pH-Dependent Silica Nanoparticle Dissolution and 1 Cargo Release

The dissolution of microporous silica nanoparticles (NP) in aqueous environments of different biologically relevant pH was studied in order to assess their potential as drug delivery vehicles. Silica NPs, loaded with fluorescein, were prepared using different organosilane precursors (tetraethoxysilane, ethyl triethoxysilane or a 1:1 molar ratio of both) and NP dissolution was evaluated in aqueous conditions at pH 4, pH 6 and pH 7.4. These conditions correspond to the acidity of the intracellular environment (late endosome, early endosome, cytosol respectively) and gastrointestinal tract (‘fed’ stomach, duodenum and jejunum respectively). All NPs degraded at pH 6 and pH 7.4, while no dissolution was observed at pH 4. NP dissolution could be clearly visualised as mesoporous hollows and surface defects using electron microscopy, and was supported by UV–vis, fluorimetry and DLS data. The dissolution profiles of the NPs are particularly suited to the requirements of oral drug delivery, whereby NPs must resist degradation in the harsh acidic conditions of the stomach (pH 4), but dissolve and release their cargo in the small intestine (pH 6–7.4). Particle cores made solely of ethyl triethoxysilane exhibited a ‘burst release’ of encapsulated fluorescein at pH 6 and pH 7.4, whereas NPs synthesised with tetraethoxysilane released fluorescein in a more sustained fashion. Thus, by varying the organosilane precursor used in NP formation, it is possible to modify particle dissolution rates and tune the release profile of encapsulated fluorescein. The flexible synthesis afforded by silica NPs to achieve pH-responsive dissolution therefore makes this class of nanomaterial an adaptable platform that may be well suited to oral delivery applications

Dye‑doped silica nanoparticles: synthesis, surface chemistry and bioapplications

Background: Fluorescent silica nanoparticles have been extensively utilised in a broad range of biological applications and are facilitated by their predictable, wellunderstood, flexible chemistry and apparent biocompatibility. The ability to couple various siloxane precursors with fluorescent dyes and to be subsequently incorporated into silica nanoparticles has made it possible to engineer these fluorophores-doped nanomaterials to specific optical requirements in biological experimentation. Consequently, this class of nanomaterial has been used in applications across immunodiagnostics, drug delivery and human-trial bioimaging in cancer research. Main body: This review summarises the state-of-the-art of the use of dye-doped silica nanoparticles in bioapplications and firstly accounts for the common nanoparticle synthesis methods, surface modification approaches and different bioconjugation strategies employed to generate biomolecule-coated nanoparticles. The use of dye-doped silica nanoparticles in immunoassays/biosensing, bioimaging and drug delivery is then provided and possible future directions in the field are highlighted. Other non-cancerrelated applications involving silica nanoparticles are also briefly discussed. Importantly, the impact of how the protein corona has changed our understanding of NP interactions with biological systems is described, as well as demonstrations of its capacity to be favourably manipulated. Conclusions: Dye-doped silica nanoparticles have found success in the immunodiagnostics domain and have also shown promise as bioimaging agents in human clinical trials. Their use in cancer delivery has been restricted to murine models, as has been the case for the vast majority of nanomaterials intended for cancer therapy. This is hampered by the need for more human-like disease models and the lack of standardisation towards assessing nanoparticle toxicity. However, developments in the manipulation of the protein corona have improved the understanding of fundamental bio–nano interactions, and will undoubtedly assist in the translation of silica nanoparticles for disease treatment to the clinic

Resource Pulses Increase the Diversity of Successful Competitors in a Multi-Species Stream Fish Assemblage

Food resources are often patchily distributed through space and time and are classified as resource pulses when hyperabundant. Resource pulses can benefit growth, reproduction, and abundance of various consumers. Yet, it is relatively unknown how such resources are partitioned among competing consumers and how this is influenced by the magnitude of the pulse. Here, we examined how the magnitude of a pulsed resource influences resource partitioning among diverse sizes and species of consumers in a natural setting over small spatial and temporal scales. We focused on salmon egg subsidies to stream fish consumers. We experimentally added different quantities of pink salmon eggs to five meter long experimental stream sections. Egg additions spanned three orders of magnitude from 6 to 3575 eggs. Stream fish (egg consumers) were captured and gastric lavaged at each experimental section to determine how many eggs each individual fish consumed. We modeled taxon‐specific individual egg consumption as a function of egg availability, individual mass, community composition, number of competitors, and stream velocity using hurdle models in a Bayesian framework. We found that there were diminishing returns for increasing egg abundance increasing egg consumption (i.e., type II functional response) for individual size classes of fish, but that higher egg numbers were needed to benefit diverse consumers. Top models indicated that egg availability and individual fish characteristics (size and taxon) drove egg consumption, while community characteristics (species composition and number of competitors) were not supported. Our results suggest that resource pulses can provide rare opportunities for less dominant sizes and species of fish to consume abundant resources. The current paradigm in the stream fish literature suggests that stream fish communities are structured by dominance hierarchies; however, dominance hierarchies may be less influential where pulsed resources comprise a large portion of the resource base

Antimicrobial resistance to 14 antimicrobials in marine coastal waters around Northern Ireland: Use of the novel Relative Resistance Index as a marker of ecological status

