Pseudomonas expression of an oxygen sensing prolyl hydroxylase homologue regulates neutrophil host responses in vitro and in vivo

Background: Pseudomonas species are adapted to evade innate immune responses and can persist at sites of relative tissue hypoxia, including the mucus-plugged airways of patients with cystic fibrosis and bronchiectasis. The ability of these bacteria to directly sense and respond to changes in local oxygen availability is in part consequent upon expression of the 2-oxoglutarate oxygenase, Pseudomonas prolyl hydroxylase (PPHD), which acts on elongation factor Tu (EF-Tu), and is homologous with the human hypoxia inducible factor (HIF) prolyl hydroxylases. We report that PPHD expression regulates the neutrophil response to acute pseudomonal infection. Methods: In vitro co-culture experiments were performed with human neutrophils and PPHD-deficient and wild-type bacteria and supernatants, with viable neutrophil counts determined by flow cytometry. In vivo consequences of infection with PPHD deficient P. aeruginosa were determined in an acute pneumonia mouse model following intra-tracheal challenge. Results: Supernatants of PPHD-deficient bacterial cultures contained higher concentrations of the phenazine exotoxin pyocyanin and induced greater acceleration of neutrophil apoptosis than wild-type PAO1 supernatants in vitro. In vivo infection with PPHD mutants compared to wild-type PAO1 controls resulted in increased levels of neutrophil apoptosis and impaired control of infection, with higher numbers of P. aeruginosa recovered from the lungs of mice infected with the PPHD-deficient strain. This resulted in an overall increase in mortality in mice infected with the PPHD-deficient strain. Conclusions: Our data show that Pseudomonas expression of its prolyl hydroxylase influences the outcome of host-pathogen interactions in vitro and in vivo, demonstrating the importance of considering how both host and pathogen adaptations to hypoxia together define outcomes of infection. Given that inhibitors for the HIF prolyl hydroxylases are in late stage trials for the treatment of anaemia and that the active sites of PPHD and human HIF prolyl hydroxylases are closely related, the results are of current clinical interest

Local structure of the set of steady-state solutions to the 2D incompressible Euler equations

It is well known that the incompressible Euler equations can be formulated in a very geometric language. The geometric structures provide very valuable insights into the properties of the solutions. Analogies with the finite-dimensional model of geodesics on a Lie group with left-invariant metric can be very instructive, but it is often difficult to prove analogues of finite-dimensional results in the infinite-dimensional setting of Euler's equations. In this paper we establish a result in this direction in the simple case of steady-state solutions in two dimensions, under some non-degeneracy assumptions. In particular, we establish, in a non-degenerate situation, a local one-to-one correspondence between steady-states and co-adjoint orbits.Comment: 81 page

The phase transition of the quantum Ising model is sharp

An analysis is presented of the phase transition of the quantum Ising model with transverse field on the d-dimensional hypercubic lattice. It is shown that there is a unique sharp transition. The value of the critical point is calculated rigorously in one dimension. The first step is to express the quantum Ising model in terms of a (continuous) classical Ising model in d+1 dimensions. A so-called `random-parity' representation is developed for the latter model, similar to the random-current representation for the classical Ising model on a discrete lattice. Certain differential inequalities are proved. Integration of these inequalities yields the sharpness of the phase transition, and also a number of other facts concerning the critical and near-critical behaviour of the model under study.Comment: Small changes. To appear in the Journal of Statistical Physic

A Historiometric Examination of Machiavellianism and a New Taxonomy of Leadership

Although researchers have extensively examined the relationship between charismatic leadership and Machiavellianism (Deluga, 2001; Gardner & Avolio, 1995; House & Howell, 1992), there has been a lack of investigation of Machiavellianism in relation to alternative forms of outstanding leadership. Thus, the purpose of this investigation was to examine the relationship between Machiavellianism and a new taxonomy of outstanding leadership comprised of charismatic, ideological, and pragmatic leaders. Using an historiometric approach, raters assessed Machiavellianism via the communications of 120 outstanding leaders in organizations across the domains of business, political, military, and religious institutions. Academic biographies were used to assess twelve general performance measures as well as twelve general controls and five communication specific controls. The results indicated that differing levels of Machiavellianism is evidenced across the differing leader types as well as differing leader orientation. Additionally, Machiavellianism appears negatively related to performance, though less so when type and orientation are taken into account.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

ASSOCIATION OF DEFECTS WITH IRON IMPURITIES IN FCC ALUMINIUM

Nous avons étudié par spectroscopie Mössbauer les effets d'un revenu isochrone sur un échantillon de Al-0,01% Fe après une déformation à 77 K. Les plus remarquables effets que nous avons observés sont dans le domaine de température compris entre 210 K et 350 K où des lignes satellites apparaissent par suite d'une association des atomes de Fe avec des lacunes.We have used Mössbauer spectroscopy to monitor the isochronal annealing of Al - 0.01% Fe after cold working at 77 K. The most striking results are for the annealing range from 210 K to 350 K where the growth and decay of a satellite line due to the association of Fe atoms with vacancies can be seen

DEFECTS AND PHASES OF IRON IN ALUMINIUM

No abstract availabl