VDR and MEK-ERK dependent induction of the antimicrobial peptide cathelicidin in keratinocytes by lithocholic acid

Cathelicidin is an antimicrobial peptide (AMP) and signaling molecule in innate immunity and a direct target of 1,25-dihydroxyvitamin D3 (1,25D3) in primary human keratinocytes (NHEK). The expression of cathelicidin is dysregulated in various skin diseases and its regulation differs depending on the epithelial cell type. The secondary bile acid lithocholic acid (LCA) is a ligand of the vitamin D receptor (VDR) and can carry out in vivo functions of vitamin D3. Therefore we analyzed cathelicidin mRNA- and peptide expression levels in NHEK and colonic epithelial cells (Caco-2) after stimulation with LCA. We found increased expression of cathelicidin mRNA and peptide in NHEK, in Caco-2 colon cells no effect was observed after LCA stimulation. The VDR as well as MEK-ERK signaled the upregulation of cathelicidin in NHEK induced by LCA. Collectively, our data indicate that cathelicidin induction upon LCA treatment differs in keratinocytes and colonic epithelial cells. Based on these observations LCA-like molecules targeting cathelicidin could be designed for the treatment of cutaneous diseases that are characterized by disturbed cathelicidin expression.

The Type IIb SN 2011dh: Two years of observations and modelling of the lightcurves

We present optical and near-infrared (NIR) photometry and spectroscopy as well as modelling of the lightcurves of the Type IIb supernova (SN) 2011dh. Our extensive dataset, for which we present the observations obtained after day 100, spans two years, and complemented with Spitzer mid-infrared (MIR) data, we use it to build an optical-to-MIR bolometric lightcurve between days 3 and 732. To model the bolometric lightcurve before day 400 we use a grid of hydrodynamical SN models, which allows us to determine the errors in the derived quantities, and a bolometric correction determined with steady-state non-local thermodynamic equilibrium (NLTE) modelling. Using this method we find a helium core mass of 3.1^+0.7<inf>-0.4</inf> M<inf>⊙</inf> for SN 2011dh, consistent within error bars with previous results obtained using the bolometric lightcurve before day 80. We compute bolometric and broad-band lightcurves between days 100 and 500 from spectral steady-state NLTE models, presented and discussed in a companion paper. The preferred 12 M<inf>⊙</inf> (initial mass) model, previously found to agree well with the observed spectra, shows a good overall agreement with the observed lightcurves, although some discrepancies exist. Time-dependent NLTE modelling shows that after day ∼600 a steady-state assumption is no longer valid. The radioactive energy deposition in this phase is likely dominated by the positrons emitted in the decay of ⁵⁶Co, but seems insufficient to reproduce the lightcurves, and what energy source is dominating the emitted flux is unclear. We find an excess in the K and the MIR bands developing between days 100 and 250, during which an increase in the optical decline rate is also observed. A local origin of the excess is suggested by the depth of the He I 20 581 Å absorption. Steady-state NLTE models with a modest dust opacity in the core (τ = 0.44), turned on during this period, reproduce the observed behaviour, but an additional excess in the Spitzer 4.5 μm band remains. Carbon-monoxide (CO) first-overtone band emission is detected at day 206, and possibly at day 89, and assuming the additional excess to bedominated by CO fundamental band emission, we find fundamental to first-overtone band ratios considerably higher than observed in SN 1987A. The profiles of the [O i] 6300 Å and Mg i] 4571 Å lines show a remarkable similarity, suggesting that these lines originate from a common nuclear burning zone (O/Ne/Mg), and using small scale fluctuations in the line profiles we estimate a filling factor of ≲ 0.07 for the emitting material. This paper concludes our extensive observational and modelling work on SN 2011dh. The results from hydrodynamical modelling, steady-state NLTE modelling, and stellar evolutionary progenitor analysis are all consistent, and suggest an initial mass of ∼12 M<inf>⊙</inf> for the progenitor.

