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101.
Malignant peripheral nerve sheath tumors (MPNSTs) are characteristic of Neurofibromatosis type 1 (NF1), a human genetic disorder affecting approximately 1 in 3000 individuals. The absence of neurofibromin in Schwann cells results in hyperactivation of Ras, which contributes to Schwann cell hyperplasia. However, additional intracellular abnormalities in Schwann cells might contribute to the malignancy. We now report that cell lines derived from MPNSTs secrete elevated levels of prostaglandin E(2) (PGE(2)), express higher levels of phosphorylated mitogen-activated protein kinase (MAPK), phosphorylated cytosolic phospholipaseA(2) (cPLA(2)) and cyclooxygenase 2 (COX-2) when compared to normal adult human Schwann cells (nhSCs). PCR analysis reveals that NF1 MPNST cell lines express mRNA for both EP2 and EP4 prostaglandin E2 receptors, whereas nhSCs express only the EP4 receptor. COX-2 inhibitors and PGE(2) receptor antagonists decrease the proliferation of MPNST cell lines. These results indicate that prostaglandin metabolism is activated in MPNSTs and might contribute to tumor growth in NF1. 相似文献
102.
Grieshammer U Le Ma Plump AS Wang F Tessier-Lavigne M Martin GR 《Developmental cell》2004,6(5):709-717
Kidney development occurs in a stereotypic position along the body axis. It begins when a single ureteric bud emerges from the nephric duct in response to GDNF secreted by the adjacent nephrogenic mesenchyme. Posterior restriction of Gdnf expression is considered critical for correct positioning of ureteric bud development. Here we show that mouse mutants lacking either SLIT2 or its receptor ROBO2, molecules known primarily for their function in axon guidance and cell migration, develop supernumerary ureteric buds that remain inappropriately connected to the nephric duct, and that the SLIT2/ROBO2 signal is transduced in the nephrogenic mesenchyme. Furthermore, we show that Gdnf expression is inappropriately maintained in anterior nephrogenic mesenchyme in these mutants. Thus our data identify an intercellular signaling system that restricts, directly or indirectly, the extent of the Gdnf expression domain, thereby precisely positioning the site of kidney induction. 相似文献
103.
Natural variation in the sexually selected feather ornaments of crested auklets (Aethia cristatella) does not predict future survival 总被引:1,自引:0,他引:1
Jones Ian L.; Hunter Fiona M.; Robertson Gregory J.; Fraser Gail 《Behavioral ecology》2004,15(2):332-337
We evaluated whether sexually selected crest and auricular plumefeather ornaments of crested auklet (Aethia cristatella) adultscovaried with individual local survival over 11 years (19912001).Crested auklets (n = 364 total) were captured near breedingsites, marked with color rings, and local survival estimateswere based on color ring resightings at a breeding colony. Survivalestimates and relationships among local survival and crest length,auricular plume length, mass and tarsus were evaluated usingthe program MARK. The best models included four groups, definedby sex and ease of resighting, that differed in resighting rate(p) but not local survival rate (). This model structure effectivelyexplained sources of variation in local survival and resightabilityamong individuals. The best fitting model showed local survivalrate varying annually, while accounting for differences in resightabilityof marked individuals between the sexes and groups ([t], p[sex*easeof resighting]). Annual local survival varied from 0.940 ±0.029 (SE) in 19931994 to 0.767 ± 0.034 in 19971998and averaged 0.859 ± 0.019. We found no evidence thatcrested auklet local survival covaried with continuous variationin individuals' ornaments. Simulations indicated that our dataset was sufficient to detect a relationship between local survivaland a covariate that equaled or exceeded a range of 8%. Theimplications for competing sexual selection mechanisms of empiricallymeasured survivalornament relationships are controversial,but our study emphasizes that survival estimates for such investigationsmust control for confounding factors such as resighting rateas well as have sufficient statistical power and time scaleto be biologically meaningful. Our results are most consistentwith the idea that the conspicuous variation in crested auklet'sshowy ornaments is arbitrary with respect to individual viabilityas quantified by their long-term survival. 相似文献
104.
Gollub J Ball CA Binkley G Demeter J Finkelstein DB Hebert JM Hernandez-Boussard T Jin H Kaloper M Matese JC Schroeder M Brown PO Botstein D Sherlock G 《Nucleic acids research》2003,31(1):94-96
The Stanford Microarray Database (SMD; http://genome-www.stanford.edu/microarray/) serves as a microarray research database for Stanford investigators and their collaborators. In addition, SMD functions as a resource for the entire scientific community, by making freely available all of its source code and providing full public access to data published by SMD users, along with many tools to explore and analyze those data. SMD currently provides public access to data from 3500 microarrays, including data from 85 publications, and this total is increasing rapidly. In this article, we describe some of SMD's newer tools for accessing public data, assessing data quality and for data analysis. 相似文献
105.
