Effects of LL-37 on Gingival Fibroblasts: A Role in Periodontal Tissue Remodeling?

Mounting evidence suggests that the host defence peptide, LL-37, plays a role in both inflammation and in wound healing; however, the role of this peptide in the remodeling and maintenance of oral tissues is not yet fully understood. Fibroblasts are the most abundant cell type within the periodontal tissues, and gingival fibroblasts play an important role in maintaining and repairing the gingival tissues which are constantly exposed to external insults. In this study we examined the direct effects of LL-37 treatment on gingival fibroblasts and found that LL-37 significantly increased secretion of both interleukin 8 (IL-8) and IL-6 from these cells. LL-37 tended to decrease matrix metalloproteinase (MMP) activity in gingival fibroblasts, but this decrease did not reach statistical significance. LL-37 significantly increased tissue inhibitor of metalloproteinase-1 (TIMP-1) production by gingival fibroblasts, but had no significant effect on TIMP-2 levels. LL-37 was also shown to significantly increase production of basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and keratinocyte growth factor (KGF) in gingival fibroblasts. Taken together, these results suggest an important role for the host defence peptide, LL-37, in modulating the fibroblast response to remodeling in periodontal tissues

Photon-noise limited sensitivity in titanium nitride kinetic inductance detectors

We demonstrate photon-noise limited performance at sub-millimeter wavelengths in feedhorn-coupled, microwave kinetic inductance detectors (MKIDs) made of a TiN/Ti/TiN trilayer superconducting film, tuned to have a transition temperature of 1.4~K. Micro-machining of the silicon-on-insulator wafer backside creates a quarter-wavelength backshort optimized for efficient coupling at 250~\micron. Using frequency read out and when viewing a variable temperature blackbody source, we measure device noise consistent with photon noise when the incident optical power is $>$~0.5~pW, corresponding to noise equivalent powers $>$~3$\times 10^{-17}$ W/$\sqrt{\mathrm{Hz}}$. This sensitivity makes these devices suitable for broadband photometric applications at these wavelengths

A massive reservoir of low-excitation molecular gas at high redshift

Molecular hydrogen is an important component of galaxies because it fuels star formation and accretion onto AGN, the two processes that generate the large infrared luminosities of gas-rich galaxies. Observations of spectral-line emission from the tracer molecule CO are used to probe the properties of this gas. But the lines that have been studied in the local Universe, mostly the lower rotational transitions of J = 1-0 and J = 2-1, have hitherto been unobservable in high-redshift galaxies. Instead, higher transitions have been used, although the densities and temperatures required to excite these higher transitions may not be reached by much of the gas. As a result, past observations may have underestimated the total amount of molecular gas by a substantial amount. Here we report the discovery of large amounts of low-excitation molecular gas around the infrared-luminous quasar, APM 08279+5255 at z = 3.91, using the two lowest excitation lines of 12CO (J = 1-0 and J = 2-1). The maps confirm the presence of hot and dense gas near the nucleus, and reveal an extended reservoir of molecular gas with low excitation that is 10 to 100 times more massive than the gas traced by higher-excitation observations. This raises the possibility that significant amounts of low-excitation molecular gas may lurk in the environments of high-redshift (z > 3) galaxies.Comment: To appear as a Letter to Nature, 4th January 200

Biodentine Reduces Tumor Necrosis Factor Alpha-induced TRPA1 Expression in Odontoblastlike Cells

International audienceIntroduction: The transient receptor potential (TRP) ion channels have emerged as important cellular sensors in both neuronal and non-neuronal cells, with TRPA1 playing a central role in nociception and neurogenic inflammation. The functionality of TRP channels has been shown to be modulated by inflammatory cytokines. The aim of this study was to investigate the effect of inflammation on odontoblast TRPA1 expression and to determine the effect of Biodentine (Septodent, Paris, France) on inflammatory-induced TRPA1 expression. Methods: Immunohistochemistry was used to study TRPA1 expression in pulp tissue from healthy and carious human teeth. Pulp cells were differentiated to odontoblastlike cells in the presence of 2 mmol/L beta-glycerophosphate, and these cells were used in quantitative polymerase chain reaction, Western blotting, calcium imaging, and patch clamp studies. Results: Immunofluorescent staining revealed. TRPA1 expression in odontoblast cell bodies and odontoblast processes, which was more intense in carious versus healthy teeth. TRPA1 gene expression was induced in cultured odontoblastlike cells by tumor necrosis factor alpha, and this expression was significantly reduced in the presence of Biodentine. The functionality of the TRPA1 channel was shown by calcium microfluorimetry and patch clamp recording, and our results showed a significant reduction in tumor necrosis factor alpha induced TRPA1 responses after Biodentine treatment. Conclusions: In conclusion, this study showed TRPA1 to be modulated by caries-induced inflammation and that Biodentine reduced TRPA1 expression and functional responses

