Stevens C

References (6)

Title : A fluorescent alternative to the synthetic strigolactone GR24 - Rasmussen_2013_Mol.Plant_6_100
Author(s) : Rasmussen A , Heugebaert T , Matthys C , Van Deun R , Boyer FD , Goormachtig S , Stevens C , Geelen D
Ref : Mol Plant , 6 :100 , 2013
Abstract : Strigolactones have recently been implicated in both above- and below-ground developmental pathways in higher plants. To facilitate the molecular and chemical properties of strigolactones in vitro and in vivo, we have developed a fluorescent strigolactone molecule, CISA-1, synthesized via a novel method which was robust, high-yielding, and used simple starting materials. We demonstrate that CISA-1 has a broad range of known strigolactone activities and further report on an adventitious rooting assay in Arabidopsis which is a highly sensitive and rapid method for testing biological activity of strigolactone analogs. In this rooting assay and the widely used Orobanche germination assay, CISA-1 showed stronger biological activity than the commonly tested GR24. CISA-1 and GR24 were equally effective at inhibiting branching in Arabidopsis inflorescence stems. In both the branching and adventitious rooting assay, we also demonstrated that CISA-1 activity is dependent on the max strigolactone signaling pathway. In water methanol solutions, CISA-1 was about threefold more stable than GR24, which may contribute to the increased activity observed in the various biological tests.
ESTHER : Rasmussen_2013_Mol.Plant_6_100
PubMedSearch : Rasmussen_2013_Mol.Plant_6_100
PubMedID: 23024210

Title : The zebrafish reference genome sequence and its relationship to the human genome - Howe_2013_Nature_496_498
Author(s) : Howe K , Clark MD , Torroja CF , Torrance J , Berthelot C , Muffato M , Collins JE , Humphray S , McLaren K , Matthews L , Mclaren S , Sealy I , Caccamo M , Churcher C , Scott C , Barrett JC , Koch R , Rauch GJ , White S , Chow W , Kilian B , Quintais LT , Guerra-Assuncao JA , Zhou Y , Gu Y , Yen J , Vogel JH , Eyre T , Redmond S , Banerjee R , Chi J , Fu B , Langley E , Maguire SF , Laird GK , Lloyd D , Kenyon E , Donaldson S , Sehra H , Almeida-King J , Loveland J , Trevanion S , Jones M , Quail M , Willey D , Hunt A , Burton J , Sims S , McLay K , Plumb B , Davis J , Clee C , Oliver K , Clark R , Riddle C , Elliot D , Threadgold G , Harden G , Ware D , Begum S , Mortimore B , Kerry G , Heath P , Phillimore B , Tracey A , Corby N , Dunn M , Johnson C , Wood J , Clark S , Pelan S , Griffiths G , Smith M , Glithero R , Howden P , Barker N , Lloyd C , Stevens C , Harley J , Holt K , Panagiotidis G , Lovell J , Beasley H , Henderson C , Gordon D , Auger K , Wright D , Collins J , Raisen C , Dyer L , Leung K , Robertson L , Ambridge K , Leongamornlert D , McGuire S , Gilderthorp R , Griffiths C , Manthravadi D , Nichol S , Barker G , Whitehead S , Kay M , Brown J , Murnane C , Gray E , Humphries M , Sycamore N , Barker D , Saunders D , Wallis J , Babbage A , Hammond S , Mashreghi-Mohammadi M , Barr L , Martin S , Wray P , Ellington A , Matthews N , Ellwood M , Woodmansey R , Clark G , Cooper J , Tromans A , Grafham D , Skuce C , Pandian R , Andrews R , Harrison E , Kimberley A , Garnett J , Fosker N , Hall R , Garner P , Kelly D , Bird C , Palmer S , Gehring I , Berger A , Dooley CM , Ersan-Urun Z , Eser C , Geiger H , Geisler M , Karotki L , Kirn A , Konantz J , Konantz M , Oberlander M , Rudolph-Geiger S , Teucke M , Lanz C , Raddatz G , Osoegawa K , Zhu B , Rapp A , Widaa S , Langford C , Yang F , Schuster SC , Carter NP , Harrow J , Ning Z , Herrero J , Searle SM , Enright A , Geisler R , Plasterk RH , Lee C , Westerfield M , de Jong PJ , Zon LI , Postlethwait JH , Nusslein-Volhard C , Hubbard TJ , Roest Crollius H , Rogers J , Stemple DL
Ref : Nature , 496 :498 , 2013
Abstract : Zebrafish have become a popular organism for the study of vertebrate gene function. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes, the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination.
ESTHER : Howe_2013_Nature_496_498
PubMedSearch : Howe_2013_Nature_496_498
PubMedID: 23594743
Gene_locus related to this paper: danre-1neur , danre-ABHD10b , danre-a9jrf7 , danre-d2x2g3 , danre-e7ezq9 , danre-e7ff77 , danre-ndr3 , danre-nlgn4a , danre-q1mti5 , danre-q6nyz4 , danre-q6p2u2 , danre-q7t359 , danre-q08c93 , danre-A2BGU9 , danre-f1q676 , danre-e7f0z8 , danre-e7ez27 , danre-e7f2w1 , danre-f1qid7 , danre-a0a0g2kru2 , danre-f1qla7 , danre-a9jr90 , danre-e7f070 , danre-f172a , danre-e7fb35 , danre-a7mbu9 , danre-f1qtr2

