456 research outputs found
Robust Weak-lensing Mass Calibration of Planck Galaxy Clusters
In light of the tension in cosmological constraints reported by the Planck
team between their SZ-selected cluster counts and Cosmic Microwave Background
(CMB) temperature anisotropies, we compare the Planck cluster mass estimates
with robust, weak-lensing mass measurements from the Weighing the Giants (WtG)
project. For the 22 clusters in common between the Planck cosmology sample and
WtG, we find an overall mass ratio of \left =
0.688 \pm 0.072. Extending the sample to clusters not used in the Planck
cosmology analysis yields a consistent value of from 38 clusters in common. Identifying the
weak-lensing masses as proxies for the true cluster mass (on average), these
ratios are lower than the default mass bias of 0.8 assumed in
the Planck cluster analysis. Adopting the WtG weak-lensing-based mass
calibration would substantially reduce the tension found between the Planck
cluster count cosmology results and those from CMB temperature anisotropies,
thereby dispensing of the need for "new physics" such as uncomfortably large
neutrino masses (in the context of the measured Planck temperature anisotropies
and other data). We also find modest evidence (at 95 per cent confidence) for a
mass dependence of the calibration ratio and discuss its potential origin in
light of systematic uncertainties in the temperature calibration of the X-ray
measurements used to calibrate the Planck cluster masses. Our results exemplify
the critical role that robust absolute mass calibration plays in cluster
cosmology, and the invaluable role of accurate weak-lensing mass measurements
in this regard.Comment: 5 pages, 2 figure
Absence of gemin5 from SMN complexes in nuclear Cajal bodies
<p>Abstract</p> <p>Background</p> <p>Spinal muscular atrophy is caused by reduced levels of the survival of motor neurons (SMN) protein. SMN is found in large complexes with Sm proteins and at least eight other proteins, including seven "gemins". These complexes are involved in the assembly of snRNPs in the cytoplasm and their transport into the nucleus, but the precise roles of the individual protein components are largely unknown.</p> <p>Results</p> <p>We have investigated the subcellular distribution of gemins using novel antibodies against gemins 3–7, and existing mAbs against SMN, gemin2, unrip, fibrillarin and profilin II. Most gemins were equally distributed between nuclear and cytoplasmic fractions of HeLa cells, but gemin5 and unrip were more abundant in the cytoplasm. In a cytoplasmic extract obtained by mild disruption of HeLa cells, nearly all the SMN and gemins 2–4 were in large complexes, but most of the gemin5 sedimented separately with a lower S value. Most of the unrip sedimented with gemins 6 and 7 near the top of the sucrose density gradients, separate from both SMN and gemin5. Anti-SMN mAbs pulled down gemin5 from cytoplasmic extracts, but not from nuclear extracts, and gemin5 did not co-sediment with large SMN complexes in nuclear extracts. These data suggest that gemin5 is easily detached from SMN-gemin complexes in the nucleus. By immuno-histochemistry, gemin5 was rarely detectable in nuclear gems/Cajal bodies, although it was accessible to antibody and easily detectable when present. This suggests that gemin5 is normally absent from SMN complexes in these nuclear storage sites.</p> <p>Conclusion</p> <p>We conclude that SMN complexes usually exist without gemin5 in nuclear gems/Cajal bodies. Gemin5 is believed to be involved in capturing snRNA into SMN complexes in the cytoplasm for transport into the nucleus. We hypothesize that gemin5, though present in the nucleus, is no longer needed for SMN complex function during the time these complexes are stored in gems/Cajal bodies.</p
Novel nesprin-1 mutations associated with dilated cardiomyopathy cause nuclear envelope disruption and defects in myogenesis
Nesprins-1 and -2 are highly expressed in skeletal and cardiac muscle and together with SUN (Sad1p/UNC84)-domain containing proteins and lamin A/C form the LInker of Nucleoskeleton-and-Cytoskeleton (LINC) bridging complex at the nuclear envelope (NE). Mutations in nesprin-1/2 have previously been found in patients with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD) as well as dilated cardiomyopathy (DCM). In this study, three novel rare variants (R8272Q, S8381C and N8406K) in the C-terminus of the SYNE1 gene (nesprin-1) were identified in seven DCM patients by mutation screening. Expression of these mutants caused nuclear morphology defects and reduced lamin A/C and SUN2 staining at the NE. GST pull-down indicated that nesprin-1/lamin/SUN interactions were disrupted. Nesprin-1 mutations were also associated with augmented activation of the ERK pathway in vitro and in hearts in vivo. During C2C12 muscle cell differentiation, nesprin-1 levels are increased concomitantly with kinesin light chain (KLC-1/2) and immunoprecipitation and GST pull-down showed that these proteins interacted via a recently identified LEWD domain in the C-terminus of nesprin-1. Expression of nesprin-1 mutants in C2C12 cells caused defects in myoblast differentiation and fusion associated with dysregulation of myogenic transcription factors and disruption of the nesprin-1 and KLC-1/2 interaction at the outer nuclear membrane. Expression of nesprin-1α2 WT and mutants in zebrafish embryos caused heart developmental and conduction defects that varied in severity. These findings support a role for nesprin-1 in myogenesis and muscle disease, and uncover a novel mechanism whereby disruption of the LINC complex may contribute to the pathogenesis of DCM
