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TRP Channels:Structural and Molecular Basis of the Assembly of the TRPP2/PKD1 Complex

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TRP Channels:Structural and Molecular Basis of the Assembly ...

“基因、进化与生理功能多样性”海内外学术研讨会暨中国生理学会第七届比较生理学学术会议

作者： Maximilian H.Ulbrich Albert C.M.Ong Ehud Y.Isacoff 杨建 Department of Molecular and Cell Biology University of CaliforniaBerkeleyCA 94720USA Kidney Genetics Group Academic Unit of NephrologySheffield Kidney InstituteSchool of Medicine and Biomedical SciencesUniversity of SheffieldSheffieldUK Department of Molecular and Cell Biology University of CaliforniaBerkeleyCA 94720USA Material Sciences & Physics Biosciences DivisionsLawrence Berkeley National LaboratoryBerkeleyCA 94720USA Department of Biological Sciences Columbia UniversityNew YorkNY 10027USA

Autosomal dominant polycystic kidney disease（ADPKD） is one of the most common genetic diseases in *** is caused by mutations in PKD1 or ***1（also known as polycystin-1 or PC1） is a 4302-amino acid,465 kDa integral membrane protein containing 11 putative transmembrane regions. Its large extracellular N terminus contains a number of well recognized repeats and domains,some of which are known to interact with extracellular matrix *** short intracellular C terminus contains a G protein activation ***,PKD1 is generally thought to function as a cell surface receptor for extracellular ligands and matrix proteins that couples extracellular stimuli,including mechanical stimuli,to intracellular signaling. TRPP2（also known as PKD2,polycystin-2 or PC2） is a member of the transient receptor potential （TRP） channel *** is a 968 amino acid,110 kDa integral membrane protein with 6 putative transmembrane segments and a pore-forming *** forms a Ca-permea- ble nonselective cation *** mutations in PKD1 and TRPP2 lead to ADPKD is *** two proteins likely participate in the same molecular and cellular processes in some kidney cells,since mutations in them produce similar pathological manifestations. Although both proteins are widely distributed, they show high levels of expression in kidney cells,where they are present on the plasma membrane and in the Golgi and endoplasmic *** also colocalize in the primary cilia of kidney *** two proteins associate physically and form functional ***,the subunit composition of this heteromeric complex and the molecular mechanism underlying its assembly are *** a combination of biochemistry, x-ray crystallography and a single molecule optical imaging method to determine the subunit composition of proteins in the plasma membrane of live cells,we find that this complex contains 3 TRPP2 and 1 PKD1. We also identified a coiled coil domain in the C terminus of TR

关键词： TRP channels Polycystic kidney disease Subunit stoichiometry Crystal structure Cross-linking Single molecule

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临床试验中复合终点的有效性

英国医学杂志中文版 2005年第5期8卷 315-318页

作者： Victor M Montori Gaietà Permanyer-Miralda Ignacio Ferreira-González Jason W Busse Valeria Pacheco-Huergo Dianne Bryant Jordi Alonso Elie A Akl Antònia Domingo-Salvany Edward Mills Holger J Schünemann Roman Jaeschke Gordon H Guyatt 杜昕 epartment ofMedicine MayoClinic Collegeof MedicineRochesterMN 55905 USAassistant professor Cardiology Service Epidemiology UnitHospital GeneralVall d'HebronBarcelona 08035 Spainsenior consultant Department de Medicina UniversitatAutònoma de BarcelonaHospital GeneralVall d'Hebronresearch fellow Department ofClinical Epidemiologyand Biostatistics McMaster UniversityHamiltonON L8N 3Z5 Canadaresearch associate Primary Care Centre Turó EAP VilapicinaInstitut Catalàde la SalutBarcelona Spaingeneral practitioner Department ofClinical Epidemiologyand Biostatistics McMaster UniversityHamiltonON L8N 3Z5instructor Health Services Research Unit Institut Municipald'InvestigacióMèdica BarcelonaSpainhead Department ofMedicine andof Social andPreventive Medicine University atBuffalo BuffaloNY 14214 USAresearchassistant professor Health Services Research Unit Institut Municipald'InvestigacióMèdica BarcelonaSpain senior scientist Department ofResearch Canadian Collegeof Naturopathic Medicine TorontoCanada M2K 1E2director ofresearch Department ofMedicine andof Social andPreventive Medicine University atBuffalo BuffaloNY 14214 USAassociate professor Department of Medicine McMaster Universityclinical professor Department ofClinical Epidemiologyand Biostatistics McMaster UniversityHamiltonON L8N 3Z5professor