The dust environment of comet 67P/Churyumov-Gerasimenko from Rosetta OSIRIS and VLT observations in the 4.5 to 2.9 au heliocentric distance range inbound

Context. The ESA Rosetta spacecraft, currently orbiting around comet 67P/Churyumov-Gerasimenko, has already provided in situ measurements of the dust grain properties from several instruments,particularly OSIRIS and GIADA. We propose adding value to those measurements by combining them with ground-based observations of the dust tail to monitor the overall, time-dependent dust-production rate and size distribution.
Aims. To constrain the dust grain properties, we take Rosetta OSIRIS and GIADA results into account, and combine OSIRIS data during the approach phase (from late April to early June 2014) with a large data set of ground-based images that were acquired with the ESO Very Large Telescope (VLT) from February to November 2014.
Methods. A Monte Carlo dust tail code, which has already been used to characterise the dust environments of several comets and active asteroids, has been applied to retrieve the dust parameters. Key properties of the grains (density, velocity, and size distribution) were obtained from Rosetta observations: these parameters were used as input of the code to considerably reduce the number of free parameters. In this way, the overall dust mass-loss rate and its dependence on the heliocentric distance could be obtained accurately.
Results. The dust parameters derived from the inner coma measurements by OSIRIS and GIADA and from distant imaging using VLT data are consistent, except for the power index of the size-distribution function, which is α = −3, instead of α = −2, for grains smaller than 1 mm. This is possibly linked to the presence of fluffy aggregates in the coma. The onset of cometary activity occurs at approximately 4.3 AU, with a dust production rate of 0.5 kg/s, increasing up to 15 kg/s at 2.9 AU. This implies a dust-to-gas mass ratio varying between 3.8 and 6.5 for the best-fit model when combined with water-production rates from the MIRO experiment.

Interactions between Siglec-7/9 receptors and ligands influence NK cell-dependent tumor immunosurveillance.

Alteration of the surface glycosylation pattern on malignant cells potentially affects tumor immunity by directly influencing interactions with glycan-binding proteins (lectins) on the surface of immunomodulatory cells. The sialic acid-binding Ig-like lectins Siglec-7 and -9 are MHC class I-independent inhibitory receptors on human NK cells that recognize sialic acid-containing carbohydrates. Here, we found that the presence of Siglec-9 defined a subset of cytotoxic NK cells with a mature phenotype and enhanced chemotactic potential. Interestingly, this Siglec-9+ NK cell population was reduced in the peripheral blood of cancer patients. Broad analysis of primary tumor samples revealed that ligands of Siglec-7 and -9 were expressed on human cancer cells of different histological types. Expression of Siglec-7 and -9 ligands was associated with susceptibility of NK cell-sensitive tumor cells and, unexpectedly, of presumably NK cell-resistant tumor cells to NK cell-mediated cytotoxicity. Together, these observations have direct implications for NK cell-based therapies and highlight the requirement to consider both MHC class I haplotype and tumor-specific glycosylation.

Improving the oral health status of functionally independent and dependent seniors residing in long-term care facilities through dental hygiene education /

The purpose of this study was to evaluate the oral health status of residents residing in 2 long-term care facilities and determine if dental hygiene education was required in order to improve their current oral health. The oral health status of 6 independent and 4 dependent individuals residing in 2 long-term care facilities was evaluated. In addition, the current oral health and disease prevention practices employed by 4 caregivers who were responsible for providing oral care to dependent residents in the long-term care facilities were evaluated. Furthermore, an evaluation of the oral care practices of independent residents who were responsible for providing their own care was conducted. Finally, the challenges that caregivers and independent residents faced when performing oral care were determined, and methodological changes were proposed. Using a generic qualitative research methodology, data collection was comprised of semi structured interviews, field observations, and documentation. The oral health status of the residents was reevaluated 3 months later. The findings of this study demonstrated an increase in plaque accumulation, gingival inflammation, and unhealthy gingival tissue colour changes among the residents over the 3-month period. The study revealed that poor oral health among the residents was a result of inadequate oral hygiene care techniques, difficulties accessing oral health care, financial limitations, insufficient care staff, insufficient time for personal care duties, lack of professional development, minimal interprofessional collaboration of health disciplines, and lack of perseverance on the part of the caregivers and residents. Overall, oral health is essential, and maintaining optimal oral health requires increased collaboration and communication between health care providers.

X-ray diffraction studies of muscle : observations on the anterior byssus retractor muscle of Mytilus edulis and the insect flight muscle from Sarcophaga bullata

The interfilament spacing of the anterior byssus retractor muscle from Mytilus edulis was studied as the muscle was extended. It was found that variations in this spacing were very small and consistent with the hypothesis that the interfilament spacing was independent of the extension of the muscle. It was observed that the interfilament spacing was dependent on the osmolarity of the bathing medium. In concentrated solutions of the artificial seawater, the interfilament spacing decreased; while in dilute solutions of artificial seawater, it was observed that the interfilament spacing was increasing. X-ray diffraction patterns were obtained from fresh, and glutaraldehyde fixed, specimens of insect flight muscle from Sarcophaga bullata. There patterns were in general agreement with previous X-ray diffraction studies of insect flight muscle. A reflexion G at 93A was observed and interpreted as arising from diffraction in the mitochondria. Specimens of dried insect flight muscle produced a diffraction pattern consisting of arc and ring reflexions. This was interpreted as suggesting an ordered arrangement of cristae, in the mitochondria from these muscles.

