Explore the vast range of titles available.

Surface charge plays a fundamental role in determining the fate of a nanoparticle, and any encapsulated contents, in vivo. Herein, we describe, and visualise in real time, light-triggered switching of liposome surface charge, from neutral to cationic, in situ and in vivo (embryonic zebrafish). Prior to light activation, intravenously administered liposomes, composed of just two lipid reagents, freely circulate and successfully evade innate immune cells present in the fish. Upon in situ irradiation and surface charge switching, however, liposomes rapidly adsorb to, and are taken up by, endothelial cells and/or are phagocytosed by blood resident macrophages. Coupling complete external control of nanoparticle targeting together with the intracellular delivery of encapsulated (and membrane impermeable) cargos, these compositionally simple liposomes are proof that advanced nanoparticle function in vivo does not require increased design complexity but rather a thorough understanding of the fundamental nano-bio interactions involved. Surface charge plays an important role in determining nanoparticle fate in vivo. Here the authors report on the development of a light triggered charge switching liposome and demonstrate light triggered liposome targeting, uptake and payload delivery in a zebrafish model.

A speech of then-Vice President Al Gore in 1998 created a vision for a Digital Earth, and played a role in stimulating the development of a first generation of virtual globes, typified by Google Earth, that achieved many but not all the elements of this vision. The technical achievements of Google Earth, and the functionality of this first generation of virtual globes, are reviewed against the Gore vision. Meanwhile, developments in technology continue, the era of “big data” has arrived, the general public is more and more engaged with technology through citizen science and crowd-sourcing, and advances have been made in our scientific understanding of the Earth system. However, although Google Earth stimulated progress in communicating the results of science, there continue to be substantial barriers in the public’s access to science. All these factors prompt a reexamination of the initial vision of Digital Earth, and a discussion of the major elements that should be part of a next generation.

Cancer is a complex disease that has proven to be difficult to understand on the single-gene level. For this reason a functional elucidation needs to take interactions among genes on a systems-level into account. In this study, we infer a colon cancer network from a large-scale gene expression data set by using the method BC3Net. We provide a structural and a functional analysis of this network and also connect its molecular interaction structure with the chromosomal locations of the genes enabling the definition of cis- and trans-interactions. Furthermore, we investigate the interaction of genes that can be found in close neighborhoods on the chromosomes to gain insight into regulatory mechanisms. To our knowledge this is the first study analyzing the genome-scale colon cancer network.

PTEN controls three-dimensional (3D) glandular morphogenesis by coupling juxtamembrane signaling to mitotic spindle machinery. While molecular mechanisms remain unclear, PTEN interacts through its C2 membrane-binding domain with the scaffold protein β-Arrestin1. Because β-Arrestin1 binds and suppresses the Cdc42 GTPase-activating protein ARHGAP21, we hypothesize that PTEN controls Cdc42 -dependent morphogenic processes through a β-Arrestin1-ARHGAP21 complex. Here, we show that PTEN knockdown (KD) impairs β-Arrestin1 membrane localization, β-Arrestin1-ARHGAP21 interactions, Cdc42 activation, mitotic spindle orientation and 3D glandular morphogenesis. Effects of PTEN deficiency were phenocopied by β-Arrestin1 KD or inhibition of β-Arrestin1-ARHGAP21 interactions. Conversely, silencing of ARHGAP21 enhanced Cdc42 activation and rescued aberrant morphogenic processes of PTEN-deficient cultures. Expression of the PTEN C2 domain mimicked effects of full-length PTEN but a membrane-binding defective mutant of the C2 domain abrogated these properties. Our results show that PTEN controls multicellular assembly through a membrane-associated regulatory protein complex composed of β-Arrestin1, ARHGAP21 and Cdc42. The protein PTEN helps to organize cells in the body to form complex structures. In particular, it collects signals from a cells’ surroundings and changes where cells divide so new cells are produced in the right places. The control of cell division by PTEN is also thought to help limit the progression and spread of cancer. PTEN can interact with another protein called β-Arrestin1, which behaves as a so-called scaffolding protein – in other words, one that helps groups of proteins to interact with each other. β-Arrestin1 has been found to control cell division via a series of other proteins, including ARHGAP21 and Cdc42. The relationship between PTEN and these other proteins in dividing cells is still not fully understood. Javadi, Deevi et al. studied PTEN in human cells grown in the laboratory to show that a part of PTEN known as the C2 domain allows it to help organize cells by moving β-Arrestin1 to the outer edge of the cell – the cell membrane. This relocation allows β-Arrestin1 to interact with ARHGAP21 and Cdc42, and control cell division. Active Cdc42 changes the orientation of cell division, allowing cells to organize into single layers of regular cells and similar tightly controlled structures. Further experiments revealed that these proteins are important to form tubes inside the glands of the gut. The C2 region of PTEN also helps to detect signals carried by fat molecules in the cell membrane, so these results provide a direct link between signaling and cell organization via PTEN. The work of Javadi, Deevi et al. provides new understanding of how PTEN links nutrient availability to cell organization during development and may also lead to new insights into the role of PTEN in limiting the growth of tumors.

