Single-cell electrical lysis of erythrocytes detects deficiencies in the cytoskeletal protein network

The network of erythrocyte cytoskeletal proteins significantly influences erythrocyte physical and biological properties. Here we show that the kinetics of erythrocyte lysis during exposure to an electric field is sensitively correlated with defects in the cytoskeletal network. Histograms compiled from single-cell electrical lysis data show characteristics of erythrocyte populations that are deficient in a specific cytoskeletal protein, revealing the presence of cell subpopulations.     

Luminescent kinase activity biosensors based on a versatile bimolecular switch

Real-time tracking of kinase activity in living systems has revealed new modes of encoding signaling information into spatiotemporal activity patterns and opened new avenues for screening kinase modulators. However, the sensitivity of kinase activity detection, which is commonly coupled to a fluorescence resonance energy transfer (FRET)-based readout, has often been a limiting factor. Here we show that a kinase-inducible bimolecular switch consisting of a substrate for the kinase of interest and a phosphoamino acid binding domain can be designed to sense different kinase activities and coupled to various readouts, thereby allowing for examination of dynamic kinase activity with increased sensitivity and versatility. Specifically, we demonstrate that bimolecular switches designed to sense protein kinase A (PKA) or protein kinase C (PKC) activities can turn on FRET as well as bioluminescence signals. Notably, the FRET-based sensors gain larger dynamic ranges in comparison with their unimolecular counterparts; the novel bioluminescence-based reporters for PKA and PKC show high sensitivity and a unique capability to detect basal kinase activities and should enable new applications in in vivo imaging of kinase activity and high-throughput compound screening. Thus, this generalizable design advances the molecular toolkit of kinase activity detection and provides a means for versatile and sensitive detection of kinase activity in various biological systems.     

Ultrastable, redispersible, small, and highly organomodified mesoporous silica nanotherapeutics

Practical biomedical application of mesoporous silica nanoparticles is limited by poor particle dispersity and stability due to serious irreversible aggregation in biological media. To solve this problem, hydrothermally treated mesoporous silica nanoparticles of small size with dual-organosilane (hydrophilic and hydrophobic silane) surface modification have been synthesized. These highly organomodified mesoporous silica nanoparticles were characterized by transmission electron microscopy, X-ray diffraction, N(2) adsorption-desorption, dynamic light scattering, zeta potential, and solid-state (29)Si NMR, and they prove to be very stable in simulated body fluid at physiological temperature. Additionally, they can be dried to a powdered solid and easily redispersed in biological media, maintaining their small size for a period of at least 15 days. Furthermore, this preparation method can be expanded to synthesize redispersible fluorescent and magnetic mesoporous silica nanoparticles. The highly stable and redispersible mesoporous silica NPs show minimal toxicity during in vitro cellular assays. Most importantly, two types of doxorubicin, water-soluble doxorubicin and poorly water-soluble doxorubicin, can be loaded into these highly stable mesoporous silica nanoparticles, and these drug-loaded nanoparticles can also be well-redispersed in aqueous solution. Enhanced cytotoxicity to cervical cancer (HeLa) cells was found upon treatment with water-soluble doxorubicin-loaded nanoparticles compared to free water-soluble doxorubicin. These results suggest that highly stable, redispersible, and small mesoporous silica nanoparticles are promising agents for in vivo biomedical applications.     

Structure of plasmonic aerogel and the breakdown of the effective medium approximation

A method for making aerogel doped with gold nanoparticles (GNPs) produces a composite material with a well-defined localized surface plasmon resonance peak at 520?nm. The width of the extinction feature indicates the GNPs are well dispersed in the aerogel, making it suited to optical study. A simple effective medium approximation cannot explain the peak extinction wavelengths. The plasmonic field extends on a scale where aerogel cannot be considered isotropic, so a new model is required: a 5?nm glass coating on the GNPs models the extinction spectrum of the composite material, with air (aerogel), methanol (alcogel), or toluene filling the pores.     

Toxicity of nano- and micro-sized ZnO particles in human lung epithelial cells

This is the first comprehensive study to evaluate the cytotoxicity, biochemical mechanisms of toxicity, and oxidative DNA damage caused by exposing human bronchoalveolar carcinoma-derived cells (A549) to 70 and 420 nm ZnO particles. Particles of either size significantly reduced cell viability in a dose- and time-dependent manner within a rather narrow dosage range. Particle mass-based dosimetry and particle-specific surface area-based dosimetry yielded two distinct patterns of cytotoxicity in both 70 and 420 nm ZnO particles. Elevated levels of reactive oxygen species (ROS) resulted in intracellular oxidative stress, lipid peroxidation, cell membrane leakage, and oxidative DNA damage. The protective effect of N-acetylcysteine on ZnO-induced cytotoxicity further implicated oxidative stress in the cytotoxicity. Free Zn²⁺ and metal impurities were not major contributors of ROS induction as indicated by limited free Zn²⁺ cytotoxicity, extent of Zn²⁺ dissociation in the cell culture medium, and inductively-coupled plasma-mass spectrometry metal analysis. We conclude that (1) exposure to both sizes of ZnO particles leads to dose- and time-dependent cytotoxicity reflected in oxidative stress, lipid peroxidation, cell membrane damage, and oxidative DNA damage, (2) ZnO particles exhibit a much steeper dose–response pattern unseen in other metal oxides, and (3) neither free Zn²⁺ nor metal impurity in the ZnO particle samples is the cause of cytotoxicity.     

Mathematics,manifest: a review of Mathematics: the Winton Gallery at the Science Museum

Mathematics: the Winton Gallery strives, like any exhibition concerning mathematics, to make meaningful contact between the abstruse realms of mathematics and the viewing audience. Unlike many other exhibitions, this is here accomplished by displaying a rich range of objects that demonstrate the essential role of mathematics in the world by emphasizing connections to the viewers’ existing cognitive environments. Through a focus on the ways that mathematical work affects and informs our human world, the exhibition succeeds in connecting a mathematical way of thinking with the lives of the viewing public in a complex and profound way, in exchange for their efforts and attention. While an approach which places the interweave of life and mathematics at its centre may invite worries about the representation of pure mathematics or whether such a strategy insulates the viewer from an understanding of ‘real’ mathematics, what this exhibition does is to offer a sense of the mind-set that underscores mathematical work. By revealing the implications of this mode of thought, the exhibition encourages the audience to understand their own lives and world in a more mathematically-oriented way, while also encouraging them to understand mathematics in terms of the ways their human world is already formed.     

Water stability of microporous coordination polymers and the adsorption of pharmaceuticals from water

The stability of a variety of microporous coordination polymers (MCPs) to water-containing solutions was studied using powder X-ray diffraction. It was determined that the stability of the MCP is related to the metal cluster present in the structure with trinuclear chromium clusters more stable than copper paddlewheel clusters which are more stable than basic zinc acetate clusters. Zn(2-methylimidizolate)(2) was found to be more water stable than zinc MCPs with carboxylate linkers; however, extended exposure to water led to decomposition of all zinc-based MCPs. Mate?riaux de l'Institut Lavoisier (MIL)-100 was also found to be completely water stable and was used to adsorb the pharmaceuticals furosemide and sulfasalazine from water with large uptakes achievable at low concentrations, indicating that the adsorption of wastewater contaminants may be a feasible application for these materials.