Native silica nanoparticles are powerful membrane disruptors

Silica nanoparticles are under development for intracellular drug delivery applications but can also have cytotoxic effects including cell membrane damage. In this study, we investigated the interactions of silica nanospheres of different size, surface chemistry and biocoating with membranes of phosphatidylcholine lipids. In liposome leakage assays many, but not all, of these nanoparticles induced dose-dependent dye leakage, indicative of membrane perturbation. It was found that 200 and 500 nm native-silica, aminated and carboxylated nanospheres induce near-total dye release from zwitterionic phosphatidylcholine liposomes at a particle/liposome ratio of ~1, regardless of their surface chemistry, which we interpret as particle-supported bilayer formation following a global rearrangement of the vesicular membrane. In contrast, 50 nm diameter native-silica nanospheres did not induce total dye leakage below a particle/liposome ratio of ~8, whereas amination or carboxylation, respectively, strongly reduced or prevented dye release. We postulate that for the smaller nanospheres, strong silica-bilayer interactions are manifested as bilayer engulfement of membrane-adsorbed particles, with localized lipid depletion eventually leading to collapse of the vesicular membrane. Protein coating of the particles considerably reduced dye leakage and lipid bilayer coating prevented dye release all together, while the inclusion of 33% anionic lipids in the liposomes reduced dye leakage for both native-silica and aminated surfaces. These results, which are compared with the effect of polystyrene nanoparticles and other engineered nanomaterials on lipid bilayers, and which are discussed in relation to nanosilica-induced cell membrane damage and cytotoxicity, indicate that a native-silica nanoparticle surface chemistry is a particularly strong membrane interaction motif

Reflections on innovation networks: contractual vs. "conventional" networks

This paper helps to define the concept of innovation networks, in the context of urbanregional development. Faced with the Schumpeterian theory of innovation, a concept based on cumulative actions within innovation processes tends to emerge. These processes are presented as forms of "organization" which more or less explicitly link several different hierarchical organizations, without merging them, according to rules and requirements which are not limited to those of the market. The first part of the paper outlines some important characteristics of innovation processes. These complex processes need to be supplied with various resources, especially information resources which are produced in rapidly increasing quantities nowadays. This increase in turn causes an increase in both the purchase and transaction costs of information resources. A possible way of reducing these costs is to work towards cooperation between firms or institutions possessing complementary resources. The second part of the paper examines the concept of innovation networks. Within these innovation networks there are, on one hand, networks established on a contractual basis, often trans-territorial, and, on the other hand, networks established on a "conventional" basis (in the sense of the "economy of conventions"). It is believed, generally speaking, that the latter type of network can only develop within "districts" according to the Marshallian theory of the concept, and only after a long process of collective learning

Belousov-Zhabotinsky droplet mixing on-chip for chemical computing applications

Without an imposed physical structure, even the most complex chemistries are limited in their ability to process information. For example, the Belousov-Zhabotinsky (BZ) oscillating reaction has been shown to have information procession potential, but only if structure is imposed e.g. using physical barriers or light-sensitive catalysts. Recently, separated BZ droplets in oil have been investigated. Another option for aqueous/oil systems is to add lipid into the oil, which self-assembles into a monolayer at the phase boundary. If the lipid-stabilised droplets are brought into contact, a bilayer is formed, separating the BZ droplets into compartments. This technique is more flexible than other methods of imparting structure, allowing for the creation of droplet arrays inspired by biological neuronal networks

Cell-free protein expression systems in microdroplets: stabilization of interdroplet bilayers

Cell-free protein expression with bacterial lysates has been demonstrated to produce soluble proteins in microdroplets. However, droplet assays with expressed membrane proteins require the presence of a lipid bilayer. A bilayer can be formed in between lipid-coated aqueous droplets by bringing these into contact by electrokinetic manipulation in a continuous oil phase, but it is not known whether such interdroplet bilayers are compatible with high concentrations of biomolecules. In this study we have characterized the lifetime and the structural integrity of interdroplet bilayers by measuring the bilayer current in the presence of three different commercial cell-free expression mixtures and their individual components. Samples of pure proteins and of a polymer were included for comparison. It is shown that complete expression mixtures reduce the bilayer lifetime to several minutes or less, and that this is mainly due to the lysate fraction itself. The fraction that contains the molecules for metabolic energy generation does not reduce the bilayer lifetime but does give rise to current steps that are indicative of lipid packing defects. Gel electrophoresis confirmed that proteins are only present at significant amounts in the lysate fractions and, when supplied separately, in the T7 enzyme mixture. Interestingly, it was also found that pure-protein and pure-polymer solutions perturb the interdroplet bilayer at higher concentrations; 10% (w/v) PEG 8000 and 3 mM lysozyme induce large bilayer currents without a reduction in bilayer lifetime, whereas 3 mM albumin causes rapid bilayer failure. It can therefore be concluded that the high protein content of the lysates and the presence of PEG polymer, a typical lysate supplement, compromise the structural integrity of interdroplet bilayers. However, we established that the addition of lipid vesicles to the cell-free expression mixture stabilizes the interdroplet bilayer, allowing the exposure of interdroplet bilayers to cell-free expression solutions. Given that cell-free expressed membrane proteins can insert in lipid bilayers, we envisage that microdroplet technology may be extended to the study of in situ expressed membrane receptors and ion channel

