Ligation of protease-activated receptor 1 enhances alpha(v)beta(6) integrin-dependent TGF-beta activation and promotes acute lung injury

Activation of latent TGF-beta by the alpha(v)beta(6) integrin is a critical step in the development of acute lung injury. However, the mechanism by which a alpha(v)beta(6)-mediated TGF-beta activation is regulated has not been identified. We show that thrombin, and other agonists of protease-activated receptor 1(PAR1), activate TGF-beta in an alpha(v)beta(6) integrin-specific manner. This effect is PART specific and is mediated by RhoA and Rho kinase. Intratracheal instillation of the PART-specific peptide TFLLRN increases lung edema during high-tidal-volume ventilation, and this effect is completely inhibited by a blocking antibody against the alpha(v)beta(6) integrin. Instillation of TFLLRN during high-tidal-volume ventilation is associated with increased pulmonary TGF-beta activation; however, this is not observed in Itgb6(-/-) mice. Furthermore, Itgb6(-/-) mice are also protected from ventilator-induced lung edema. We also demonstrate that pulmonary edema and TGF-beta activity are similarly reduced in Par1(-/-) mice following bleomycin-induced lung injury. These results suggest that PART-mediated enhancement of a alpha(v)beta(6)-dependent TGF-beta activation could be one mechanism by which activation of the coagulation cascade contributes to the development of acute lung injury, and they identify PART and the alpha(v)beta(6) integrin as potential therapeutic targets in this condition

Predicting the Need for Ventilation in Term and Near-Term Neonates

To determine whether the need for respiratory support can be predicted by oxygen requirement within the first 72 h in term and near-term infants. Methods: To mimic the population of infants that would often be delivered outside a tertiary centre we studied a retrospective cohort of infants greater than or equal to 32 weeks requiring oxygen, divided into three groups: cot oxygen only, nasal continuous positive airway pressure (NCPAP) only, or intermittent positive pressure ventilation (IPPV). We recorded each infant's peak fraction of inspired oxygen (FiO2) - i.e. FiO 2 in the first 72 h in the cot oxygen only group or maximum FiO2 prior to commencing the highest level of respiratory support. The peak FiO2 was used as a diagnostic test to predict any respiratory support or IPPV-sensitivity and specificity were calculated and receiver operating characteristic (ROC) curves plotted (FiO2 0.21-1.00) to identify the best balance point for prediction. Results: The cohort included 592 infants: 516 cot oxygen only, 46 NCPAP only and 30 IPPV. The proportion ventilated increased with increasing peak FiO2 - above 0.45 the proportion of infants ventilated exceeded 50%. To predict any respiratory support, the cut-point balancing sensitivity and specificity was a FiO2 greater than or equal to 0.35-58/136 required respiratory support (sensitivity = 0.76, specificity = 0.85, positive predictive value (PPV) = 43%, negative predictive value (NPV) = 96%). To predict IPPV the cut-point was a FiO2 greater than or equal to 0.5-28/47 treated with IPPV (sensitivity = 0.93, specificity = 0.97, PPV = 60%, NPV = 100%). Conclusion: The need for respiratory support can be predicted by oxygen requirement within the first 72 h in term and near-term infants with reasonable sensitivity and excellent specificity

The JCMT Legacy Survey of the Gould Belt: Mapping 13CO and C 18O in Orion A

The Gould Belt Legacy Survey will map star-forming regions within 500 pc, using Heterodyne Array Receiver Programme (HARP), Submillimetre Common-User Bolometer Array 2 (SCUBA-2) and Polarimeter 2 (POL-2) on the James Clerk Maxwell Telescope (JCMT). This paper describes HARP observations of the J= 3 → 2 transitions of 13CO and C18O towards Orion A. The 15 arcsec resolution observations cover 5 pc of the Orion filament, including OMC 1 (including BN–KL and Orion bar), OMC 2/3 and OMC 4, and allow a comparative study of the molecular gas properties throughout the star-forming cloud. The filament shows a velocity gradient of ∼1 km s−1 pc−1 between OMC 1, 2 and 3, and high-velocity emission is detected in both isotopologues. The Orion Nebula and Bar have the largest masses and linewidths, and dominate the mass and energetics of the high-velocity material. Compact, spatially resolved emission from CH3CN, 13CH3OH, SO, HCOOCH3, CH3CHO and CH3OCHO is detected towards the Orion Hot Core. The cloud is warm, with a median excitation temperature of ∼24 K; the Orion Bar has the highest excitation temperature gas, at >80 K. The C18O excitation temperature correlates well with the dust temperature (to within 40 per cent). The C18O emission is optically thin, and the 13CO emission is marginally optically thick; despite its high mass, OMC 1 shows the lowest opacities. A virial analysis indicates that Orion A is too massive for thermal or turbulent support, but is consistent with a model of a filamentary cloud that is threaded by helical magnetic fields. The variation of physical conditions across the cloud is reflected in the physical characteristics of the dust cores. We find similar core properties between starless and protostellar cores, but variations in core properties with position in the filament. The OMC 1 cores have the highest velocity dispersions and masses, followed by OMC 2/3 and OMC 4. The differing fragmentation of these cores may explain why OMC 1 has formed clusters of high-mass stars, whereas OMC 4 produces fewer, predominantly low-mass stars

