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| 1 | Androgen receptor: structure, role in prostate cancer and drug discovery显示文摘Androgens and androgen receptors (AR) play a pivotal role in expression of the male phenotype. Several diseases, such as androgen insensitivity syndrome (AIS) and prostate cancer, are associated with alterations in AR functions. Indeed, androgen blockade by drugs that prevent the production of androgens and/or block the action of the AR inhibits prostate cancer growth. However, resistance to these drugs often occurs after 2-3 years as the patients develop castration-resistant prostate cancer (CRPC). In CRPC, a functional AR remains a key regulator. Early studies focused on the functional domains of the AR and its crucial role in the pathology. The elucidation of the structures of the AR DNA binding domain (DBD) and ligand binding domain (LBD) provides a new framework for understanding the functions of this receptor and leads to the development of rational drug design for the treatment of prostate cancer. An overview of androgen receptor structure and activity, its actions in prostate cancer, and how structural information and high-throughput screening have been or can be used for drug discovery are provided herein. | MH Eileen TAN Jun LI H Eric XU Karsten MELCHER Eu-leong YONG | 2015 | Acta Pharmacologica Sinica2015，36，1： | 39 |
| 2 | Amyloid beta: structure, biology and structure-based therapeutic development显示文摘淀粉的贝它肽(A) 通过 transmembrane 蛋白质的解朊的处理被生产,淀粉的先锋蛋白质(应用软件) ,由 - 并且 -secretases。在大脑的累积被建议是在 Alzheimers 疾病的致病的一个早有毒的事件,它是在大脑与匾和混乱联系的痴呆的最普通的形式。当前, A 的生理、病理学的形式是什么,是不清楚的并且由由什么机制, A 引起痴呆。而且,没有有效的药停止或逆行 Alzheimers 的前进疾病。在这份报纸,我们考察 A 的结构,生物功能,和 neurotoxicity 角色。我们也讨论与 A 交往并且调停的潜在的受体吸入,清理,和新陈代谢。另外,我们为治疗 Alzheimers 疾病总结治疗学的开发和不同策略的最近的进展。最后,我们将在象为 Alzheimers 疾病的治疗答应策略选择一样寻找新奇、潜在地有效的代理人在进步上报导。这些前景包括对 A,它的受体和字形物蛋白质起作用的代理人,例如对 A 的小分子,疫苗和抗体;禁止者或调节的人 - 并且 -secretase;降级 A 的朊酶;字形物蛋白质禁止者和疫苗;淀粉的染料和 microRNAs。 | Guo-fang CHEN Ting-hai XU Yan YAN Yu-ren ZHOU Yi JIANG Karsten MELCHER H Eric XU | 2017 | Acta Pharmacologica Sinica2017，38，9： | 39 |
| 3 | On the combined effect of soil fertility and topography on tree growth in subtropical forest ecosystems—a study from SE China显示文摘Aims The aim of our research was to understand small-scale effects of topography and soil fertility on tree growth in a forest biodiversity and ecosystem functioning(BEF)experiment in subtropical SE China.Methods Geomorphometric terrain analyses were carried out at a spatial resolution of 5×5 m.Soil samples of different depth increments and data on tree height were collected from a total of 566 plots(667 m2 each).The soils were analyzed for carbon(soil organic carbon[SOC]),nitrogen,acidity,cation exchange capacity(CEC),exchangeable