Mechanism of cellular uptake of genotoxic silica nanoparticles.

Mechanisms for cellular uptake of nanoparticles have important implications for nanoparticulate drug delivery and toxicity. We have explored the mechanism of uptake of amorphous silica nanoparticles of 14 nm diameter, which agglomerate in culture medium to hydrodynamic diameters around 500 nm. In HT29, HaCat and A549 cells, cytotoxicity was observed at nanoparticle concentrations ≥ 1 μg/ml, but DNA damage was evident at 0.1 μg/ml and above. Transmission electron microscopy (TEM) combined with energy-dispersive X-ray spectroscopy confirmed entry of the silica particles into A549 cells exposed to 10 μg/ml of nanoparticles. The particles were observed in the cytoplasm but not within membrane bound vesicles or in the nucleus. TEM of cells exposed to nanoparticles at 4°C for 30 minutes showed particles enter cells when activity is low, suggesting a passive mode of entry. Plasma lipid membrane models identified physical interactions between the membrane and the silica NPs. Quartz crystal microbalance experiments on tethered bilayer lipid membrane systems show that the nanoparticles strongly bind to lipid membranes, forming an adherent monolayer on the membrane. Leakage assays on large unilamellar vesicles (400 nm diameter) indicate that binding of the silica NPs transiently disrupts the vesicles which rapidly self-seal. We suggest that an adhesive interaction between silica nanoparticles and lipid membranes could cause passive cellular uptake of the particles

Active Set methods for solving large sample average approximations of chance constrained optimisation problems

This article describes a novel approach to chance-constrained programming based on the sample average approximation (SAA) method. Recent work focuses on heuristic approximations to the SAA problem and we introduce a novel approach which improves on some existing methods. Our Active Set method allows one to solve SAAs of chance-constrained programs with very large numbers of scenarios quickly. We demonstrate that increasing the number of scenarios is more important than improving accuracy with small numbers of scenarios. We use an example of the portfolio selection problem to demonstrate the relative performance of previous and new methods. Extending the Active Set method to an integer-programming model further highlights its applicability and further improves over previous approaches.Comment: 26 pages, 7 figures, This paper sets forth the material presented at the Decision Making Under Uncertainty workshop held at the University of Queensland, 11 July 202

Extracellular Electron Transfer: Respiratory or Nutrient Homeostasis?

Exoelectrogens are able to transfer electrons extracellularly, enabling them to respire on insoluble terminal electron acceptors. Extensively studied exoelectrogens, such as Geobacter sulfurreducens and Shewanella oneidensis, are Gram negative. More recently, it has been reported that Gram-positive bacteria, such as Listeria monocytogenes and Enterococcus faecalis, also exhibit the ability to transfer electrons extracellularly, although it is still unclear whether this has a function in respiration or in redox control of the environment, for instance, by reducing ferric iron for iron uptake. In this issue of Journal of Bacteriology, Hederstedt and colleagues report on experiments that directly compare extracellular electron transfer (EET) pathways for ferric iron reduction and respiration and find a clear difference (L. Hederstedt, L. Gorton, and G. Pankratova, J Bacteriol 202:e00725-19, 2020, https://doi.org/10.1128/JB.00725-19), providing further insights and new questions into the function and metabolic pathways of EET in Gram-positive bacteria

Participatory plant breeding: a way to arrive at better-adapted onion varieties

The search for varieties that are better adapted to organic farming is a current topic in the organic sector. Breeding programmes specific for organic agriculture should solve this problem. Collaborating with organic farmers in such programmes, particularly in the selection process, can potentially result in varieties better adapted to their needs. Here, we assume that organic farmers' perceptive of plant health is broader than that of conventional breeders. Two organic onion farmers and one conventional onion breeder were monitored in their selection activities in 2004 and 2005 in order to verify whether and in which way this broader view on plant health contributes to improvement of organic varieties. They made selections by positive mass selection in three segregating populations under organic conditions. The monitoring showed that the organic farmers selected in the field for earliness and downy mildew and after storage for bulb characteristics. The conventional breeder selected only after storage. Farmers and breeder applied identical selection directions for bulb traits as a round shape, better hardness and skin firmness. This resulted in smaller bulbs in the breeders’ populations, while the bulbs in the farmer populations were bigger than in the original population. In 2006 and 2007 the new onion populations will be compared with each other and the original populations to determine the selection response