定量分析调控人类免疫缺陷病毒潜伏与激活的动力学机制

目的 治疗艾滋病最大的障碍在于无法根除人类免疫缺陷病毒（HIV）潜伏于人体细胞所形成的病毒存储库。构建描述病毒存储库建立分子机制的动力学模型需考虑生物体内的噪声环境和多重影响因素,本文通过一种全新的动力学结构分解方法将随机微分方程的确定性部分与随机性噪声分开,从而在仅需分析常微分方程不动点的情况下即可判断不同药物靶点的作用效果。方法 使用连续的随机微分方程构建了HIV转录过程的动力学模型,简化了描述系统所需方程的维度,增大了模型的可探索空间,在此基础上,通过计算得到的势能函数和概率分布函数直观表示病毒潜伏与激活的不同表达状态以及它们之间的关系。结果 定量分析了不同动力学参数对系统稳态和势函数的影响程度,分别得到了系统处于双稳态和单稳态时的参数范围,并将不同因素对动力系统分岔的影响程度与生物学实验结果对比,验证了本工作的理论基础。结论 本文突破了以往离散、随机的方法,可以通过常微分方程定量分析HIV转录调控的动力学机制,有利于推广到处理高维情况,进一步研究艾滋病在生物体内的发生发展,从而指导设计实验寻找临床上的治疗方案。     

研究报告: 电化学适配体传感器用于乳酸快速检测的研究

目的 构建用于检测L-乳酸的新型电化学适配体传感器。方法 基于金钯-掺氮多壁碳纳米管纳米复合材料（Au/Pd-N-MWCNTs）修饰的玻碳电极,通过三螺旋分子开关（triple-helix molecular switch,THMS）触发具有RNA剪切活性的Pb²⁺辅助的脱氧核酶（DNAzyme）对电极表面固定化信号探针的循环剪切效应,实现L-乳酸的超灵敏电化学检测。采用差分脉冲伏安法（DPV）记录电流信号变化。结果 信号探针浓度4 μmol/L、Pb²⁺浓度4 μmol/L、DNAzyme剪切孵育时间60 min为传感器最优测试条件。在最优实验条件下,该L-乳酸传感器线性范围为1~20 mmol/L,检出限为0.51 mmol/L。此外,该适配体传感器具有优异的稳定性（RSD=4.56%）、重现性（RSD=2.80%）和选择性。在人血清样本中检测L-乳酸时回收率为105.60%~110.80%,RSD为2.35%~4.56%,与传统方法具有较好的一致性。结论 该适配体传感器能实现L-乳酸的超灵敏检测,在生物医学诊断、食品工业和环境监测等领域具有广泛的应用前景。     

Loss of LRP1 promotes acquisition of contractile-myofibroblast phenotype and release of active TGF-β1 from ECM stores

In healing tissue, fibroblasts differentiate to α-smooth muscle actin (SMA)-expressing contractile-myofibroblasts, which pull the wound edges together ensuring proper tissue repair. Uncontrolled expansion of the myofibroblast population may, however, lead to excessive tissue scarring and finally to organ dysfunction. Here, we demonstrate that the loss of low-density lipoprotein receptor-related protein (LRP) 1 overactivates the JNK1/2-c-Jun-Fra-2 signaling pathway leading to the induction of α-SMA and periostin expression in human lung fibroblasts (hLF). These changes are accompanied by increased contractility of the cells and the integrin- and protease-dependent release of active transforming growth factor (TGF)-β1 from the extracellular matrix (ECM) stores. Liberation of active TGF-β1 from the ECM further enhances α-SMA and periostin expression thus accelerating the phenotypic switch of hLF. Global gene expression profiling of LRP1-depleted hLF revealed that the loss of LRP1 affects cytoskeleton reorganization, cell-ECM contacts, and ECM production. In line with these findings, fibrotic changes in the skin and lung of Fra-2 transgenic mice were associated with LRP1 depletion and c-Jun overexpression. Altogether, our results suggest that dysregulation of LRP1 expression in fibroblasts in healing tissue may lead to the unrestrained expansion of contractile myofibroblasts and thereby to fibrosis development. Further studies identifying molecules, which regulate LRP1 expression, may provide new therapeutic options for largely untreatable human fibrotic diseases.     

Infestation of commercial bumblebee (Bombus impatiens) field colonies by small hive beetles (Aethina tumida)

Abstract.  1. The small hive beetle, Aethina tumida , is a parasite of honeybee ( Apis mellifera ) colonies native to sub-Saharan Africa and has become an invasive species. In North America the beetle is now sympatric with bumblebees, Bombus , not occurring in its native range. Laboratory studies have shown that small hive beetles can reproduce in bumblebee colonies but it was not known whether infestations occur in the field.
2. For the first time, infestation of bumblebee colonies by small hive beetles was investigated in the field. Commercial Bombus impatiens colonies ( n = 10) were installed in proximity to infested apiaries. Within 8 weeks, all colonies that were alive in the 5-week observation period ( n = 9) became naturally infested with adult small hive beetles and successful small hive beetle reproduction occurred in five colonies.
3. In four-square choice tests, the beetles were attracted to both adult bumblebee workers and pollen from bumblebee nests, suggesting that these odours may serve as cues for host finding.
4. The data indicate that bumblebee colonies may serve as alternative hosts for small hive beetles in the field. To foster the conservation of these essential native pollinators, investigations on the actual impact of small hive beetles on wild bumblebee populations are suggested.     

Interactions in pseudorotoxanes based on crown ether-secondary ammonium motifs. A theoretical study

A theoretical analysis of the nature of the interactions in dibenzo[24]crown-8 (DB24C8)-n-dibutylammonium (DBM)—pseudorotaxane complex at the MP2 and DFT levels shows that the main contribution to the binding energy is the electrostatic interaction with moderate (20–25%) correlation stabilization. The total binding energy in the DB24C8-DBM complex represents a sum of the binding energies of two NH–O and one CH–O hydrogen bonds and the latter constitutes about 25% of the total interaction energy, giving the total binding energy of −41.2 kcal mol⁻¹ at the BHandHLYP/6-311++G** level. Deprotonation of the DB24C8-DBM complex reduces the binding energy by some 50 kcal mol⁻¹, giving metastable complexes DB24C8-DBA-1 or DB24C8-DBA-2, which will dissociate to give free crown ether and n-dibutylamine because of the strong exchange repulsion that prevails in neutral complexes. Figure Formation of DB24C8-DBM pseudorotoxane complex