Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate

As alterations in tissue pH underlie many pathological processes, the capability to image tissue pH in the clinic could offer new ways of detecting disease and response to treatment. Dynamic nuclear polarization is an emerging technique for substantially increasing the sensitivity of magnetic resonance imaging experiments. Here we show that tissue pH can be imaged in vivo from the ratio of the signal intensities of hyperpolarized bicarbonate (H(13)CO(3)(-)) and (13)CO(2) following intravenous injection of hyperpolarized H(13)CO(3)(-). The technique was demonstrated in a mouse tumour model, which showed that the average tumour interstitial pH was significantly lower than the surrounding tissue. Given that bicarbonate is an endogenous molecule that can be infused in relatively high concentrations into patients, we propose that this technique could be used clinically to image pathological processes that are associated with alterations in tissue pH, such as cancer, ischaemia and inflammation.     

Ca2+/calmodulin binds to and modulates P/Q-type calcium channels.

Neurotransmitter release at many central synapses is initiated by an influx of calcium ions through P/Q-type calcium channels, which are densely localized in nerve terminals. Because neurotransmitter release is proportional to the fourth power of calcium concentration, regulation of its entry can profoundly influence neurotransmission. N- and P/Q-type calcium channels are inhibited by G proteins, and recent evidence indicates feedback regulation of P/Q-type channels by calcium. Although calcium-dependent inactivation of L-type channels is well documented, little is known about how calcium modulates P/Q-type channels. Here we report a calcium-dependent interaction between calmodulin and a novel site in the carboxy-terminal domain of the alpha1A subunit of P/Q-type channels. In the presence of low concentrations of intracellular calcium chelators, calcium influx through P/Q-type channels enhances channel inactivation, increases recovery from inactivation and produces a long-lasting facilitation of the calcium current. These effects are prevented by overexpression of a calmodulin-binding inhibitor peptide and by deletion of the calmodulin-binding domain. Our results reveal an unexpected association of Ca2+/calmodulin with P/Q-type calcium channels that may contribute to calcium-dependent synaptic plasticity.     

The Realised–Implied Volatility Relationship: Recent Empirical Evidence from FTSE‐100 Stocks

This paper examines the long‐run relationship between implied and realised volatility for a sample of 16 FTSE‐100 stocks. We find strong evidence of long‐memory, fractional integration in equity volatility and show that this long‐memory characteristic is not an outcome of structural breaks experienced during the sample period. Fractional cointegration between the implied and realised volatility is shown using recently developed rank cointegration tests by Robinson and Yajima (2002). The predictive ability of individual equity options is also examined and composite implied volatility estimates are shown to contain information on future idiosyncratic or stock‐specific risk that is not captured using popular statistical approaches. Implied volatilities on individual UK equities are thus closely related to realised volatility and are an effective forecasting method particularly over medium forecasting horizons. Copyright © 2011 John Wiley & Sons, Ltd.     

Cellular maintenance of nuclear protein homeostasis

The accumulation and aggregation of misfolded proteins is the primary hallmark for more than 45 human degenerative diseases. These devastating disorders include Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis. Over 15 degenerative diseases are associated with the aggregation of misfolded proteins specifically in the nucleus of cells. However, how the cell safeguards the nucleus from misfolded proteins is not entirely clear. In this review, we discuss what is currently known about the cellular mechanisms that maintain protein homeostasis in the nucleus and protect the nucleus from misfolded protein accumulation and aggregation. In particular, we focus on the chaperones found to localize to the nucleus during stress, the ubiquitin–proteasome components enriched in the nucleus, the signaling systems that might be present in the nucleus to coordinate folding and degradation, and the sites of misfolded protein deposition associated with the nucleus.     

Infective transmission and characterisation of a C-type virus released by cultured human myeloid leukaemia cells.

A C-type virus isolated from long term cultures of myeloid cells from a patient with acute myelogenous leukaemia is infectious for a wide variety of cells. The establishment of chronically infected cells enabled us to characterise the virus by biological, immunological, and biochemical tests. The virus is closely related to the simian sarcoma-associated virus isolated from a woolly monkey fibrosarcoma.     

Low-loss hollow-core silica/air photonic bandgap fibre

Photonic bandgap structures use the principle of interference to reflect radiation. Reflection from photonic bandgap structures has been demonstrated in one, two and three dimensions and various applications have been proposed. Early work in hollow-core photonic bandgap fibre technology used a hexagonal structure surrounding the air core; this fibre was the first demonstration of light guided inside an air core of a photonic bandgap fibre. The potential benefits of guiding light in air derive from lower Rayleigh scattering, lower nonlinearity and lower transmission loss compared to conventional waveguides. In addition, these fibres offer a new platform for studying nonlinear optics in gases. Owing largely to challenges in fabrication, the early air-core fibres were only available in short lengths, and so systematic studies of loss were not possible. More recently, longer lengths of fibre have become available with reported losses of 1,000 dB km(-1). We report here the fabrication and characterization of long lengths of low attenuation photonic bandgap fibre. Attenuation of less than 30 dB km(-1) over a wide transmission window is observed with minimum loss of 13 dB km(-1) at 1,500 nm, measured on 100 m of fibre. Coupling between surface and core modes of the structure is identified as an important contributor to transmission loss in hollow-core photonic bandgap fibres.     

Heparan sulphate bound growth factors: a mechanism for stromal cell mediated haemopoiesis

The proliferation and development of haemopoietic stem cells takes place in close association with marrow stromal cells. This intimate cell contact presumably enables the stem cells and their progeny to respond to stimuli present on the stromal cell surface. While the nature of these stimuli has not been determined, it is likely that growth factors play some role. Recently, it was demonstrated that the natural and the recombinant haemopoietic growth factor, granulocyte/macrophage colony stimulating factor (GM-CSF), could be adsorbed out of solution by an extract of human marrow stromal extracellular matrix (ECM) with retention of biological activity. However, the precise ECM molecules involved were not identified. Here, we clearly demonstrate that the major sulphated glycosaminoglycan of mouse marrow stroma, heparan sulphate, possesses the ability to adsorb both GM-CSF and the multilineage haemopoietic growth factor, Interleukin 3 (IL-3). Furthermore, these growth factors, once bound, can be presented in the biologically active form to haemopoietic cells.     

The potent tremorgenic neurotoxins lolitrem B and aflatrem: a comparison of the tremor response in mice

Tremor dose-response curves were determined for mice dosed with the ryegrass neurotoxin lolitrem B, and the tremor-genic mycotoxin aflatrem. A family of characteristic curves was revealed for each tremorgenic, with lolitrem B eliciting a sustained tremor response persisting for over 24 h.