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中国病理生理学会第十三届肿瘤、第十四届免疫专业委员会学术会议

作者： Lili Lil,2,3#,Wei Lil,2#,Lanbo Xiaol,2,Juan Xul,2,Xue Chenl,2,Min Tangl,2, Zigang Dong4,Qian Tao3,Ya Cao 1,2 1 Cancer Research institute,XiangYa School of Medicine,Central South university, Changsha,China 2Carcinogenesis and Invasion Key Laboratory of Education Ministry of China,Central South university,Changsha,China 3Cancer Epigenetics Laboratory,Department of Clinical Oncology,State Key Laboratory of Oncology in South China,Sir YK Pao Center for Cancer and Li Ka Shing institute of Health Sciences,The Chinese university of Hong Kong and CUHK Shenzhen Research institute 4the hormel institute,university of minnesota,usa

Disruption of the gatekeeper p53 tumor suppressor is involved in various virus-associated tumorigeneses,with aberrant ubiquitination as the major cause of abnormal p53 accumulation in virus-associated *** previously showed that p53 is accumulated and phosphorylated by Epstein-Barr virus(EBV) latent membrane protein 1(LMPl) in nasopharyngeal carcinoma(NPC) which is constantly associated with EBV in our ***,we further identified that LMPl upregulated p53 expression via two-distinct ubiquitin ***1 promoted p53 stability and accumulation by suppressing the E3 ligase MDM2-mediated K48 ubiquitination,associated with p53 Ser20 phosphorylation,but increased the total level of p53 *** also induced p53 UbK63-linked ubiquitination by interacting with tumor necrosis factor receptor-associated factor 2(TRAF2), resulting in p53 accumulation without its proteasomal ***, LMPl rescued p53-UbK63 ubiquitination-mediated regulation of cell apoptosis and cell cycle ***,these results demonstrate that the regulation of p53 accumulation/stability and functions via different ubiquitin-modifications mediated by viral protein LMPl,which has broad implications to the pathogenesis of multiple EBV-associated tumors.

关键词： apoptosis Viral oncoprotein LMPl disrupts p53-induced cell cycle arrest and apoptosis through modulating K63-linked ubiquitination of p53 EBV cycle

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LOD score exclusion analyses for candidate disease susceptibility genes using case-parents design

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Progress in Natural Science:Materials International 2006年第1期16卷 30-38页

作者： DENG Hongwen1,2,3 and GAO Guimin2,4 (1.Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal university, Changsha 410081, China 2.Osteoporosis Research Center, Creighton university Medical Center, Omaha NE 68131, usa 3. Department of Biomedical Sciences, Creighton university, Omaha NE 68131, usa 4. Virginia Bioin format ics institute and Department of Statistics, Virginia Polytechnic institute and State university, Blacksburg VA 24061-0315, usa) Laboratory of Molecular and Statistical Genetics College of Life Sciences Hunan Normal University Changsha 410081 China Osteoporosis Research Center Creighton University Medical Center Omaha NE 68131 United States Department of Biomedical Sciences Creighton University Omaha NE 68131 United States Virginia Bioinformatics institute and Department of Statistics Virginia Polytechnic Institute and State University Blacksburg VA 24061-0315 United States

The focus of almost all the association studies of candidate genes is to test for their importance. We recently developed a LOD score approach that can be used to test against the importance of candidate genes for complex diseases and quantitative traits in random samples. As a complementary method to regular association analyses, our LOD score approach is powerful but still affected by the population admixture, though it is more conservative. To control the confounding effect of population heterogeneity, we develop here a LOD score exclusion analysis using case-parents design, the basic design of the transmission disequilibrium test (TDT) approach that is immune to population admixture. In the analysis, specific genetic effects and inheritance models at candidate genes can be analyzed and if a LOD score is ≤ - 2. 0, the locus can be excluded from having an effect larger than that specified. Simulations show that this approach has reasonable power to exclude a candidate gene having small genetic effects if it is not a disease susceptibility locus (DSL) with sample size often employed in TDT studies. Similar to association analyses with the TDT in nuclear families, our exclusion analyses are generally not affected by population admixture. The exclusion analyses may be implemented to rule out candidate genes with no or minor genetic effects as supplemental analyses for the TDT. The utility of the approach is illustrated with an application to test the importance of vitamin D receptor (VDR) gene underlying the differential risk to osteoporosis.

