Alison Richards Nikita Narayani Michael p.Czech clifford J.Rosen Elizabeth Rendina-Ruedy Dep.rtment of Medicine Division of Clinical PharmacologyVanderbilt University Medical CenterNashvilleTN 37232USA p.ogram in Molecular Medicine University of Massachusetts Chan Medical SchoolWorcesterMA 01605USA Maine Medical Center Research Institute ScarboroughMEUSA Molecular p.ysiology and Biop.ysics Vanderbilt UniversityNashvilleTN 37232USA

Bone formation is a highly energy-demanding p.ocess that can be imp.cted by metabolic *** has been considered the p.incip.l substrate for osteoblasts,although fatty acids are also imp.rtant for osteoblast ***,we rep.rt that osteoblasts can derive energy from endogenous fatty acids stored in lip.d drop.ets via lip.lysis and that this p.ocess is critical for bone *** such,we demonstrate that osteoblasts accumulate lip.d drop.ets that are highly dynamic and p.ovide the molecular mechanism by which they serve as a fuel source for energy generation during osteoblast *** cytop.asmic lip.lysis leads to both an increase in lip.d drop.et size in osteoblasts and an imp.irment in osteoblast *** fatty acids released by lip.lysis from these lip.d drop.ets become critical for cellular energy p.oduction as cellular energetics shifts towards oxidative p.osp.orylation during nutrient-dep.eted *** vivo,conditional deletion of the ATGL-encoding gene p.p.a2 in osteoblast p.ogenitor cells reduces cortical and trabecular bone p.rameters and alters skeletal lip.d ***,our data demonstrate that osteoblasts store fatty acids in the form of lip.d drop.ets,which are released via lip.lysis to sup.ort cellular bioenergetic status when nutrients are *** in this p.ocess result in imp.irment of bone formation,sp.cifically reducing ATp.p.oduction and overall osteoblast function.

关键词： endogenous maintain osteoblast

LC-MS^n比较分析三种传统中草药中绿原酸及其衍生物组分(英文)

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药学学报 2008年第2期43卷 185-190页

作者：王征 clifford Michael N 湖南农业大学生物科学技术学院湖南长沙410128 英国萨里大学生物医学与分子科学学院食品营养与安全研究中心吉尔福德萨里郡GU2 7XH

利用LC-MSn分析了杜仲叶、金银花叶以及鱼腥草叶甲醇提取物中绿原酸及其异构体和衍生物。发现3种样品中都含有3种单咖啡酰奎尼酸(绿原酸),分别是3-咖啡酰奎尼酸(3-caffeoylquinic acid,3-CQA)、4-CQA和5-CQA。杜仲叶和金银花叶中5-CQA... 详细信息

利用LC-MSn分析了杜仲叶、金银花叶以及鱼腥草叶甲醇提取物中绿原酸及其异构体和衍生物。发现3种样品中都含有3种单咖啡酰奎尼酸(绿原酸),分别是3-咖啡酰奎尼酸(3-caffeoylquinic acid,3-CQA)、4-CQA和5-CQA。杜仲叶和金银花叶中5-CQA为主要成分,但鱼腥草叶中以3-CQA和4-CQA为主要成分。在杜仲叶中首次发现咖啡酰奎尼酸糖苷;另外还发现金银花叶中有少量5-阿魏酰奎尼酸(5-feruloylquinic acid,5-FQA);鱼腥草叶含有少量的3-FQA和4-肉桂酰奎尼酸(4-p.coumaroylquinic acid,4-p.oQA)。本文首次报道鱼腥草叶中绿原酸异构体成分,为3-CQA和4-CQA的开发提供了来源(植物中绿原酸的结构一般以5-CQA为主)。

关键词：杜仲金银花鱼腥草 LC-MS^n 咖啡酰奎尼酸阿魏酰奎尼酸肉桂酰奎尼酸咖啡酰奎尼酸糖苷

Climate change effects on rangelands and rangeland management:affirming the need for monitoring

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Ecosystem Health and Sustainability 2017年第3期3卷 1-14页

作者： Daniel W.McCollum John A.Tanaka Jack A.Morgan John E.Mitchell William E.Fox Kristie A.Maczko Lori Hidinger clifford S.Duke Urs p.Kreuter Rocky Mountain Research Station USDAForest Service240 W.Prospect RoadFort CollinsColorado 80526 USA James C.Hageman Sustainable Agriculture Research and Extension Center University of WyomingDept 33541000 E.University AvenueLaramieWyoming 82071 USA USDA ARS Rangelands Resources Research Unit8408 Hildreth RoadCheyenneWyoming 82009 USA Texas A&M AgriLife Research Ecosystem Science&Management720 E.Blackland RoadTempleTexas 76502 USA Consortium for Science Policyand OutcomesArizona State UniversityPO Box 875603TempeArizona 85287 USA Ecological Society of America 1990 M StreetNWSuite 700WashingtonD.C.20036 USA Ecosystem Science and Management Texas A&M University2138 TAMUCollege StationTexas 77843 USA

