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排序方式: 共有473条查询结果,搜索用时 140 毫秒
221.
Alessandro Mascioni Breagh E. Bentley Rosaria Camarda Deborah A. Dilts Pamela Fink Viktoria Gusarova Susan K. Hoiseth Jaison Jacob Shuo L. Lin Karl Malakian Lisa K. McNeil Terri Mininni Franklin Moy Ellen Murphy Elena Novikova Scott Sigethy Yingxia Wen Gary W. Zlotnick D��sir��e H. H. Tsao 《The Journal of biological chemistry》2009,284(13):8738-8746
222.
Melita Dvorak-Ewell Dan Wendt Chuck Hague Terri Christianson Vish Koppaka Danielle Crippen Emil Kakkis Michel Vellard 《PloS one》2010,5(8)
Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disorder caused by deficiency of N-acetylgalactosamine-6-sulfatase (GALNS), an enzyme that degrades keratan sulfate (KS). Currently no therapy for MPS IVA is available. We produced recombinant human (rh)GALNS as a potential enzyme replacement therapy for MPS IVA. Chinese hamster ovary cells stably overexpressing GALNS and sulfatase modifying factor-1 were used to produce active (∼2 U/mg) and pure (≥97%) rhGALNS. The recombinant enzyme was phosphorylated and was dose-dependently taken up by mannose-6-phosphate receptor (Kuptake = 2.5 nM), thereby restoring enzyme activity in MPS IVA fibroblasts. In the absence of an animal model with a skeletal phenotype, we established chondrocytes isolated from two MPS IVA patients as a disease model in vitro. MPS IVA chondrocyte GALNS activity was not detectable and the cells exhibited KS storage up to 11-fold higher than unaffected chondrocytes. MPS IVA chondrocytes internalized rhGALNS into lysosomes, resulting in normalization of enzyme activity and decrease in KS storage. rhGALNS treatment also modulated gene expression, increasing expression of chondrogenic genes Collagen II, Collagen X, Aggrecan and Sox9 and decreasing abnormal expression of Collagen I. Intravenous administration of rhGALNS resulted in biodistribution throughout all layers of the heart valve and the entire thickness of the growth plate in wild-type mice. We show that enzyme replacement therapy with recombinant human GALNS results in clearance of keratan sulfate accumulation, and that such treatment ameliorates aberrant gene expression in human chondrocytes in vitro. Penetration of the therapeutic enzyme throughout poorly vascularized, but clinically relevant tissues, including growth plate cartilage and heart valve, as well as macrophages and hepatocytes in wild-type mouse, further supports development of rhGALNS as enzyme replacement therapy for MPS IVA. 相似文献
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224.
Weiland AA Peairs FB Randolph TL Rudolph JB Haley SD Puterka GJ 《Journal of economic entomology》2008,101(2):569-574
The biotypic diversity of the Russian wheat aphid, Diuraphis noxia (Kurdjumov) (Hemiptera: Aphididae), was assessed in five isolates collected in Colorado. Three isolates, RWA 1, RWA 2, and an isolate from Montezuma County, CO, designated RWA 6, were originally collected from cultivated wheat, Triticum aestivum L., and obtained from established colonies at Colorado State University. The fourth isolate, designated RWA 7, was collected from Canada wildrye, Elymus canadensis L., in Baca County, CO. The fifth isolate, designated RWA 8, was collected from crested wheatgrass, Agropyron cristatum (L.) Gaertn., in Montezuma County, CO. The four isolates were characterized in a standard seedling assay, by using 24 plant differentials, 22 wheat lines and two barley, Hordeum vulgare L., lines. RWA 1 was the least virulent of the isolates, killing only the four susceptible entries. RWA 8 also killed only the four susceptible entries, but it expressed intermediate virulence on seven wheat lines. RWA 6, killing nine entries, and RWA 7, killing 11 entries, both expressed an intermediate level of virulence overall, but differed in their level of virulence to 'CO03797' (Dn1), 'Yumar' (Dn4), and 'CO960293-2'. RWA 2 was the most virulent isolate, killing 14 entries, including Dn4- and Dny-containing wheat. Four wheat lines, '94M370' (Dn7), 'STARS 02RWA2414-11', CO03797, and 'CI2401', were resistant to the five isolates. The results of this screening confirm the presence of five unique Russian wheat aphid biotypes in Colorado. 相似文献
225.
