Ultrasound delivery of Surface Enhanced InfraRed Absorption active gold-nanoprobes into fibroblast cells: a biological study via Synchrotron-based InfraRed microanalysis at single cell level

Ultrasound (US) induced transient membrane permeabilisation has emerged as a hugely promising tool for the delivery of exogenous vectors through the cytoplasmic membrane, paving the way to the design of novel anticancer strategies by targeting functional nanomaterials to specific biological sites. An essential step towards this end is the detailed recognition of suitably marked nanoparticles in sonoporated cells and the investigation of the potential related biological effects. By taking advantage of Synchrotron Radiation fourier transform infrared micro-spectroscopy (SR-microftiR) in providing highly sensitive analysis at the single cell level, we studied the internalisation of a nanoprobe within fibroblasts (NIH-3T3) promoted by low-intensity US. To this aim we employed 20 nm gold nanoparticles conjugated with the IR marker 4-aminothiophenol. The significant Surface Enhanced Infrared Absorption provided by the nanoprobes, with an absorbance increase up to two orders of magnitude, allowed us to efficiently recognise their inclusion within cells. Notably, the selective and stable SR- microftiR detection from single cells that have internalised the nanoprobe exhibited clear changes in both shape and intensity of the spectral profile, highlighting the occurrence of biological effects. Flow cytometry, immunofluorescence and murine cytokinesis-block micronucleus assays confirmed the presence of slight but significant cytotoxic and genotoxic events associated with the US-nanoprobe combined treatments. our results can provide novel hints towards US and nanomedicine combined strategies for cell spectral imaging as well as drug delivery-based therapies

Daemonic ergotropy in continuously-monitored open quantum batteries

The amount of work that can be extracted from a quantum system can be increased by exploiting the information obtained from a measurement performed on a correlated ancillary system. The concept of daemonic ergotropy has been introduced to properly describe and quantify this work extraction enhancement in the quantum regime. We here explore the application of this idea in the context of continuously-monitored open quantum systems, where information is gained by measuring the environment interacting with the energy-storing quantum device. We first show that the corresponding daemonic ergotropy takes values between the ergotropy and the energy of the corresponding unconditional state. The upper bound is achieved by assuming an initial pure state and a perfectly efficient projective measurement on the environment, independently of the kind of measurement performed. On the other hand, if the measurement is inefficient or the initial state is mixed, the daemonic ergotropy is generally dependent on the measurement strategy. This scenario is investigated via a paradigmatic example of an open quantum battery: a two-level atom driven by a classical field and whose spontaneously emitted photons are continuously monitored via either homodyne, heterodyne, or photo-detection.Comment: 6 pages, 4 figure

"Non-retinotopic processing" in Ternus motion displays modeled by spatiotemporal filters

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spatiotemporal filtering and motion illusions

