Intestinal inflammation and increased intestinal permeability in Plasmodium chabaudi AS infected mice.

Background: Gastrointestinal symptoms are commonly associated with acute Plasmodium spp infection. Malaria-associated enteritis may provide an opportunity for enteric pathogens to breach the intestinal mucosa, resulting in life-threatening systemic infections. Methods: To investigate whether intestinal pathology also occurs during infection with a murine model of mild and resolving malaria, C57BL/6J mice were inoculated with recently mosquito-transmitted Plasmodium chabaudi AS. At schizogony, intestinal tissues were collected for quantification and localisation of immune mediators and malaria parasites, by PCR and immunohistochemistry. Inflammatory proteins were measured in plasma and faeces and intestinal permeability was assessed by FITC-dextran translocation after oral administration. Results: Parasitaemia peaked at approx. 1.5% at day 9 and resolved by day 14, with mice experiencing significant and transient anaemia but no weight loss. Plasma IFN-γ, TNF-α and IL10 were significantly elevated during peak infection and quantitative RT-PCR of the intestine revealed a significant increase in transcripts for ifng and cxcl10. Histological analysis revealed parasites within blood vessels of both the submucosa and intestinal villi and evidence of mild crypt hyperplasia. In faeces, concentrations of the inflammatory marker lactoferrin were significantly raised on days 9 and 11 and FITC-dextran was detected in plasma on days 7 to 14. At day 11, plasma FITC-dextran concentration was significantly positively correlated with peripheral parasitemia and faecal lactoferrin concentration. Conclusions: In summary, using a relevant, attenuated model of malaria, we have found that acute infection is associated with intestinal inflammation and increased intestinal permeability. This model can now be used to explore the mechanisms of parasite-induced intestinal inflammation and to assess the impact of increased intestinal permeability on translocation of enteropathogens.

Hybrid life cycle assessment of agro-industrial wastewater valorisation.

Wastewater from food processing facilities can have high nutrient valorisation potential. Valorising sugar-rich agro-industrial wastewater may have significant impacts on sustainability of wastewater treatment plant (WWTP). The objective of this study is to evaluate the environmental, economic and social impacts of a novel wastewater valorisation technology. This technology is designed to produce single cell protein (SCP) from wastewater of a fruit juice processing facility. To evaluate the comprehensive sustainability impacts on WWTP and overall background economy, a hybrid life cycle assessment model was developed by combining the multi-regional input-output database (Exiobase) with process-based life cycle inventories of conventional and AgroCycle WWTP. The results indicated the upstream impacts of wastewater could have significant influence on sustainability of WWTP with nutrient valorisation. Therefore the 'zero burden assumption' should not be adopted for upstream wastewater. For the sustainability performance, valorising nutrients from WWTP with AgroCycle technology can improve the environmental performance of WWTP. However, the positive social-economic impacts were directly associated with WWTP system, not the whole background economy. The production of SCP could reduce the Gross Value Added (GVA) and employment in the 'oil seeds sector'. In order to improve the social-economic impacts and promote a circular bioeconomy model in the fruit juice sector, further development is required to improve valorisation productivity and create a better value chain for valorised products.

Biochar, compost and biochar-compost blend as options to recover nutrients and sequester carbon.

This work assessed the potential environmental impact of recycling organic materials in agriculture via pyrolysis (biochar) and composting (compost), as well its combination (biochar-compost blend) versus business-as-usual represented by mineral fertiliser. Life cycle assessment methodology was applied using data sourced from experiments (FP7 project Fertiplus) in three countries (Spain, Italy and Belgium), and considering three environmental impact categories, (i) global warming; (ii) acidification and (iii) eutrophication. The novelty of this analysis is the inclusion of the biochar-compost blend with a focus on multiple European countries, and the inclusion of the acidification and eutrophication impact categories. Biochar, compost and biochar-compost blend all resulted in lower environmental impacts than mineral fertiliser from a systems perspective. Regional differences were found between biochar, compost and biochar-compost blend. The biochar-compost blend offered benefits related to available nutrients and sequestered C. It also produced yields of similar magnitude to mineral fertiliser, which makes its acceptance by farmers more likely whilst reducing environmental impacts. However, careful consideration of feedstock is required.

Worldwide Protein Data Bank biocuration supporting open access to high-quality 3D structural biology data.

Database URL: https://www.wwpdb.org/.

Review of the sustainability of food systems and transition using the Internet of Food.