关键词： association studies candidate genes case-parents design disease susceptibility locus exclusion mapping LOD score.

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No apparent lock-in depth of the Laschamp geomagnetic excursion: Evidence from the Malan loess

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Science China Earth Sciences 2006年第9期49卷 960-967页

作者： ZHU Rixiang1, LIU Qingsong1,2, PAN Yongxin1, DENG Chenglong1, ZHANG Rui1 & WANG Xianfeng3 1. Paleomagnetism and Geochronology Laboratory (SKL of Lithosphere Evolution), institute of Geology and Geophysics, Chi- nese Academy of Sciences, Beijing 100029, China 2. institute of Geophysics and Planetary Geophysics, university of California, Santa Cruz, CA 95064, usa 3. Department of Geology and Geophysics, university of minnesota, Minneapolis, MN 55455, usa Paleomagnetism and Geochronology Laboratory (SKL of Lithosphere Evolution) Institute of Geology and Geophysics Chinese Academy of Sciences Beijing China institute of Geophysics and Planetary Geophysics University of California Santa Cruz USA Department of Geology and Geophysics University of Minnesota Minneapolis USA

The first-order chronological framework of the long-term Chinese loess/paleosol sequences was based mainly on magnetostratigraphy. However, there remain arguments on the lock-in ages of the major geomagnetic reversals. This study systematically compared the stratigraphic locations of the Laschamp excursion and Henrich events (H4 at～39 ka and H5 at～48 ka) recorded by the Luochuan loess profile in the central Chinese Loess Plateau. Results show that the Lascchamp excursion is bracketed well by these two cold events, and the corresponding estimated age is between about 41.7-43.7 ka, which is close to the widely accepted age of ～40-41 ka for the ***, our new results do not suggest apparent lock-in effects in the last glacial Malan loess.

关键词： Chinese loess, Laschamp excursion, Henrich event, lock-in depth.

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Advanced information feedback strategy in intelligent two-route traffic flow systems

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Science China(Information Sciences) 2010年第11期53卷 2265-2271页

作者： DONG ChuanFei1,2, MA Xu1,3 & WANG BingHong1,4 1Department of Modern Physics and Nonlinear Science Center, university of Science and Technology of China (USTC), Hefei 230026, China 2School of Earth and Atmospheric Sciences, Georgia institute of Technology, Atlanta, GA 30332, usa 3 Department of Physics, Syracuse university, Syracuse, NY 13244, usa 4the Research Center for Complex System Science, university of Shanghai for Science and Technology and Shanghai Academy of System Science, Shanghai 200093, China Department of Modern Physics and Nonlinear Science Center University of Science and Technology of China (USTC) Hefei China School of Earth and Atmospheric Sciences Georgia Institute of Technology Atlanta USA Department of Physics Syracuse University Syracuse USA The Research Center for Complex System Science University of Shanghai for Science and Technology and Shanghai Academy of System Science Shanghai China

The optimal information feedback has a significant effect on many socioeconomic systems like stock market and traffic systems aiming to make full use of resources. In this paper, we study dynamics of traffic flow with real-time information. The influence of a feedback strategy named vehicle number feedback strategy (VNFS) is introduced, in which we only calculate the vehicle number of first 500 route sites from the entrance. Moreover, the two-route traffic system has only one entrance and one exit, which is different from those in the previous work. Our model incorporates the effects of adaptability into the cellular automaton models of traffic flow, and simulation results by adopting this optimal information feedback strategy have demonstrated higher efficiency in controlling spatial distribution of traffic patterns than the other three information feedback strategies, i.e., TTFS, MVFS and CCFS.

