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Early life adversity (ELA) has been associated with inflammation and immunosenescence, as well as hyporeactivity of the HPA axis. Because the immune system and the HPA axis are tightly intertwined around the glucocorticoid receptor (GR), we examined peripheral GR functionality in the EpiPath cohort among participants who either had been exposed to ELA (separation from parents and/or institutionalization followed by adoption; n = 40) or had been reared by their biological parents (n = 72).
Expression of the strict GR target genes FKBP5 and GILZ as well as total and 1F and 1H GR transcripts were similar between groups. Furthermore, there were no differences in GR sensitivity, examined by the effects of dexamethasone on IL6 production in LPS-stimulated whole blood. Although we did not find differences in methylation at the GR 1F exon or promoter region, we identified a region of the GR 1H promoter (CpG 1-9) that showed lower methylation levels in ELA.
Our results suggest that peripheral GR signaling was unperturbed in our cohort and the observed immune phenotype does not appear to be secondary to an altered GR response to the perturbed HPA axis and glucocorticoid (GC) profile, although we are limited in our measures of GR activity and time points.
Background: Spinal muscular atrophy (SMA) is a children’s neuromuscular disorder. Although motor neuron loss is a major feature of the disease, we have identified fatty acid abnormalities in SMA patients and in preclinical animal models, suggesting metabolic perturbation is also an important component of SMA. Methods: Biochemical, histological, proteomic, and high resolution respirometry were used. Results: SMA patients are more susceptible to dyslipidemia than the average population as determined by a standard lipid profile in a cohort of 72 pediatric patients. As well, we observed a non-alcoholic liver disease phenotype in apreclinical mouse model. Denervation alone was not sufficient to induce liver steatosis, as a mouse model of ALS, did not develop fatty liver. Hyperglucagonemia in Smn2B/-mice could explain the hepatic steatosis by increasing plasma substrate availability via glycogen depletion and peripheral lipolysis. Proteomic analysis identified mitochondrion and lipid metabolism as major clusters. Alterations in mitochondrial function were revealed by high-resolution respirometry. Finally, low-fat diets led to increased survival in Smn2B/-mice. Conclusions: These results provide strong evidence for lipid metabolism defects in SMA. Further investigation will be required to establish the primary mechanism of these alterations and understand how they lead to additional co-morbidities in SMA patients.
In 2005 an airborne survey was carried out from a Twin Otter aircraft at Pâkitsup Akuliarusersua (Paakitsoq) near Ilulissat in West Greenland. The survey aimed to measure ice thickness with a 60 MHz coherent radar and surface elevation with a scanning laser altimeter. Positioning information came from multiple on-board differential GPS units and an inertial navigation system. The region surveyed covers >80km along the ice margin and has a total area of ~2700km2 with varying density of measurements: the between-track distance was ~1 km near the margin, increasing to ~3km away from the margin. Regional high-resolution maps of basal topography under the Greenland ice sheet are useful for resolving important glaciological and hydrological questions and for enhancing related process studies, such as the influence of basal meltwater on ice dynamics. The ice-sheet margin in this region is also currently under consideration for hydropower development and has a long and continuing history of glaciological investigations, lately with emphasis on the connection between surface meltwater formation and surface velocity of the ice sheet. Here we present a new regional map of the surface and basal topography of the ice-sheet margin and discuss some of the implications for reported observations at Swiss Camp.
Gaia DR1 was released in September 2016 and contained a photometric catalogue of over 1 billion sources. At this stage, this only included mean G-band photometry and an estimate of the error. Even though this may sound limited in nature, interesting science can still be achieved with this data thanks to its quality. A high level overview of the photometric processing and some validation results will be presented. Additionally, epoch photometry in the G-band was released in Gaia DR1 for a small number of variable sources in the South Ecliptic Pole which covers the LMC. The second data release (Gaia DR2) is currently being prepared and, if available, some preliminary validation results will be presented. It is planned that this release will contain colour information in the form of integrated BP and RP photometry in addition to the latest G-band photometry.
