Docking and molecular dynamics studies of peripheral site ligand–oximes as reactivators of sarin-inhibited human acetylcholinesterase

In the present work, we performed docking and molecular dynamics simulations studies on two groups of long-tailored oximes designed as peripheral site binders of acetylcholinesterase (AChE) and potential penetrators on the blood brain barrier. Our studies permitted to determine how the tails anchor in the peripheral site of sarin-inhibited human AChE, and which aminoacids are important to their stabilization. Also the energy values obtained in the docking studies corroborated quite well with the experimental results obtained before for these oximes.     

The response of phytoplankton community to anthropogenic pressure gradient in the coastal waters of the eastern Adriatic Sea

In order to test the response of phytoplankton to anthropogenic pressure, data of chlorophyll a concentration, phytoplankton abundance, and composition are analyzed in relation to anthropogenic pressure gradient and environmental variables such as temperature, salinity and nutrients. Investigated sites encompassed wide tropic range according to a preliminary determination of anthropogenic pressure, quantified through the LUSI index. Statistical analyses indicated nitrates and silicates as proxies of freshwater influence, and phytoplankton single metrics such as concentrations of chlorophyll a and abundances as indicators of anthropogenic pressure. Boundary values for different water quality classes for coastal waters under indirect freshwater influence (Type II) are obtained according to gradient between concentration of chlorophyll a and pressure index (LUSI), which empirically fit to exponential equation. The response of phytoplankton diversity was not linear, as the highest diversity was observed in the area with intermediate disturbance level. CCA analysis identified Skeletonema marinoii, Scrippsiella trochoidea, Guinardia flaccida, Leptocylindrus spp., Prorocentrum spp., Proboscia alata, Eutreptiella spp., and Pseudonitzschia spp. as local eutrophication indicators, whose abundances increased with nutrients loads.     

D-Cycloserine: Agonist turned antagonist

Summary D-Cycloserine can enhance activation of the NMDA receptor complex and could enhance the induction of long-term potentiation (LTP). In animals and humans, D-cycloserine can enhance performance in learning and memory tasks. This enhancing effect can disappear during repeated administration. The enhancing effects are also lost when higher doses are used, and replaced by behavioral and biochemical effects like those produced by NMDA antagonists. It has been reported that NMDA agonists, applied before or after tetanic stimulation, can block the induction of LTP. This may be the result of feedback inhibition of second messenger pathways stimulated by receptor activation. This may explain the antagonist-like effects of glycine partial agonists like D-cycloserine. In clinical trials of D-cycloserine in age-associated memory impairment (AAMI) and Alzheimer's disease, chronic treatment provided few positive effects on learning and memory. This may be due to inhibition of second messenger pathways following chronic stimulation of the receptor complex.     

The significance of mycotoxins in the framework of assessing workplace related risks

Mycotoxins are fungal metabolite which may in some cases exhibit a high health hazard potential. Mycotoxins can show carcinogenic, mutagenic, toxic, teratogenic or immunotoxic effects. Mycotoxin exposure in the workplace may occur through inhalation and skin contact,e.g. during occupational handling of organic matter such as livestock feed, food products, or waste. Various studies suggest that both acute and chronic effects can occur, depending at least on the exposure level. The magnitude of the potential health risks associated with a respiratory or dermal intake of mycotoxins has largely remained unclear to date. However, according to the directive 2000/54/EC on biological agents and the corresponding German Biological Agents Ordinance, employers are also required to consider the potential hazards posed by toxic effects of biological agents when assessing workplace risks. The aim of this article, therefore, is to present some basis information that should facilitate an evaluation of the significance of mycotoxins in the context of assessing workplace risks. It also provides suggestions for occupational health and safety measures.     

DNA replication stress: Causes,resolution and disease

DNA replication is a fundamental process of the cell that ensures accurate duplication of the genetic information and subsequent transfer to daughter cells. Various pertubations, originating from endogenous or exogenous sources, can interfere with proper progression and completion of the replication process, thus threatening genome integrity. Coordinated regulation of replication and the DNA damage response is therefore fundamental to counteract these challenges and ensure accurate synthesis of the genetic material under conditions of replication stress. In this review, we summarize the main sources of replication stress and the DNA damage signaling pathways that are activated in order to preserve genome integrity during DNA replication. We also discuss the association of replication stress and DNA damage in human disease and future perspectives in the field.     

The impact of hybrids between genetically modified crop plants and their related species: general considerations

Factors influencing the fate and impact of hybrids between crop plants and their related species operate from the early zygote, through to plant establishment in different habitats, to their ability to form self-sustaining populations. Many of the classes of genes being introduced by modern methods of genetic modification are similar to those manipulated by conventional plant breeding. In assessing the impact of transgenes in hybrids between crops and related species, therefore, it is important to be informed about the consequences of hybridization between conventionally bred varieties and their relatives. Some transgenes will have novel effects (e.g. production of pharmaceutical substances or certain fatty acids) on plants, and are likely to need specific assessment studies to determine their impact on hybrids. This will be particularly important if there is the possibility of these transgenes becoming established in wild populations. Some recommendations for further research are outlined.     