Many current food systems are unsustainable because they cause significant resource depletion and unacceptable environmental impacts. This problem is so severe, it can be argued that the food eaten today is equivalent to a fossil resource. The transition to sustainable food systems will require many changes but of particular importance will be the harnessing of internet technology, in the form of an 'Internet of Food', which offers the chance to use global resources more efficiently, to stimulate rural livelihoods, to develop systems for resilience and to facilitate responsible governance by means of computation, communication, education and trade without limits of knowledge and access. A brief analysis of the evidence of resource depletion and environmental impact associated with food production and an outline of the limitations of tools like life cycle assessment, which are used to quantify the impact of food products, indicates that the ability to combine data across the whole system from farm to human will be required in order to design sustainable food systems. Developing an Internet of Food, as a precompetitive platform on which business models can be built, much like the internet as we currently know it, will require agreed vocabularies and ontologies to be able to reason and compute across the vast amounts of data that are becoming available. The ability to compute over large amounts of data will change the way the food system is analysed and understood and will permit a transition to sustainable food systems.

Validation of Structures in the Protein Data Bank.

The Worldwide PDB recently launched a deposition, biocuration, and validation tool: OneDep. At various stages of OneDep data processing, validation reports for three-dimensional structures of biological macromolecules are produced. These reports are based on recommendations of expert task forces representing crystallography, nuclear magnetic resonance, and cryoelectron microscopy communities. The reports provide useful metrics with which depositors can evaluate the quality of the experimental data, the structural model, and the fit between them. The validation module is also available as a stand-alone web server and as a programmatically accessible web service. A growing number of journals require the official wwPDB validation reports (produced at biocuration) to accompany manuscripts describing macromolecular structures. Upon public release of the structure, the validation report becomes part of the public PDB archive. Geometric quality scores for proteins in the PDB archive have improved over the past decade.

OneDep: Unified wwPDB System for Deposition, Biocuration, and Validation of Macromolecular Structures in the PDB Archive.

OneDep, a unified system for deposition, biocuration, and validation of experimentally determined structures of biological macromolecules to the PDB archive, has been developed as a global collaboration by the worldwide PDB (wwPDB) partners. This new system was designed to ensure that the wwPDB could meet the evolving archiving requirements of the scientific community over the coming decades. OneDep unifies deposition, biocuration, and validation pipelines across all wwPDB, EMDB, and BMRB deposition sites with improved focus on data quality and completeness in these archives, while supporting growth in the number of depositions and increases in their average size and complexity. In this paper, we describe the design, functional operation, and supporting infrastructure of the OneDep system, and provide initial performance assessments.

An environmental analysis of options for utilising wasted food and food residue.

The potential environmental impact of wasted food minimisation versus its utilisation in a circular bioeconomy is investigated based on a case study of Ireland. The amount of wasted food and food residue (WFFR) produced in 2010 was used for business-as-usual, (a) and four management options were assessed, (b) minimisation, (c) composting, (d) anaerobic digestion and (e) incineration. The environmental impacts Global Warming Potential (GWP), Acidification Potential (AP) and Eutrophication Potential (EP) were considered. A carbon return on investment (CRoI) was calculated for the three processing technologies (c-e). The results showed that a minimisation strategy for wasted food would result in the greatest reduction of all three impacts, -4.5 Mt CO2-e (GWP), -11.4 kt PO43-e (EP) and -43.9 kt SO2-e (AP) compared to business as usual. For WFFR utilisation in the circular bioeconomy, anaerobic digestion resulted in the lowest environmental impact and best CRoI of -0.84 kg CO2-e per Euro. From an economic perspective, for minimisation to be beneficial, 0.15 kg of wasted food would need to be reduced per Euro spent.

PDBe: improved accessibility of macromolecular structure data from PDB and EMDB.

The Protein Data Bank in Europe (http://pdbe.org) accepts and annotates depositions of macromolecular structure data in the PDB and EMDB archives and enriches, integrates and disseminates structural information in a variety of ways. The PDBe website has been redesigned based on an analysis of user requirements, and now offers intuitive access to improved and value-added macromolecular structure information. Unique value-added information includes lists of reviews and research articles that cite or mention PDB entries as well as access to figures and legends from full-text open-access publications that describe PDB entries. A powerful new query system not only shows all the PDB entries that match a given query, but also shows the 'best structures' for a given macromolecule, ligand complex or sequence family using data-quality information from the wwPDB validation reports. A PDBe RESTful API has been developed to provide unified access to macromolecular structure data available in the PDB and EMDB archives as well as value-added annotations, e.g. regarding structure quality and up-to-date cross-reference information from the SIFTS resource. Taken together, these new developments facilitate unified access to macromolecular structure data in an intuitive way for non-expert users and support expert users in analysing macromolecular structure data.

PDBe: Protein Data Bank in Europe.