Title : Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects - Herman_2006_J.Clin.Pharmacol_46_876
Author(s) : Herman GA , Bergman A , Liu F , Stevens C , Wang AQ , Zeng W , Chen L , Snyder K , Hilliard D , Tanen M , Tanaka W , Meehan AG , Lasseter K , Dilzer S , Blum R , Wagner JA
Ref : Journal of Clinical Pharmacology , 46 :876 , 2006
Abstract : Sitagliptin (MK-0431) is an oral, potent, and selective dipeptidyl peptidase-IV (DPP-4) inhibitor developed for the treatment of type 2 diabetes. This multicenter, randomized, double-blind, placebo-controlled study examined the pharmacokinetic and pharmacodynamic effects of sitagliptin in obese subjects. Middle-aged (45-63 years), nondiabetic, obese (body mass index: 30-40 kg/m2) men and women were randomized to sitagliptin 200 mg bid (n = 24) or placebo (n = 8) for 28 days. Steady-state plasma concentrations of sitagliptin were achieved within 2 days of starting treatment, and >90% of the dose was excreted unchanged in urine. Sitagliptin treatment led to approximately 90% inhibition of plasma DPP-4 activity, increased active glucagon-like peptide-1 (GLP-1) levels by 2.7-fold (P < .001), and decreased post-oral glucose tolerance test glucose excursion by 35% (P < .050) compared to placebo. In nondiabetic obese subjects, treatment with sitagliptin 200 mg bid was generally well tolerated without associated hypoglycemia and led to maximal inhibition of plasma DPP-4 activity, increased active GLP-1, and reduced glycemic excursion.
ESTHER : Herman_2006_J.Clin.Pharmacol_46_876
PubMedSearch : Herman_2006_J.Clin.Pharmacol_46_876
PubMedID: 16855072

Title : Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes - Herman_2006_J.Clin.Endocrinol.Metab_91_4612
Author(s) : Herman GA , Bergman A , Stevens C , Kotey P , Yi B , Zhao P , Dietrich B , Golor G , Schrodter A , Keymeulen B , Lasseter KC , Kipnes MS , Snyder K , Hilliard D , Tanen M , Cilissen C , De Smet M , De Lepeleire I , Van Dyck K , Wang AQ , Zeng W , Davies MJ , Tanaka W , Holst JJ , Deacon CF , Gottesdiener KM , Wagner JA
Ref : J Clinical Endocrinology Metab , 91 :4612 , 2006
Abstract : CONTEXT: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control. Normally these incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors are a novel class of oral antihyperglycemic agents in development for the treatment of type 2 diabetes. The degree of DPP-4 inhibition and the level of active incretin augmentation required for glucose lowering efficacy after an oral glucose tolerance test (OGTT) were evaluated. OBJECTIVE: The objective of the study was to examine the pharmacodynamics, pharmacokinetics, and tolerability of sitagliptin. DESIGN: This was a randomized, double-blind, placebo-controlled, three-period, single-dose crossover study. SETTING: The study was conducted at six investigational sites. PATIENTS: The study population consisted of 58 patients with type 2 diabetes who were not on antihyperglycemic agents. INTERVENTIONS: Interventions included sitagliptin 25 mg, sitagliptin 200 mg, or placebo. MAIN OUTCOME MEASURES: Measurements included plasma DPP-4 activity; post-OGTT glucose excursion; active and total incretin GIP levels; insulin, C-peptide, and glucagon concentrations; and sitagliptin pharmacokinetics.
RESULTS: Sitagliptin dose-dependently inhibited plasma DPP-4 activity over 24 h, enhanced active GLP-1 and GIP levels, increased insulin/C-peptide, decreased glucagon, and reduced glycemic excursion after OGTTs administered at 2 and 24 h after single oral 25- or 200-mg doses of sitagliptin. Sitagliptin was generally well tolerated, with no hypoglycemic events.
CONCLUSIONS: In this study in patients with type 2 diabetes, near maximal glucose-lowering efficacy of sitagliptin after single oral doses was associated with inhibition of plasma DPP-4 activity of 80% or greater, corresponding to a plasma sitagliptin concentration of 100 nm or greater, and an augmentation of active GLP-1 and GIP levels of 2-fold or higher after an OGTT.
ESTHER : Herman_2006_J.Clin.Endocrinol.Metab_91_4612
PubMedSearch : Herman_2006_J.Clin.Endocrinol.Metab_91_4612
PubMedID: 16912128

