Structural variability of C3larvin toxin. Intrinsic dynamics of the α/β fold of the C3-like group of mono-ADP-ribosyltransferase toxins

C3larvin toxin is a new member of the C3 class of the mono-ADP-ribosyltransferase toxin family. The C3 toxins are known to covalently modify small G-proteins, e.g. RhoA, impairing their function, and serving as virulence factors for an offending pathogen. A full-length X-ray structure of C3larvin (2.3 Å) revealed that the characteristic mixed α/β fold consists of a central β-core flanked by two helical regions. Topologically, the protein can be separated into N and C lobes, each formed by a β-sheet and an α-motif, and connected by exposed loops involved in the recognition, binding, and catalysis of the toxin/enzyme, i.e. the ADP-ribosylation turn–turn and phosphate–nicotinamide PN loops. Herein, we provide two new C3larvin X-ray structures and present a systematic study of the toxin dynamics by first analyzing the experimental variability of the X-ray data-set followed by contrasting those results with theoretical predictions based on Elastic Network Models (GNM and ANM). We identify residues that participate in the stability of the N-lobe, putative hinges at loop residues, and energy-favored deformation vectors compatible with conformational changes of the key loops and 3D-subdomains (N/C-lobes), among the X-ray structures. We analyze a larger ensemble of known C3bot1 conformations and conclude that the characteristic ‘crab-claw’ movement may be driven by the main intrinsic modes of motion. Finally, via computational simulations, we identify harmonic and anharmonic fluctuations that might define the C3larvin ‘native state.’ Implications for docking protocols are derived.     

Unravelling the Leishmania genome

The past few years have seen significant advances in our understanding of eukaryotic genomes. In the field of parasitology, this is best exemplified by the application of genome mapping techniques to the study of genome structure and function in the protozoan parasite, Leishmania. Although much is known about the organism and the diseases it causes, molecular genetics has only recently begun to play a major part in elucidating some of the unusual characteristics of this interesting parasite. Mapping of the small (35 Mb) genome and determination of the functional role of genes by the application of in vitro homologous gene targeting techniques are revealing novel avenues for the development of prophylactic measures.     

Evidence for increases in vegetation species richness across UK Environmental Change Network sites linked to changes in air pollution and weather patterns

We analysed trends in vegetation monitored at regular intervals over the past two decades (1993–2012) at the twelve terrestrial Environmental Change Network (ECN) sites. We sought to determine the extent to which flora had changed and link any such changes to potential environmental drivers. We observed significant increases in species richness, both at a whole network level, and when data were analysed within Broad Habitat groupings representing the open uplands, open lowlands and woodlands. We also found comparable increases in an indicator of vegetation response to soil pH, Ellenberg R. Species characteristic of less acid soils tended to show more consistent increases in frequency across sites relative to species with a known tolerance for strongly acidic soils. These changes are, therefore, broadly consistent with a response to increases in soil solution pH observed for the majority of ECN sites that, in turn, are likely to be driven by large reductions in acid deposition in recent decades. Increases in species richness in certain habitat groupings could also be linked to increased soil moisture availability in drier lowland sites that are likely to have been influenced by a trend towards wetter summers in recent years, and possibly also to a reduction in soil nitrogen availability in some upland locations. Changes in site management are also likely to have influenced trends at certain sites, particularly with respect to agricultural practices. Our results are therefore indicative of widescale responses to major regional-scale changes in air pollution and recent weather patterns, modified by local management effects. The relative consistency of management of ECN sites over time is atypical of much of the wider countryside and it is therefore not appropriate to scale up these observations to infer national scale trends. Nevertheless the results provide an important insight into processes that may be operating nationally. It will now be necessary to test for the ubiquity of these changes using appropriate broader spatial scale survey data.     

Changes in plant species richness and productivity in response to decreased nitrogen inputs in grassland in southern England

Biomass production and plant species diversity in grassland in southern England was monitored before and after a change from conventional to organic farming. Our 18-year study, part of the UK's Environmental Change Network long-term monitoring programme, showed that the cessation of artificial fertiliser use on grassland after conversion to organic farming resulted in a decrease in biomass production and an increase in plant species richness. Grassland productivity decreased immediately after fertiliser application ceased, and after two years the annual total biomass production had fallen by over 50%. In the subsequent decade, total annual grassland productivity did not change significantly, and yields reached 31–66% of the levels recorded pre-management change. Plant species richness that had remained stable during the first 5 years of our study under conventional farming, increased by 300% over the following 13 years under organic farm management. We suggest that the change in productivity is due to the altered composition of species within the plots. In the first few years after the change in farming practice, high yielding, nitrogen-loving plants were outcompeted by lower yielding grasses and forbs, and these species remained in the plots in the following years. This study shows that grassland can be converted from an environment lacking in plant species diversity to a relatively species-rich pasture within 10–15 years, simply by stopping or suspending nitrogen additions. We demonstrate that the trade-off for increasing species richness is a decrease in productivity. Grassland in the UK is often not only managed from a conservation perspective, but to also produce a profitable yield. By considering the species composition and encouraging specific beneficial species such as legumes, it may be possible to improve biomass productivity and reduce the trade-off.     