采用复合终点作为随机临床试验的主要结局指标有时会掩盖各个终点事件间的巨大差别，在临床实践中如何参照这些临床试验的结果呢？

关键词：随机临床试验终点复合临床实践

Acknowledgments to reviewers of World Journal of Obstetrics and Gynecology

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World Journal of Obstetrics and Gynecology 2012年第1期1卷 3-3页

作者： Byron Asimakopoulos Chie-Pein Chen, MD Emmanuel Bujold Erich Cosmi MD Fanuel Lampiao Federico Coccolini Ioannis E Messinis Marjan Khajehei Polat Dursun Shi-Yann Cheng Sorina Grisaru-Granovsky PhD Assistant Professor Laboratory of Physiology School of Medicine Democritus University of Thrace Dragana 68100 Alexandroupolis Greece MD PhDDivision of High Risk Pregnancy Mackay Memorial Hospital 92 Sec. 2 Zhong-Shan North Road Tai-pei 104 Taiwan China MD MSc Associate Professor Department of Obstetrics and Gynecology CHUQ Centre Mère-Enfant Uni-versité Laval 2705 boul. Laurier Québec QC G1V 4G2 Canada PhD Assistant Professor Department of Child and Woman Health Obstetrics and Gynecology Unit Univer-sity of Padua Via Giustiniani n 3 35128 Padua Italy PhD Department of Basic Medical Science Physiology Division P/Bag 360 Blantyre 3 Malawi MD General and Emergency Surgery Depart-ment Ospedali Riuniti Largo Barozzi 1 24126 Bergamo Italy MD PhD Professor Department of Ob-stetrics and Gynaecology University of Thessalia Medical School 41110 Larissa Greece MSc PhD Sexology Department School of Public Health Curtin University Bentley 6102 Western Australia associate Professor Department of Obstetrics and Gynecology School of Medicine Baskent University Ankara Turkey MD Department of Obstetrics and Gynecol-ogy China Medical University Beigang Hospital 123 Shinder Road Beigang Town Yunlin County 65152 Taiwan China MD PhD Department Obstetrics and Gynecology Shaare Zedek Medical Center Jerusalem 91031 Is-rael

Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Obstetrics and *** editors and authors of the articles submitted to the journal are grateful to the following reviewers for evaluating the articles(including those published in this issue and those rejected for this issue)during the last editing time period.

关键词：《世界妇产科杂志》期刊编辑工作发行工作

Empathy Gender in Dental Students in Latin America: An Exploratory and Cross-Sectional Study

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Health 2015年第11期7卷 1527-1535页

作者： Víctor Patricio Díaz-Narváez Ana María Erazo Coronado Jorge Luis Bilbao Farith González Mariela Padilla Madeline Howard María Guadalupe Silva Mirian Bullen Fredy Gutierrez Teresa Varela de Villalba Mercedes Salcedo Rioja Joyce Huberman Doris Carrasco Robert Utsman School of Dentistry Universidad San Sebastián Santiago Chile associate Investigator Universidad Autónoma de Chile Santiago Chile Universidad Metropolitana Barranquilla Colombia School of Medicine Universidad Libre Seccional Barranquilla y Fundación Universitaria San Martín Sede Puerto Colombia Barranquilla Colombia School of Dentistry Universidad de Cartagena Campus de la Salud Barrio Zaragocilla Cartagena Colombia School of Health Sciences Universidad Latinoamericana de Ciencia y Tecnología San José Costa Rica School of Dentistry Universidad de Costa Rica San Pedro de Montes de Oca San José Costa Rica Institute for Scientific Research Universidad Central del Este San Pedro de Macorís Dominican Republic School of Dentistry Universidad de Panamá Panama City Panama Facultad de Estomatología Roberto Beltrán Universidad Peruana Cayetano Heredia Lima Peru School of Medicine Universidad Católica de Córdoba Córdoba Argentina Department of Pediatric Dentistry School of Dentistry Universidad Nacional Mayor de San Marcos Lima Peru School of Dentistry Faculty of Clinical Medicine Universidad del Desarrollo Santiago Chile School of Dentistry Universidad de Concepción Concepción Chile Investigation of the School of Health Sciences Universidad Latinoamericana de Ciencia y Tecnología San José Costa Rica

Background: It is well-founded that empathy is an attribute that increases the likelihood of good communication between health professionals and patients, and it is usual that there is the conviction that empathy levels are higher in women than in men. Aims: A study comparing levels of empathy gender of students in 18 schools of dentistry from six Latin American countries was conducted. Method: An exploratory cross-sectional study of which empathy levels were measured by the Jefferson Scale of Empathy for dental students (S version) and these levels were compared between genders by t-student test, after verification of normal distribution and homoscedasticity. Results: Variability was found in the results of the comparisons. In some cases, empathy levels were higher in women, others in men and in most of them there were no differences between genders. Conclusions: The observed results do not support the belief that women are more empathetic than men. However, more studies must be performed in more powers and countries to verify that the results described constitute a scientific fact and not just a feature of dental students specifically in the countries studied.