Wolman disease/cholesteryl ester storage disease: efficacy of plant-produced human lysosomal acid lipase in mice 总被引:1,自引:0,他引:1
Du H Cameron TL Garger SJ Pogue GP Hamm LA White E Hanley KM Grabowski GA 《Journal of lipid research》2008,49(8):1646-1657
Lysosomal acid lipase (LAL) is an essential enzyme that hydrolyzes triglycerides (TGs) and cholesteryl esters (CEs) in lysosomes. Genetic LAL mutations lead to Wolman disease (WD) and cholesteryl ester storage disease (CESD). An LAL-null (lal(-/-)) mouse model resembles human WD/CESD with storage of CEs and TGs in multiple organs. Human LAL (hLAL) was expressed in Nicotiana benthamiana using the GENEWARE expression system (G-hLAL). Purified G-hLAL showed mannose receptor-dependent uptake into macrophage cell lines (J774E). Intraperitoneal injection of G-hLAL produced peak activities in plasma at 60 min and in the liver and spleen at 240 min. The t(1/2) values were: approximately 90 min (plasma), approximately 14 h (liver), and approximately 32 h (spleen), with return to baseline by approximately 150 h in liver and approximately 200 h in spleen. Ten injections of G-hLAL (every 3 days) into lal(-/-) mice produced normalization of hepatic color, decreases in hepatic cholesterol and TG contents, and diminished foamy macrophages in liver, spleen, and intestinal villi. All injected lal(-/-) mice developed anti-hLAL protein antibodies, but suffered no adverse events. These studies demonstrate the feasibility of using plant-expressed, recombinant hLAL for the enzyme therapy of human WD/CESD with general implications for other lysosomal storage diseases. 相似文献
226.
Bo Niklasson Knud E. Heller Bryan Sch?necker Mogens Bilds?e Terri Daniels Christiane S. Hampe Per Widlund William T. Simonson Jonathan B. Schaefer Terri Daniels Elizabeth Rutledge Lynn Bekris A. Michael Lindberg Susanne Johansson Eva ?rtqvist Bengt Persson ?ke Lernmark 《Experimental diabetes research》2003,4(1):35-44
Wild bank voles (Clethrionomys glareolus) may develop diabetes in laboratory captivity. The aim of this study was to test whether bank voles develop type 1 diabetes in association with Ljungan virus. Two groups of bank voles were analyzed for diabetes, pancreas histology, autoantibodies to glutamic acid decarboxylase (GAD65), IA-2, and insulin by standardized radioligand-binding assays as well as antibodies to in vitro transcribed and translated Ljungan virus antigens. Group A represented 101 trapped bank voles, which were screened for diabetes when euthanized within 24 hours of capture. Group B represented 67 bank voles, which were trapped and kept in the laboratory for 1 month before being euthanized. Group A bank voles did not have diabetes. Bank voles in group B (22/67; 33%) developed diabetes due to specific lysis of pancreatic islet beta cells. Compared to nondiabetic group B bank voles, diabetic animals had increased levels of GAD65 (P < .0001), IA-2 (P < .0001), and insulin (P = .03) autoantibodies. Affected islets stained positive for Ljungan virus, a novel picorna virus isolated from bank voles. Ljungan virus inoculation of nondiabetic wild bank voles induced beta-cell lysis. Compared to group A bank voles, Ljungan virus antibodies were increased in both nondiabetic (P < .0001) and diabetic (P = .0015) group B bank voles. Levels of Ljungan virus antibodies were also increased in young age at onset of newly diagnosed type 1 diabetes in children (P < .01). These findings support the hypothesis that the development of type 1 diabetes in captured wild bank voles is associated with Ljungan virus. It is speculated that bank voles may have a possible zoonotic role as a reservoir and vector for virus that may contribute to the incidence of type 1 diabetes in humans. 相似文献
227.