Failure to diagnose fatal disseminated toxoplasmosis in a bone marrow transplant recipient : the possible significance of declining antibody titres.

Contains fulltext : 4489.pdf (publisher's version ) (Open Access

Climate fluctuations and the spring invasion of the North Sea by Calanus finmarchicus

The population of Calanus finmarchicus in the North Sea is replenished each spring by invasion from an overwintering stock located beyond the shelf edge. A combincation of field observations, statistical analysis of Continuous Plankton Recorder (CPR) data, and particle tracking model simulations, was used to investigate the processes involved in the cross-shelf invasion. The results showed that the main source of overwintering animals entering the North Sea in the spring is at depths of greater than 600m in the Faroe Shetland Channel, where concentrations of up to 620m -3 are found in association with the overflow of Norwegian Sea Deep Water (NSDW) across the Iceland Scotland Ridge. The input of this water mass to the Faroe Shetland Channel, and hence the supply of overwintering C. finmarchicus, has declined since the late 1960s due to changes in convective processes in the Greenland Sea. Beginning in February, animals start to emerge from the overwintering state and migrate to the surface waters, where their transport into the North Sea is mainly determined by the incidence of north-westerly winds that have declined since the 1960s. Together, these two factors explain a high proportion of the 30-year trends in spring abundance in the North Sea as measured by the CPR survey. Both the regional winds and the NSDW overflow are connected to the North Atlantic Oscillation Index (NAO), which is an atmospheric climate index, but with different time scales of response. Thus, interannual fluctuations in the NAO can cause immediate changes in the incidence of north-westerly winds without leading to corresponding changes in C. finmarchicus abundance in the North Sea, because the NSDW overflow responds over longer (decadal) time scales

New cod war of words:'Cod is God' versus 'sod the cod'—Two opposed discourses on the North Sea Cod Recovery Programme

New insights into the North Sea Cod Recovery Programme (CRP), initiated in 2003 by the European Commission to reverse the long-term decline in cod stocks, are presented using discourse analysis. The main conservation measures taken under the CRP have been to reduce catch limits drastically and to increase control over vessels' fishing activities. There has been considerable controversy over the programme from its inception, with protagonists broadly divided into two discourses: (1) 'cod is God'-in which cod has assumed the status of the defining test of the European Union's (EU) resolve to manage fish stocks sustainably in EU waters; (2) 'sod the cod'-in which cod is regarded as one of a number of target commercial fish species, with no special status. Drawing on Frank Fischer's distinction between hegemonic and challenging discourses, we analyse the conflict between them at three levels: empirical; conceptual; and political. We consider moves to reconcile the two discourses in a policy consensus on a revised CRP, which suggest that the challenging discourse (sod-the-cod) has had some success in modifying the impact of the hegemonic discourse (cod-is-God

A game-theoretic model of interspecific brood parasitism with sequential decisions

The interaction between hosts and parasites in bird populations has been studied extensively. This paper uses game-theoretic methods to model this interaction. This has been done in previous papers but has not been studied taking into account the detailed sequential nature of this game. We introduce a model allowing the host and parasite to make a number of decisions which will depend on various natural factors. The sequence of events begins with the host forming a nest and laying a number of eggs, followed by the possibility that a parasite bird will arrive at the nest; if it does it can choose to destroy some of the host eggs and lay one of its own. A sequence of events follows, which is broken down into two key stages; firstly the interaction between the host and the parasite adult, and secondly that between the host and the parasite chick. The final decision involves the host choosing whether to raise or abandon the chicks that are in the nest. There are certain natural parameters and probabilities which are central to these various decisions; in particular the host is generally uncertain whether parasitism has taken place, but can assess the likelihood of parasitism based upon certain cues (e.g. how many eggs remain in its nest). We then use this methodology to model two real-world interactions, that of the Reed Warbler with the Common Cuckoo and also the Yellow Warbler with the Brown-headed Cowbird. These parasites have different methods in the way they parasitize the nests of their hosts, and the hosts can in turn have different reactions to these parasites. Our model predictions generally match the real results well, and the model also makes predictions of the effect of changes in various key parameters on the type of parasitic interactions that should occur