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本研究利用前人1233个亚洲高山流域沉积物宇宙成因核素10Be数据统一计算了地表剥蚀速率,以约束构造、气候和地形如何影响和控制地表剥蚀过程.基于高程数据逐个像元的核素产率,使用蒙特卡洛模拟方法重新计算了10Be流域剥蚀速率.剥蚀速率变化范围从（7.4±0.7）mm ka-1（1σ;青藏高原内部）到（9,646744+777）mm ka-1（1σ;青藏高原南部）跨四个数量级,中位数为186mm ka-1.逐个像元计算的核素产率与传统模型使用质心坐标和平均高程计算的核素产率相比,后者96.6%核素产率被低估,其中高程差越大越被低估.两种方法计算的产率偏差可达40%,究其原因可能是流域高程分布不均和核素产率随海拔和纬度呈非线性变化.通过量化地表剥蚀速率与构造、气候、地形和岩性之间的相关性将有助于推演未知流域的剥蚀速率.从局部小尺度分析,亚热带台湾岛地区剥蚀速率可能主要受降水和新构造驱动的山体滑坡影响,而降水变化范围较窄的青藏高原东部的剥蚀速率主要受控于地形;冰川覆盖的高原地区剥蚀速率受冰川作用影响,如帕米尔、青藏高原内部和南部地区;青藏高原内部剥蚀速率较低是因为较低的降水和较高的侵蚀基准面,从而限制了河流的下切和地表起伏度演化.与局部小尺度强调单一主控因素不同,本研究对亚洲高山流域宏观大尺度进行量化分析发现:（1）地形指标（包括坡度、地形起伏度和河道陡峭指数）与剥蚀速率在千年尺度呈现一致的幂函数关系,而非简单线性;（2）剥蚀速率与气候（包括与海拔相关的降水、温度和植被覆盖度）和新构造活动（地震核密度分布）呈近似幂函数关系,为次要控制因素;（3）岩性与剥蚀速率没有明显的相关性,可能受限于流域复杂的岩性混合和低分辨率的可侵蚀指数数据.

关键词： 10Be剥蚀速率气候变化构造抬升地形梯度亚洲高山流域

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Constitutive androstane receptor agonist, TCPOBOP,attenuates steatohepatitis in the methionine choline-deficientdiet-fed mouse

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World journal of Gastroenterology 2007年第42期13卷 5635-5641页

作者： Edwina s Baskin-Bey Akira Anan Hajime Isomoto steven F Bronk Gregory j Gores Department of Medicine Division of Gastroenterology and Hepatology Miles and Shirely Fitterman Center for Digestive Diseases Mayo Clinic College of Medicine Rochester MN 55905 United States

AIM： To ascertain whether constitutive androstane receptor （CAR） activation by 1,4-bis-[2-（3,5,- dichloropyridyloxy）] benzene （TCPOBOP） modulates steatohepatitis in the methionine choline-deficient （MCD） diet-fed ***： C57/BL6 wild-type mice were fed the MCD or standard diet for 2 wk and were treated with either the CAR agonist, TCPOBOP, or the CAR inverse agonist, ***： Expression of CYP2B10 and CYP3A11, known CAR target genes, increased 30-fold and 45-fold, respectively, in TCPOBOP-treated mice fed the MCD diet. TCPOBOP treatment reduced hepatic steatosis （44.6 ＋ 5.4% vs 30.4 ＋ 4.5%, P 〈 0.05） and serum triglyceride levels （48 ＋ 8 vs 20 ＋ 1 mg/dL, P 〈 0.05） in MCD diet- fed mice as compared with the standard diet-fed mice. This reduction in hepatic steatosis was accompanied by an increase in enzymes involved in fatty acid microsomal co-oxidation and peroxisomal p-oxidation, namely CYP4A10, LPBE, and 3-ketoacyI-CoA thiolase. The reduction in steatosis was also accompanied by a reduction in liver cell apoptosis and inflammation. In contrast, androstanol was without effect on any of the above ***： CAR activation stimulates induction of genes involved in fatty acid oxidation, and ameliorates hepatic steatosis, apoptosis and inflammation.

