A zebrafish model for Mycobacterium leprae granulomatous infection

Understanding the pathogenesis of leprosy granulomas has been hindered by a paucity of tractable experimental animal models. Mycobacterium leprae, which causes leprosy, grows optimally at ~30°C, so we sought to model granulomatous disease in the ectothermic zebrafish. We find noncaseating granulomas develop rapidly, and eventually eradicate infection. rag1 mutant zebrafish, which lack lymphocytes, also form noncaseating granulomas with similar kinetics, but these control infection more slowly. Our findings establish the zebrafish as a facile, genetically tractable model for leprosy, and reveal the interplay between innate and adaptive immune determinants mediating leprosy granuloma formation and function

Outbreak of Aeromonas hydrophila wound infections association with mud football

On 16 February 2002, a total of 26 people presented to the emergency department of the local hospital in the rural town of Collie in southwest Western Australia with many infected scratches and pustules distributed over their bodies. All of the patients had participated in a “mud football” competition the previous day, in which there had been 100 participants. One patient required removal of an infected thumbnail, and another required surgical debridement of an infected toe. Aeromonas hydrophila was isolated from all 3 patients from whom swab specimens were obtained. To prepare the mud football fields, a paddock was irrigated with water that was pumped from an adjacent river during the 1-month period before the competition. A. hydrophila was subsequently isolated from a water sample obtained from the river. This is the first published report of an outbreak of A. hydrophila wound infections associated with exposure to mud.Hassan Vally, Amanda Whittle, Scott Cameron, Gary K. Dowse and Tony Watso

Likelihood inference for exponential-trawl processes

Integer-valued trawl processes are a class of serially correlated, stationary and infinitely divisible processes that Ole E. Barndorff-Nielsen has been working on in recent years. In this Chapter, we provide the first analysis of likelihood inference for trawl processes by focusing on the so-called exponential-trawl process, which is also a continuous time hidden Markov process with countable state space. The core ideas include prediction decomposition, filtering and smoothing, complete-data analysis and EM algorithm. These can be easily scaled up to adapt to more general trawl processes but with increasing computation efforts.Comment: 29 pages, 6 figures, forthcoming in: "A Fascinating Journey through Probability, Statistics and Applications: In Honour of Ole E. Barndorff-Nielsen's 80th Birthday", Springer, New Yor

Should physical activity recommendations be ethnicity-specific? Evidence from a cross-sectional study of south Asian and European men

Background Expert bodies and health organisations recommend that adults undertake at least 150 min.week−1 of moderate-intensity physical activity (MPA). However, the underpinning data largely emanate from studies of populations of European descent. It is unclear whether this level of activity is appropriate for other ethnic groups, particularly South Asians, who have increased cardio-metabolic disease risk compared to Europeans. The aim of this study was to explore the level of MPA required in South Asians to confer a similar cardio-metabolic risk profile to that observed in Europeans undertaking the currently recommended MPA level of 150 min.week−1.<p></p> Methods Seventy-five South Asian and 83 European men, aged 40–70, without cardiovascular disease or diabetes had fasted blood taken, blood pressure measured, physical activity assessed objectively (using accelerometry), and anthropometric measures made. Factor analysis was used to summarise measured risk biomarkers into underlying latent ‘factors’ for glycaemia, insulin resistance, lipid metabolism, blood pressure, and overall cardio-metabolic risk. Age-adjusted regression models were used to determine the equivalent level of MPA (in bouts of ≥10 minutes) in South Asians needed to elicit the same value in each factor as Europeans undertaking 150 min.week−1 MPA.<p></p> Findings For all factors, except blood pressure, equivalent MPA values in South Asians were significantly higher than 150 min.week−1; the equivalent MPA value for the overall cardio-metabolic risk factor was 266 (95% CI 185-347) min.week−1.<p></p> Conclusions South Asian men may need to undertake greater levels of MPA than Europeans to exhibit a similar cardio-metabolic risk profile, suggesting that a conceptual case can be made for ethnicity-specific physical activity guidance. Further study is needed to extend these findings to women and to replicate them prospectively in a larger cohort.<p></p&gt

