297 research outputs found
In Silico Analysis of Putative Paralytic Shellfish Poisoning Toxins Export Proteins in Cyanobacteria
Lopez-Cortes, XA (Lopez-Cortes, Xaviera A.) Univ Talca, Nanobiotechnol Div, Fraunhofer Chile Res Fdn, Ctr Syst Biotechnol, Talca, Chile.Paralytic shellfish poisoning toxins (PSTs) are a family of more than 30 natural alkaloids synthesized by dinoflagellates and cyanobacteria whose toxicity in animals is mediated by voltage-gated Na+ channel blocking. The export of PST analogues may be through SxtF and SxtM, two putative MATE (multidrug and toxic compound extrusion) family transporters encoded in PSTs biosynthetic gene cluster (sxt). sxtM is present in every sxt cluster analyzed; however, sxtF is only present in the Cylindrospermopsis-Raphidiopsis clade. These transporters are energetically coupled with an electrochemical gradient of proton (H+) or sodium (Na+) ions across membranes. Because the functional role of PSTs remains unknown and methods for genetic manipulation in PST-producing organisms have not yet been developed, protein structure analyses will allow us to understand their function. By analyzing the sxt cluster of eight PST-producing cyanobacteria, we found no correlation between the presence of sxtF or sxtM and a specific PSTs profile. Phylogenetic analyses of SxtF/M showed a high conservation of SxtF in the Cylindrospermopsis-Raphidiopsis clade, suggesting conserved substrate affinity. Two domains involved in Na+ and drug recognition from NorM proteins (MATE family) of Vibrio parahaemolyticus and V. cholerae are present in SxtF/M. The Na+ recognition domain was conserved in both SxtF/M, indicating that Na+ can maintain the role as a cation anti-transporter. Consensus motifs for toxin binding differed between SxtF and SxtM implying differential substrate binding. Through protein modeling and docking analysis, we found that there is no marked affinity between the recognition domain and a specific PST analogue. This agrees with our previous results of PST export in R. brookii D9, where we observed that the response to Na+ incubation was similar to different analogues. These results reassert the hypothesis regarding the involvement of Na+ in toxin export, as well as the motifs L(398)XGLQD(403) (SxtM) and L(390)VGLRD(395) (SxtF) in toxin recognition
Fitting the integrated Spectral Energy Distributions of Galaxies
Fitting the spectral energy distributions (SEDs) of galaxies is an almost
universally used technique that has matured significantly in the last decade.
Model predictions and fitting procedures have improved significantly over this
time, attempting to keep up with the vastly increased volume and quality of
available data. We review here the field of SED fitting, describing the
modelling of ultraviolet to infrared galaxy SEDs, the creation of
multiwavelength data sets, and the methods used to fit model SEDs to observed
galaxy data sets. We touch upon the achievements and challenges in the major
ingredients of SED fitting, with a special emphasis on describing the interplay
between the quality of the available data, the quality of the available models,
and the best fitting technique to use in order to obtain a realistic
measurement as well as realistic uncertainties. We conclude that SED fitting
can be used effectively to derive a range of physical properties of galaxies,
such as redshift, stellar masses, star formation rates, dust masses, and
metallicities, with care taken not to over-interpret the available data. Yet
there still exist many issues such as estimating the age of the oldest stars in
a galaxy, finer details ofdust properties and dust-star geometry, and the
influences of poorly understood, luminous stellar types and phases. The
challenge for the coming years will be to improve both the models and the
observational data sets to resolve these uncertainties. The present review will
be made available on an interactive, moderated web page (sedfitting.org), where
the community can access and change the text. The intention is to expand the
text and keep it up to date over the coming years.Comment: 54 pages, 26 figures, Accepted for publication in Astrophysics &
Space Scienc
Common variations in estrogen-related genes are associated with severe large-joint osteoarthritis: a multicenter genetic and functional study
OBJECTIVE:
Several lines of evidence suggest that estrogens influence the development of osteoarthritis (OA). The aim of this study was to explore the association of two common polymorphisms within the aromatase (CYP19A1) and estrogen receptor (ER) alpha (ESR1) genes with severe OA of the lower limbs.
METHODS:
The rs1062033 (CYP19A1) and rs2234693 (ESR1) single nucleotide polymorphisms were genotyped in 5528 individuals (3147 patients with severe hip or knee OA, and 2381 controls) from four centres in Spain and the United Kingdom. Gene expression was measured in femoral bone samples from a group of patients.
