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| 1 | High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes显示文摘Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening(HTS) data for 3 762 distinct global gene knockout(KO) mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type(WT) cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging,ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass: 23 previously reported genes(Calcr, Cebpb, Crtap, Dcstamp, Dkk1, Duoxa2, Enpp1, Fgf23, Kiss1/Kiss1 r, Kl(Klotho),Lrp5, Mstn, Neo1, Npr2, Ostm1, Postn, Sfrp4, Slc30a5, Slc39a13, Sost, Sumf1, Src, Wnt10b), five novel genes extensively characterized(Cldn18, Fam20 c, Lrrk1, Sgpl1, Wnt16), five novel genes with preliminary characterization(Agpat2, Rassf5, Slc10a7, Slc26a7, Slc30a10) and three novel undisclosed genes coding for potential osteoporosis drug targets. | Robert Brommage Jeff Liu Gwenn M Hansen Laura L Kirkpatrick David G Potter Arthur T Ss Brian Zambrowicz David R Powell Peter Vogel | 2014 | Bone Research2014，2，3： | 7 |
| 2 | Senescent human hepatocytes express a unique secretory phenotype and promote macrophage migration显示文摘AIM:To develop a model of stress-induced senescence to study the hepatocyte senescence associated secretory phenotype(SASP).METHODS:Hydrogen peroxide treatment was used to induce senescence in the human Hep G2 hepatocyte cell line.Senescence was confirmed by cytochemical staining for a panel of markers including Ki67,p21,heterochromatin protein 1β,and senescence-associated-β-galactosidase activity.Senescent hepatocytes were characterised by gene expression arrays and quantitative polymerase chain reaction(q PCR),and conditioned media was used in proteomic analyses,a human chemokine protein array,and cell migration assays to characterise the composition and function of the hepatocyte SASP.RESULTS:Senescent hepatocytes induced classical markers of senescence(p21,heterochromatin protein1β,and senescence-associated-β-galactosidase activity);and downregulated the proliferation marker,Ki67.Hepatocyte senescence induced a 4.6-fold increase in total secreted protein(P=0.06)without major alterations in the protein profile.Senescence-induced genes were identified by microarray(Benjamini Hochbergcorrected P<0.05);and,consistent with the increase in secreted protein,gene ontology analysis revealed a significant enrichment of secreted proteins among inducible genes.The hepatocyte SASP included characteristic factors such as interleukin(IL)-8 and IL-6,as well as novel components such as SAA4,IL-32and Fibrinogen,which were validated by q PCR and/or chemokine protein array.Senescent hepatocyteconditioned medium elicited migration of inflammatory(granulocyte-macrophage colony stimulating factor,GM-CSF-derived),but not non-inflammatory(CSF-1-derived)human macrophages(P=0.022),which could contribute to a pro-inflammatory microenvironment in vivo,or facilitate the clearance of senescent cells.CONCLUSION:Our novel model of hepatocyte senescence provides insights into mechanisms by which senescent hepatocytes may promote chronic liver disease pathogenesis. | Katharine M Irvine Richard Skoien Nilesh J Bokil Michelle Melino Gethin P Thomas Dorothy Loo Brian Gabrielli Michelle M Hill Matthew J Sweet Andrew D Clouston Elizabeth E Powell | 2014 | World Journal of Gastroenterology2014，20，47： | 2 |
| 3 | 机辅语言学习的运用显示文摘八十年代,随着微机的普及和教育各个领域中技术的进步,机辅学习引起了人们越来越大的兴趣。机辅语言学习(computer assisted language learning)作为其中的一个方面,在一些基金组织的关心和支持下也得到了很大的发展,因此受到不少人士的推崇。 | Brian Powell 褚骊 | 1999 | 外语教学理论与实践1999，，1： | 2 |
