Numerically Modelling Time and Dose Dependent Cytotoxicity

Dose-response curves are fundamental tools of in vitro toxicology, extensively employed in toxicant or drug screening. They are expressed by a variety of end-points and assays, measured at different time-points in a choice of cell-lines, but are typically quantified only using the mean concentration for 50% response (e.g. drug efficacy or pathway inhibition) as an indicator of overall effect. However, the response is the result of a complex and dynamic cascade of events which occur between the initial exposure and the measured end-point, and the characteristic rates of the contributing stages govern the dose response and ultimately the measured characteristic concentration. A better understanding of the effects and interdependencies of these can help in interpreting the response curves. The system can be modelled according to a phenomenological rate equation approach, in which each stage of the process is characterised by a rate constant, and causal relationships between different processes are incorporated. The current study utilises such an approach to simulate some common response cascades of cell populations to exogenous agents and explores the dependences of the dose dependent response on, for example, number of steps in a cascade, time-point, and scenarios such as additive, synergistic and antagonistic response of multiple exogenous agents

Label-Free, High Content Screening Using Raman Microspectroscopy: The Toxicological Response of Different Cell Lines to Amine-Modified Polystyrene Nanoparticles

Nanotoxicology has become an established area of science due to growing concerns over the production and potential use of nanomaterials in a wide-range of areas from pharmaceutics to nanomedicine. Although different cytotoxicity assays have been developed and are widely used to determine the toxicity of nanomaterials, the production of multi-parametric information in a rapid and non-invasive way is still challenging, when the amount and diversity of physicochemical properties of nanomaterials are considered. High content screening can provide such analysis, but is often prohibitive in terms of capital and recurrent costs in academic environments. As a label-free technique, the applicability of Raman microspectroscopy for the analysis of cells, tissues and bodily fluids has been extensively demonstrated. The multi-parametric information in the fingerprint region has also been used for the determination of nanoparticle localisation and toxicity. In this study, the applicability of Raman microspectroscopy as a \u27high content nanotoxicological screening technique\u27 is demonstrated, with the aid of multivariate analysis, on non-cancerous (immortalized human bronchial epithelium) and cancerous cell-lines (human lung carcinoma and human lung epidermoid cells). Aminated polystyrene nanoparticles are chosen as model nanoparticles due to their well-established toxic properties and cells were exposed to the nanoparticles for periods from 24-72 hours. Spectral markers of cellular responses such as oxidative stress, cytoplasmic RNA aberrations and liposomal rupture are identified and cell-line dependent systematic variations in these spectral markers, as a function of the exposure time, are observed using Raman microspectroscopy, and are correlated with cellular assays and imaging techniques

A new galloping gait in an insect

An estimated three million insect species all walk using variations of the alternating tripod gait. At any one time, these animals hold one stable triangle of legs steady while swinging the opposite triangle forward. Here, we report the discovery that three different flightless desert dung beetles use an additional gallop-like gait, which has never been described in any insect before. Like a bounding hare, the beetles propel their body forward by synchronously stepping with both middle legs and then both front legs. Surprisingly, this peculiar galloping gait delivers lower speeds than the alternating tripod gait. Why these beetles have shifted so radically away from the most widely used walking style on our planet is as yet unknown

Exploring the Potential of Feature Selection Methods in the Classification of Urban Trees Using Field Spectroscopy Data

Mapping of vegetation at the species level using hyperspectral satellite data can be effective and accurate because of its high spectral and spatial resolutions that can detect detailed information of a target object. Its wide application, however, not only is restricted by its high cost and large data storage requirements, but its processing is also complicated by challenges of what is known as the Hughes effect. The Hughes effect is where classification accuracy decreases once the number of features or wavelengths passes a certain limit. This study aimed to explore the potential of feature selection methods in the classification of urban trees using field hyperspectral data. We identified the best feature selection method of key wavelengths that respond to the target urban tree species for effective and accurate classification. The study compared the effectiveness of Principal Component Analysis Discriminant Analysis (PCA-DA), Partial Least Squares Discriminant Analysis (PLS-DA) and Guided Regularized Random Forest (GRRF) in feature selection of the key wavelengths for classification of urban trees. The classification performance of Random Forest (RF) and Support Vector Machines (SVM) algorithms were also compared to determine the importance of the key wavelengths selected for the detection of the target urban trees. The feature selection methods managed to reduce the high dimensionality of the hyperspectral data. Both the PCA-DA and PLS-DA selected 10 wavelengths and the GRRF algorithm selected 13 wavelengths from the entire dataset (n = 1523). Most of the key wavelengths were from the short-wave infrared region (1300-2500 nm). SVM outperformed RF in classifying the key wavelengths selected by the feature selection methods. The SVM classifier produced overall accuracy values of 95.3%, 93.3% and 86% using the GRRF, PLS-DA and PCA-DA techniques, respectively, whereas those for the RF classifier were 88.7%, 72% and 56.8%, respectively

Night sky orientation with diurnal and nocturnal eyes: dim-light adaptations are critical when the moon is out of sight

The visual systems of many animals feature energetically costly specializations to enable them to function in dim light. It is often unclear, however, how large the behavioural benefit of these specializations is, because a direct comparison in a behaviourally relevant task between closely related day- and night-active species is not usually possible. Here we compared the orientation performance of diurnal and nocturnal species of dung beetles, Scarabaeus (Kheper) lamarcki and Scarabaeus satyrus, respectively, attempting to roll dung balls along straight paths both during the day and at night. Using video tracking, we quantified the straightness of paths and the repeatability of roll bearings as beetles exited a flat arena in their natural habitat or under controlled conditions indoors. Both species oriented equally well when either the moon or an artificial point light source was available, but when the view of the moon was blocked and only wide-field cues such as the lunar polarization pattern or the stars were available for orientation, nocturnal beetles were oriented substantially better. We found no evidence that ball-rolling speed changed with light level, which suggests little or no temporal summation in the visual system. Finally, we found that both diurnal and nocturnal beetles tended to choose bearings that led them towards a bright light source, but away from a dim one. Our results show that even diurnal insects, at least those with superposition eyes, could orient by the light of the moon, but that dim-light adaptations are needed for precise orientation when the moon is not visible

