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| 1 | Differential regulation of protein synthesis in skeletal muscle and liver of neonatal pigs by leucine through an mTORC1-dependent pathway显示文摘Neonatal growth is characterized by a high protein synthesis rate that is largely due to an enhanced sensitivity to the postprandial rise in insulin and amino acids, especially leucine. The mechanism of leucine's action in vivo is not well understood. In this study, we investigated the effect of leucine infusion on protein synthesis in skeletal muscle and liver of neonatal pigs. To evaluate the mode of action of leucine, we used rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) complex-1 (mTORC1). Overnight-fasted 7-day-old piglets were treated with rapamycin for 1 hour and then infused with leucine (400 μmol·kg -1 ·h -1 ) for 1 hour. Leucine infusion increased the rate of protein synthesis, and ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein-1 (4E-BP1) phosphorylation in gastrocnemius and masseter muscles (P < 0.05), but not in the liver. The leucine-induced stimulation of protein synthesis and S6K1 and 4E-BP1 phosphorylation were completely blocked by rapamycin, suggesting that leucine action is by an mTORC1-dependent mechanism. Neither leucine nor rapamycin had any effect on the activation of the upstream mTORC1 regulators, AMP-activated protein kinase and protein kinase B, in skeletal muscle or liver. The activation of eIF2a and elongation factor 2 was not affected by leucine or rapamycin, indicating that these two pathways are not limiting steps of leucine-induced protein synthesis. These results suggest that leucine stimulates muscle protein synthesis in neonatal pigs by inducing the activation of mTORC1 and its downstream pathway leading to mRNA translation. | Agus Suryawan Hanh V Nguyen Rosemarie D Almonaci Teresa A Davis | 2012 | Journal of Animal Science and Biotechnology2012，3，1： | 9 |
| 2 | Osteoprotegerin Ligand Is a Cytokine that Regulates Osteoclast Differentiation and Activation显示文摘 | D.L Lacey E Timms H.-L Tan M.J Kelley C.R Dunstan T Burgess R Elliott A Colombero G Elliott S Scully H Hsu J Sullivan N Hawkins E Davy C Capparelli A Eli Y.-X Qian S Kaufman I Sarosi V Shalhoub G Senaldi J Guo J Delaney W.J Boyle | 1998 | Cell1998，，2： | 4 |
| 3 | Thiopurine-methyltransferase variants in inflammatory bowel disease:Prevalence and toxicity in Brazilian patients显示文摘AIM:To analyze the prevalence of thiopurine-methyltransferase(TPMT)genotypes and their associationwith drug toxicity in inflammatory bowel disease(IBD)patients from southeastern Brazil.METHODS:A total of 219 consecutive patients with IBD,of which 146 had Crohn’s disease and 73 had ulcerative colitis,regularly seen at the outpatient unit of the Division of Gastroenterology at the University Hospital Pedro Ernesto of the State University of Rio de Janeiro,a tertiary referral center,were enrolled in this study from February 2009 to January 2011.We analyzed the presence of major TPMT genetic variants(TPMT*2,*3A,*3C)in IBD patients by means of a specific allele and RFLP-PCR.Genomic DNA was isolated from peripheral blood leukocytes by proteinase-K/Sodium Dodecyl Sulfate digestion and phenol-chloroform extraction.TPMT*2(C238G),TPMT*3A(G460A/A719G),and TPMT*3C(A719G)genotypes were detected by real-time polymerase chain reaction followed by direct sequencing with specific primers.Clinical data were systematically recorded,and correlated with the genotype results.RESULTS:The distribution of the selected TPMT gene polymorphism TPMT*2(C238G),TPMT*3A(G460A/A719G),and TPMT*3C(A719G)genotypes was 3.6%,5.4%,and 7.7%of the patients,respectively.Among the side effects recorded from patients taking azathioprine,14 patients presented with pancreatitis and/or an elevation of pancreatic enzymes,while 6 patients had liver toxicity,and 2 patients exhibited myelosuppression/neutropenia.TPMT polymorphisms were detected in 37/219 patients(8 heterozygous for*2,11 heterozygous for*3A,and 18 heterozygous for*3C).No homozygotic polymorphisms were found.Despite the prevalence of the TPMT*3C genotype,no differences among the genotype frequencies were