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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 | Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse显示文摘Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC binding.Using primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA synthesis.Furthermore,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production.Similar effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th subset.These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell binding.We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation.These data point to a pivotal role for HA in DC–T cell interactions at the IS. | Paul L Bollyky Stephen P Evanko Rebecca P Wu Susan Potter-Perigo S Alice Long Brian Kinsella Helena Reijonen Kelly Guebtner Brandon Teng Christina K Chan Kathy R Braun John A Gebe Gerald T Nepom Thomas N Wight | 2010 | Cellular & Molecular Immunology2010，7，3： | 3 |
| 3 | The effect ofGibbs adsorption on Marangoni instability in penetration mass transfer显示文摘 | Brian P L T Ross J R | 1972 | AIChE J1972，18，： | 1 |
| 4 | Interaction of endosialin/TEM 1 with extracellular matrix proteins mediates cell adhesion and migration 显示文摘 | Brian T Katherine R | 2007 | PNAS2007，13，17： | 1 |
| 5 | One - way wave equations for seismoacoustic propagation in elastic waveguides 显示文摘 | BRIAN T R WETTON GARY H BROOKE | 1990 | JASA1990，87，： | 1 |
| 6 | Induction of PAH-catabolism in mushroom compost and its use in the biodegradation of soil-associated phenanthrene 显示文摘 | Brian J R Fermor T R Semple K T | 2002 | Environmental Pollution2002，18，1： | 1 |
| 7 | Effect of feed restriction on adipose tissue transcript concentrationsin genetically lean and obese pigs显示文摘 | McNeel R L Ding S T O'Brian Smith E et ol | 2000 | J Anim Sci2000，78，： | 1 |
| 8 | Light gap disturbance,recruitment limitation,and tree diversity in a neotropical forest显示文摘 | Hubbell S P Foster R B O'Brian S T Harms K E Condit R Wechsler B Wright S J Loo de Lao S | | 0，，： | 1 |
| 9 | Frost deposition on cold surfaces显示文摘 | Brian P L T Reid R C Shah Y T | 1970 | Industrial Engineering Chemistry Fundamentals1970，9，3： | 1 |
| 10 | Induction of PAH-catabolism in mushroom compost and its use in the Biodegradation of soil-associated phenanthrene 显示文摘 | Brian J R Fermor T R Semple K T | 2002 | Environmental Pollution2002，118，1： | 1 |
| 11 | Genetic features of resident biofilms determine attach ment of Listeria monocytogenes 显示文摘 | Habimana O Meyrand M Meylheuc T Kulakauskas S Brian det R | 2009 | Appl Environ Microhiol2009，75，： | 1 |
| 12 | The Table Rocks Sandstone: A fluvi- al, friction-dominated lobate mouth bar sandbody in the West- phalian B Coal Measures,NE England显示文摘 | Brian R T Gillian N T | 2006 | Sedimentary Geolo- gy2006，190，： | 1 |
| 13 | Effects of flood duration and season on germination of black, cherrybark, northern red, and water oak acorns显示文摘 | Yanfei G Michael G T Brian R L | 1998 | New Forests1998，15，： | 1 |
| 14 | Outsoureing to a Powerful Contract Manufacturer: Tile Effect of Learning - by - doing显示文摘 | John V G Brian T Aleda V R | 2009 | Production and Operations Management2009，18，5： | 1 |
| 15 | Product design and supply chain coordination under extended producer responsibility显示文摘 | Subramanian R Sudheer G Brian T | 2009 | Production and Operations Management2009，18，3： | 1 |
| 16 | Vdl Mode 3 Subnet Simulation Modeling In Opnet显示文摘 | Paul T R Wang Brian T L Hung Bruce E Eckstein | 1999 | IEEE1999，，： | 1 |
| 17 | Comparison of four Acti- graph GT3X accelerometers during walking and running 显示文摘 | DINESH J Brian T DAVID R | 2010 | Med Sci Sports Exerc2010，42，2： | 1 |
| 18 | Ionic liquid-mediated selective conversion of COz to CO at low overpotentials 显示文摘 | Brian A R Michael R T | 2011 | Science2011，643，： | 1 |
| 19 | Induction of PAH-catabolism in mushroom compost and its use in the biodegradation of soil-associated phenanthrene显示文摘 | Brian J R Fermor T R Semple K T | 2002 | Environmental Pollution2002，118，1： | 1 |
| 20 | Simultaneous diode laser based in situ quantification of oxygen, carbon monoxide, water vapor, and liquid water in a dense water mist environment 显示文摘 | Andrew R Awtry Brian T Fisher Robert A Moffatt | 2007 | Proceedings of the Combustion Institute2007，31，1： | 1 |
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