NFKB1 promoter variation implicates shear-induced NOS3 gene expression and endothelial function in prehypertensives and stage I hypertensives

In endothelial cells, NF-kappaB is an important intracellular signaling molecule by which changes in wall shear stress are transduced into the nucleus to initiate downstream endothelial nitric oxide synthase (NOS3) gene expression. We investigated whether NF-kappa light-chain gene enhancer in B cells 1 (NFKB1) promoter polymorphism ((-94)NFKB1 I/D, where I is the insertion allele and D is the deletion allele) was associated with 1) NOS3 gene expression in endothelial cells under physiological levels of unidirectional laminar shear stress (LSS) and 2) endothelial function in prehypertensive and stage I hypertensive individuals before and after a 6-mo supervised endurance exercise intervention. Competitive EMSAs revealed that proteins present in the nuclei of endothelial cells preferentially bound to the I allele NFKB1 promoter compared with the D allele. Reporter gene assays showed that the I allele promoter had significantly higher activity than the D allele. In agreement with these observations, homozygous II genotype cells had higher p50 expression levels than homozygous DD genotype cells. Cells with the homozygous II genotype showed a greater increase in NOS3 protein expression than did homozygous DD genotype cells under LSS. Functional experiments on volunteers confirmed higher baseline reactive hyperemic forearm blood flow, and, furthermore, the subgroup analysis revealed that DD homozygotes were significantly less prevalent in the exercise responder group compared with II and ID genotypes. We conclude that the (-94)NFKB1 I/D promoter variation contributes to the modulation of vascular function and adaptability to exercise-induced flow shear stress, most likely due to differences in NFKB1 gene transactivity.     

防风体细胞胚发生发育中的淀粉体和多糖动态

以防风体细胞胚的发生体系为材料,通过半薄切片技术研究了培养物中淀粉体的组织化学定位,并采用分光光度法测定了不同培养阶段的多糖含量.结果发现在胚性细胞内积累了大量的淀粉体;含4%蔗糖的培养基中的胚性愈伤组织阶段多糖含量最高.研究表明糖类物质的活跃代谢为胚性细胞的分化和发育直接提供了物质和能源;大量淀粉体的存在可作为胚性细胞分化的标记.     

血管紧张素转换酶抑制剂和醛固酮受体阻断剂对钙超载大鼠心功能的影响

目的:观察血管紧张素转换酶抑制剂(ACEI)和醛固酮(ALDO)受体阻断剂(spironolactone,安体舒通)对钙超载大鼠心功能的影响,以探讨钙超载引起心功能降低和心肌损伤的机制。方法:维生素D3加尼古丁诱导心肌钙超载,放射免疫法测定心肌组织AngⅡ和ALDO含量,Powerlab仪测定心功能,原子吸收测定心肌和血管钙含量,生化法测定心肌MDA和conjugated diene变化,自动生化分析仪测定血浆LDH和CPK含量。结果:心肌钙超载后,心肌和血管钙含量较对照组分别增加3.2和5.8倍,LVdp/dtmax和LVdp/dtmin分别降低27%和34%,LVESP和LVEDP增加42%和32%;心肌MDA和conjugated diene增加22%和68%;血浆LDH和CPK增加4.5和3.1倍(均P<0.01)。运用ACEI和ALDO受体阻断剂可缓解上述指标变化,与钙超载组相比,心肌钙含量分别低44%和39%,主动脉钙含量也低57%和34%,MDA低20%和30%,conjugated diene低44%和35%,LDH、CPK分别减少28%和34%、20%和27%(均P<0.01)。结论:心肌钙超载可以导致心功能下降和心肌损伤,运用ACEI和ALDO受体阻断剂可以减轻心肌钙超载和改善心功能,心肌损伤程度减轻。     

黄瑞木果实红色素的分离及其化学结构研究

采用纸层析、紫外-可见光谱、红外光谱和液-质联用等技术对福建野生黄瑞木〔Adinandra millettii(Hook. et Arn.)Benth.〕果实红色素进行了分析研究。结果表明,该红色素主要含有矢车菊素-3-芸香糖苷(cyanidin-3-rutinoside)和矢车菊素-3-葡萄糖苷(cyanidin-3-glucoside)2种花色苷,呈鲜艳的红色,可作为天然保健食品的色素添加剂加以推广应用。     

