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141.
Yuan M Luo M Song Y Xu Q Wang X Cao Y Bu X Ren Y Hu X 《Bioorganic & medicinal chemistry》2011,19(3):1189-1196
Several recent developments suggest that the human glyoxalase I (GLO I) is a potential target for anti-tumor drug development. In present study, a series of curcumin derivatives with high inhibitory activity against human GLO I were discovered. Inhibition constant (K(i)) values of compounds 8, 9, 10, 11 and 13 to GLO I are 4.600μM, 2.600μM, 3.200μM, 3.600μM and 3.600μM, respectively. To elucidate the structural features of potent inhibitors, docking-based three-dimensional structure-activity relationship (3D-QSAR) analyses were performed. Satisfactory agreement between experiment and theory suggests that comparative molecular similarity index analysis (CoMSIA) modeling exhibit much better correlation and predictive power. The cross-validated q(2) value is 0.638 while no-validation r(2) value is 0.930. Integrated with docking-based 3D-QSAR CoMSIA modeling, molecular surface property (electrostatic and steric) mapping and molecular dynamics simulation, a set of receptor-ligand binding models and bio-affinity predictive models for rational design of more potent inhibitors of GLO I are established. 相似文献
142.
Zhaojun Bu Joosten Hans Hongkai Li Gaolin Zhao Xingxing Zheng Jinze M Jing Zeng 《生态学报》2011,31(3):157-162
Peatlands hold a large portion of the Earth’s terrestrial organic carbon and serve as important pools in the global carbon cycle. Due to their strong feedbacks, peatlands are one of the most important ecosystems with respect to climate warming. This paper reviews the effects of climate warming on peatland ecosystems. Climate warming will shift the point in time when vascular peatland plants flower and reach maximum biomass to an earlier date. Flower production for some plants will increase, but how the phenology of peatland bryophytes will react is still unknown. Climate warming may increase productivity of peatlands, especially ombrotrophic Sphagnum bogs, but in the long run the negative effects from decreased water availability may prevail. Climate warming will change the basic characteristics of peatlands: their wetness and the related cold environment and nutrient shortage. By increased mineralization and nitrogen and phosphorus availability, climate warming will facilitate the growth of vascular plants. This will suppress endangered plant species (which usually grow in low-productive, phosphorus-limited habitats) and lead to a change in vegetation composition and a decrease in peatland biodiversity. Climate warming will change the competitive balance between bryophytes and between Sphagnum and vascular plants. Climate warming in the Late Pleistocene facilitated the initiation of peatland formation, but most current experiments show an obvious tendency for climate warming to drive many peatlands to regressive succession with a shift in dominance from Sphagnum to vascular plants. This change in vegetation will increase the flux of CH4 and possibly also CO2. The effect of accelerated peat decay as a result of climate warming will vary between types of peatlands. Since climate warming will generally enhance peat respiration more than net primary production, more and more peatlands will become carbon sources rather than carbon sinks, which will aggravate climate warming by positive feedback. Finally, this paper addresses some problems with current manipulative experimental studies on peatland response to climate warming and makes suggestions for further studies. 相似文献
143.
大兴安岭呼中林区虫害与火干扰交互作用的长期模拟 总被引:1,自引:1,他引:0
虫害和林火是森林生态系统的两种主要干扰类型,各种干扰在大时空尺度上存在一定的交互作用.本文采用空间直观景观模型LANDIS模拟虫害和林火在300年内的交互作用.结果表明:虫害干扰降低了细可燃物载量,提高了模拟前期(0~100 a)和中期(100~200 a)的粗可燃物载量,降低了模拟前期和中期的林火频率,不同干扰预案模拟后期(200~300 a)火烧频率的结果比较接近;虫害干扰降低了模拟前期和后期的火烧强度,增加了模拟中期的火烧强度,提高了模拟中期的森林火险等级,降低了模拟前期和后期的火险等级.人类灭火可增加虫害的发生面积,因此建议森林管理部门采取适当的防虫措施,不可只注重灭火,可以采取可燃物去除和计划火烧等方式管理林火,促进森林生态系统的可持续发展. 相似文献
144.
145.
