Intrinsically disordered proteins and biomolecular condensates as drug targets

Intrinsically disordered domains represent attractive therapeutic targets because they play key roles in cancer, as well as in neurodegenerative and infectious diseases. They are, however, considered undruggable because they do not form stable binding pockets for small molecules and, therefore, have not been prioritized in drug discovery. Under physiological solution conditions many biomedically relevant intrinsically disordered proteins undergo phase separation processes leading to the formation of mesoscopic highly dynamic assemblies, generally known as biomolecular condensates that define environments that can be quite different from the solutions surrounding them. In what follows, we review key recent findings in this area and show how biomolecular condensation can offer opportunities for modulating the activities of intrinsically disordered targets.     

Zum 70. Geburtstag Von Professor Dr. Habil. Theo Wetzel

Information on the structure of the population of Phomopsis species in Ukraine, that describes the structure of Phomopsis spp. cultivated on medium: the morfological characteristics, properties of pathogenicity and phytotoxicity. It is described the method of evaluation and selection of unsusceptible forms of sunflower to phomopsis. It includes the optimal infection level, the forms of an inoculum that is effective and optimal way for artificial infection.     

GMP Production of Liposomes—A New Industrial Approach

A new scalable liposome production system is presented, which is based on the ethanol injection technique. The system permits liposome manufacture regardless of production scale, as scale is determined only by free disposable vessel volumes. Once the parameters are defined, an easy scale up can be performed by just changing the process vessels. These vessels are fully sterilizeable and all raw materials are transferred into the sanitized and sterilized system via 0.2 μm filters to guarantee an aseptic production.

Liposome size can be controlled by the local lipid concentration at the injection point depending on process parameters like injection pressure, lipid concentration and injection rate. These defined process parameters are furthermore responsible for highly reproducible results with respect to vesicle diameters and encapsulation rates Compared to other technologies like the film method which is normally followed by size reduction through high pressure homogenization, ultrasonication or extrusion, no mechanical forces are needed to generate homogeneous and narrow distributed liposomes.

Another important advantage of this method is the suitability for the entrapment of many different drug substances such as large hydrophilic proteins by passive encapsulation, small amphiphilic drugs by a one step remote loading technique or membrane association of antigens for vaccination approaches     

武汉城市圈生态网络时空演变及管控分析

武汉城市圈正历经城乡发展转型升级和空间格局调整，生态用地受到一定挤压和切割占用，生态系统功能和景观生态格局受到一定程度的扰动，为贯彻生态文明建设和绿色低碳环保发展的要求，构建以生态廊道、生态节点所组成的整体城市圈的生态网络空间体系。基于形态学空间格局方法和最小累积阻力模型构建4个时期（1990、2000、2010和2018年）的生态网络，利用景观连通性指数和重力模型对源地和廊道进行重要性评价，并提出武汉城市圈生态网络管控的建议。结果表明：（1）1990-2018年，武汉城市圈生态源地总体上表现为逐渐减少的趋势，从16个减少为10个；从空间上看，大型源地斑块并未发生变化，主要分布在研究区南部和北部，林地和水域是生态源地的主要组成景观，但细碎斑块大量减少对区域生态网络具有较大影响。（2）4个时期研究区的生态廊道分别为66条、120条、99条和45条，廊道数量呈现减少的趋势；重要廊道主要分布在研究区北部和东南部，对南北之间的物质和能量交换具有重要作用。（3）景观连通性南北高东西低，中部地区受人类活动干扰综合阻力大，东西部生态节点较少，物种迁移阻碍较大。（4）通过建设踏脚石、修复生态断裂点和廊道差异化保护策略以增强区域景观连通性，促进生物多样性保护，提升生态网络的稳定性。"两型社会"试验区设置后武汉城市圈生态网络水平呈现优化态势，但生态源地之间的相互作用关系还有待增强。研究结果为城市圈未来的国土空间规划和重要生态系统保护和修复工程提供科学参考。     