水淹胁迫下10个树种某些生理指标的变化及其耐水淹能力的比较

以游离脯氨酸和丙二醛(MDA)含量及相对电导率为指标,比较了水淹条件下10个树种的耐水淹能力。结果表明,水淹胁迫下,不同树种的相对电导率及丙二醛含量均呈上升趋势,而游离脯氨酸含量的变化则有显著差异。根据生理指标的变化可以看出,黄连木(Pistacia chinensis Bunge)和石楠(Photinia serrulata Lindl.)的耐水淹能力较弱,耐水淹时间仅为5至10 d;蓝果树(Nyssa sinensis Oliv.)、薄壳山核桃〔Carya illinoensis(Wangenh.)Koch〕、榉树(Zelkova schneideriana Hand.-Mazz.)和一球悬铃木(Platanus occidentalis L.)具有一定的耐水淹能力,耐水淹时间约为25 d;乌桕〔Sapium sebiferum(L.) Roxb.〕和白蜡(Fraxinus chinensis Roxb.)的耐水淹能力较强,耐水淹时间超过45 d;墨西哥落羽杉(Taxodium macronatum Ten.)和花叶杞柳(Salixintegra‘Hakuro Nishiki’)的耐水淹能力最强,受水淹的60 d内无受害现象。     

一氧化氮在炎性疼痛中的作用

一氧化氮（nitric oxide,NO）是细胞内重要的信使分子和神经递质,它参与多种生命活动,包括炎性疼痛.NO对炎性疼痛的发展和维持起到了重要的作用.研究NO在疼痛中所起到的作用及其机制有利于阐明痛觉生理和发现疼痛治疗的新手段.目前研究表明,脊髓水平NO参与炎性疼痛调制的可能机制主要有NO/cGMP途径、参与调控即刻早期基因、与其他神经递质的协同作用.另外研究表明,3种类型的一氧化氮合酶（nitric oxide synthases,NOS）在炎性疼痛过程中被激活或者有不同程度的增强表达.     

Small conformationally restricted piperidine N-arylsulfonamides as orally active gamma-secretase inhibitors

The design and development of a new class of small 2,6-disubstituted piperidine N-arylsulfonamide gamma-secretase inhibitors is reported. Lowering molecular weight including the use of conformational constraint led to compounds with less CYP 3A4 liability compared to early leads. Compounds active orally in lowering Abeta levels in Tg CRND8 mice were identified as potential treatments for Alzheimer's disease.     

Identification and synthesis of major metabolites of Vasopressin V2-receptor agonist WAY-151932, and antagonist, Lixivaptan

Small molecule agonists and antagonists of the V(2)-vasopressin receptor have been discovered and have undergone clinical trials. In conjunction with these discovery programs, the synthesis and biological testing of various metabolites associated with these clinical targets were actively pursued. We now report the results of our synthetic efforts and the corresponding biological data generated for several of the metabolites of WAY-151932 and CL-347985 (Lixivaptan).     

Self-assembly of coiled-coil tetramers in the 1.40 A structure of a leucine-zipper mutant

The hydrophobic core of the GCN4 leucine-zipper dimerization domain is formed by a parallel helical association between nonpolar side chains at the a and d positions of the heptad repeat. Here we report a self-assembling coiled-coil array formed by the GCN4-pAe peptide that differs from the wild-type GCN4 leucine zipper by alanine substitutions at three charged e positions. GCN4-pAe is incompletely folded in normal solution conditions yet self-assembles into an antiparallel tetraplex in crystals by formation of unanticipated hydrophobic seams linking the last two heptads of two parallel double-stranded coiled coils. The GCN4-pAe tetramers in the lattice associate laterally through the identical interactions to those in the intramolecular dimer-dimer interface. The van der Waals packing interaction in the solid state controls extended supramolecular assembly of the protein, providing an unusual atomic scale view of a mesostructure.     

Cholera toxin B protein in transgenic tomato fruit induces systemic immune response in mice

Cholera toxin B (CTB) subunit is a well-characterized antigen against cholera. Transgenic plants can offer an inexpensive and safe source of edible CTB vaccine and may be one of the best candidates for the production of plant vaccines. The present study aimed to develop transgenic tomato expressing CTB protein, especially in the ripening tomato fruit under the control of the tomato fruit-specific E8 promoter by using Agrobacterium-mediated transformation. Transgenic plants were selected using PCR and Southern blot analysis. Exogenous protein extracted from leaf, stem, and fruit tissues of transgenic plants was detected by ELISA and Western blot analysis, showing specific expression in the ripening fruit, with the highest amount of CTB protein being 0.081% of total soluble protein. Gavage of mice with ripe transgenic tomato fruits induced both serum and mucosal CTB specific antibodies. These results demonstrate the immunogenicity of the CTB protein in transgenic tomato and provide a considerable basis for exploring the utilization of CTB in the development of tomato-based edible vaccine against cholera. The rCTB antigen resulted in much lower antibody titers than an equal amount of exgenous CTB in trangenic fruits, suggesting the protective effect of the fibrous tissue of the fruit to the exogenous CTB protein against the degradation of protease in the digestive tracts of mice. Xiao-Ling Jiang and Zhu-Mei He contributed equally to this work.