Functional analysis of an unusual type IV pilus in the Gram-positive Streptococcus sanguinis

Type IV pili (Tfp), which have been studied extensively in a few Gram-negative species, are the paradigm of a group of widespread and functionally versatile nano-machines. Here, we performed the most detailed molecular characterisation of Tfp in a Gram-positive bacterium. We demonstrate that the naturally competent Streptococcus sanguinis produces retractable Tfp, which like their Gram-negative counterparts can generate hundreds of piconewton of tensile force and promote intense surface-associated motility. Tfp power 'train-like' directional motion parallel to the long axis of chains of cells, leading to spreading zones around bacteria grown on plates. However, S. sanguinis Tfp are not involved in DNA uptake, which is mediated by a related but distinct nano-machine, and are unusual because they are composed of two pilins in comparable amounts, rather than one as normally seen. Whole genome sequencing identified a locus encoding all the genes involved in Tfp biology in S. sanguinis. A systematic mutational analysis revealed that Tfp biogenesis in S. sanguinis relies on a more basic machinery (only 10 components) than in Gram-negative species and that a small subset of four proteins dispensable for pilus biogenesis are essential for motility. Intriguingly, one of the piliated mutants that does not exhibit spreading retains microscopic motility but moves sideways, which suggests that the corresponding protein controls motion directionality. Besides establishing S. sanguinis as a useful new model for studying Tfp biology, these findings have important implications for our understanding of these widespread filamentous nano-machines

In Vivo Fluorescence-Based Endoscopic Detection of Colon Dysplasia in the Mouse Using a Novel Peptide Probe

Colorectal cancer (CRC) is a major cause of cancer-related deaths in much of the world. Most CRCs arise from pre-malignant (dysplastic) lesions, such as adenomatous polyps, and current endoscopic screening approaches with white light do not detect all dysplastic lesions. Thus, new strategies to identify such lesions, including non-polypoid lesions, are needed. We aim to identify and validate novel peptides that specifically target dysplastic colonic epithelium in vivo. We used phage display to identify a novel peptide that binds to dysplastic colonic mucosa in vivo in a genetically engineered mouse model of colo-rectal tumorigenesis, based on somatic Apc (adenomatous polyposis coli) gene inactivation. Binding was confirmed using confocal microscopy on biopsied adenomas and excised adenomas incubated with peptide ex vivo. Studies of mice where a mutant Kras allele was somatically activated in the colon to generate hyperplastic epithelium were also performed for comparison. Several rounds of in vivo T7 library biopanning isolated a peptide, QPIHPNNM. The fluorescent-labeled peptide bound to dysplastic lesions on endoscopic analysis. Quantitative assessment revealed the fluorescent-labeled peptide (target/background: 2.17±0.61) binds ∼2-fold greater to the colonic adenomas when compared to the control peptide (target/background: 1.14±0.15), p<0.01. The peptide did not bind to the non-dysplastic (hyperplastic) epithelium of the Kras mice. This work is first to image fluorescence-labeled peptide binding in vivo that is specific towards colonic dysplasia on wide-area surveillance. This finding highlights an innovative strategy for targeted detection to localize pre-malignant lesions that can be generalized to the epithelium of hollow organs

Diffraction-limited near-IR imaging at Keck reveals asymmetric, time-variable nebula around carbon star CIT 6

We present multi-epoch, diffraction-limited images of the nebula around the carbon star CIT 6 at 2.2 microns and 3.1 microns from aperture masking on the Keck-I telescope. The near-IR nebula is resolved into two main components, an elongated, bright feature showing time-variable asymmetry and a fainter component about 60 milliarcseconds away with a cooler color temperature. These images were precisely registered (~35 milliarcseconds) with respect to recent visible images from the Hubble Space Telescope (Trammell et al. 2000), which showed a bipolar structure in scattered light. The dominant near-IR feature is associated with the northern lobe of this scattering nebula, and the multi-wavelength dataset can be understood in terms of a bipolar dust shell around CIT 6. Variability of the near-IR morphology is qualitatively consistent with previously observed changes in red polarization, caused by varying illumination geometry due to non-uniform dust production. The blue emission morphology and polarization properties can not be explained by the above model alone, but require the presence of a wide binary companion in the vicinity of the southern polar lobe. The physical mechanisms responsible for the breaking of spherical symmetry around extreme carbon stars, such as CIT 6 and IRC+10216, remain uncertain.Comment: 18 pages, 5 figures (one in color), to appear in the Astrophysical Journa

