HilE regulates HilD by blocking DNA binding in Salmonella enterica serovar Typhimurium

ABSTRACT The Salmonella type three secretion system (T3SS), encoded in the Salmonella pathogenicity island 1 (SPI1) locus, mediates the invasion of the host intestinal epithelium. SPI1 expression is dependent upon three AraC-like regulators: HilD, HilC, and RtsA. These regulators act in a complex feed-forward loop to activate each other and hilA , which encodes the activator of the T3SS structural genes. HilD has been shown to be the major integration point of most signals known to activate the expression of the SPI1 T3SS, acting as a switch to control induction of the system. HilE is a negative regulator that acts upon HilD. Here we provide genetic and biochemical data showing that HilE specifically binds to HilD but not to HilC or RtsA. This protein-protein interaction blocks the ability of HilD to bind DNA as shown by both an in vivo reporter system and an in vitro gel shift assay. HilE does not affect HilD dimerization, nor does it control the stability of the HilD protein. We also investigated the role of HilE during the infection of mice using competition assays. Although deletion of hilE does not confer a phenotype, the hilE mutation does suppress the invasion defect conferred by loss of FliZ, which acts as a positive signal controlling HilD protein activity. Together, these data suggest that HilE functions to restrict low-level HilD activity, preventing premature activation of SPI1 until positive inputs reach a threshold required to fully induce the system. IMPORTANCE Salmonella is a leading cause of gastrointestinal and systemic disease throughout the world. The SPI1 T3SS is required for Salmonella to induce inflammatory diarrhea and to gain access to underlying tissue. A complex regulatory network controls expression of SPI1 in response to numerous physiological inputs. Most of these signals impinge primarily on HilD translation or activity. The system is triggered when HilD activity crosses a threshold that allows efficient activation of its own promoter. This threshold is set by HilE, which binds to HilD to prevent the inevitable minor fluctuations in HilD activity from inappropriately activating the system. The circuit also serves as a paradigm for systems that must integrate numerous environmental parameters to control regulatory output. </jats:p

Lophelia reefs

PHASECam is the fringe tracker for the Large Binocular Telescope Interferometer (LBTI). It is a near-infrared camera that is used to measure both tip/tilt and fringe phase variations between the two adaptive optics-corrected apertures of the Large Binocular Telescope (LBT). Tip/tilt and phase sensing are currently performed in the H (1.65 mu m) and K (2.2 mu m) bands at 1 kHz, but only the K-band phase telemetry is used to send corrections to the system in order to maintain fringe coherence and visibility. However, due to the cyclic nature of the fringe phase, only the phase, modulo 360 deg, can be measured. PHASECam's phase unwrapping algorithm, which attempts to mitigate this issue, occasionally fails in cases of fast, large phase variations or low signal-to-noise ratio. This can cause a fringe jump in which case the optical path difference correction will be incorrect by a wavelength. This can currently be manually corrected by the operator. However, as the LBTI commissions further modes that require robust, active phase control and for which fringe jumps are harder to detect, including multiaxial (Fizeau) interferometry and dual-aperture nonredundant aperture masking interferometry, a more reliable and automated solution is desired. We present a multiwavelength method of fringe jump capture and correction that involves direct comparison between the K-band and H-band phase telemetry. We demonstrate the method utilizing archival PHASECam telemetry, showing it provides a robust, reliable way of detecting fringe jumps that can potentially recover a significant fraction of the data lost to them. (C) 2020 Society of Photo-Optical Instrumentation Engineers (SPIE)This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Co-phasing the Large Binocular Telescope: status and performance of LBTI/PHASECam

The Large Binocular Telescope Interferometer is a NASA-funded nulling and imaging instrument designed to coherently combine the two 8.4-m primary mirrors of the LBT for high-sensitivity, high-contrast, and high-resolution infrared imaging (1.5-13 um). PHASECam is LBTI's near-infrared camera used to measure tip-tilt and phase variations between the two AO-corrected apertures and provide high-angular resolution observations. We report on the status of the system and describe its on-sky performance measured during the first semester of 2014. With a spatial resolution equivalent to that of a 22.8-meter telescope and the light-gathering power of single 11.8-meter mirror, the co-phased LBT can be considered to be a forerunner of the next-generation extremely large telescopes (ELT).Comment: 8 pages, 5 figures, SPIE Conference proceeding

First-light LBT nulling interferometric observations: warm exozodiacal dust resolved within a few AU of eta Corvi

We report on the first nulling interferometric observations with the Large Binocular Telescope Interferometer (LBTI), resolving the N' band (9.81 - 12.41 um) emission around the nearby main-sequence star eta Crv (F2V, 1-2 Gyr). The measured source null depth amounts to 4.40% +/- 0.35% over a field-of-view of 140 mas in radius (~2.6\,AU at the distance of eta Corvi) and shows no significant variation over 35{\deg} of sky rotation. This relatively low null is unexpected given the total disk to star flux ratio measured by Spitzer/IRS (~23% across the N' band), suggesting that a significant fraction of the dust lies within the central nulled response of the LBTI (79 mas or 1.4 AU). Modeling of the warm disk shows that it cannot resemble a scaled version of the Solar zodiacal cloud, unless it is almost perpendicular to the outer disk imaged by Herschel. It is more likely that the inner and outer disks are coplanar and the warm dust is located at a distance of 0.5-1.0 AU, significantly closer than previously predicted by models of the IRS spectrum (~3 AU). The predicted disk sizes can be reconciled if the warm disk is not centrosymmetric, or if the dust particles are dominated by very small grains. Both possibilities hint that a recent collision has produced much of the dust. Finally, we discuss the implications for the presence of dust at the distance where the insolation is the same as Earth's (2.3 AU).Comment: 9 pages, 6 figures, accepted for publication in Ap

