The dendritic cell niche in chronic obstructive pulmonary disease.

The pulmonary innate immune system is heavily implicated in the perpetual airway inflammation and impaired host defense characterizing Chronic Obstructive Pulmonary Disease (COPD). The airways of patients suffering from COPD are infiltrated by various immune and inflammatory cells including macrophages, neutrophils, T lymphocytes, and dendritic cells. While the role of macrophages, neutrophils and T lymphocytes is well characterized, the contribution of dendritic cells to COPD pathogenesis is still the subject of emerging research. A paper by Botelho and colleagues in the current issue of Respiratory Research investigates the importance of dendritic cell recruitment in cigarette-smoke induced acute and chronic inflammation in mice. Dendritic cells of the healthy lung parenchyma and airways perform an important sentinel function and regulate immune homeostasis. During inflammatory responses the function and migration pattern of these cells is dramatically altered but the underlying mechanisms are incompletely understood. Botelho and colleagues demonstrate here the importance of IL-1R1/IL-1α related mechanisms including CCL20 production in cigarette-smoke induced recruitment of dendritic cells and T cell activation in the mouse lung

Improved Measurement of the Positive Muon Lifetime and Determination of the Fermi Constant

The mean life of the positive muon has been measured to a precision of 11 ppm using a low-energy, pulsed muon beam stopped in a ferromagnetic target, which was surrounded by a scintillator detector array. The result, tau_mu = 2.197013(24) us, is in excellent agreement with the previous world average. The new world average tau_mu = 2.197019(21) us determines the Fermi constant G_F = 1.166371(6) x 10^-5 GeV^-2 (5 ppm). Additionally, the precision measurement of the positive muon lifetime is needed to determine the nucleon pseudoscalar coupling g_P.Comment: As published version (PRL, July 2007

Biofortification of UK food crops with selenium

Se is an essential element for animals. In man low dietary Se intakes are associated with health disorders including oxidative stress-related conditions, reduced fertility and immune functions and an increased risk of cancers. Although the reference nutrient intakes for adult females and males in the UK are 60 and 75 μg Se/d respectively, dietary Se intakes in the UK have declined from >60 μg Se/d in the 1970s to 35 μg Se/d in the 1990s, with a concomitant decline in human Se status. This decline in Se intake and status has been attributed primarily to the replacement of milling wheat having high levels of grain Se and grown on high-Se soils in North America with UK-sourced wheat having low levels of grain Se and grown on low-Se soils. An immediate solution to low dietary Se intake and status is to enrich UK-grown food crops using Se fertilisers (agronomic biofortification). Such a strategy has been adopted with success in Finland. It may also be possible to enrich food crops in the longer term by selecting or breeding crop varieties with enhanced Se-accumulation characteristics (genetic biofortification). The present paper will review the potential for biofortification of UK food crops with Se

Influence of cell cycle phase on calcification in the coccolithophore Emiliania huxleyi

Calcification of the cosmopolitan coccolithophore species Emiliania huxleyi was investigated in relation to the cell division cycle with the use of batch cultures. With a 12 : 12 h light : dark cycle, the population was synchronised to undergo division as a cohort, simultaneously passing through the G1 (assimilation), S (DNA replication), and G2+M (cell division and mitosis) phases. Cell division was followed with the use of quantitative DNA staining and flow cytometry. Simultaneously, carbon-14 (14C) assimilation in organic and inorganic carbon as well as cell abundance, size, and organic nitrogen content were measured at 2-h intervals. In additional experiments, changes in calcification and cell cycle stages were investigated in nitrogen-, phosphorus-, and light-limited cultures. Calcification occurred only during the G1 cell cycle phase, as seen by the very tight correlation between the percentage of cells in G1 and calcification during the dark period. When growth was limited by nitrogen, cells decreased in size, remained in the G1 phase, and showed a moderate increase in the cell-specific calcite content. Limitation of growth by phosphorus, however, caused a significant increase in cell size and a dramatic increase in cellular calcite. Light limitation, by slowing the growth rate, prolonged the time cells spent in the G1 phase with a corresponding increase in the cellular calcite content. These results help explain the differing responses of coccolithophorid growth to nitrogen, phosphorus, and light limitation

Measurement of the Positive Muon Lifetime and Determination of the Fermi Constant to Part-per-Million Precision

We report a measurement of the positive muon lifetime to a precision of 1.0 parts per million (ppm); it is the most precise particle lifetime ever measured. The experiment used a time-structured, low-energy muon beam and a segmented plastic scintillator array to record more than 2 x 10^{12} decays. Two different stopping target configurations were employed in independent data-taking periods. The combined results give tau_{mu^+}(MuLan) = 2196980.3(2.2) ps, more than 15 times as precise as any previous experiment. The muon lifetime gives the most precise value for the Fermi constant: G_F(MuLan) = 1.1663788 (7) x 10^-5 GeV^-2 (0.6 ppm). It is also used to extract the mu^-p singlet capture rate, which determines the proton's weak induced pseudoscalar coupling g_P.Comment: Accepted for publication in Phys. Rev. Let

Screening for familial hypercholesterolaemia in primary care: Time for general practice to play its part

Fifty per cent of first-degree relatives of index cases with familial hypercholesterolemia (FH) inherit the disorder. Despite cascade screening being the most cost-effective method for detecting new cases, only a minority of individuals with FH are currently identified. Primary care is a key target area to increase identification of new index cases and initiate cascade screening, thereby finding close relatives of all probands. Increasing public and health professional awareness about FH is essential. In the United Kingdom and in Australia, most of the population are reviewed by a General Practitioner (GP) at least once over a three-year period, offering opportunities to check for FH as part of routine clinical consultations. Such opportunistic approaches can be supplemented by systematically searching electronic health records with information technology tools that identify high risk patients. GPs can help investigate and implement results of this data retrieval. Current evidence suggests that early detection of FH and cascade testing meet most of the criteria for a worthwhile screening program. Among heterozygous patients the long latent period before the expected onset of coronary artery disease provides an opportunity for initiating effective drug and lifestyle changes. The greatest challenge for primary care is to implement an efficacious model of care that incorporates sustainable identification and management pathways

Statistics for the Luria-Delbr\"uck distribution

The Luria-Delbr\"uck distribution is a classical model of mutations in cell kinetics. It is obtained as a limit when the probability of mutation tends to zero and the number of divisions to infinity. It can be interpreted as a compound Poisson distribution (for the number of mutations) of exponential mixtures (for the developing time of mutant clones) of geometric distributions (for the number of cells produced by a mutant clone in a given time). The probabilistic interpretation, and a rigourous proof of convergence in the general case, are deduced from classical results on Bellman-Harris branching processes. The two parameters of the Luria-Delbr\"uck distribution are the expected number of mutations, which is the parameter of interest, and the relative fitness of normal cells compared to mutants, which is the heavy tail exponent. Both can be simultaneously estimated by the maximum likehood method. However, the computation becomes numerically unstable as soon as the maximal value of the sample is large, which occurs frequently due to the heavy tail property. Based on the empirical generating function, robust estimators are proposed and their asymptotic variance is given. They are comparable in precision to maximum likelihood estimators, with a much broader range of calculability, a better numerical stability, and a negligible computing time