Accretion and outflow of gas in Markarian 509

A major uncertainty in models for photoionised outflows in AGN is the distance of the gas to the central black hole. We present the results of a massive multiwavelength monitoring campaign on the bright Seyfert 1 galaxy Mrk 509 to constrain the location of the outflow components dominating the soft X-ray band. Mrk 509 was monitored by XMM-Newton, Integral, Chandra, HST/COS and Swift in 2009. We have studied the response of the photoionised gas to the changes in the ionising flux produced by the central regions. We were able to put tight constraints on the variability of the absorbers from day to year time scales. This allowed us to develop a model for the time-dependent photoionisation in this source. We find that the more highly ionised gas producing most X-ray line opacity is at least 5 pc away from the core; upper limits to the distance of various absorbing components range between 20 pc up to a few kpc. The more lowly ionised gas producing most UV line opacity is at least 100 pc away from the nucleus. These results point to an origin of the dominant, slow (v<1000 km/s) outflow components in the NLR or torus-region of Mrk 509. We find that while the kinetic luminosity of the outflow is small, the mass carried away is likely larger than the 0.5 Solar mass per year accreting onto the black hole. We also determined the chemical composition of the outflow as well as valuable constraints on the different emission regions. We find for instance that the resolved component of the Fe-K line originates from a region 40-1000 gravitational radii from the black hole, and that the soft excess is produced by Comptonisation in a warm (0.2-1 keV), optically thick (tau~10-20) corona near the inner part of the disk.Comment: 4 pages, 1 figure, Proceedings of IAUS 290 "Feeding Compact Objects: Accretion on All Scales", C. M. Zhang, T. Belloni, M. Mendez & S. N. Zhang (eds.

Physicochemical-guided design of cathelicidin-derived peptides generates membrane active variants with therapeutic potential.

The spread of multi-drug resistance and the slow pace at which antibiotics come onto the market are undermining our ability to treat human infections, leading to high mortality rates. Aiming to overcome this global crisis, antimicrobial peptides are considered promising alternatives to counter bacterial infections with multi-drug resistant bacteria. The cathelicidins comprise a well-studied class of AMPs whose members have been used as model molecules for sequence modifications, aiming at enhanced biological activities and stability, along with reduced toxic effects on mammalian cells. Here, we describe the antimicrobial activities, modes of action and structural characterization of two novel cathelicidin-like peptides, named BotrAMP14 and CrotAMP14, which were re-designed from snake batroxicidin and crotalicidin, respectively. BotrAMP14 and CrotAMP14 showed broad-spectrum antibacterial activity against susceptible microorganisms and clinical isolates with minimal inhibitory concentrations ranging from 2-35.1 μM. Moreover, both peptides had low cytotoxicity against Caco-2 cells in vitro. In addition, in vivo toxicity against Galleria mellonella moth larvae revealed that both peptides led to>76% larval survival after 144 h. Microscopy studies suggest that BotrAMP14 and CrotAMP14 destabilize E. coli membranes. Furthermore, circular dichroism and molecular dynamics simulations indicate that, in a membrane-like environment, both peptides adopt α-helical structures that interact with bilayer phospholipids through hydrogen bonds and electrostatic interaction. Thus, we concluded that BotrAMP14 and CrotAMP14 are helical membrane active peptides, with similar antibacterial properties but lower cytotoxicity than the larger parent peptides batroxicidin and crotalicidin, having advantages for drug development strategies

Accretion and outflow of gas in Markarian 509

A major uncertainty in models for photoionised outflows in AGN is the distance of the gas to the central black hole. We present the results of a massive multiwavelength monitoring campaign on the bright Seyfert 1 galaxy Mrk 509 to constrain the location of the outflow components dominating the soft X-ray band. Mrk 509 was monitored by XMM-Newton, Integral, Chandra, HST/COS and Swift in 2009. We have studied the response of the photoionised gas to the changes in the ionising flux produced by the central regions. We were able to put tight constraints on the variability of the absorbers from day to year time scales. This allowed us to develop a model for the time-dependent photoionisation in this source. We find that the more highly ionised gas producing most X-ray line opacity is at least 5 pc away from the core; upper limits to the distance of various absorbing components range between 20 pc up to a few kpc. The more lowly ionised gas producing most UV line opacity is at least 100 pc away from the nucleus. These results point to an origin of the dominant, slow (v<1000 km s−1) outflow components in the NLR or torus-region of Mrk 509. We find that while the kinetic luminosity of the outflow is small, the mass carried away is likely larger than the 0.5 Solar mass per year accreting onto the black hole. We also determined the chemical composition of the outflow as well as valuable constraints on the different emission regions. We find for instance that the resolved component of the Fe-K line originates from a region 40-1000 gravitational radii from the black hole, and that the soft excess is produced by Comptonisation in a warm (0.2-1 keV), optically thick (τ~ 10-20) corona near the inner part of the dis

Impact of Yeast-Derived β-Glucans on the Porcine Gut Microbiota and Immune System in Early Life.

