Cell bystander effect induced by radiofrequency electromagnetic fields and magnetic nanoparticles

Induced effects by direct exposure to ionizing radiation (IR) are a central issue in many fields like radiation protection, clinic diagnosis and oncological therapies. Direct irradiation at certain doses induce cell death, but similar effects can also occur in cells no directly exposed to IR, a mechanism known as bystander effect. Non-IR (radiofrequency waves) can induce the death of cells loaded with MNPs in a focused oncological therapy known as magnetic hyperthermia. Indirect mechanisms are also able to induce the death of unloaded MNPs cells. Using in vitro cell models, we found that colocalization of the MNPs at the lysosomes and the non-increase of the temperature induces bystander effect under non-IR. Our results provide a landscape in which bystander effects are a more general mechanism, up to now only observed and clinically used in the field of radiotherapy.Comment: 16 pages, 4 figures, submitted to International Journal of Radiation Biolog

Validity of the N\'{e}el-Arrhenius model for highly anisotropic Co_xFe_{3-x}O_4 nanoparticles

We report a systematic study on the structural and magnetic properties of Co_{x}Fe_{3-x}O_{4} magnetic nanoparticles with sizes between $5$ to $25$ nm, prepared by thermal decomposition of Fe(acac)_{3} and Co(acac)_{2}. The large magneto-crystalline anisotropy of the synthesized particles resulted in high blocking temperatures ($42$ K \leqq $T_B$ $\leqq 345$ K for $5 \leqq$ d $\leqq 13$ nm ) and large coercive fields ($H_C \approxeq 1600$ kA/m for $T = 5$ K). The smallest particles ($=5$ nm) revealed the existence of a magnetically hard, spin-disordered surface. The thermal dependence of static and dynamic magnetic properties of the whole series of samples could be explained within the N\'{e}el-Arrhenius relaxation framework without the need of ad-hoc corrections, by including the thermal dependence of the magnetocrystalline anisotropy constant $K_1(T)$ through the empirical Br\"{u}khatov-Kirensky relation. This approach provided $K_1(0)$ values very similar to the bulk material from either static or dynamic magnetic measurements, as well as realistic values for the response times ($\tau_0 \simeq 10^{-10}$ s). Deviations from the bulk anisotropy values found for the smallest particles could be qualitatively explained based on Zener\'{}s relation between $K_1(T)$ and M(T)

Protein adsorption onto Fe3O4 nanoparticles with opposite surface charge and its impact on cell uptake

Nanoparticles (NPs) engineered for biomedical applications are meant to be in contact with protein-rich physiological fluids. These proteins are usually adsorbed onto the NP surface, forming a swaddling layer called protein corona that influences cell internalization. We present a study on protein adsorption onto different magnetic NPs (MNPs) when immersed in cell culture medium, and how these changes affect the cellular uptake. Two colloids with magnetite cores of 25 nm, same hydrodynamic size and opposite surface charge were in situ coated with (a) positive polyethyleneimine (PEI-MNPs) and (b) negative poly(acrylic acid) (PAA-MNPs). After few minutes of incubation in cell culture medium the wrapping of the MNPs by protein adsorption resulted in a 5-fold size increase. After 24 h of incubation large MNP-protein aggregates with hydrodynamic sizes 1500 to 3000 nm (PAA-MNPs and PEI-MNPs respectively) were observed. Each cluster contained an estimated number of magnetic cores between 450 and 1000, indicating the formation of large aggregates with a "plum pudding" structure of MNPs embedded into a protein network of negative surface charge irrespective of the MNP_core charge. We demonstrated that PEI-MNPs are incorporated in much larger amounts than the PAA-MNPs units. Quantitative analysis showed that SH-SY5Y cells can incorporate 100 per cent of the added PEI-MNPs up to about 100 pg per cell, whereas for PAA-MNPs the uptake was less than 50 percent. The final cellular distribution showed also notable differences regarding partial attachment to the cell membrane. These results highlight the need to characterize the final properties of MNPs after protein adsorption in biological media, and demonstrate the impact of these properties on the internalization mechanisms in neural cells.Comment: 32 pages, 10 figure

Application of magnetically induced hyperthermia on the model protozoan Crithidia fasciculata as a potential therapy against parasitic infections