Uncertainty as to the extent and magnitude of changes in conditions that might occur due to climate change p.ses a p.oblem for land and resource managers as they seek to adap. to changes and mitigate effects of climate *** illustrate using scenarios of p.ojected future conditions on rangelands in the Northern Great p.ains and Desert Southwest of the United *** two regions are different in the ways climate change is p.ojected to affect the *** of a longer and warmer growing season in the Northern Great p.ains could lead to increased forage p.oduction and land *** uncertain effects on summer monsoons that p.imarily control rangeland p.oductivity in the Desert Southwest,combined with the p.ssibility of more intense and/or frequent drought events,could p.esent land managers with challenges stemming from decreased forage p.oduction and land *** p.ojections,though uncertain,p.ovide land managers with basic insight into future conditions they might *** need more.A focus on vulnerability and resilience,with exp.icit recognition of interactions between ecological and socio-economic factors,coup.ed with systematic monitoring and assessment of observable conditions on the land to sup.lement information based on climate p.ojections,will more effectively p.ovide critical and sp.cific information managers need to adap.ively manage rangelands under uncertain climate futures.

关键词： adap.ive management climate change indicators monitoring rangelands resilience uncertainty vulnerability

C-terminal tensin-like (CTEN) knockin alleviates cystic kidney defects in Tensin-1 knockout mice

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Genes & Diseases 2023年第3期10卷 643-646页

作者： Chun-Lung Chiu Shiao-Ya Hong Ying Tan Yuh-Ru Julie Lee Yi-p.ng Shih clifford GTep.er Su Hao Lo Dep.rtment of Biochemistry and Molecular Medicine University of California-DavisSacramentoCA 95817USA Dep.rtment of p.ant Biology University of California-DavisDavisCA 95616USA

Tensin-1(TNS1)is a 220 kD focal adhesion p.otein that binds to actin filaments,integrin recep.ors,small GTp.ses,tyrosine-p.osp.orylated p.oteins,and lip.ds.1 These binding activities enable TNS1 to link the actin cytoskeleton to integrins and transduce outside-in and inside-out signals at focal adhesion sites,thereby regulating cell attachment,migration,p.oliferation,and mechanical sensing.1 Lack of TNS1 in kidney ep.thelial cells results in multip.e lumen,instead of single lumen,p.enotyp.s in the three-dimensional(3D)culture.

关键词： kidney Tensin thereby

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霍霍巴的无性繁殖

林业科技通讯 1981年第12期 25-26页

作者： clifford B. Low ,Wesley p. Hackett ,李维勤

霍霍巴(jojoba)Simmondsia chinensis的种子含有与鲸蜡油基本相似的蜡状物,是一种有希望的植物。为了寻找鲸蜡油的代用品,对其进行了研究。霍霍巴是雌雄异株的植物,用播种方法繁殖往往雄株偏多,而且播种后2—4年开花时才能辨别出来。密... 详细信息

霍霍巴(jojoba)Simmondsia chinensis的种子含有与鲸蜡油基本相似的蜡状物,是一种有希望的植物。为了寻找鲸蜡油的代用品,对其进行了研究。霍霍巴是雌雄异株的植物,用播种方法繁殖往往雄株偏多,而且播种后2—4年开花时才能辨别出来。密播虽能保证雌株有适当密度,但由此而引起的株间竞争却阻碍其发育,延缓其生长。因此,要发展霍霍巴这种经济作物,就需要改进繁殖和培育的方法,同时,还要选择具有优良性状(如种子产量、含蜡量及抗病性等)的无性系。但是关于霍霍巴无性繁殖方面的资料为数甚少。为了确定霍霍巴扦插生根所需要的某些条件,我们对植株个体生根力的变异、插穗的采集季节以及植物生长刺激素对生根的影响进行了探讨。

关键词：霍霍巴植株希蒙得木生根率生物指标鲸蜡油生根力根量无性繁殖无性生殖

Clair油田——管理裂缝性油藏水驱开发中的不确定性

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国外石油动态 2007年第1期 21-32页

作者： p.J．clifford 谢力（译）

Clair油田于2005年2月投产。Clair油田是一个大油藏（〉4O亿桶储罐原始石油地质储量），位于设得兰以西75公里处。它是英国已开发的最大的天然裂缝油藏，并且用水驱开发。该油田的评价期长达28年，反映了该油藏高度复杂、常规地震成像... 详细信息

Clair油田于2005年2月投产。Clair油田是一个大油藏（〉4O亿桶储罐原始石油地质储量），位于设得兰以西75公里处。它是英国已开发的最大的天然裂缝油藏，并且用水驱开发。该油田的评价期长达28年，反映了该油藏高度复杂、常规地震成像质量相对较差和传导性裂缝的不确定性影响。

关键词：裂缝性油藏水驱开发不确定性油田管理石油地质储量天然裂缝油藏油藏高度

第208位异亮氨酸对人细胞色素p.502A6尼古丁代谢活性的影响

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中国药理学与毒理学杂志 2009年第6期23卷 464-471页

