Penetration and intracellular uptake of poly(glycerol-adipate)nanoparticles into 3-dimensional brain tumour cell culture models

Nanoparticle (NP) drug delivery systems may potentially enhance the efficacy of therapeutic agents. It is difficult to characterise many important properties of NPs in vivo and therefore attempts have been made to use realistic in vitro multicellular spheroids instead. In this paper we have evaluated poly(glycerol-adipate) (PGA) NPs as a potential drug carrier for local brain cancer therapy. Various 3-dimensional (3-D) cell culture models have been used to investigate the delivery properties of PGA NPs. Tumour cells in 3-D culture showed a much higher level of endocytic uptake of NPs than a mixed normal neonatal brain cell population. Differences in endocytic uptake of NPs in 2-D and 3-D models strongly suggest that it is very important to use in vitro 3-D cell culture models for evaluating this parameter. Tumour penetration of NPs is another important parameter which could be studied in 3-D cell models. The penetration of PGA NPs through 3-D cell culture varied between models, which will therefore require further study to develop useful and realistic in vitro models. Further use of 3-D cell culture models will be of benefit in the future development of new drug delivery systems, particularly for brain cancers which are more difficult to study in vivo

Quantum oscillations in the anomalous phase in Sr3Ru2O7

This is the final version. Available from American Physical Society via the DOI in this recordWe report measurements of quantum oscillations detected in the putative nematic phase of Sr3Ru2O7. Improvements in sample purity enabled the resolution of small amplitude de Haas-van Alphen (dHvA) oscillations between two first order metamagnetic transitions delimiting the phase. Two distinct frequencies were observed, whose amplitudes follow the normal Lifshitz-Kosevich profile. Variations of the dHvA frequencies are explained in terms of a chemical potential shift produced by reaching a peak in the density of states, and an anomalous field dependence of the oscillatory amplitude provides information on domains. © 2009 The American Physical Society.Engineering and Physical Sciences Research Council (EPSRC

Isolation of a wide range of minerals from a thermally treated plant: Equisetum arvense, a Mare’s tale

Silica is the second most abundant biomineral being exceeded in nature only by biogenic CaCO3. Many land plants (such as rice, cereals, cucumber, etc.) deposit silica in significant amounts to reinforce their tissues and as a systematic response to pathogen attack. One of the most ancient species of living vascular plants, Equisetum arvense is also able to take up and accumulate silica in all parts of the plant. Numerous methods have been developed for elimination of the organic material and/or metal ions present in plant material to isolate biogenic silica. However, depending on the chemical and/or physical treatment applied to branch or stem from Equisetum arvense; other mineral forms such glass-type materials (i.e. CaSiO3), salts (i.e. KCl) or luminescent materials can also be isolated from the plant material. In the current contribution, we show the chemical and/or thermal routes that lead to the formation of a number of different mineral types in addition to biogenic silica

Quantum oscillations near the metamagnetic transition in Sr3Ru2O7

This is the final version. Available from American Physical Society via the DOI in this recordWe report a detailed investigation of quantum oscillations in Sr 3 Ru2 O7, observed inductively (the de Haas-van Alphen effect) and thermally (the magnetocaloric effect). Working at fields from 3 to 18 T allowed us to straddle the metamagnetic transition region and probe the low- and high-field Fermi liquids. The observed frequencies are strongly field dependent in the vicinity of the metamagnetic transition, and there is evidence for magnetic breakdown. We also present the results of a comprehensive rotation study. The most surprising result concerns the field dependence of the measured quasiparticle masses. Contrary to conclusions previously drawn by some of us as a result of a study performed with a much poorer signal-to-noise ratio, none of the five Fermi-surface branches for which we have good field-dependent data gives evidence for a strong-field dependence of the mass. The implications of these experimental findings are discussed. © 2010 The American Physical Society.Engineering and Physical Sciences Research Council (EPSRC

Structure of the TPR Domain of AIP: Lack of Client Protein Interaction with the C-Terminal alpha-7 Helix of the TPR Domain of AIP Is Sufficient for Pituitary Adenoma Predisposition

PMCID: PMC3534021This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Evaluating the potential for the environmentally sustainable control of foot and mouth disease in Sub-Saharan Africa

