The gastric pathogen Helicobacter pylori requires a noncanonical cytosolic chemoreceptor transducer-like protein D (TlpD) for efficient colonization of the mammalian stomach. Here, we reconstituted a ...complete chemotransduction signaling complex in vitro with TlpD and the chemotaxis (Che) proteins CheW and CheA, enabling quantitative assays for potential chemotaxis ligands. We found that TlpD is selectively sensitive at micromolar concentrations to bleach (hypochlorous acid, HOCl), a potent antimicrobial produced by neutrophil myeloperoxidase during inflammation. HOCl acts as a chemoattractant by reversibly oxidizing a conserved cysteine within a 3His/1Cys Zn-binding motif in TlpD that inactivates the chemotransduction signaling complex. We found that H. pylori is resistant to killing by millimolar concentrations of HOCl and responds to HOCl in the micromolar range by increasing its smooth-swimming behavior, leading to chemoattraction to HOCl sources. We show related protein domains from Salmonella enterica and Escherichia coli possess similar reactivity toward HOCl. We propose that this family of proteins enables host-associated bacteria to sense sites of tissue inflammation, a strategy that H. pylori uses to aid in colonizing and persisting in inflamed gastric tissue.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present the Red Cluster Sequence Lensing Survey (RCSLenS), an application of the methods developed for the Canada–France–Hawaii Telescope Lensing Survey (CFHTLenS) to the ∼785 deg2, multi-band ...imaging data of the Red-sequence Cluster Survey 2. This project represents the largest public, sub-arcsecond seeing, multi-band survey to date that is suited for weak gravitational lensing measurements. With a careful assessment of systematic errors in shape measurements and photometric redshifts, we extend the use of this data set to allow cross-correlation analyses between weak lensing observables and other data sets. We describe the imaging data, the data reduction, masking, multi-colour photometry, photometric redshifts, shape measurements, tests for systematic errors, and a blinding scheme to allow for more objective measurements. In total, we analyse 761 pointings with r-band coverage, which constitutes our lensing sample. Residual large-scale B-mode systematics prevent the use of this shear catalogue for cosmic shear science. The effective number density of lensing sources over an unmasked area of 571.7 deg2 and down to a magnitude limit of r ∼ 24.5 is 8.1 galaxies per arcmin2 (weighted: 5.5 arcmin−2) distributed over 14 patches on the sky. Photometric redshifts based on four-band griz data are available for 513 pointings covering an unmasked area of 383.5 deg2. We present weak lensing mass reconstructions of some example clusters as well as the full survey representing the largest areas that have been mapped in this way. All our data products are publicly available through Canadian Astronomy Data Centre at http://www.cadc-ccda.hia-iha.nrc-cnrc.gc.ca/en/community/rcslens/query.html in a format very similar to the CFHTLenS data release.
Context. Age, metallicity, and spatial distribution of globular clusters (GCs) provide a powerful tool for reconstructing major star-formation episodes in galaxies. IKN is a faint dwarf spheroidal ...(dSph) in the M 81 group of galaxies. It contains five old GCs, which makes it the galaxy with the highest known specific frequency (SN = 126). Aims. We estimate the photometric age, metallicity, and spatial distribution of the poorly studied IKN GCs. We search SDSS for GC candidates beyond the HST/ACS field of view, which covers half of IKN. Methods. To break the age-metallicity degeneracy in the colour, we used WHT/LIRIS KS-band photometry and derived photometric ages and metallicities by comparison with SSP models in the V,I,Ks colour space. Results. IKN GCs’ VIKs colours are consistent with old ages (≥8 Gyr) and a metallicity distribution with a higher mean than is typical for such a dSph (Fe/H ≃ -1.4-0.2+0.6 dex). Their photometric mass range (0.5 < ℳGC< 4 × 105 M⊙) implies an unusually high mass ratio between GCs and field stars, of 10.6%. Mixture model analysis of the RGB field stars’ metallicity suggests that 72% of the stars may have formed together with the GCs. Using the most massive GC−SFR relation, we calculated a star formation rate (SFR) of ~10 M⊙/yr during its formation epoch. We note that the more massive GCs are closer to the galaxy photometric centre. IKN GCs also appear spatially aligned along a line close to the major axis of the IKN and nearly orthogonal to the plane of spatial distribution of galaxies in the M 81 group. We identify one new IKN GC candidate based on colour and the PSF analysis of the SDSS data. Conclusions. The evidence of i) broad and high metallicity distribution of the field IKN RGB stars and its GCs, ii) high fraction, and iii) spatial alignment of IKN GCs supports a scenario for tidally triggered, complex IKN’s star formation history in the context of interactions with galaxies in the M 81 group.