Piglets are susceptible to infections in early life and around weaning due to rapid environmental and dietary changes. A compelling target to improve pig health in early life is diet, as it constitutes a pivotal determinant of gut microbial colonization and maturation of the host's immune system. In the present study, we investigated how supplementation of yeast-derived β-glucans affects the gut microbiota and immune function pre- and post-weaning, and how these complex systems develop over time. From day two after birth until two weeks after weaning, piglets received yeast-derived β-glucans or a control treatment orally and were subsequently vaccinated against Salmonella Typhimurium. Faeces, digesta, blood, and tissue samples were collected to study gut microbiota composition and immune function. Overall, yeast-derived β-glucans did not affect the vaccination response, and only modest effects on faecal microbiota composition and immune parameters were observed, primarily before weaning. This study demonstrates that the pre-weaning period offers a 'window of opportunity' to alter the gut microbiota and immune system through diet. However, the observed changes were modest, and any long-lasting effects of yeast-derived β-glucans remain to be elucidated

From Conceptualization to Implementation: FAIR Assessment of Research Data Objects

Funders and policy makers have strongly recommended the uptake of the FAIR principles in scientific data management. Several initiatives are working on the implementation of the principles and standardized applications to systematically evaluate data FAIRness. This paper presents practical solutions, namely metrics and tools, developed by the FAIRsFAIR project to pilot the FAIR assessment of research data objects in trustworthy data repositories. The metrics are mainly built on the indicators developed by the RDA FAIR Data Maturity Model Working Group. The tools’ design and evaluation followed an iterative process. We present two applications of the metrics: an awareness-raising self-assessment tool and an automated FAIR data assessment tool. Initial results of testing the tools with researchers and data repositories are discussed, and future improvements suggested including the next steps to enable FAIR data assessment in the broader research data ecosystem

Simple measures of climate, soil properties and plant traits predict national scale grassland soil carbon stocks

1. Soil carbon (C) storage is a key ecosystem service. Soil C stocks play a vital role in soil fertility and climate regulation, but the factors that control these stocks at regional and national scales are unknown, particularly when their composition and stability are considered. As a result, their mapping relies on either unreliable proxy measures or laborious direct measurements. 2. Using data from an extensive national survey of English grasslands we show that surface soil (0-7cm) C stocks in size fractions of varying stability can be predicted at both regional and national scales from plant traits and simple measures of soil and climatic conditions. 3. Soil C stocks in the largest pool, of intermediate particle size (50-250 µm), were best explained by mean annual temperature (MAT), soil pH and soil moisture content. The second largest C pool, highly stable physically and biochemically protected particles (0.45-50 µm), was explained by soil pH and the community abundance weighted mean (CWM) leaf nitrogen (N) content, with the highest soil C stocks under N rich vegetation. The C stock in the small active fraction (250-4000 µm) was explained by a wide range of variables: MAT, mean annual precipitation, mean growing season length, soil pH and CWM specific leaf area; stocks were higher under vegetation with thick and/or dense leaves. 4. Testing the models describing these fractions against data from an independent English region indicated moderately strong correlation between predicted and actual values and no systematic bias, with the exception of the active fraction, for which predictions were inaccurate. 5. Synthesis and Applications: Validation indicates that readily available climate, soils and plant survey data can be effective in making local- to landscape-scale (1-100,000 km2) soil C stock predictions. Such predictions are a crucial component of effective management strategies to protect C stocks and enhance soil C sequestration

An acidic model pro-peptide affects the secondary structure, membrane interactions and antimicrobial activity of a crotalicidin fragment

In order to study how acidic pro-peptides inhibit the antimicrobial activity of antimicrobial peptides, we introduce a simple model system, consisting of a 19 amino-acid long antimicrobial peptide, and an N-terminally attached, 10 amino-acid long acidic model pro-peptide. The antimicrobial peptide is a fragment of the crotalicidin peptide, a member of the cathelidin family, from rattlesnake venom. The model pro-peptide is a deca (glutamic acid). Attachment of the model pro-peptide only leads to a moderately large reduction in the binding to- and induced leakage of model liposomes, while the antimicrobial activity of the crotalicidin fragment is completely inhibited by attaching the model pro-peptide. Attaching the pro-peptide induces a conformational change to a more helical conformation, while there are no signs of intra- or intermolecular peptide complexation. We conclude that inhibition of antimicrobial activity by the model pro-peptide might be related to a conformational change induced by the pro-peptide domain, and that additional effects beyond induced changes in membrane activity must also be involved.</p

Insight into trade‐off between wood decay and parasitism from the genome of a fungal forest pathogen

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91191/1/j.1469-8137.2012.04128.x.pd

In vitro epithelial-to-mesenchymal transformation in human adult epicardial cells is regulated by TGFβ-signaling and WT1

Adult epicardial cells are required for endogenous cardiac repair. After myocardial injury, they are reactivated, undergo epithelial-to-mesenchymal transformation (EMT) and migrate into the injured myocardium where they generate various cell types, including coronary smooth muscle cells and cardiac interstitial fibroblasts, which contribute to cardiac repair. To understand what drives epicardial EMT, we used an in vitro model for human adult epicardial cells. These cells have an epithelium-like morphology and markedly express the cell surface marker vascular cell adhesion marker (VCAM-1). In culture, epicardial cells spontaneously undergo EMT after which the spindle-shaped cells now express endoglin. Both epicardial cells before and after EMT express the epicardial marker, Wilms tumor 1 (WT1). Adding transforming growth factor beta (TGFβ) induces loss of epithelial character and initiates the onset of mesenchymal differentiation in human adult epicardial cells. In this study, we show that TGFβ-induced EMT is dependent on type-1 TGFβ receptor activity and can be inhibited by soluble VCAM-1. We also show that epicardial-specific knockdown of Wilms tumor-1 (WT1) induces the process of EMT in human adult epicardial cells, through transcriptional regulation of platelet-derived growth factor receptor alpha (Pdgfrα), Snai1 and VCAM-1. These data provide new insights into the process of EMT in human adult epicardial cells, which might provide opportunities to develop new strategies for endogenous cell-based cardiac repair