Regulation of gene expression in pulmonary inflammation and differentiation : a role for C/EBP transcription factors

CCAAT/enhancer-binding protein (C/EBP) transcription factors play essential roles in gene regulation. The lung-enriched isoform C/EBPα is known to inhibit proliferation, promote differentiation and stimulate gene expression characteristic of the mature differentiated pulmonary epithelium. C/EBPβ, also enriched in the lung, plays a role in cell differentiation and the regulation of inflammatory and host defense genes in several organs. The activity of C/EBPβ is decreased in smokers with chronic obstructive pulmonary disease (COPD), indicating a role in COPD pathogenesis. The objective of this thesis was to investigate the unique or overlapping roles of C/EBPα and C/EBPβ in lung epithelial differentiation, and to assess the contribution of C/EBPβ in regulating pulmonary inflammation. To investigate unique vs. overlapping roles of C/EBPα and C/EBPβ in the lung, the pulmonary phenotype of mice lacking C/EBPα (Cebpa ΔLE mice), C/EBPβ (Cebpb ΔLE mice) or both C/EBPα and C/EBPβ (Cebpa ΔLE ; Cebpb ΔLE mice) specifically in the lung epithelium, all generated by SFTPC-Cre mediated excision, was investigated. Cell culture experiments suggested that C/EBPα and C/EBPβ bind the same elements within a lungspecific promoter, and that their functions are partially overlapping. Pre-natal Cebpa ΔLE mice and Cebpa ΔLE ; Cebpb ΔLE mice displayed immature lungs similar to the lungs of premature infants, and Cebpa ΔLE ; Cebpb ΔLE mice exhibited even more impaired airway epithelial cell differentiation than the Cebpa ΔLE mice. The proportion of Cebpa ΔLE mice that survived and reached adulthood spontaneously developed a majority of the histopathological hallmarks of COPD, possibly caused by infiltrating inflammatory cells – similar to what is observed in COPD and what is mechanistically proposed to drive COPD pathogenesis. These findings are indicative of a relationship between immature lungs at birth, C/EBPs and the development of inflammatory lung disease. Considering the previous documentation of decreased airway epithelial C/EBPβ activity in smokers with COPD, C/EBPβ could have a role in COPD pathogenesis. The role of C/EBPβ in regulating inflammatory and innate immune responses in the lung was on this account investigated by employing a translational approach encompassing clinical samples as well as in vitro and in vivo experiments. CEBPB was significantly down-regulated in the airway epithelium of both current and former smokers compared to never-smokers, and in cigarette smoke extract-treated primary human airway epithelial cells in vitro, suggesting that C/EBPβ plays a role in smoking-induced disease. Supporting this, inhibition of CEBPB in human airway cells in vitro resulted in a compromised inflammatory response to smoke. Moreover, cigarette smoke-exposed Cebpb ΔLE mice displayed reduced respiratory neutrophilia and induction of inflammatory mediators, including the neutrophil chemoattractant Groa, compared to smoke-exposed controls. LPS-challenged Cebpb ΔLE mice also exhibited blunted respiratory neutrophilia and lower pulmonary expression of Groa, compared to LPS-challenged control littermates. In addition, suppression of LPSinduced neutrophilia and inflammatory gene expression by formoterol, a long acting β2- adrenoceptor agonist used in treatment of COPD, was impaired in Cebpb ΔLE mice. C/EBP transactivation was increased by treatment with formoterol in vitro, possibly through a β2- adrenoceptor and cAMP-dependent mechanism. This demonstrates that both inflammatory as well as anti-inflammatory stimuli involve regulation of gene transcription by C/EBPβ. Taken together, these findings demonstrate that C/EBPα and C/EBPβ play pivotal and partly overlapping roles in airway epithelial differentiation, and that C/EBPβ and the lung epithelium orchestrates inflammatory responses as well as anti-inflammatory signaling by β2-adrenoceptor agonists in the lung. Thus, C/EBPs may influence tissue regeneration in lung homeostasis and disease as well as inflammatory and anti-inflammatory signaling, and are potential contributors to COPD pathogenesi

Oat-enriched diet reduces inflammatory status assessed by circulating cell-derived microparticle concentrations in type 2 diabetes