Size dependent fluorescence spectroscopy of nanocolloids of ZnO

In this article we present size dependent spectroscopic observations of nanocolloids of ZnO. ZnO is reported to show two emission bands, an ultraviolet (UV) emission band and another in the green region. Apart from the known band gap 380 nm and impurity 530 nm emissions, we have found some peculiar features in the fluorescence spectra that are consistent with the nanoparticle size distribution. Results show that additional emissions at 420 and 490 nm are developed with particle size. The origin of the visible band emission is discussed. The mechanism of the luminescence suggests that UV luminescence of ZnO colloid is related to the transition from conduction band edge to valence band, and visible luminescence is caused by the transition from deep donor level to valence band due to oxygen vacancies and by the transition from conduction band to deep acceptor level due to impurities and defect states. A correlation analysis between the particle size and spectroscopic observations is also discussed.

Estimating surface CO2 fluxes from space-borne dry air mole fraction observations using an Ensemble Kalman filter

We have developed an ensemble Kalman Filter (EnKF) to estimate 8-day regional surface fluxes of CO2 from space-borne CO2 dry-air mole fraction observations (XCO2) and evaluate the approach using a series of synthetic experiments, in preparation for data from the NASA Orbiting Carbon Observatory (OCO). The 32-day duty cycle of OCO alternates every 16 days between nadir and glint measurements of backscattered solar radiation at short-wave infrared wavelengths. The EnKF uses an ensemble of states to represent the error covariances to estimate 8-day CO2 surface fluxes over 144 geographical regions. We use a 12×8-day lag window, recognising that XCO2 measurements include surface flux information from prior time windows. The observation operator that relates surface CO2 fluxes to atmospheric distributions of XCO2 includes: a) the GEOS-Chem transport model that relates surface fluxes to global 3-D distributions of CO2 concentrations, which are sampled at the time and location of OCO measurements that are cloud-free and have aerosol optical depths <0.3; and b) scene-dependent averaging kernels that relate the CO2 profiles to XCO2, accounting for differences between nadir and glint measurements, and the associated scene-dependent observation errors. We show that OCO XCO2 measurements significantly reduce the uncertainties of surface CO2 flux estimates. Glint measurements are generally better at constraining ocean CO2 flux estimates. Nadir XCO2 measurements over the terrestrial tropics are sparse throughout the year because of either clouds or smoke. Glint measurements provide the most effective constraint for estimating tropical terrestrial CO2 fluxes by accurately sampling fresh continental outflow over neighbouring oceans. We also present results from sensitivity experiments that investigate how flux estimates change with 1) bias and unbiased errors, 2) alternative duty cycles, 3) measurement density and correlations, 4) the spatial resolution of estimated flux estimates, and 5) reducing the length of the lag window and the size of the ensemble. At the revision stage of this manuscript, the OCO instrument failed to reach its orbit after it was launched on 24 February 2009. The EnKF formulation presented here is also applicable to GOSAT measurements of CO2 and CH4.

Cone model-based SEP event calculations for applications to multipoint observations

The problem of modeling solar energetic particle (SEP) events is important to both space weather research and forecasting, and yet it has seen relatively little progress. Most important SEP events are associated with coronal mass ejections (CMEs) that drive coronal and interplanetary shocks. These shocks can continuously produce accelerated particles from the ambient medium to well beyond 1 AU. This paper describes an effort to model real SEP events using a Center for Integrated Space weather Modeling (CISM) MHD solar wind simulation including a cone model of CMEs to initiate the related shocks. In addition to providing observation-inspired shock geometry and characteristics, this MHD simulation describes the time-dependent observer field line connections to the shock source. As a first approximation, we assume a shock jump-parameterized source strength and spectrum, and that scatter-free transport occurs outside of the shock source, thus emphasizing the role the shock evolution plays in determining the modeled SEP event profile. Three halo CME events on May 12, 1997, November 4, 1997 and December 13, 2006 are used to test the modeling approach. While challenges arise in the identification and characterization of the shocks in the MHD model results, this approach illustrates the importance to SEP event modeling of globally simulating the underlying heliospheric event. The results also suggest the potential utility of such a model for forcasting and for interpretation of separated multipoint measurements such as those expected from the STEREO mission.

