Analysis of conformational motions and related key residue interactions responsible for a specific function of proteins with elastic network model

Protein collective motions play a critical role in many biochemical processes. How to predict the functional motions and the related key residue interactions in proteins is important for our understanding in the mechanism of the biochemical processes. Normal mode analysis (NMA) of the elastic network model (ENM) is one of the effective approaches to investigate the structure-encoded motions in proteins. However, the motion modes revealed by the conventional NMA approach do not necessarily correspond to a specific function of protein. In the present work, a new analysis method was proposed to identify the motion modes responsible for a specific function of proteins and then predict the key residue interactions involved in the functional motions by using a perturbation approach. In our method, an internal coordinate that accounts for the specific function was introduced, and the Cartesian coordinate space was transformed into the internal/Cartesian space by using linear approximation, where the introduced internal coordinate serves as one of the axes of the coordinate space. NMA of ENM in this internal/Cartesian space was performed and the function-relevant motion modes were identified according to their contributions to the specific function of proteins. Then the key residue interactions important for the functional motions of the protein were predicted as the interactions whose perturbation largely influences the fluctuation along the internal coordinate. Using our proposed methods, the maltose transporter (MalFGK₂) from E. Coli was studied. The functional motions and the key residue interactions that are related to the channel-gating function of this protein were successfully identified.     

Ecological and social determinants of association and proximity patterns in the fission–fusion society of spider monkeys (Ateles geoffroyi)

Some social species exhibit high levels of fission–fusion dynamics (FFD) that improve foraging efficiency. In this study, we shed light on the way that FFD allows animal groups to cope with fluctuations in fruit availability. We explore the relative contribution of fruit availability and social factors like sex in determining association and proximity patterns in spider monkeys. We tested the influence of fruit availability and social factors on the association and proximity patterns using three-year data from a group of spider monkeys in the Yucatan Peninsula of Mexico. We identified subgroup members and estimated their Interindividual distances through instantaneous scan sampling. We evaluated fruit availability by monitoring the phenology of the 10 most important food tree species for spider monkeys in the study site. Social network analyses allowed us to evaluate association and proximity patterns in subgroups. We showed that association patterns vary between seasons, respond to changes in fruit availability, and are influenced by the sex of individuals, likely reflecting biological and behavioral differences between sexes and the interplay between ecological and social factors. In contrast, proximity patterns were minimally affected by changes in fruit availability, suggesting that social factors are more important than food availability in determining cohesion within subgroups.     

Evaluating regional water security through a freshwater ecosystem service flow model: A case study in Beijing-Tianjian-Hebei region,China

Freshwater ecosystem service is essential to human’s survival and development. Many studies have documented the spatial differences in the supply and demand of ecosystem services and proposed the concept of ecosystem services flows. However, few studies characterize freshwater ecosystem service flow quantitatively. Therefore, our paper aims to quantify the effects of freshwater ecosystem service flow on downstream areas. We developed a freshwater ecosystem service flow model and applied it in the Beijing–Tianjin–Hebei (BTH) region, China, for the year of 2000, 2005, and 2010. We assessed the regional water security with an improved freshwater security index by integrating freshwater service provision, consumption and flow; and found that most areas of the BTH region (69.2%) were affected by upstream freshwater flows. The areas achieving water security in the region also expanded to 66.9%, 66.1%, and 71.3%, which were 6.4%, 6.8% and 5.7% increments compared to no-flow situation, in 2000, 2005 and 2010, respectively. Setting quota for human water consumption is suggested to further improve water security. These results highlight the need to fully understand the connections between distant freshwater ecosystem service provision and local freshwater ecosystem service consumption. This approach may also help managers to choose more sustainable strategies for critical freshwater resource management across different regions.     

Biodiversity on the brink: Evaluating a transdisciplinary research collaboration

Global biodiversity is facing an extinction crisis. Australia has one of the highest terrestrial species extinction rates in the world. Scientists, policy advisors and governments have recommended that the issue be addressed at a landscape-scale, while noting that there are significant knowledge gaps that are hampering implementation of such an approach. From 2011–2015, the Australian Government funded a transdisciplinary research program, the Landscapes and Policy Hub, to meet this need. Transdisciplinary research is widely acknowledged as essential to address the complexity of contemporary environmental problems. Given that such research programs are in their infancy, it is important to evaluate their efficacy and provide an empirical basis for improving their design. This paper presents an evaluation of the strategies fostering transdisciplinarity adopted by the Landscapes and Policy Hub. A heavy emphasis on communication, with skilled knowledge brokering, regular face-to-face meetings using participatory activities and shared field engagements enhanced transdisciplinary interaction between researchers and research users. However, establishing a fully integrated interdisciplinary research program remained a challenge. Efforts to enable shared conceptual frameworks to emerge through adaptive application of theory in practice could have been balanced with increased effort at the outset for researchers and research users to collaboratively formulate shared research questions, leading to the establishment of teams that could address these questions through cross-mobilisation of interdisciplinary expertise.     