关键词： Empathy Gender Dental Students

测定血清S100蛋白用于诊断克-雅病:前瞻性病例对照研究

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英国医学杂志中文版 1998年第1期1卷 22-27页

作者： Markus Otto Jens Wiltfang Ekkehard Schtz Ingo Zerr Anke Otto Annette Pfahlberg Olaf Gefeller Manfred Uhr Armin Giese Thomas Weber Hans A Kretzschmar Sigrid Poser 张星虎 Neurologische Klink und Poliklinik Georg-August Universitt Gttingen Robert-koch strasse 40 D-37075 Cttingen Germany group Leaderlaboratory diagnosis of CJD Psychiatrische Klinik und Poliklinik Georg-AugustUniversitt Gttingen senior research fellow Abteilung Klinische Chemie Georg-August-Universitt Gttingenresearch fellow Neurologische Klink und Poliklinik Georg-August Universitt Gttingen Robert-koch strasse 40 D-37075 Cttingen Germany research fellow Neurologische Klink und Poliklinik Georg-August Universitt Gttingen Robert-koch strasse 40 D-37075 GttingenGermany research fellow Abteilung Klinische Chemie Georg-August-Universitt Gttingen statistician Abteilung Medizinische Statistik Georg-August-Universitt Gttingen associate professor of medical statistics continued over Max-Planck lnstitut ftir Psychiatrie Kraepelinstrasse 10 D-80804 MunichGermany research fellow Institut fr Neuropathologie Georg-August-Universitt Gttingen research fellow Neurologische Abteilung Marienkrankenhaus Hamburg Alfredstrasse 9D-22087 Hamburg Germany headdepartment of neruology Institut fr Neuropathologie Georg-August-Universitt Gttingen headdepartment of neuropathology Neurologische Klink und Poliklinik Georg-August Universitt Gttingen Robert-koch strasse 40 D-37075 Gttingen Germany headedidemiology and early diagnosis of CJD

目的:分析克-雅病(Creutzfeldt-Jakob dis-ease,CJD)患者及对照组血清中脑特异性 S100蛋白浓度。设计:前瞻性病例对照研究。研究单位:国家 CJD 监测站。研究对象:224例疑为 CJD 的转诊患者及35例无痴呆的对照病例。主要结果测定:CJD 患... 详细信息

目的:分析克-雅病(Creutzfeldt-Jakob dis-ease,CJD)患者及对照组血清中脑特异性 S100蛋白浓度。设计:前瞻性病例对照研究。研究单位:国家 CJD 监测站。研究对象:224例疑为 CJD 的转诊患者及35例无痴呆的对照病例。主要结果测定:CJD 患者、其他疾病引起的痴呆患者及对照组血清 S100浓度。结果:224例疑为 CJD 的患者中,65例经病理证实确诊;6例有基因突变而肯定诊断;43例很可能患 CJD;36例可能患 CJD;74例患有其他疾病。108例为肯定或很可能 CJD 患者,其血清 S100浓度中位数为395 pg/ml(SD 387 pg/ml)。这明显高于患其他疾病的74例患者(S100浓度中位数为109pg/ml,SDl77pg/ml;P=0.0001)。以213pg/ml为界值,S100测定用于 CJD 诊断的敏感性为77.8%(95%的可信区间为66.8%～85.2%),特异性为81.1%(70.3%～89.3%)。在 Kaplan-Meier 曲线上,不同浓度 S100患者的存活时间差异有显著性(P=0.023)。结论:S100血清浓度测定是一种有价值的工具,在 CJD 的鉴别诊断中,较测定脑脊液更有价值。尚需更多的研究以确定连续测定是否有助于提高此病的诊断准确性。

关键词：克-雅病 S100蛋白脑特异性存活时间差异有显著性鉴别诊断基因突变无痴截点病例对照研究

Psoraleae induces hepatotoxicity by affecting bile acid balance

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Asian Toxicology Tesearch 2021年第1期3卷 15-22页

作者： Wei-Ling Pu Bin Yu An-Hong Wang Ya-Nan Bi Hong Shi Kun Zhou Institute of Traditional Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China School of Integrative Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China Gansu Provincial Hospital Lanzhou731600China Tianjin Key laboratory of Chinese medicine Pharmacology Tianjin 301617China