Summer drought in northern midlatitudes in a time-dependent CO2 climate experiment

A time-dependent climate-change experiment with a coupled ocean–atmosphere general circulation model has been used to study changes in the occurrence of drought in summer in southern Europe and central North America. In both regions, precipitation and soil moisture are reduced in a climate of greater atmospheric carbon dioxide. A detailed investigation of the hydrology of the model shows that the drying of the soil comes about through an increase in evaporation in winter and spring, caused by higher temperatures and reduced snow cover, and a decrease in the net input of water in summer. Evaporation is reduced in summer because of the drier soil, but the reduction in precipitation is larger. Three extreme statistics are used to define drought, namely the frequency of low summer precipitation, the occurrence of long dry spells, and the probability of dry soil. The last of these is arguably of the greatest practical importance, but since it is based on soil moisture, of which there are very few observations, the authors’ simulation of it has the least confidence. Furthermore, long time series for daily observed precipitation are not readily available from a sufficient number of stations to enable a thorough evaluation of the model simulation, especially for the frequency of long dry spells, and this increases the systematic uncertainty of the model predictions. All three drought statistics show marked increases owing to the sensitivity of extreme statistics to changes in their distributions. However, the greater likelihood of long dry spells is caused by a tendency in the character of daily rainfall toward fewer events, rather than by the reduction in mean precipitation. The results should not be taken as firm predictions because extreme statistics for small regions cannot be calculated reliably from the output of the current generation of GCMs, but they point to the possibility of large increases in the severity of drought conditions as a consequence of climate change caused by increased CO2.

Physically consistent responses of the global atmospheric hydrological cycle in models and observations

Robust and physically understandable responses of the global atmospheric water cycle to a warming climate are presented. By considering interannual responses to changes in surface temperature (T), observations and AMIP5 simulations agree on an increase in column integrated water vapor at the rate 7 %/K (in line with the Clausius­Clapeyron equation) and of precipitation at the rate 2-­3 %/K (in line with energetic constraints). Using simple and complex climate models, we demonstrate that radiative forcing by greenhouse gases is currently suppressing global precipitation (P) at ~ -0.15 %/decade. Along with natural variability, this can explain why observed trends in global P over the period 1988-2008 are close to zero. Regional responses in the global water cycle are strongly constrained by changes in moisture fluxes. Model simulations show an increased moisture flux into the tropical wet region at 900 hPa and an enhanced outflow (of smaller magnitude) at around 600 hPa with warming. Moisture transport explains an increase in P in the wet tropical regions and small or negative changes in the dry regions of the subtropics in CMIP5 simulations of a warming climate. For AMIP5 simulations and satellite observations, the heaviest 5-day rainfall totals increase in intensity at ~15 %/K over the ocean with reductions at all percentiles over land. The climate change response in CMIP5 simulations shows consistent increases in P over ocean and land for the highest intensities, close to the Clausius-Clapeyron scaling of 7 %/K, while P declines for the lowest percentiles, indicating that interannual variability over land may not be a good proxy for climate change. The local changes in precipitation and its extremes are highly dependent upon small shifts in the large-scale atmospheric circulation and regional feedbacks.

Comparison of the open-closed separatrix in a global magnetospheric simulation with observations: the role of the ring current

The development of global magnetospheric models, such as Space Weather Modeling Framework (SWMF), which can accurately reproduce and track space weather processes has high practical utility. We present an interval on 5 June 1998, where the location of the polar cap boundary, or open-closed field line boundary (OCB), can be determined in the ionosphere using a combination of instruments during a period encompassing a sharp northward to southward interplanetary field turning. We present both point- and time-varying comparisons of the observed and simulated boundaries in the ionosphere and find that when using solely the coupled ideal magnetohydrodynamic magnetosphere-ionosphere model, the rate of change of the OCB to a southward turning of the interplanetary field is significantly faster than that computed from the observational data. However, when the inner magnetospheric module is incorporated, the modeling framework both qualitatively, and often quantitatively, reproduces many elements of the studied interval prior to an observed substorm onset. This result demonstrates that the physics of the inner magnetosphere is critical in shaping the boundary between open and closed field lines during periods of southward interplanetary magnetic field (IMF) and provides significant insight into the 3-D time-dependent behavior of the Earth's magnetosphere in response to a northward-southward IMF turning. We assert that during periods that do not include the tens of minutes surrounding substorm expansion phase onset, the coupled SWMF model may provide a valuable and reliable tool for estimating both the OCB and magnetic field topology over a wide range of latitudes and local times.