Chogle A Bu HF Wang X Brown JB Chou PM Tan XD 《Molecular medicine (Cambridge, Mass.)》2011,17(5-6):502-507
Milk fat globule-EGF factor 8 (MFG-E8) has been shown to play an important role in maintaining the integrity of the intestinal mucosa and to accelerate healing of the mucosa in septic mice. Herein, we (a) analyzed the expression of MFG-E8 in the gut of wild-type (WT) C57BL/6 (MFG-E8(+/+)) mice with and without dextran sulfate sodium (DSS)-induced colitis, (b) characterized the pathological changes in intestinal mucosa of MFG-E8(+/+) and MFG-E8(-/-) mice with DSS-induced colitis and (c) examined the therapeutic role of MFG-E8 in inflammatory bowel disease by using DSS-induced colitis model. Our data documented that there was an increase in colonic and rectal MFG-E8 expression in MFG-E8(+/+) mice during the development of DSS colitis. MFG-E8 levels in both tissues decreased to below baseline during the recovery phase in mice with colitis. Changes in MFG-E8 gene expression correlated to the levels of inflammatory response and crypt-epithelial injury in both colonic and rectal mucosa in MFG-E8(+/+) mice. MFG-E8(-/-)mice developed more severe crypt-epithelial injury than MFG-E8(+/+) mice during exposure to DSS with delayed healing of intestinal epithelium during the recovery phase of DSS colitis. Administration of MFG-E8 during the recovery phase ameliorated colitis and promoted mucosal repair in both MFG-E8(-/-) and MFG-E8(+/+) mice, indicating that lack of MFG-E8 causes increased susceptibility to colitis and delayed mucosal healing. These data suggest that MGF-E8 is an essential protective factor for gut epithelial homeostasis, and exogenous administration of MFG-E8 may represent a novel therapeutic target in inflammatory bowel disease. 相似文献
146.
Biological invasions are impacting biota worldwide, and explaining why some taxa tend to become invasive is of major scientific interest. North American crayfish species, particularly of the family Cambaridae, are prominent invaders in freshwaters, defying the "tens rule" which states that only a minority of species introduced to new regions become established, and only a minority of those become invasive and pests. So far, success of cambarid invaders has largely been attributed to rapid maturation, high reproductive output, aggressiveness, and tolerance to pollution. We provide experimental evidence that females of one cambarid species particularly widespread in Europe, the spiny-cheek crayfish Orconectes limosus, are capable of facultative parthenogenesis. Such reproductive mode has never before been recognized in decapods, the most diverse crustacean order. As shown by analysis of seven microsatellite loci, crayfish females kept physically separated from males produced genetically homogeneous offspring identical with maternal individuals; this suggests they reproduced by apomixis, unlike those females which mated with males and had a diverse offspring. Further research is needed to clarify what environmental conditions are necessary for a switch to parthenogenesis in O. limosus, and what role it plays in natural crayfish populations. However, if such reproductive plasticity is present in other cambarid crayfish species, it may contribute to the overwhelming invasive success of this group. 相似文献
147.
Inhalational anthrax is caused by B. anthracis, a virulent sporeforming bacterium which secretes anthrax toxins consisting of protective antigen (PA), lethal factor (LF) and edema factor (EF). LF is a Zn-dependent metalloprotease and is the main determinant in the pathogenesis of anthrax. Here we report the identification of a lead small-molecule inhibitor of anthrax lethal factor by screening an available synthetic small-molecule inhibitor library using fluorescence-based high-throughput screening (HTS) approach. Seven small molecules were found to have inhibitory effect against LF activity, among which SM157 had the highest inhibitory activity. All theses small molecule inhibitors inhibited LF in a noncompetitive inhibition mode. SM157 and SM167 are from the same family, both having an identical group complex, which is predicted to insert into S1' pocket of LF. More potent small-molecule inhibitors could be developed by modifying SM157 based on this identical group complex. 相似文献
148.
