Serum adiponectin is positively associated with lung function in young adults, independent of obesity: The CARDIA study

<p>Abstract</p> <p>Rationale</p> <p>Adipose tissue produces adiponectin, an anti-inflammatory protein. Adiponectin deficiency in mice is associated with abnormal post-natal alveolar development.</p> <p>Objective</p> <p>We hypothesized that lower serum adiponectin concentrations are associated with lower lung function in humans, independent of obesity. We explored mediation of this association by insulin resistance and systemic inflammation.</p> <p>Methods and Measurements</p> <p>Spirometry testing was conducted at years 10 and 20 follow-up evaluation visits in 2,056 eligible young adult participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Body mass index, serum adiponectin, serum C-reactive protein (a marker of systemic inflammation), and insulin resistance were assessed at year 15.</p> <p>Main Results</p> <p>After controlling for body mass index, years 10 and 20 forced vital capacity (FVC) were 81 ml and 82 ml lower respectively (p = 0.004 and 0.01 respectively) in the lowest <it>vs</it>. highest adiponectin quartiles. Similarly, years 10 and 20 forced expiratory volume in one second (FEV₁) were 50 ml and 38 ml lower (p = 0.01 and 0.09, respectively) in the lowest <it>vs</it>. highest adiponectin quartiles. These associations were no longer significant after adjustment for insulin resistance and C-reactive protein. Serum adiponectin was not associated with FEV₁/FVC or peak FEV₁.</p> <p>Conclusions</p> <p>Independent of obesity, lower serum adiponectin concentrations are associated with lower lung function. The attenuation of this association after adjustment for insulin resistance and systemic inflammation suggests that these covariates are on a causal pathway linking adiponectin and lung function.</p

Beam-forming errors in Murchison Widefield array phased array antennas and their effects on epoch of reionization science

Accurate antenna beam models are critical for radio observations aiming to isolate the redshifted 21 cm spectral line emission from the Dark Ages and the Epoch of Reionization (EOR) and unlock the scientific potential of 21 cm cosmology. Past work has focused on characterizing mean antenna beam models using either satellite signals or astronomical sources as calibrators, but antenna-to-antenna variation due to imperfect instrumentation has remained unexplored. We characterize this variation for the Murchison Widefield Array (MWA) through laboratory measurements and simulations, finding typical deviations of the order of ±10%-20% near the edges of the main lobe and in the sidelobes. We consider the ramifications of these results for image- and power spectrum-based science. In particular, we simulate visibilities measured by a 100 m baseline and find that using an otherwise perfect foreground model, unmodeled beam-forming errors severely limit foreground subtraction accuracy within the region of Fourier space contaminated by foreground emission (the "wedge"). This region likely contains much of the cosmological signal, and accessing it will require measurement of per-antenna beam patterns. However, unmodeled beam-forming errors do not contaminate the Fourier space region expected to be free of foreground contamination (the "EOR window"), showing that foreground avoidance remains a viable strategy

The murchison widefield array 21 cm power spectrum analysis methodology

We present the 21 cm power spectrum analysis approach of the Murchison Widefield Array Epoch of Reionization project. In this paper, we compare the outputs of multiple pipelines for the purpose of validating statistical limits cosmological hydrogen at redshifts between 6 and 12. Multiple independent data calibration and reduction pipelines are used to make power spectrum limits on a fiducial night of data. Comparing the outputs of imaging and power spectrum stages highlights differences in calibration, foreground subtraction, and power spectrum calculation. The power spectra found using these different methods span a space defined by the various tradeoffs between speed, accuracy, and systematic control. Lessons learned from comparing the pipelines range from the algorithmic to the prosaically mundane; all demonstrate the many pitfalls of neglecting reproducibility. We briefly discuss the way these different methods attempt to handle the question of evaluating a significant detection in the presence of foregrounds

Measuring phased-array antenna beampatterns with high dynamic range for the Murchison Widefield Array using 137MHz ORBCOMM satellites