Graphical Abstract

Gene therapy mediated by synthetic vectors may provide opportunities for new treatments for cystic fibrosis (CF) via aerosolisation. Vectors for CF must transfect the airway epithelium efficiently and not cause inflammation so they are suitable for repeated dosing. The inhaled aerosol should be deposited in the airways since the cystic fibrosis transmembrane conductance regulator gene (CFTR) is expressed predominantly in the epithelium of the submucosal glands and in the surface airway epithelium. The aim of this project was to develop an optimised aerosol delivery approach applicable to treatment of CF lung disease by gene therapy. The vector suspension investigated in this study comprises receptor-targeting peptides, cationic liposomes and plasmid DNA that self-assemble by electrostatic interactions to form a receptor-targeted nanocomplex (RTN) of approximately 150 nm with a cationic surface charge of +50 mV. The aerodynamic properties of aerosolised nanocomplexes produced with three different nebulisers were compared by determining aerosol deposition in the different stages of a Next Generation Pharmaceutical Impactor (NGI). We also investigated the yield of intact plasmid DNA by agarose gel electrophoresis and densitometry, and transfection efficacies in vitro and in vivo. RTNs nebulised with the AeroEclipse II BAN were the most effective, compared to other nebulisers tested, for gene delivery both in vitro and in vivo. The biophysical properties of the nanocomplexes were unchanged after nebulisation while the deposition of RTNs suggested a range of aerosol aerodynamic sizes between 5.5 µm-1.4 µm cut off (NGI stages 3-6) compatible with deposition in the central and lower airways. RTNs showed their ability at delivering genes via nebulisation, thus suggesting their potential applications for therapeutic interventions of cystic fibrosis and other respiratory disorders.

Inhibition of defined molecular steps of tumorigenesis by natural nontoxic compounds may be an efficient means to tackle the population cancer burden. Extensive research has addressed the chemotherapeutic potential of curcumin (diferuloylmethane), a relatively nontoxic plant-derived polyphenol. This review considers the following properties of curcumin: anticancer effects in animal model systems; metabolism; biological structure and pharmacokinetics; biological properties implicated in chemoprevention; antioxidant properties; influences upon Phase I and II carcinogen-metabolizing enzymes; signal transduction properties and the neoplastic phenotype; apoptosis evasion, cell proliferation, de-differentiation, migration and invasion and clinical studies. This review will summarize the unique properties of curcumin that may be exploited for successful clinical cancer prevention.

Research findings suggest that campers and managers subscribe to similar goals associated with camping, but they disagree about the types of activities appropriate to attaining those goals. In addition, there seem to be important differences in the way both groups perceive behavioral problems in campgrounds. Campers express less concern than managers about problems such as vandalism, theft, and nuisance behaviors. These differences are thought to be attributed to the social goals and urban behavior patterns of campers compared to the more traditional, natural environment-oriented expectations for camping behavior held by recreation managers. Certain changes in recreation user populations and in the organization of public campgrounds are discussed in relation to behavior problems. A strategy is recommended to avert problems inherent in continued change in the camping scene.