This work was funded by the Chief Scientists Office of the Scottish Government by a joint grant to the University of the Highland and Islands, Grampian Health Board, Biomathematics and Statistics Scotland and the Rowett Institute of Nutrition and Health, University of Aberdeen. Additional support was provided by Provexis plc.Peer reviewedPublisher PD

In-belt vibration monitoring of conveyor belt idler bearings by using wavelet package decomposition and artificial intelligence

Visual and acoustic methods are commonly used to identify faulty or failing idler bearings but these methods can become tedious and time consuming in practice. While vibration monitoring might look like an obvious choice to explore, the instrumentation of individual idler bearings would be prohibitively expensive. The potential for using an accelerometer that moves with the belt while tracking the condition of all bearings encountered along the way is therefore potentially interesting. This possibility is explored in this work on a laboratory scale test rig. Wavelet package decomposition is used to extract the bearing features and present it to an artificial neural network and support vector machine to identify and classify faulty idler bearings. The system could not only identify faulty bearings but also classify the faults accurately.http://www.inderscience.com/jhome.php?jcode=IJMME2022-05-06hj2021Mechanical and Aeronautical Engineerin

Three-Body Kick to a Bright Quasar out of Its Galaxy During a Merger

The quasar HE0450-2958 was recently discovered to reside ~7kpc away from a galaxy that was likely disturbed by a recent merger. The lack of a massive spheroid of stars around the quasar raised the unlikely suggestion that it may have formed in a dark galaxy. Here we explain this discovery as a natural consequence of a dynamical kick imparted to the quasar as it interacted with a binary black hole system during a galaxy merger event. The typical stalling radius for a ~10^9 solar mass binary provides a kick of order the escape velocity of the stellar spheroid, bringing the quasar out to around the observed radius before it turns around. This is consistent with the observed low relative velocity between the quasar and the merger-remnant galaxy. The gas carried with the black hole throughout the three-body interaction fuels the quasar for the duration of its journey, ~2x10^7 years. Gravitational radiation recoil could not have produced the required kick.Comment: 5 pages, 2 figures, ApJ Letters, in pres

Geometric acceleration of complex chemical equilibrium calculations —performance in two- to five-component systems

DATA AVAILABILITY : Data will be made available on request.Please read abstract in the article.Ex Mente Technologies and Glencore through their funding of the Chair in Pyrometallurgical Modelling at the University of Pretoria.http://www.elsevier.com/locate/calphadhj2023Materials Science and Metallurgical Engineerin

The Galaxy Population of Low-Redshift Abell Clusters

We present a study of the luminosity and color properties of galaxies selected from a sample of 57 low-redshift Abell clusters. We utilize the non-parametric dwarf-to-giant ratio (DGR) and the blue galaxy fraction (fb) to investigate the clustercentric radial-dependent changes in the cluster galaxy population. Composite cluster samples are combined by scaling the counting radius by r200 to minimize radius selection bias. The separation of galaxies into a red and blue population was achieved by selecting galaxies relative to the cluster color-magnitude relation. The DGR of the red and blue galaxies is found to be independent of cluster richness (Bgc), although the DGR is larger for the blue population at all measured radii. A decrease in the DGR for the red and red+blue galaxies is detected in the cluster core region, while the blue galaxy DGR is nearly independent of radius. The fb is found not to correlate with Bgc; however, a steady decline toward the inner-cluster region is observed for the giant galaxies. The dwarf galaxy fb is approximately constant with clustercentric radius except for the inner cluster core region where fb decreases. The clustercentric radial dependence of the DGR and the galaxy blue fraction, indicates that it is unlikely that a simple scenario based on either pure disruption or pure fading/reddening can describe the evolution of infalling dwarf galaxies; both outcomes are produced by the cluster environment.Comment: 28 pages, 6 figures, accepted for publication in Ap

Can long-term periodic variability and jet helicity in 3C 120 be explained by jet precession?