Title : Pharmacokinetic and pharmacodynamic properties of multiple oral doses of sitagliptin, a dipeptidyl peptidase-IV inhibitor: a double-blind, randomized, placebo-controlled study in healthy male volunteers - Bergman_2006_Clin.Ther_28_55
Author(s) : Bergman AJ , Stevens C , Zhou Y , Yi B , Laethem M , De Smet M , Snyder K , Hilliard D , Tanaka W , Zeng W , Tanen M , Wang AQ , Chen L , Winchell G , Davies MJ , Ramael S , Wagner JA , Herman GA
Ref : Clin Ther , 28 :55 , 2006
Abstract : BACKGROUND: Dipeptidyl peptidase-IV (DPP-IV) inhibitors represent a new class of oral antihyperglycemic agents. Sitagliptin is an orally active and selective DPP-IV inhibitor currently in Phase III development for the treatment of type 2 diabetes mellitus. OBJECTIVE: The aim of this study was to assess the pharmacokinetic and pharmacodynamic (PK/PD) properties and tolerability of multiple oral once-daily or twice-daily doses of sitagliptin.
METHODS: This double-blind, randomized, placebo-controlled,incremental oral-dose study was conducted at SGS Biopharma, Antwerp, Belgium. Healthy, nonsmoking male volunteers aged 18 to 45 years with a creatinine clearance rate of >80 mL/min and normoglycemia and weighing within 15% of their ideal height/weight range were randomly assigned to 1 of 8 treatment groups: sitagliptin 25, 50, 100, 200, or 400 mg or placebo, QD for 10 days; a single dose of sitagliptin 800 mg administered on day 1 followed by 600 mg QD on days 3 to 10; or sitagliptin 300 mg BID for 10 days. For analysis of PK properties, plasma and urine samples were obtained before study drug administration on day 1 and at 0.5, 1, 2, 4, 6, 8, 10, 12, and 16 hours after study drug administration on day 1; before study drug administration on days 2 to 9; and every 24 hours for 96 hours after the last dose on day 10, and analyzed for sitagliptin concentrations. Assays were used to measure inhibition of plasma DPP-IV activity and plasma concentrations of active and total glucagon-like peptide-1 (GLP-1), glucose, and glucagon, and serum concentrations of insulin, C-peptide, insulin-like growth factor-1, and insulin like growth factor binding protein-3. Tolerability was assessed throughout the study using physical examination, including vital sign measurements; 12-lead electrocardiography; and laboratory analysis, including hematology, biochemistry (hepatic aminotransferase and creatine phosphokinase), and urinalysis.
RESULTS: Seventy subjects were enrolled (mean age, 32.9 years [range, 18-45 years]; mean weight, 79.7 kg [range, 63.4-97.7 kg]; 8 patients per sitagliptin study group and 14 patients in the control group). In the sitagliptin groups, the plasma concentration-time profiles and principal PK parameters (T(max), C(max), and t((1/2))) were statistically similar at days 1 (single dose) and 10 (steady state). In the groups receiving sitagliptin QD doses, accumulation of sitagliptin was modest (AUC accumulation ratio [day 10/day 1] range, 1.05-1.29), and the apparent terminal elimination t((1/2)) was 11.8 to 14.4 hours. At steady state in the sitagliptin QD groups, the mean proportion of drug excreted unchanged in the urine was approximately 70.6%. Dose-dependent inhibition of plasma DPP-IV activity was apparent, and the pattern of inhibition at steady state (day 10) was statistically similar to that observed on day 1. Day-10 weighted mean inhibition of plasma DPP-IV activity over 24 hours was > or = 80% for doses of > or = 50 mg QD. After a standard meal, active GLP-1 concentrations were significantly increased in the sitagliptin groups by approximately 2-fold compared with that in the control group, a finding consistent with near-maximal acute glucose lowering in preclinical studies. Across doses, no apparent adverse effects, including hypoglycemia, were found or reported.
CONCLUSIONS: The results from this study in a select population of healthy male volunteers suggest that multiple oral doses of sitagliptin inhibited plasma DPP-IV activity and affected active GLP-1 concentrations in a dose-dependent manner, without producing hypoglycemia. Multiple dosing of sitagliptin exhibited a PK/PD profile consistent with that of a QD regimen and was well tolerated.
ESTHER : Bergman_2006_Clin.Ther_28_55
PubMedSearch : Bergman_2006_Clin.Ther_28_55
PubMedID: 16490580

Title : Barley-fungal interactions: signals and the environment of the host-pathogen interface -
Author(s) : Gurr S , Titarenko E , Ogel Z , Stevens C , Carver T , Dewey M , Hargreaves J
Ref : Biochemical Society Symposium , 60 :75 , 1994
PubMedID: 7639794