We present a new approach to probe the properties of the most massive, ionizing stars with respect to the less massive, non-ionizing stars. The new technique utilizes stellar-wind lines, instead of the previously employed nebular lines. This allows us to probe the timescale of the dust dispersal in a very young obscured starburst from purely stellar diagnostics.
It is recognised that ageing induces various changes to the human colonic microbiota. Most relevant is a reduction in bifidobacteria, which is a health-positive genus. Prebiotics, such as galacto-oligosaccharides (GOS), are dietary ingredients that selectively fortify beneficial gut microbial groups. Therefore, they have the potential to reverse the age-related decline in bifidobacteria and modulate associated health parameters. We assessed the effect of GOS mixture (Bimuno (B-GOS)) on gut microbiota, markers of immune function and metabolites in forty elderly (age 65–80 years) volunteers in a randomised, double-blind, placebo (maltodextrin)-controlled, cross-over study. The intervention periods consisted of 10 weeks with daily doses of 5·5 g/d with a 4-week washout period in between. Blood and faecal samples were collected for the analyses of faecal bacterial populations and immune and metabolic biomarkers. B-GOS consumption led to significant increases in bacteroides and bifidobacteria, the latter correlating with increased lactic acid in faecal waters. Higher IL-10, IL-8, natural killer cell activity and C-reactive protein and lower IL-1β were also observed. Administration of B-GOS to elderly volunteers may be useful in positively affecting the microbiota and some markers of immune function associated with ageing.
Epidemiological studies have identified increased colorectal cancer (CRC) risk with high red meat (HRM) intakes, whereas dietary fibre intake appears to be protective. In the present study, we examined whether a HRM diet increased rectal O6-methyl-2-deoxyguanosine (O6MeG) adduct levels in healthy human subjects, and whether butyrylated high-amylose maize starch (HAMSB) was protective. A group of twenty-three individuals consumed 300 g/d of cooked red meat without (HRM diet) or with 40 g/d of HAMSB (HRM+HAMSB diet) over 4-week periods separated by a 4-week washout in a randomised cross-over design. Stool and rectal biopsy samples were collected for biochemical, microbial and immunohistochemical analyses at baseline and at the end of each 4-week intervention period. The HRM diet increased rectal O6MeG adducts relative to its baseline by 21 % (P< 0·01), whereas the addition of HAMSB to the HRM diet prevented this increase. Epithelial proliferation increased with both the HRM (P< 0·001) and HRM+HAMSB (P< 0·05) diets when compared with their respective baseline levels, but was lower following the HRM+HAMSB diet compared with the HRM diet (P< 0·05). Relative to its baseline, the HRM+HAMSB diet increased the excretion of SCFA by over 20 % (P< 0·05) and increased the absolute abundances of the Clostridium coccoides group (P< 0·05), the Clostridiumleptum group (P< 0·05), Lactobacillus spp. (P< 0·01), Parabacteroides distasonis (P< 0·001) and Ruminococcus bromii (P< 0·05), but lowered Ruminococcus torques (P< 0·05) and the proportions of Ruminococcus gnavus, Ruminococcus torques and Escherichia coli (P< 0·01). HRM consumption could increase the risk of CRC through increased formation of colorectal epithelial O6MeG adducts. HAMSB consumption prevented red meat-induced adduct formation, which may be associated with increased stool SCFA levels and/or changes in the microbiota composition.
We have obtained high spectral resolution (R ≈ 9000), integral field observations of the three spiral galaxies NGC 3521, NGC 7217 and NGC 7331 using the new fiber-based Integral Field Unit instrument VIRUS-W at the 2.7 m telescope of the McDonald Observatory in Texas. Our data allow us to revisit previous claims of counter rotation in these objects. A detailed kinematic decomposition of NGC 7217 shows that no counter rotating stellar component is present. We find that NGC 7217 hosts a low dispersion, rotating disk that is embedded in a high velocity dispersion stellar halo or bulge that is co-rotating with the disk. Due to the very different velocity dispersions (≈ 20 km s−1 vs. 150 km s−1) , we are further able to perform a Lick index analysis on both components separately which indicates that the two stellar populations are clearly separated in (Mgb,〈Fe〉) space. The velocities and dispersions of the faster component are very similar to those of the interstellar gas as measured from the [O iii] emission. Morphological evidence of active star formation in this component further suggests that NGC 7217 may be in the process of (re)growing a disk inside a more massive and higher dispersion stellar halo.