When corridors collide: Road-related disturbance in commuting bats

As an increasingly dominant feature in the landscape, transportation corridors are becoming a major concern for bats. Although wildlife–vehicle collisions are considered to be a major source of mortality, other negative implications of roads on bat populations are just now being realized. Recent studies have revealed that bats, like many other wildlife species, will avoid roads rather than cross them. The consequence is that roads act as barriers or filters to movement, restricting bats from accessing critical resources. Our objective was to assess specific features along the commuting route, road, or surrounding landscape (alone or in combination) that exacerbated or alleviated the likelihood of a commuting bat exhibiting an avoidance behavior in response to an approaching vehicle. At 5 frequently used commuting routes bisected by roads, we collected data on vehicles travelling along the roads (such as visibility and audibility), commuting bats (such as height), and composition of the commuting route. We revealed that commuting route structure dictated the frequency at which bats turned back along their commuting routes and avoided the road. We found that gaps (>2 m) in commuting routes, such as the road itself, caused bats to turn away just before they reached the road. Furthermore, we found that turning frequencies of bats increased with vehicle noise levels and the locations at which bats responded to vehicles corresponded with areas where noise levels were greatest, including gaps <2 m. This suggested that bats had a disturbance threshold, and only reacted to vehicles when associated noise reached a certain level. We found that threshold levels for our study species were approximately 88 dB, but this value was likely to vary among species. Thus, our findings indicate that restoring (e.g., replanting native trees and shrubs in gaps) and establishing commuting routes (such as planting tree-lines and wooded hedgerows), as well as creating road-crossing opportunities (such as interlinking canopies) will improve the permeability of a road-dominated landscape to bats. Furthermore, our study highlights the influence of the soundscape. We recommend that effective management and mitigation strategies should take into account the ecological design of the acoustic environment. © 2012 The Wildlife Society.     

Farms,pastures and woodlands: the fine‐scale distribution of Palearctic Culicoides spp. biting midges along an agro‐ecological gradient

The spatial epidemiology of Bluetongue virus (BTV) at the landscape level relates to the fine‐scale distribution and dispersal capacities of its vectors, midges belonging to the genus Culicoides Latreille (Diptera: Ceratopogonidae). Although many previous researches have carried out Culicoides sampling on farms, little is known of the fine‐scale distribution of Culicoides in the landscape immediately surrounding farms. The aim of this study was to gain a better understanding of Culicoides populations at increasing distances from typical dairy farms in north‐west Europe, through the use of eight Onderstepoort‐type black‐light traps positioned along linear transects departing from farms, going through pastures and entering woodlands. A total of 16 902 Culicoides were collected in autumn 2008 and spring 2009. The majority were females, of which more than 97% were recognized as potential vectors. In pastures, we found decreasing numbers of female Culicoides as a function of the distance to the farm. This pattern was modelled by leptokurtic models, with parameters depending on season and species. By contrast, the low number of male Culicoides caught were homogeneously distributed along the transects. When transects entered woodlands, we found a higher abundance of Culicoides than expected considering the distance of the sampling sites to the farm, although this varied according to species.     

Rinvenimenti Floristici Marchigiani

Summary

The author communicates the list of taxa not commonly occurring in the “Marche”, which he has collected in localities not yet mentioned in the bibliography of that area. The list includes also several species more or less widely cultivated in that zone.     

格网尺度下典型旅游城市生态服务价值估算和时空分异特征——以三亚为例

以典型旅游城市三亚市为案例地，利用2006-2018年4期Landsat遥感影像数据，借助ENVI、ArcGIS平台定量识别土地利用演变特征，在1km×1km格网尺度下估算旅游地生态系统服务价值，并结合空间探索性数据分析揭示生态系统服务价值时空分异特征及其与旅游地发展的时空耦合关系。结果表明：（1）2006-2018年间，三亚市生态系统服务价值总量呈逐年下降趋势，由6.73×10⁹元降至5.76×10⁹元，累计减少9.78×10⁸元；（2）空间格局上，三亚市呈"南低北高"空间分异格局，2006-2018年增值区域连片分布于崖州区、天涯区、吉阳区南部区域，且呈逐年减少趋势，减值区域集聚于天涯区东北部、海棠区；（3）空间集聚上，生态系统服务价值截面各年份均呈显著空间正相关且相关性先降后增。高高集聚区位于天涯区北部区域，低低集聚区分布于沿海、海湾地区；（4）旅游发展与生态系统服务价值时空演化特征关联性较强。三亚市天涯区北部林地生态环境良好，生态系统服务价值略有下降但绝对数值稳定，是生态系统服务价值主要来源；旅游发展较为迅速的三亚湾、崖州湾以及海棠湾，相对增值区域较多，但绝对生态系统服务价值损失显著，严重滞后于其他区域。