Several conserved neutralizing epitopes have been identified in the HIV Env protein and among these, the MPER of gp41 has received great attention and is widely recognized as a promising target. However, little success has been achieved in eliciting MPER-specific HIV neutralizing antibodies by a number of different vaccine strategies. We investigated the ability of HA/gp41 chimeric protein-based vaccines, which were designed to enhance the exposure of the MPER in its native conformation, to induce MPER-specific HIV neutralizing antibodies. In characterization of the HA/gp41 chimeric protein, we found that by mutating an unpaired Cys residue (Cys-14) in its HA1 subunit to a Ser residue, the modified chimeric protein HA-C14S/gp41 showed increased reactivity to a conformation-sensitive monoclonal antibody against HA and formed more stable trimers in VLPs. On the other hand, HA-C14S/gp41 and HA/gp41 chimeric proteins expressed on the cell surfaces exhibited similar reactivity to monoclonal antibodies 2F5 and 4E10. Immunization of guinea pigs using the HA-C14S/gp41 DNA or VLP vaccines induced antibodies against the HIV gp41 as well as to a peptide corresponding to a segment of MPER at higher levels than immunization by standard HIV VLPs. Further, sera from vaccinated guinea pigs were found to exhibit HIV neutralizing activities. Moreover, sera from guinea pigs vaccinated by HA-C14S/gp41 DNA and VLP vaccines but not the standard HIV VLPs, were found to neutralize HIV pseudovirions containing a SIV-4E10 chimeric Env protein. The virus neutralization could be blocked by a MPER-specific peptide, thus demonstrating induction of MPER-specific HIV neutralizing antibodies by this novel vaccine strategy. These results show that induction of MPER-specific HIV neutralizing antibodies can be achieved through a rationally designed vaccine strategy. 相似文献
149.
Vrabec R Vatavuk Z Pavlović D Sesar A Cala S Mandić K Bućan K 《Collegium antropologicum》2005,29(Z1):95-98
The aim of this paper was to evaluate the ocular findings in patients with chronic renal failure (CRF) undergoing haemodialysis (HD). In 64 patients undergoing haemodialysis (30 female and 34 male), aged 24-83 years (mean 58 years) on haemodialysis 1-213 months (mean 47 months) complete ocular examination were performed: visual acuity (VA), intraocular pressure (IOP), biomicroscopic examination and fundoscopy. On right eye sixty-nine percent of patents had VA 0.6 or better, and on left eye 84% of patients had VA 0.6 or better. Mean IOP before dialysis was 15 mmHg and after dialysis was 14 mmHg. In 9 patients (14%) we found corneo-conjunctival calcium deposits. No correlation of ocular calcification and parathyroid hormone (PTH) level or calcium and phosphate product were observed. 39 (60%) patients had cataract. Hypertensive vascular changes were seen in 44 (68%) patients and in 6 (7%) patients age-related macular degeneration. Seven patients had diabetes mellitus and in 5 diabetic retinopathy was observed. Patients with CRF or who are receiving HD represent unique group of patients. Pathologic change could be found in many tissue and organs, therefore we suggest ocular examination more frequently in dialysis patients. 相似文献
150.
van Kerkhof P Lee J McCormick L Tetrault E Lu W Schoenfish M Oorschot V Strous GJ Klumperman J Bu G 《The EMBO journal》2005,24(16):2851-2861
The low-density lipoprotein (LDL) receptor-related protein (LRP) is a multiligand endocytic receptor and a member of the LDL receptor family. Here we show that sorting nexin 17 (Snx 17) is part of the cellular sorting machinery that regulates cell surface levels of LRP by promoting its recycling. While the phox (PX) domain of Snx 17 interacts with phosphatidylinositol-3-phosphate for membrane association, the FERM domain and the carboxyl-terminal region participate in LRP binding. Immunoelectron microscopy shows that the membrane-bound fraction of Snx 17 is localized to the limiting membrane and recycling tubules of early endosomes. The NPxY motif, proximal to the plasma membrane in the LRP cytoplasmic tail, is identified as the Snx 17-binding motif. Functional mutation of this motif did not interfere with LRP endocytosis, but decreased LRP recycling from endosomes, resulting in increased lysosomal degradation. Similar effects are found after knockdown of endogenous Snx 17 expression by short interfering RNA. We conclude that Snx 17 binds to a motif in the LRP tail distinct from the endocytosis signals and promotes LRP sorting to the recycling pathway in the early endosomes. 相似文献