cations and base saturation as soil fertility attributes.All plots were classified into geomorphological units.Analyses of variance and linear regressions were applied to all terrain,soil fertility and tree growth attributes.Important Findings In general,young and shallow soils and relatively small differences in stable soil properties suggest that soil erosion has truncated the soils to a large extent over the whole area of the experiment.This explains the concurrently increasing CEC and SOC stocks downslope,in hollows and in valleys.However,colluvial,carbon-rich sediments are missing widely due to the convexity of the footslopes caused by uplift and removal of eroded sediments by adjacent waterways.The results showed that soil fertility is mainly influenced by topography.Monte-Carlo flow accumulation(MCCA),curvature,slope and aspect significantly affected soil fertility.Furthermore,soil fertility was affected by the different geomorphological positions on the experimental sites with ridge and spur positions showing lower exchangeable base cation contents,especially potassium(K),due to leaching.This geomorphological effect of soil fertility is most pronounced in the topsoil and decreases when considering the subsoil down to 50 cm depth.Few soil fertility attributes affect tree height after 1-2 years of growth,among which C stocks proved to be most important while pH_(KCl)and CEC only played minor roles.Nevertheless,soil acidity and a high proportion of Al on the exchange complex affected tree height even after only 1-2 years growth.Hence,our study showed that forest nutrition is coupled to a recycling of litter nutrients,and does not only depend on subsequent supply of nutrients from the mineral soil.Besides soil fertility,topography affected tree height.We found that especially MCCA as indicator of water availability affected tree growth at small-scale,as well as aspect.Overall,our synthesis on the interrelation between fertility,topography and tree growth in a subtropical forest ecosystem in SE China showed that topographic heterogeneity lead to ecological gradients across geomorphological positions.In this respect,small-scale soil-plant interactions in a young forest can serve as a driver for the future development of vegetation and biodiversity control on soil fertility.In addition,it shows that terrain attributes should be accounted for in ecological research. | Thomas Scholten Philipp Goebes Peter Kühn Steffen Seitz Thorsten Assmann Jürgen Bauhus Helge Bruelheide Francois Buscot Alexandra Erfmeier Markus Fischer Werner Härdtle Jin-Sheng He Keping Ma Pascal A.Niklaus Michael Scherer-Lorenzen Bernhard Schmid Xuezheng Shi Zhengshan Song Goddert von Oheimb Christian Wirth Tesfaye Wubet Karsten Schmidt | 2017 | Journal of Plant Ecology2017，10，1： | 22 |
