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81.
Shao K Hou Q Go ML Duan W Cheung NS Feng SS Wong KP Yoram A Zhang W Huang Z Li QT 《Cellular and molecular life sciences : CMLS》2007,64(4):506-515
Tenascin-C is an extracellular matrix glycoprotein, whose expression is highly restricted in normal adult tissues, but markedly
up-regulated in a range of tumors, and therefore serves as a potential receptor for targeted anticancer drug or gene delivery.
We describe here a liposomal carrier system in which the targeting ligand is sulfatide. Experiments with tenascin-C-expressing
glioma cells demonstrated that binding of liposomes to the extracellular matrix relied essentially on the sulfatide-tenascin-C
interaction. Following binding to the extracellular matrix, the sulfatide-containing liposomes were internalized via both
caveolae/lipid raft- and clathrin-dependent pathways, which would ensure direct cytoplasmic release of the cargoes carried
in the liposomes. Such natural lipid-guided intracellular delivery targeting at the extracellular matrix glycoproteins of
tumor cells thus opens a new direction for development of more effective anticancer chemotherapeutics in future.
K. Shao & Q. Hou: These authors contributed equally to this work.
Received 22 September 2006; received after revision 5 December 2006; accepted 9 January 2007 相似文献
82.
Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus 总被引:1,自引:0,他引:1
Lee-Kirsch MA Gong M Chowdhury D Senenko L Engel K Lee YA de Silva U Bailey SL Witte T Vyse TJ Kere J Pfeiffer C Harvey S Wong A Koskenmies S Hummel O Rohde K Schmidt RE Dominiczak AF Gahr M Hollis T Perrino FW Lieberman J Hübner N 《Nature genetics》2007,39(9):1065-1067
TREX1 acts in concert with the SET complex in granzyme A-mediated apoptosis, and mutations in TREX1 cause Aicardi-Goutières syndrome and familial chilblain lupus. Here, we report monoallelic frameshift or missense mutations and one 3' UTR variant of TREX1 present in 9/417 individuals with systemic lupus erythematosus but absent in 1,712 controls (P = 4.1 x 10(-7)). We demonstrate that two mutant TREX1 alleles alter subcellular targeting. Our findings implicate TREX1 in the pathogenesis of SLE. 相似文献
83.
This review article describes new enzymatic methods developed for the efficient and irreversible synthesis of peptides based on native and modified proteases, and for the synthesis of polypeptides containing D- and/or unnatural amino acids. Potential opportunities for future developments in the field based on new enzymes, tailormade catalytic antibodies, and on the technique of in vitro mutagenesis are also described. 相似文献
84.
1,2,4-Triazolidine-3,5-diones and the 3,5-isoxazolidinedione were observed to be potent inhibitors of rat lens aldose reductase activity. In vivo in streptozotocin-diabetic rats, selected agents at 20 mg/kg/day, orally for 21 days reduced significantly the sorbitol levels of rbc, lens and sciatic nerves, suggesting that these derivatives may have some usefulness to treat clinical complications of diabetes mellitus. 相似文献
85.
Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen 总被引:45,自引:0,他引:45
Stover CK Pham XQ Erwin AL Mizoguchi SD Warrener P Hickey MJ Brinkman FS Hufnagle WO Kowalik DJ Lagrou M Garber RL Goltry L Tolentino E Westbrock-Wadman S Yuan Y Brody LL Coulter SN Folger KR Kas A Larbig K Lim R Smith K Spencer D Wong GK Wu Z Paulsen IT Reizer J Saier MH Hancock RE Lory S Olson MV 《Nature》2000,406(6799):959-964
Pseudomonas aeruginosa is a ubiquitous environmental bacterium that is one of the top three causes of opportunistic human infections. A major factor in its prominence as a pathogen is its intrinsic resistance to antibiotics and disinfectants. Here we report the complete sequence of P. aeruginosa strain PAO1. At 6.3 million base pairs, this is the largest bacterial genome sequenced, and the sequence provides insights into the basis of the versatility and intrinsic drug resistance of P. aeruginosa. Consistent with its larger genome size and environmental adaptability, P. aeruginosa contains the highest proportion of regulatory genes observed for a bacterial genome and a large number of genes involved in the catabolism, transport and efflux of organic compounds as well as four potential chemotaxis systems. We propose that the size and complexity of the P. aeruginosa genome reflect an evolutionary adaptation permitting it to thrive in diverse environments and resist the effects of a variety of antimicrobial substances. 相似文献
86.