关键词： vehicle number feedback strategy two-route selecting traffic flow intelligent vehicle cellular automaton model

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Effect of 7-hydroxystaurosporine on glioblastoma cell invasion and migration

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Acta Pharmacologica Sinica 2005年第4期26卷 492-499页

作者： Qing-hui MENG~2 Li-xin ZHOU~3 Jia-lin LUO~4 Jian-ping CAO~4 Jian TONG~4 Sai-jun FAN~(2,4,5) 2 Department of Oncology, Lombardi Comprehensive Caneer Center,Georgetown university,Washington DC 20057,usa 3 institute of Medicine and Biotechnology,Chinese Academy of Medical Sciences,Beijing 100050,China 4 School of Radiation Medicine and Public Health,Soochow university,Suzhou 215007,China Department of Oncology Lombardi Comprehensive Cancer Center Georgetown University Washington DC USA institute of Medicine and Biotechnology Chinese Academy of Medical Sciences Beijing China School of Radiation Medicine and Public Health Soochow University Suzhou China

Aim:To investigate the effect of 7-hydroxystaurosporine（UCN-01）,a selectiveprotein kinase C（PKC）inhibitor,on cell growth,migration,and invasion in inva-sive human glioblastoma U-87MG ***:PKC activity was determinedbased on the PKC-catalyzed transfer of the32p-phosphate group from[g-32p]ATPinto a PKC-specific peptide *** viability was measured by MTT *** invasion and migration were evaluated by a Boyden chamber assay andscratch wound assay,*** expression was analyzed using West-ern blot *** formation of 3-dimensional cellular aggregates was examinedby a cell-cell aggregation ***:UCN-01 treatment resulted in concen-tration-and time-dependent inhibition of U-87MG cell growth at higher doses（>100 nmol/L）,and reduced cell invasion and migration capability at less cytotoxicdoses（<100 nmol/L）.UCN-01 significantly repressed PKC *** this result,UCN-01 blocked cell invasion stimulated by phorbel 12-myristate-13-acetate（PMA）and ethanol（EtOH）,2 PKC *** expression ofthe tumor suppressor genes BRCA1 and PTEN increased the anti-invasion poten-tial of *** to UCN-01 caused a dose-dependent increase in celladhesion molecule *** effect of UCN-01 on the formation of cell-cellaggregation was significantly reduced by the addition of an ***:UCN-01 inhibits the invasion and migration of humanglioma ***,UCN-01 can have potential clinical applications for thetreatment of human glioma metastasis.

关键词： 7-hydroxystaurosporine protein kinase C cell movement cadherins BRCA1 protein

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Neuroprotection of Insulin against Oxidative Stress-induced Apoptosis in Cultured Retinal Neurons:Involvement of Phosphoinositide 3-kinase/Akt Signal Pathway

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Acta Biochimica et Biophysica Sinica 2006年第4期38卷 241-248页

作者： Xiao-Rui YU~(1,2*) Guo-Rong JIA~1 Guang-Dao GAO~3 Shu-Hong WANG~1 Yan HAN~1 Wei CAO~4 1 Department of Biochemistry and Molecular Biology, 2 Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, 3 Department of Pathobiology,School of Medicine,Xi'an Jiaotong university,Xi'an 710061,China 4 Department of Ophthalmology,university of Oklahoma Health Science Center,Dean A,McGee Eye institute,Oklahoma City,Oklahoma 73104,usa Department of Biochemistry and Molecular Biology Xi'an Jiaotong UniversityXi'an 710061 China Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education Xi'an Jiaotong UniversityXi'an 710061 China Department of Pathobiology School of Medicine Xi'an Jiaotong UniversityXi'an 710061 China Department of Ophthalmology University of Oklahoma Health Science Center Dean A. McGee Eye InstituteOklahoma City Oklahoma 73104 USA