| 4 | An ABA-mimicking ligand that reduces water loss and promotes drought resistance in plants显示文摘Abscisic 酸(骆驼毛的织物) 是最重要的荷尔蒙让植物抵抗干旱和另外的不能生活的压力。骆驼毛的织物直接绑在骆驼毛的织物受体的 PYR/PYL 家庭,导致类型 2C 磷酸酶(PP2C ) 和下游的骆驼毛的织物发信号的激活的抑制。骆驼毛的织物由小分子发信号的干预能帮助植物克服象干旱,寒冷和土壤咸度那样的不能生活的压力,这被想象。然而,由植物酶的化学不稳定性和快速的分解代谢限制骆驼毛的织物本身的实际申请。这里,我们报导一件小分子骆驼毛的织物的鉴定模仿(AM1 ) 那充当骆驼毛的织物受体的家庭的多重成员的有势力使活跃之物。在 Arabidopsis, AM1 激活高度类似于由骆驼毛的织物导致了那的一个基因网络。有 AM1 的处理禁止种子萌芽,阻止叶水损失,并且支持干旱抵抗。我们与 PYL2 骆驼毛的织物受体和 HAB1 PP2C 在建筑群解决了 AM1 的水晶结构,它表明 AM1 调停交往的 gate-latch-lock 网络,在骆驼毛的织物界限 receptor/PP2C 建筑群被保存的一个结构的特征。一起,这些结果证明一件单个小分子骆驼毛的织物模仿能激活多重骆驼毛的织物受体并且保护植物免受水损失和干旱应力的伤害。而且, AM1 复杂水晶结构为设计 ABA-mimicking 小分子的下一代提供一个结构的基础。 | Minjie Cao Xue Liu Yan Zhang Xiaoqian Xue X EdwardZhou Karsten Melcher Pan Gao Fuxing Wang Liang Zeng Yang Zhao Pan Deng Dafang Zhong Jian-Kang Zhu H Eric Xu Yong Xu | 2013 | Cell Research2013，23，8： | 17 |
| 5 | Structural basis of AMPK regulation by adenine nucleotides and glycogen显示文摘激活安培的蛋白质 kinase (AMPK ) 为糖尿病,肥胖,和癌症的治疗是一个中央细胞的精力传感器和精力动态平衡,和一个有希望的药目标的管理者。这里我们人的 α 的现在的低分辨率的水晶结构; 1 β 2 γ 1 holo-AMPK 建筑群跳了到它的 allosteric 调节的人安培和肝糖模仿 cyclodextrin,两个在 phosphorylated (4.05 Å) 并且 non-phosphorylated (4.60 Å) 状态。另外,我们解决了 2.95 Å人的 kinase 领域(KD ) 的结构跳了到邻近的 autoinhibitory 领域(帮助) 并且表现了广泛生物化学并且 mutational 研究。一起,这些研究由安培和肝糖说明 allosteric AMPK 调整的内在的机制,其绑定改变在交替的帮助(安培) 和糖类绑定模块(肝糖) 之间的 equilibria 相互作用。 | Xiaodan Li Lili Wang X Edward Zhou Jiyuan Ke Parker W de Waal Xin Gu M H Eileen Tan Dongye Wang Donghai Wu H Eric Xu Karsten Melcher | 2015 | Cell Research2015，25，1： | 8 |
| 6 | Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-1igase signaling effector DWARF3显示文摘 | Li-Hua Zhao X Edward Zhou Wei Yi Zhongshan Wu Yue Liu Yanyong Kang Li Hou Parker W de Waal Suling Li Yi Jiang Adrian Scaffidi Gavin R Flematti Steven M Smith Vinh Q Lam Patrick R Griffin YonghongWang Jiayang Li Karsten Melcher H Eric Xu | 2015 | Cell Research2015，25，11： | 7 |
| 7 | Structure and mechanism for recognition of peptide hormones by Class B G-protein-coupled receptors显示文摘班 B G-protein-coupled 受体(GPCR ) 是为包括 glucagon,甲状旁腺的荷尔蒙,和 calcitonin 的肽荷尔蒙的受体。这些受体涉及大量生理的活动,从到骨胳的系统的开发和维护的新陈代谢的规定和压力控制。因此,他们是重要的药目标因为糖尿病,骨质疏松症,和应力的处理联系了混乱。班 B GPCR 被组织成二个模块化的领域:一个细胞外的领域(ECD ) 和包含七 transmembrane helices (TM 领域) 的螺旋状的捆。ECD 为荷尔蒙绑定的高亲密关系和特性负责,并且 TM 域为联合到下游的 G 蛋白质的受体激活和信号被要求。尽管全身的受体的结构仍然保持未知, ECD 结构是为很多班 B GPCR 描绘的井,揭示为 ligand 识别的普通褶层。这评论总结为治疗学的目的在肽荷尔蒙类似物的设计由班 B ECD 和他们的含意指导荷尔蒙绑定的一般结构的原则。 | Kuntal PAL Karsten MELCHER H Eric XU | 2012 | Acta Pharmacologica Sinica2012，33，3： | 5 |