Relatively little work has been published on the incidence of antibiotic resistance (ABR) in the marine microbiological environment, which is of importance to animal (fish, mammals, birds) health, zoonotic transmission, distribution of ABR bacteria with oceanic drift, and ultimately human health. A study was performed to determine the diversity of total ABR (intrinsic and acquired resistance) in marine bacteria in shallow coastal waters surrounding Northern Ireland through the use of a novel Relative Resistance Index (RRI) as a surrogate marker for ecological change, particularly in comparing marine water in commercial versus non-commercial sites. Total antibiotic resistance was observed to varying degrees in all marine water specimens and specific resistance levels were as follows, in order of diminishing antibacterial effectiveness: fluoroquinolones \u3e rifampicin \u3e polymyxin \u3e tetracycline \u3e sulphamethoxazole/trimethoprim \u3e third generation cephalosporin and streptomycin \u3e carbapenem \u3e macrolide \u3e clindamycin \u3e vancomycin \u3e fucidic acid \u3e penicillin. None of the sampling sites contained endogenous bacteria that were resistant to ciprofloxacin, while nearly all (19 of 20 sites; 95%) contained bacteria that were resistant to penicillin. Commercial sites had a higher mean RRI score of 6.57±3.58 than non-commercial sites (RRI = 4.08 ± 2.02), which was statistically significant (p = 0.037), indicating that bacteria isolated from seawater in commercial coastal harbors had a higher frequency of antibiotic resistance than non-commercial sources. This novel RRI marker may be useful in assessing ecological change in marine water environments. In conclusion, this study demonstrated that there can be a high level of total ABR (intrinsic and acquired) in bacterial populations in marine water environments, which are multi- and pan-resistant to up to 11 major classes of antibiotics simultaneously. Ecological studies are urgently needed to help define the fate of ABR marine bacteria in their natural environment and their ability to act as reservoirs and donors of ABR to pathogenic bacteria, many of which transiently inhabit the natural environment

Engineered Nanomaterials and Human Health: Part 2. Applications and Nanotoxicology (IUPAC Technical Report) (Review)

Research on engineered nanomaterials (ENM) has progressed rapidly from the very early stages of studying their unique, size-dependent physicochemical properties and commercial exploration to the development of products that influence our everyday lives. We have previously reviewed various methods for synthesis, surface functionalization, and analytical characterization of ENM in a publication titled \u27Engineered Nanomaterials: Preparation, Functionalization and Characterization\u27. In this second, inter-linked document, we first provide an overview of important applications of ENM in products relevant to human healthcare and consumer goods, such as food, textiles, and cosmetics. We then highlight the challenges for the design and development of new ENM for bio-applications, particularly in the rapidly developing nanomedicine sector. The second part of this document is dedicated to nanotoxicology studies of ENM in consumer products. We describe the various biological targets where toxicity may occur, summarize the four nanotoxicology principles, and discuss the need for careful consideration of the biodistribution, degradation, and elimination routes of nanosized materials before they can be safely used. Finally, we review expert opinions on the risk, regulation, and ethical aspects of using engineered nanomaterials in applications that may have direct or indirect impact on human health or our environment

Non-Standard Structure Formation Scenarios

Observations on galactic scales seem to be in contradiction with recent high resolution N-body simulations. This so-called cold dark matter (CDM) crisis has been addressed in several ways, ranging from a change in fundamental physics by introducing self-interacting cold dark matter particles to a tuning of complex astrophysical processes such as global and/or local feedback. All these efforts attempt to soften density profiles and reduce the abundance of satellites in simulated galaxy halos. In this contribution we are exploring the differences between a Warm Dark Matter model and a CDM model where the power on a certain scale is reduced by introducing a narrow negative feature (''dip''). This dip is placed in a way so as to mimic the loss of power in the WDM model: both models have the same integrated power out to the scale where the power of the Dip model rises to the level of the unperturbed CDM spectrum again. Using N-body simulations we show that that the new Dip model appears to be a viable alternative to WDM while being based on different physics: where WDM requires the introduction of a new particle species the Dip stems from a non-standard inflationary period. If we are looking for an alternative to the currently challenged standard LCDM structure formation scenario, neither the LWDM nor the new Dip model can be ruled out with respect to the analysis presented in this contribution. They both make very similar predictions and the degeneracy between them can only be broken with observations yet to come.Comment: 4 pages, 3 figures; to appear in "The Evolution of Galaxies III. From Simple Approaches to Self-Consistent Models", proceedings of the 3rd EuroConference on the evolution of galaxies, held in Kiel, Germany, July 16-20, 200

The Roles of Extrinsic and Intrinsic Factors in the Freshwater Life-History Dynamics of a Migratory Salmonid

Key life-cycle transitions, such as metamorphosis or migration, can be altered by a variety of external factors, such as climate variation, strong species interactions, and management intervention, or modulated by density dependence. Given that these life-history transitions can influence population dynamics, understanding the simultaneous effects of intrinsic and extrinsic controls on life-history expression is particularly relevant for species of management or conservation importance. Here, we examined how life histories of steelhead (Oncorhynchus mykiss) are affected by weather, pink salmon abundance (Oncorhynchus gorbuscha), experimental nutrient addition, and density-dependent processes. We tested for impacts on the size of steelhead smolts (juveniles migrating to the sea), as well as their age and abundance across four decades in the Keogh River, British Columbia, Canada. Larger steelhead smolts were associated with warmer years and artificial nutrient addition. In addition, higher pink salmon abundance and artificial nutrient addition correlated with juvenile steelhead migrating at younger ages. While density dependence appeared to be the primary factor regulating the abundance of steelhead smolts, nutrient addition and temperature were positively and negatively associated with smolt production, respectively, prior to 1991, and pink salmon spawning abundance was positively associated with smolt production after 1990. Thus, this study provides evidence that the temporal dynamics of one species of salmon is linked to the juvenile life history of co-occurring steelhead. A complex interplay of species interactions, nutrient subsidies, density dependence, and climatic variation can control the life-history expression of species with complex life cycles