Drug Loaded Biodegradable Load-Bearing Nanocomposites for Damaged Bone Repair

In this paper we present a short review-scientific report on processing and properties, including in vitro degradation, of load bearing biodegradable nanocomposites as well as of macroporous 3D scaffolds for bone ingrowth. Biodegradable implantable devices should slowly degrade over time and disappear with ingrown of natural bone replacing the synthetic graft. Compared to low strength biodegradable polymers, and brittle CaP ceramics, biodegradable CaP-polymer and CaP-metal nanocomposites, mimicking structure of natural bone, as well as strong and ductile metal nanocomposites can provide to implantable devices both strengths and toughness. Nanostructuring of biodegradable [beta]- TCP (tricalcium phosphate)-polymer (PCL and PLA), [beta]-TCP-metal (FeMg and FeAg) and of Fe-Ag composites was achieved employing high energy attrition milling of powder blends. Nanocomposite powders were consolidated to densities close to theoretical by high pressure consolidation at ambient temperature-cold sintering, with retention of nanoscale structure. The strength of developed nanocomposites was significantly higher as compared with microscale composites of the same or similar composition. Heat treatment at moderate temperatures in hydrogen flow resulted in retention of nanoscale structure and higher ductility. Degradation of developed biodegradable [beta]-TCP-polymer, [beta]-TCPmetal and of Fe-Ag nanocomposites was studied in physiological solutions. Immersion tests in Ringer's and saline solution for 4 weeks resulted in 4 to 10% weight loss and less than 50% decrease in compression or bending strength, the remaining strength being significantly higher than the values reported for other biodegradable materials. Nanostructuring of Fe-Ag based materials resulted also in an increase of degradation rate because of creation on galvanic Fe-Ag nanocouples. In cell culture experiments, the developed nanocomposites supported the attachment the human osteoblast cells and exhibited no signs of cytotoxicity. Interconnected system of nanopores formed during processing of nanocomposites was used for incorporation of drugs, including antibiotics and anticancer drugs, and can be used for loading of bioactive molecules enhancing bone ingrowth

PDBe: Protein Data Bank in Europe

The Protein Data Bank in Europe (PDBe; pdbe.org) is a partner in the Worldwide PDB organization (wwPDB; wwpdb.org) and as such actively involved in managing the single global archive of biomacromolecular structure data, the PDB. In addition, PDBe develops tools, services and resources to make structure-related data more accessible to the biomedical community. Here we describe recently developed, extended or improved services, including an animated structure-presentation widget (PDBportfolio), a widget to graphically display the coverage of any UniProt sequence in the PDB (UniPDB), chemistry- and taxonomy-based PDB-archive browsers (PDBeXplore), and a tool for interactive visualization of NMR structures, corresponding experimental data as well as validation and analysis results (Vivaldi)

Холодное спекание нанокомпозитов Fe-Ag и Fe-Cu консолидацией в поле высоких давлений

The paper states the results of obtaining Fe—Ag and Fe—Cu dense nanocomposites from composite powders consolidated by cold sintering in the high pressure gradient, as well as from nanosize powders of silver (Ag), iron (Fe) and copper (Cu). The results of mechanical tests conducted on Fe—Ag and Fe—Cu nanocomposites are provided. Nanocomposite powders were obtained by high energy attrition milling of carbonyl iron (Fe) micron scale powder and nanosize silver oxide powder (Ag2O), as well as iron and cuprous oxide (Cu2O) nanopowders. High resolution scanning electron microscopy was used to study the microstructure. Compacts featuring approximately 70 % of full density were annealed in hydrogen atmosphere to reduce silver and cuprous oxides to metals and to remove oxide layers from the surface of iron powder particles. This was followed by cold sintering — consolidation under high pressure at a room temperature. The data on specimen density dependence on pressure in the range of 0,25 —3,0 GPa were obtained. Densities were above 95 % of the full density for all nanocomposites, and close to 100 % of the full density under 3,0 GPa for Ag and Cu powders. High mechanical properties in three-point bending and compression were observed for all nanocomposites. It was found that mechanical properties of nanocomposites are substantially higher as compared with composites obtained from micron scale powders. Higher ductility was observed in Fe—Ag and Fe—Cu nanocomposites as compared with specimens obtained from nanostructured Fe.Изложены результаты получения плотных нанокомпозитов Fe—Ag и Fe—Cu из смесей порошков, консолидированных холодным спеканием в поле высоких давлений, а также из наноразмерных порошков серебра (Ag), железа (Fe) и меди (Cu). Приведены результаты механических испытаний нанокомпозитов Fe—Ag и Fe—Cu. Нанокомпозитные порошки были получены помолом микронного порошка карбонильного железа (Fe) и порошка наноразмерного оксида серебра (Ag2O), а также нанопорошков железа и оксида меди (CU2O) в высокоэнергетическом аттриторе. Микроструктура изучалась с помощью сканирующего электронного микроскопа высокого разрешения. Компакты с плотностью около 70 % от теоретической отжигались в атмосфере водорода для восстановления оксида серебра и оксида меди до металлов и удаления оксидных пленок с поверхности частиц порошка железа. За этим следовало холодное спекание — консолидация в поле высоких давлений при комнатной температуре. Получены данные по зависимости плотности образцов от давления в диапазоне 0,25—3,0 ГПа. Для всех нанокомпозитов при давлении 3,0 ГПа достигнуты плотности более 95 % от теоретической, а для порошков Ag и Cu получена плотность около 100 %. На всех составах получены высокие механические свойства в опытах на трехопорный изгиб и на сжатие. Установлено, что механические свойства нанокомпозитов заметно выше, чем у композитов, полученных из микронных порошков. В нанокомпозитах Fe—Ag и Fe—Cu наблюдалась более высокая пластичность по сравнению с образцами, полученными из наноструктурного Fe