Buguzhi(Psoraleae fructus),the seed of Psoralea corylifolia Linn,is used to treat osteoporosis,nephritis,vitiligo and other ***,long-term routine or overdose of Psoraleae fructus may lead to hepatotoxicity and become a major obstacle of its clinical *** was a key active component of Psoraleae fructus,and a main cause of Psoraleae fructus *** research was to investigate the hepatotoxicity of psoralen and whether it’s related with bile acid ***:C57BL/6 mice were randomly divided into 4 groups(n=10).Psoralen(20 mg/kg,40 mg/kg and 80 mg/kg)was administrated intragastrically once every day and control group with equivalent water until 4 ***:The results showed that psoralen caused an increase in liver coefficient and the injury of hepatocytes microstructure of *** also inhibited cell viability of HepG2 *** treated with psoralen exerted liver total bile acid increased while serum total bile acid decreased,which indicated that psoralen-induced liver injury may partly associate with *** further study of liver transporters,high dose of psoralen inhibited the expression of some important hepatic efflux transporters(including BSEP,p-gp and ABCG5)in vivo and in ***:We provide evidence for the first time that psoralen may induce cholestatic hepatotoxicity for the bile acid retention by inhibition on bile acid export pumps.

关键词： Psoralen Hepatotoxicity Bile acid Hepatic transporter

Comparing independent climate-sensitive models of aboveground biomass and diame ter grow th with their compatible simultaneous model system for three larch species in China

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International Journal of Biomathematics 2019年第7期12卷 1-20页

作者： Zhigang Gao Qiuyan Wang Zongda Hus Peng Luo Guangshuang Duan Ram PSharma Qiaolin Ye Wenqiang Gao Xinyu Song Liyong Fut College of Animal Science and Technology Inner Mongolia University for Nationalities Tongliao 028000 P.R.China Research Institute of Forest Resource Information Techniques Chinese Academy of Forestry Beijing 100091P.R.China Key laboratory of Forest Management and Growth Modelling National Forestry and Grassland Administration Beijing 100091 P.R.China College of Resources Sichuan Agricultural University Chengdu 611130Sichuan provinceP.R.China Faculty of Forestry and Wood Sciences Czech University of Life Sciences Prague Prague 6-SuchdolCzech Republic College of Information Science and Technology Nanjing Forestry University Nanjing Jiangsu 210037P.R.China College of Computer and Information Techniques Xinyang Normal University Xinyang 464000 Henan ProvinceP.R.China

Accurate estimate of tree biomass is essential for forest *** recent years,several climate-sensitive allometric biomass models with diameter at breast height(D)as a predictor have been proposed for various tree species and climate zones to estimate tree aboveground biomass(AGB).But the allometric models only account for the potential effects of climate on tree biomass and do not simultaneously explain the influence of climate on D *** this study,based on the AGB data from 256 destructively sampled trees of three larch species randomly distributed across the five secondary climate zones in northeastern and northern China,we first developed a climate-sensitive AGB base model and a climate-sensitive D growth base model using a nonlinear least square regression separately.A compatible simultaneous model system was then developed with the climate-sensitive AGB and D growth models using a nonlinear seemingly unrelated *** potential effects of several temperature and precipitation variables on AGB and D growth were *** fitting results of climatic sensitive base models were compared against those of their compatible simultaneous model *** was found that a decreased isothermality([mean of monthly(maximum temperatureminimum temperature)]/(Maximum temperature of the warmest month-Minimum temperature of the coldest month))and total growing season precipitation,and increased annual precipitation significantly increased the values of AGB;an increase of temperature seasonality(a standard deviation of the mean monthly temperature)and precipitation seasonality(a standard deviation of the mean monthly precipitation)could lead to the increase of *** differences of the model fitting results between the compatible simultaneous system with the consideration of climate effects on both AGB and D growth and its corresponding climate-sensitive AGB and D growth base models were very small and insignificant(p>0.05).Compared to the base models,the in

关键词： Larch aboveground biomass diameter at breast height climate change seemingly unrelated regression leave-one-out cross-validation

Extreme Events Assessment Methodology Coupling Debris Flow,Flooding and Tidal Levels in the Coastal Floodplain of the Sao Paulo North Coast(Brazil)

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International Journal of Geosciences 2013年第5期4卷 30-38页