RESULTS:
In the global analysis, both polymorphisms were associated with OA, but there was a significant sex interaction. The GG genotype at rs1062033 was associated with an increased risk of knee OA in women [odds ratio (OR) 1.23; P=0.04]. The CC genotype at rs2234693 tended to be associated with reduced OA risk in women (OR 0.76, P=0.028, for knee OA; OR=0.84, P=0.076 for hip OA), but with increased risk of hip OA in men (OR 1.28; P=0.029). Women with unfavourable genotypes at both loci had an OR of 1.61 for knee OA (P=0.006). The rs1062033 genotype associated with higher OA risk was also associated with reduced expression of the aromatase gene in bone.
CONCLUSIONS:
Common genetic variations of the aromatase and ER genes are associated with the risk of severe OA of the large joints of the lower limb in a sex-specific manner. These results are consistent with the hypothesis that estrogen activity may influence the development of large-joint OA
Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter
Data collected by the Pierre Auger Observatory through 31 August 2007 showed
evidence for anisotropy in the arrival directions of cosmic rays above the
Greisen-Zatsepin-Kuz'min energy threshold, \nobreak{eV}. The
anisotropy was measured by the fraction of arrival directions that are less
than from the position of an active galactic nucleus within 75 Mpc
(using the V\'eron-Cetty and V\'eron catalog). An updated
measurement of this fraction is reported here using the arrival directions of
cosmic rays recorded above the same energy threshold through 31 December 2009.
The number of arrival directions has increased from 27 to 69, allowing a more
precise measurement. The correlating fraction is , compared
with expected for isotropic cosmic rays. This is down from the early
estimate of . The enlarged set of arrival directions is
examined also in relation to other populations of nearby extragalactic objects:
galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in
hard X-rays by the Swift Burst Alert Telescope. A celestial region around the
position of the radiogalaxy Cen A has the largest excess of arrival directions
relative to isotropic expectations. The 2-point autocorrelation function is
shown for the enlarged set of arrival directions and compared to the isotropic
expectation.Comment: Accepted for publication in Astroparticle Physics on 31 August 201
Search for First Harmonic Modulation in the Right Ascension Distribution of Cosmic Rays Detected at the Pierre Auger Observatory
We present the results of searches for dipolar-type anisotropies in different
energy ranges above eV with the surface detector array of
the Pierre Auger Observatory, reporting on both the phase and the amplitude
measurements of the first harmonic modulation in the right-ascension
distribution. Upper limits on the amplitudes are obtained, which provide the
most stringent bounds at present, being below 2% at 99% for EeV
energies. We also compare our results to those of previous experiments as well
as with some theoretical expectations.Comment: 28 pages, 11 figure
The BRIDGE HadCM3 family of climate models: HadCM3@Bristol v1.0
Understanding natural and anthropogenic climate change processes involves using computational models that represent the main components of the Earth system: the atmosphere, ocean, sea ice, and land surface. These models have become increasingly computationally expensive as resolution is increased and more complex process representations are included. However, to gain robust insight into how climate may respond to a given forcing, and to meaningfully quantify the associated uncertainty, it is often required to use either or both ensemble approaches and very long integrations. For this reason, more computationally efficient models can be very valuable tools. Here we provide a comprehensive overview of the suite of climate models based around the HadCM3 coupled general circulation model. This model was developed at the UK Met Office and has been heavily used during the last 15 years for a range of future (and past) climate change studies, but has now been largely superseded for many scientific studies by more recently developed models. However, it continues to be extensively used by various institutions, including the BRIDGE (Bristol Research Initiative for the Dynamic Global Environment) research group at the University of Bristol, who have made modest adaptations to the base HadCM3 model over time. These adaptations mean that the original documentation is not entirely representative, and several other relatively undocumented configurations are in use. We therefore describe the key features of a number of configurations of the HadCM3 climate model family, which together make up HadCM3@Bristol version 1.0. In order to differentiate variants that have undergone development at BRIDGE, we have introduced the letter B into the model nomenclature. We include descriptions of the atmosphere- only model (HadAM3B), the coupled model with a low-resolution ocean (HadCM3BL), the high-resolution atmosphere- only model (HadAM3BH), and the regional model (HadRM3B). These also include three versions of the land surface scheme. By comparing with observational datasets, we show that these models produce a good representation of many aspects of the climate system, including the land and sea surface temperatures, precipitation, ocean circulation, and vegetation. This evaluation, combined with the relatively fast computational speed (up to 1000 times faster than some CMIP6 models), motivates continued development and scientific use of the HadCM3B family of coupled climate models, predominantly for quantifying uncertainty and for long multi-millennial-scale simulations
