南美蟛蜞菊中的酚酸类化学成分

为了解南美蟛蜞菊[Wedelia trilobata (L.) Hitchc.]的化学成分, 从其全株中分离得到9 个酚酸类化合物。经光谱分析, 分别鉴定为6-乙酰基-7-羟基-2,3-二甲基色原酮 (1)、七叶内酯 (2)、丁香醛 (3)、5-羟甲基糠醛 (4)、对羟基苯甲酸 (5)、水杨酸 (6)、反式对羟基桂皮酸 (7)、咖啡酸甲酯 (8) 和反式咖啡酸 (9)。化合物1~8 为首次从该植物中分离得到。     

Binding of Ca<Superscript>2+</Superscript> and Zn<Superscript>2+</Superscript> to factor IX/X-binding protein from venom of <Emphasis Type="Italic">Agkistrodon halys</Emphasis> Pallas: stabilization of the structure during GdnHCl-induced and thermally induced denaturation

Coagulation factor IX/coagulation factor X binding protein from the venom of Agkistrodon halys Pallas (AHP IX/X-bp) is a unique coagulation factor IX/coagulation factor X binding protein (IX/X-bp). Among all IX/X-bps identified, only AHP IX/X-bp is a Ca²⁺- and Zn²⁺-binding protein. The binding properties of Ca²⁺ and Zn²⁺ ions binding to apo-AHP IX/X-bp and their effects on the stability of the protein have been investigated by isothermal titration calorimetry, fluorescence spectroscopy, and differential scanning calorimetry. The results show that AHP IX/X-bp has two metal binding sites, one specific for Ca²⁺ with lower affinity for Zn²⁺ and one specific for Zn²⁺ with lower affinity for Ca²⁺. The bindings of Ca²⁺ and Zn²⁺ in the two sites are entropy- and enthalpy-driven. The binding affinity of AHP IX/X-bp for Zn²⁺ is 1 order of magnitude higher than for Ca²⁺ for either high-affinity binding or low-affinity binding, which accounts for the existence of one Zn²⁺ in the purified AHP IX/X-bp. Guanidine hydrochloride (GdnHCl)-induced and thermally induced denaturations of Ca²⁺–Ca²⁺-AHP IX/X-bp, Zn²⁺–Zn²⁺-AHP IX/X-bp, and Ca²⁺–Zn²⁺-AHP IX/X-bp are all a two-state processes with no detectable intermediate state(s), indicating the Ca²⁺/Zn²⁺-induced tight packing of the protein. Ca²⁺ and Zn²⁺ increase the structural stability of AHP IX/X-bp against GdnHCl or thermal denaturation to a similar extent. Although Ca²⁺ and Zn²⁺ have no obvious effect on the secondary structure of AHP IX/X-bp, they induce different rearrangements in local conformation. The Zn²⁺-stabilized specific conformation of AHP IX/X-bp may be helpful to its recognition of the structure of coagulation factor IX. This work suggests that in vitro, Ca²⁺ plays a structural rather than an active role in the anticoagulation of AHP IX/X-bp, whereas Zn²⁺ plays both structural and active roles in the anticoagulation. In blood, Ca²⁺ binds to AHP IX/X-bp and stabilizes its structure, whereas Zn²⁺ cannot bind to AHP IX/X-bp owing to the low Zn²⁺ concentration. AHP IX/X-bp prolongs the clotting time in vivo through its binding only with coagulation factor X/activated coagulation factor X.     

Synthesis and acrosin inhibitory activity of substituted 4-amino-N-(diaminomethylene) benzenesulfonamide derivatives

A series of new substituted 4-amino-N-(diaminomethylene) benzenesulfonamides were synthesized and their in vitro acrosin inhibitory activities were evaluated. Most of the compounds showed potent acrosin inhibitory activities with compounds 4o and 4p being significantly more potent than the control compound N-alpha-tosyl-l-lysyl-chloromethyl-ketone (TLCK). The compounds provide a new scaffold for the development of acrosin inhibitory agents.     