Efforts towards engaging communities to promote the benefits of biological control research and implementation in South Africa

In the last decade, biological control in South Africa has evolved from a classical applied science, allied to an extension service, to a more community engagement-based activity. Therefore, capacity building is important for the sustainability of biological control research and its implementation. In South Africa, a broad approach has been taken to build capacity in weed biological control, starting at grass-roots level with primary and secondary school learner programmes, through to developing research capacity at the tertiary level and enhancing technical capacity through adult education. Non-specialists are empowered through access to knowledge. The dissemination of accurate information through the most appropriate outlets has become increasingly important, including non-traditional science communication through the internet and, more importantly, social media, which has the potential to reach a far wider audience. Public understanding of biological control has the potential to contribute significantly to the green and knowledge economies of South Africa, but relies on government support for the sustainability of this discipline

Three new biological control programmes for South Africa: Brazilian pepper, Tamarix and Tradescantia

Three weed biological control (biocontrol) programmes are described, all of which are considered to be ‘transfer projects’ that were initiated elsewhere, and on which South Africa has piggybacked its biocontrol efforts. Using knowledge and expertise from international collaborators, South African weed researchers are following a long tradition of transfer projects, which has been a largely successful and practical approach to biocontrol. Two Brazilian weeds, the Brazilian pepper tree Schinus terebinthifolia and the spiderwort Tradescantia fluminensis are being targeted, along with the Old-World trees Tamarix ramosissima and T. chinensis. The potential biocontrol agents are described and ranked for the two trees according to what has been discovered elsewhere, while the agent already released against T. fluminensis is rated (as poor), and other potential agents are considered. The addition of molecular techniques, climate matching and remote sensing in transfer projects can increase the chance of successful biocontrol and the inclusion of these techniques in the three new programmes is discussed. Transfer projects are a cost-effective and pragmatic way to pick winning biocontrol programmes

The Dung Beetle Dance: An Orientation Behaviour?

An interesting feature of dung beetle behaviour is that once they have formed a piece of dung into a ball, they roll it along a straight path away from the dung pile. This straight-line orientation ensures that the beetles depart along the most direct route, guaranteeing that they will not return to the intense competition (from other beetles) that occurs near the dung pile. Before rolling a new ball away from the dung pile, dung beetles perform a characteristic “dance,” in which they climb on top of the ball and rotate about their vertical axis. This dance behaviour can also be observed during the beetles' straight-line departure from the dung pile. The aim of the present study is to investigate the purpose of the dung beetle dance. To do this, we explored the circumstances that elicit dance behaviour in the diurnal ball-rolling dung beetle, Scarabaeus (Kheper) nigroaeneus. Our results reveal that dances are elicited when the beetles lose control of their ball or lose contact with it altogether. We also find that dances can be elicited by both active and passive deviations of course and by changes in visual cues alone. In light of these results, we hypothesise that the dung beetle dance is a visually mediated mechanism that facilitates straight-line orientation in ball-rolling dung beetles by allowing them to 1) establish a roll bearing and 2) return to this chosen bearing after experiencing a disturbance to the roll path

Cold Atmospheric Plasma Stimulates Clathrin-Dependent Endocytosis to Repair Oxidised Membrane and Enhance Uptake of Nanomaterial in Glioblastoma Multiforme Cells

peer-reviewedCold atmospheric plasma (CAP) enhances uptake and accumulation of nanoparticles and promotes synergistic cytotoxicity against cancer cells. However, the mechanisms are not well understood. In this study, we investigate the enhanced uptake of theranostic nanomaterials by CAP. Numerical modelling of the uptake of gold nanoparticle into U373MG Glioblastoma multiforme (GBM) cells predicts that CAP may introduce a new uptake route. We demonstrate that cell membrane repair pathways play the main role in this stimulated new uptake route, following non-toxic doses of dielectric barrier discharge CAP. CAP treatment induces cellular membrane damage, mainly via lipid peroxidation as a result of reactive oxygen species (ROS) generation. Membranes rich in peroxidised lipids are then trafficked into cells via membrane repairing endocytosis. We confirm that the enhanced uptake of nanomaterials is clathrin-dependent using chemical inhibitors and silencing of gene expression. Therefore, CAP-stimulated membrane repair increases endocytosis and accelerates the uptake of gold nanoparticles into U373MG cells after CAP treatment. We demonstrate the utility of CAP to model membrane oxidative damage in cells and characterise a previously unreported mechanism of membrane repair to trigger nanomaterial uptake. This knowledge will underpin the development of new delivery strategies for theranostic nanoparticles into cancer cells

Systems biologists seek fuller integration of systems biology approaches in new cancer research programs

Systems biology takes an interdisciplinary approach to the systematic study of complex interactions in biological systems. This approach seeks to decipher the emergent behaviors of complex systems rather than focusing only on their constituent properties. As an increasing number of examples illustrate the value of systems biology approaches to understand the initiation, progression, and treatment of cancer, systems biologists from across Europe and the United States hope for changes in the way their field is currently perceived among cancer researchers. In a recent EU-US workshop, supported by the European Commission, the German Federal Ministry for Education and Research, and the National Cancer Institute of the NIH, the participants discussed the strengths, weaknesses, hurdles, and opportunities in cancer systems biology