Densities and filling factors of the DIG in the Solar neighbourhood

For the first time we have combined dispersion measures and emission measures towards 38 pulsars at KNOWN distances from which we derived the mean electron density in clouds, N_c, and their volume filling factor, F_v, averaged along the line of sight. The emission measures were corrected for absorption by dust and contributions from beyond the pulsar distance. Results: The scale height of the electron layer for our sample is 0.93+/-0.13 kpc and the midplane electron density is 0.023+/-0.004 cm^-3, in agreement with earlier results. The average density along the line of sight is = 0.018+/-0.002 cm^-3 and nearly constant. Since = F_v N_c, an inverse relationship between F_v and N_c is expected. We find F_v(N_c) = (0.011+/-0.003) N_c^{-1.20+/-0.13}, which holds for the ranges N_c = 0.05-1 cm^-3 and F_v = 0.4-0.01. Near the Galactic plane the dependence of F_v on N_c is significantly stronger than away from the plane. F_v does not systematically change along or perpendicular to the Galactic plane, but the spread about the mean value of 0.08+/-0.02 is considerable. Conclusions: The inverse F_v-N_c relation is consistent with a hierarchical, fractal density distribution in the diffuse ionized gas (DIG) caused by turbulence. The observed near constancy of then is a signature of fractal structure in the ionized medium, which is most pronounced outside the thin disk.Comment: 9 pages, 9 figures. Accepted for publication in A&

E-BOSS: an Extensive stellar BOw Shock Survey. I: Methods and First Catalogue

Context: Bow shocks are produced by many astrophysical objects where shock waves are present. Stellar bow shocks, generated by runaway stars, have been previously detected in small numbers and well-studied. Along with progress in model development and improvements in observing instruments, our knowledge of the emission produced by these objects and its origin can now be more clearly understood. Aims: We produce a stellar bow-shock catalogue by applying uniform search criteria and a systematic search process. This catalogue is a starting point for statistical studies, to help us address fundamental questions such as, for instance, the conditions under wich a stellar bow shock is detectable. Methods: By using the newest infrared data releases, we carried out a search for bow shocks produced by early-type runaway stars. We first explored whether a set of known IRAS bow shock candidates are visible in the most recently available IR data, which has much higher resolution and sensitivity. We then carried out a selection of runaway stars from the latest, large runaway catalogue available. In this first release, we focused on OB stars and searched for bow-shaped features in the vicinity of these stars. Results: We provide a bow-shock candidate survey that gathers a total of 28 members which we call the Extensive stellar BOw Shock Survey (E-BOSS). We derive the main bow-shock parameters, and present some preliminary statistical results on the detected objects. Conclusions: Our analysis of the initial sample and the newly detected objects yields a bow-shock detectability around OB stars of $\sim$ 10 per cent. The detections do not seem to depend particularly on either stellar mass, age or position. The extension of the E-BOSS sample, with upcoming IR data, and by considering, for example, other spectral types as well, will allow us to perform a more detailed study of the findings.Comment: A&A accepted (25-NOV-2011), 15 pages, 4 tables, 11 figure

A Measurement of the Angular Power Spectrum of the Anisotropy in the Cosmic Microwave Background

We report on a measurement of the angular power spectrum of the anisotropy in the Cosmic Microwave Background. The anisotropy is measured in 23 different multipole bands from l=54 (~3 deg) to l=404 (~0.45 deg) and in 6 frequency bands from 26 GHz to 46 GHz over three observing seasons. The measurements are consistent from year to year. The frequency spectral index of the fluctuations (measured at low l) is consistent with that of the CMB and inconsistent with either dust or Galactic free-free emission. Furthermore, the observations of the MSAM1-92 experiment (Cheng et al. 1994) are repeated and confirmed. The angular spectrum shows a distinct rise from dT_l = \sqrt{l(2l+1)/4pi} = 49(+8,-5) \uK at l=87 to dT_l=85(+10,-8) uK at l = 237. These values do not include an overall +/-14\% (1sigma) calibration uncertainty. The analysis and possible systematic errors are discussed.Comment: latex file is called spect.tex. 25 pages with 11 Postscript figures. Uses aas2pp4.sty (included). Submitted to Ap