Ong JM Aoki AM Seigel GM Sacerio I Castellon R Nesburn AB Kenney MC 《Neurochemical research》2003,28(6):883-891
Studies have shown an intimate relationship between cholesterol and retinal diseases; we examined the effects of cholesterol oxides on cultured cells. Using the rat retinal precursor cell line R28 and the human RPE cell line ARPE-19, we investigated the potential cytotoxicity of cholesterol oxides. Cultured R28 and ARPE-19 cells were treated with either 25-hydroxycholesterol and 7-ketocholesterol (0–50 µg/ml). Cell viability was determined by the WST-1 colorimetric assay. Production of reactive oxygen intermediate (ROI) was assessed by a fluorescent probe–based assay (2,7-dichlorodihydrofluorescein diacetate [H2DCFDA]). To detect the presence of apoptosis, DNA fragmentation gel analysis and Hoescht nuclear staining were performed. Both cholesterol oxides tested were toxic in a time- and dose-dependent fashion to the two cell lines used in this study. Treatment of R28 cells with either 25-hydroxycholesterol or 7-ketocholesterol at a concentration of 25 µg/ml resulted in greater than 50% loss of cell viability after 24 h. ARPE-19 cells were slightly less affected, with a loss of cell viability of approximately 20% and 40% after 24 h-exposure of 25-hydroxycholesterol and 7-ketocholesterol, respectively. DNA fragmentation and chromatin condensation demonstrated apoptotic events occurring in 7-ketocholesterol–treated cells. The fluorescent assay for ROI production showed that after an hour of exposure to 7-ketocholesterol, R28 cells responded with increased levels of ROIs, whereas no immediate production of ROIs were detected with treated ARPE-19 cells. These in vitro findings provide evidence that cholesterol oxides can directly damage cultured retinal and RPE cells. The oxysterol-induced oxidative stress in these cells may be a factor in the pathology of retinal degenerative diseases. 相似文献
106.
Tumor necrosis factor receptor-associated factor 2 (TRAF2)-deficient B lymphocytes reveal novel roles for TRAF2 in CD40 signaling 总被引:2,自引:0,他引:2
Hostager BS Haxhinasto SA Rowland SL Bishop GA 《The Journal of biological chemistry》2003,278(46):45382-45390
CD40 function is initiated by tumor necrosis factor (TNF) receptor-associated factor (TRAF) adapter proteins, which play important roles in signaling by numerous receptors. Characterizing roles of individual TRAFs has been hampered by limitations of available experimental models and the poor viability of most TRAF-deficient mice. Here, B cell lines made deficient in TRAF2 using a novel homologous recombination system reveal new roles for TRAF2. We demonstrate that TRAF2 participates in synergy between CD40 and B cell antigen receptor signals, and in CD40-mediated, TNF-dependent IgM production. We also find that TRAF2 participates in the degradation of TRAF3 associated with CD40 signaling, a role that may limit inhibitory actions of TRAF3. Finally, we show that TRAF2 and TRAF6 have overlapping functions in CD40-mediated NF-kappaB activation and CD80 up-regulation. These findings demonstrate previously unappreciated roles for TRAF2 in signaling by TNF receptor family members, using an approach that facilitates the analysis of genes critical to the viability of whole organisms. 相似文献
107.
108.
A retrospective study was conducted to identify causes of morbidity and mortality of free-living raptors in northeast Colorado and the surrounding areas of Nebraska and Wyoming. The study included 409 raptors, representing 23 species, admitted to the Colorado State University Veterinary Teaching Hospital, Fort Collins, Colorado, USA, from 1995 to 1998. Causes of morbidity and mortality were identified as trauma (66.3%), orphaned young (15.6%), unknown (9.0%), infectious disease (4.4%), metabolic and nutritional disease (2.2%), toxicosis (2.0%), and degenerative disease (0.5%). Trauma was the most frequent cause of morbidity and mortality for all species and during all seasons. 相似文献
109.
Receptors belonging to the tumor necrosis factor receptor (TNF-R) family utilize cytoplasmic adapter proteins called TNF-R-associated factors (TRAFs) as key elements in their signaling pathways. However, it is not yet clear how individual TRAFs regulate signaling by this large and growing receptor family. Signaling via the TNF-R family member CD40 has recently been shown to result in recruitment of TRAF2 to plasma membrane detergent-resistant microdomains (lipid rafts) as well as to subsequently initiate TRAF2 degradation. As TRAF2 associates with most members of the TNF-R family, we wished to determine how this degradation occurs. We show here that CD40-mediated TRAF2 degradation requires the zinc-binding RING domain of TRAF2 and is preceded by TRAF2 ubiquitination, suggesting that the TRAF2 RING may promote ubiquitination although the RING itself is not a target of ubiquitination. Several approaches show that ubiquitination and proteasomal activity are integral to TRAF2 degradation, and inhibition of this process potentiates CD40 signaling. 相似文献
110.
Roti EC Myers CD Ayers RA Boatman DE Delfosse SA Chan EK Ackerman MJ January CT Robertson GA 《The Journal of biological chemistry》2002,277(49):47779-47785
Many mutations in the Human Ether-à-go-go-Related Gene (HERG) cause type 2 congenital long QT syndrome (LQT2) by disrupting trafficking of the HERG-encoded potassium channel. Beyond observations that some mutations trap channels in the endoplasmic reticulum, little is known about how trafficking fails. Even less is known about what checkpoints are encountered in normal trafficking. To identify protein partners encountered as HERG channels are transported among subcellular compartments, we screened a human heart library with the C terminus of HERG using yeast two-hybrid technology. Among the proteins isolated was GM130, a Golgi-associated protein involved in vesicular transport. The interaction mapped to two non-contiguous regions of HERG and to a region just upstream of the GRASP-65 interaction domain of GM130. GM130 did not interact with the N or C terminus of either KvLQT1 or Shaker channels. LQT2-causing mutations in the HERG C terminus selectively disrupted interactions with GM130 but not Tara, another HERG-interacting protein. Native GM130 and stably expressed HERG were co-immunoprecipitated from HEK-293 cells using GM130 antibodies. In rat cardiac myocytes and HEK-293 cells, confocal immunocytochemistry showed co-localization of GM130 and HERG to the Golgi apparatus. Overexpression of GM130 suppressed HERG current amplitude in Xenopus oocytes, as if by providing an excess of substrate at the Golgi checkpoint. These findings indicate that GM130 plays a previously undefined role in cargo transport. We propose that the cytoplasmic C terminus of HERG participates in the tethering or possibly targeting of HERG-containing vesicles within the Golgi via its interaction with GM130. 相似文献