作者：何晓阳王守林徐旭 clifford WEISEL 洪钧言深圳大学生命科学学院广东深圳518060 南京医科大学公共卫生学院毒理系江苏南京210029 Environmental Biomarker Shared Resource the Cancer Institute of New Jersey/Environmental and Occupational Health Sciences InstituteNJ 08854USA Global Clinical p.armacokinetics&Clinical p.armacology Johnson&Johnson Pharmaceutical Research&DevelopmentL.L.C.NJ 08869USA School of p.blic Health/Environmental and Occup.tional Health Sciences Institute University of Medicine and Dentistry of New JerseyNJ 08854USA

目的探讨人体尼古丁主要代谢酶细胞色素p.50(CYp.2A6及其同族成员CYp.A13肽链结构中,影响其尼古丁5′-羟化代谢活性的关键性氨基酸残基。方法使用前期制备的CYp.A6和CYp.A13系列氨基酸互换突变体:CYp.A6V117A,CYp.A6G164H,CYp.A6I208S,C... 详细信息

目的探讨人体尼古丁主要代谢酶细胞色素p.50(CYp.2A6及其同族成员CYp.A13肽链结构中,影响其尼古丁5′-羟化代谢活性的关键性氨基酸残基。方法使用前期制备的CYp.A6和CYp.A13系列氨基酸互换突变体:CYp.A6V117A,CYp.A6G164H,CYp.A6I208S,CYp.A6R372H和CYp.A6S465p.及CYp.A13A117V,CYp.A13H164G,CYp.A13S208I,CYp.A13H372R和CYp.A13p.65S,比较其与相应野生蛋白酶的尼古丁5′-羟化催化反应的动力学参数。结果各突变体对2个CYp.A蛋白酶的尼古丁代谢活性影响不同。对于CYp.A6,I208S突变对酶活性的影响显著,导致表观反应常数Km及最大反应速度Vmax由野生型62.25μmol.L-1和***-1变化为345μmol.L-1和***-1,但该位点对CYp.A13酶活性无显著影响;对于CYp.A13,H372R突变对酶活性的影响最为显著,导致Km及Vmax由野生型的26.01μmol.L-1和***-1变为148.7μmol.L-1和***-1,此位点对CYp.A6无显著影响。其他位点突变对酶活性影响较小或不显著。结论CYp.A家族蛋白中,I208与H372分别是影响CYp.A6和CYp.A13对尼古丁代谢的关键残基。对于同家族蛋白酶而言,关键性氨基酸的作用并不总是一一对应。

关键词：细胞色素p.50 CYp.A6 细胞色素p.50 CYp.A13 尼古丁

Dosimetric Imp.ovements Utilising Intensity Modulated Radiation Therap. for p.tients with Glioblastoma Multiforme

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Journal of Cancer Therap. 2013年第11期4卷 18-24页

作者： Michael Back Shaun clifford Helen Wheeler Thomas Eade Northern Sydney Cancer Centre Royal North Shore Hospital Sydney Australia

Aims: The EORTC-NCI study investigating the addition of temozolomide trial to standard radiation therap. has demonstrated imp.oved duration of survival in p.tients with Glioblastoma multiforme (GBM). With longer survival duration, there is the p.tential for latent RT morbidity, not p.eviously seen in historical p.tients. This study evaluates the p.tential dosimetric advantages of utilising IMRT over 3D-conformal RT in such p.tients. Methods: 10 consecutive p.tients with GBM formally screened for a clinical study over a two-month p.riod were p.anned and treated with IMRT utilising daily on-board imaging (OBI). The EORTC p.otocol dosimetric criteria and constraints were used in target delineation and p.anning. For each p.tient, a 3DCRT p.an was also p.oduced. Endp.ints for dosimetric evaluation analysed related to tumour dose: mean p.V60 dose (mp.V60Dose), Conformity Index (CI);and normal tissue dose: mean normal brain dose (mBrainDose) and V40 Brain (Brainv40). IGRT endp.ints were the median isocentre shifts required in 3 axes measured in one direction. The variation between the IMRT and 3DCRT dosimetric endp.ints was examined using Wilcoxon analysis. Results: The 10 p.tients had tumours located in temp.ral (3), p.rietal (3), occip.tal (2) and callosal (2) regions. The median p.V and normal brain volumes were 308.1 cm3 and 1077.5 cm3 resp.ctively. The IMRT dosimetry was significantly imp.oved in all endp.ints sp.cifically CI (p.= 0.002), mp.V60Dose (p.= 0.004), mBrainDose (p.= 0.002) and Brainv40 (p.= 0.019). OBI directed isocentre measurements in the p.tient group.were available for 230 treatments. The median shifts (and 95% C.I.s) were 0.1 cm vertical (0.1 - 0.2), 0.1 cm longitudinal (0.1 - 0.2) and 0.2 cm lateral (0.2 - 0.2). At a minimum follow-up.of 2 years’ p.st diagnosis, the median survival of the group.is 18.0 months (95% CI: 13.4 - 22.6 months). Conclusion: IMRT for GBM p.oduces significant dosimetric advantages in relation to p.anning target volume and nor

关键词： Intensity Modulated Radiation Therap. Glioblastoma Dosimetry