Incoherent scatter radar observations related to magnetospheric dynamics

Over the past decade incoherent scatter radars have provided fundamental observations of velocities and plasma parameters in the high-latitude ionosphere which relate to the dynamical processes responsible for the excitation of flow in the coupled solar wind-magnetosphere-ionosphere system. These observations have played a central role in inspiring a change of paradigm from a picture of quasi-steady flows parameterised by the direction of the interplanetary magnetic field to a picture of inherently time-dependent flows driven by coupling processes at the magnetopause and in the tail. Flows and particle precipitation in the dayside ionosphere are reasonably well understood in principle in terms of the effects of time-dependent reconnection at the magnetopause, though coordinated high- and low-altitude observations are lacking. Related phenomena also appear to occur in the tail, forming the “equatorward-drifting arcs” which are present during quiet times, as well as during the growth and early expansion phases of substorms. At expansion onset, the substorm bulge forms well equatorward of the arc formation region, and may take ∼ 10 min or more to reach it in its poleward expansion. Nightside ionospheric flows are then considerably perturbed by the effects of strong precipitation-induced conductivity gradients.

A regime-dependent parametrization of subgrid-scale cloud water content variability

The subgrid-scale spatial variability in cloud water content can be described by a parameter f called the fractional standard deviation. This is equal to the standard deviation of the cloud water content divided by the mean. This parameter is an input to schemes that calculate the impact of subgrid-scale cloud inhomogeneity on gridbox-mean radiative fluxes and microphysical process rates. A new regime-dependent parametrization of the spatial variability of cloud water content is derived from CloudSat observations of ice clouds. In addition to the dependencies on horizontal and vertical resolution and cloud fraction included in previous parametrizations, the new parametrization includes an explicit dependence on cloud type. The new parametrization is then implemented in the Global Atmosphere 6 (GA6) configuration of the Met Office Unified Model and used to model the effects of subgrid variability of both ice and liquid water content on radiative fluxes and autoconversion and accretion rates in three 20-year atmosphere-only climate simulations. These simulations show the impact of the new regime-dependent parametrization on diagnostic radiation calculations, interactive radiation calculations and both interactive radiation calculations and in a new warm microphysics scheme. The control simulation uses a globally constant f value of 0.75 to model the effect of cloud water content variability on radiative fluxes. The use of the new regime-dependent parametrization in the model results in a global mean which is higher than the control's fixed value and a global distribution of f which is closer to CloudSat observations. When the new regime-dependent parametrization is used in radiative transfer calculations only, the magnitudes of short-wave and long-wave top of atmosphere cloud radiative forcing are reduced, increasing the existing global mean biases in the control. When also applied in a new warm microphysics scheme, the short-wave global mean bias is reduced.

Media damage following detergent sclerotherapy appears to be secondary to the induction of inflammation and apoptosis: an immunohistochemical study elucidating previous histological observations

Objective/Background: Traditionally, sclerotherapy has been thought to work by the cytotoxic effect of the sclerosant upon the endothelium alone. However, studies have shown that sclerotherapy is more successful in smaller veins than in larger veins. This could be explained by the penetration of the sclerosant, or its effect, into the media. This study aimed to investigate intimal and medial damage profiles after sclerosant treatment. Methods: Fresh human varicose veins were treated ex vivo with either 1% or 3% sodium tetradecyl sulphate (STS) for 1 or 10 minutes. The effect of the sclerosant on the vein wall was investigated by immunofluorescent labelling of transverse vein sections using markers for endothelium (CD31), smooth muscle (a-actin), apoptosis (p53) and inflammation (intercellular adhesion molecule-1 [ICAM-1]). Polidocanol (POL; 3%) treatment at 10 minutes was similarly investigated. Results: Endothelial cell death was concentration- and time-dependent for STS but incomplete for both sclerosants. Time, but not concentration, significantly affected cell death (p > .001). A 40% and 30% maximum reduction was observed for STS and POL, respectively. Destruction of 20e30% of smooth muscle cells was found up to 250 mm from the lumen after 3% STS treatment for 10 minutes. POL treatment for 10 minutes showed inferior destruction of medial cells. Following STS treatment and 24-hour tissue culture, p53 and ICAM-1 were upregulated to a depth of around 300 mm. This effect was not observed with POL. Conclusion: Inflammatory and apoptotic markers show the same distribution as medial cell death, implying that sclerotherapy with STS works by inducing apoptosis in the vein wall rather than having an effect restricted to the endothelium. Incomplete loss of endothelial cells and penetration of the sclerosant effect up to 250 mm into the media suggest that medial damage is crucial to the success of sclerotherapy and may explain why it is less effective in larger veins.