We compile a sample of spectroscopically and photometrically selected cluster galaxies from four high-redshift galaxy clusters ( ) from the Spitzer Adaptation of the Red-Sequence Cluster Survey ...(SpARCS), and a comparison field sample selected from the UKIDSS Deep Survey. Using near-infrared imaging from the Hubble Space Telescope, we classify potential mergers involving massive ( ) cluster members by eye, based on morphological properties such as tidal distortions, double nuclei, and projected near neighbors within 20 kpc. With a catalog of 23 spectroscopic and 32 photometric massive cluster members across the four clusters and 65 spectroscopic and 26 photometric comparable field galaxies, we find that after taking into account contamination from interlopers, of the cluster members are involved in potential mergers, compared to of the field galaxies. We see no evidence of merger enhancement in the central cluster environment with respect to the field, suggesting that galaxy-galaxy merging is not a stronger source of galaxy evolution in cluster environments compared to the field at these redshifts.
Bacteria that colonize animals must overcome, or coexist, with the reactive oxygen species products of inflammation, a front-line defense of innate immunity. Among these is the neutrophilic oxidant ...bleach, hypochlorous acid (HOCl), a potent antimicrobial that plays a primary role in killing bacteria through nonspecific oxidation of proteins, lipids, and DNA. Here, we report that in response to increasing HOCl levels, Escherichia coli regulates biofilm production via activation of the diguanylate cyclase DgcZ. We identify the mechanism of DgcZ sensing of HOCl to be direct oxidation of its regulatory chemoreceptor zinc-binding (CZB) domain. Dissection of CZB signal transduction reveals that oxidation of the conserved zinc-binding cysteine controls CZB Zn
occupancy, which in turn regulates the catalysis of c-di-GMP by the associated GGDEF domain. We find DgcZ-dependent biofilm formation and HOCl sensing to be regulated
by the conserved zinc-coordinating cysteine. Additionally, point mutants that mimic oxidized CZB states increase total biofilm. A survey of bacterial genomes reveals that many pathogenic bacteria that manipulate host inflammation as part of their colonization strategy possess CZB-regulated diguanylate cyclases and chemoreceptors. Our findings suggest that CZB domains are zinc-sensitive regulators that allow host-associated bacteria to perceive host inflammation through reactivity with HOCl.
Immune cells are well equipped to eliminate invading bacteria, and one of their primary tools is the synthesis of bleach, hypochlorous acid (HOCl), the same chemical used as a household disinfectant. In this work, we present findings showing that many host-associated bacteria possess a bleach-sensing protein that allows them to adapt to the presence of this chemical in their environment. We find that the bacterium Escherichia coli responds to bleach by hunkering down and producing a sticky matrix known as biofilm, which helps it aggregate and adhere to surfaces. This behavior may play an important role in pathogenicity for E. coli and other bacteria, as it allows the bacteria to detect and adapt to the weapons of the host immune system.
