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991.
992.
Jin P Zhang J Sumariwalla PF Ni I Jorgensen B Crawford D Phillips S Feldmann M Shepard HM Paleolog EM 《Arthritis research & therapy》2008,10(4):R73
Introduction
Despite the advent of biological therapies for the treatment of rheumatoid arthritis, there is a compelling need to develop alternative therapeutic targets for nonresponders to existing treatments. Soluble receptors occur naturally in vivo, such as the splice variant of the cell surface receptor for vascular endothelial growth factor (VEGF) – a key regulator of angiogenesis in rheumatoid arthritis. Bioinformatics analyses predict that the majority of human genes undergo alternative splicing, generating proteins – many of which may have regulatory functions. The objective of the present study was to identify alternative splice variants (ASV) from cell surface receptor genes, and to determine whether the novel proteins encoded exert therapeutic activity in an in vivo model of arthritis. 相似文献993.
Eaton S 《Developmental cell》2008,14(1):4-6
Wntless is a sorting receptor required for Wnt secretion. Wntless is retrieved from endosomes to the Golgi by retromer, permitting Wntless reutilization in Wnt transport. In the absence of retromer, Wntless is degraded in lysosomes and Wnt secretion is impaired. 相似文献
994.
Tong J Taylor P Jovceva E St-Germain JR Jin LL Nikolic A Gu X Li ZH Trudel S Moran MF 《Journal of proteome research》2008,7(3):1067-1077
To identify phosphotyrosine (pY) sites in the epidermal growth factor receptor (EGFR) network, a tandem immunoprecipitation-mass spectrometry method (TIPY-MS) was applied wherein protease-digested EGFR immune complexes were extracted with anti-pY after Rush et al. ( Nat. Biotech. 2005, 23, 94 ) and analyzed by LC-MS/MS. New pY sites in the pathway were found, including SOS1 Y1065, SOS2 Y1275, CBL-B Y889, and in the EGFR regulatory protein Mig-6 Y458. The novel human C19orf19 gene product was found EGFR-associated and phosphorylated at 5 tyrosines in response to EGFR activation and, therefore, represents a new component of the EGFR signaling network. 相似文献
995.
Biphenyl amide p38 kinase inhibitors 3: Improvement of cellular and in vivo activity 总被引:1,自引:0,他引:1
Angell R Aston NM Bamborough P Buckton JB Cockerill S deBoeck SJ Edwards CD Holmes DS Jones KL Laine DI Patel S Smee PA Smith KJ Somers DO Walker AL 《Bioorganic & medicinal chemistry letters》2008,18(15):4428-4432
The biphenyl amides (BPAs) are a novel series of p38α MAP kinase inhibitor. The optimisation of the series to give compounds that are potent in an in vivo disease model is discussed. SAR is presented and rationalised with reference to the crystallographic binding mode. 相似文献
996.
Voelckel C Heenan PB Janssen B Reichelt M Ford K Hofmann R Lockhart PJ 《Molecular ecology》2008,17(21):4740-4753
New Zealand is diverse in alpine and subalpine environments, a consequence of Late Tertiary tectonic and climatic change. However, few studies have sought to evaluate the importance of these environments as abiotic drivers in the diversification of plant species. Of particular interest is the Late Tertiary radiation of Pachycladon, an endemic New Zealand genus of alpine cress. Here we report observations on genome-wide levels of differential expression measured in the habitats of two closely related species of Pachycladon with distinct altitudinal preferences. Using Arabidopsis microarrays, we have identified 310 predominantly hormone- and stress-response genes up-regulated in Pachycladon fastigiata and 324 genes up-regulated in Pachycladon enysii. Expression patterns for glucosinolate biosynthesis and hydrolysis genes (MAM1, MAM-I, MAM-D, AOP2, ESP, ESM1) as well as flavonoid biosynthesis genes (F3'H, FLS, FAH1) were found to be species specific. Predicted differences in flavonoid contents were partly confirmed by high performance liquid chromatography analysis. Differences in glucosinolate profiles and glucosinolate hydrolysis products obtained by high performance liquid chromatography and gas chromatography-mass spectrometry analysis, respectively, also supported inferences from expression analyses. Five glucosinolate chemotypes were matched to known Arabidopsis ecotypes, and the potential adaptive significance of these chemotypes has been discussed. Our findings, in contrast to expectations for evolution of the New Zealand flora, suggest that biotic drivers, such as plant-herbivore interactions, are likely to be as important as abiotic drivers in the diversification of Pachycladon. 相似文献
997.
