On the problem of interactions in quantum theory

The structure of representations describing systems of free particles in the theory with the invariance group SO(1,4) is investigated. The property of the particles to be free means as usual that the representation describing a many-particle system is the tensor product of the corresponding single-particle representations (i.e. no interaction is introduced). It is shown that the mass operator contains only continuous spectrum in the interval $(-\infty,\infty)$ and such representations are unitarily equivalent to ones describing interactions (gravitational, electromagnetic etc.). This means that there are no bound states in the theory and the Hilbert space of the many-particle system contains a subspace of states with the following property: the action of free representation operators on these states is manifested in the form of different interactions. Possible consequences of the results are discussed.Comment: 35 pages, Late

Trauma management incorporating focused assessment with computed tomography in trauma (FACTT) - potential effect on survival

Background Immediate recognition of life-threatening conditions and injuries is the key to trauma management. To date, the impact of focused assessment with computed tomography in trauma (FACTT) has not been formally assessed. We aimed to find out whether the concept of using FACTT during primary trauma survey has a negative or positive effect on survival. Methods In a retrospective, multicentre study, we compared our time management and probability of survival (Ps) in major trauma patients who received FACTT during trauma resuscitation with the trauma registry of the German Trauma Society (DGU). FACTT is defined as whole-body computed tomography (WBCT) during primary trauma survey. We determined the probability of survival according to the Trauma and Injury Severity Score (TRISS), the Revised Injury Severity Classification score (RISC) and the standardized mortality ratio (SMR). Results We analysed 4.817 patients from the DGU database from 2002 until 2004, 160 (3.3%) were from our trauma centre at the Ludwig-Maximilians-University (LMU) and 4.657 (96.7%) from the DGU group. 73.2% were male with a mean age of 42.5 years, a mean ISS of 29.8. 96.2% had suffered from blunt trauma. Time from admission to FAST (focused assessment with sonography for trauma)(4.3 vs. 8.7 min), chest x-ray (8.1 vs. 16.0 min) and whole-body CT (20.7 vs. 36.6 min) was shorter at the LMU compared to the other trauma centres (p < 0.001). SMR calculated by TRISS was 0.74 (CI95% 0.40-1.08) for the LMU (p = 0.24) and 0.92 (CI95% 0.84-1.01) for the DGU group (p = 0.10). RISC methodology revealed a SMR of 0.69 (95%CI 0.47-0.92) for the LMU (p = 0.043) and 1.00 (95%CI 0.94-1.06) for the DGU group (p = 0.88). Conclusion Trauma management incorporating FACTT enhances a rapid response to life-threatening problems and enables a comprehensive assessment of the severity of each relevant injury. Due to its speed and accuracy, FACTT during primary trauma survey supports rapid decision-making and may increase survival

Cigarette smoke extract affects mitochondrial function in alveolar epithelial cells.

Cigarette smoke is the main risk factor for chronic obstructive pulmonary disease (COPD). Exposure of cells to cigarette smoke induces an initial adaptive cellular stress response involving increased oxidative stress and induction of inflammatory signaling pathways. Exposure of mitochondria to cellular stress alters their fusion/fission dynamics. While mild stress induces a pro-survival response termed stress induced mitochondrial hyperfusion, severe stress results in mitochondrial fragmentation and mitophagy. In the present study, we analyzed the mitochondrial response to mild and non-toxic doses of cigarette smoke extract (CSE) in alveolar epithelial cells. We characterized mitochondrial morphology, expression of mitochondrial fusion and fission genes, markers of mitochondrial proteostasis as well as mitochondrial functions such as membrane potential and oxygen consumption. Murine lung epithelial (MLE)12, as well as primary mouse alveolar epithelial cells revealed pronounced mitochondrial hyperfusion upon treatment with CSE, accompanied by increased expression of the mitochondrial fusion protein mitofusin (MFN) 2 and increased metabolic activity. We did not observe any alterations in mitochondrial proteostasis, i.e. induction of the mitochondrial unfolded protein response or mitophagy. Therefore, our data indicate an adaptive pro-survival response of mitochondria of alveolar epithelial cells to non-toxic concentrations of CSE. A hyperfused mitochondrial network, however, renders the cell more vulnerable to additional stress such as sustained cigarette smoke exposure. As such cigarette smoke induced mitochondrial hyperfusion - although being part of a beneficial adaptive stress response in the first place - may contribute to the pathogenesis of COPD

Cell-specific expression of runt-related transcription factor 2 contributes to pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with limited therapeutic options and unknown etiology. IPF is characterized by epithelial cell injury, impaired cellular crosstalk between epithelial cells and fibroblasts, and the formation of fibroblast foci with increased extracellular matrix deposition (ECM). We investigated the role of runt-related transcription factor 2 (RUNX2), a master regulator of bone development that has been linked to profibrotic signaling. RUNX2 expression was up-regulated in lung homogenates from patients with IPF and in experimental bleomycin-induced lung fibrosis. The RUNX2 level correlated with disease severity as measured by decreased diffusing capacity and increased levels of the IPF biomarker, matrix metalloproteinase 7. Nuclear RUNX2 was observed in prosurfactant protein C-positive hyperplastic epithelial cells and was rarely found in myofibroblasts. We discovered an up-regulation of RUNX2 in fibrotic alveolar epithelial type II (ATII) cells as well as an increase of RUNX2-negative fibroblasts in experimental and human pulmonary fibrosis. Functionally, small interfering RNA-mediated RUNX2 knockdown decreased profibrotic ATII cell function, such as proliferation and migration, whereas fibroblasts displayed activation markers and increased ECM expression after RUNX2 knockdown. This study reveals that RUNX2 is differentially expressed in ATII cells vs. fibroblasts in lung fibrosis, which contributes to profibrotic cell function. Cell-specific targeting of RUNX2 pathways may represent a therapeutic approach for IPF

Systematic phenotyping and correlation of biomarkers with lung function and histology in lung fibrosis.