Context. Measuring and calibrating relations between cluster observables is critical for resource-limited studies. The mass–richness relation of clusters offers an observationally inexpensive way of ...estimating masses. Its calibration is essential for cluster and cosmological studies, especially for high-redshift clusters. Weak gravitational lensing magnification is a promising and complementary method to shear studies, that can be applied at higher redshifts. Aims. We aim to employ the weak lensing magnification method to calibrate the mass–richness relation up to a redshift of 1.4. We used the Spitzer Adaptation of the Red-Sequence Cluster Survey (SpARCS) galaxy cluster candidates (0.2 < z < 1.4) and optical data from the Canada France Hawaii Telescope (CFHT) to test whether magnification can be effectively used to constrain the mass of high-redshift clusters. Methods. Lyman-break galaxies (LBGs) selected using the u-band dropout technique and their colours were used as a background sample of sources. LBG positions were cross-correlated with the centres of the sample of SpARCS clusters to estimate the magnification signal, which was optimally-weighted using an externally-calibrated LBG luminosity function. The signal was measured for cluster sub-samples, binned in both redshift and richness. Results. We measured the cross-correlation between the positions of galaxy cluster candidates and LBGs and detected a weak lensing magnification signal for all bins at a detection significance of 2.6–5.5σ. In particular, the significance of the measurement for clusters with z> 1.0 is 4.1σ; for the entire cluster sample we obtained an average M200 of 1.28 -0.21+0.23 × 1014 M⊙. Conclusions. Our measurements demonstrated the feasibility of using weak lensing magnification as a viable tool for determining the average halo masses for samples of high redshift galaxy clusters. The results also established the success of using galaxy over-densities to select massive clusters at z > 1. Additional studies are necessary for further modelling of the various systematic effects we discussed.
To prospectively determine if a combined magnetic resonance (MR) protocol that includes T1-weighted dynamic contrast agent-enhanced (DCE) MR imaging, hydrogen 1 (1H) MR spectroscopy, and T2*-weighted ...perfusion MR imaging improves specificity in the diagnosis of breast cancer.
The combined MR imaging-MR spectroscopy protocol was performed in 50 patients after positive findings at mammography but prior to biopsy. Single-voxel proton MR spectroscopy and perfusion MR imaging were conducted only if DCE MR images showed rapid contrast enhancement in the lesion. Biopsy results were used as the reference for comparison with MR results and for calculation of sensitivity and specificity in the detection of breast malignancy.
DCE MR imaging alone showed 100% sensitivity and 62.5% specificity. The specificity improved to 87.5% with the addition of 1H MR spectroscopy and to 100% with the further addition of perfusion MR imaging. Twenty-eight patients underwent both MR spectroscopy and perfusion MR imaging. Two patients underwent MR spectroscopy but declined to undergo perfusion MR imaging. The remaining 20 patients had negative results at DCE MR imaging and therefore did not undergo the additional examinations.
The combined MR protocol of DCE MR imaging, 1H MR spectroscopy, and perfusion MR imaging has high sensitivity and specificity in the diagnosis of breast cancer.
To assess the accuracy of the shutter-speed approach compared with standard approach dynamic contrast material-enhanced magnetic resonance (MR) imaging pharmacokinetic analysis for breast cancer ...diagnosis.
This study was approved by the institutional review board and was HIPAA compliant. Informed consent was obtained from 89 high-risk women (age range, 28-83 years) who had 92 suspicious lesions with negative findings at mammography (but visible at MR imaging). Each underwent a research dynamic contrast-enhanced MR imaging examination just prior to a clinical MR imaging-guided interventional procedure. Tumor region of interest (ROI) averaged and (for some) pixel-by-pixel dynamic contrast-enhanced time-course data, together with mean arterial input function, were subjected to serial standard and shutter-speed approach analyses to extract pharmacokinetic parameters, including rate constant for passive contrast reagent transfer between plasma and interstitium (K(trans)) and interstitial space volume fraction, or v(e). Pathologic findings were used as reference standards. Diagnostic accuracy was assessed with receiver operating characteristic analyses.