Magnetic hyperthermia is currently an EU-approved clinical therapy against tumor cells that uses magnetic nanoparticles under a time varying magnetic field (TVMF). The same basic principle seems promising against trypanosomatids causing Chagas disease and sleeping sickness, since therapeutic drugs available display severe side effects and drug-resistant strains. However, no applications of this strategy against protozoan-induced diseases have been reported so far. In the present study, Crithidia fasciculata, a widely used model for therapeutic strategies against pathogenic trypanosomatids, was targeted with Fe_{3}O_{4} magnetic nanoparticles (MNPs) in order to remotely provoke cell death using TVMFs. The MNPs with average sizes of d approx. 30 nm were synthesized using a precipitation of FeSO_{4}4 in basic medium. The MNPs were added to Crithidia fasciculata choanomastigotes in exponential phase and incubated overnight. The amount of uploaded MNPs per cell was determined by magnetic measurements. Cell viability using the MTT colorimetric assay and flow cytometry showed that the MNPs were incorporated by the cells with no noticeable cell-toxicity effects. When a TVMF (f = 249 kHz, H = 13 kA/m) was applied to MNP-bearing cells, massive cell death was induced via a non-apoptotic mechanism. No effects were observed by applying a TVMF on control (without loaded MNPs) cells. No macroscopic rise in temperature was observed in the extracellular medium during the experiments. Scanning Electron Microscopy showed morphological changes after TVMF experiments. These data indicate (as a proof of principle) that intracellular hyperthermia is a suitable technology to induce the specific death of protozoan parasites bearing MNPs. These findings expand the possibilities for new therapeutic strategies that combat parasitic infections.Comment: 9 pages, four supplementary video file

On the Commutative Equivalence of Context-Free Languages

The problem of the commutative equivalence of context-free and regular languages is studied. In particular conditions ensuring that a context-free language of exponential growth is commutatively equivalent with a regular language are investigated

Uncertainties in gas kinematics arising from stellar continuum modelling in integral field spectroscopy data: the case of NGC2906 observed with MUSE/VLT

We study how the use of several stellar subtraction methods and line fitting approaches can affect the derivation of the main kinematic parameters (velocity and velocity dispersion fields) of the ionized gas component. The target of this work is the nearby galaxy NGC 2906, observed with the MUSE instrument at Very Large Telescope. A sample of twelve spectra is selected from the inner (nucleus) and outer (spiral arms) regions, characterized by different ionization mechanisms. We compare three different methods to subtract the stellar continuum (FIT3D, STARLIGHT and pPXF), combined with one of the following stellar libraries: MILES, STELIB and GRANADA+MILES. The choice of the stellar subtraction method is the most important ingredient affecting the derivation of the gas kinematics, followed by the choice of the stellar library and by the line fitting approach. In our data, typical uncertainties in the observed wavelength and width of the H\alpha and [NII] lines are of the order of _rms \sim 0.1\AA\ and _rms \sim 0.2\AA\ (\sim 5 and 10km/s, respectively). The results obtained from the [NII] line seem to be slightly more robust, as it is less affected by stellar absorption than H\alpha. All methods considered yield statistically consistent measurements once a mean systemic contribution \Delta\bar\lambda=\Delta\bar\sigma=0.2xDelta_{MUSE} is added in quadrature to the line fitting errors, where \Delta_{MUSE} = 1.1\AA\ \sim 50 km/s denotes the instrumental resolution of the MUSE spectra. Although the subtraction of the stellar continuum is critical in order to recover line fluxes, any method (including none) can be used in order to measure the gas kinematics, as long as an additional component of 0.2 x Delta_MUSE is added to the error budget.Comment: 20 pages, 14 figure

On the Progenitor System of Nova V2491 Cygni

Nova V2491 Cyg is one of just two detected pre-outburst in X-rays. The light curve of this nova exhibited a rare "re-brightening" which has been attributed by some as the system being a polar, whilst others claim that a magnetic WD is unlikely. By virtue of the nature of X-ray and spectroscopic observations the system has been proposed as a recurrent nova, however the adoption of a 0.1 day orbital period is generally seen as incompatible with such a system. In this research note we address the nature of the progenitor system and the source of the 0.1 day periodicity. Through the combination of Liverpool Telescope observations with published data and archival 2MASS data we show that V2491 Cyg, at a distance of 10.5 - 14 kpc, is likely to be a recurrent nova of the U Sco-class; containing a sub-giant secondary and an accretion disk, rather than accretion directly onto the poles. We show that there is little evidence, at quiescence, supporting a ~ 0.1 day periodicity, the variation seen at this stage is likely caused by flickering of a re-established accretion disk. We propose that the periodicity seen shortly after outburst is more likely related to the outburst rather than the - then obscured - binary system. Finally we address the distance to the system, and show that a significantly lower distance (~ 2 kpc) would result in a severely under-luminous outburst, and as such favour the larger distance and the recurrent nova scenario.Comment: 5 pages, 3 images, accepted for publication in A&A as a research not