4,314 research outputs found
Pulmonary ORMDL3 is critical for induction of Alternaria -induced allergic airways disease
Genome-wide association studies have identified the ORM (yeast)-like protein isoform 3 (ORMDL3) gene locus on human chromosome 17q to be a highly significant risk factor for childhood-onset asthma.
Objective
We sought to investigate in vivo the functional role of ORMDL3 in disease inception.
Methods
An Ormdl3-deficient mouse was generated and the role of ORMDL3 in the generation of allergic airways disease to the fungal aeroallergen Alternaria alternata was determined. An adeno-associated viral vector was also used to reconstitute ORMDL3 expression in airway epithelial cells of Ormdl3 knockout mice.
Results
Ormdl3 knockout mice were found to be protected from developing allergic airways disease and showed a marked decrease in pathophysiology, including lung function and airway eosinophilia induced by Alternaria. Alternaria is a potent inducer of cellular stress and the unfolded protein response, and ORMDL3 was found to play a critical role in driving the activating transcription factor 6âmediated arm of this response through Xbp1 and downstream activation of the endoplasmic reticulumâassociated degradation pathway. In addition, ORMDL3 mediated uric acid release, another marker of cellular stress. In the knockout mice, reconstitution of Ormdl3 transcript levels specifically in the bronchial epithelium resulted in reinstatement of susceptibility to fungal allergenâinduced allergic airways disease.
Conclusions
This study demonstrates that ORMDL3, an asthma susceptibility gene identified by genome-wide association studies, contributes to key pathways that promote changes in airway physiology during allergic immune responses
DECam integration tests on telescope simulator
The Dark Energy Survey (DES) is a next generation optical survey aimed at
measuring the expansion history of the universe using four probes: weak
gravitational lensing, galaxy cluster counts, baryon acoustic oscillations, and
Type Ia supernovae. To perform the survey, the DES Collaboration is building
the Dark Energy Camera (DECam), a 3 square degree, 570 Megapixel CCD camera
which will be mounted at the Blanco 4-meter telescope at the Cerro Tololo
Inter- American Observatory. DES will survey 5000 square degrees of the
southern galactic cap in 5 filters (g, r, i, z, Y). DECam will be comprised of
74 250 micron thick fully depleted CCDs: 62 2k x 4k CCDs for imaging and 12 2k
x 2k CCDs for guiding and focus. Construction of DECam is nearing completion.
In order to verify that the camera meets technical specifications for DES and
to reduce the time required to commission the instrument, we have constructed a
full sized telescope simulator and performed full system testing and
integration prior to shipping. To complete this comprehensive test phase we
have simulated a DES observing run in which we have collected 4 nights worth of
data. We report on the results of these unique tests performed for the DECam
and its impact on the experiments progress.Comment: Proceedings of the 2nd International Conference on Technology and
Instrumentation in Particle Physics (TIPP 2011). To appear in Physics
Procedia. 8 pages, 3 figure
Female bone physiology resilience in a past Polynesian Outlier community
Remodelling is a fundamental biological process involved in the maintenance of bone physiology and function. We know that a range of health and lifestyle factors can impact this process in living and past societies, but there is a notable gap in bone remodelling data for populations from the Pacific Islands. We conducted the first examination of femoral cortical histology in 69 individuals from ca. 440â150Â BP Taumako in Solomon Islands, a remote âPolynesian Outlierâ island in Melanesia. We tested whether bone remodelling indicators differed between age groups, and biological sex validated using ancient DNA. Bone vascular canal and osteon size, vascular porosity, and localised osteon densities, corrected by femoral robusticity indices were examined. Females had statistically significantly higher vascular porosities when compared to males, but osteon densities and ratios of canal-osteon (~â8%) did not differ between the sexes. Our results indicate that, compared to males, localised femoral bone tissue of the Taumako females did not drastically decline with age, contrary to what is often observed in modern populations. However, our results match findings in other archaeological samplesâa testament to past female bone physiology resilience, also now observed in the Pacific region.Introduction - Bone remodelling through human lifeâcourse. - Bone remodelling in archaeological humans. Results - Femoral vascular porosity and bone remodelling indicators at Taumako. Discussion - Sex and cortical bone histology at Taumako. - The effect of age on bone histology at Taumako. Remarks on temporal and spatial bone histology data Limitations Conclusions Materials and method
Female bone physiology resilience in 750-300 BP âPolynesian Outlierâ community