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

© 2015 The Authors. Published by OUP. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1093/nar/gkv1047The 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.The Wellcome Trust [88944, 104948]; UK Biotechnology and Biological Sciences Research Council [BB/J007471/1, BB/K016970/1, BB/M013146/1, BB/M011674/1]; National Institutes of Health [GM079429]; UK Medical Research Council [MR/L007835/1]; European Union [284209]; CCP4; European Molecular Biology Laboratory (EMBL). Funding for open access charge: The Wellcome Trust.Published versio

A 3D cellular context for the macromolecular world

We report the outcomes of the discussion initiated at the workshop entitled A 3D Cellular Context for the Macromolecular World and propose how data from emerging three-dimensional (3D) cellular imaging techniques—such as electron tomography, 3D scanning electron microscopy and soft X-ray tomography—should be archived, curated, validated and disseminated, to enable their interpretation and reuse by the biomedical community

An intrinsically disordered proteins community for ELIXIR.

Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) are now recognised as major determinants in cellular regulation. This white paper presents a roadmap for future e-infrastructure developments in the field of IDP research within the ELIXIR framework. The goal of these developments is to drive the creation of high-quality tools and resources to support the identification, analysis and functional characterisation of IDPs. The roadmap is the result of a workshop titled "An intrinsically disordered protein user community proposal for ELIXIR" held at the University of Padua. The workshop, and further consultation with the members of the wider IDP community, identified the key priority areas for the roadmap including the development of standards for data annotation, storage and dissemination; integration of IDP data into the ELIXIR Core Data Resources; and the creation of benchmarking criteria for IDP-related software. Here, we discuss these areas of priority, how they can be implemented in cooperation with the ELIXIR platforms, and their connections to existing ELIXIR Communities and international consortia. The article provides a preliminary blueprint for an IDP Community in ELIXIR and is an appeal to identify and involve new stakeholders

PDBe-KB: a community-driven resource for structural and functional annotations.

The Protein Data Bank in Europe-Knowledge Base (PDBe-KB, https://pdbe-kb.org) is a community-driven, collaborative resource for literature-derived, manually curated and computationally predicted structural and functional annotations of macromolecular structure data, contained in the Protein Data Bank (PDB). The goal of PDBe-KB is two-fold: (i) to increase the visibility and reduce the fragmentation of annotations contributed by specialist data resources, and to make these data more findable, accessible, interoperable and reusable (FAIR) and (ii) to place macromolecular structure data in their biological context, thus facilitating their use by the broader scientific community in fundamental and applied research. Here, we describe the guidelines of this collaborative effort, the current status of contributed data, and the PDBe-KB infrastructure, which includes the data exchange format, the deposition system for added value annotations, the distributable database containing the assembled data, and programmatic access endpoints. We also describe a series of novel web-pages-the PDBe-KB aggregated views of structure data-which combine information on macromolecular structures from many PDB entries. We have recently released the first set of pages in this series, which provide an overview of available structural and functional information for a protein of interest, referenced by a UniProtKB accession