| 4 | A Method for Assessing Hydrologic Alteration Within Ecosystems显示文摘 | Brian D Richter J eff rey V Baumgartner J ennifer Powell | 1996 | Conservation Biology1996，10，4： | 1 |
| 5 | A method for assessing hydrologic alteration within ecosystems显示文摘 | Brian D Richter Jeffrey V Baumgartner Jennifer Powell | 1996 | Conservation Biology1996，10，4： | 1 |
| 6 | Papillary Thyroid Carcinoma Managed at the Mayo Clinic during Six Decades (1940–1999): Temporal Trends in Initial Therapy and Long-term Outcome in 2444 Consecutively Treated Patients显示文摘 | Ian D. Hay Geoffrey B. Thompson Clive S. Grant Eric J. Bergstralh Catherine E. Dvorak Colum A. Gorman Megan S. Maurer Bryan McIver Brian P. Mullan Ann L. Oberg Claudia C. Powell Jon A. van Heerden John R. Goellner | 2002 | World Journal of Surgery2002，，8： | 1 |
| 7 | White matter integrity and vulnerability to Alzheimer’s disease: Preliminary findings and future directions显示文摘 | Brian T. Gold Nathan F. Johnson David K. Powell Charles D. Smith | 2011 | BBA - Molecular Basis of Disease2011，，3： | 1 |
| 8 | A phase II study of the heparanase inhibitor PI-88 in patients with advanced melanoma显示文摘 | Karl D. Lewis William A. Robinson Michael J. Millward Alex Powell Timothy J. Price Damien B. Thomson Euan T. Walpole Andrew M. Haydon Brian R. Creese Kaye L. Roberts John R. Zalcberg Rene Gonzalez | 2008 | Investigational New Drugs2008，，1： | 1 |
| 9 | A method for assessing hydrologic alter- ation within ecosystems显示文摘 | RICHTER BRIAN D BAUMGARTNER JEFFREY V POWELL JENNIFER | 1996 | Conservation Biology1996，4，10： | 1 |
| 10 | Investigating the effect of carbon shape on virus adsorption显示文摘 | Powell T Brian G M Jagtoyen M | 2000 | Environ Sci Techn- oi2000，34，13： | 1 |
| 11 | A method for assessing hydrologic alteration within ecosystems 显示文摘 | Brian D Richter Jeffrey V Baumgartner Jennifer Powell | 1996 | Conservation Biology1996，10，4： | 1 |
| 12 | Effect of whole-body vibration on bone properties in aging mice显示文摘 | Karl H. Wenger James D. Freeman Sadanand Fulzele David M. Immel Brian D. Powell Patrick Molitor Yuh J. Chao Hong-Sheng Gao Mohammed Elsalanty Mark W. Hamrick Carlos M. Isales Jack C. Yu | 2010 | Bone2010，，4： | 1 |
| 13 | A method for assessing hydrologic alteration within ecosys-tems显示文摘 | Brian D Richter Jeffrey V Baumgartner Jennifer Powell | | 0，，04： | 1 |
| 14 | Reconsidering the effects of sibling configuration: Recent advances and challenges显示文摘 | Lala Carr Steelman Powell Brian Werum Regina Carter Scott | 2002 | Annual Review of Sociology2002，，： | 1 |
| 15 | Reconsidering the effects of sibling configuration: recent advances and challenges 显示文摘 | Steelman Lala Cart Brian Powell Regina Wemm and Scott Carter | 2002 | In Annual Review of Sociology2002，，28： | 1 |
| 16 | White matter integrity and vulnerability to Alzheimer’s disease: Preliminary findings and future directions显示文摘 | Brian T. Gold Nathan F. Johnson David K. Powell Charles D. Smith | 2011 | BBA - Molecular Basis of Disease2011，，3： | 1 |
| 17 | Squamous cell carcinoma arising in a dermoid cyst of the ovary显示文摘 | John L Powell Jeffrey A Stinson G.Patrick Connor Brian S Shiro Michael Mattison | 2003 | Gynecologic Oncology2003，，3： | 1 |
| 18 | Effects of task interdependence on the relationship between helping behavior and group performance显示文摘 | DANIEL G BACHRACH BENJAMIN C POWELL BRIAN J COLLINS | 2006 | J Appl Psychol2006，91，13： | 1 |
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