We are perplexed by Clarke et al.'s (2013) criticisms on our recent contribution to Journal of Vision (Pooresmaeili, Cicchini, Morrone, & Burr, 2012). Our group has long championed the idea that perceptual processing of information can be anchored in a dynamic coordinate system that need not correspond to the instantaneous retinal representation. Our recent evidence shows that temporal duration (Burr, Tozzi, & Morrone, 2007; Morrone, Cicchini, & Burr, 2010), orientation (Zimmermann, Morrone, Fink, & Burr, 2013), motion (Melcher & Morrone, 2003; Turi & Burr, 2012) and saccadic error-correction (Zimmermann, Burr, & Morrone, 2011) are all processed to some extent in spatiotopic coordinates. Imaging studies reinforce these studies (d'Avossa et al., 2007; Crespi et al., 2011). Much earlier, we showed that the processing of smoothly moving objects was not anchored in instantaneous, retinotopic coordinates, but in the reference frame given by the trajectory of motion. There is an effective interpolation along the trajectory, so temporal offsets in spatially collinear stimuli causes them to appear spatially offset, corresponding to the physical reality of stimuli moving over large regions of space, behind occluders (Burr, 1979; Burr & Ross, 1979). Our explanation for this surprising effect was that it could be a direct consequence of the spatiotemporal orientation of the impulsive response of motion detectors, providing the spatiotemporal reference frame needed to account for the interactions between time and space (Burr & Ross, 1986; Burr, Ross, & Morrone, 1986; Burr & Ross, 2004; Nishida, 2004). Recently, we have applied the concept of spatiotemporal oriented receptive fields to account for ''predictive remapping,'' the ''nonretinotopic'' effects that occur on each saccadic eye-movement (Burr & Morrone, 2010; Burr & Morrone, 2012; Cicchini, Binda, Burr, & Morrone, 2012). We were most impressed by the compelling demonstrations of Herzog's group, clearly showing that the reference frame of processing is not the instantaneous retinal position, but is flexible, depending not only on real physical motion, but on an illusory apparent motion where the stimuli do not actually move (Boi, Ogmen, Krummenacher, Otto, & Herzog, 2009). This seemed to us important, worthy of quantitative measurement and modeling, particularly to see whether these new effects may fall within the framework that so successfully explained previous demonstrations, such as spatiotemporal interpolation. It is reassuring that Clarke et al. (2013) confirm our results, albeit with some variability between subjects. But more importantly add a very nice result in showing that our simplified version of the ''litmus test'' can be enhanced by attending to the motion. This is an excellent point that we overlooked. The strength of this type of motion is well known to depend on attention (Cavanagh, 1992), and it is indeed interesting that the strength of motion-induced effects depends not only on the physical conditions, but on internal states such as attention. Perhaps attention may also provide the flexibility in choosing the most appropriate scale for analysis, which in this case would be lower, given that attention is diverted to the periphery. This would add strength to our model, and an idea worth following up

Differential effects on membrane permeability and viability of human keratinocyte cells undergoing very low intensity megasonic fields

Among different therapeutic applications of Ultrasound (US), transient membrane sonoporation (SP) - a temporary, non-lethal porosity, mechanically induced in cell membranes through US exposure - represents a compelling opportunity towards an efficient and safe drug delivery. Nevertheless, progresses in this field have been limited by an insufficient understanding of the potential cytotoxic effects of US related to the failure of the cellular repair and to the possible activation of inflammatory pathway. In this framework we studied the in vitro effects of very low-intensity US on a human keratinocyte cell line, which represents an ideal model system of skin protective barrier cells which are the first to be involved during medical US treatments. Bioeffects linked to US application at 1 MHz varying the exposure parameters were investigated by fluorescence microscopy and fluorescence activated cell sorting. Our results indicate that keratinocytes undergoing low US doses can uptake drug model molecules with size and efficiency which depend on exposure parameters. According to sub-cavitation SP models, we have identified the range of doses triggering transient membrane SP, actually with negligible biological damage. By increasing US doses we observed a reduced cells viability and an inflammatory gene overexpression enlightening novel healthy relevant strategies

Spatiotopic selectivity of adaptation-based compression of event duration

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Charging a quantum battery in a non-Markovian environment: a collisional model approach

We study the effect of non-Markovianity in the charging process of an open-system quantum battery. We employ a collisional model framework, where the environment is described by a discrete set of ancillary systems and memory effects in the dynamics can be introduced by allowing these ancillas to interact. We study in detail the behaviour of the steady-state ergotropy and the impact of the information backflow to the system on the different features characterizing the charging process. Remarkably, we find that there is a maximum value of the ergotropy achievable: this value can be obtained either in the presence of memoryless environment, but only in the large-loss limit, as derived in [D. Farina et al., Phys. Rev. B 99, 035421 (2019)], or in the presence of an environment with memory also beyond the large-loss limit. In general, we show that the presence of an environment with memory allows us to generate steady-state ergotropy near to its maximum value for a much larger region in the parameter space and thus potentially in a shorter time. Relying on the geometrical measure of non-Markovianity, we show that in both the cases of an environment with and without memory the ergotropy maximum is obtained when the non-Markovianity of the dynamics of the battery is zero, possibly as the result of a non-trivial interplay between the memory effects induced by, respectively, the environment and the charger connected to the battery

