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71.
72.
Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F 总被引:2,自引:0,他引:2
Kuestner RE Taft DW Haran A Brandt CS Brender T Lum K Harder B Okada S Ostrander CD Kreindler JL Aujla SJ Reardon B Moore M Shea P Schreckhise R Bukowski TR Presnell S Guerra-Lewis P Parrish-Novak J Ellsworth JL Jaspers S Lewis KE Appleby M Kolls JK Rixon M West JW Gao Z Levin SD 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(8):5462-5473
The proinflammatory cytokines IL-17A and IL-17F have a high degree of sequence similarity and share many biological properties. Both have been implicated as factors contributing to the progression of inflammatory and autoimmune diseases. Moreover, reagents that neutralize IL-17A significantly ameliorate disease severity in several mouse models of human disease. IL-17A mediates its effects through interaction with its cognate receptor, the IL-17 receptor (IL-17RA). We report here that the IL-17RA-related molecule, IL-17RC is the receptor for IL-17F. Notably, both IL-17A and IL-17F bind to IL-17RC with high affinity, leading us to suggest that a soluble form of this molecule may serve as an effective therapeutic antagonist of IL-17A and IL-17F. We generated a soluble form of IL-17RC and demonstrate that it effectively blocks binding of both IL-17A and IL-17F, and that it inhibits signaling in response to these cytokines. Collectively, our work indicates that IL-17RC functions as a receptor for both IL-17A and IL-17F and that a soluble version of this protein should be an effective antagonist of IL-17A and IL-17F mediated inflammatory diseases. 相似文献
73.
The conformational states sampled by the Alzheimer amyloid beta (10-35) (Abeta 10-35) peptide were probed using replica-exchange molecular dynamics (REMD) simulations in explicit solvent. The Abeta 10-35 peptide is a fragment of the full-length Abeta 40/42 peptide that possesses many of the amyloidogenic properties of its full-length counterpart. Under physiological temperature and pressure, our simulations reveal that the Abeta 10-35 peptide does not possess a single unique folded state. Rather, this peptide exists as a mixture of collapsed globular states that remain in rapid dynamic equilibrium with each other. This conformational ensemble is dominated by random coil and bend structures with insignificant presence of an alpha-helical or beta-sheet structure. The 3D structure of Abeta 10-35 is seen to be defined by a salt bridge formed between the side-chains of K28 and D23. This salt bridge is also observed in Abeta fibrils and our simulations suggest that monomeric conformations of Abeta 10-35 contain pre-folded structural motifs that promote rapid aggregation of this peptide. 相似文献
74.
75.
Angell RM Atkinson FL Brown MJ Chuang TT Christopher JA Cichy-Knight M Dunn AK Hightower KE Malkakorpi S Musgrave JR Neu M Rowland P Shea RL Smith JL Somers DO Thomas SA Thompson G Wang R 《Bioorganic & medicinal chemistry letters》2007,17(5):1296-1301
The identification and exploration of a novel, potent and selective series of N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amide inhibitors of JNK2 and JNK3 kinases is described. Compounds 5a and 11a were identified as potent inhibitors of JNK3 (pIC50 6.7 and 6.6, respectively), with essentially equal potency against JNK2 (pIC50 6.5). Selectivity within the mitogen-activated protein kinase (MAPK) family, against JNK1, p38alpha and ERK2, was observed for the series. X-ray crystallography of 5e and 8a in JNK3 revealed a unique binding mode, with the 3-cyano substituent forming an H-bond acceptor interaction with the hinge region of the ATP-binding site. 相似文献
76.
77.
The dynamics of axonal transport are often colloquially described using highway traffic as a model system. Examination of the physics of traffic patterns, with emphasis on traffic jams and accidents, provides unique and perhaps counterintuitive insight into the aberrant accumulation of neurofilaments that accompanies amyotrophic lateral sclerosis/motor neuron disease. 相似文献
78.
R Gon?alves LA Szmuchrowski LS Prado BP Couto JCQ Machado VO Damasceno JA Lamounier 《Biology of sport / Institute of Sport》2015,32(3):255-260
The aim of this study was to assess the suitability of body mass index, waist circumference, waist-to-height ratio and aerobic fitness as predictors of cardiovascular risk factor clustering in children. A cross-sectional study was conducted with 290 school boys and girls from 6 to 10 years old, randomly selected. Blood was collected after a 12-hour fasting period. Blood pressure, waist circumference (WC), height and weight were evaluated according to international standards. Aerobic fitness (AF) was assessed by the 20-metre shuttle-run test. Clustering was considered when three of these factors were present: high systolic or diastolic blood pressure, high low-density lipoprotein (LDL) cholesterol, high triglycerides, high plasma glucose, high insulin concentrations and low high-density lipoprotein (HDL) cholesterol. A ROC curve identified the cut-off points of body mass index (BMI), WC, waist-to-height ratio (WHtR) and AF as predictors of risk factor clustering. BMI, WC and WHR resulted in significant areas under the ROC curves, which was not observed for AF. The anthropometric variables were good predictors of cardiovascular risk factor clustering in both sexes, whereas aerobic fitness should not be used to identify cardiovascular risk factor clustering in these children. 相似文献
79.
Tassilo?Gleede Barbara?Riehl Colleen?Shea Lena?Kersting Aylin?Sibel?Cankaya David?Alexoff Michael?Schueller Joanna?S.?Fowler Wenchao?QuEmail author 《Amino acids》2015,47(3):525-533
Carbon-11 (β+ emitter, t 1/2 = 20.4 min) radiolabeled l-glutamine is a potentially useful molecular imaging agent that can be utilized with positron emission tomography for both human oncological diagnosis and plant imaging research. Based upon a previously reported [11C]cyanide end-capping labeling method, a systematic investigation of nucleophilic cyanation reactions and acidic hydrolysis reaction parameters, including base, metal ion source, phase transfer catalyst, solvent, reaction temperature and reaction time, was conducted. The result was a milder, more reliable, two-step method which provides l-[5-11C]-glutamine with a radiochemical yield of 63.8 ± 8.7 % (range from 51 to 74 %, n = 10) with >90 % radiochemical purity and >90 % enantiomeric purity. The total synthesis time was 40–50 min from the end of bombardment. In addition, an Fmoc derivatization method was developed to measure the specific activity of this radiotracer. 相似文献
80.
David Gendron Anne-Marie Lemay Claudine Tremblay Laetitia JA Lai Anick Langlois émilie Bernatchez Nicolas Flamand Marie-Renée Blanchet Anthony S Don Ynuk Bossé élyse Bissonnette David Marsolais 《Respiratory research》2015,16(1)