The HOSTS Survey for Exozodiacal Dust: Preliminary results and future prospects

[abridged] The presence of large amounts of dust in the habitable zones of nearby stars is a significant obstacle for future exo-Earth imaging missions. We executed an N band nulling interferometric survey to determine the typical amount of such exozodiacal dust around a sample of nearby main sequence stars. The majority of our data have been analyzed and we present here an update of our ongoing work. We find seven new N band excesses in addition to the high confidence confirmation of three that were previously known. We find the first detections around Sun-like stars and around stars without previously known circumstellar dust. Our overall detection rate is 23%. The inferred occurrence rate is comparable for early type and Sun-like stars, but decreases from 71% [+11%/-20%] for stars with previously detected mid- to far-infrared excess to 11% [+9%/-4%] for stars without such excess, confirming earlier results at high confidence. For completed observations on individual stars, our sensitivity is five to ten times better than previous results. Assuming a lognormal luminosity function of the dust, we find upper limits on the median dust level around all stars without previously known mid to far infrared excess of 11.5 zodis at 95% confidence level. The corresponding upper limit for Sun-like stars is 16 zodis. An LBTI vetted target list of Sun-like stars for exo-Earth imaging would have a corresponding limit of 7.5 zodis. We provide important new insights into the occurrence rate and typical levels of habitable zone dust around main sequence stars. Exploiting the full range of capabilities of the LBTI provides a critical opportunity for the detailed characterization of a sample of exozodiacal dust disks to understand the origin, distribution, and properties of the dust.Comment: To appear in SPIE Astronomical Telescopes + Instrumentation 2018 proceedings. Some typos fixed, one reference adde

Co-Phasing the Large Binocular Telescope:

The Large Binocular Telescope Interferometer is a NASA-funded nulling and imaging instrument designed to coherently combine the two 8.4-m primary mirrors of the LBT for high-sensitivity, high-contrast, and high-resolution infrared imaging (1.5-13 micrometer). PHASECam is LBTI's near-infrared camera used to measure tip-tilt and phase variations between the two AO-corrected apertures and provide high-angular resolution observations. We report on the status of the system and describe its on-sky performance measured during the first semester of 2014. With a spatial resolution equivalent to that of a 22.8-meter telescope and the light-gathering power of single 11.8-meter mirror, the co-phased LBT can be considered to be a forerunner of the next-generation extremely large telescopes (ELT)

Adora2b Adenosine Receptor Engagement Enhances Regulatory T Cell Abundance during Endotoxin-Induced Pulmonary Inflammation

Anti-inflammatory signals play an essential role in constraining the magnitude of an inflammatory response. Extracellular adenosine is a critical tissue-protective factor, limiting the extent of inflammation. Given the potent anti-inflammatory effects of extracellular adenosine, we sought to investigate how extracellular adenosine regulates T cell activation and differentiation. Adenosine receptor activation by a pan adenosine-receptor agonist enhanced the abundance of murine regulatory T cells (Tregs), a cell type critical in constraining inflammation. Gene expression studies in both naïve CD4 T cells and Tregs revealed that these cells expressed multiple adenosine receptors. Based on recent studies implicating the Adora2b in endogenous anti-inflammatory responses during acute inflammation, we used a pharmacologic approach to specifically activate Adora2b. Indeed, these studies revealed robust enhancement of Treg differentiation in wild-type mice, but not in Adora2b−/− T cells. Finally, when we subjected Adora2b-deficient mice to endotoxin-induced pulmonary inflammation, we found that these mice experienced more severe inflammation, characterized by increased cell recruitment and increased fluid leakage into the airways. Notably, Adora2b-deficient mice failed to induce Tregs after endotoxin-induced inflammation and instead had an enhanced recruitment of pro-inflammatory effector T cells. In total, these data indicate that the Adora2b adenosine receptor serves a potent anti-inflammatory role, functioning at least in part through the enhancement of Tregs, to limit inflammation

The HOSTS survey: evidence for an extended dust disk and constraints on the presence of giant planets in the Habitable Zone of β\beta Leo

The young (50-400 Myr) A3V star $\beta$ Leo is a primary target to study the formation history and evolution of extrasolar planetary systems as one of the few stars with known hot ($\sim$1600$^\circ$K), warm ($\sim$600$^\circ$K), and cold ($\sim$120$^\circ$K) dust belt components. In this paper, we present deep mid-infrared measurements of the warm dust brightness obtained with the Large Binocular Telescope Interferometer (LBTI) as part of its exozodiacal dust survey (HOSTS). The measured excess is 0.47\%$\pm$0.050\% within the central 1.5 au, rising to 0.81\%$\pm$0.026\% within 4.5 au, outside the habitable zone of $\beta$~Leo. This dust level is 50 $\pm$ 10 times greater than in the solar system's zodiacal cloud. Poynting-Robertson drag on the cold dust detected by Spitzer and Herschel under-predicts the dust present in the habitable zone of $\beta$~Leo, suggesting an additional delivery mechanism (e.g.,~comets) or an additional belt at $\sim$5.5 au. A model of these dust components is provided which implies the absence of planets more than a few Saturn masses between $\sim$5 au and the outer belt at $\sim$40 au. We also observationally constrain giant planets with the LBTI imaging channel at 3.8~$\mu$m wavelength. Assuming an age of 50 Myr, any planet in the system between approximately 5 au to 50 au must be less than a few Jupiter masses, consistent with our dust model. Taken together, these observations showcase the deep contrasts and detection capabilities attainable by the LBTI for both warm exozodiacal dust and giant exoplanets in or near the habitable zone of nearby stars.Comment: 11 pages, 9 figures, accepted for publication in Astronomical Journa