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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 | Desferrioxamine in warm reperfusion media decreases liver injury aggravated by cold storage显示文摘AIM:To evaluate whether desferrioxamine decreases ischemia and perfusion injury aggravated by cold storage(CS)in a rat liver perfusion model. METHODS:Isolated rat livers were kept in CS in University of Wisconsin Solution for 20 h at 4℃,then exposed to 25 min of warm ischemia(WI)at 37℃ followed by 2 h of warm perfusion(WP)at 37℃with oxygenated(95%oxygen and 5%carbon dioxide) Krebs-Henseleit buffer.Desferrioxamine(DFO),an iron chelator,was added at different stages of storage,ischemia and perfusion:in CS only,in WI only,in WP only, in WI and perfusion,or in all stages.Effluent samples were collected after CS and after WI.Perfusate samples and bile were collected every 30 min(0,0.5,1,1.5 and 2 h)during liver perfusion.Cellular injury was assessed by the determination of lactate dehydrogenase(LDH) and aspartate aminotransferase(AST)in the effluent and perfusate samples.Total iron was analysed in the perfusate samples.After WP,the liver was collected for the determination of liver swelling(wet to dry ratio) and liver morphological examination(hematoxylin and eosin staining). RESULTS:Increased CS time caused increased liver dysfunction during WP.After 2 h of WP,liver injury was indicated by increased release of AST(0.5 h CS:9.4± 2.2 U/g liver vs 20 h CS:45.9±10.8 U/g liver,P<0.05) and LDH(0.5 h CS:59±14 U/g liver vs 20 h CS:297 ±71 U/g liver,P<0.05).There was an associated increase in iron release into the perfusate(0.5 h CS:0.11 ±0.03μmoL/g liver vs 20 h CS:0.58±0.10μmoL/g liver,P<0.05)and reduction in bile flow(0.5 h CS: 194±12μL/g vs 20 h CS:71±8μL/g liver,P<0.05). When DFO was added during WI and WP following 20 h of CS,release of iron into the perfusate was de- creased(DFO absent 0.58±0.10μmoL/g liver vs DFO present 0.31±0.06μmoL/g liver,P<0.05),and liver function substantially improved with decreased release of AST(DFO absent 45.9±10.8 U/g liver vs DFO present 8.1±0.9 U/g liver,P<0.05)and LDH(DFO absent 297±71 U/g liver vs DFO present 56±7 U/g liver,P<0.05),and increased bile flow(DFO absent 71±8μL/g liver vs DFO present 237±36μL/g liver, P<0.05).DFO was also shown to improve liver morphology after WP.Cellular injury(the release of LDH and AST)was significantly reduced with the addition of DFO in CS medium but to a lesser extent compared to the addition of DFO in WP or WI and perfusion.There was no effect on liver swelling or bile flow when DFO was only added to the CS medium. CONCLUSION:DFO added during WI and perfusion decreased liver perfusion injury aggravated by extended CS. | Peter G Arthur Xian-Wa Niu Wen-Hua Huang Bastiaan DeBoer Ching Tat Lai Enrico Rossi John Joseph Gary P Jeffrey | 2013 | World Journal of Gastroenterology2013，19，5： | 2 |
| 3 | Association between serosal intestinal microcirculation and blood pressure during major abdominal surgery显示文摘Background:In clinical practice,blood pressure is used as a resuscitation goal on a daily basis,with the aim of maintaining adequate perfusion and oxygen delivery to target organs.Compromised perfusion is often indicated as a key factor in the pathophysiology of anastomotic leakage.This study was aimed at assessing the extent to which the microcirculation of the bowel coheres with blood pressure during abdominal surgery.Methods:We performed a prospective and observational cohort study.In patients undergoing abdominal surgery,the serosal microcirculation of either the small intestine or the colon was visualized using handheld vital mi-croscopy(HVM).From the acquired HVM image sequences,red blood cell velocity(RBCv)and total vessel density(TVD)were calculated using MicroTools and AVA software,respectively.The association between microcircula-tory parameters and blood pressure was assessed using Pearson’s correlation analysis.We considered a two-sided P-value of<0.050 to be significant.Results:In 28 patients undergoing abdominal surgery,a total of 76 HVM images were analyzed.The RBCv was 335±96μm/s and the TVD was 13.7±3.4 mm/mm ^(2).Mean arterial pressure(MAP)was 71±12 mm Hg during microcirculatory imaging.MAP was not correlated with RBCv(Pearson’s r=−0.049,P=0.800)or TVD(Pearson’s r=0.310,P=0.110).Conclusion:In 28 patients undergoing abdominal surgery,we found no association between serosal intestinal microcirculatory parameters and blood pressure. | Arthur LM Tavy Anton FJ de Bruin E Christiaan Boerma Can Ince Matthias P Hilty Peter G Noordzij Djamila Boerma Mat van Iterson | 2021 | Journal of Intensive Medicine2021，1，1： | 1 |
| 4 | Nutritioual control of storage protein synthesis in developing grain of wheat and barley显示文摘 | Peter R S Arthur S T Nigel G H | 2001 | Plant Growth Regulation2001，34，1： | 1 |
| 5 | Genotype-Phenotype Correlation in the Long-QT Syndrome: Gene-Specific Triggers for Life-Threatening Arrhythmias显示文摘 | Peter J. Schwartz Silvia G. Priori Carla Spazzolini Arthur J. Moss G. Michael Vincent Carlo Napolitano Isabelle Denjoy Pascale Guicheney Günter Breithardt Mark T. Keating Jeffrey A. Towbin Alan H. Beggs Paul Brink Arthur A.M. Wilde Lauri Toivonen Wojciech | 2001 | Circulation: Journal of the American Heart Association2001，，： | 1 |
| 6 | Inhibitors of c-Jun N-terminal kinases-JuNK no more?显示文摘 | Marie A Bogoyevitch Peter G Arthur | 2008 | Biochimica et Biophysica Acta2008，1784，1： | 1 |
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