抗生素与抗菌药物协同作用防控生物膜的研究进展

生物膜(Biofilm)是指微生物为适应周围环境,黏附于介质表面并被其自身分泌的胞外基质包裹而形成的一种复杂的、高度异质的聚合结构。生物膜对宿主防御和药物具有很强的抵御能力,使用单一药物防治往往效果不显著,而利用协同作用将不同抗菌药物的优势联合起来用于生物膜的防控则优势明显。重点阐述了抗生素与抗生素、抗生素与中药、抗生素与噬菌体、抗生素与酶的协同作用研究,以期为生物膜的防控提供新思路。     

The Thr300Ala variant of ATG16L1 is associated with decreased risk of brain metastasis in patients with non-small cell lung cancer

Non-small cell lung cancer (NSCLC) often metastasizes to the brain, but identifying which patients will develop brain metastases (BM) is difficult. Macroautophagy/autophagy is critical for cancer initiation and progression. We hypothesized that genetic variants of autophagy-related genes may affect brain metastases (BM) in NSCLC patients. We genotyped 16 single nucleotide polymorphisms (SNPs) in 7 autophagy-related (ATG) genes (ATG3, ATG5, ATG7, ATG10, ATG12, ATG16L1, and MAP1LC3/LC3) by using DNA from blood samples of 323 NSCLC patients. Further, we evaluated the potential associations of these genes with subsequent BM development. Lung cancer cell lines stably transfected with ATG16L1: rs2241880 (T300A) were established. Mouse models of brain metastasis were developed using cells transfected with ATG16L1–300T or ATG16L1–300A. ATG10: rs10036653 and ATG16L1: rs2241880 were significantly associated with a decreased risk of BM (respective hazard ratios [HRs]=0.596, 95% confidence interval [CI] 0.398–0.894, P = 0.012; and HR = 0. 655, 95% CI 0.438–0.978, P = 0.039, respectively). ATG12: rs26532 was significantly associated with an increased risk of BM (HR=1.644, 95% CI 1.049–2.576, P = 0.030). Invasion and migration assays indicated that transfection with ATG16L1–300T (vs. 300A) stimulated the migration of A549 cells. An in vivo metastasis assay revealed that transfection with ATG16L1–300T (vs. 300A) significantly increased brain metastasis. Our results indicate that genetic variations in autophagy-related genes can predict BM and that genome analysis would facilitate stratification of patients for BM prevention trials.     

中国东北地区非点源污染研究进展

为掌握东北地区非点源污染研究动态和明确研究中存在的问题和不足,对近20年（1991-2008年）东北地区有关非点源污染研究成果进行检索、分类和统计分析,以便更好地进行区域水环境治理和污染防治.东北地区非点源污染研究总体呈增加趋势;研究内容包括水环境污染源调查分析与评价、污染负荷量化、机理探索、模型模拟和污染防治5类;研究对象包括氮、磷、泥沙、农药和重金属;经验方法估算污染负荷较多,机理模型应用成功实例较少;研究性论文中以农业非点源污染较多,城市非点源污染较少;治理措施停留在水土保持措施层面上,缺乏对水土保持措施的优选评价和对最佳管理措施的评价研究.目前,东北地区非点源污染研究处在理论探索阶段,非点源污染是否是主要污染源还存在争议.今后应着力于措施应用、评价和基础数据收集及区域非点源污染物的确定和污染负荷的量化研究;尝试新技术和多领域交叉合作,为区域水环境治理提供科学依据.     

Bear deterrence with scare devices,a non-lethal tool in the use-of-force continuum

Wild animals eating agricultural products and coming close to people's residences are primary causes of human–wildlife conflict worldwide. When carnivores eat anthropogenic foods and cause human safety concerns, it often results in the removal of the animals and public demand for reduced wildlife populations. The use of remote methods, such as scare devices, to deter carnivores has been touted in the literature; however, efficacy evidence remains thin. I test the efficacy of a widely available motion-activated solar alarm lamp to deter grizzly bears (Ursus arctos) from farms in Montana, USA. When scare devices were activated, there was a 46% reduction in the odds bears would access an attractant. For every additional scare device, there was an additional 44% reduction in the odds of a bear getting the food. Additionally, scare devices caused bears to be more vigilant and increase movement behavior. More bears in a group led to loss of deterrence efficacy, and there was no evidence for habituation to the aversive stimuli. This deterrence method was most effective in August and for fungicide-treated wheat. Out of 21 farms, scare devices stopped bears from returning to 11 sites. Overall, scare devices can be a cheap and easy first step to preventing, or resolving, some grizzly bear issues in the use-of-force continuum, which hierarchically organizes conflict responses from non-lethal to more severe.     

