Non-invasive methods of monitoring Fe3O4 magnetic nanoparticle toxicity in human liver HepaRG cells using impedance biosensing and Coherent anti-Stokes Raman spectroscopic (CARS) microscopy.

Functionalized nanoparticles have been developed for use in nanomedicines for treating life threatening diseases including various cancers. To ensure safe use of these new nanoscale reagents, various assays for biocompatibility or cytotoxicity in vitro using cell lines often serve as preliminary assessments prior to in vivo animal testing. However, many of these assays were designed for soluble, colourless materials and may not be suitable for coloured, non-transparent nanoparticles. Moreover, cell lines are not always representative of mammalian organs in vivo. In this work, we use non-invasive impedance sensing methods with organotypic human liver HepaRG cells as a model to test the toxicity of PEG-Fe3O4 magnetic nanoparticles. We also use Coherent anti-Stokes Raman Spectroscopic (CARS) microscopy to monitor the formation of lipid droplets as a parameter to the adverse effect on the HepaRG cell model. The results were also compared with two commercial testing kits (PrestoBlue and ATP) for cytotoxicity. The results suggested that the HepaRG cell model can be a more realistic model than commercial cell lines while use of impedance monitoring of Fe3O4 nanoparticles circumventing the uncertainties due to colour assays. These methods can play important roles for scientists driving towards the 3Rs principle - Replacement, Reduction and Refinement.

Tri-modal imaging of gold-dotted magnetic nanoparticles for magnetic resonance imaging, computed tomography and intravascular ultrasound: an in vitro study.

Aim: To examine the multimodal contrasting ability of gold-dotted magnetic nanoparticles (Au*MNPs) for magnetic resonance (MR), computed tomography (CT) and intravascular ultrasound (IVUS) imaging. Materials & methods: Au*MNPs were prepared by adapting an impregnation method, without using surface capping reagents and characterized (transmission electron microscopy, x-ray diffraction and Fourier-transform infrared spectroscopy) with their in vitro cytotoxicity assessed, followed by imaging assessments. Results: The contrast-enhancing ability of Au*MNPs was shown to be concentration-dependent across MR, CT and IVUS imaging. The Au content of the Au*MNP led to evident increases of the IVUS signal. Conclusion: We demonstrated that Au*MNPs showed concentration-dependent contrast-enhancing ability in MRI and CT imaging, and for the first-time in IVUS imaging due to the Au content. These Au*MNPs are promising toward solidifying tri-modal imaging-based theragnostics.

Selective binding of antibiotics using magnetic molecular imprint polymer (MMIP) networks prepared from vinyl-functionalized magnetic nanoparticles.

Adverse effects of pharmaceutical emerging contaminants (PECs), including antibiotics, in water supplies has been a global concern in recent years as they threaten fresh water security and lead to serious health problems to human, wildlife and the environment. However, detection of these contaminants in water sources, as well as food products, is difficult due to their low concentration. Here, we prepared a new family of magnetic molecular imprinted polymer (MMIP) networks for binding antibiotics via a microemulsion polymerization technique using vinyl silane modified Fe3O4 magnetic nanoparticles. The cross-linked polymer backbone successfully integrated with 20-30 nm magnetic nanoparticles and generated a novel porous polymeric network structure. These networks showed a high binding capacity for both templates, erythromycin and ciprofloxacin at 70 and 32 mg/g. Both MMIPs were also recyclable, retaining 75 % and 68 % of the binding capacity after 4 cycles. These MMIPs have showed a clear preference for binding the template molecules, with a binding capacity 4- to 7-fold higher than the other antibiotics in the same matrix. These results demonstrate our MMIP networks, which offered high binding capacity and selectivity as well as recyclability, can be used for both removal and monitoring hazardous antibiotic pollutants in different sources/samples and food products.

A spacing account of negative recency in final free recall.

The well-known recency effect in immediate free recall reverses when subjects attempt to recall items studied and tested on a series of prior lists, as in the final-free-recall procedure (Craik, 1970). In this case, the last few items on each list are actually remembered less well than are the midlist items. Because dual-store theories of recall naturally predict negative recency, this phenomenon has long been cited as evidence favoring these models. In a final-free-recall study, we replicate the negative-recency effect for the within-list serial position curve and the positive-recency effect for the between-list serial position curve. Whereas we find prominent negative recency for items recalled early in the initial recall period, this effect is markedly reduced for items recalled later in the recall period. When considering initial recall as a second presentation of studied items, we find that the probability of final free recall increases as the number of items between initial presentation and initial recall increases. These results suggest that negative recency may reflect the beneficial effects of spaced practice, in which end-of-list items recalled early constitute massed repetitions and end-of-list items recalled late are spaced repetitions. To help distinguish between the spacing account and the prevailing dual-store, rehearsal-based account, we examined negative recency in continual-distractor free recall. Contrary to the dual-store account, but in accord with the spacing account, we find robust negative recency in continual-distractor free recall, which is greater for those items recalled early in output. (PsycINFO Database Record

Coding of episodic memory in the human hippocampus.

Neurocomputational models have long posited that episodic memories in the human hippocampus are represented by sparse, stimulus-specific neural codes. A concomitant proposal is that when sparse-distributed neural assemblies become active, they suppress the activity of competing neurons (neural sharpening). We investigated episodic memory coding in the hippocampus and amygdala by measuring single-neuron responses from 20 epilepsy patients (12 female) undergoing intracranial monitoring while they completed a continuous recognition memory task. In the left hippocampus, the distribution of single-neuron activity indicated that only a small fraction of neurons exhibited strong responding to a given repeated word and that each repeated word elicited strong responding in a different small fraction of neurons. This finding reflects sparse distributed coding. The remaining large fraction of neurons exhibited a concurrent reduction in firing rates relative to novel words. The observed pattern accords with longstanding predictions that have previously received scant support from single-cell recordings from human hippocampus.

Sparse and distributed coding of episodic memory in neurons of the human hippocampus.

Neurocomputational models hold that sparse distributed coding is the most efficient way for hippocampal neurons to encode episodic memories rapidly. We investigated the representation of episodic memory in hippocampal neurons of nine epilepsy patients undergoing intracranial monitoring as they discriminated between recently studied words (targets) and new words (foils) on a recognition test. On average, single units and multiunits exhibited higher spike counts in response to targets relative to foils, and the size of this effect correlated with behavioral performance. Further analyses of the spike-count distributions revealed that (i) a small percentage of recorded neurons responded to any one target and (ii) a small percentage of targets elicited a strong response in any one neuron. These findings are consistent with the idea that in the human hippocampus episodic memory is supported by a sparse distributed neural code.