Impact of modulation on CMB B-mode polarization experiments

We investigate the impact of both slow and fast polarization modulation strategies on the science return of upcoming ground-based experiments aimed at measuring the B-mode polarization of the CMB. Using simulations of the Clover experiment, we compare the ability of modulated and un-modulated observations to recover the signature of gravitational waves in the polarized CMB sky in the presence of a number of anticipated systematic effects. The general expectations that fast modulation is helpful in mitigating low-frequency detector noise, and that the additional redundancy in the projection of the instrument's polarization sensitivity directions onto the sky when modulating reduces the impact of instrumental polarization, are borne out by our simulations. Neither low-frequency polarized atmospheric fluctuations nor systematic errors in the polarization sensitivity directions are mitigated by modulation. Additionally, we find no significant reduction in the effect of pointing errors by modulation. For a Clover-like experiment, pointing jitter should be negligible but any systematic mis-calibration of the polarization coordinate reference system results in significant E-B mixing on all angular scales and will require careful control. We also stress the importance of combining data from multiple detectors in order to remove the effects of common-mode systematics (such as 1/f atmospheric noise) on the measured polarization signal. Finally we compare the performance of our simulated experiment with the predicted performance from a Fisher analysis. We find good agreement between the Fisher predictions and the simulations except for the very largest scales where the power spectrum estimator we have used introduces additional variance to the B-mode signal recovered from our simulations.Comment: Replaced with version accepted by MNRAS. Analysis of half-wave plate systematic (differential transmittance) adde

Evaluation of the Ability of LL-37 to Neutralise LPS In Vitro and Ex Vivo

BACKGROUND: Human cathelicidin LL-37 is a cationic antimicrobial peptide (AMP) which possesses a variety of activities including the ability to neutralise endotoxin. In this study, we investigated the role of LPS neutralisation in mediating LL-37's ability to inhibit Pseudomonas aeruginosa LPS signalling in human monocytic cells. METHODOLOGY/PRINCIPAL FINDINGS: Pre-treatment of monocytes with LL-37 significantly inhibited LPS-induced IL-8 production and the signalling pathway of associated transcription factors such as NF-κB. However, upon removal of LL-37 from the media prior to LPS stimulation, these inhibitory effects were abolished. These findings suggest that the ability of LL-37 to inhibit LPS signalling is largely dependent on extracellular LPS neutralisation. In addition, LL-37 potently inhibited cytokine production induced by LPS extracted from P. aeruginosa isolated from the lungs of cystic fibrosis (CF) patients. In the CF lung, polyanionic molecules such as glycosaminoglycans (GAGs) and DNA bind LL-37 and impact negatively on its antibacterial activity. In order to determine whether such interactions interfere with the LPS neutralising ability of LL-37, the status of LL-37 and its ability to bind LPS in CF sputum were investigated. Overall our findings suggest that in the CF lung, the ability of LL-37 to bind LPS and inhibit LPS-induced IL-8 production is attenuated as a result of binding to DNA and GAGs. However, LL-37 levels and its concomitant LPS-binding activity can be increased with a combination of DNase and GAG lyase (heparinase II) treatment. CONCLUSIONS/SIGNIFICANCE: Overall, these findings suggest that a deficiency in available LL-37 in the CF lung may contribute to greater LPS-induced inflammation during CF lung disease

Resolved nuclear CO(1-0) emission in APM08279+5255: Gravitational lensing by a naked cusp?

The ultraluminous broad absorption line quasar APM08279+5255 is one of the most luminous systems known. Here, we present an analysis of its nuclear CO(1-0) emission. Its extended distribution suggests that the gravitational lens in this system is highly elliptical, probably a highly inclined disk. The quasar core, however, lies in the vicinity of naked cusp, indicating that APM08279+5255 is truly the only odd-image gravitational lens. This source is the second system for which the gravitational lens can be used to study structure on sub-kpc scales in the molecular gas associated with the AGN host galaxy. The observations and lens model require CO distributed on a scale of $\sim 400$ pc. Using this scale, we find that the molecular gas mass makes a significant, and perhaps dominant, contribution to the total mass within a couple hundred parsecs of the nucleus of APM08279+5255.Comment: 5 Pages, 2 Figures, to appear in MNRAS Letters - Resolution of Figure 2 reduce

L-Edge Spectroscopy of Dilute, Radiation-Sensitive Systems Using a Transition-Edge-Sensor Array

We present X-ray absorption spectroscopy and resonant inelastic X-ray scattering (RIXS) measurements on the iron L-edge of 0.5 mM aqueous ferricyanide. These measurements demonstrate the ability of high-throughput transition-edge-sensor (TES) spectrometers to access the rich soft X-ray (100-2000eV) spectroscopy regime for dilute and radiation-sensitive samples. Our low-concentration data are in agreement with high-concentration measurements recorded by conventional grating-based spectrometers. These results show that soft X-ray RIXS spectroscopy acquired by high-throughput TES spectrometers can be used to study the local electronic structure of dilute metal-centered complexes relevant to biology, chemistry and catalysis. In particular, TES spectrometers have a unique ability to characterize frozen solutions of radiation- and temperature-sensitive samples.Comment: 19 pages, 4 figure