关键词： Apoptosis CYP4A Fatty acid oxidation,Inflammation

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Functional brain imaging of gastrointestinal sensation in health and disease

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World journal of Gastroenterology 2007年第25期13卷 3438-3445页

作者： Lukas Van Oudenhove steven j Coen Qasim Aziz Department of Neurosciences Division of Psychiatry & Department of Pathophysiology Gastroenterology Section University Hospital Gasthuisberg University of Leuven Belgium Centre for Neuroimaging sciences Institute of Psychiatry London United Kingdom Division of Neuroscience & Medicine Department of GI Sciences Hope Hospital University of Manchester United Kingdom

It has since long been known, from everyday experience as well as from animal and human studies, that psychological processes-both affective and cognitive- exert an influence on gastrointestinal sensorimotor function. More specifically, a link between psychological factors and visceral hypersensitivity has been suggested, mainly based on research in functional gastrointestinal disorder patients. However, until recently, the exact nature of this putative relationship remained unclear, mainly due to a lack of non-invasive methods to study the （neurobiological） mechanisms underlying this relationship in non-sleeping humans. As functional brain imaging, introduced in visceral sensory neuroscience some 10 years ago, does provide a method for in vivo study of brain-gut interactions, insight into the neurobiological mechanisms underlying visceral sensation in general and the influence of psychological factors more particularly, has rapidly grown. In this article, an overview of brain imaging evidence on gastrointestinal sensation will be given, with special emphasis on the brain mechanisms underlying the interaction between affective ＆ cognitive processes and visceral sensation. First, the reciprocal neural pathways between the brain and the gut （brain- gut axis） will be briefly outlined, including brain imaging evidence in healthy volunteers. second, functional brain imaging studies assessing the influence of psychological factors on brain processing of visceral sensation in healthy humans will be discussed in more detail. Finally, brain imaging work investigating differences in brain responses to visceral distension between healthy volunteers and functional gastrointestinal disorder patients will be highlighted.

关键词： Functional brain imaging Functionalgastro-intestinal disorders Visceral hypersensitivity Gastrointestinal sensation Psychological factors

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Proteasome inhibition-induces endoplasmic reticulum dysfunction and cell death of human cholangiocarcinoma cells

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World journal of Gastroenterology 2007年第6期13卷 851-857页

作者： Yucel Ustundag steven F Bronk Gregory j Gores Mayo Clinic College of Medicine Rochester MN 55905 United States

AIM: To determine if proteasome inhibition induces apoptosis in human cholangiocarcinoma cells, and if so, to elucidate the cellular mechanisms. METHODs: studies were performed in the human KMCH, KMBC, and Mz-ChA-1 cholangiocarcinoma, and normal rat cell lines. MG132, a peptide aldehyde, which inhibits the chymotrypsin-like activity of the proteaosome was employed for this study. Apoptosis was assessed morphologically by 4'-6-Diamidino-2-phenylindole (DAPI) nuclear staining and fluorescence microscopy. Mitochondrial membrane potential was examined using a fluorescent unquenching assay. Ultrastructural changes during cell death were examined using transmission electron microscopy (TEM). Caspase 3/7 activity was assessed using an enzymatic-based fluorescent assay. Cytosolic-free calcium concentrations were measured using Fura-2 and digitized fluorescent microscopy. REsULTs: MG132, a proteasome inhibitor, induced apoptosis in all the cholangiocarcinoma cell lines examined. In contrast, minimal cytotoxicity was observed in normal rat cholangiocytes. Apoptosis was time-and -concentration-dependent. There was no change in the mitochondrial membrane potential between treated and untreated cells. Ultrastructural examination by transmission electron microscopy displayed the classic features of apoptosis, but in addition, there was also dramatic vacuolization of the endoplasmic reticulum (ER). Unexpectedly, no increase in caspase 3/7 activity was observed in MG132 treated cells, nor did the pancaspase inhibitor, Q-VD-OPh prevent cell death. The protein synthesis inhibitor, cycloheximide, blocked apoptosis induced by proteosome inhibitor indicating that ER dysfunction was dependent upon the formation of new proteins. CONCLUsION: Proteosome inhibition induces ERdysfunction and caspase-independent cell death selectively in human cholangiocarcinoma cells. Proteasome inhibitors warrant evaluation as anticancer agents for the treatment of human cholangiocarcinoma.

