Multiple flavonoid-binding sites within multidrug resistance protein MRP1

Recombinant nucleotide-binding domains (NBDs) from human multidrug resistance protein MRP1 were overexpressed in bacteria and purified to measure their direct interaction with high-affinity flavonoids, and to evaluate a potential correlation with inhibition of MRP1-mediated transport activity and reversion of cellular multidrug resistance. Among different classes of flavonoids, dehydrosilybin exhibited the highest affinity for both NBDs, the binding to N-terminal NBD1 being prevented by ATP. Dehydrosilybin increased vanadate-induced 8-N₃-[-³²P]ADP trapping, indicating stimulation of ATPase activity. In contrast, dehydrosilybin strongly inhibited leukotriene C₄ (LTC₄) transport by membrane vesicles from MRP1-transfected cells, independently of reduced glutathione, and chemosensitized cell growth to vincristine. Hydrophobic C-isoprenylation of dehydrosilybin increased the binding affinity for NBD1, but outsite the ATP site, lowered the increase in vanadate-induced 8-N₃-[-³²P]ADP trapping, weakened inhibition of LTC₄ transport which became glutathione dependent, and induced some cross-resistance. The overall results indicate multiple binding sites for dehydrosilybin and its derivatives, on both cytosolic and transmembrane domains of MRP1.Received 1 May 2003; received after revision 18 June 2003; accepted 24 June 2003     

温度周期对诱发亚洲玉米螟滞育的影响

在光周期不变的情况下，使光周期中的暗时相与温度周期中的冷时相相同步时，亚洲玉米螟Ｏｓｔｒｉｎｉａｆｕｒｎａｃａｌｉｓ（Ｇｕｅｎｅｅ＇）（Ｌｅｐｉｄｏｐｔｅｒａ：Ｐｙｒａｌｉｄａｅ）的滞育率就高；而当光周期中的暗时相与温度周期中的温时相相同步时，不足育的发生率就低。     

Purification of breast cancer resistance protein ABCG2 and role of arginine-482

Human ABCG2 was efficiently overexpressed in insect cell membranes, solubilized with 3-[(3-cholamidopropyl)dimethyl ammonio]-1-propanesulfonate, and purified through N-terminal hexahistidine tag. Its functionality was assessed by high vanadate-sensitive ATPase activity, and nucleotide-binding capacity. Interestingly, the R482T point mutation increased both maximal hydrolysis rate and affinity for MgATP, and lowered sensitivity to vanadate inhibition. Direct nucleotide binding, as monitored by quenching of intrinsic fluorescence, indicated a mutation-related preference for ATP over ADP. The R482T mutation only produced a limited change, if any, on the binding of drug substrates, indicating that methotrexate, on the one hand, and rhodamine 123 or doxorubicin, on the other hand, bound similarly to wild-type and mutant transporters whether or not they were subject to cellular transport. In addition, the characteristic inhibitors GF120918 and 6-prenylchrysin, which alter mitoxantrone efflux much better for wild-type than mutant ABCG2, bound similarly to purified ABCG2, while the highly-potent Ko143 bound in the nanomolar range also effective in inhibition of drug transport. All results indicate that the role of the arginine-482 mutation on substrate drug transport and inhibitor efficiency is not mediated by changes in drug binding. Received 10 April 2006; received after revision 22 May 2006; accepted 12 June 2006 A. Pozza and J. M. Perez-Victoria contributed equally to this work     

Atomic model of human cystic fibrosis transmembrane conductance regulator: Membrane-spanning domains and coupling interfaces

We describe herein an atomic model of the outward-facing three-dimensional structure of the membrane-spanning domains (MSDs) and nucleotide-binding domains (NBDs) of human cystic fibrosis transmembrane conductance regulator (CFTR), based on the experimental structure of the bacterial transporter Sav1866. This model, which is in agreement with previous experimental data, highlights the role of some residues located in the transmembrane passages and directly involved in substrate translocation and of some residues within the intracellular loops (ICL1-ICL4) making MSD/NBD contacts. In particular, our model reveals that D173 ICL1 and N965 ICL3 likely interact with the bound nucleotide and that an intricate H-bond network (involving especially the ICL4 R1070 and the main chain of NBD1 F508) may stabilize the interface between MSD2 and the NBD1F508 region. These observations allow new insights into the ATP-binding sites asymmetry and into the molecular consequences of the F508 deletion, which is the most common cystic fibrosis mutation.     