We aimed to assess cancer risk in congenital heart defect patients, with and without Down's syndrome, compared with the general population.
We identified all patients born and diagnosed with congenital heart defects from 1977 to 2008 using the Danish National Registry of Patients, covering all Danish hospitals. We compared cancer incidence in the congenital heart defect cohort with that expected in the general population (∼5.5 million) using the Danish Cancer Registry, and computed age- and gender-standardised incidence ratios.
We identified 15,905 congenital heart defect patients, contributing a total of 151,172 person-years at risk; the maximum length of follow-up was 31 years (median 8 years). In all, 53 patients were diagnosed with cancer, including 30 female and 23 male patients (standardised incidence ratio = 1.63; 95% confidence interval: 1.22–2.13). Risks were increased for leukaemia, brain tumours, and basal cell carcinoma. After excluding 801 patients with Down's syndrome, the standardised incidence ratio was 1.19 (95% confidence interval: 0.84–1.64). In the subgroup of 5660 non-Down's syndrome patients undergoing cardiac surgery or catheter-based interventions, the standardised incidence ratio was 1.45 (95% confidence interval: 0.86–2.29).
The overall risk of cancer among congenital heart defect patients without Down's syndrome was not statistically significantly elevated. Cancer risk in the congenital heart defect cohort as a whole, including patients with Down's syndrome, was increased compared with the general population, although the absolute risk was low. Studies with longer follow-up and more information on radiation doses are needed to further examine a potential cancer risk associated with diagnostic radiation exposure.
Biodegradable magnetic nanoparticles were synthesized using Poly(L-Lactic Acid) and magnetite nanoparticles (∼14 nm) at different dosages, and then these nanaoparticles (nanocomposites) and pure magnetic particles were targeted in external magnetic fields by changing the test parameters. The magnetic field test results showed that magnetic saturation, fluid speed, magnetic field distance and particle size were extremely effective for a magnetic guidance system that is needed for an effective drug delivery approach. Thus, it is assumed that such nanoparticles can carry drugs (chemotherapy) to be able to cure cancer tumors as well as many other diseases.
Photoemission spectra from HTSC materials ( primarily 123 -type ), cleaved and measured at 20K, reveal a rich DOS structure which compares favorably with a calculated band structure, except for a residual 0.5 eV shift which may reflect some correlation effects. Band dispersion is observed throughout the valence bands, with clear evidence for a 0.2 eV wide band dispersing through EF. The orbital character at EF is a mix of Cu-3d and O-2p. There is unambiguous evidence for a large BCS-like gap (2Δ≥ 4kTc).
We have formed suspended bridges of carbon nanotubes between microcantilevers using electron beam dissociation of metal-organic vapours. By electron beam exposure of a surface in the presence of gold-carbon molecules emitted inside an environmental scanning electron microscope, we are able to form tips and other freestanding nanostructures of high metallic content. Suspended bridges made entirely of this material exhibit resistances less than 50 times that of pure gold, and consist of dense metallic cores surrounded by a crust of nanoparticles. We used standard microfabrication techniques to produce silicon chips with multiple microcantilevers extending over the edge. Individual multiwalled carbon nanotubes grown catalyticcally by chemical vapour deposition, were positioned across two cantilevers using in-situ nanomanipulation tools. Drawing a cross-shaped gold-carbon bond on each end of the carbon nanotube consistently resulted in electrical contact with resistances in the range 1-90 Ω and linear current-voltage characteristics. We found that soldering bonds having a line width down to 10-15 nm form connections and last for days in ambient conditions.
