Dynamic interactions of a conserved enterotoxigenic Escherichia coli adhesin with intestinal mucins govern epithelium engagement and toxin delivery

At present, there is no vaccine for enterotoxigenic Escherichia coli (ETEC), an important cause of diarrheal illness. Nevertheless, recent microbial pathogenesis studies have identified a number of molecules produced by ETEC that contribute to its virulence and are novel antigenic targets to complement canonical vaccine approaches. EtpA is a secreted two-partner adhesin that is conserved within the ETEC pathovar. EtpA interacts with the tips of ETEC flagella to promote bacterial adhesion, toxin delivery, and intestinal colonization by forming molecular bridges between the bacteria and the epithelial surface. However, the nature of EtpA interactions with the intestinal epithelium remains poorly defined. Here, we demonstrate that EtpA interacts with glycans presented by transmembrane and secreted intestinal mucins at epithelial surfaces to facilitate pathogen-host interactions that culminate in toxin delivery. Moreover, we found that a major effector molecule of ETEC, the heat-labile enterotoxin (LT), may enhance these interactions by stimulating the production of the gel-forming mucin MUC2. Our studies suggest, however, that EtpA participates in complex and dynamic interactions between ETEC and the gastrointestinal mucosae in which host glycoproteins promote bacterial attachment while simultaneously limiting the epithelial engagement required for effective toxin delivery. Collectively, these data provide additional insight into the intricate nature of ETEC interactions with the intestinal epithelium that have potential implications for rational approaches to vaccine design

Confirmation Via the Continuum-Fitting Method that the Spin of the Black Hole in Cygnus X-1 is Extreme

In Gou et al. (2011), we reported that the black hole primary in the X-ray binary Cygnus X-1 is a near-extreme Kerr black hole with a spin parameter a*>0.95(3{\sigma}). We confirm this result while setting a new and more stringent limit: a*>0.983 at the 3{\sigma}(99.7%) level of confidence. The earlier work, which was based on an analysis of all three useful spectra that were then available, was possibly biased by the presence in these spectra of a relatively strong Compton power-law component: The fraction of the thermal seed photons scattered into the power law was f_s=23-31%, while the upper limit for reliable application of the continuum-fitting method is f_s<25%. We have subsequently obtained six additional spectra of Cygnus X-1 suitable for the measurement of spin. Five of these spectra are of high quality with f_s in the range 10% to 19%, a regime where the continuum-fitting method has been shown to deliver reliable results. Individually, the six spectra give lower limits on the spin parameter that range from a*>0.95 to a*>0.98, allowing us to conservatively conclude that the spin of the black hole is a*>0.983 (3{\sigma}).Comment: 14 pages in emulated ApJ format, including 6 figures and 4 tables, ApJ in press. Discussion on the pileup effect to our spin measurement is added, including a subsection and a new figure, to reflect the referee's comments; the conclusions are unchange

Using X-ray continuum-fitting to estimate the spin of MAXI J1305-704

MAXI J1305-704 is a transient X-ray binary with a black hole primary. It was discovered on April 9, 2012, during its only known outburst. MAXI J1305-704 is also a high inclination low-mass X-ray binary with prominent dip features in its light curves, so we check the full catalog of 92 \emph{Swift}/XRT continuous observations of MAXI J1305-704, focusing only on the stable spectra. We select 13 ``gold" spectra for which the root mean square RMS <0.075 and the coronal scattered fraction $f_{\mathrm{sc}} \lesssim 25 \%$. These ``gold" data are optimal thermal-state observations for continuum-fitting modeling, in which the disk extends to the innermost-stable circular orbit and is geometrically thin. The black hole spin was unknown for this object before. By utilizing the X-ray continuum fitting method with the relativistic thin disk model \texttt{kerrbb2} and supplying the known dynamical binary system parameters, we find MAXI J1305-704 has a moderate spin ($a_{*}=0.87_{-0.13}^{+0.07}$) at a 68.3\% confidence level. This is the first determination of MAXI J1305-704's spin.Comment: 13 pages, 10 figures, submitted to MNRA

The spin measurement of the black hole in 4U 1543-47 constrained with the X-ray reflected emission

4U 1543-47 is a low-mass X-ray binary that harbours a stellar-mass black hole located in our Milky Way galaxy. In this paper, we revisit seven data sets that were in the Steep Power Law state of the 2002 outburst. The spectra were observed by the Rossi X-ray Timing Explorer. We have carefully modelled the X-ray reflection spectra and made a joint-fit to these spectra with relxill for the reflected emission. We found a moderate black hole spin, which is 0.67^(+0.15)_(−0.08) at 90 per cent statistical confidence. Negative and low spins (<0.5) at more than 99 per cent statistical confidence are ruled out. In addition, our results indicate that the model requires a supersolar iron abundance: 5.05^(+1.21)_(−0.26), and the inclination angle of the inner disc is 36.3^(+5.3)_(−3.4) deg. This inclination angle is appreciably larger than the binary orbital inclination angle (∼21 deg); this difference is possibly a systematic artefact of the artificially low density employed in the reflection model for this X-ray binary system

