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991.
Mulvihill MJ Ji QS Werner D Beck P Cesario C Cooke A Cox M Crew A Dong H Feng L Foreman KW Mak G Nigro A O'Connor M Saroglou L Stolz KM Sujka I Volk B Weng Q Wilkes R 《Bioorganic & medicinal chemistry letters》2007,17(4):1091-1097
A series of novel 8-amino-1,3-disubstituted-imidazo[1,5-a]pyrazines was designed and synthesized as IGF-IR inhibitors. 相似文献
992.
Physiological and biochemical responses to acute ozone-induced oxidative stress in Medicago truncatula. 总被引:1,自引:0,他引:1
Michael C Puckette Hua Weng Ramamurthy Mahalingam 《Plant Physiology and Biochemistry》2007,45(1):70-79
Oxidative signaling mediated by reactive oxygen species (ROS) is a central component of biotic and abiotic stresses in plants. Acute ozone (O(3)) fumigation is a useful non-invasive treatment for eliciting endogenous ROS in planta. In this study, 38 different accessions of the model legume, Medicago truncatula, from various geographical regions were fumigated with 300 nmol mol(-1) of O(3) for a period of six hours. Phenotypic symptoms were evaluated 24 and 48 h after the end of treatment. A majority of the accessions showed distinct visible damage. Eight accessions showing varying sensitivities to ozone were subjected to biochemical analysis to evaluate correlations between ozone damage and levels of ROS, antioxidants, and lipid peroxidation. Two-way analysis of variance indicated highly significant interactions between O(3) damage and levels of ROS, ascorbate, glutathione and lipid peroxidation. There were significant differences among the accessions for these traits before and after the end of O(3) fumigation, as indicated by equal variance Student's t-test. This study suggests that multiple physiological and biochemical mechanisms may govern O(3) tolerance or sensitivity. Surveying a large collection of germplasm led to identification of multiple resistant and sensitive lines for investigating molecular basis of O(3) phytotoxicity. The most resistant JE154 accession also showed enhanced tolerance to chronic O(3) and dehydration stress, suggesting germplasm with increased tolerance to acute O(3) can be a useful resource for improving resistance to multiple abiotic stressors. 相似文献
993.
Wang L Zhao WL Yan JS Liu P Sun HP Zhou GB Weng ZY Wu WL Weng XQ Sun XJ Chen Z Sun HD Chen SJ 《Cell death and differentiation》2007,14(2):306-317
Diterpenoids isolated from Labiatae family herbs have strong antitumor activities with low toxicity. In this study, Eriocalyxin B (EriB), a diterpenoid extracted from Isodon eriocalyx, was tested on human leukemia/lymphoma cells and murine leukemia models. Acute myeloid leukemia cell line Kasumi-1 was most sensitive to EriB. Significant apoptosis was observed, concomitant with Bcl-2/Bcl-XL downregulation, mitochondrial instability and caspase-3 activation. AML1-ETO oncoprotein was degraded in parallel to caspase-3 activation. EriB-mediated apoptosis was associated with NF-kappaB inactivation by preventing NF-kappaB nuclear translocation and inducing IkappaBalpha cleavage, and disturbance of MAPK pathway by downregulating ERK1/2 phosphorylation and activating AP-1. Without affecting normal hematopoietic progenitor cells proliferation, EriB was effective on primary t(8;21) leukemia blasts and caused AML1-ETO degradation. In murine t(8;21) leukemia models, EriB remarkably prolonged the survival time or decreased the xenograft tumor size. Together, EriB might be a potential treatment for t(8;21) leukemia by targeting AML1-ETO oncoprotein and activating apoptosis pathways. 相似文献
994.
995.
Synthesis and characterization of photo-cross-linked hydrogels based on biodegradable polyphosphoesters and poly(ethylene glycol) copolymers 总被引:1,自引:0,他引:1
Novel biodegradable hydrogels by photo-cross-linking macromers based on polyphosphoesters and poly(ethylene glycol) (PEG) are reported. Photo-cross-linkable macromers were synthesized by ring-opening polymerization of the cyclic phosphoester monomer 2-(2-oxo-1,3,2-dioxaphospholoyloxy) ethyl methacrylate (OPEMA) using PEG as the initiator and stannous octoate as the catalyst. The macromers were characterized by 1H NMR, Fourier transform infrared spectroscopy, and gel permeation chromatography measurements. The content of polyphosphoester in the macromer was controlled by varying the feed ratio of OPEMA to PEG. Hydrogels were fabricated by exposing aqueous solutions of macromers with 0.05% (w/w) photoinitiator to UV light irradiation, and their swelling kinetics as well as degradation behaviors were evaluated. The results demonstrated that cross-linking density and pH values strongly affected the degradation rates. The macromers was compatible to osteoblast cells, not exhibiting significant cytotoxicity up to 0.5 mg/mL. "Live/dead" cell staining assay also demonstrated that a large majority of the osteoblast cells remained viable after encapsulation into the hydrogel constructs, showing their potential as tissue engineering scaffolds. 相似文献
996.