High Interstitial Fluid Pressure Is Associated with Tumor-Line Specific Vascular Abnormalities in Human Melanoma Xenografts

PURPOSE: Interstitial fluid pressure (IFP) is highly elevated in many solid tumors. High IFP has been associated with low radiocurability and high metastatic frequency in human melanoma xenografts and with poor survival after radiation therapy in cervical cancer patients. Abnormalities in tumor vascular networks have been identified as an important cause of elevated tumor IFP. The aim of this study was to investigate the relationship between tumor IFP and the functional and morphological properties of tumor vascular networks. MATERIALS AND METHODS: A-07-GFP and R-18-GFP human melanomas growing in dorsal window chambers in BALB/c nu/nu mice were used as preclinical tumor models. Functional and morphological parameters of the vascular network were assessed from first-pass imaging movies and vascular maps recorded after intravenous bolus injection of 155-kDa tetramethylrhodamine isothiocyanate-labeled dextran. IFP was measured in the center of the tumors using a Millar catheter. Angiogenic profiles of A-07-GFP and R-18-GFP cells were obtained with a quantitative PCR array. RESULTS: High IFP was associated with low growth rate and low vascular density in A-07-GFP tumors, and with high growth rate and high vascular density in R-18-GFP tumors. A-07-GFP tumors showed chaotic and highly disorganized vascular networks, while R-18-GFP tumors showed more organized vascular networks with supplying arterioles in the tumor center and draining venules in the tumor periphery. Furthermore, A-07-GFP and R-18-GFP cells differed substantially in angiogenic profiles. A-07-GFP tumors with high IFP showed high geometric resistance to blood flow due to high vessel tortuosity. R-18-GFP tumors with high IFP showed high geometric resistance to blood flow due to a large number of narrow tumor capillaries. CONCLUSIONS: High IFP in A-07-GFP and R-18-GFP human melanoma xenografts was primarily a consequence of high blood flow resistance caused by tumor-line specific vascular abnormalities

A Robotic Wide-Angle H-Alpha Survey of the Southern Sky

We have completed a robotic wide-angle imaging survey of the southern sky (declination less than +15 degrees) at 656.3 nm wavelength, the H-alpha emission line of hydrogen. Each image of the resulting Southern H-Alpha Sky Survey Atlas (SHASSA) covers an area of the sky 13 degrees square at an angular resolution of approximately 0.8 arcminute, and reaches a sensitivity level of 2 rayleigh (1.2 x 10^-17 erg cm^-2 s^-1 arcsec^-2) per pixel, corresponding to an emission measure of 4 cm^-6 pc, and to a brightness temperature for microwave free-free emission of 12 microkelvins at 30 GHz. Smoothing over several pixels allows features as faint as 0.5 rayleigh to be detected.Comment: LATEX, 33 pages, 15 figures. Accepted for publication in PASP, 113, November 2001. Further information at http://amundsen.swarthmore.edu/SHASSA

All-sky component separation for the Planck mission

An harmonic-space maximum-entropy method (MEM) is presented for separating the emission from different physical components in all-sky observations by the forthcoming Planck satellite. The analysis is performed at full Planck resolution, with a pixel size of 1.7 arcmin, which corresponds to a maximum multipole of around 6000. The simulated Planck data include emission from the CMB, the kinetic and thermal Sunyaev-Zel'dovich (SZ) effects from galaxy clusters, as well as Galactic dust, free-free and synchrotron emission. Our simulations also assume homogeneous, uncorrelated pixel noise, although this is not a requirement of the method. We find that the MEM technique produces faithful reconstructions of the main input components over the whole sky, without the need to perform a Galactic cut. The CMB power spectrum is accurately recovered up to a multipole of around 2000. The algorithm is parallelised so that the entire reconstruction can be performed in around 6 hr using 30 R10000 processors on an SGI Origin 2000 supercomputer and requires 14 Gb of memory.Comment: 16 pages, 13 figures; changed to match version accepted by MNRAS. Version with high-resolution figures available from http://www.mrao.cam.ac.uk/projects/cpac/pub.htm