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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 | 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 |
| 5 | 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 |
| 6 | 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 |
| 7 | Particle nu- cleation in the tropical boundary layer and its cou- pling to marine sulfur sources 显示文摘 | Clarke A Davis D Kapustin V e a/ | 1998 | Science1998，282，5386： | 1 |
| 8 | Abdominal aortic aneurysms are associated with altered matrix proteins of the nonaneurysmal aortic segments显示文摘 | BAXTER B T DAVIS V A Minion D J | 1994 | J Vasc Surg1994，19，： | 1 |
| 9 | Transverse response of underground cavities and pipes to incident SV waves显示文摘 | Davis C A Lee V W Bardet J P | 2001 | Earthquake Engineering and Structural Dynamics2001，30，： | 1 |
| 10 | Arabidopsis and nicotiana antho- cyanin production activated by maize regulators R and Cl 显示文摘 | Lloyd A M Walbot V Davis R W | 1992 | Sci- ence1992，258，： | 1 |
| 11 | Origin and maintenance of the in- testinal cancer stem cell显示文摘 | Davies E J Marsh V Clarke A R | 2011 | Mol Carcinog2011，50，4： | 1 |
| 12 | The role of seed banks in the vegetation dynamics of prairie glacial marshes显示文摘 | VANDER V A G DAVIS C B | 1978 | Ecology1978，59，： | 1 |
| 13 | In sire formation of lead phosphates in soils as a method to immobilize lead显示文摘 | Ruby M V Davis A Nicholson A | 1994 | Environ Sci Technol1994，28，： | 1 |
| 14 | Normal human CD4^+ memory T cells display broad heterogeneity in their activation threshold for cytokine synthesis 显示文摘 | Waldrop S L Davis K A Maino V C | 1998 | J Immunol1998，161，10： | 1 |
| 15 | Mycobacterium tuberculosis inhibition of phagolysosome biogenesis and autophagy as a host defence mechanism显示文摘 | Deretic V Singh S Master S Harris J Roberts E Kyei G Davis A Haro S Naylor J Lee HH Vergne I | | Cell Microbiol0，8，5： | 1 |
| 16 | Using the Fi- nite Element Method to Determine Temperature Distributions in Orthogonal Machining显示文摘 | Tay A O Stevenson M G Davis G V | 1974 | Proceed- ings of the Institution of Mechanical Engineers 1847-19961974，188，： | 1 |
| 17 | A comparison of gas exchange indices used to detect the anaerobic threshold显示文摘 | Caiozzo V J Davis J A Ellis J F | 1982 | J Appl Physiol Respirat Environ Exercise Physiol1982，53，： | 1 |
| 18 | Novel sample preparation method for safe and rapid detection of Bacillus anthracis spores in environmental powders and nasal swabs显示文摘 | Luna V A King D Davis C | 2003 | Clin Microbiol2003，，41： | 1 |
| 19 | In-duction of cachexia in mice by systemically adminis-tered myostatin显示文摘 | Zimmers T A Davies M V Koniaris L G | 2002 | Science2002，296，5572： | 1 |
| 20 | A classification of nucleotide-diphospho-sugar glycosyltransferases based on amino acid sequence similarities 显示文摘 | Campbelt J A Davies G J Bulone V | 1997 | Biochem J1997，326，： | 1 |
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