Identify sectors’ role on the embedded CO2 transfer networks through China’s regional trade

This study developed a framework for combining multi-regional input-output analysis and network indicators to assess the interregional CO₂ flows in China. The interregional CO₂ flows of eight regions were calculated and visualized based on a multiregional input-output (MRIO) model for China. The focus of the research was intermediate use. The results of the network indicators showed that refined petroleum, coke, nuclear fuel and chemical products (07), and basic metals and fabricated metal sectors (09) played key roles in the complex networks. and these sectors in most regions controlled a large share of CO₂ transfer by functioning as key hubs and authorities. They along with commerce, transport, storage, and post (16) acted as agents that brokered the CO₂ flows within and between regions. The roles of some other industrial sectors were also identified, e.g., construction (15) functioned as the largest authority. The results demonstrated the importance and effectiveness of network indicators for identifying the characteristics of CO₂ emissions embedded in the domestic supply chain, and provided new information relevant to policy implementation.     

基于网络药理学探讨皂角刺治疗乳痈的作用机制

摘要 目的：基于网络药理学探讨皂角刺治疗乳痈的作用机制。方法：通过建立皂角刺药物靶点数据集、乳痈相关疾病靶点数据集，构建皂角刺治疗急性乳腺炎的蛋白互作（PPI）网络，构建并分析"皂角刺活性成分-潜在靶点-急性乳腺炎"网络。开展基因本体（GO）功能富集分析和京都基因与基因组百科全书（KEGG）通路富集分析，探讨皂角刺治疗乳痈的可能机制。结果：共得到皂角刺活性成分11个，筛选出活性成分所对应的不重复靶点共97个，其中1个活性成分无对应靶点。通过搜集GeneCards 和OMIM数据库，共得到292个急性乳腺炎的相关靶点基因。将疾病靶点基因与药物活性成分所对应的靶点进行比对后，得到10个交集靶点，即皂角刺治疗急性乳腺炎的潜在靶点。皂角刺活性成分按degree值排前3名的依次为槲皮素（quercetin）、漆黄素（fisetin）、山奈酚（kaempferol），其中皂角刺治疗乳痈的靶点包括白细胞介素-6（IL-6）、表皮生长因子受体（EGFR）、酪氨酸激酶受体2（ERBB2）、细胞间黏附分子-1（ICAM1）、雌激素受体1（ESR1）等5个关键靶点，主要涉及乳腺癌疾病通路、TNF信号通路和雌激素信号通路等3条信号通路。结论：皂角刺治疗乳痈的作用机制可能与机体的炎症反应以及雌激素水平变化等密切相关。     

Network environ analysis for socio-economic water system

Embodied water in a socio-economic system refers to the hidden water contained in products traded from one region or one sector to another and has been the center of concern for water management in recent years. However, most models developed for water system analysis ignore cycling and indirect flows, making it difficult to explain the effects of structure on these factors among sectors. Therefore, those models fail to examine the water utilization efficiency from an integral view. In this study, we investigate an embodied socio-economic water system using network analysis developed originally for ecological systems. In this manner, we identify structural and throughflow indicators, such as Finn Cycling Index, Indirect effects ratio, and aggradation, to show the efficiency of water utilization. The three indicators show different perspectives of the system's efficiency change over time, indicating that only the combination of these three indicators can provide a holistic portray about efficiency. Results showed that the structure influenced the cycling and indirect flows, and from a throughflow perspective, the system depends on large boundary inputs of fresh water. Furthermore, the values of Cycling Index and Indirect effect ratio are much lower than for natural food webs, implying that the policies that led to the structural change and reduction of boundary fresh water inputs do not lead to positive water utilization seen in natural systems. This study provides a novel perspective and methodology for assessing the structure and efficiency of water utilization system with a whole perspective.     

Geographic Information System (GIS) modeling approach to determine the fastest delivery routes

This study involves the adoption of the Geographic Information System (GIS) modeling approach to determine the quickest routes for fresh vegetable delivery. During transport, fresh vegetables mainly deteriorate on account of temperature and delivery time. Nonetheless, little attention has been directed to transportation issues in most areas within Kuala Lumpur. In addition, perishable food normally has a short shelf life, thus timely delivery significantly affects delivery costs. Therefore, selecting efficient routes would consequently reduce the total transportation costs. The regression model is applied in this study to determine the parameters that affect route selection with respect to the fastest delivery of fresh vegetables. For the purpose of this research, ArcGIS software with network analyst extension is adopted to solve the problem of complex networks. The final output of this research is a map of quickest routes with the best delivery times based on all variables. The variables tested from regression analysis are the most effective parameters to make the flow of road networks slower. The objective is to improve the delivery services by achieving the least drive time. The main findings of this research are that Land use such as residential area and population as variables are the effective parameters on drive time.     

pH Biosensing by PI4P Regulates Cargo Sorting at the TGN

1. Download : Download high-res image (187KB)
2. Download : Download full-size image