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Decorin is a member of the small leucine-rich proteoglycan (SLRP) gene family that has recently become a focus in various areas of cancer research. The decorin protein consists of a core protein and a covalently linked glycosaminoglycan chain. Decorin binds to collagens type I, II and IV in vivo and promotes the formation of fibers with increased stability and changes in solubility. Further, the decorin core protein binds to growth factors, including transforming growth factor-beta (TGF-beta), to other intercellular matrix molecules such as fibronectin and thrombospondin, and to the decorin endocytosis receptor. Decorin may directly interfere with the cell cycle via the induction of p21WAF1/CIP1 (p21), a potent inhibitor of cyclin-dependent kinases (CDKs). Here, we discuss interactions of decorin with TGF-beta and with p21, both of which are relevant to carcinogenesis and tumor progression. TGF-beta is released by tumors of various histogenetic origins and promotes immunosuppression in the host and tumor immune escape by induction of growth arrest and apoptosis in immune cells, by downregulation of MHC II antigen expression and by changes in the cytokine release profiles of immune and tumor cells. Moreover, TGF-beta may modulate tumor growth in an autocrine and paracrine fashion, may mediate drug resistance, and may facilitate tumor angiogenesis. Decorin binds to TGF-beta, thus inhibiting its bioactivity, and is a direct or indirect negative modulator of TGF-beta synthesis. Ectopic expression of decorin results in the regression of rat C6 gliomas, an antineoplastic effect attributed to the reversal of TGF-beta-induced immunosuppression. On the other hand, de novo expression of decorin in colon cancer cells and some other tumor cells, even though not in glioma cells, results in an upregulation of p21 expression and a cell cycle arrest, presumably in a TGF-beta-independent manner. Decorin expression is downregulated in many tumors but upregulated in the peritumoral stroma. By virtue of its growth regulatory and immunomodulatory properties, decorin promises to become a novel target for the experimental therapy of human cancers. 相似文献
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Charlotte Weiß Jos Kramer Kai Holländer Joël Meunier 《Ethology : formerly Zeitschrift fur Tierpsychologie》2014,120(9):923-932
The evolution of group living is generally associated with the emergence of social behaviors that ensure fitness benefits to group members. However, the expression of these behaviors may depend on group composition, which can vary over time with respect to sex, starvation status, and relatedness. Here, we investigated (1) whether adults of the group‐living European earwig, Forficula auricularia, show cooperative behaviors toward conspecifics and (2) whether sex, food availability, and relatedness shape the nature and frequency of these behaviors. We conducted a full‐factorial experiment using 108 unisexual pairs of adults, in which we manipulated these three factors and video‐recorded the earwig behaviors for 45 min. Our results revealed that adults mostly expressed self‐directed and aggressive behaviors. Nevertheless, they also showed allogrooming, a social behavior that offers scope for cooperation. Pairs of males displayed longer bouts of aggression and allogrooming (when it occurred) than pairs of females. Food deprivation had no effect on male behaviors, but females spent less time self‐grooming and walking when they were food deprived. Finally, low relatedness between adults did not influence any of the measured behaviors, but exacerbated frass production, possibly due to social stress. Overall, these results indicate the limited role of cooperation among F. auricularia adults during their group‐living phase. 相似文献
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An animal’s home range use is influenced by the landscape type. European hare (Lepus europaeus) home ranging behaviour has been studied only in agricultural areas with medium to large fields. In agricultural areas with small fields, European hares’ locomotor behaviour is expected to be more localised. We tracked nine European hares by means of global positioning system (GPS) and very high-frequency (VHF) collars during summer in an agricultural area with small fields in Lower Austria. In particular, we analysed the hares’ space use at a fine temporal scale, such as when they were active and resting within single 24-h periods. Furthermore, we compared data (day–day distances and day–night distances travelled) calculated from GPS and VHF telemetry. Home ranges were smaller, and the distances between areas used for activity and inactivity were shorter, in this agricultural area with small fields than has ever been measured in other agricultural areas with larger fields. Both active and inactive European hares expressed a preference for areas near field edges. Our findings suggest that with GPS, it is possible to distinguish between the movement path and the relative location of distinctly used areas within an animal’s home range, whereas with VHF these two parameters may be difficult to separate. In conclusion, our results show that in areas where resources are easily accessible, such as in agricultural areas with small fields, the European hare is able to reduce its home range size to almost half of the minimum size that has been recorded so far in other habitats. As small home ranges involve less energy expenditure for movement, our results suggest that animals living in agro-ecosystems may benefit from small fields. 相似文献
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Olesen PH Tønder JE Hansen JB Hansen HC Rimvall K 《Bioorganic & medicinal chemistry》2000,8(6):1443-1450
Bioisosteric replacement of the isoxazole heterocycle in (3-methyl-5-isoxazolyl)methylene-azacyclic compounds with pyridine, oxadiazole, or an acyl group resulted in ligands with high to moderate affinity for the central nicotinic cholinergic receptors (IC50 = 2.0 to IC50 > 1000 nM) labeled by [3H]methylcarbamylcholine. Additionally, further support of an important distance parameter for high-affinity nicotinic compounds has been provided. 相似文献
239.
Viral inhibitor of apoptosis vFLIP/K13 protects endothelial cells against superoxide-induced cell death
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Thurau M Marquardt G Gonin-Laurent N Weinländer K Naschberger E Jochmann R Alkharsah KR Schulz TF Thome M Neipel F Stürzl M 《Journal of virology》2009,83(2):598-611
Human herpesvirus 8 (HHV-8) is the etiological agent of Kaposi's sarcoma (KS). HHV-8 encodes an antiapoptotic viral Fas-associated death domain-like interleukin-1β-converting enzyme-inhibitory protein (vFLIP/K13). The antiapoptotic activity of vFLIP/K13 has been attributed to an inhibition of caspase 8 activation and more recently to its capability to induce the expression of antiapoptotic proteins via activation of NF-κB. Our study provides the first proteome-wide analysis of the effect of vFLIP/K13 on cellular-protein expression. Using comparative proteome analysis, we identified manganese superoxide dismutase (MnSOD), a mitochondrial antioxidant and an important antiapoptotic enzyme, as the protein most strongly upregulated by vFLIP/K13 in endothelial cells. MnSOD expression was also upregulated in endothelial cells upon infection with HHV-8. Microarray analysis confirmed that MnSOD is also upregulated at the RNA level, though the differential expression at the RNA level was much lower (5.6-fold) than at the protein level (25.1-fold). The induction of MnSOD expression was dependent on vFLIP/K13-mediated activation of NF-κB, occurred in a cell-intrinsic manner, and was correlated with decreased intracellular superoxide accumulation and increased resistance of endothelial cells to superoxide-induced death. The upregulation of MnSOD expression by vFLIP/K13 may support the survival of HHV-8-infected cells in the inflammatory microenvironment in KS. 相似文献
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Jana Zimmermann Isolde Saalbach Doreen Jahn Martin Giersberg Sigrun Haehnel Julia Wedel Jeanette Macek Karen Zoufal Gerhard Glünder Dieter Falkenburg Sergey M Kipriyanov 《BMC biotechnology》2009,9(1):1-22