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| 1 | Bone morphogenetic protein-2 gene controls tooth root development in coordination with formation of the periodontium显示文摘Formation of the periodontium begins following onset of tooth-root formation in a coordinated manner after birth. Dental follicle progenitor cells are thought to form the cementum, alveolar bone and Sharpey's fibers of the periodontal ligament (PDL). However, little is known about the regulatory morphogens that control differentiation and function of these progenitor cells, as well as the progenitor cells involved in crown and root formation. We investigated the role of bone morphogenetic protein-2 (Bmp2) in these processes by the conditional removal of the Bmp2 gene using the Sp7-Cre-EGFP mouse model. Sp7-Cre-EGFP first becomes active at E18 in the first molar, with robust Cre activity at postnatal day 0 (P0), followed by Cre activity in the second molar, which occurs after P0. There is robust Cre activity in the periodontium and third molars by 2 weeks of age. When the Bmp2 gene is removed from Sp7+ (Osterix+) cells, major defects are noted in root, cellular cementum and periodontium formation. First, there are major cell autonomous defects in root-odontoblast terminal differentiation. Second, there are major alterations in formation of the PDLs and cellular cementum, correlated with decreased nuclear factor IC (Nfic), periostin and α-SMA+ cells. Third, there is a failure to produce vascular endothelial growth factor A (VEGF-A) in the periodontium and the pulp leading to decreased formation of the microvascular and associated candidate stem cells in the Bmp2-cKOSp7-Cre-EGFP . Fourth, ameloblast function and enamel formation are indirectly altered in the Bmp2-cKOSp7-Cre-EGFP . These data demonstrate that the Bmp2 gene has complex roles in postnatal tooth development and periodontium formation. | Audrey Rakian Wu-Chen Yang Jelica Gluhak-Heinrich Yong Cui Marie A Harris Demitri Villarreal Jerry Q Feng Mary MacDougall Stephen E Harris | 2013 | International Journal of Oral Science2013，5，2： | 14 |
| 2 | Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis显示文摘AIM: To evaluate the effect of orally administeredplecanatide or dolcanatide, analogs of uroguanylin, on amelioration of colitis in murine models.METHODS: The cyclic guanosine monophosphate(cG MP) stimulatory potency of plecanatide and dolcanatide was measured using a human colon carcinoma T84 cellbased assay. For animal studies all test agents were formulated in phosphate buffered saline. Sulfasalazine or 5-amino salicylic acid(5-ASA) served as positive controls. Effect of oral treatment with test agents on amelioration of acute colitis induced either by dextran sulfate sodium(DSS) in drinking water or by rectal instillation of trinitrobenzene sulfonic(TNBS) acid, was examined in BALB/c and/or BDF1 mice. Additionally, the effect of orally administered plecanatide on the spontaneous colitis in T-cell receptor alpha knockout(TCRα-/-) mice was also examined. Amelioration of colitis was assessed by monitoring severity of colitis, disease activity index and by histopathology. Frozen colon tissues were used to measure myeloperoxidase activity.RESULTS: Plecanatide and dolcanatide are structurally related analogs of uroguanylin, which is an endogenous ligand of guanylate cyclase-C(GC-C). As expected from the agonists of GC-C, both plecanatide and dolcanatide exhibited potent cG MP-stimulatory activity in T84 cells. Once-daily treatment by oral gavage with either of these analogs(0.05-0.5 mg/kg) ameliorated colitis in both DSS and TNBS-induced models of acute colitis, as assessed by body weight, reduction in colitis severity(P < 0.05) and disease activity index(P < 0.05). Amelioration of colitis by either of the drug candidates was comparable to that achieved by orally administered sulfasalazine or 5-ASA. Plecanatide also effectively ameliorated colitis in TCRα-/- mice, a model of spontaneous colitis. As dolcanatide exhibited higher resistance to proteolysis in simulated gastric and intestinal juices, it was selected for further studies. CONCLUSION: This is the first-ever study reporting the therapeutic utility of GC-C agonists as a new class of orally delivered and mucosally active drug candidates for the treatment of inflammatory bowel diseases. | Kunwar Shailubhai Vaseem Palejwala Krishna Priya Arjunan Sayali Saykhedkar Bradley Nefsky John A Foss Stephen Comiskey Gary S Jacob Scott E Plevy | 2015 | World Journal of Gastrointestinal Pharmacology and Therapeutics2015，6，4： | 5 |