Wayne R. Munns Glenn W. Suter II Terri Damstra Robert Kroes Lawrence W. Reiter Erminio Marafante 《人类与生态风险评估》2003,9(1):379-386
The World Health Organization's International Programme on Chemical Safety and international partners have developed a framework for integrated assessment of human health and ecological risks and four case studies. An international workshop was convened to consider how ecological and health risk assessments might be integrated, the benefits of and obstacles to integration, and the research and mechanisms needed to facilitate implementation of integrated risk assessment. Using the case studies, workshop participants identified a number of opportunities to integrate the assessment process. Improved assessment quality, efficiency, and predictive capability were considered to be principal benefits of integration. Obstacles to acceptance and implementation of integrated risk assessment included the disciplinary and organizational barriers between ecological and health disciplines. A variety of mechanisms were offered to overcome these obstacles. Research recommendations included harmonization of exposure characterization and surveillance methods and models, development of common risk endpoints across taxa, improved understanding of mechanisms of effect at multiple scales of biological organization, and development of methods to facilitate comparison of risks among endpoints. 相似文献
228.
John B. Cook Hyung‐Seok Kim Terri C. Lin Chun‐Han Lai Bruce Dunn Sarah H. Tolbert 《Liver Transplantation》2017,7(2)
A synthesis methodology is demonstrated to produce MoS2 nanoparticles with an expanded atomic lamellar structure that are ideal for Faradaic‐based capacitive charge storage. While much of the work on MoS2 focuses on the high capacity conversion reaction, that process is prone to poor reversibility. The pseudocapacitive intercalation‐based charge storage reaction of MoS2 is investigated, which is extremely fast and highly reversible. A major challenge in the field of pseudocapacitive‐based energy storage is the development of thick electrodes from nanostructured materials that can sustain the fast inherent kinetics of the active nanocrystalline material. Here a composite electrode comprised of a poly(acrylic acid) binder, carbon fibers, and carbon black additives is utilized. These electrodes deliver a specific capacity of 90 mAh g?1 in less than 20 s and can be cycled 3000 times while retaining over 80% of the original capacity. Quantitative kinetic analysis indicates that over 80% of the charge storage in these MoS2 nanocrystals is pseudocapacitive. Asymmetric full cell devices utilizing a MoS2 nanocrystal‐based electrode and an activated carbon electrode achieve a maximum power density of 5.3 kW kg?1 (with 6 Wh kg?1 energy density) and a maximum energy density of 37 Wh kg?1 (with 74 W kg?1power density). 相似文献
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230.
Shelter dogs are typically cared for by staff and volunteers. At the Boston location of the Massachusetts Society for the Prevention of Cruelty to Animals, prior to 2009, any member of the public who was older than 16 years of age and attended 1 orientation could walk dogs available for adoption. There was no systematic method of training volunteers or staff to walk unruly, strong, or fearful dogs, nor was there any organized system of enrichment in the form of in-kennel or out-of-kennel training for the population of 20 to 40 dogs in the shelter. Using the Dick and Carey (1996) model of instructional design, a curriculum called “Safewalk” was devised and implemented. Safewalk created a hierarchical training system for volunteers. After training was implemented, outcomes and lengths of stay were then compared for dogs for the 3 years before and 4 years after Safewalk. Changes in adoption rates for pit bull-type dogs and non-pit bulls were significantly improved, and length of stay for non-pit bulls was significantly decreased. Other components of shelter life for dogs and people were also improved. 相似文献