Detection of the fluctuations in a 21 cm line emission from neutral hydrogen during the Epoch of Reionization in thousand hour integrations poses stringent requirements on calibration and image quality, both of which necessitate accurate primary beam models. The Murchison Widefield Array (MWA) uses phased-array antenna elements which maximize collecting area at the cost of complexity. To quantify their performance, we have developed a novel beam measurement system using the 137 MHz ORBCOMM satellite constellation and a reference dipole antenna. Using power ratio measurements, we measure the in situ beampattern of the MWA antenna tile relative to that of the reference antenna, canceling the variation of satellite flux or polarization with time. We employ angular averaging to mitigate multipath effects (ground scattering) and assess environmental systematics with a null experiment in which the MWA tile is replaced with a second-reference dipole. We achieve beam measurements over 30 dB dynamic range in beam sensitivity over a large field of view (65% of the visible sky), far wider and deeper than drift scans through astronomical sources allow. We verify an analytic model of the MWA tile at this frequency within a few percent statistical scatter within the full width at half maximum. Toward the edges of the main lobe and in the sidelobes, we measure tens of percent systematic deviations. We compare these errors with those expected from known beamforming errors

KNOWN PULSARS IDENTIFIED in the GMRT 150 MHz ALL-SKY SURVEY

We have used the 150 MHz radio continuum survey (TGSS ADR) from the Giant Metrewave Radio Telescope (GMRT) to search for phase-averaged emission toward all well-localized radio pulsars north of -53° decl. We detect emission toward 200 pulsars with high confidence (=5s) and another 88 pulsars at fainter levels. We show that most of our identifications are likely from pulsars, except for a small number where the measured flux density is confused by an associated supernova or pulsar-wind nebula, or a globular cluster. We investigate the radio properties of the 150 MHz sample and find an unusually high number of gamma-ray binary millisecond pulsars with very steep spectral indices. We also note a discrepancy in the measured flux densities between GMRT and LOFAR pulsar samples, suggesting that the flux density scale for the LOFAR pulsar sample may be in error by approximately a factor of two. We carry out a separate search of 30 well-localized gamma-ray, radio-quiet pulsars in an effort to detect a widening of the radio beam into the line of sight at lower frequencies. No steep-spectrum emission was detected either toward individual pulsars or in a weighted stack of all 30 images

Targeted plasmid integration into the human genome by an engineered zinc-finger recombinase

The development of new methods for gene addition to mammalian genomes is necessary to overcome the limitations of conventional genetic engineering strategies. Although a variety of DNA-modifying enzymes have been used to directly catalyze the integration of plasmid DNA into mammalian genomes, there is still an unmet need for enzymes that target a single specific chromosomal site. We recently engineered zinc-finger recombinase (ZFR) fusion proteins that integrate plasmid DNA into a synthetic target site in the human genome with exceptional specificity. In this study, we present a two-step method for utilizing these enzymes in any cell type at randomly-distributed target site locations. The piggyBac transposase was used to insert recombinase target sites throughout the genomes of human and mouse cell lines. The ZFR efficiently and specifically integrated a transfected plasmid into these genomic target sites and into multiple transposons within a single cell. Plasmid integration was dependent on recombinase activity and the presence of recombinase target sites. This work demonstrates the potential for broad applicability of the ZFR technology in genome engineering, synthetic biology and gene therapy

Constraining Polarized Foregrounds for EoR Experiments. II. Polarization Leakage Simulations in the Avoidance Scheme