Introgression of chromosome 3Ns from Psathyrostachys huashanica into wheat specifying resistance to stripe rust

Wheat stripe rust is a destructive disease in the cool and humid wheat-growing areas of the world. Finding diverse sources of stripe rust resistance is critical for increasing genetic diversity of resistance for wheat breeding programs. Stripe rust resistance was identified in the alien species Psathyrostachys huashanica, and a wheat-P. huashanica amphiploid line (PHW-SA) with stripe rust resistance was reported previously. In this study, a P. huashanica 3Ns monosomic addition line (PW11) with superior resistance to stripe rust was developed, which was derived from the cross between PHW-SA and wheat J-11. We evaluated the alien introgressions PW11-2, PW11-5 and PW11-8 which were derived from line PW11 for reaction to new Pst race CYR32, and used molecular and cytogenetic tools to characterize these lines. The introgressions were remarkably resistant to CYR32, suggesting that the resistance to stripe rust of the introgressions thus was controlled by gene(s) located on P. huashanica chromosome 3Ns. All derived lines were cytologically stable in term of meiotic chromosome behavior. Two 3Ns chromosomes of P. huashanica were detected in the disomic addition line PW11-2. Chromosomes 1B of substitution line PW11-5 had been replaced by a pair of P. huashanica 3Ns chromosomes. In PW11-8, a small terminal segment from P. huashanica chromosome arm 3NsS was translocated to the terminal region of wheat chromosomes 3BL. Thus, this translocated chromosome is designated T3BL-3NsS. These conclusions were further confirmed by SSR analyses. Two 3Ns-specific markers Xgwm181 and Xgwm161 will be useful to rapidly identify and trace the translocated fragments. These introgressions, which had significant characteristics of resistance to stripe rust, could be utilized as novel germplasms for wheat breeding.     

Matrix recruitment and calcium sequestration for spatial specific otoconia development

Otoconia are bio-crystals anchored to the macular sensory epithelium of the utricle and saccule in the inner ear for motion sensing and bodily balance. Otoconia dislocation, degeneration and ectopic calcification can have detrimental effects on balance and vertigo/dizziness, yet the mechanism underlying otoconia formation is not fully understood. In this study, we show that selected matrix components are recruited to form the crystal matrix and sequester Ca(2+) for spatial specific formation of otoconia. Specifically, otoconin-90 (Oc90) binds otolin through both domains (TH and C1q) of otolin, but full-length otolin shows the strongest interaction. These proteins have much higher expression levels in the utricle and saccule than other inner ear epithelial tissues in mice. In vivo, the presence of Oc90 in wildtype (wt) mice leads to an enrichment of Ca(2+) in the luminal matrices of the utricle and saccule, whereas absence of Oc90 in the null mice leads to drastically reduced matrix-Ca(2+). In vitro, either Oc90 or otolin can increase the propensity of extracellular matrix to calcify in cell culture, and co-expression has a synergistic effect on calcification. Molecular modeling and sequence analysis predict structural features that may underlie the interaction and Ca(2+)-sequestering ability of these proteins. Together, the data provide a mechanism for the otoconial matrix assembly and the role of this matrix in accumulating micro-environmental Ca(2+) for efficient CaCO(3) crystallization, thus uncover a critical process governing spatial specific otoconia formation.     

血清色氨酸、酪氨酸与阿尔茨海默病之间的关系

目的 越来越多的研究表明,代谢物的失衡与阿尔茨海默病（Alzheimer’s disease,AD）之间存在密切的联系。近年来,代谢组学的发展使研究AD周围代谢的特征性变化成为可能。有研究表明,血清色氨酸（tryptophan,Trp）、酪氨酸 （tyrosine,Tyr）水平与轻度认知功能障碍（mild cognitive impairment,MCI）、AD相关。本文拟进一步阐明MCI和AD中色氨酸、酪氨酸水平的特征。方法 将来自阿尔茨海默病神经影像学倡议1（Alzheimer’s Disease Neuroimaging Initiative-1,ADNI-1）队列的765位参与者,分为认知正常（cognitive normal,CN,n=207）、稳定性轻度认知功能障碍（stable mild cognitive impairments,sMCI,n=201）、进行性认知功能障碍（progressive mild cognitive impairments,pMCI,n=171）和AD所致痴呆（n=186）。分析血清色氨酸、酪氨酸对MCI、AD是否具有诊断价值。分析在不同诊断组中,血清色氨酸、酪氨酸分别与脑脊液生物标志物、脑结构、脑代谢及认知功能之间的关系。结果 与CN组相比,sMCI、pMCI、AD组血清色氨酸水平偏低。pMCI组、AD组血清酪氨酸水平显著低于CN组。血清色氨酸对pMCI、AD有诊断价值。血清酪氨酸仅对AD有诊断价值。结论 血清色氨酸、酪氨酸有助于AD的早期诊断。色氨酸、酪氨酸的检测可以为AD的病理学机制研究提供新思路。血清色氨酸、酪氨酸与AD核心标志物、认知功能、脑结构、脑代谢之间均无明显相关性,故血清色氨酸、酪氨酸可能不是AD较好的外周生物标志物。