High-energy particle transport in 3D hydrodynamic models of colliding-wind binaries

Massive stars in binary systems (as WR140, WR147 or $\eta$ Carinae) have long been regarded as potential sources of high-energy $\gamma$-rays. The emission is thought to arise in the region where the stellar winds collide and produce relativistic particles which subsequently might be able to emit $\gamma$-rays. Detailed numerical hydrodynamic simulations have already offered insight in the complex dynamics of the wind collision region (WCR), while independent analytical studies, albeit with simplified descriptions of the WCR, have shed light on the spectra of charged particles. In this paper, we describe a combination of these two approaches. We present a 3D-hydrodynamical model for colliding stellar winds and compute spectral energy distributions of relativistic particles for the resulting structure of the WCR. The hydrodynamic part of our model incorporates the line-driven acceleration of the winds, gravity, orbital motion and the radiative cooling of the shocked plasma. In our treatment of charged particles we consider diffusive shock acceleration in the WCR and the subsequent cooling via inverse Compton losses (including Klein-Nishina effects), bremsstrahlung, collisions and other energy loss mechanisms.Comment: 28 pages, 9 figures / accepted for publication in The Astrophysical Journa

Alcohol dehydrogenase 1 of barley modulates susceptibility to the parasitic fungus Blumeria graminis f.sp. hordei

Plant primary energy metabolism is profoundly reorganized under biotic stress conditions and there is increasing evidence for a role for the fermentative pathway in biotic interactions. However, the mechanisms regulating metabolic reprogramming are not well understood despite its critical function in the biotic stress response. Here the function of alcohol dehydrogenase (ADH) in the interaction of barley with the parasitic fungus Blumeria graminis f.sp. hordei (Bgh) is addressed. Challenge of susceptible barley leaves with Bgh resulted in transcriptional activation of HvADH1 and an induction of ADH enzyme activity starting 24 h after infection and reaching a clear-cut effect 4 d after infection. This increase in ADH enzyme activity was not observed in the resistant near-isogenic mlo5 line. Moreover, an induction of ADH enzyme activity by Bgh was enhanced in the presence of sucrose in hydroponically grown seedlings. Transient knock-down or overexpression of HvADH1 in barley epidermal cells mediated a decrease or increase in the penetration success of Bgh, respectively. Inhibition of ADH activity by pyrazole resulted in a delay in symptoms. The pyrazole effect could be overcome by adding glucose to the incubation medium, pinpointing a nutritional effect of ADH in the barley–Bgh interaction. Taken together, misexpression of pathogen-inducible HvADH1 or variation of ADH activity modulates the pathogen response of barley to the biotrophic fungal parasite Bgh. In this way, ADH knock-down/inhibition results in reduced fungal success. The possibility is discussed that ADH activity supports biotrophy by maintaining glycolytic metabolism in pathogen-stressed barley

The 2.35 year itch of Cygnus OB2 #9: III. X-ray and radio emission analysis based on 3D hydrodynamical modelling

Context. The wind-wind collision in a massive star binary system leads to the generation of high temperature shocks that emit at X-ray wavelengths and, if particle acceleration is effective, may exhibit non-thermal radio emission. Cyg OB2 is one of a small number of massive star binary systems in this class. Aims. X-ray and radio data recently acquired as part of a project to study Cyg OB2 are used to constrain physical models of the binary system, providing in-depth knowledge about the wind-wind collision and the thermal, and non-thermal, emission arising from the shocks. Methods. We use a 3D, adaptive mesh refinement simulation (including wind acceleration, radiative cooling, and the orbital motion of the stars) to model the gas dynamics of the wind-wind collision. The simulation output is used as the basis for radiative transfer calculations considering the thermal X-ray emission and the thermal/non-thermal radio emission. Results. The flow dynamics in the simulation show that wind acceleration (between the stars) is inhibited at all orbital phases by the opposing star's radiation field, reducing pre-shock velocities below terminal velocities. To obtain good agreement with the X-ray observations, our initial mass-loss rate estimates require a down-shift by a factor of ∼7.7 to 6.5 × 10-7 M yr-1 and 7.5 × 10-7 M yr-1 for the primary and secondary star, respectively. Furthermore, the low gas densities and high shock velocities in Cyg OB2 are suggestive of unequal electron and ion temperatures, and the X-ray analysis indicates that an immediately post-shock electron-ion temperature ratio of 0.1 is also required. The radio emission is dominated by non-thermal synchrotron emission. A parameter space exploration provides evidence against models assuming equipartition between magnetic and relativistic energy densities. However, fits of comparable quality can be attained with models having stark contrasts in the ratio of magnetic-to-relativistic energy densities. Both X-ray and radio lightcurves are largely insensitive to viewing angle. The variations in X-ray emission with orbital phase can be traced back to an inverse relation with binary separation and pre-shock velocity. The radio emission also scales with pre-shock velocity and binary separation, but to positive powers (i.e. not inversely). The radio models also reveal a subtle effect whereby inverse Compton cooling leads to an increase in emissivity as a result of the synchrotron characteristic frequency being significantly reduced. Finally, using the results of the radio analysis, we estimate the surface magnetic field strengths to be 0.3-52G

Nuclear pores as versatile reference standards for quantitative superresolution microscopy

Quantitative fluorescence and superresolution microscopy are often limited by insufficient data quality or artifacts. In this context, it is essential to have biologically relevant control samples to benchmark and optimize the quality of microscopes, labels and imaging conditions. Here, we exploit the stereotypic arrangement of proteins in the nuclear pore complex as in situ reference structures to characterize the performance of a variety of microscopy modalities. We created four genome edited cell lines in which we endogenously labeled the nucleoporin Nup96 with mEGFP, SNAP-tag, HaloTag or the photoconvertible fluorescent protein mMaple. We demonstrate their use (1) as three-dimensional resolution standards for calibration and quality control, (2) to quantify absolute labeling efficiencies and (3) as precise reference standards for molecular counting. These cell lines will enable the broader community to assess the quality of their microscopes and labels, and to perform quantitative, absolute measurements