An active intracellular device to prevent lethal disease outcomes in virus-infected bacterial cells

Synthetic biology includes an effort to logically control cellular behavior. One long-term goal is to implement medical interventions inside living cells, creating intracellular "disease fighters"; one may imagine a system that detects viral infection and responds to halt the spread of the virus. Here, we explore a system designed to display some of the qualitative features that such disease prevention systems should have, while not claiming that the system itself has any medical application. An intracellular disease prevention mechanism should: lie dormant in the absence of the disease state; detect the onset of a lethal disease pathway; respond to halt or mitigate the disease's effects; and be subject to external deactivation when required. We have created a device that displays these properties, in the highly simplified case of a bacterial viral disease. Our system detects the onset of the lytic phase of bacteriophage lambda in Escherichia coli, responds by preventing this lethal pathway from being followed, and is deactivated by a temperature shift. We have formulated a mathematical model of the engineered system, using parameters obtained from the literature and by local experimental measurement, and shown that the model captures the essential experimental behavior of the system in most parameter regimes.     

Gold from the sea: marine compounds as inhibitors of the hallmarks of cancer

Cancer is one of the most deadly diseases in the world. Although advances in the field of chemo-preventive and therapeutic medicine have been made regularly over the last ten years, the search for novel anticancer treatments continues. In this field, the marine environment, with its rich variety of organisms, is a largely untapped source of novel compounds with potent antitumor activity. Although many reviews of marine anticancer compounds have been published, we focus here on selected marine compounds that act on the six hallmarks of cancer presented namely self-sufficiency in growth signals, insensitivity to anti-growth signals, evasion of apoptosis, limitless replication, sustained angiogenesis and tissue invasion and metastasis.     

Verbascoside — A review of its occurrence, (bio)synthesis and pharmacological significance

Phenylethanoid glycosides are naturally occurring water-soluble compounds with remarkable biological properties that are widely distributed in the plant kingdom. Verbascoside is a phenylethanoid glycoside that was first isolated from mullein but is also found in several other plant species. It has also been produced by in vitro plant culture systems, including genetically transformed roots (so-called ‘hairy roots’). Verbascoside is hydrophilic in nature and possesses pharmacologically beneficial activities for human health, including antioxidant, anti-inflammatory and antineoplastic properties in addition to numerous wound-healing and neuroprotective properties. Recent advances with regard to the distribution, (bio)synthesis and bioproduction of verbascoside are summarised in this review. We also discuss its prominent pharmacological properties and outline future perspectives for its potential application.     

Role of caffeine in DNA recognition of a potential food‐carcinogen benzo[a]pyrene and UVA induced DNA damage

Electron transfer (ET) reactions are important for their implications in both oxidative and reductive DNA damages. The current contribution investigates the efficacy of caffeine, a xanthine alkaloid in preventing UVA radiation induced ET from a carcinogen, benzo[a]pyrene (BP) to DNA by forming stable caffeine–BP complexes. While steady‐state emission and absorption results emphasize the role of caffeine in hosting BP in aqueous medium, the molecular modeling studies propose the energetically favorable structure of caffeine–BP complex. The picosecond‐resolved emission spectroscopic studies precisely explore the caffeine‐mediated inhibition of ET from BP to DNA under UVA radiation. The potential therapeutic activity of caffeine in preventing DNA damage has been ensured by agarose gel electrophoresis. Furthermore, time‐gated fluorescence microscopy has been used to monitor caffeine‐mediated exclusion of BP from various cell lines including squamous epithelial cells, WI‐38 (fibroblast), MCF‐7 (breast cancer) and HeLa (cervical cancer) cells. Our in vitro and ex vivo experimental results provide imperative evidences about the role of caffeine in modified biomolecular recognition of a model carcinogen BP by DNA resulting dissociation of the carcinogen from various cell lines, implicating its potential medicinal applications in the prevention of other toxic organic molecule induced cellular damages. Copyright © 2014 John Wiley & Sons, Ltd.