Pasteurella multocida toxin- induced osteoclastogenesis requires mTOR activation

Background: Pasteurella multocida toxin (PMT) is a potent inducer of osteoclast formation. Pigs suffering from an infection with toxigenic Pasteurella multocida strains develop atrophic rhinitis characterised by a loss of turbinate bones and conchae. However, on the molecular level the process of bone loss remains largely uncharacterised. Results: Recently it was found that PMT activates the serine/threonine kinase mammalian target of rapamycin (mTOR) in fibroblasts. Using RAW264.7 macrophages, we investigated the role of the mTOR complex 1 (mTORC1) in PMT-mediated osteoclast formation. PMT induces the differentiation of RAW264.7 macrophages into multinucleated, tartrate resistant acid phosphatase (TRAP) positive osteoclasts that are capable to resorb bone. In the presence of the mTORC1 inhibitor rapamycin, PMT was significantly less able to induce the formation of TRAP-positive osteoclasts. Accordingly, the resulting resorption of bone was strongly reduced. A major target of mTOR is the 70 kDa ribosomal protein S6 kinase 1 (p70 S6K1). Activated p70 S6K1 decreases the expression of programmed cell death protein 4 (PDCD4), a negative transcriptional regulator of osteoclastogenesis, at the protein and gene level. Ultimately this results in the activation of c-Jun, a component of the activator protein 1 (AP-1) complex, which is a major transcription factor for the induction of osteoclast-specific genes. We now demonstrate that c-Jun and its downstream target, the osteoclast-specific bone degrading protease cathepsin K, are upregulated upon PMT treatment in an mTOR-dependent manner. Conclusions: Activation of mTOR signalling plays a central role in the formation of osteoclasts through the bacterial toxin PMT. On the molecular level, PMT-induced activation of mTOR leads to down regulation of PDCD4, a known repressor of AP-1 complex, culminating in the activation of c-Jun, an essential transcription factor for triggering osteoclastogenesis

The Orbit of Warm Jupiter WASP-106 b is aligned with its Star

Understanding orbital obliquities, or the misalignment angles between a star's rotation axis and the orbital axis of its planets, is crucial for unraveling the mechanisms of planetary formation and migration. In this study, we present an analysis of Rossiter-McLaughlin (RM) observations of the warm Jupiter exoplanet WASP-106 b. The high-precision radial velocity measurements were made with HARPS and HARPS-N during the transit of this planet. We aim to constrain the orientation of the planet's orbit relative to its host star's rotation axis. The RM observations are analyzed using a code which models the RM anomaly together with the Keplerian orbit given several parameters in combination with a Markov chain Monte Carlo implementation. We measure the projected stellar obliquity in the WASP-106 system for the first time and find $\lambda = (-1 \pm 11)^\circ$, supporting the theory of quiescent migration through the disk.Comment: 12 pages, 3 figures, 4 tables, submitted to AA

Living together with age related macular degeneration:an interpretative phenomenological analysis of sense-making within a dyadic relationship

In this article, we present an idiographic analysis of a couple's experience of living and coming to terms with age-related macular degeneration. Interpretative phenomenological analysis was used to explore three joint interviews, conducted over an 18-month period, with a married couple (aged 82 and 77 years) both living with age-related macular degeneration. Three themes are discussed: the disruption of vision impairment, managing mutual deterioration and resilience through togetherness. We discuss the existential challenges of vision impairment and consider the applicability of Galvin and Todres' typology of well-being as a means of understanding well-being in older adults

Examining the orbital decay targets KELT-9 b, KELT-16 b, and WASP-4b, and the transit-timing variations of HD 97658 b

Context. Tidal orbital decay is suspected to occur for hot Jupiters in particular, with the only observationally confirmed case of this being WASP-12b. By examining this effect, information on the properties of the host star can be obtained using the so-called stellar modified tidal quality factor Q*′, which describes the efficiency with which the kinetic energy of the planet is dissipated within the star. This can provide information about the interior of the star. Aims. In this study, we aim to improve constraints on the tidal decay of the KELT-9, KELT-16, and WASP-4 systems in order to find evidence for or against the presence of tidal orbital decay. With this, we want to constrain the Q*′ value for each star. In addition, we aim to test the existence of the transit timing variations (TTVs) in the HD 97658 system, which previously favoured a quadratic trend with increasing orbital period. Methods. Making use of newly acquired photometric observations from CHEOPS (CHaracterising ExOplanet Satellite) and TESS (Transiting Exoplanet Survey Satellite), combined with archival transit and occultation data, we use Markov chain Monte Carlo (MCMC) algorithms to fit three models to the data, namely a constant-period model, an orbital-decay model, and an apsidal-precession model. Results. We find that the KELT-9 system is best described by an apsidal-precession model for now, with an orbital decay trend at over 2 σ being a possible solution as well. A Keplerian orbit model with a constant orbital period provides the best fit to the transit timings of KELT-16 b because of the scatter and scale of their error bars. The WASP-4 system is best represented by an orbital decay model at a 5 σ significance, although apsidal precession cannot be ruled out with the present data. For HD 97658 b, using recently acquired transit observations, we find no conclusive evidence for a previously suspected strong quadratic trend in the data

