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

Improving the surface characteristics of Ti-6Al-4V and Timetal 834 using PIRAC nitriding treatments

Despite the popularity of a number of techniques of thermochemical diffusion for titanium, in many cases the surface engineering processes used may not be economically viable options for industry. This work focuses on the application of Powder Immersion Reaction Assisted Coating (PIRAC), a relatively inexpensive nitriding treatment that can provide a remarkable improvement in the surface characteristics of titanium alloys. The aim of this work was to determine whether PIRAC could be successfully applied to Ti-6Al-4V and the high-performance near-α titanium alloy Timetal 834. In order to study the response of these materials to PIRAC nitriding, techniques such as X-ray diffraction, micro-indentation hardness, surface profilometry, optical and electron microscopy, nano-scratch adhesion testing and ball-on-plate reciprocating-sliding wear testing were employed. These techniques highlighted the markedly different response between the two alloys to the PIRAC treatment; namely, that Ti-6Al-4V forms a thick compound layer, while at the same processing temperature and time Timetal834 does not form any appreciable Ti 2 N phase instead forming a nitrogen-diffusion case with a thin TiN compound layer at the surface. This inherent difference in nitridability influences the metallurgical response of each alloy. Despite this, the surfaces of both alloys were still hardened considerably and their tribological performance in dry sliding conditions improved compared to the untreated alloys

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

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

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

NleG Type 3 Effectors from Enterohaemorrhagic Escherichia coli Are U-Box E3 Ubiquitin Ligases

NleG homologues constitute the largest family of type 3 effectors delivered by pathogenic E. coli, with fourteen members in the enterohaemorrhagic (EHEC) O157:H7 strain alone. Identified recently as part of the non-LEE-encoded (Nle) effector set, this family remained uncharacterised and shared no sequence homology to other proteins including those of known function. The C-terminal domain of NleG2-3 (residues 90 to 191) is the most conserved region in NleG proteins and was solved by NMR. Structural analysis of this structure revealed the presence of a RING finger/U-box motif. Functional assays demonstrated that NleG2-3 as well as NleG5-1, NleG6-2 and NleG9′ family members exhibited a strong autoubiquitination activity in vitro; a characteristic usually expressed by eukaryotic ubiquitin E3 ligases. When screened for activity against a panel of 30 human E2 enzymes, the NleG2-3 and NleG5-1 homologues showed an identical profile with only UBE2E2, UBE2E3 and UBE2D2 enzymes supporting NleG activity. Fluorescence polarization analysis yielded a binding affinity constant of 56±2 µM for the UBE2D2/NleG5-1 interaction, a value comparable with previous studies on E2/E3 affinities. The UBE2D2 interaction interface on NleG2-3 defined by NMR chemical shift perturbation and mutagenesis was shown to be generally similar to that characterised for human RING finger ubiquitin ligases. The alanine substitutions of UBE2D2 residues Arg5 and Lys63, critical for activation of eukaryotic E3 ligases, also significantly decreased both NleG binding and autoubiquitination activity. These results demonstrate that bacteria-encoded NleG effectors are E3 ubiquitin ligases analogous to RING finger and U-box enzymes in eukaryotes

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