作者： Rafael de Oliveira Sakai Diego Lourenco Cartacho Emilia Arasaki Paolo Alfredini Alessandro Pezzoli Wilson Cabral de Sousa Junior Maurizio Rosso Luca Magni Polytechnic School of Sao Paulo University Department of Hydraulic and Environmental EngineeringHarbour and Coastal Area of the Hydraulic LaboratoryAvenida Professor Luciano GualbertoTravessa 3n.380Cidade UniversitariaSao PauloBrazil National Institute of for Space Research Av.Dos Astronautas n.1758Sao Jose dos CamposSao PauloBrazil Polytechnic of Torino Engineering FacultyDepartment of EnvironmentLand and Infrastructure EngineeringCorso Duca degli Abruzzi n.24TorinoItaly Technological Institute of Aeronautics Infrastructure Engineering DivisionDepartment of Hydric Resources and Environmental SanitationPraca Marechal Eduardo Gomes n.50ITA-IEISao Jose dos CamposSao PauloBrazil Studio Rosso Ingegneri Associati s.r.l. Corso Principe OddoneTorinoItaly

The North Coastal Region of the State of S?o Paulo, which comprises the Municipalities of Caraguatatuba, S?o Sebasti?o, Ilhabela and Ubatuba, is one of the most prone to flooding and debris flow deposition Brazilian areas, owing to hydrological extreme rainfall events usually coupled with extreme tidal levels. This risk is also high due to human lives and material assets, with increasing population rates and the establishment of large companies such as the Oil industry, with reduced defense/prevention measures and *** catastrophic scenario of the city of Caraguatatuba, in March 1967, resulting from one of the most serious natural disasters in Brazil, fosters discussions about probabilities of heavy rainfall-caused events and rise in the sea level in coastal areas. Hence, this research is a consequence of this reality. The research is founded on an innovative methodology based on the analysis of past data of rainfall and tidal stations, complemented with debris flow registers in the region of the north coastal zone of the State of S?o Paulo (Brazil). The anaysis developed involved the meteorological, hydraulic, geotechnical and statistical knowledge *** results are intended to be used for urban planning, designs of macro-drainage, fluvial, maritime projects and debris flow retention structures. These practical applications will then associate the probability of occurrence of certain types of heavy rainfall-caused events such as flooding or debris flow coupled with a corresponding increase in tidal levels.

关键词： Meteorology Hydrology Maritime Hydraulics Rainfall Tidal Levels Extreme Events Natural Disasters Geomorphology Debris-Flow Flooding

A single nucleotide polymorphism in the matrix metalloproteinase 2 promoter is closely associated with high risk of nasopharyngeal carcinoma in Cantonese from southern China

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Chinese Journal of Cancer 2011年第9期30卷 620-626页

作者： Jian-Yong Shao Yun Cao Xiao-Ping Miao Ma-Yan Huang Ling Deng Jian-Jun Hao Xiao-Man Liang Li-Fu Hu Ingemar Ernberg Dong-Xin Lin Yi-Xin Zeng State Key laboratory of Oncology in South China Guangzhou Guangdong 510060 P. R. China Department of Pathology Sun Yat-sen University Cancer Center Guangzhou Guangdong 510060 P. R. China Department of Epidemiology and Biostatistics School of Public Health Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430030 P. R. China Huangpu Chinese Traditional Medicine Hospital Guangzhou Guangdong 510360 P. R. China Microbiology and Tumor Biology Center Karolinska Institute Stockholm S171 77 Sweden Department of Etiology and Carcinogenesis Cancer Institute Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 P. R. China Department of Experiment Research Sun Yat-sen University Cancer Center Guangzhou Guangdong 510060 P. R. China.

Matrix metalloproteinase 2(MMP2) has been shown to play an important role in several steps of cancer ***-1306C/T polymorphism of the MMP2 gene displays a strikingly lower promoter activity than the T allele,and the CC genotype in the MMP2 promoter has been reported to associate with the development of several *** assess the contribution of the MMP2-1306C/T polymorphism to the risk of nasopharyngeal carcinoma(NPC),we conducted a case-control study and analyzed MMP2 genotypes in 370 patients with NPC and 390 frequency-matched controls using real-time PCR-based TaqMan allele *** found that subjects with the CC genotype had an increased risk(OR = 1.55,95% CI = 1.05-2.27) of developing NPC compared to those with the CT or TT ***,we found that the risk of NPC was markedly increased in subjects who were smokers(OR = 15.04,95% CI = 6.65-33.99),heavy smokers who smoked ≥20 pack-years(OR = 18.66,95% CI = 7.67-45.38),or young(associated with NPC risk,and this association is especially noteworthy in heavy smokers.

关键词：单个核苷酸多态性基质金属蛋白酶鼻咽癌风险中国南部 TaqMan探针全国人民代表大会局长