Graphene-VP40 interactions and potential disruption of the Ebola virus matrix filaments

Ebola virus infections cause hemorrhagic fever that often results in very high fatality rates. In addition to exploring vaccines, development of drugs is also essential for treating the disease and preventing the spread of the infection. The Ebola virus matrix protein VP40 exists in various conformational and oligomeric forms and is a potential pharmacological target for disrupting the virus life-cycle. Here we explored graphene-VP40 interactions using molecular dynamics simulations and graphene pelleting assays. We found that graphene sheets associate strongly with VP40 at various interfaces. We also found that the graphene is able to disrupt the C-terminal domain (CTD-CTD) interface of VP40 hexamers. This VP40 hexamer-hexamer interface is crucial in forming the Ebola viral matrix and disruption of this interface may provide a method to use graphene or similar nanoparticle based solutions as a disinfectant that can significantly reduce the spread of the disease and prevent an Ebola epidemic

Plasma membrane association facilitates conformational changes in the Marburg virus protein VP40 dimer

Filovirus infections cause hemorrhagic fever in humans and non-human primates that often results in high fatality rates. The Marburg virus is a lipid-enveloped virus from the Filoviridae family and is closely related to the Ebola virus. The viral matrix layer underneath the lipid envelope is formed by the matrix protein VP40 (VP40), which is also involved in other functions during the viral life-cycle. As in the Ebola virus VP40 (eVP40), the recently determined X-ray crystal structure of the Marburg virus VP40 (mVP40) features loops containing cationic residues that form a lipid binding basic patch. However, the mVP40 basic patch is significantly flatter with a more extended surface than in eVP40, suggesting the possibility of differences in the plasma membrane interactions and phospholipid specificity between the VP40 dimers. In this paper, we report on molecular dynamics simulations that investigate the roles of various residues and lipid types in PM association as well as the conformational changes of the mVP40 dimer facilitated by membrane association. We compared the structural changes of the mVP40 dimer with the mVP40 dimer in both lipid free and membrane associated conditions. Despite the significant structural differences in the crystal structure, the Marburg VP40 dimer is found to adopt a configuration very similar to the Ebola VP40 dimer after associating with the membrane. This conformational rearrangement upon lipid binding allows Marburg VP40 to localize and stabilize at the membrane surface in a manner similar to the Ebola VP40 dimer. Consideration of the structural information in its lipid-interacting condition may be important in targeting mVP40 for novel drugs to inhibit viral budding from the plasma membrane

Flavonoid intake in European adults (18 to 64 years).

BACKGROUND: Flavonoids are a group of phenolic secondary plant metabolites that are ubiquitous in plant-based diets. Data from anthropological, observational and intervention studies have shown that many flavonoids are bioactive. For this reason, there is an increasing interest in investigating the potential health effects of these compounds. The translation of these findings into the context of the health of the general public requires detailed information on habitual dietary intake. However, only limited data are currently available for European populations. OBJECTIVE: The objective of this study is to determine the habitual intake and main sources of anthocyanidins, flavanols, flavanones, flavones, flavonols, proanthocyanidins, theaflavins and thearubigins in the European Union. DESIGN: We use food consumption data from the European Food Safety Authority (EFSA) and the FLAVIOLA Food Composition Database to estimate intake of flavonoids. RESULTS: Mean (±SEM) intake of total flavonoids in Europe was 428±49 mg/d, of which 136±14 mg/d were monomeric compounds. Gallated flavan-3-ols (53±12 mg/d) were the main contributor. The lowest flavonoid intake was observed in Mediterranean countries (monomeric compounds: 95±11 mg/d). The distribution of intake was skewed in many countries, especially in Germany (monomeric flavonoids; mean intake: 181 mg/d; median intake: 3 mg/d). CONCLUSIONS: The habitual intake of flavonoids in Europe is below the amounts found to have a significant health effect.This project was supported by the European Union (grant 226588, “Flaviola”). Mars, Inc., a member of the FLAVIOLA research consortium, provided support in the form of salaries for author HS, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final published version. It first appeared at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0128132

Spatially-resolved electronic and vibronic properties of single diamondoid molecules

Diamondoids are a unique form of carbon nanostructure best described as hydrogen-terminated diamond molecules. Their diamond-cage structures and tetrahedral sp3 hybrid bonding create new possibilities for tuning electronic band gaps, optical properties, thermal transport, and mechanical strength at the nanoscale. The recently-discovered higher diamondoids (each containing more than three diamond cells) have thus generated much excitement in regards to their potential versatility as nanoscale devices. Despite this excitement, however, very little is known about the properties of isolated diamondoids on metal surfaces, a very relevant system for molecular electronics. Here we report the first molecular scale study of individual tetramantane diamondoids on Au(111) using scanning tunneling microscopy and spectroscopy. We find that both the diamondoid electronic structure and electron-vibrational coupling exhibit unique spatial distributions characterized by pronounced line nodes across the molecular surfaces. Ab-initio pseudopotential density functional calculations reveal that the observed dominant electronic and vibronic properties of diamondoids are determined by surface hydrogen terminations, a feature having important implications for designing diamondoid-based molecular devices.Comment: 16 pages, 4 figures. to appear in Nature Material

Exact Speedup Factors and Sub-Optimality for Non-Preemptive Scheduling

Fixed priority scheduling is used in many real-time systems; however, both preemptive and non-preemptive variants (FP-P and FP-NP) are known to be sub-optimal when compared to an optimal uniprocessor scheduling algorithm such as preemptive earliest deadline first (EDF-P). In this paper, we investigate the sub-optimality of fixed priority non-preemptive scheduling. Specifically, we derive the exact processor speed-up factor required to guarantee the feasibility under FP-NP (i.e. schedulability assuming an optimal priority assignment) of any task set that is feasible under EDF-P. As a consequence of this work, we also derive a lower bound on the sub-optimality of non-preemptive EDF (EDF-NP). As this lower bound matches a recently published upper bound for the same quantity, it closes the exact sub-optimality for EDF-NP. It is known that neither preemptive, nor non-preemptive fixed priority scheduling dominates the other, in other words, there are task sets that are feasible on a processor of unit speed under FP-P that are not feasible under FP-NP and vice-versa. Hence comparing these two algorithms, there are non-trivial speedup factors in both directions. We derive the exact speed-up factor required to guarantee the FP-NP feasibility of any FP-P feasible task set. Further, we derive the exact speed-up factor required to guarantee FP-P feasibility of any constrained-deadline FP-NP feasible task set

Simulation Modelling in Ophthalmology : Application to Cost Effectiveness of Ranibizumab and Aflibercept for the Treatment of Wet Age-Related Macular Degeneration in the United Kingdom

Previously developed models in ophthalmology have generally used a Markovian structure. There are a number of limitations with this approach, most notably the ability to base patient outcomes on best-corrected visual acuity (BCVA) in both eyes, which may be overcome using a different modelling structure. Simulation modelling allows for this to be modelled more precisely, and therefore may provide more accurate and relevant estimates of the cost effectiveness of ophthalmology interventions

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Epidemiological Interactions between Urogenital and Intestinal Human Schistosomiasis in the Context of Praziquantel Treatment across Three West African Countries

© 2015 Knowles et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article