Variable millimetre radiation from the colliding-wind binary Cygnus OB2 #8A

Context. Massive binaries have stellar winds that collide. In the colliding-wind region, various physically interesting processes occur, leading to enhanced X-ray emission, non-thermal radio emission, as well as non-thermal X-rays and gamma-rays. Non-thermal radio emission (due to synchrotron radiation) has so far been observed at centimetre wavelengths. At millimetre wavelengths, the stellar winds and the colliding-wind region emit more thermal free-free radiation, and it is expected that any non-thermal contribution will be difficult or impossible to detect. Aims. We aim to determine if the material in the colliding-wind region contributes substantially to the observed millimetre fluxes of a colliding-wind binary. We also try to distinguish the synchrotron emission from the free-free emission. Methods. We monitored the massive binary Cyg OB2 #8A at 3 mm with the NOrthern Extended Millimeter Array (NOEMA) interferometer of the Institut de Radioastronomie Millimétrique (IRAM). The data were collected in 14 separate observing runs (in 2014 and 2016), and provide good coverage of the orbital period. Results. The observed millimetre fluxes range between 1.1 and 2.3 mJy, and show phase-locked variability, clearly indicating that a large part of the emission is due to the colliding-wind region. A simple synchrotron model gives fluxes with the correct order of magnitude, but with a maximum that is phase-shifted with respect to the observations. Qualitatively this phase shift can be explained by our neglect of orbital motion on the shape of the colliding-wind region. A model using only free-free emission results in only a slightly worse explanation of the observations. Additionally, on the map of our observations we also detect the O6.5 III star Cyg OB2 #8B, for which we determine a 3 mm flux of 0.21 ± 0.033 mJy. Conclusions. The question of whether synchrotron radiation or free-free emission dominates the millimetre fluxes of Cyg OB2 #8A remains open. More detailed modelling of this system, based on solving the hydrodynamical equations, is required to give a definite answer

Resistance to mesenchymal reprogramming sustains clonal propagation in metastatic breast cancer

The acquisition of mesenchymal traits is considered a hallmark of breast cancer progression. However, the functional relevance of epithelial-to-mesenchymal transition (EMT) remains controversial and context dependent. Here, we isolate epithelial and mesenchymal populations from human breast cancer metastatic biopsies and assess their functional potential in vivo. Strikingly, progressively decreasing epithelial cell adhesion molecule (EPCAM) levels correlate with declining disease propagation. Mechanistically, we find that persistent EPCAM expression marks epithelial clones that resist EMT induction and propagate competitively. In contrast, loss of EPCAM defines clones arrested in a mesenchymal state, with concomitant suppression of tumorigenicity and metastatic potential. This dichotomy results from distinct clonal trajectories impacting global epigenetic programs that are determined by the interplay between human ZEB1 and its target GRHL2. Collectively, our results indicate that susceptibility to irreversible EMT restrains clonal propagation, whereas resistance to mesenchymal reprogramming sustains disease spread in multiple models of human metastatic breast cancer, including patient-derived cells in vivo

Aggressive PDACs show hypomethylation of repetitive elements and the execution of an intrinsic IFN program linked to a ductal cell of origin

Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia, which challenges the molecular analyses of bulk tumor samples. Here we FACS-purified epithelial cells from human PDAC and normal pancreas and derived their genome-wide transcriptome and DNA methylome landscapes. Clustering based on DNA methylation revealed two distinct PDAC groups displaying different methylation patterns at regions encoding repeat elements. Methylation(low) tumors are characterized by higher expression of endogenous retroviral (ERV) transcripts and dsRNA sensors which leads to a cell intrinsic activation of an interferon signature (IFNsign). This results in a pro-tumorigenic microenvironment and poor patient outcome. Methylation(low)/IFNsign(high) and Methylation(high)/IFNsign(low) PDAC cells preserve lineage traits, respective of normal ductal or acinar pancreatic cells. Moreover, ductal-derived Kras(G12D)/Trp53(−/−) mouse PDACs show higher expression of IFNsign compared to acinar-derived counterparts. Collectively, our data point to two different origins and etiologies of human PDACs, with the aggressive Methylation(low)/IFNsign(high) subtype potentially targetable by agents blocking intrinsic IFN-signaling

Resistance to mesenchymal reprogramming sustains clonal propagation in metastatic breast cancer

The acquisition of mesenchymal traits is considered a hallmark of breast cancer progression. However, the functional relevance of epithelial-to-mesenchymal transition (EMT) remains controversial and context dependent. Here, we isolate epithelial and mesenchymal populations from human breast cancer metastatic biopsies and assess their functional potential in vivo. Strikingly, progressively decreasing epithelial cell adhesion molecule (EPCAM) levels correlate with declining disease propagation. Mechanistically, we find that persistent EPCAM expression marks epithelial clones that resist EMT induction and propagate competitively. In contrast, loss of EPCAM defines clones arrested in a mesenchymal state, with concomitant suppression of tumorigenicity and metastatic potential. This dichotomy results from distinct clonal trajectories impacting global epigenetic programs that are determined by the interplay between human ZEB1 and its target GRHL2. Collectively, our results indicate that susceptibility to irreversible EMT restrains clonal propagation, whereas resistance to mesenchymal reprogramming sustains disease spread in multiple models of human metastatic breast cancer, including patient-derived cells in vivo