Genome‐wide analysis of Italian sheep diversity reveals a strong geographic pattern and cryptic relationships between breeds

Italy counts several sheep breeds, arisen over centuries as a consequence of ancient and recent genetic and demographic events. To finely reconstruct genetic structure and relationships between Italian sheep, 496 subjects from 19 breeds were typed at 50K single nucleotide polymorphism loci. A subset of foreign breeds from the Sheep HapMap dataset was also included in the analyses. Genetic distances (as visualized either in a network or in a multidimensional scaling analysis of identical by state distances) closely reflected geographic proximity between breeds, with a clear north–south gradient, likely because of high levels of past gene flow and admixture all along the peninsula. Sardinian breeds diverged more from other breeds, a probable consequence of the combined effect of ancient sporadic introgression of feral mouflon and long‐lasting genetic isolation from continental sheep populations. The study allowed the detection of previously undocumented episodes of recent introgression (Delle Langhe into the endangered Altamurana breed) as well as signatures of known, or claimed, historical introgression (Merino into Sopravissana and Gentile di Puglia; Bergamasca into Fabrianese, Appenninica and, to a lesser extent, Leccese). Arguments that would question, from a genomic point of view, the current breed classification of Bergamasca and Biellese into two separate breeds are presented. Finally, a role for traditional transhumance practices in shaping the genetic makeup of Alpine sheep breeds is proposed. The study represents the first exhaustive analysis of Italian sheep diversity in an European context, and it bridges the gap in the previous HapMap panel between Western Mediterranean and Swiss breeds.     

Muon disrupts AKT hydrogen bond network in cancer

A cancer microenvironment generates strong hydrogen bond network system by the positive feedback loops supporting cancer complexity and robustness. Such network functions through the AKT locus generating high entropic energy supporting cancer metastatic robustness. Charged lepton particle muon follows the rule of Bragg effect during a collision with hydrogen network in cancer cells. Muon beam dismantles hydrogen bond network in cancer by the muon-catalyzed fusion, leading to apoptosis of cancer cells. Muon induces cumulative energy appearance on the hydrogen bond network in a cancer cell with its fast decay to an electron and two neutrinos. Thus, muon beam, muonic atom, muon neutrino shower, and electrons simultaneously cause fast neutralization of the AKT hydrogen bond network by the conversion of hydrogen into deuterium or helium, inactivating the hydrogen bond networks and inducing failure of cancer complexity and robustness with the disappearance of a malignant phenotype.     

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.     

Continental mapping of forest ecosystem functions reveals a high but unrealised potential for forest multifunctionality

Humans require multiple services from ecosystems, but it is largely unknown whether trade‐offs between ecosystem functions prevent the realisation of high ecosystem multifunctionality across spatial scales. Here, we combined a comprehensive dataset (28 ecosystem functions measured on 209 forest plots) with a forest inventory dataset (105,316 plots) to extrapolate and map relationships between various ecosystem multifunctionality measures across Europe. These multifunctionality measures reflected different management objectives, related to timber production, climate regulation and biodiversity conservation/recreation. We found that trade‐offs among them were rare across Europe, at both local and continental scales. This suggests a high potential for ‘win‐win’ forest management strategies, where overall multifunctionality is maximised. However, across sites, multifunctionality was on average 45.8‐49.8% below maximum levels and not necessarily highest in protected areas. Therefore, using one of the most comprehensive assessments so far, our study suggests a high but largely unrealised potential for management to promote multifunctional forests.     

Decision analysis approach to risk/benefit evaluation in the ethical review of controlled human infection studies

Risks and benefit evaluation for controlled human infection studies, where healthy volunteers are deliberately exposed to infectious agents to evaluate vaccine efficacy, should be explicit, systematic, thorough, and non-arbitrary. Decision analysis promotes these qualities using four steps: (1) determining explicit criteria and measures for evaluation, (2) identifying alternatives to the study, (3) defining the models used to estimate the measures for each alternative, and (4) running the models to produce the estimates and compare the alternatives. In this paper, we describe how decision analysis might be applied by funders and regulators, as well as by others contemplating the use of novel controlled human infection studies for vaccine development and evaluation.