To date, phenotyping and disease course prediction in idiopathic pulmonary fibrosis (IPF) primarily relies on lung function measures. Blood biomarkers were recently proposed for diagnostic and outcome prediction in IPF, yet their correlation with lung function and histology remains unclear. Here, we comprehensively assessed biomarkers in liquid biopsies and correlated their abundance with lung function and histology during the onset, progression, and resolution of lung fibrosis, with the aim to more precisely evaluate disease progression in the pre-clinical model of bleomycin-induced pulmonary fibrosis in vivo. Importantly, the strongest correlation of lung function with histological extent of fibrosis was observed at day 14, while lung function was unchanged at day 28 and 56, even when histology showed marked fibrotic lesions. While MMP7, MMP9, and PAI1 were significantly elevated in BAL of fibrotic mice, only sICAM1 was elevated in the peripheral blood of fibrotic mice and strongly correlated with the extent of fibrosis. Importantly, tissue-bound ICAM1 was also elevated in lung homogenates, with prominent staining in hyperplastic type II alveolar epithelial and endothelial cells. In sum, we show that lung function decline is not a prerequisite for histologically evident fibrosis, particularly during the onset or resolution thereof. Plasma levels of sICAM1 strongly correlate with the extent of lung fibrosis, and may thus be considered for the assessment of intraindividual therapeutic studies in preclinical studies of pulmonary fibrosis

Rabbit haemorrhagic disease: Macquarie Island rabbit eradication adds to knowledge on both pest control and epidemiology

Rabbit haemorrhagic disease virus (RHDV), introduced into in Australia and New Zealand as a biological-control agent for wild rabbits, is least efficacious in cool humid areas where a non-pathogenic calicivirus (RCV-A1) also circulates. Heavy rabbit mortality following release of RHDV on cold sub-Antarctic Macquarie Island, where RCV-A1 was apparently absent, not only complemented the planned rabbit eradication operations, especially by reducing secondary poisoning of sea-birds from aerial baiting, but also ruled out cool or humid climate as a major limiting factor of disease spread. In turn, this has advanced the idea that RCV-A1 antibodies inhibit RHDV spread as well as reducing disease severity and mortality.</p

CARM1 regulates alveolar epithelial senescence and elastase-induced emphysema susceptibility.

Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible loss of lung function and is one of the most prevalent and severe diseases world-wide. A major feature of COPD is emphysema -the progressive loss of alveolar tissue. Coactivator-associated arginine methyltransferase-1 (CARM1) regulates histone-methylation and the transcription of genes involved in senescence, proliferation and differentiation. Complete loss of CARM1 leads to disrupted differentiation and maturation of alveolar epithelial type-II cells (ATII). We thus hypothesized that CARM1 regulates the development and progression of emphysema. To address this, we investigated the contribution of CARM1 to alveolar rarefication using the mouse model of elastase-induced emphysema in vivo and siRNA-mediated knockdown in ATII-like LA4 cells in vitro. We demonstrate that emphysema progression in vivo is associated with a time-dependent down-regulation of CARM1. Importantly, elastase-treated CARM1 haploinsufficient mice show significantly increased airspace enlargement (52.5&plusmn;9.6 &micro;m vs. 38.8&plusmn;5.5 &micro;m, p&lt;0.01) and lung compliance (2.8&plusmn;0.32 &micro;l/cmH20 vs. 2.4&plusmn;0.4 &micro;l/cmH20, p&lt;0.04) compared with controls. The knockdown of CARM1 in LA4 cells led to decreased SIRT1 expression (0.034&plusmn;0.003 vs. 0.022&plusmn;0.001, p&lt;0.05), but increased expression of p16 (0.27&plusmn;0.013 vs. 0.31&plusmn;0.010, p&lt;0.5), p21 (0.81&plusmn;0.088 vs. 1.28&plusmn; 0.063, p&lt;0.01) and higher beta-galactosidase-positive senescent cells (50.57%&plusmn;7.36 vs. 2.21%&plusmn;0.34, p&lt;0.001), compared with scrambled siRNA. We further demonstrated that CARM1 haploinsufficiency impairs trans-differentiation and wound healing (32.18%&plusmn;0.9512 vs. 8.769%&plusmn;1.967, p&lt;0.001) of alveolar epithelial cells. Overall, these results reveal a novel function of CARM1 in regulating emphysema development and premature lung aging via alveolar senescence, as well as impaired regeneration, repair and differentiation of ATII cells