Toxicity and imaging of multi-walled carbon nanotubes in human macrophage cells.

Multi-walled carbon nanotubes (MWNTs) have been proposed for use in many applications and concerns about their potential effect on human health have led to the interest in understanding the interactions between MWNTs and human cells. One important technique is the visualisation of the intracellular distribution of MWNTs. We exposed human macrophage cells to unpurified MWNTs and found that a decrease in cell viability was correlated with uptake of MWNTs due to mainly necrosis. Cells treated with purified MWNTs and the main contaminant Fe(2)O(3) itself yielded toxicity only from the nanotubes and not from the Fe(2)O(3). We used 3-D dark-field scanning transmission electron microscopy (DF-STEM) tomography of freeze-dried whole cells as well as confocal and scanning electron microscopy (SEM) to image the cellular uptake and distribution of unpurified MWNTs. We observed that unpurified MWNTs entered the cell both actively and passively frequently inserting through the plasma membrane into the cytoplasm and the nucleus. These suggest that MWNTs may cause incomplete phagocytosis or mechanically pierce through the plasma membrane and result in oxidative stress and cell death.

Short-term in vitro responses of human peripheral blood monocytes to ferritic stainless steel fiber networks.

Beneficial effects on bone-implant bonding may accrue from ferromagnetic fiber networks on implants which can deform in vivo inducing controlled levels of mechanical strain directly in growing bone. This approach requires ferromagnetic fibers that can be implanted in vivo without stimulating undue inflammatory cell responses or cytotoxicity. This study examines the short-term in vitro responses, including attachment, viability, and inflammatory stimulation, of human peripheral blood monocytes to 444 ferritic stainless steel fiber networks. Two types of 444 networks, differing in fiber cross section and thus surface area, were considered alongside austenitic stainless steel fiber networks, made of 316L, a widely established implant material. Similar high percent seeding efficiencies were measured by CyQuant® on all fiber networks after 48 h of cell culture. Extensive cell attachment was confirmed by fluorescence and scanning electron microscopy, which showed round monocytes attached at various depths into the fiber networks. Medium concentrations of lactate dehydrogenase (LDH) and tumor necrosis factor alpha (TNF-α) were determined as indicators of viability and inflammatory responses, respectively. Percent LDH concentrations were similar for both 444 fiber networks at all time points, whereas significantly lower than those of 316L control networks at 24 h. All networks elicited low-level secretions of TNF-α, which were significantly lower than that of the positive control wells containing zymosan. Collectively, the results indicate that 444 networks produce comparable responses to medical implant grade 316L networks and are able to support human peripheral blood monocytes in short-term in vitro cultures without inducing significant inflammatory or cytotoxic effects.

A high-resolution atlas and statistical model of the human heart from multislice CT

Atlases and statistical models play important roles in the personalization and simulation of cardiac physiology. For the study of the heart, however, the construction of comprehensive atlases and spatio-temporal models is faced with a number of challenges, in particular the need to handle large and highly variable image datasets, the multi-region nature of the heart, and the presence of complex as well as small cardiovascular structures. In this paper, we present a detailed atlas and spatio-temporal statistical model of the human heart based on a large population of 3D+time multi-slice computed tomography sequences, and the framework for its construction. It uses spatial normalization based on nonrigid image registration to synthesize a population mean image and establish the spatial relationships between the mean and the subjects in the population. Temporal image registration is then applied to resolve each subject-specific cardiac motion and the resulting transformations are used to warp a surface mesh representation of the atlas to fit the images of the remaining cardiac phases in each subject. Subsequently, we demonstrate the construction of a spatio-temporal statistical model of shape such that the inter-subject and dynamic sources of variation are suitably separated. The framework is applied to a 3D+time data set of 138 subjects. The data is drawn from a variety of pathologies, which benefits its generalization to new subjects and physiological studies. The obtained level of detail and the extendability of the atlas present an advantage over most cardiac models published previously. © 1982-2012 IEEE.