In order to investigate the neuroprotection of insulin in retinal neurons,we used retinal neuronalculture as a model system to study the protective effects of insulin against H2O2-induced cytotoxicity andapoptotic *** retinal neuronal cultures were grown from retinas of 0-2-day old *** viability was measured by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl-tetrazolium bromide *** cell death was evaluated by the TdT-mediated digoxigenin-dUTP nick-end labeling assay,and byDNA laddering *** 3-kinase （PI3K） activity was measured using phosphoinositide4,5-bisphophate and [γ-32P]ATP as *** blot analysis with anti-phospho-Akt （pS473） antibodywas performed to examine the level of phosphorylated *** observed that treatment with 100μM H2O2for 24 h significantly decreased cell viability and induced apoptotic death of retinal neurons,and that pretreatmentwith 10 nM insulin significantly inhibited or attenuated H2O2-induced cytotoxicity and *** LY294002,a specific PI3K inhibitor,abolished the cytoprotective effect of *** also stronglyactivated both PI3K and the downstream effector *** results suggest that insulin protects retinalneurons from oxidative stress-induced apoptosis and that the PI3K/Akt signal pathway is involved in insulin-mediated retinal neuroprotection.

关键词： apoptosis insulin phosphoinositide 3-kinase/Akt oxidative stress neuroprotection retinal neuronal culture

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Role of inositol 1,4,5-trisphosphate receptors in α1-adrenergic receptorinduced cardiomyocyte hypertrophy

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Acta Pharmacologica Sinica 2006年第7期27卷 895-900页

作者： Da-li LUO~(2,3,5) Jian GAO~2 Xiao-mei LAN~3 Gang WANG~4 Sheng WEI~4 Rui-ping XIAO~4 Qi-de HAN~32 Department of Pharmacology,School of Chemical Biology & Pharmaceutical Sciences,Capital university of Medical Sciences,Beijing 100069,China 3 institute of Cardiovascular Science at Health Science Center,Peking university Beijing 100083,China 4 institute of Molecular Medicine and College of Life Science,Peking university,Beijing 100871,China Department of Pharmacology School of Chemical Biology & Pharmaceutical Sciences Capital University of Medical Sciences Beijing China institute of Cardiovascular Science at Health Science Center Peking University Beijing China institute of Molecular Medicine and College of Life Science Peking University Beijing China

Aim:Intracellular Ca2+plays pivotal roles in diverse cellular functions,includinggene transcription that underlies cardiac remodeling during stress ***,the role of inositol 1,4,5-trisphosphate receptors（IP3Rs）in the media-tion of cardiac intracellular Ca2+and hypertrophic growth remains *** with neonatal rat ventricular myocytes suggests that activation of IP3Rsmay be linked to α1adrenergic receptor（α1AR）increased stereotyped Ca2+sparkoccurrence and global Ca2+***,we hypothesized that Ca2+releasethrough IP3Rs was necessary for α1AR-stimulated cardiac ***:We used myoinositol 1,4,5-trisphosphate hexakis（butyryloxymethyl）ester（IP3BM）,a membrane-permeant ester of IP3,to activate IP3Rs directly,and Fluo 4/AM tomeasure intracellular Ca2+***:IP3BM(10μmol·L-1)mimicked theeffects of phenylephrine,a selective agonist of α1AR,in increments in local Ca2+spark release（especially in the perinuclear area）and global Ca2+*** importantly,IP3R inhibitors,2-aminoethoxydiphenyl borateand Xestospongin C,abolished the IP3BM-induced Ca2+responses,and signifi-cantly suppressed α1AR-induced cardiomyocyte hypertrophy assayed by cellsize,[3H]leucine incorporation and atrial natriuretic factor gene expression,dur-ing sustained（48 h）phenylephrine ***:These results,therefore,provide cellular mechanisms that link IP3R signaling to α1AR-stimulatedgene expression and cardiomyocyte hypertrophy.