The Protein Data Bank in Europe (pdbe.org) is a founding member of the Worldwide PDB consortium (wwPDB; wwpdb.org) and as such is actively engaged in the deposition, annotation, remediation and dissemination of macromolecular structure data through the single global archive for such data, the PDB. Similarly, PDBe is a member of the EMDataBank organisation (emdatabank.org), which manages the EMDB archive for electron microscopy data. PDBe also develops tools that help the biomedical science community to make effective use of the data in the PDB and EMDB for their research. Here we describe new or improved services, including updated SIFTS mappings to other bioinformatics resources, a new browser for the PDB archive based on Gene Ontology (GO) annotation, updates to the analysis of Nuclear Magnetic Resonance-derived structures, redesigned search and browse interfaces, and new or updated visualisation and validation tools for EMDB entries.

The role of structural bioinformatics resources in the era of integrative structural biology.

The history and the current state of the PDB and EMDB archives is briefly described, as well as some of the challenges that they face. It seems natural that the role of structural biology archives will change from being a pure repository of historic data into becoming an indispensable resource for the wider biomedical community. As part of this transformation, it will be necessary to validate the biomacromolecular structure data and ensure the highest possible quality for the archive holdings, to combine structural data from different spatial scales into a unified resource and to integrate structural data with functional, genetic and taxonomic data as well as other information available in bioinformatics resources. Some recent developments and plans to address these challenges at PDBe are presented.

SIFTS: Structure Integration with Function, Taxonomy and Sequences resource.

The Structure Integration with Function, Taxonomy and Sequences resource (SIFTS; http://pdbe.org/sifts) is a close collaboration between the Protein Data Bank in Europe (PDBe) and UniProt. The two teams have developed a semi-automated process for maintaining up-to-date cross-reference information to UniProt entries, for all protein chains in the PDB entries present in the UniProt database. This process is carried out for every weekly PDB release and the information is stored in the SIFTS database. The SIFTS process includes cross-references to other biological resources such as Pfam, SCOP, CATH, GO, InterPro and the NCBI taxonomy database. The information is exported in XML format, one file for each PDB entry, and is made available by FTP. Many bioinformatics resources use SIFTS data to obtain cross-references between the PDB and other biological databases so as to provide their users with up-to-date information.

A Java applet for multiple linked visualization of protein structure and sequence.

The amount of biological data available from experimental techniques is huge, and rapidly expanding. The ability to make sense of this vast amount of data requires that we make correlations between distinct biological disciplines using visualization techniques to highlight the critical information. This article describes the visualization techniques of dynamic data brushing, view context maintenance, fisheye sequence view, and a magic lens that have been developed to display protein structure and sequence information.

Automated tracing of electron-density maps of proteins.

The tracing of experimental electron maps in the field of protein crystallography is not a rate-limiting step for structure elucidation, but does represent the process that requires the most expertise and user time. This paper presents a method for automatically tracing the electron-density maps of proteins which can reliably generate a C(alpha) trace for protein maps with data in the resolution range 1.5-4 A. The number of C(alpha) atoms placed and the precision of atom placement depends on the quality of the map, but even with poor maps (FOM approximately 0.5) the algorithm can provide a significant saving in time over conventional methods of interpretation. The interpretation of six experimental maps is presented at different resolutions and levels of phase error; these show that data with an FOM of 0.7 or better can be entirely traced with no user intervention.

High-resolution crystallographic map interpretation.

This article describes a method for rapid interpretation of high-resolution crystallographic electron-density maps. The implemented algorithm searches for fragments of structure found in proteins and links these together to identify uniquely the atomic structure and sequence order of the atoms within a protein. The algorithm uses a two-dimensional sub-graph isomorphism method with a subsequent post-processing step to screen the results to find correct three-dimensional solutions to each search fragment. The final screening of ambiguous solutions found is performed using incomplete difference distance matrices. The algorithm has an intrinsic error-correction technique that is necessary for analysis of experimental data and should be applicable to a number of fields of bioinfomatics.

Pattern-recognition methods to identify secondary structure within X-ray crystallographic electron-density maps.

The interpretation of macromolecular crystallographic electron-density maps is a difficult and traditionally a manual step in the determination of a protein structure. The visualization of information within an electron-density map can be extremely arduous owing to the amount and complexity of information present. The ability to see the overall fold and structure of the molecule is usually lost among all the detail, particularly with larger structures. This paper describes a novel method of analysis of electron density in real space that can determine the secondary structure of a protein within minutes without any user intervention. The method is able to work with poor data as well as good data at resolutions down to 3.5A and is integral to the functionality of QUANTA. This article describes the methodology of the pattern recognition and its use with a number of sets of experimental data.