Harnessing the extracellular bacterial production of nanoscale cobalt ferrite with exploitable magnetic properties

Nanoscale ferrimagnetic particles have a diverse range of uses from directed cancer therapy and drug delivery systems to magnetic recording media and transducers. Such applications require the production of monodisperse nanoparticles with well-controlled size, composition, and magnetic properties. To fabricate these materials purely using synthetic methods is costly in both environmental and economical terms. However, metal-reducing microorganisms offer an untapped resource to produce these materials. Here, the Fe(III)-reducing bacterium Geobacter sulfurreducens is used to synthesize magnetic iron oxide nanoparticles. A combination of electron microscopy, soft X-ray spectroscopy, and magnetometry techniques was employed to show that this method of biosynthesis results in high yields of crystalline nanoparticles with a narrow size distribution and magnetic properties equal to the best chemically synthesized materials. In particular, it is demonstrated here that cobalt ferrite (CoFe2O4) nanoparticles with low temperature coercivity approaching 8 kOe and an effective anisotropy constant of ∼106 erg cm−3 can be manufactured through this biotechnological route. The dramatic enhancement in the magnetic properties of the nanoparticles by the introduction of high quantities of Co into the spinel structure represents a significant advance over previous biomineralization studies in this area using magnetotactic bacteria. The successful production of nanoparticulate ferrites achieved in this study at high yields could open up the way for the scaled-up industrial manufacture of nanoparticles using environmentally benign methodologies

Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis

Objective: To investigate whether antidrug antibodies and/or drug non-trough levels predict the long-term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.  Methods: A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme-linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non-trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.  Results: Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.  Conclusion: Pharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months

Radiation Damage Effects in Chlorite Investigated Using Microfocus Synchrotron Techniques

A detailed understanding of the mechanisms and effects of radiation damage in phyllosilicate minerals is a necessary component of the evaluation of the safety case for a deep geological disposal facility (GDF) for radioactive waste. Structural and chemical changes induced by alpha-particle damage will affect the performance of these minerals as reactive barrier materials (both in the near and far-field) over time scales relevant to GDF integrity. In this study, two examples of chlorite group minerals have been irradiated at a-particle doses comparable to those predicted to be experienced by the clay buffer material surrounding high-level radioactive waste canisters. Crystallographic aberrations induced by the focused He-4(2+) ion beam are revealed via high-resolution, microfocus X-ray diffraction mapping. Interlayer collapse by up to 0.5 angstrom is prevalent across both macrocrystalline and microcrystalline samples, with the macrocrystalline specimen displaying a breakdown of the phyllosilicate structure into loosely connected, multioriented crystallites displaying variable lattice parameters. The damaged lattice parameters suggest a localized breakdown and collapse of the OH(- )rich, "brucite-like" interlayer. Microfocus Fe K-edge X-ray absorption spectroscopy illustrates this defect accumulation, manifest as a severe damping of the X-ray absorption edge. Subtle Fe2+/Fe3+ speciation changes are apparent across the damaged structures. A trend toward Fe reduction is evident at depth in the damaged structures at certain doses (8.76 X 10(15) alpha particles/cm(2)). Interestingly, this reductive trend does not increase with radiation dose; indeed, at the maximum dose (1.26 x 10(16) alpha particles/cm(2)) administered in this study, there is evidence for a slight increase in Fe binding energy, suggesting the development of a depth-dependent redox gradient concurrent with light ion damage. At the doses examined here, these damaged structures are likely highly reactive, as sorption capacity will, to an extent, be largely enhanced by lattice disruption and an increase in available "edge" sites.Peer reviewe