Bolden-Tiller OU Chiarini-Garcia H Poirier C Alves-Freitas D Weng CC Shetty G Meistrich ML 《Biology of reproduction》2007,77(2):237-246
Male mice that are homozygous for the juvenile spermatogonial depletion (jsd) mutation in the Utp14b gene undergo several waves of spermatogenesis. However, spermatogonial differentiation ceases and in adults, spermatogonia are the only germ cells that remain. To understand further the blockage in spermatogonial differentiation in Utp14b(jsd) mutant mice, we correlated the rate and severity of spermatogonial depletion and the restoration of spermatogenesis following the suppression of testosterone or elevation of testicular temperature with the genetic background. Testes from Utp14b(jsd) mutant mice on B6, C3H, and mixed C3H-B6-129 (HB129) genetic backgrounds all showed steady decreases in the numbers of normal spermatogonia between 8 wk and 20 wk of age. The percentages of tubules with differentiating germ cells were higher and the spermatogonia were more advanced in C3H- background than in B6- or HB129-background Utp14b(jsd) mice. Genetic crosses showed that the source of the Y chromosome was a major factor in determining the severity of spermatogonial depletion in Utp14b(jsd) mutant mice. When Utp14b(jsd) mutants were subjected to total androgen ablation or unilateral cryptorchidization, spermatogenic development recovered markedly in the C3H and HB129 background but showed less recovery in the B6-background mice. The differences noted between the strains in terms of the severity of spermatogonial depletion were not dependent upon testosterone level or scrotal temperature but correlated with the magnitudes of the effects of elevated temperature on normal and Utp14b(jsd) mutant spermatogenic cells. Thus, the abilities of germ cells in certain strains to survive elevated temperatures may be related to their abilities to maintain some degree of differentiation potential after the Utp14b(jsd) gene is mutated. 相似文献
997.
Dictyostelium gnt15 encodes a protein with similarity to LARGE and plays an essential role in development 总被引:2,自引:0,他引:2
Pang TL Wu CJ Chen PA Weng YL Chen MY 《Biochemical and biophysical research communications》2007,360(1):83-89
LARGE is a putative glycosyltransferase found to be mutated in mice with myodystrophy or patients with congenital muscular dystrophy. By homology searches, we identified in the Dictyostelium discoideum genome four open reading frames, i.e. gnt12-15, encoding proteins with sequence similarity to LARGE. Semi-quantitative RT-PCR analysis revealed distinct temporal expression patterns of the four gnt genes throughout Dictyostelium development. To explore the gene function, we performed targeted disruptions of gnt14 and gnt15. The gnt14(-) strains showed no obvious phenotypes. However, gnt15(-) cells grew slowly, changed in morphology, and displayed a developmental phenotype arresting at early stages. Compared with the wild type, gnt15(-) cells were more adhesive and exhibited altered levels of some surface adhesion molecules. Moreover, lectin-binding analysis demonstrated that gnt15 disruption affected profiles of membrane glycoproteins. Taken together, our data suggest that Gnt15 is essential for Dictyostelium development and may have a role in modulating cell adhesion and glycosylation. 相似文献
998.
Han?Li Qunli?Zeng Yu?Weng Deqiang?Lu Huai?Jiang Zhengping?XuEmail author 《中国科学C辑(英文版)》2005,48(5):506-514
Extremely Low Frequency Magnetic Fields (ELF MF) has been considered as a “possible human carcinogen” by International Agency
for Research on Cancer (IARC) while credible mechanisms of its carcinogenicity remain unknown. In this study, a proteomics
approach was employed to investigate the changes of protein expression profile induced by ELF MF in human breast cancer cell
line MCF7, in order to determine ELF MF-responsive proteins. MCF7 cells were exposed to 50 Hz, 0.4 mT ELF MF for 24 h and
the changes of protein profile were examined using two dimensional electrophoresis. Up to 6 spots have been statistically
significantly altered (their expression levels were changed at least 5 fold up or down) compared with sham-exposed group.
19 ones were only detected in exposure group while 19 ones were missing. Three proteins were identified by LC-IT Tandem MS
as RNA binding protein regulatory subunit Proteasome subunit beta type 7 precursor and Translationally Controlled Tumor Protein.
Our finding showed that 50 Hz, 0.4 mT ELF MF alternates the protein profile of MCF7 cell and may affect many physiological
functions of normal cell and 2-DE coupled with MS is a promising approach to elucidating cellular effects of electromagnetic
fields. 相似文献
999.
A Ramachandran plot is a visual representation of the main-chain conformational tendencies of an amino acid. Despite forty years of research, the shape of Ramachandran plots is still a matter of debate. The issue in making a Ramachandran plot based on experimental data is deciding whether sparse data represent genuine conformations. We present here a simple solution to settle the ambiguities of the sparse data, and explain how we verified the accuracies of our plots using an independent dataset. To obtain our results, we then measured the pair-wise distances of main-chain conformational tendencies among amino acids, and showed that the conformational relationships of amino acids are well preserved in a two-dimensional map, leading to the conclusion that the conformational diversity space of amino acids is largely two dimensional. We further noticed that amino acids in early and late evolutionary stages are located in different zones in the two-dimensional map. In addition to these conclusions, we here present an amino acid substitution table derived from experimental data. 相似文献
1000.
We present a new version of the Protein-Protein Docking Benchmark, reconstructed from the bottom up to include more complexes, particularly focusing on more unbound-unbound test cases. SCOP (Structural Classification of Proteins) was used to assess redundancy between the complexes in this version. The new benchmark consists of 72 unbound-unbound cases, with 52 rigid-body cases, 13 medium-difficulty cases, and 7 high-difficulty cases with substantial conformational change. In addition, we retained 12 antibody-antigen test cases with the antibody structure in the bound form. The new benchmark provides a platform for evaluating the progress of docking methods on a wide variety of targets. The new version of the benchmark is available to the public at http://zlab.bu.edu/benchmark2. 相似文献