| 3 | Hospitalized prevalence and 5-year mortality for IBD:Record linkage study显示文摘AIM:To establish the hospitalized prevalence of severe Crohn's disease(CD) and ulcerative colitis(UC) in Wales from 1999 to 2007;and to investigate long-term mortality after hospitalization and associations with social deprivation and other socio-demographic factors.METHODS:Record linkage of administrative inpatient and mortality data for 1467 and 1482 people hospitalised as emergencies for ≥ 3d for CD and UC,respectively.The main outcome measures were hospitalized prevalence,mortality rates and standardized mortality ratios for up to 5 years follow-up after hospitalization.RESULTS:Hospitalized prevalence was 50.1 per 100 000 population for CD and 50.6 for UC.The hospitalized prevalence of CD was significantly higher(P < 0.05) in females(57.4) than in males(42.2),and was highest in people aged 16-29 years,but the prevalence of UC was similar in males(51.0) and females(50.1),and increased continuously with age.The hospital-ized prevalence of CD was slightly higher in the most deprived areas,but there was no association between social deprivation and hospitalized prevalence of UC.Mortality was 6.8% and 14.6% after 1 and 5 years follow-up for CD,and 9.2% and 20.8% after 1 and 5 years for UC.For both CD and UC,there was little discernible association between mortality and social deprivation,distance from hospital,urban/rural residence and geography.CONCLUSION:CD and UC have distinct demographic profiles.The higher prevalence of hospitalized CD in more deprived areas may reflect higher prevalence and higher hospital dependency. | Lori A Button Stephen E Roberts Michael J Goldacre Ashley Akbari Sarah E Rodgers John G Williams | 2010 | World Journal of Gastroenterology2010，16，4： | 3 |
| 4 | Evidence That the Diabetes Gene Encodes the Leptin Receptor: Identification of a Mutation in the Leptin Receptor Gene in db / db Mice显示文摘 | Hong Chen Olga Charlat Louis A Tartaglia Elizabeth A Woolf Xun Weng Stephen J Ellis Nathan D Lakey Janice Culpepper Karen J More Roger E Breitbart Geoffrey M Duyk Robert I Tepper Jay P Morgenstern | 1996 | Cell1996，，3： | 2 |
| 5 | Cholesterol and Bile Acid Metabolism Are Impaired in Mice Lacking the Nuclear Oxysterol Receptor LXRα显示文摘 | Daniel J Peet Stephen D Turley Wenzhen Ma Bethany A Janowski Jean-Marc A Lobaccaro Robert E Hammer David J Mangelsdorf | 1998 | Cell1998，，： | 2 |
| 6 | Direct dating of sulfides by Rb-Sr:Acritical test using the Polaris Mississippi Valley-type Zn-Pb deposit显示文摘 | Christensen J N Halliday A N Kenneth E L Roderick N R and Stephen E K | | 0，，： | 1 |
| 7 | Measurement and prediction of voltage flicker magnitude and frequency显示文摘 | Girgis A A Stephens J W Makram E B | 1995 | IEEE Trans on Power Delivery1995，10，3： | 1 |
| 8 | Resistance spot welding of aluminum alloy to steel with transition material显示文摘 | Sun X Stephens E V Khaleel M A | 2004 | Welding Journal2004，83，6： | 1 |
| 9 | Testing modds of large-scale crustal fluid flow using direct dating of sulfides:Rb-Sr evidence for early dewatering and formation of Mississippi Valley-type deposits,Canning Basin,Australia显示文摘 | Christensen J N Halliday A N Veamcombe J R Stephen E K | | 0，，： | 1 |
| 10 | An intertemporal general equilibrium model of asset prices and theory of the term struc- ture of interest rates显示文摘 | JOHN C JONATHAN E STEPHEN A | 1985 | Econometrica1985，53，2： | 1 |
| 11 | Primary leiomyosarcoma of extragnathic bone clinicopathologic features and reevaluation of prognosis显示文摘 | Muyibat A Adelani Stephen J Schultenover Ginger E Holt | | 0，，09： | 1 |
| 12 | Food andwater economy and its relation to growth in fifth instarlarvae of tobacco homworm, Manduca sexta显示文摘 | Reynolds S E Nottingham S F Stephens A E | 1985 | Journalof Insect Physiology1985，31，： | 1 |
| 13 | Effects of fusion zone size and failure mode on peak load and energy absorption of advanced high strength steel spot welds under lap shear loading conditions显示文摘 | Sun X Stephens E V Khaleel M A | 2008 | Engineering Failure Analysis2008，15，4： | 1 |
| 14 | Effects of repeated prenatal ultrasound examinations on childhood outcome up to 8 years of age: follow-up of a randomised controlled trial显示文摘 | John P Newnham Dorota A Doherty Garth E Kendall Stephen R Zubrick | 2004 | Lancet2004，364，9450： | 1 |
| 15 | Alloysof platinum and early transition metals as oxygen reduc- tion electrocatalysts显示文摘 | Greeley J Stephens I E L Bondarenko A S | 2009 | Nature Chemistry2009，1，7： | 1 |
| 16 | The patterns and dynamics of genomic instability in metastatic pancreatic cancer显示文摘 | Campbell P J Yachida S Mudie L J Stephens P J Pleasance E D Stebbings L A | 2010 | Nature2010，467，： | 1 |
| 17 | Genome-wide comparative diversity uncovers multiple targets of selection for improvement in hexaploid wheat landraces and cultivars 显示文摘 | Cavanagh CS Chao S Wang BE Huang BE Stephen S Kiani S Forrest K Saintenac C Brown-Guedira GL Akhunova A See D Bai G Pumphrey M Tomar L Wong D Kong S Reynolds M da Silva ML Bockelman H Talbert L Anderson JA Dreisigacker S Baenziger S Carter A Korzun V Morrell PL Dubcovsky J Morell MK Sorrells ME Hayden MJ Akhunov E | 2013 | PNAS2013，110，： | 1 |
| 18 | A com- parison of surface water natural organic matter in raw filtered wa- ter samples, XAD, and reverse osmosis isolates 显示文摘 | PATRICIA A M M1VHAEL J P STEPHEN E C | 2002 | Water Re- search2002，36，： | 1 |
| 19 | An Intertemporal General Equilibrium Model of Asset Prices显示文摘 | Cox John C Jonathan E Ingersoll Stephen A Ross | 1985 | Econometrica1985，53，： | 1 |
| 20 | Global lithium resources : relative importanceof pegmatite,brine and other deposits 显示文摘 | Stephen E Kealer Paul W Gruber Pablo A Medina Gregory A Keoleian Mark P Everson Timothy J Wall-ington | 2012 | Ore GeologyReviews2012，48，： | 1 |
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