Identification of new susceptibility loci for osteoarthritis (arcOGEN):a genome-wide association study
To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Osteoarthritis is the most common form of arthritis worldwide and is a major cause of pain and disability in elderly people. The health economic burden of osteoarthritis is increasing commensurate with obesity prevalence and longevity. Osteoarthritis has a strong genetic component but the success of previous genetic studies has been restricted due to insufficient sample sizes and phenotype heterogeneity. We undertook a large genome-wide association study (GWAS) in 7410 unrelated and retrospectively and prospectively selected patients with severe osteoarthritis in the arcOGEN study, 80% of whom had undergone total joint replacement, and 11,009 unrelated controls from the UK. We replicated the most promising signals in an independent set of up to 7473 cases and 42,938 controls, from studies in Iceland, Estonia, the Netherlands, and the UK. All patients and controls were of European descent. We identified five genome-wide significant loci (binomial test pâ€5·0Ă10(-8)) for association with osteoarthritis and three loci just below this threshold. The strongest association was on chromosome 3 with rs6976 (odds ratio 1·12 [95% CI 1·08-1·16]; p=7·24Ă10(-11)), which is in perfect linkage disequilibrium with rs11177. This SNP encodes a missense polymorphism within the nucleostemin-encoding gene GNL3. Levels of nucleostemin were raised in chondrocytes from patients with osteoarthritis in functional studies. Other significant loci were on chromosome 9 close to ASTN2, chromosome 6 between FILIP1 and SENP6, chromosome 12 close to KLHDC5 and PTHLH, and in another region of chromosome 12 close to CHST11. One of the signals close to genome-wide significance was within the FTO gene, which is involved in regulation of bodyweight-a strong risk factor for osteoarthritis. All risk variants were common in frequency and exerted small effects. Our findings provide insight into the genetics of arthritis and identify new pathways that might be amenable to future therapeutic intervention.Arthritis Research UK
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On the sensitivity of the HAWC observatory to gamma-ray bursts
We present the sensitivity of HAWC to Gamma Ray Bursts (GRBs). HAWC is a very
high-energy gamma-ray observatory currently under construction in Mexico at an
altitude of 4100 m. It will observe atmospheric air showers via the water
Cherenkov method. HAWC will consist of 300 large water tanks instrumented with
4 photomultipliers each. HAWC has two data acquisition (DAQ) systems. The main
DAQ system reads out coincident signals in the tanks and reconstructs the
direction and energy of individual atmospheric showers. The scaler DAQ counts
the hits in each photomultiplier tube (PMT) in the detector and searches for a
statistical excess over the noise of all PMTs. We show that HAWC has a
realistic opportunity to observe the high-energy power law components of GRBs
that extend at least up to 30 GeV, as it has been observed by Fermi LAT. The
two DAQ systems have an energy threshold that is low enough to observe events
similar to GRB 090510 and GRB 090902b with the characteristics observed by
Fermi LAT. HAWC will provide information about the high-energy spectra of GRBs
which in turn could help to understanding about e-pair attenuation in GRB jets,
extragalactic background light absorption, as well as establishing the highest
energy to which GRBs accelerate particles
The rapid atmospheric monitoring system of the Pierre Auger Observatory
The Pierre Auger Observatory is a facility built to detect air showers produced by cosmic rays above 10(17) eV. During clear nights with a low illuminated moon fraction, the UV fluorescence light produced by air showers is recorded by optical telescopes at the Observatory. To correct the observations for variations in atmospheric conditions, atmospheric monitoring is performed at regular intervals ranging from several minutes (for cloud identification) to several hours (for aerosol conditions) to several days (for vertical profiles of temperature, pressure, and humidity). In 2009, the monitoring program was upgraded to allow for additional targeted measurements of atmospheric conditions shortly after the detection of air showers of special interest, e. g., showers produced by very high-energy cosmic rays or showers with atypical longitudinal profiles. The former events are of particular importance for the determination of the energy scale of the Observatory, and the latter are characteristic of unusual air shower physics or exotic primary particle types. The purpose of targeted (or 'rapid') monitoring is to improve the resolution of the atmospheric measurements for such events. In this paper, we report on the implementation of the rapid monitoring program and its current status. The rapid monitoring data have been analyzed and applied to the reconstruction of air showers of high interest, and indicate that the air fluorescence measurements affected by clouds and aerosols are effectively corrected using measurements from the regular atmospheric monitoring program. We find that the rapid monitoring program has potential for supporting dedicated physics analyses beyond the standard event reconstruction
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