The optical, electronic and mechanical properties of synthetic and biological materials consisting of polymer chains depend sensitively on the conformation adopted by these chains. The range of conformations available to such systems has accordingly been of intense fundamental as well as practical interest, and distinct conformational classes have been predicted, depending on the stiffness of the polymer chains and the strength of attractive interactions between segments within a chain. For example, flexible polymers should adopt highly disordered conformations resembling either a random coil or, in the presence of strong intrachain attractions, a so-called 'molten globule'. Stiff polymers with strong intrachain interactions, in contrast, are expected to collapse into conformations with long-range order, in the shape of toroids or rod-like structures. Here we use computer simulations to show that the anisotropy distribution obtained from polarization spectroscopy measurements on individual poly[2-methoxy-5-(2'-ethylhexyl)oxy-1,4-phenylenevinylene] polymer molecules is consistent with this prototypical stiff conjugated polymer adopting a highly ordered, collapsed conformation that cannot be correlated with ideal toroid or rod structures. We find that the presence of so-called 'tetrahedral chemical defects', where conjugated carbon-carbon links are replaced by tetrahedral links, divides the polymer chain into structurally identifiable quasi-straight segments that allow the molecule to adopt cylindrical conformations. Indeed, highly ordered, cylindrical conformations may be a critical factor in dictating the extraordinary photophysical properties of conjugated polymers, including highly efficient intramolecular energy transfer and significant local optical anisotropy in thin films. 相似文献
87.
Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation 总被引:20,自引:0,他引:20
Wong KK Chang S Weiler SR Ganesan S Chaudhuri J Zhu C Artandi SE Rudolph KL Gottlieb GJ Chin L Alt FW DePinho RA 《Nature genetics》2000,26(1):85-88
Telomeres are specialized nucleoprotein complexes that serve as protective caps of linear eukaryotic chromosomes. Loss of telomere function is associated with rampant genetic instability and loss of cellular viability and renewal potential. The telomere also participates in processes of chromosomal repair, as evidenced by the 'capture' or de novo synthesis of telomere repeats at double-stranded breaks and by the capacity of yeast telomeres to serve as repositories of essential components of the DNA repair machinery, particularly those involved in non-homologous end-joining (NHEJ). Here we used the telomerase-deficient mouse, null for the essential telomerase RNA gene (Terc), to assess the role of telomerase and telomere function on the cellular and organismal response to ionizing radiation. Although the loss of telomerase activity per se had no discernable impact on the response to ionizing radiation, the emergence of telomere dysfunction in late-generation Terc-/- mice imparted a radiosensitivity syndrome associated with accelerated mortality. On the cellular level, the gastrointestinal crypt stem cells and primary thymocytes showed increased rates of apoptosis, and mouse embryonic fibroblasts (MEFs) showed diminished dose-dependent clonogenic survival. The radiosensitivity of telomere dysfunctional cells correlated with delayed DNA break repair kinetics, persistent chromosomal breaks and cytogenetic profiles characterized by complex chromosomal aberrations and massive fragmentation. Our findings establish a intimate relationship between functionally intact telomeres and the genomic, cellular and organismal response to ionizing radiation. 相似文献
88.
1 Introduction1 Preserving natural heritage has been identified as an important task in many countries. However, if damage to such heritage is unavoidable during the development, we may want to record the natural heritage before damaging it. One way is to acquire the 3D geometric information of the natural heritage. So that we can render it later. However, if the natural heritage is very large in scale and very complex in geometry, acquisition of such large-scale environment is infeasible an… 相似文献
89.
90.