The Spin of the Black Hole Microquasar XTE J1550-564 via the Continuum-Fitting and Fe-Line Methods

We measure the spin of XTE J1550-564 in two ways: by modelling the thermal continuum spectrum of the accretion disc, and independently by modeling the broad red wing of the reflection fluorescence Fe-K line. We find that the spin measurements conducted independently using both leading methods are in agreement with one another. For the continuum-fitting analysis, we use a data sample consisting of several dozen RXTE spectra, and for the Fe-K analysis, we use a pair of ASCA spectra from a single epoch. Our spin estimate for the black hole primary using the continuum-fitting method is -0.11 < a* < 0.71 (90 per cent confidence), with a most likely spin of a* = 0.34. In obtaining this result, we have thoroughly explored the dependence of the spin value on a wide range of model-dependent systematic errors and observational errors; our precision is limited by uncertainties in the distance and orbital inclination of the system. For the Fe-line method, our estimate of spin is a* = 0.55(+0.15,-0.22). Combining these results, we conclude that the spin of this black hole is moderate, a* = 0.49(+0.13,-0.20), which suggests that the jet of this microquasar is powered largely by its accretion disc rather than by the spin energy of the black hole.Comment: 19 pages, 15 figures, submitted to MNRAS, updated abstrac

The Extreme Spin of the Black Hole in Cygnus X-1

The compact primary in the X-ray binary Cygnus X-1 was the first black hole to be established via dynamical observations. We have recently determined accurate values for its mass and distance, and for the orbital inclination angle of the binary. Building on these results, which are based on our favored (asynchronous) dynamical model, we have measured the radius of the inner edge of the black hole's accretion disk by fitting its thermal continuum spectrum to a fully relativistic model of a thin accretion disk. Assuming that the spin axis of the black hole is aligned with the orbital angular momentum vector, we have determined that Cygnus X-1 contains a near-extreme Kerr black hole with a spin parameter a/M>0.95 (3\sigma). For a less probable (synchronous) dynamical model, we find a/M>0.92 (3\sigma). In our analysis, we include the uncertainties in black hole mass, orbital inclination angle and distance, and we also include the uncertainty in the calibration of the absolute flux via the Crab. These four sources of uncertainty totally dominate the error budget. The uncertainties introduced by the thin-disk model we employ are particularly small in this case given the extreme spin of the black hole and the disk's low luminosity.Comment: Paper III of three papers on Cygnus X-1; 21 pages including 5 figures and 12 tables, ApJ in press. The paper is significantly restructured; two further tests of the robustness of our spin measurement are presented, and our error analysis has been substantially improved; the conclusions are unchange

MEASURING BLACK HOLE SPIN VIA THE X-RAY CONTINUUM-FITTING METHOD: BEYOND THE THERMAL DOMINANT STATE

All prior work on measuring the spins of stellar-mass black holes (BHs) via the X-ray continuum-fitting (CF) method has relied on the use of weakly Comptonized spectra obtained in the thermal dominant (TD) state. Using a self-consistent Comptonization model, we show that one can analyze spectra that exhibit strong power-law components and obtain values of the inner disk radius, and hence spin, that are consistent with those obtained in the TD state. Specifically, we analyze many RXTE spectra of two BH transients, H1743–322 and XTE J1550–564, and we demonstrate that the radius of the inner edge of the accretion disk remains constant to within a few percent as the strength of the Comptonized component increases by an order of magnitude, i.e., as the fraction of the thermal seed photons that are scattered approaches 25%. We conclude that the CF method can be applied to a much wider body of data than previously thought possible, and to sources that have never been observed to enter the TD state (e.g., Cyg X-1).United States. National Aeronautics and Space Administration (NASA grant NNX08AH32G)National Science Foundation (U.S.) (NSF grant AST-0805832)Smithsonian Institution (Endowment Funds

mTOR Signalling in Health and Disease 443 Signalling by amino acid nutrients

Abstract It is clear that mTORC1 (mammalian target of rapamycin complex 1) is regulated by the presence of ambient amino acid nutrients. However, the mechanism by which amino acids regulate mTORC1 is still open to question, despite extensive efforts. Our recent work has revealed that PR61ε, a B56 family regulatory subunit of PP2A (protein phosphatase 2A), associates with and regulates the activity of MAP4K3 (mitogenactivated protein kinase kinase kinase kinase 3), a protein kinase regulated by amino acid sufficiency that acts upstream of mTORC1. In searching for a physiological process regulated by amino acids, we have demonstrated recently that arginine plays a role in the activation of LPS (lipopolysaccharide)-induced MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase]/ERK signalling in macrophages. PP2A similarly associates with the upstream regulator of MEK in this signalling pathway, TPL-2 (tumour progression locus-2), in response to arginine availability. Thus PP2A is a negative regulator of both MAP4K3 and TPL-2 in both mTORC1 and MEK/ERK signalling pathways