A critical challenge in the observation of the redshifted 21 cm line is its separation from bright Galactic and extragalactic foregrounds. In particular, the instrumental leakage of polarized foregrounds, which undergo significant Faraday rotation as they propagate through the interstellar medium, may harmfully contaminate the 21 cm power spectrum. We develop a formalism to describe the leakage due to instrumental widefield effects in visibility-based power spectra measured with redundant arrays, extending the delay-spectrum approach presented in Parsons et al. We construct polarized sky models and propagate them through the instrument model to simulate realistic full-sky observations with the Precision Array to Probe the Epoch of Reionization. We find that the leakage due to a population of polarized point sources is expected to be higher than diffuse Galactic polarization at any k mode for a 30 m reference baseline. For the same reference baseline, a foreground-free window at k > 0.3 h Mpc-1 can be defined in terms of leakage from diffuse Galactic polarization even under the most pessimistic assumptions. If measurements of polarized foreground power spectra or a model of polarized foregrounds are given, our method is able to predict the polarization leakage in actual 21 cm observations, potentially enabling its statistical subtraction from the measured 21 cm power spectrum

The Association Between Blood Coagulation Activity and Lung Function: A Population-Based Study

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Increased in susceptibility to thrombotic disease may be associated with lower lung function. If causal, this association may suggest an area for development of new interventions for lung disease. The aim of this study was to investigate the association between blood coagulation activation as measured by plasma d-dimers and lung function.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology/Principal Findings:&lt;/b&gt; We conducted a cross-sectional study on 2463 randomly selected adults in 1991 and followed up 1252 of these individuals in 2000. Plasma D-dimer levels, a marker of activity of blood coagulation pathways, were analysed in the baseline 1991 samples. There was an inverse cross-sectional association between plasma D-dimer and Forced Expiratory Volume in one second, with a decrease of 71 ml per mg FEU/ml increment in plasma D-dimer (95% confidence intervals CI: -135 to -6), and a decrease in Forced Vital Capacity (97 ml per mg FEU/ml increase in D-dimer, 95% CI: -170 to -24). These associations were attenuated after adjustment for serum highly sensitive CRP. No association was observed between plasma D-dimer and the decline in lung function between 1991 and 2000.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions/Significance:&lt;/b&gt; The cross-sectional findings are consistent with the hypothesis that activation of blood coagulation pathways is associated with decreased lung function, and that systemic inflammation may contribute to this relation. However, the lack of an association with decline in lung function suggests that clotting pathways that involve d-dimers may not be a promising therapeutic target for new interventions for respiratory disease.&lt;/p&gt

Heterogeneous Nuclear Ribonucleoprotein K Interacts with Abi-1 at Postsynaptic Sites and Modulates Dendritic Spine Morphology

BACKGROUND: Abelson-interacting protein 1 (Abi-1) plays an important role for dendritic branching and synapse formation in the central nervous system. It is localized at the postsynaptic density (PSD) and rapidly translocates to the nucleus upon synaptic stimulation. At PSDs Abi-1 is in a complex with several other proteins including WASP/WAVE or cortactin thereby regulating the actin cytoskeleton via the Arp 2/3 complex. PRINCIPAL FINDINGS: We identified heterogeneous nuclear ribonucleoprotein K (hnRNPK), a 65 kDa ssDNA/RNA-binding-protein that is involved in multiple intracellular signaling cascades, as a binding partner of Abi-1 at postsynaptic sites. The interaction with the Abi-1 SH3 domain is mediated by the hnRNPK-interaction (KI) domain. We further show that during brain development, hnRNPK expression becomes more and more restricted to granule cells of the cerebellum and hippocampal neurons where it localizes in the cell nucleus as well as in the spine/dendritic compartment. The downregulation of hnRNPK in cultured hippocampal neurons by RNAi results in an enlarged dendritic tree and a significant increase in filopodia formation. This is accompanied by a decrease in the number of mature synapses. Both effects therefore mimic the neuronal morphology after downregulation of Abi-1 mRNA in neurons. CONCLUSIONS: Our findings demonstrate a novel interplay between hnRNPK and Abi-1 in the nucleus and at synaptic sites and show obvious similarities regarding both protein knockdown phenotypes. This indicates that hnRNPK and Abi-1 act synergistic in a multiprotein complex that regulates the crucial balance between filopodia formation and synaptic maturation in neurons