The pre-main sequence binary HK Ori : Spectro-astrometry and EXPORT data

In this paper we present multi-epoch observations of the pre-main sequence binary HK Ori. These data have been drawn from the EXPORT database and are complemented by high quality spectro-astrometric data of the system. The spectroscopic data appear to be very well represented by a combination of an A dwarf star spectrum superposed on a (sub-)giant G-type spectrum. The radial velocity of the system is consistent with previous determinations, and does not reveal binary motion, as expected for a wide binary. The spectral, photometric and polarimetric properties and variability of the system indicate that the active object in the system is a T Tauri star with UX Ori characteristics. The spectro-astrometry of HK Ori is sensitive down to milli-arcsecond scales and confirms the speckle interferometric results from Leinert et al. The spectro-astrometry allows with fair certainty the identification of the active star within the binary, which we suggest to be a G-type T Tauri star based on its spectral characteristics.Comment: MNRAS in press 8 pages 7 figure

Transit Photometry as an Exoplanet Discovery Method

Photometry with the transit method has arguably been the most successful exoplanet discovery method to date. A short overview about the rise of that method to its present status is given. The method's strength is the rich set of parameters that can be obtained from transiting planets, in particular in combination with radial velocity observations; the basic principles of these parameters are given. The method has however also drawbacks, which are the low probability that transits appear in randomly oriented planet systems, and the presence of astrophysical phenomena that may mimic transits and give rise to false detection positives. In the second part we outline the main factors that determine the design of transit surveys, such as the size of the survey sample, the temporal coverage, the detection precision, the sample brightness and the methods to extract transit events from observed light curves. Lastly, an overview over past, current and future transit surveys is given. For these surveys we indicate their basic instrument configuration and their planet catch, including the ranges of planet sizes and stellar magnitudes that were encountered. Current and future transit detection experiments concentrate primarily on bright or special targets, and we expect that the transit method remains a principal driver of exoplanet science, through new discoveries to be made and through the development of new generations of instruments.Comment: Review chapte

Epigenetics as a mechanism driving polygenic clinical drug resistance

Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene : one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance

The Role of TLR4 in the Paclitaxel Effects on Neuronal Growth In Vitro

Paclitaxel (Pac) is an antitumor agent that is widely used for treatment of solid cancers. While being effective as a chemotherapeutic agent, Pac in high doses is neurotoxic, specifically targeting sensory innervations. In view of these toxic effects associated with conventional chemotherapy, decreasing the dose of Pac has been recently suggested as an alternative approach, which might limit neurotoxicity and immunosuppression. However, it remains unclear if low doses of Pac retain its neurotoxic properties or might exhibit unusual effects on neuronal cells. The goal of this study was to analyze the concentration-dependent effect of Pac on isolated and cultured DRG neuronal cells from wild-type and TLR4 knockout mice. Three different morphological parameters were analyzed: the number of neurons which developed neurites, the number of neurites per cell and the total length of neurites per cell. Our data demonstrate that low concentrations of Pac (0.1 nM and 0.5 nM) do not influence the neuronal growth in cultures in both wild type and TLR4 knockout mice. Higher concentrations of Pac (1-100 nM) had a significant effect on DRG neurons from wild type mice, affecting the number of neurons which developed neurites, number of neurites per cell, and the length of neurites. In DRG from TLR4 knockout mice high concentrations of Pac showed a similar effect on the number of neurons which developed neurites and the length of neurites. At the same time, the number of neurites per cell, indicating the process of growth cone initiation, was not affected by high concentrations of Pac. Thus, our data showed that Pac in high concentrations has a significant damaging effect on axonal growth and that this effect is partially mediated through TLR4 pathways. Low doses of Pac are devoid of neuronal toxicity and thus can be safely used in a chemomodulation mode. © 2013 Ustinova et al