基于聚类算法的电力制造业ERP数据分类

鉴于传统制造业企业仓储分类方法分类边界不明确、难以适应现代企业信息化发展趋势的问题,提出了基于聚类算法的ABC库存分类算法,提升了传统库存分类模型的分类精度和效率。以某电力制造业企业的库存产品数据为研究对象,结合聚类算法与ABC分类法提出了适用于实际研究场景的评价函数,并给出了新的基于k-means 算法的ABC分类法。采用该分类模型对库存环网柜产品进行分类,并基于ERP系统中存储的产品数据将库存环网柜产品分为A、B、C三类,根据分类结果对不同类别的环网柜产品采取不同的库存控制策略。研究结果表明,将数据挖掘算法应用于库存管理实现了企业库存管理决策的科学化和智能化。     

性激素受体在大肠癌中的表达及临床意义

为研究性激素 (SR)在大肠癌及正常大肠组织中的表达情况及临床意义 ,采用免疫组化ABC法对 80例大肠癌、10例正常大肠粘膜进行雌激素受体 (ER)、孕激素受体 (PR)及雄激素受体 (AR)指标的检测 .80例大肠癌中ER、PR、AR的阳性率分别为 80 %、75 %、40 % ,正常大肠粘膜中三项指标表达很低 ,甚至无表达 .二者间有显著差异 (P <0 0 1) ,大肠癌中SR的高度表达说明其生理学行为与性激素有关 .因此对SR阳性大肠癌病人进行内分泌治疗可能是除手术、化疗及免疫治疗外一种新的治疗方法 ,并为早期诊断大肠癌及判定预后、指导临床治疗提供依据     

钦州湾外湾东北部近岸区域大型底栖动物群落特征

【目的】研究钦州湾外湾东北部近岸区域大型底栖动物群落结构,判断其受环境干扰的程度,并分析其多样性指数与环境因子之间的相关性。【方法】2010年6月和12月,采用拖网法进行底栖生物样品采集。使用PRIMER和SPSS软件对调查所得数据进行分析。【结果】共采集到大型底栖动物种类148种,其中软体动物57种,节肢动物42种,底栖鱼类20种,其他动物共29种。【结论】调查区域大型底栖动物夏季可划分为3个群落,冬季可划分为2个群落。夏季多样性好于冬季,但冬季各站之间多样性变化范围较小。有少数站位受到中度干扰,个别站位受到稍微干扰。夏季大型底栖动物种类数与悬浮物含量呈显著负相关,生物量、丰度、种类数均与沉积物中的油类含量呈显著负相关,均匀度与沉积物中值粒径呈显著负相关,丰度与沉积物的中值粒径呈显著正相关,Shannon-Wiener指数与沉积物中的粘土含量呈显著正相关;冬季种类数与水体中的盐度、pH值、溶解氧呈显著正相关,与水质中的油类含量呈显著负相关,丰富度指数与溶解氧呈显著正相关。     

基于一种改进人工蜂群算法的认知无线电频谱分配

摘要：为提高人工蜂群算法的开采能力和收敛速度,在人工蜂群算法中引入动态加速因子和种群自适应比例因子,得到一种新的动态加速种群自适应人工蜂群算法. 将认知无线电TV频段频谱分配模型中的分配矩阵与动态加速种群自适应人工蜂群算法中的可行解相对应,分别以网络效益最大化和比例公平性为目标函数,实现了空闲TV频段频谱的合理分配. 仿真结果表明,与其他算法相比,该算法能更好地实现网络效益的最大化以及用户之间的比例公平性.     

具有禁忌策略的蜂群算法评定圆柱度误差

针对最小二乘法评定误差较大,遗传、蚁群等仿生算法设置参数较多、收敛速度较慢的问题,结合圆柱度误差评定的特点,提出采用蜂群算法,来实现圆柱度误差的最小区域法评定.该算法借鉴了禁忌搜索算法的禁忌策略,用禁忌表存储局部最优解,增强对参数Limit的控制作用,提高全局搜索能力.实验研究结果表明,该方法能收敛到全局最优解,并且计算结果稳定,收敛速度很快,平均运算时间在1.2 S左右,适用于三坐标测量机等实时处理系统.