Strategies to control transboundary diseases have in the past generated unintended negative consequences for both the environment and local human populations. Integrating perspectives from across disciplines, including livestock, veterinary and conservation sectors, is necessary for identifying disease control strategies that optimise environmental goods and services at the wildlife-livestock interface. Prompted by the recent development of a global strategy for the control and elimination of foot-and-mouth disease (FMD), this paper seeks insight into the consequences of, and rational options for potential FMD control measures in relation to environmental, conservation and human poverty considerations in Africa. We suggest a more environmentally nuanced process of FMD control that safe-guards the integrity of wild populations and the ecosystem dynamics on which human livelihoods depend while simultaneously improving socio-economic conditions of rural people. In particular, we outline five major issues that need to be considered: 1) improved understanding of the different FMD viral strains and how they circulate between domestic and wildlife populations; 2) an appreciation for the economic value of wildlife for many African countries whose presence might preclude the country from ever achieving an FMD-free status; 3) exploring ways in which livestock production can be improved without compromising wildlife such as implementing commodity-based trading schemes; 4) introducing a participatory approach involving local farmers and the national veterinary services in the control of FMD; and 5) finally the possibility that transfrontier conservation might offer new hope of integrating decision-making at the wildlife-livestock interface

The effect of cigarette smoke exposure on the development of inflammation in lungs, gut and joints of TNFΔARE mice

The inflammatory cytokine TNF-alpha is a central mediator in many immune-mediated diseases, such as Crohn's disease (CD), spondyloarthritis (SpA) and chronic obstructive pulmonary disease (COPD). Epidemiologic studies have shown that cigarette smoking (CS) is a prominent common risk factor in these TNF-dependent diseases. We exposed TNF Delta ARE mice; in which a systemic TNF-alpha overexpression leads to the development of inflammation; to 2 or 4 weeks of air or CS. We investigated the effect of deregulated TNF expression on CS-induced pulmonary inflammation and the effect of CS exposure on the initiation and progression of gut and joint inflammation. Upon 2 weeks of CS exposure, inflammation in lungs of TNF Delta ARE mice was significantly aggravated. However, upon 4 weeks of CS-exposure, this aggravation was no longer observed. TNF Delta ARE mice have no increases in CD4+ and CD8+ T cells and a diminished neutrophil response in the lungs after 4 weeks of CS exposure. In the gut and joints of TNF Delta ARE mice, 2 or 4 weeks of CS exposure did not modulate the development of inflammation. In conclusion, CS exposure does not modulate gut and joint inflammation in TNF Delta ARE mice. The lung responses towards CS in TNF Delta ARE mice however depend on the duration of CS exposure

Cost-effective scat-detection dogs: unleashing a powerful new tool for international mammalian conservation biology

Recently, detection dogs have been utilized to collect fecal samples from cryptic and rare mammals. Despite the great promise of this technique for conservation biology, its broader application has been limited by the high cost (tens to hundreds of thousands of dollars) and logistical challenges of employing a scat-detection dog team while conducting international, collaborative research. Through an international collaboration of primatologists and the Chinese Ministry of Public Security, we trained and used a detection dog to find scat from three species of unhabituated, free-ranging primates, for less than $3,000. We collected 137 non-human primate fecal samples that we confirmed by sequencing taxonomically informative genetic markers. Our detection dog team had a 92% accuracy rate, significantly outperforming our human-only team. Our results demonstrate that detection dogs can locate fecal samples from unhabituated primates with variable diets, locomotion, and grouping patterns, despite challenging field conditions. We provide a model for in-country training, while also building local capacity for conservation and genetic monitoring. Unlike previous efforts, our approach will allow for the wide adoption of scat-detection dogs in international conservation biology

Development of quality indicators for monitoring outcomes of frail elderly hospitalised in acute care health settings: Study Protocol

Background: Frail older people admitted to acute care hospitals are at risk of a range of adverse outcomes, including geriatric syndromes, although targeted care strategies can improve health outcomes for these patients. It is therefore important to assess inter-hospital variation in performance in order to plan and resource improvement programs. Clinical quality outcome indicators provide a mechanism for identifying variation in performance over time and between hospitals, however to date there has been no routine use of such indicators in acute care settings. A barrier to using quality indicators is lack of access to routinely collected clinical data. The interRAI Acute Care (AC) assessment system supports comprehensive geriatric assessment of older people within routine daily practice in hospital and includes process and outcome data pertaining to geriatric syndromes. This paper reports the study protocol for the development of aged care quality indicators for acute care hospitals. Methods/Design. The study will be conducted in three phases:. 1. Development of a preliminary inclusive set of quality indicators set based on a literature review and expert panel consultation,. 2. A prospective field study including recruitment of 480 patients aged 70 years or older across 9 Australian hospitals. Each patient will be assessed on admission and discharge using the interRAI AC, and will undergo daily monitoring to observe outcomes. Medical records will be independently audited, and. 3. Analysis and compilation of a definitive quality indicator set, including two anonymous voting rounds for quality indicator inclusion by the expert panel. Discussion. The approach to quality indicators proposed in this protocol has four distinct advantages over previous efforts: the quality indicators focus on outcomes; they can be collected as part of a routinely applied clinical information and decision support system; the clinical data will be robust and will contribute to better understanding variations in hospital care of older patients; The quality indicators will have international relevance as they will be built on the interRAI assessment instrument, an internationally recognised clinical system