Ferritins are ubiquitous proteins that oxidise and store iron within a protein shell to protect cells from oxidative damage. We have characterized the structure and function of a new member of the ferritin superfamily that is sequestered within an encapsulin capsid. We show that this encapsulated ferritin (EncFtn) has two main alpha helices, which assemble in a metal dependent manner to form a ferroxidase center at a dimer interface. EncFtn adopts an open decameric structure that is topologically distinct from other ferritins. While EncFtn acts as a ferroxidase, it cannot mineralize iron. Conversely, the encapsulin shell associates with iron, but is not enzymatically active, and we demonstrate that EncFtn must be housed within the encapsulin for iron storage. This encapsulin nanocompartment is widely distributed in bacteria and archaea and represents a distinct class of iron storage system, where the oxidation and mineralization of iron are distributed between two proteins.DOI: http://dx.doi.org/10.7554/eLife.18972.001
The efficacy of pharmaceutical agents can be greatly improved through nanocarrier delivery. Encapsulation of pharmaceutical agents into a nanocarrier can enhance their bioavailability and biocompatibility, whilst also facilitating targeted drug delivery to specific locations within the body. However, detailed understanding of the in vivo activity of the nanocarrier-drug conjugate is required prior to regulatory approval as a safe and effective treatment strategy. A comprehensive understanding of how nanocarriers travel to, and interact with, the intended target is required in order to optimize the dosing strategy, reduce potential off-target effects, and unwanted toxic effects. Raman spectroscopy has received much interest as a mechanism for label-free, non-invasive imaging of nanocarrier modes of action in vivo. Advanced Raman imaging techniques, including coherent anti-Stokes Raman scattering (CARS) and stimulated Raman scattering (SRS), are paving the way for rigorous evaluation of nanocarrier activity at the single-cell level. This review focuses on the development of Raman imaging techniques to study organic nanocarrier delivery in cells and tissues.
Polymeric nanoparticles (NPs) are attractive candidates for the controlled and targeted delivery of therapeutics in vitro and in vivo. However, detailed understanding of the uptake, location, and ultimate cellular fate of the NPs is necessary to satisfy safety concerns, which is difficult because of the nanoscale size of these carriers. In this work, we show how small chemical labels can be appended to poly(lactic acid-co-glycolic acid) (PLGA) to synthesize NPs that can then be imaged by stimulated Raman scattering microscopy, a vibrational imaging technique that can elucidate bond-specific information in biological environments, such as the identification of alkyne signatures in modified PLGA terpolymers. We show that both deuterium and alkyne labeled NPs can be imaged within primary rat microglia, and the alkyne NPs can also be imaged in ex vivo cortical mouse brain tissue. Immunohistochemical analysis confirms that the NPs localize in microglia in the mouse brain tissue, demonstrating that these NPs have the potential to deliver therapeutics selectively to microglia.
22Ferritins are ubiquitous proteins that oxidise and store iron within a protein shell to protect cells 23 from oxidative damage. We have characterized the structure and function of a new member of the 24 ferritin superfamily that is sequestered within an encapsulin capsid. We show that this 25 encapsulated ferritin (EncFtn) has two main alpha helices, which assemble in a metal dependent 26 manner to form a ferroxidase centre at a dimer interface. EncFtn adopts an open decameric 27 structure that is topologically distinct from other ferritins. While EncFtn acts as a ferroxidase, it 28 cannot mineralize iron. Conversely, the encapsulin shell associates with iron, but is not 29 enzymatically active, and we demonstrate that EncFtn must be housed within the encapsulin for 30 iron storage. This encapsulin nanocompartment is widely distributed in bacteria and archaea and 31 represents a distinct class of iron storage system where the oxidation and mineralization of iron are 32 distributed between two proteins.
The aim of this study was to explore the synergies and discords in attitudes towards research data management (RDM) drivers and barriers for both researchers and institutions. Previous work has studied RDM from a single perspective, but not compared researchers’ and institutions’ perspectives. We carried out qualitative interviews with researchers as well as institutional representatives to identify drivers and barriers, and to explore synergies and discords of both towards RDM. We mapped these to a data lifecycle model and found that the contradictions occur at early stages in the lifecycle of data and the synergies occur at the later stages. This means that for future successful RDM, the points of discord at the start of the data lifecycle must be overcome. Finally, we conclude by proposing key recommendations that could help institutions when addressing both researcher and institutional RDM needs.
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