Encoding of marginal utility across time in the human brain.

Marginal utility theory prescribes the relationship between the objective property of the magnitude of rewards and their subjective value. Despite its pervasive influence, however, there is remarkably little direct empirical evidence for such a theory of value, let alone of its neurobiological basis. We show that human preferences in an intertemporal choice task are best described by a model that integrates marginally diminishing utility with temporal discounting. Using functional magnetic resonance imaging, we show that activity in the dorsal striatum encodes both the marginal utility of rewards, over and above that which can be described by their magnitude alone, and the discounting associated with increasing time. In addition, our data show that dorsal striatum may be involved in integrating subjective valuation systems inherent to time and magnitude, thereby providing an overall metric of value used to guide choice behavior. Furthermore, during choice, we show that anterior cingulate activity correlates with the degree of difficulty associated with dissonance between value and time. Our data support an integrative architecture for decision making, revealing the neural representation of distinct subcomponents of value that may contribute to impulsivity and decisiveness.

Human pavlovian-instrumental transfer.

The vigor with which a participant performs actions that produce valuable outcomes is subject to a complex set of motivational influences. Many of these are believed to involve the amygdala and the nucleus accumbens, which act as an interface between limbic and motor systems. One prominent class of influences is called pavlovian-instrumental transfer (PIT), in which the motivational characteristics of a predictor influence the vigor of an action with respect to which it is formally completely independent. We provide a demonstration of behavioral PIT in humans, with an audiovisual predictor of the noncontingent delivery of money inducing participants to perform more avidly an action involving squeezing a handgrip to earn money. Furthermore, using functional magnetic resonance imaging, we show that this enhanced motivation was associated with a trial-by-trial correlation with the blood oxygenation level-dependent (BOLD) signal in the nucleus accumbens and a subject-by-subject correlation with the BOLD signal in the amygdala. Our data dovetails well with the animal literature and sheds light on the neural control of vigor.

Contingency awareness in human aversive conditioning involves the middle frontal gyrus.

In contrast to the wealth of data describing the neural mechanisms underlying classical conditioning, we know remarkably little about the mechanisms involved in acquisition of explicit contingency awareness. Subjects variably acquire contingency awareness in classical conditioning paradigms, in which they are able to describe the temporal relationship between a conditioned cue and its outcome. Previous studies have implicated the hippocampus and prefrontal cortex in the acquisition of explicit knowledge, although their specific roles remain unclear. We used functional magnetic resonance imaging to track the trial-by-trial acquisition of explicit knowledge in a concurrent trace and delay conditioning paradigm. We show that activity in bilateral middle frontal gyrus and parahippocampal gyrus correlates with the accuracy of explicit contingency awareness on each trial. In contrast, amygdala activation correlates with conditioned responses indexed by skin conductance responses (SCRs). These results demonstrate that brain regions known to be involved in other aspects of learning and memory also play a specific role, reflecting on each trial the acquisition and representation of contingency awareness.

Short-term cytotoxic and inflammatory responses of human monocytes to stainless steel fibre networks

The aim of the current work was to examine the human monocyte response to 444 ferritic stainless steel fibre networks. 316L austenitic fibre networks, of the same fibre volume fraction, were used as control surfaces. Fluorescence and scanning electron microscopies suggest that the cells exhibited a good degree of attachment and penetration throughout both networks. Lactate Dehydrogenase (LDH) and TNF-α releases were used as indicators of cytotoxicity and inflammatory responses respectively. LDH release indicated similar levels of monocyte viability when in contact with the 444 and 316L fibre networks. Both networks elicited a low level secretion of TNF-α, which was significantly lower than that of the positive control wells containing zymosan. Collectively, the results suggest that 444 ferritic and 316L austenitic networks induced similar cytotoxic and inflammatory responses from human monocytes. © 2012 Materials Research Society.