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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 | Leukemia:研究鉴定出与34种AML白血病亚群相关联的基因突变显示文摘针对成年急性髓细胞白血病(acute myeloid leukemia,AML)患者的一项新的大型研究将80种癌症相关基因突变与5种AML亚型相关联。这5种AML亚型可通过特异性的染色体异常加以确定。在未来,这些发现可能有助指导基因突变测试和治疗决策。 | A-K Eisfeld K Mrózek J Kohlschmidt D Nicolet S Orwick C J Walker K W Kroll J S Blachly A J Carroll J E Kolitz B L Powell E S Wang R M Stone A de la Chapelle J C Byrd C D Bloomfield | 2017 | 现代生物医学进展2017，17，15： | 7 |
| 3 | Macrophage secretory products induce an inflammatory phenotype in hepatocytes显示文摘AIM:To investigate the influence of macrophages on hepatocyte phenotype and function.METHODS:Macrophages were differentiated from THP-1 monocytes via phorbol myristate acetate stimulation and the effects of monocyte or macrophageconditioned medium on HepG2 mRNA and protein expression determined.The in vivo relevance of these findings was confirmed using liver biopsies from 147 patients with hepatitis C virus(HCV)infection.RESULTS:Conditioned media from macrophages,but not monocytes,induced a transient morphological change in hepatocytes associated with upregulation of vimentin(7.8±2.5-fold,P=0.045)and transforming growth factor(TGF)-β1(2.6±0.2-fold,P<0.001)and downregulation of epithelial cadherin(1.7±0.02-fold,P=0.017)mRNA expression.Microarray analysis revealed significant upregulation of lipocalin-2(17-fold,P <0.001)and pathways associated with inflammation,and substantial downregulation of pathways related to hepatocyte function.In patients with chronic HCV,realtime polymerase chain reaction and immunohistochemistry confirmed an increase in lipocalin-2 mRNA(F0 1.0 ±0.3,F1 2.2±0.2,F2 3.0±9.3,F3/4 4.0±0.8,P= 0.003)and protein expression(F1 1.0±0.5,F2 1.3± 0.4,F3/4 3.6±0.4,P=0.014)with increasing liver injury.High performance liquid chromatography-tandem mass spectrometry analysis identified elevated levels of matrix metalloproteinase(MMP)-9 in macrophageconditioned medium,and a chemical inhibitor of MMP-9 attenuated the change in morphology and mRNA expression of TGF-β1(2.9±0.2 vs 1.04±0.1,P<0.001) in macrophage-conditioned media treated HepG2 cells.In patients with chronic HCV infection,hepatic mRNA expression of CD163(F0 1.0±0.2,F1/2 2.8±0.3,F3/4 5.3±1.0,P=0.001)and MMP-9(F0 1.0±0.4,F1/2 2.8±0.3,F3/4 4.1±0.8,P=0.011)was significantly associated with increasing stage of fibrosis.CONCLUSION:Secreted macrophage products alter the phenotype and function of hepatocytes,with increased expression of inflammatory mediators,suggesting that hepatocytes actively participate in liver injury. | Michelle Melino Victoria L Gadd Gene V Walker Richard Skoien Helen D Barrie Dinesh Jothimani Leigh Horsfall Alun Jones Matthew J Sweet Gethin P Thomas Andrew D Clouston Julie R Jonsson Elizabeth E Powell | 2012 | World Journal of Gastroenterology2012，18，15： | 3 |
| 4 | Situ immunoassay (ISIA)of field grapefruit trees inoculated with mild isolates of citrus tristeza virus indicates mixed infections with severe isolates显示文摘 | Youjian L Rundell P A Powell C A | 2002 | Plant Disease2002，，86： | 2 |
| 5 | Bit-wise paral lel algorithms for efficient software correlation applied to a GPS soft ware receiver显示文摘 | LEDVINA B M PSIAKI M L POWELL S P | 2004 | IEEE Transactions on Wireless Communications2004，3，5： | 1 |
| 6 | Growth and sexual size dimorphism in Alberta populations of the eastern short-homed lizard,Phrynosoma douglassi brevirostre 显示文摘 | POWELL G L RUSSELL A P | 1985 | Can J Zool1985，63，： | 1 |
| 7 | Inorganic -organic hybrids by exfoliation of MoS2 显示文摘 | Powell A V Kosidowski L McDowall A | 2001 | Journal of Materials Chemistry2001，11，： | 1 |
| 8 | CFC phase-out: have we met the challenge? 显示文摘 | Powell R L | 2002 | Journal of Fluorine Chemistry2002，114，2： | 1 |
| 9 | The influence of cytokinins on in vitro shoot development of 'Concord Grape'显示文摘 | Pool R M Powell L E | 1975 | J Amer Soc Hort Sci1975，100，2： | 1 |
| 10 | Adoptive immu- notherapy for cancer: building on success 显示文摘 | Gattinoni L Powell DJ Jr Rosenberg SA | 2006 | Nat Rev hnnmnol2006，6，5： | 1 |
| 11 | Caries risk assessment:relevance to the practitioner显示文摘 | Powell L V | 1998 | J Am Dent Assoc1998，129，3： | 1 |
| 12 | Nonparametric estimation of triangular simultaneous equations models 显示文摘 | Whitney K Newey James L Powell Francis Vella | 1999 | Econometrica1999，67，3： | 1 |
| 13 | Interorganizational collaboration and the locus of innovation:Networks of learning in biotechnology显示文摘 | Powell W Koput K Smith-Doerr L | 1996 | Administrative Science Quarterly1996，41，1： | 1 |
| 14 | Transgenic expression of pear PGIP in tomato limits fungal colonization 显示文摘 | Powell A L T van Kan J ten Have A | 2000 | Molecular Plant-Microbe Interaction2000，13，： | 1 |
| 15 | CFC phase-out: Have we met the challenge 显示文摘 | Powell R L | 2002 | Journal Fluorine Chemistry2002，，114： | 1 |
| 16 | Adoptive im munotherapy for cancer: building on suceess显示文摘 | Gattiononi L Powell DJ Tr Rosenberg SA | 2006 | Nat Rev Immu- nol2006，6，5： | 1 |
| 17 | Some alkaloid relationships among seedings and mature plants of FCT 显示文摘 | Moore E L Gwynn G R Powell N T | 1963 | Tobacco Science1963，7，： | 1 |
| 18 | Isolated cardiac myocytes显示文摘 | DOW O W HARDING N G L POWELL T | 1981 | CardiovascRes1981，15，： | 1 |
| 19 | Interorganizational collaboration and the locus of innovation:networks of learning in biotechnology显示文摘 | Powell W.W Koput K.W Smith-Doerr L | | 0，，： | 1 |
| 20 | Interorgani- zational collaboration and the locus of innovation: networks of learning in biotechnology 显示文摘 | Powell W W Koput K W Smith-Doe:rr L | 1996 | Administra- tive Science Quarterly1996，41，1： | 1 |
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