Optical variability of 3C 120 is discussed in the framework of jet precession. Specifically, we assume that the observed long-term periodic variability is produced by the emission from an underlying jet with a time-dependent boosting factor driven by precession. The differences in the apparent velocities of the different superluminal components in the milliarcsecond jet can also be explained by the precession model as being related to changes in the viewing angle. The evolution of the jet components has been used to determine the parameters of the precession model, which also reproduce the helical structure seen at large scales. Among the possible mechanisms that could produce jet precession, we consider that 3C 120 harbours a super-massive black hole binary system in its nuclear region and that torques induced by misalignment between the accretion disc and the orbital plane of the secondary black hole are responsible for this precession; we estimated upper and lower limits for the black holes masses and their mean separation.Comment: 10 pages, 4 figures, accepted for publication in MNRA

Daphnia Inhibits the Emergence of Spatial Pattern in a Simple Consumer-Resource System

Spatial self-organization can occur in many ecosystems with important effects on food web dynamics and the maintenance of biodiversity. The consumer-resource interaction is known to generate spatial patterning, but only a few empirical studies have investigated the effect of the consumer on resource distribution. Here we report results from a large aquatic mesocosm experiment used to investigate the effect of the consumer Daphnia magna on the distribution of its resource, the green algae Chlorella vulgaris. We maintained large tanks with capacity for 26 ,000 L with either algae or both algae and Daphnia in different temperature conditions. We found that the presence of D. magna inhibited spatial structure in algal distribution that arose as a consequence of increasing temperature. We conjecture that this homogenization effect might be caused by a combination of high mobility combined with high rates of algal consumption by Daphnia. Our study emphasizes the importance of both local constraints on growth and behavioral responses in either promoting or suppressing spatial self-organization in natural populations

Localizing Sagittarius A* and M87 on Microarcsecond Scales with Millimeter VLBI

With the advent of the Event Horizon Telescope (EHT), a millimeter/sub-millimeter very-long baseline interferometer (VLBI), it has become possible to image a handful of black holes with sub-horizon resolutions. However, these images do not translate into microarcsecond absolute positions due to the lack of absolute phase information when an external phase reference is not used. Due to the short atmospheric coherence time at these wavelengths, nodding between the source and phase reference is impractical. However, here we suggest an alternative scheme which makes use of the fact that many of the VLBI stations within the EHT are arrays in their own right. With this we show that it should be possible to absolutely position the supermassive black holes at the centers of the Milky Way (Sgr A*) and M87 relative to nearby objects with precisions of roughly 1 microarcsecond. This is sufficient to detect the perturbations to Sgr A*'s position resulting from interactions with the stars and stellar-mass black holes in the Galactic cusp on year timescales, and severely constrain the astrophysically relevant parameter space for an orbiting intermediate mass black hole, implicated in some mechanisms for producing the young massive stars in the Galactic center. For M87, it allows the registering of millimeter images, in which the black hole may be identified by its silhouette against nearby emission, and existing larger scale radio images, eliminating present ambiguities in the nature of the radio core and inclination, opening angle, and source of the radio jet.Comment: 18 pages, 4 figures, Accepted for publication in Ap

On the central black hole mass in Mkn~501

We analyse the apparent disagreement between the mass estimates of the central black hole(s) in Mkn~501 based on (i) the observations of the host galaxy, (ii) the high energy (HE) emission mechanism, and (iii) the modulation of the beamed radiation by a black hole (BH) binary system. While method (i) seems to imply a central mass > 5\times 10^8 M_{sun}, method (ii) suggests a BH mass less than 6 \times 10^7 M_{sun}. We critically discuss the estimates inferred from (i) showing that current uncertainties may permit a central mass as low as ~(2-3)\times 10^8 M_{sun}. We demonstrate that in this case the estimates (i) and (ii) might be brought into agreement by assuming a binary BH system where the jet dominating the HE emission originates from the less massive (secondary) BH as suggested by method (iii). On the other hand, if Mkn~501 has in fact a high central BH mass of order 10^9 M_{sun}, a change of fundamental assumptions seems to be required in the context of several HE emission models. We show, that in this case a binary scenario following (iii) may be still possible if the jet which dominates the emission emerges from the more massive (primary) BH and if the binary evolution passes through phases of super-Eddington accretion and/or decreased conversion efficiency.Comment: 6 pages, 1 figure; accepted for publication in A&