Remodelling is a fundamental biological process involved in the maintenance of bone physiology and function. We know that a range of health and lifestyle factors can impact this process in living and past societies, but there is a notable gap in bone remodelling data for populations from the Pacific Islands. We conducted the first examination of femoral cortical histology in n = 69 individuals from 750 â 300 BP Taumako in Solomon Islands, a remote âPolynesian Outlierâ island in Melanesia. We tested whether bone remodelling indicators differed between age-at-death groups, and biological sex validated using ancient DNA. Bone vascular canal and osteon size, vascular porosity, and localised osteon densities, corrected by femoral robusticity indices were examined. Females had statistically significantly higher vascular porosities when compared to males, but osteon densities and ratios of canal-to-osteon (~10%) did not differ between the sexes. Compared to males, the femora of Taumako females experienced higher frequencies of remodelling events, which mirrors bone health paradigms through the life-course today. However, contrary to modern populations, female femoral bone tissue did not decline with age. This matches findings in other archaeological samples, and is testament to ancient female bone physiology resilience also in the Pacific region.Introduction - The importance of bone remodelling through human life-course - Bone remodelling in archaeological humans Results - Trends in bone remodelling at Taumako Discussion - Sex-specific trends in cortical bone remodelling - Bone remodelling with age at Taumako Limitations and remarks on temporal and spatial data Conslusions Materials and Method
The FirstMurchisonWidefield Array low-frequency radio observations of cluster scale non-thermal emission: the case of Abell 3667
We present the first Murchison Widefield Array observations of the well-known cluster of galaxies Abell 3667 (A3667) between 105 and 241 MHz. A3667 is one of the best known examples of a galaxy cluster hosting a double radio relic and has been reported to contain a faint radio halo and bridge. The origin of radio haloes, relics and bridges is still unclear, however galaxy cluster merger seems to be an important factor. We clearly detect the north-west (NW) and south-east radio relics in A3667 and find an integrated flux density at 149MHz of 28.1 ± 1.7 and 2.4 ± 0.1 Jy, respectively, with an average spectral index, between 120 and 1400 MHz, of -0.9 ± 0.1 for both relics. We find evidence of a spatial variation in the spectral index across the NW relic steepening towards the centre of the cluster, which indicates an ageing electron population. These properties are consistent with higher frequency observations. We detect emission that could be associated with a radio halo and bridge. However, due to the presence of poorly sampled large-scale Galactic emission and blended point sources we are unable to verify the exact nature of these features
A First Search for Cosmogenic Neutrinos with the ARIANNA Hexagonal Radio Array
The ARIANNA experiment seeks to observe the diffuse flux of neutrinos in the
10^8 - 10^10 GeV energy range using a grid of radio detectors at the surface of
the Ross Ice Shelf of Antarctica. The detector measures the coherent Cherenkov
radiation produced at radio frequencies, from about 100 MHz to 1 GHz, by
charged particle showers generated by neutrino interactions in the ice. The
ARIANNA Hexagonal Radio Array (HRA) is being constructed as a prototype for the
full array. During the 2013-14 austral summer, three HRA stations collected
radio data which was wirelessly transmitted off site in nearly real-time. The
performance of these stations is described and a simple analysis to search for
neutrino signals is presented. The analysis employs a set of three cuts that
reject background triggers while preserving 90% of simulated cosmogenic
neutrino triggers. No neutrino candidates are found in the data and a
model-independent 90% confidence level Neyman upper limit is placed on the all
flavor neutrino+antineutrino flux in a sliding decade-wide energy bin. The
limit reaches a minimum of 1.9x10^-23 GeV^-1 cm^-2 s^-1 sr^-1 in the 10^8.5 -
10^9.5 GeV energy bin. Simulations of the performance of the full detector are
also described. The sensitivity of the full ARIANNA experiment is presented and
compared with current neutrino flux models.Comment: 22 pages, 22 figures. Published in Astroparticle Physic
A Multi-wavelength View of the TeV Blazar Markarian 421: Correlated Variability, Flaring, and Spectral Evolution
We report results from a multi-wavelength monitoring campaign on Mrk 421 over
the period of 2003-2004. The source was observed simultaneously at TeV and
X-ray energies, with supporting observations frequently carried out at optical
and radio wavelengths. The large amount of simultaneous data has allowed us to
examine the variability of Mrk 421 in detail. The variabilities are generally
correlated between the X-ray and gamma-ray bands, although the correlation
appears to be fairly loose. The light curves show the presence of flares with
varying amplitudes on a wide range of timescales both at X-ray and TeV
energies. Of particular interest is the presence of TeV flares that have no
coincident counterparts at longer wavelengths, because the phenomenon seems
difficult to understand in the context of the proposed emission models for TeV
blazars. We have also found that the TeV flux reached its peak days before the
X-ray flux during a giant flare in 2004. Such a difference in the development
of the flare presents a further challenge to the emission models. Mrk 421
varied much less at optical and radio wavelengths. Surprisingly, the normalized
variability amplitude in optical seems to be comparable to that in radio,
perhaps suggesting the presence of different populations of emitting electrons
in the jet. The spectral energy distribution (SED) of Mrk 421 is seen to vary
with flux, with the two characteristic peaks moving toward higher energies at
higher fluxes. We have failed to fit the measured SEDs with a one-zone SSC
model; introducing additional zones greatly improves the fits. We have derived
constraints on the physical properties of the X-ray/gamma-ray flaring regions
from the observed variability (and SED) of the source. The implications of the
results are discussed. (Abridged)Comment: 32 pages, 12 figures, to appear in Ap
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