关键词： inositol 1,4,5-trisphosphate receptors Ca2+sparks α1 adrenergic stimulation cardiac hypertrophy

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Tetramethylpyrazine suppresses HIF-1α,TNF-α,and activated caspase-3 expression in middle cerebral artery occlusion-induced brain ischemia in rats

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Acta Pharmacologica Sinica 2007年第3期28卷 327-333页

作者： Yi CHANG~(2,3) George HSIAO~4 Seu-hwa CHEN~4 Yi-cheng CHEN~4 Jiing-han LIN~4 Kuang-hung LIN~4 Duen-suey CHOU~4 Joen-rong SHEU~(4,5)2 Department of Anesthesiology,Shin Kong Wu Ho-Su Memorial Hospital,Taipei 110,Taiwan,China 3 School of Medicine,Fu-Jen Catholic university,Taipei,110,Taiwan,China 4 Graduate institute of Medical Sciences,Taipei Medical university,Tuipei 110,Taiwan,China Department of Anesthesiology Shin Kong Wu Ho-Su Memorial Hospital Taipei China School of Medicine Fu-Jen Catholic University Taipei China Graduate institute of Medical Sciences Taipei Medical University Taipei China

Aim:To examine the detailed mechanisms underlying the inhibitory effect oftetramethylpyrazine(TMPZ)in inflammatory and apoptotic responses inducedby middle cerebral artery occlusion(MCAO)in ***:MCAO-inducedfocal cerebral ischemia in rats was used in this *** hypoxia-induciblefactor-1α(HIF-1α),activation of caspase-3,and TNF-αmRNA transcription inischemic regions were detected by immunoblotting and RT-PCR,***-oxidative activity was investigated using a thiobarbituric acid-reactive sub-stance(TBARS)test in rat brain homogenate ***:We showedthe statistical results of the infarct areas of solvent-and TMPZ(20 mg/kg)-treatedgroups at various distances from the frontal pole in MCAO-induced focal cerebralischemia in *** with TMPZ(20 mg/kg)markedly reduced the infarctarea in all regions,especially in the third to fifth ***-induced focalcerebral ischemia was associated with increases in HIF-lαand the activation ofcaspase-3,as well as TNF-αtranscription in ischemic *** expressionswere markedly inhibited by treatment with TMPZ(20 mg/kg).However,TMPZ(0.5-5mmol/L)did not significantly inhibit TBARS reaction in rat brain ***:The neuroprotective effect of TMPZ may be mediated at least by aportion of the inhibition of HIF-1αand TNF-αactivations,followed by the inhibi-tion of apoptosis formation(active caspase-3),resulting in a reduction in theinfarct volume in ischemia-reperfusion brain ***,TMPZ treatment mayrepresent an ideal approach to lowering the risk of or improving function in is-chemia-reperfusion brain injury-related disorders.

关键词： tetramethylpyrazine middle cerebral artery occlusion HIF-Iα caspase-3 TNF-α thiobarbituric acid-reactive substance

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Genistein stimulates osteoblastic differentiation via p38 MAPK-Cbfa1 pathway in bone marrow culture

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Acta Pharmacologica Sinica 2007年第10期28卷 1597-1602页

作者： Qing-chuan LIAO~2,Zhou-sheng XIAO~(4,5),Yan-fang QIN~3,Hong-hao ZHOU~4~2 Affiliated Children's Hospital,Nanjing Medical university,Nanjing 210008,China,~3 Department of Pathology,School of Medicine,Jinanuniversity,Guangzhou 510632,China ~4 institute of Clinical Pharmacology,Central South university,Changsha 410078,China Affiliated Children's Hospital Nanjing Medical University Nanjing China institute of Clinical Pharmacology Central South University Changsha China Department of Pathology School of Medicine Jinan University Guangzhou China