基于指标自动筛选的新疆开孔河流域生态健康评价

生态健康评价对了解区域生态健康状况和促进区域可持续发展具有重要意义,如何自动筛选出能反映生态系统特性的重要指标,是生态健康定量评估的关键问题。基于压力-状态-响应(PSR,Press-State-Response)框架和生态等级网络框架(EHN,Ecological Hierarchy Network),通过文献调研和因果分析建立要素层与指标层之间的交叉联系,构建了生态健康评价"网状"指标体系;在保证指标体系完备性基础上,通过结合主成分分析和熵权法的候选指标权重的客观计算,基于目标优化理论构建了评价指标的自动筛选模型,并基于中选指标计算了新疆开孔河流域2001—2017年生态健康指数(EHCI,Ecological Health Comprehensive Indexes),分析其空间分异和时间变化特征。结果表明:利用所建立的评价指标自动筛选模型,开孔河流域生态健康评价指标由31个候选指标自动筛选出了17个中选指标,用54.8%的指标表达了85.98%的信息,中选的17个指标在干旱/半干旱区域有关文献中应用较多,使用频次比例都在20%以上,其中归一化植被指数(NDVI,Normalized Difference Vegetation Index)、年降水量和植被覆盖度(FVC,Fractional Vegetation Coverage)3个指标的使用频次百分比均超过了50%,说明指标自动筛选模型的合理性;开孔河流域空间分布差异显著,总体上西北高、东南低,东南部和中部绿洲区外围生态健康状况较差,西北部河谷地带和中部两大绿洲区生态健康状况较好;17年来,流域生态质量整体趋于改善,显著改善区域占10.26%,远高于显著退化的1.61%,显著改善区域以孔雀河绿洲最为明显。开孔河流域生态健康的总体好转趋势说明区域生态综合治理取得一定成效。     

Geochemical baseline determination and pollution assessment of heavy metals in urban soils of Karachi,Pakistan

Karachi is one of the most populated urban agglomerations in the world. No categorical study has yet discussed the geochemical baseline concentrations of metals in the urban soil of Karachi. The main objectives of this study were to establish geochemical baseline values and to assess the pollution status of different heavy metals. Geochemical baseline concentrations of heavy metals were estimated using the cumulative frequency distribution (CDF) curves. The estimated baseline concentrations of Pb, Cr, Cu, Zn and Fe were 56.23, 12.9, 36.31, 123.03 and 11,776 mg kg⁻¹, respectively. The pollution status of heavy metals in urban soils was evaluated using different quantitative indices (enrichment factor–EF, Geo-accumulation Index–I_geo, and pollution index–PI). Enrichments factors of the selected heavy metals determined by using Fe as a normalizer showed that metal contamination was the product of anthropogenic activities. The urban soils of Karachi were found to have a moderate to moderately severe enrichment with Pb, whereas Cr and Cu has moderate and Zn has minor enrichment. I_geo results indicated moderate soil contamination by Pb at some of the sampling locations. PI for Pb, Cr, Cu and Zn was found in the range of 0.04–3.42, 0.19–1.55, 0.27–2.45 and 0.32–1.57, respectively. Large variations in PI values of Pb revealed that soil in those areas of the city which are influenced by intensive anthropogenic activities have exceptionally high concentrations of Pb. The findings of this study would contribute to the environmental database of the soil of the region and would also facilitate both at the local and the international scales, in a more accurate global environmental monitoring, which will eventually facilitate the development of management and remediation strategies for heavy metal contaminated urban soil.     

城市景观生态风险评估框架与实践——以北京天坛地区为例

当前，城市景观生态风险研究缺少科学合理、方便实用的评估框架。作者基于景观生态风险评估基本范式，明确了城市景观生态服务价值的测算方法，分析了引起生态损害的自然因素和人类活动因素，形成了城市景观生态风险评估的技术框架和参数体系；继而以北京天坛地区为研究区，开展了典型城市景观生态风险的定量评估。结果表明：（1）天坛地区景观生态价值总量约为2.41亿元。区域的历史文化价值最高，教育和美学景观价值紧随其后。（2）城市景观生态受损概率呈现"北高南低"的空间分布格局。生态受损概率的高值区面积占整个区域总面积的22.2%，主要分布在珠市口、磁器口和崇文门附近区域。（3）城市景观生态风险呈现"北低南高"的空间分布格局。高风险区主要分布在天坛公园内的文物建筑周边。本研究提供了一个可参考的城市景观生态风险评估应用框架，对生态风险评估中的不确定性进行了讨论，研究针对天坛案例区的具体结论有助于城市管理者避免潜在的风险。