Saenko SV French V Brakefield PM Beldade P 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2008,363(1496):1549-1555
The origin and diversification of evolutionary novelties-lineage-specific traits of new adaptive value-is one of the key issues in evolutionary developmental biology. However, comparative analysis of the genetic and developmental bases of such traits can be difficult when they have no obvious homologue in model organisms. The finding that the evolution of morphological novelties often involves the recruitment of pre-existing genes and/or gene networks offers the potential to overcome this challenge. Knowledge about shared developmental processes obtained from extensive studies in model organisms can then be used to understand the origin and diversification of lineage-specific structures. Here, we illustrate this approach in relation to eyespots on the wings of Bicyclus anynana butterflies. A number of spontaneous mutations isolated in the laboratory affect eyespots, lepidopteran-specific features, and also processes that are shared by most insects. We discuss how eyespot mutants with disturbed embryonic development may help elucidate the genetic pathways involved in eyespot formation, and how venation mutants with altered eyespot patterns might shed light on mechanisms of eyespot development. 相似文献
998.
Ward AJ Duff AJ Horsfall JS Currie S 《Proceedings. Biological sciences / The Royal Society》2008,275(1630):101-105
Chemical cues are of enormous importance in mediating the behaviour of animals, enabling them to navigate throughout their habitats, to detect the presence of predators or prey and for social recognition-identifying and discriminating between conspecifics. In many species of freshwater fish, social recognition is known to be based primarily on chemical cues. Such recognition mechanisms are vulnerable to disruption by the presence of anthropogenic contaminants in the aquatic environment. Here we show that acute exposure to low, environmentally relevant dosages of the ubiquitous contaminant, 4-nonylphenol, can seriously affect social recognition and ultimately social organization in fishes. A 1 hour 0.5 microgl-1 dose was sufficient to alter the response of members of a shoaling fish species (juvenile banded killifish, Fundulus diaphanus) to conspecific chemical cues. Dosages of 1-2 microgl-1 caused killifish to orient away from dosed conspecifics, in both a flow channel and an arena. Given the overall importance of shoaling as an adaptive strategy against predators and for locating food, it is likely that its disruption by anthropogenic contaminants would have serious implications for fishes' fitness. 相似文献
999.
1000.
Randall S. Wells Jason B. Allen Suzanne Hofmann Kim Bassos‐Hull Deborah A. Fauquier Nélio B. Barros Ruth E. DeLynn Gretchen Sutton Victoria Socha Michael D. Scott 《Marine Mammal Science》2008,24(4):774-794
Accurate identification of human‐induced injuries that lead to death or interfere with reproduction is important for marine mammal management, as deaths exceeding established limits can lead to restrictions on fisheries or vessel operations. The fates of cetaceans last seen swimming with attached gear, particularly in pelagic fisheries, or with vessel strike lacerations, have been difficult to predict. Survival and reproduction data from long‐term research on resident common bottlenose dolphins near Sarasota, Florida were examined relative to consequences of fishing gear ingestion, line entanglements, vessel strikes, and amputations of unknown origins. Fishing hooks embedded in the throat, goosebeak, or esophagus, or line wrapped around the goosebeak, generally lead to death. Multiple, constrictive line wraps around fin insertions can lead to amputation, blood loss, impaired mobility, or infection. Dolphins with ingested gear or severe entanglements may swim away with the gear, but likely die later. Propeller injuries involving only soft tissue were often survivable. Some dolphins survived amputations of the distal ends of fins, and continued to reproduce. As a precautionary approach, dolphins with ingested gear or severe constrictive entanglements should be considered mortalities, but extrapolations of findings from coastal bottlenose dolphins to other cetaceans and different gear must be done with caution. 相似文献