Aim:To test the hypothesis that genistein stimulates the osteoblastic differentia-tion through the p38 mitogen activated protein kinase (MAPK)-core-binding fac-tor 1 (Cbfa1) ***:The activation of p38 MAPK was detected byWestern *** phosphatase (ALP) activity and calcium depositionwere assessed for osteoblastic differentiation of bone marrow-derived mesenchy-mal stem cell (BMSC) *** expression of Cbfa1 was analyzed at both themRNA and protein *** activity of Cbfa1 was detected by electrophoreticmobility shift *** sialoprotein (BSP),ALP,osteocalcin (OC),andosteopontin (OPN) gene transcription were also evaluated by either RT-PCR orNorthern ***:Genistein (0.01-1 μmol/L) dose dependently led tothe rapid and sustained activation of the p38 MAPK pathway in mouse *** with genistein (1 μmol/L) resulted in increased ALP activityand calcium deposition of BMSC cultures as a function of *** alsoenhanced Cbfa1 DNA binding activity and promoted the expressions of Cbfa1itself as well as several Cbfa1-regulated genes,including ALP,BSP,OC,and *** treatment with p38 MAPK inhibitor (SB203580) diminished thegenistein-induced osteoblastic maturation and p38 MAPK-Cbfa1 activation inmouse BMSC ***:These results indicated that genistein couldstimulate the osteoblastic differentiation of BMSC cultures through the p38MAPK-Cbfa1 pathway.

关键词： bone marrow-derived mesenchymal stem cells core-binding factor 1 osteoblastic differentiation genistein mitogen-activated protein kinase

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Distributions of fatty acids in a stalagmite related to paleoclimate change at Qingjiang in Hubei,southern China

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Science China Earth Sciences 2005年第9期48卷 1463-1469页

作者： XIE Shucheng1,HUANG Junhua1,WANG Hongmei2,YI Yi1,HU Chaoyong1, CAI Yanjun3 & CHENG Hai4 1. Faculty of Earth Science,China university of Geosciences,Wuhan 430074,China 2. School of Environmental Studies,China university of Geosciences,Wuhan 430074,China 3. SKLLQG,institute of Earth Environment,Chinese Academy of Sciences,Xi’an 710075,China 4. Department of Geology and Geophysics,university of minnesota,MN55455,usa Faculty of Earth Science China University of Geosciences Wuhan China School of Environmental Studies China University of Geosciences Wuhan China SKLLQG Institute of Earth Environment Chinese Academy of Sciences Xi’an China Department of Geology and Geophysics University of Minnesota USA

Fatty acids extracted from a subtropical stalagmite at Qingjiang in Southern China’s Hubei Province were analysed using gas chromatography-mass spectrometry. These n-alkanoic acids range from C14 to C26 in carbon number, maximizing at C16, with a second dominance at C22. In contrast to the stalagmite analysed, the overlying soils are characterized by the dominance of heavy-molecular-weight homologues (>C20). The n-fatty acids in the stalagmite were proposed to be contributed by both the soil ecosystems and the microbes harboring in the percolating water and the cave. The ratios of unsaturated to saturated n-fatty acids (C16:1i/C16:0, C18:1/C18:0) appear to show trends comparable with the oxygen isotope records of the stalagmite carbonate, with enhanced values associated with the cold episode such as Heinrich event 1. This paleoclimate-dependent record of the n-fatty acids might reflect microbial changes in physiology and activity in response to the temperature. This record shows somewhat difference from the previous paleoclimate signal extracted from n-alkanols and n-alkan-2-ones of the same stalagmite. The acid record fails to document the well-known Younger Dryas event which was effectively shown by the latter two biomarkers derived from soil ecosystems. This discrepancy might result from the changing biogeochemical impact on different lipid fractions as well as the varied organism populations in different ecosystems.

关键词： biomarker, ecosystem, microbe, speleothem, paleoclimate, Quaternary.

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