significant.Although no association was detected regarding myelotoxicity or hepatotoxicity,a trend towards the elevation of pancreatic enzymes was observed for TPMT*2 and TPMT*3C genotypes.CONCLUSION:The prevalence of TPMT genotypes was high among Brazilian patients.Variants genes*2and*3C may be associated with azathioprine pancreatic toxicity in a IBD southeastern Brazilian population. | Ana Teresa P Carvalho Barbara C Esberard Renata S B Fróes Davy C M Rapozo Ana B Grinman Tatiana A Simo Juliana C V C Santos Antonio José V Carneiro Luis Felipe Ribeiro-Pinto Heitor S P de Souza | 2014 | World Journal of Gastroenterology2014，20，12： | 3 |
| 4 | Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial显示文摘 | Kris V Kowdley Eric Lawitz Israel Crespo Tarek Hassanein Mitchell N Davis Michael DeMicco David E Bernstein Nezam Afdhal John M Vierling Stuart C Gordon Jane K Anderson Robert H Hyland Hadas Dvory-Sobol Di An Robert G Hindes Efsevia Albanis William T Symo | 2013 | The Lancet2013，，9883： | 3 |
| 5 | Mathematical modeling of the extrusion of 6061/A12O3/20p composite 显示文摘 | CHEN W C DAVIES C H J SAMARASEKERA I V | 1996 | Matallurgical and Materials Transactions1996，，27： | 2 |
| 6 | User acceptance of information technology: toward a unified view 显示文摘 | VENKATESH V MORRIS M G DAVIS G B | 2003 | MIS Quarterly2003，27，3： | 1 |
| 7 | High level expression of hepatitis B viral antigens in fibrosing cholestatic hepatitis 显示文摘 | Lau J Y N Davis GL Bain V G | 1992 | Gastroenterology1992，102，： | 1 |
| 8 | Calibration of near infrared reflectance spectroscopy to estimate nitrogen concentration in potato tissues显示文摘 | YOUNG M W MACKRRON D K L DAVIES H V | 1997 | PotatoResearch1997，，40： | 1 |
| 9 | A new and highly efficient grubbs initiator for ring-opening metathesis polymerization显示文摘 | Robson D A Gibson V C Davies R G | 1999 | Macromolecules1999，32，19： | 1 |
| 10 | Circulating Transforming Growth Factor- 1 Levels in Asymptomatic Carotid Plaques显示文摘 | Ferroni P Novo S Davi V | 2005 | Stroke2005，36，3： | 1 |
| 11 | Commutation failures in HVDC transmission systems显示文摘 | Thio C V Davies J B Kent K L | 1996 | IEEE Trans on Power Delivery1996，11，2： | 1 |
| 12 | A survey of mobility models for ad hoc network research显示文摘 | CAMP T BOLENG J DAVIES V | 2002 | Wireless Communications & MobileComputing (WCMC):Special Issue on Mobile ad hoc Networking:Research Trends and Applications2002，2，5： | 1 |
| 13 | The development and application of genetic markers for the Kuruma prawn Penaeus japonicus显示文摘 | Moore S S Whan V Davis G P | 1999 | Aquaculture1999，173，14： | 1 |
| 14 | Deciphering the biology of My cobacterium tuberculosis from the complete genome sequence 显示文摘 | Cole S T Brosch R Parkhill J Gamier T Churcher C Harris D Gordon S V Eiglmeier K Gas S Barry C E Tekaia F Badcock K Basham D Brown D Chillingworth T Cormor R Davies R Devlin K FeltweU T Gentles S Hamlin N Holroyd S Hornsby T Jagels K Kroghs A McLean J Moule S Murphy L Oliver K Osborne J Quail M A Rafandream M A Rogers J Rutter S Seeger K Skelton J Squaraes R Squares S Sulston J E Taylo K Whitehead S Barrell B G | 1998 | Nature1998，393，： | 1 |
| 15 | A theoretical extension of the technology acceptance model:four longitudinal field studies显示文摘 | VENKATESH V DAVIS F D | 2000 | Management Science2000，46，2： | 1 |
| 16 | Risk factors for progression of common carotid atherosclerosis the atheroscle- rosis risk in communities study, 1987-1998显示文摘 | Chambless LE Folsom AR Davis V | 2002 | Am J Epide- miol2002，155，1： | 1 |
| 17 | A theoretical extension of the technology acceptance model:tbr kmgitudinal field studies显示文摘 | VENKATESH V DAVIS F D | 2003 | Management Science2003，46，2： | 1 |
| 18 | Commutation Failures in HVDC Transmission Systems显示文摘 | THIO C V DAVIES J B KENT K L | | 0，，02： | 1 |
| 19 | Calcium anidotrihydroborate:a hydrogen storage material显示文摘 | Diyabalanage H V K Shrestha R P Semelsberger TA Scott B L Bowden M E Davis B L Burrell A K | | 0，，47： | 1 |
| 20 | Evidence on the political economy of the urbanization process 显示文摘 | Davis J C Henderson J V | 2003 | Journal of Urban Economics2003，53，1： | 1 |
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