We report the synthesis and sol-gel polymerization of 4-nitro-N,N-bis[(3- triethoxysilyl)propyl]aniline 1. An efficient synthesis of the monomer was developed by the hydrosilylation of N, N-diallyl-4-nitroaniline. Optical quality thin films were synthesized by spin coating an n-butanol solution of 1 using formic acid as catalyst and source of water. We improved the temporal stability of the NLO signal from films prepared from 4-nitro-N,N-bis[(3-triethoxysilyl)propyl]aniline by increasing the intensity of the poling field and extending the heating period during the poling/curing stage. By Maker fringe analysis, a X(2) value of 9 × 10−8 esu was measured for these polysilsesquioxanes. If one assumes that the major component of the NLO effect is along the z-axis, the X(2) value corresponds to a d33 coefficient of 18.9 pm/V and a r33 value of 4.7 pm/V.
Organic chromophores have been exploited for a wide range of discrete optical and electronic functions as well as a growing number of combined opto-electronic functions. We are pursuing development of organic and polymer materials for a range of applications that require properties including liquid crystallinity, second order optical nonlinearity, photorefractivity and, more recently, special nonlinear optical behavior involving molecular chirality.
Layer-by-layer molecular self-assembly of nanosized magnetite (Fe3O4) particles and polyimide precursor molecules into multilayer ultrathin films has been accomplished on single crystal silicon and quartz substrates. This process involves the alternate dipping of a substrate into an aqueous solution of cationic polymer which coats on nanoscale Fe3O4 particles as a stabilizer followed by dipping into an aqueous solution of anionie polyimide precursor (polyamic acid salt, PAATEA). The growth process and the structure have been characterized using UV-vis spectroscopy, FT-IR, and scanning electron microscopy. The results demonstrate that well-ordered uniform monolayer and multilayer magnetic films have been formed on silicon and silica surfaces.
This contribution describes the use of self-limiting siloxane chemisoroption processes to self-assemble building blocks for the modification of vacuum-deposited organic LED (OLED) devices. One approach consists of the use of self-assembling OLED hole transport materials for application in hybrid self-assembled + vapor deposited two-layer devices. Another approach involves the application of self-limiting, chemisorptive self-assembly techniques to introduce thin dielectric films between the anode and hole transport layer of a vapor deposited two-layer OLED device.
We study the photovoltaic response of inorganic/organic composite devices containing the conjugated polymer, MEH-PPV, and a semi-transparent layer of titanium dioxide (TiO2) nanoparticles, which is similar to that employed in the Grätzel photoelectrochemical cell. Comparison of the photovoltage obtainable under illumination with either a Au, Ag, Al or Ca back electrode suggests that the built in potential is determined largely by the difference between the quasi Fermi level of the TiO2 under illumination and the work function of the back electrode. A qualitative model for charge generation and transport through the device is presented.
New combined main- and side-chain azobenzene polyesters, which exhibit an intensity dependent refractive index, have been prepared in order to optically fabricate nonlinear waveguides. Novel sulfone azobenzenes, a diester, (4-[[5-(ethoxycarbonyl)pentyl]sulfonyl]-4'-[[5-(ethoxycarbonyl)pentyl]methylamino] azobenzene, and a diol, 4-[[(8-hydroxy-7-methylhydroxy)-octyl]sulfonyl]-4'-N, N-dimethylamino azobenzene, have been used to prepare new polyesters by transesterification in the molten state. The polyesters have been characterized by UV-visible spectroscopy, differential scanning calorimetry (DSC), size exclusion chromatography (SEC), third harmonic generation (THG) and optical anisotropy measurements. The molar masses of the polyesters were in the range of 5000-10000 g mol−1, which was sufficient in order to spin coat thin films. From THG measurements the polymers are shown to possess an offresonance electronic X(3) of the order 10−12 esu corresponding to a nonlinear refractive index of 2.3×10−14 cm2/W.