Using psychophysical performance to predict short-term ocular dominance plasticity in human adults

Binocular rivalry has become an important index of visual performance, both to measure ocular dominance or its plasticity, and to index bistable perception. We investigated its interindividual variability across 50 normal adults and found that the duration of dominance phases in rivalry is linked with the duration of dominance phases in another bistable phenomenon (structure from motion). Surprisingly, it also correlates with the strength of center-surround interactions (indexed by the tilt illusion), suggesting a common mechanism supporting both competitive interactions: center-surround and rivalry. In a subset of 34 participants, we further investigated the variability of short-term ocular dominance plasticity, measured with binocular rivalry before and after 2 hours of monocular deprivation. We found that ocular dominance shifts in favor of the deprived eye and that a large portion of ocular dominance variability after deprivation can be predicted from the dynamics of binocular rivalry before deprivation. The single best predictor is the proportion of mixed percepts (phases without dominance of either eye) before deprivation, which is positively related to ocular dominance unbalance after deprivation. Another predictor is the duration of dominance phases, which interacts with mixed percepts to explain nearly 50% of variance in ocular dominance unbalance after deprivation. A similar predictive power is achieved by substituting binocular rivalry dominance phase durations with tilt illusion magnitude, or structure from motion phase durations. Thus, we speculate that ocular dominance plasticity is modulated by two types of signals, estimated from psychophysical performance before deprivation, namely, interocular inhibition (promoting binocular fusion, hence mixed percepts) and inhibition for perceptual competition (promoting longer dominance phases and stronger center-surround interactions)

Epstein-Barr virus lytic infection promotes activation of Toll-like receptor 8 innate immune response in systemic sclerosis monocytes

BACKGROUND: Monocytes/macrophages are activated in several autoimmune diseases, including systemic sclerosis (scleroderma; SSc), with increased expression of interferon (IFN)-regulatory genes and inflammatory cytokines, suggesting dysregulation of the innate immune response in autoimmunity. In this study, we investigated whether the lytic form of Epstein-Barr virus (EBV) infection (infectious EBV) is present in scleroderma monocytes and contributes to their activation in SSc. METHODS: Monocytes were isolated from peripheral blood mononuclear cells (PBMCs) depleted of the CD19+ cell fraction, using CD14/CD16 negative-depletion. Circulating monocytes from SSc and healthy donors (HDs) were infected with EBV. Gene expression of innate immune mediators were evaluated in EBV-infected monocytes from SSc and HDs. Involvement of Toll-like receptor (TLR)8 in viral-mediated TLR8 response was investigated by comparing the TLR8 expression induced by infectious EBV to the expression stimulated by CL075/TLR8/agonist-ligand in the presence of TLR8 inhibitor in THP-1 cells. RESULTS: Infectious EBV strongly induced TLR8 expression in infected SSc and HD monocytes in vitro. Markers of activated monocytes, such as IFN-regulated genes and chemokines, were upregulated in SSc- and HD-EBV-infected monocytes. Inhibiting TLR8 expression reduced virally induced TLR8 in THP-1 infected cells, demonstrating that innate immune activation by infectious EBV is partially dependent on TLR8. Viral mRNA and proteins were detected in freshly isolated SSc monocytes. Microarray analysis substantiated the evidence of an increased IFN signature and altered level of TLR8 expression in SSc monocytes carrying infectious EBV compared to HD monocytes. CONCLUSION: This study provides the first evidence of infectious EBV in monocytes from patients with SSc and links EBV to the activation of TLR8 and IFN innate immune response in freshly isolated SSc monocytes. This study provides the first evidence of EBV replication activating the TLR8 molecular pathway in primary monocytes. Immunogenicity of infectious EBV suggests a novel mechanism mediating monocyte inflammation in SSc, by which EBV triggers the innate immune response in infected cells