稲垣足穂『少年愛の美学』の読書論的研究 --念者としての語り--

千葉大学大学院人文社会科学研究科研究プロジェクト報告書第144集 『パフォーマンスの民族誌的研究』橋本裕之

Climate Dynamics: A Network-Based Approach for the Analysis of Global Precipitation

Precipitation is one of the most important meteorological variables for defining the climate dynamics, but the spatial patterns of precipitation have not been fully investigated yet. The complex network theory, which provides a robust tool to investigate the statistical interdependence of many interacting elements, is used here to analyze the spatial dynamics of annual precipitation over seventy years (1941-2010). The precipitation network is built associating a node to a geographical region, which has a temporal distribution of precipitation, and identifying possible links among nodes through the correlation function. The precipitation network reveals significant spatial variability with barely connected regions, as Eastern China and Japan, and highly connected regions, such as the African Sahel, Eastern Australia and, to a lesser extent, Northern Europe. Sahel and Eastern Australia are remarkably dry regions, where low amounts of rainfall are uniformly distributed on continental scales and small-scale extreme events are rare. As a consequence, the precipitation gradient is low, making these regions well connected on a large spatial scale. On the contrary, the Asiatic South-East is often reached by extreme events such as monsoons, tropical cyclones and heat waves, which can all contribute to reduce the correlation to the short-range scale only. Some patterns emerging between mid-latitude and tropical regions suggest a possible impact of the propagation of planetary waves on precipitation at a global scale. Other links can be qualitatively associated to the atmospheric and oceanic circulation. To analyze the sensitivity of the network to the physical closeness of the nodes, short-term connections are broken. The African Sahel, Eastern Australia and Northern Europe regions again appear as the supernodes of the network, confirming furthermore their long-range connection structure. Almost all North-American and Asian nodes vanish, revealing that extreme events can enhance high precipitation gradients, leading to a systematic absence of long-range patterns

Delineation of individual human chromosomes in metaphase and interphase cells by in situ suppression hybridization using recombinant DNA libraries

A method of in situ hybridization for visualizing individual human chromosomes from pter to qter, both in metaphase spreads and interphase nuclei, is reported. DNA inserts from a single chromosomal library are labeled with biotin and partially preannealed with a titrated amount of total human genomic DNA prior to hybridization with cellular or chromosomal preparations. The cross-hybridization of repetitive sequences to nontargeted chromosomes can be markedly suppressed under appropriate preannealing conditions. The remaining single-stranded DNA is hybridized to specimens of interest and detected with fluorescent or enzymelabeled avidin conjugates following post-hybridization washes. DNA inserts from recombinant libraries for chromosomes 1, 4, 7, 8, 13, 14, 18, 20, 21, 22, and X were assessed for their ability to decorate specifically their cognate chromosome; most libraries proved to be highly specific. Quantitative densitometric analyses indicated that the ratio of specific to nonspecific hybridization signal under optimal preannealing conditions was at least 8:1. Interphase nuclei showed a cohesive territorial organization of chromosomal domains, and laserscanning confocal fluorescence microscopy was used to aid the 3-D visualization of these domains. This method should be useful for both karyotypic studies and for the analysis of chromosome topography in interphase cells

The Supertree Tool Kit

<p>Abstract</p> <p>Background</p> <p>Large phylogenies are crucial for many areas of biological research. One method of creating such large phylogenies is the supertree method, but creating supertrees containing thousands of taxa, and hence providing a comprehensive phylogeny, requires hundred or even thousands of source input trees. Managing and processing these data in a systematic and error-free manner is challenging and will become even more so as supertrees contain ever increasing numbers of taxa. Protocols for processing input source phylogenies have been proposed to ensure data quality, but no robust software implementations of these protocols as yet exist.</p> <p>Findings</p> <p>The aim of the Supertree Tool Kit (STK) is to aid in the collection, storage and processing of input source trees for use in supertree analysis. It is therefore invaluable when creating supertrees containing thousands of taxa and hundreds of source trees. The STK is a Perl module with executable scripts to carry out various steps in the processing protocols. In order to aid processing we have added meta-data, via XML, to each tree which contains information such as the bibliographic source information for the tree and how the data were derived, for instance the character data used to carry out the original analysis. These data are essential parts of previously proposed protocols.</p> <p>Conclusions</p> <p>The STK is a bioinformatics tool designed to make it easier to process source phylogenies for inclusion in supertree analysis from hundreds or thousands of input source trees, whilst reducing potential errors and enabling easy sharing of such datasets. It has been successfully used to create the largest known supertree to date containing over 5000 taxa from over 700 source phylogenies.</p