The pathologic analyses revealed 20 malignant and 72 benign lesions. Positive predictive value of the institutional clinical breast MR imaging protocol was 22%. At 100% sensitivity, ROI-averaged shutter-speed approach K(trans) had significantly (P = .008) higher diagnostic specificity than standard approach K(trans): 86.1% versus 77.8%. The difference in the ROI-averaged K(trans) parameter value, or ΔK(trans) (≡ K(trans) shutter-speed approach - K(trans) standard approach), had even higher specificity (88.9%). Combined use of ROI analysis and pixel-by-pixel mapping of ΔK(trans) achieved 98.6% specificity at 100% sensitivity.
The use of the shutter-speed dynamic contrast-enhanced MR imaging method has the potential to improve breast cancer diagnostic accuracy and reduce putatively unnecessary biopsy procedures that yield benign pathologic findings.
http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11102413/-/DC1.
Abstract Three dimensional bilateral imaging is the standard for most clinical breast dynamic contrast-enhanced (DCE) MRI protocols. Because of high spatial resolution (sRes) requirement, the typical ...1–2 min temporal resolution (tRes) afforded by a conventional full-k-space-sampling gradient echo (GRE) sequence precludes meaningful and accurate pharmacokinetic analysis of DCE time-course data. The commercially available, GRE-based, k-space undersampling and data sharing TWIST (time-resolved angiography with stochastic trajectories) sequence was used in this study to perform DCE-MRI exams on thirty one patients (with 36 suspicious breast lesions) before their biopsies. The TWIST DCE-MRI was immediately followed by a single-frame conventional GRE acquisition. Blinded from each other, three radiologist readers assessed agreements in multiple lesion morphology categories between the last set of TWIST DCE images and the conventional GRE images. Fleiss’ κ test was used to evaluate inter-reader agreement. The TWIST DCE time-course data were subjected to quantitative pharmacokinetic analyses. With a four-channel phased-array breast coil, the TWIST sequence produced DCE images with 20 s or less tRes and ~ 1.0×1.0×1.4 mm3 sRes. There were no significant differences in signal-to-noise ( P =.45) and contrast-to-noise ( P =.51) ratios between the TWIST and conventional GRE images. The agreements in morphology evaluations between the two image sets were excellent with the intra-reader agreement ranging from 79% for mass margin to 100% for mammographic density and the inter-reader κ value ranging from 0.54 ( P <.0001) for lesion size to 1.00 ( P <.0001) for background parenchymal enhancement. Quantitative analyses of the DCE time-course data provided higher breast cancer diagnostic accuracy (91% specificity at 100% sensitivity) than the current clinical practice of morphology and qualitative kinetics assessments. The TWIST sequence may be used in clinical settings to acquire high spatiotemporal resolution breast DCE-MRI images for both precise lesion morphology characterization and accurate pharmacokinetic analysis.
The pharmacokinetic analysis of dynamic-contrast-enhanced (DCE) MRI data yields Ktrans and kep, two parameters independently measuring the capillary wall contrast reagent transfer rate. The almost ...universally used standard model (SM) embeds the implicit assumption that equilibrium transcytolemmal water exchange is effectively infinitely fast. In analyses of routine DCE-MRI data from 22 patients with suspicious breast lesions initially ruled positive by institutional screening protocols, the SM Ktrans values for benign and malignant lesions exhibit considerable overlap. A form of the shutter-speed model (SSM), which allows for finite exchange kinetics, agrees with the SM Ktrans value for each of the 15 benign lesions. However, it reveals that the SM underestimates Ktrans for each of the seven malignant tumors in this population. The fact that this phenomenon is unique to malignant tumors allows their complete discrimination from the benign lesions, as validated by comparison with gold-standard pathology analyses of subsequent biopsy tissue samples. Likewise, the SM overestimates kep, particularly for the benign tumors. Thus, incorporation of the SSM into the screening protocols would have precluded all 68% of the biopsy/pathology procedures that yielded benign findings. The SM/SSM difference is well understood from molecular first principles.
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