Impaired natural killer cell phenotype and function in idiopathic and heritable pulmonary arterial hypertension

BACKGROUND: Beyond their role as innate immune effectors, natural killer (NK) cells are emerging as important regulators of angiogenesis and vascular remodeling. Pulmonary arterial hypertension (PAH) is characterized by severe pulmonary vascular remodeling and has long been associated with immune dysfunction. Despite this association, a role for NK cells in disease pathology has not yet been described. METHODS AND RESULTS: Analysis of whole blood lymphocytes and isolated NK cells from PAH patients revealed an expansion of the functionally defective CD56(-)/CD16(+) NK subset that was not observed in patients with chronic thromboembolic pulmonary hypertension. NK cells from PAH patients also displayed decreased levels of the activating receptor NKp46 and the killer immunoglobulin-like receptors 2DL1/S1 and 3DL1, reduced secretion of the cytokine macrophage inflammatory protein-1β, and a significant impairment in cytolytic function associated with decreased killer immunoglobulin-like receptor 3DL1 expression. Genotyping patients (n=222) and controls (n=191) for killer immunoglobulin-like receptor gene polymorphisms did not explain these observations. Rather, we show that NK cells from PAH patients exhibit increased responsiveness to transforming growth factor-β, which specifically downregulates disease-associated killer immunoglobulin-like receptors. NK cell number and cytotoxicity were similarly decreased in the monocrotaline rat and chronic hypoxia mouse models of PAH, accompanied by reduced production of interferon-γ in NK cells from hypoxic mice. NK cells from PAH patients also produced elevated quantities of matrix metalloproteinase 9, consistent with a capacity to influence vascular remodeling. CONCLUSIONS: Our work is the first to identify an impairment of NK cells in PAH and suggests a novel and substantive role for innate immunity in the pathobiology of this disease

Variations in architecture and cyclicity in fault-bounded carbonate platforms: Early Miocene Red Sea Rift, NW Saudi Arabia

The Early Miocene was a period of active rifting and carbonate platform development in the Midyan Peninsula, NW Saudi Arabia. However, there is no published literatures available dealing with detail characterization of the different carbonate platforms in this study area. Therefore, this study aims at presenting new stratigraphic architectural models that illustrate the formation of different carbonate platforms in the region and its forcing mechanisms that likely drove their formation. This study identified the following features formed during active rifting: a) a Late Aquitanian (N4) fault-block hangingwall dipslope carbonate ramp b) a Late Burdigalian (N7-N8) isolated normal fault-controlled carbonate platform with associated slope deposits, and c) a Late Burdigalian (N7-N8) attached fault-bounded, rimmed shelf developed on a footwall fault-tip within a basin margin structural relay zone formed coinciding with the second stage of rifting. Variations in cyclicity have been observed within the internal stratigraphic architecture of each platform and also between platforms. High-resolution sequence stratigraphic analysis show parasequences observed as the smallest depositional packages (meter-scale cycles) within the platforms. The hangingwall dipslope carbonate ramp and the attached platform demonstrate aggradational-progradational parasequence stacking patterns. These locations appear to have been more sensitive to eustatic cyclicities, despite the active tectonic setting. The isolated, fault-controlled carbonate platform reveals disorganized stratal geometries in both platform-top and slope facies, suggesting a more complex interplay of rates of tectonic uplift and subsidence, variation in carbonate productivity, and resedimentation of carbonates, such that any sea-level cyclicity is obscure. This study explores the interplay between different forcing mechanisms in the evolution of carbonate platforms in active extensional tectonic regions. Characterization of detailed parasequence-scale internal architecture allows the spatial variation in syn-depositional relative base-level changes to be inferred and is critical for understanding the development of rift basin carbonate platforms. Such concepts may be useful for the prediction of subsurface facies relationships beyond interwell areas in hydrocarbon exploration and reservoir modeling activities

Low frequency observations of linearly polarized structures in the interstellar medium near the south Galactic pole

This is an author-created, un-copyedited version of an article published in The Astrophysical Journal. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at https://doi.org/10.3847/0004-637X/830/1/38We present deep polarimetric observations at 154 MHz with the Murchison Widefield Array (MWA), covering 625 deg^2 centered on RA=0 h, Dec=-27 deg. The sensitivity available in our deep observations allows an in-band, frequency-dependent analysis of polarized structure for the first time at long wavelengths. Our analysis suggests that the polarized structures are dominated by intrinsic emission but may also have a foreground Faraday screen component. At these wavelengths, the compactness of the MWA baseline distribution provides excellent snapshot sensitivity to large-scale structure. The observations are sensitive to diffuse polarized emission at ~54' resolution with a sensitivity of 5.9 mJy beam^-1 and compact polarized sources at ~2.4' resolution with a sensitivity of 2.3 mJy beam^-1 for a subset (400 deg^2) of this field. The sensitivity allows the effect of ionospheric Faraday rotation to be spatially and temporally measured directly from the diffuse polarized background. Our observations reveal large-scale structures (~1 deg - 8 deg in extent) in linear polarization clearly detectable in ~2 minute snapshots, which would remain undetectable by interferometers with minimum baseline lengths >110 m at 154 MHz. The brightness temperature of these structures is on average 4 K in polarized intensity, peaking at 11 K. Rotation measure synthesis reveals that the structures have Faraday depths ranging from -2 rad m^-2 to 10 rad m^-2 with a large fraction peaking at ~+1 rad m^-2. We estimate a distance of 51+/-20 pc to the polarized emission based on measurements of the in-field pulsar J2330-2005. We detect four extragalactic linearly polarized point sources within the field in our compact source survey. Based on the known polarized source population at 1.4 GHz and non-detections at 154 MHz, we estimate an upper limit on the depolarization ratio of 0.08 from 1.4 GHz to 154 MHz.Peer reviewedFinal Accepted Versio

Cognitive styles and learning strategies : understanding style differences in learning and behaviour/Riding

217 p.: ill, tab.; 23 cm

Cognitive style, gender and learning from multi-media materials in 11 year-old children

Eighty 11 year-old pupils (40 males and 40 females) from an urban primary school were assessed for cognitive style by means of the Cognitive Styles Analysis which indicated their positions on each of the two style dimensions, the Wholist-Analytic and the Verbal-Imagery. They then studied parts of three CD-ROM multi-media packages on science topics and after each, completed a multiple choice recall test. An indication of their performance on traditionally taught science was taken to be the performance on science SATs at 11 years. A comparison between multi-media and traditional work indicated that, (a) in terms of overall science performance (traditional and multi-media), Wholist-Imagers and Analytic-Verbalisers were superior to Wholist-Verbalisers and Analytic-Imagers, and (b) Analytics did better on traditional work than multi-media, with the reverse for the Wholists. With the multi-media materials there were three modes of presentation---picture and sound (PS), picture and text (PT), and picture, text and sound (PTS). Female Wholist-Imagers and Analytic-Verbalisers were better with PS than PT, with the reverse for Wholist-Verbalisers and Analytic-Imagers, while the opposite applied for males. For all style and gender groups performance was best with PTS. The findings are discussed in terms of their practical implications and further research

Editorship : British journal of educational psychology

142 page(s