| 8 | Abscisic acid perception and signaling: structura mechanisms and applications显示文摘不利环境条件是对农业产量的威胁因此在生计,健康和经济上施加全球效果。Abscisic 酸(骆驼毛的织物) 是调整不能生活的压力忍耐的重要植物荷尔蒙,从而允许种应付环境压力。以前,试图开发发信号的内在的骆驼毛的织物被困难在真正的骆驼毛的织物受体的鉴定妨碍了的机制的完全的理解。骆驼毛的织物受体的 PYR/PYL/RCAR 家庭的发现因此在克服这些障碍的努力代表了一个主要里程碑;从那以后,许多结构、功能的研究提供了详细卓见进从骆驼毛的织物感觉到骆驼毛的织物应答的基因抄写的激活的过程。这理解骆驼毛的织物感觉的机制并且发信号在压力抵抗的庄稼的遗传工程以及在新合成骆驼毛的织物收缩筋的设计用作最近的、初步的开发的基础,它为应力公差的农业改进保持大诺言。 | Ley Moy NG Karsten MELCHER Bin Tean TEH H Eric XU | 2014 | Acta Pharmacologica Sinica2014，35，5： | 4 |
| 9 | Structure and activation of rhodopsin显示文摘视紫红质是第一 G-protein-coupled 受体(GPCR ) ,它的三维的结构由 X 光检查晶体学解决了。视紫红质的水晶结构在视觉系统揭示了 photoreception 和信号 transduction 的分子的机制。尽管几另外的 GPCR 水晶结构在过去几年被报导了,视紫红质结构为理解另外的 GPCR 的结构、功能的特征仍然是一个重要模型。这评论总结结构的特征, photoactivation,和视紫红质的 G 蛋白质信号 transduction。 | X Edward ZHOU Karsten MELCHER H Eric XU | 2012 | Acta Pharmacologica Sinica2012，33，3： | 4 |
| 10 | The structural basis of the dominant negative phenotype of the Gαi1β1Y2 G203A/A326S heterotrimer显示文摘 | Ping LIU Ming-zhu JIA X Edward ZHOU Parker W DE WAAL Bradley M DICKSON Bo LlU Li HOU Yan-ting YIN Ya n-yong KANG Yi SHI Karsten MELCHER H Eric XU Yi JIANG | 2016 | Acta Pharmacologica Sinica2016，37，9： | 3 |
| 11 | Structural basis of the Norrin-Frizzled 4 interaction显示文摘 | Guobo Shen Jiyuan Ke Zhizhi Wang Zhihong Cheng Xin Gu Yuquan Wei Karsten Melcher H Eric Xu Wenqing Xu | 2015 | Cell Research2015，25，9： | 3 |
| 12 | Docosahexaenoic acid suppresses arachidonic acid-induced proliferation of LS-174T human colon carcinoma cells显示文摘AIM:To investigate the impact of arachidonic acid (AA) and docosahexaenoic acid (DHA) and their combination on colon cancer cell growth.METHODS:The LS-174T colon cancer cell line was used to study the role of the prostaglandin precursor AA and the omega-3 polyunsaturated fatty acid DHA on cell growth. Cell viability was assessed in XTT assays. For analysis of cell cycle and cell death,flow cytometry and DAPI staining were applied. Expression of cyclooxygenase-2 (COX-2),p21 and bcl-2 in cells incubated with AA or DHA was examined by real-time RT-PCR. Prostaglandin E2 (PGE2) generation in the presence of AA and DHA was measured using a PGE2-ELISA.RESULTS:AA increased cell growth,whereas DHAreduced viability of LS 174T cells in a time-and dose-dependent manner. Furthermore,DHA down-regulated mRNA of bcl-2 and up-regulated p21. Interestingly,DHA was able to suppress AA-induced cell proliferation and significantly lowered AA-derived PGE2 formation. DHA also down-regulated COX-2 expression. In addition to the effect on PGE2 formation,DHA directly reduced PGE2-induced cell proliferation in a dose-dependent manner. CONCLUSION:These results suggest that DHA can inhibit the pro-proliferative effect of abundant AA or PGE2. | Piet Habbel Karsten H Weylandt Katja Lichopoj Johannes Nowak Martin Purschke Jing-Dong Wang Cheng-Wei He Daniel C Baumgart Jing X Kang | 2009 | World Journal of Gastroenterology2009，15，9： | 2 |