The Orbit of Warm Jupiter WASP-106b is aligned with its Star

Understanding orbital obliquities, or the misalignment angles between a star's rotation axis and the orbital axis of its planets, is crucial for unraveling the mechanisms of planetary formation and migration. In this study, we present an analysis of Rossiter–McLaughlin (RM) observations of the warm Jupiter exoplanet WASP-106 b. The high-precision radial velocity measurements were made with HARPS and HARPS-N during the transit of this planet. We aim to constrain the orientation of the planet's orbit relative to its host star's rotation axis. The RM observations are analyzed using a code which models the RM anomaly together with the Keplerian orbit given several parameters in combination with a Markov chain Monte Carlo implementation. We measure the projected stellar obliquity in the WASP-106 system for the first time and find λ = (−1 ± 11)°, supporting the theory of quiescent migration through the disk

Theoretical studies of the historical development of the accounting discipline: a review and evidence

Many existing studies of the development of accounting thought have either been atheoretical or have adopted Kuhn's model of scientific growth. The limitations of this 35-year-old model are discussed. Four different general neo-Kuhnian models of scholarly knowledge development are reviewed and compared with reference to an analytical matrix. The models are found to be mutually consistent, with each focusing on a different aspect of development. A composite model is proposed. Based on a hand-crafted database, author co-citation analysis is used to map empirically the entire literature structure of the accounting discipline during two consecutive time periods, 1972–81 and 1982–90. The changing structure of the accounting literature is interpreted using the proposed composite model of scholarly knowledge development

A pedagogy of friendship: young children's friendships and how schools can support them?

Children’s friendships are often neglected by teachers and researchers. This phenomenological study conducted with seven children aged five and six years explores young children’s perceptions of their everyday friendship experiences. This multi-method study used role play interviews, drawings and persona doll scenarios to consider children’s everyday experiences of friendship in school. The paper discusses the importance of socio-cultural aspects of children’s friendship including: imaginary friends; losing friends; protecting time and space to develop friendships and children’s routines and practices as they form and maintain friendships. Data and findings are discussed, leading to an original conceptual framework: a ‘Pedagogy of Friendship’. This is designed to help children make meaning from their friendship experiences and also provide practitioners with the opportunity to nurture and scaffold children through their friendship experiences in schools. We suggest that there is a need to raise the profile of children’s friendships in early childhood education and generate an educational perspective on friendship. Finally we conclude that listening to children’s views of friendship indicates that the application of the framework of a ‘Pedagogy of Friendship’ would be beneficial to children’s all round learning and development. Keywords - children's perceptions, phenomenology, friendship, key stage one, Pedagogy of Friendshi

The Influence of Recovery and Training Phases on Body Composition, Peripheral Vascular Function and Immune System of Professional Soccer Players

Professional soccer players have a lengthy playing season, throughout which high levels of physical stress are maintained. The following recuperation period, before starting the next pre-season training phase, is generally considered short but sufficient to allow a decrease in these stress levels and therefore a reduction in the propensity for injury or musculoskeletal tissue damage. We hypothesised that these physical extremes influence the body composition, blood flow, and endothelial/immune function, but that the recuperation may be insufficient to allow a reduction of tissue stress damage. Ten professional football players were examined at the end of the playing season, at the end of the season intermission, and after the next pre-season endurance training. Peripheral blood flow and body composition were assessed using venous occlusion plethysmography and DEXA scanning respectively. In addition, selected inflammatory and immune parameters were analysed from blood samples. Following the recuperation period a significant decrease of lean body mass from 74.4±4.2 kg to 72.2±3.9 kg was observed, but an increase of fat mass from 10.3±5.6 kg to 11.1±5.4 kg, almost completely reversed the changes seen in the pre-season training phase. Remarkably, both resting and post-ischemic blood flow (7.3±3.4 and 26.0±6.3 ml/100 ml/min) respectively, were strongly reduced during the playing and training stress phases, but both parameters increased to normal levels (9.0±2.7 and 33.9±7.6 ml/100 ml/min) during the season intermission. Recovery was also characterized by rising levels of serum creatinine, granulocytes count, total IL-8, serum nitrate, ferritin, and bilirubin. These data suggest a compensated hypo-perfusion of muscle during the playing season, followed by an intramuscular ischemia/reperfusion syndrome during the recovery phase that is associated with muscle protein turnover and inflammatory endothelial reaction, as demonstrated by iNOS and HO-1 activation, as well as IL-8 release. The data provided from this study suggest that the immune system is not able to function fully during periods of high physical stress. The implications of this study are that recuperation should be carefully monitored in athletes who undergo intensive training over extended periods, but that these parameters may also prove useful for determining an individual's risk of tissue stress and possibly their susceptibility to progressive tissue damage or injury