关键词： MG132 Cholangiocarcinoma Proteosome Apoptosis Calcium

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Activation of Plasma Membrane NADPH Oxidase and Generation of H_2O_2 Mediate the Induction of PAL Activity and saponin synthesis byEndogenous Elicitor in suspension-Cultured Cells of Panax ginseng

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Acta Botanica sinica 2003年第12期45卷 1434-1441页

作者：胡向阳 steven j NEILL 蔡伟明汤章城中国科学院上海生命科学研究院植物生理生态研究所上海200032 CentreforResearchinPlantscience UniversityoftheWestofEnglandBristolColdharbourLaneBristolBS161QYUnitedKingdom

Endogenous elicitor, termed cellulase-degraded cell wall (CDW), was prepared from the cell wall of suspension-cultured ginseng (Panax ginseng C.A. Meyer) cells via cellulase degradation. CDW activated the NADPH oxidase activity of isolated plasma membranes and stimulated in vivo H2O2 generation in ginseng cell suspensions. CDW also increased the activity of phenylalanine ammonia lyase (PAL), expression of a P. ginseng squalene epoxidase (sqe) gene and saponin synthesis. NADPH oxidase inhibitors inhibited both in vitro NADPH oxidase activity and in vivo H2O2 generation. Induction of PAL activity, saponin synthesis and sqe gene expression were all inhibited by such inhibitor treatments and reduced by incubation with catalase and HA scavengers. These data indicate that activation of NADPH oxidase and generation of H2O2 are essential signalling events mediating defence responses induced by the endogenous elicitor(s) present in CDW.

关键词： plasma membrane NADPH oxidase H2O2 elicitor Panax ginseng

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MgCl2和Gpp（NH）p对腺苷A1受体激动剂和拮抗剂结合的作用比较（英文）

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Acta Pharmacologica sinica 2003年第8期24卷 3-14+110页

作者： Keith FINLAYsON,MAEMOTO Takuya,steven P BUTCHER,john sHARKEY,Henry j OLVERMAN Fujisawa Institute of Neuroscience Fujisawa Institute of Neuroscience Fujisawa Institute of Neuroscience Division of Neuroscience University of Edinburgh Level 6 Appleton Tower Crichton street. Edinburgh EH8 9LE UK Division of Neuroscience University of Edinburgh Level 6 Appleton Tower Crichton street. Edinburgh EH8 9LE UK

AIM: To investigate modulation of antagonist and agonist binding to adenosine A1receptors by MgCl2and 5'-guanylimidodiphosphate (Gpp（NH）p) using rat brain membranes and the A1antagonist [3H]-8-cyclopentyl-1,3-dipropylxanthine （[3H]DPCPX） and the A1agonist [3H]-2-chloro-N6-cyclopentyladenosine （[3H]CCPA）. METHODs: Parallel saturation and inhibition studies were performed using well-characterised radioligand binding assays and a Brandel Cell Harvester. REsULTs: MgCl2produced a concentration-dependent decrease （44%）, whereas Gpp（NH）p increased [3H]DPCPX binding （19%）. In [3H]DPCPX competition studies, agonist affinity was 1.5-14.6-fold higher and 4.6-10-fold lower in the presence of 10 mmol/L MgCl2and 10 μmol/L Gpp（NH）p respectively; antagonist affinity was unaffected. The decrease in agonist affinity with increasing Gpp（NH）p concentrations was due to a reduction in the proportion of binding to the high affinity receptor state. In contrast to [3H]DPCPX, MgCl2produced a concentration-

关键词：嘌呤P1受体放射配位体测定氯化镁鸟苷酰亚氨二磷酸脑

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