| 13 | Generation and characterization of a human nanobody against VEGFR-2显示文摘瞄准:Nanobody 是由一个单个 monomeric 变量抗体领域组成的抗体碎片,它能被用于许多 biotechnological 和治疗学的目的。这个工作的目的是从噬菌体显示器 library.Methods 对 VEGFR-2 domain3 (VEGFR D3 ) 孤立并且描绘人的信号域抗体:与与 VEGFR2 D3 的高亲密关系生产抗原特定的 recombinant nanobodies,液体阶段 panning 策略被用于 panning 的 all rounds。为 nanobody 表示和纯化,四 VEGFR2 堵住 D3 克隆是进 pETduet-biotin-MBP 表示向量的 subcloned。recombinant 蛋白质带了一个 MBP 标签由亲密关系层析便于纯化。Recombinant NTV (1-4 ) 在另外的胶化过滤层析步以后被获得。在 VEGFR2 D3 和 NTV (1-4 ) 之间的相互作用与基于光的 AlphaScreen 试金和 SPR 试金被估计。Anti-angiogenesis 效果在人的脐的静脉 endothelial 房间(HUVEC ) 被检验 .Results:在 AlphaScreen 试金, NTV1 (100 和 200 nmol/L ) 与 VEGFR2 D3 得到了最高有约束力的信号;NTV2 与 VEGFR2 D3 显示出中等相互作用;NTV3 和 NTV4 展出了有 VEGFR2 D3 的很少或没有相互作用。在 SPR 试金, NTV1 与一个平衡分离常数为 VEGFR2 D3 显示了一种高亲密关系(K 49 ± 的 D ) ; 1.8 nmol/L。NTV1 (1-1000 nmol/L ) dose-dependently 由 HUVECs.Conclusion 禁止了 HUVEC 和 endothelial 试管形成的增长:nanobody NTV1 是堵住 VEGFR2 的一个潜在的治疗学的候选人。这研究为指向 VEGFR2 的基于 nanobody 的癌症治疗学的开发提供新奇、有希望的策略。 | Lin MA Kai GU Cheng-hai ZHANG Xue-tao CHEN Yi JIANG Karsten MELCHER Juan ZHANG Min WANG H Eric XU | 2016 | Acta Pharmacologica Sinica2016，37，6： | 2 |
| 14 | Structure of the PRC2 complex and application to drug discovery显示文摘polycomb 压抑的建筑群 2 (PRC2 ) 建筑群催化 histone H3 离氨酸 27 的 tri-methylation (H3K27 ) ,与基因 silencing 联系的一个压抑的染色质标记。PRC2 的 Overexpression 和变化在许多癌症被发现,使 PRC2 的催化活动成为癌症治疗的一个重要目标。这评论加亮人的 PRC2 复杂界限的最近的结构的突破到 H3K27 肽和一个小分子禁止者,它提供极其需要的卓见进指向 PRC2 的药发现。 | Yi SHI Xiao-xi WANG You-wen ZHUANG Yi JIANG Karsten MELCHER H Eric XU | 2017 | Acta Pharmacologica Sinica2017，38，7： | 2 |
| 15 | Broad-band OFDM radio transmission for multimedia applications显示文摘 | Rohling H May T Karsten B | 1999 | Proc IEEE1999，87，10： | 2 |
| 16 | Therapeutic and prophylactic application of TPA (recombinant tissue plasminogen activator) into the anterior chamber of the eye显示文摘 | Karsten Rehfeldt Helmut H?h | 1999 | Der Ophthalmologe1999，，9： | 1 |
| 17 | The protozoan parasite Toxoplasma gondii targets proteins to dense granules and the vacuolarspace using both conserved and unusual mechanisms显示文摘 | Karsten V Qi H Beckers CJ | 1998 | J Cell Biol1998，141，： | 1 |
| 18 | Dynamic headspace gas chromatography/mass spectrometry characterization of volatiles produced in fish oil enriched mayonnaise during storage 显示文摘 | KARSTEN H PIA L LOTTE F | 2000 | Agric Food Chem2000，，48： | 1 |
| 19 | A Recent Polyploidy Superim-posed on Older Large-Scale Duplications in the Arabidopsis Genome 显示文摘 | GUILLAUME B KARSTEN H KENNETH H W | 2003 | Genome Research2003，13，2： | 1 |
| 20 | Deuitrifying bacteria in N2O the Earthworm gastro intestinal tract and invivo emission of nitrous ox- ide (N20) by earthworms 显示文摘 | Karsten G R D rake H L | 1997 | Applied and Environmental Mi- crobiology1997，63，： | 1 |
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