Pyocyanin, a contributory factor in haem acquisition and virulence enhancement of Porphyromonas gingivalis in the lung

Several recent studies show that the lungs infected with Pseudomonas aeruginosa are often co-colonised by oral bacteria including black-pigmenting anaerobic (BPA) Porphyromonas species. The BPAs have an absolute haem requirement and their presence in the infected lung indicates that sufficient haem, a virulence up-regulator in BPAs, must be present to support growth. Haemoglobin from micro-bleeds occurring during infection is the most likely source of haem in the lung. Porphyromonas gingivalis displays a novel haem acquisition paradigm whereby haemoglobin must be firstly oxidised to methaemoglobin, facilitating haem release, either by gingipain proteolysis or capture via the haem-binding haemophore HmuY. P. aeruginosa produces the blue phenazine redox compound, pyocyanin. Since phenazines can oxidise haemoglobin, it follows that pyocyanin may also facilitate haem acquisition by promoting methaemoglobin production. Here we show that pyocyanin at concentrations found in the CF lung during P. aeruginosa infections rapidly oxidises oxyhaemoglobin in a dose-dependent manner. We demonstrate that methaemoglobin formed by pyocyanin is also susceptible to proteolysis by P. gingivalis Kgp gingipain and neutrophil elastase, thus releasing haem. Importantly, co-incubation of oxyhaemoglobin with pyocyanin facilitates haem pickup from the resulting methemoglobin by the P. gingivalis HmuY haemophore. Mice intra-tracheally challenged with viable P. gingivalis cells plus pyocyanin displayed increased mortality compared to those administered P. gingivalis alone. Pyocyanin significantly elevated both methaemoglobin and total haem levels in homogenates of mouse lungs and increased the level of arginine-specific gingipain activity from mice inoculated with viable P. gingivalis cells plus pyocyanin compared with mice inoculated with P. gingivalis only. These findings indicate that pyocyanin, by promoting haem availability through methaemoglobin formation and stimulating of gingipain production, may contribute to virulence of P. gingivalis and disease severity when co-infecting with P. aeruginosa in the lung

Parameter Study of Star-Discs Encounters

Interactions between disc-surrounded stars might play a vital role in the formation of planetary systems. Here a first parameter study of the effects of encounters on low-mass discs is presented. The dependence of the mass and angular momentum transport on the periastron distance, the relative mass of the encountering stars and eccentricity of the encounter is investigated in detail. This is done for prograde and retrograde coplanar encounters as well as non-coplanar encounters. For distant coplanar encounters our simulation results agree with the analytical approximation of the angular momentum loss by Ostriker(1994). However, for close or high-mass encounters, significant differences to this approximation are found. This is especially so in the case of retrograde encounters, where the analytical result predict no angular momentum loss regardless of the periastron distance whereas the simulations find up to ~ 20% loss for close encounters. For the non-coplanar case a more complex dependency on the inclination between orbital path and disc plane is found than for distant encounters. For the coplanar prograde case new fitting formulae for the mass and angular momentum loss are obtained, which cover the whole range from grazing to distant encounters. In addition, the final disc size and the mass exchange between discs is examined, demonstrating that for equal mass stars in encounters as close as 1.5 the disc radius, the disc size only is reduced by approximately 10%.Comment: 11 pages, 9 figure

Methane regulation in the EU: Stakeholder perspectives on MRV and emissions reductions

Published online 19 September 2022Methane is potent greenhouse gas (GHG) accounting for 11% of all EU emissions, but in contrast to CO2 it has received relatively little attention. Although methane is regulated under the EU Effort Sharing framework, this policy lacks methane-specific regulations or targets, leaving the Member States considerable discretion over whether to prioritize methane reduction or not. The European Commission presented a proposal for EU methane regulation on 15 December 2021. However, our understanding of how to design measurement, reporting and verification (MRV) regulation for methane is limited. MRV involves many stakeholders at different steps in the process (policymakers, industry, civil society, MRV service providers, etc.), whose perspectives may differ, and our study aims to gain an insight into what constitutes an effective MRV by garnering the different stakeholders’ perspectives. The study reveals that: (1) the limits of voluntary MRV initiatives justify regulatory intervention, (2) the major barrier to the implementation of methane-specific MRV is not economic, but relates to an incomplete understanding of methane sources and available measurement technologies, (3) verification is likely to be the most challenging MRV element to implement, partly due to the limited number of accredited verifiers and overlapping tasks (4) MRV needs to be accompanied by methane mitigation policies incentivising continuous improvement of companies’ performance. The study recommends enhancing the proposed regulation by: introducing equal requirements for operated and non-operated assets; an obligation to report measurement uncertainties; a closer integration of MRV and LDAR; clear verification rules; and an introduction of minimum and optimum methane control standards

Simulations of the Hyades

Context: Using the recent observational data of R\"oser et al. we present $N$-body simulations of the Hyades open cluster. Aims: We make an attempt to determine initial conditions of the Hyades cluster at the time of its formation in order to reproduce the present-day cumulative mass profile, stellar mass and luminosity function (LF). Methods: We performed direct $N$-body simulations of the Hyades in an analytic Milky Way potential that account for stellar evolution and include primordial binaries in a few models. Furthermore, we applied a Kroupa (2001) IMF and used extensive ensemble-averaging. Results: We find that evolved single-star King initial models with King parameters $W_0 = 6-9$ and initial particle numbers $N_0 = 3000$ provide good fits to the observational present-day cumulative mass profile within the Jacobi radius. The best-fit King model has an initial mass of $1721\ M_\odot$ and an average mass loss rate of $-2.2 \ M_\odot/\mathrm{Myr}$. The K-band LFs of models and observations show a reasonable agreement. Mass segregation is detected in both observations and models. If 33% primordial binaries are included the initial particle number is reduced by 5% as compared to the model without primordial binaries. Conclusions: The present-day properties of the Hyades can be well reproduced by a standard King or Plummer initial model when choosing appropriate initial conditions. The degeneracy of good-fitting models can be quite high due to the large dimension of the parameter space. More simulations with different Roche-lobe filling factors and primordial binary fractions are required to explore this degeneracy in more detail.Comment: 14 pages, 16+1 figures, hopefully final version, contains a note added in proo

HmuY Haemophore and Gingipain Proteases Constitute a Unique Syntrophic System of Haem Acquisition by Porphyromonas gingivalis

Haem (iron protoporphyrin IX) is both an essential growth factor and virulence regulator for the periodontal pathogen Porphyromonas gingivalis, which acquires it mainly from haemoglobin via the sequential actions of the R- and K-specific gingipain proteases. The haem-binding lipoprotein haemophore HmuY and its cognate receptor HmuR of P. gingivalis, are responsible for capture and internalisation of haem. This study examined the role of the HmuY in acquisition of haem from haemoglobin and the cooperation between HmuY and gingipain proteases in this process. Using UV-visible spectroscopy and polyacrylamide gel electrophoresis, HmuY was demonstrated to wrest haem from immobilised methaemoglobin and deoxyhaemoglobin. Haem extraction from oxyhaemoglobin was facilitated after oxidation to methaemoglobin by pre-treatment with the P. gingivalis R-gingipain A (HRgpA). HmuY was also capable of scavenging haem from oxyhaemoglobin pre-treated with the K-gingipain (Kgp). This is the first demonstration of a haemophore working in conjunction with proteases to acquire haem from haemoglobin. In addition, HmuY was able to extract haem from methaemalbumin, and could bind haem, either free in solution or from methaemoglobin, even in the presence of serum albumin

Encounter-Triggered Disc Mass Loss in the ONC

The relevance of encounters on the destruction of protoplanetary discs in the Orion Nebula Cluster (ONC) is investigated by combining two different types of numerical simulation. First, star-cluster simulations are performed to model the stellar dynamics of the ONC, the results of which are used to investigate the frequency of encounters, the mass ratio and separation of the stars involved, and the eccentricity of the encounter orbits. The results show that interactions that could influence the star-surrounding disc are more frequent than previously assumed in the core of the ONC, the so-called Trapezium cluster. Second, a parameter study of star-disc encounters is performed to determine the upper limits of the mass loss of the discs in encounters. For simulation times of $\sim$ 1-2 Myr (the likely age of the ONC) the results show that gravitational interaction might account for a significant disc mass loss in dense clusters. Disc destruction is dominated by encounters with high-mass stars, especially in the Trapezium cluster, where the fraction of discs destroyed due to stellar encounters can reach 10-15%. These estimates are in accord with observations of (Lada et al. 2000) who determined a stellar disc fraction of 80-85%. Thus, it is shown that in the ONC - a typical star-forming region - stellar encounters do have a significant effect on the mass of protoplanetary discs and thus affect the formation of planetary systems.Comment: 32 pages, 12 figures, 3 tables. accepted by Ap

A natural formation scenario for misaligned and short-period eccentric extrasolar planets

Recent discoveries of strongly misaligned transiting exoplanets pose a challenge to the established planet formation theory which assumes planetary systems to form and evolve in isolation. However, the fact that the majority of stars actually do form in star clusters raises the question how isolated forming planetary systems really are. Besides radiative and tidal forces the presence of dense gas aggregates in star-forming regions are potential sources for perturbations to protoplanetary discs or systems. Here we show that subsequent capture of gas from large extended accretion envelopes onto a passing star with a typical circumstellar disc can tilt the disc plane to retrograde orientation, naturally explaining the formation of strongly inclined planetary systems. Furthermore, the inner disc regions may become denser, and thus more prone to speedy coagulation and planet formation. Pre-existing planetary systems are compressed by gas inflows leading to a natural occurrence of close-in misaligned hot Jupiters and short-period eccentric planets. The likelihood of such events mainly depends on the gas content of the cluster and is thus expected to be highest in the youngest star clusters.Comment: 7 pages, 4 figures. Accepted for publication in MNRAS. Updated to match published versio