Weighing the Giants - I. Weak-lensing masses for 51 massive galaxy clusters: project overview, data analysis methods and cluster images
This is the first in a series of papers in which we measure accurate
weak-lensing masses for 51 of the most X-ray luminous galaxy clusters known at
redshifts 0.15<z<0.7, in order to calibrate X-ray and other mass proxies for
cosmological cluster experiments. The primary aim is to improve the absolute
mass calibration of cluster observables, currently the dominant systematic
uncertainty for cluster count experiments. Key elements of this work are the
rigorous quantification of systematic uncertainties, high-quality data
reduction and photometric calibration, and the "blind" nature of the analysis
to avoid confirmation bias. Our target clusters are drawn from RASS X-ray
catalogs, and provide a versatile calibration sample for many aspects of
cluster cosmology. We have acquired wide-field, high-quality imaging using the
Subaru and CFHT telescopes for all 51 clusters, in at least three bands per
cluster. For a subset of 27 clusters, we have data in at least five bands,
allowing accurate photo-z estimates of lensed galaxies. In this paper, we
describe the cluster sample and observations, and detail the processing of the
SuprimeCam data to yield high-quality images suitable for robust weak-lensing
shape measurements and precision photometry. For each cluster, we present
wide-field color optical images and maps of the weak-lensing mass distribution,
the optical light distribution, and the X-ray emission, providing insights into
the large-scale structure in which the clusters are embedded. We measure the
offsets between X-ray centroids and Brightest Cluster Galaxies in the clusters,
finding these to be small in general, with a median of 20kpc. For offsets
<100kpc, weak-lensing mass measurements centered on the BCGs agree well with
values determined relative to the X-ray centroids; miscentering is therefore
not a significant source of systematic uncertainty for our mass measurements.
[abridged]Comment: 26 pages, 19 figures (Appendix C not included). Accepted after minor
revisio
Limits on the adaptability of coastal marshes to rising sea level
Assumptions of a static landscape inspire predictions that about half of the world's coastal wetlands will submerge during this century in response to sea-level acceleration. In contrast, we use simulations from five numerical models to quantify the conditions under which ecogeomorphic feedbacks allow coastal wetlands to adapt to projected changes in sea level. In contrast to previous sea-level assessments, we find that non-linear feedbacks among inundation, plant growth, organic matter accretion, and sediment deposition, allow marshes to survive conservative projections of sea-level rise where suspended sediment concentrations are greater than similar to 20 mg/L. Under scenarios of more rapid sea-level rise (e. g., those that include ice sheet melting), marshes will likely submerge near the end of the 21st century. Our results emphasize that in areas of rapid geomorphic change, predicting the response of ecosystems to climate change requires consideration of the ability of biological processes tomodify their physical environment
An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics
For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types
Genetic analysis of the capsule polysaccharide (K antigen) and exopolysaccharide genes in pandemic Vibrio parahaemolyticus O3:K6
<p>Abstract</p> <p>Background</p> <p>Pandemic <it>Vibrio parahaemolyticus </it>has undergone rapid changes in both K- and O-antigens, making detection of outbreaks more difficult. In order to understand these rapid changes, the genetic regions encoding these antigens must be examined. In <it>Vibrio cholerae </it>and <it>Vibrio vulnificus</it>, both O-antigen and capsular polysaccharides are encoded in a single region on the large chromosome; a similar arrangement in pandemic <it>V. parahaemolyticus </it>would help explain the rapid serotype changes. However, previous reports on "capsule" genes are controversial. Therefore, we set out to clarify and characterize these regions in pandemic <it>V. parahaemolyticus </it>O3:K6 by gene deletion using a chitin based transformation strategy.</p> <p>Results</p> <p>We generated different deletion mutants of putative polysaccharide genes and examined the mutants by immuno-blots with O and K specific antisera. Our results showed that O- and K-antigen genes are separated in <it>V. parahaemolyticus </it>O3:K6; the region encoding both O-antigen and capsule biosynthesis in other vibrios, i.e. genes between <it>gmhD </it>and <it>rjg</it>, determines the K6-antigen but not the O3-antigen in <it>V. parahaemolyticus</it>. The previously identified "capsule genes" on the smaller chromosome were related to exopolysaccharide synthesis, not K-antigen.</p> <p>Conclusion</p> <p>Understanding of the genetic basis of O- and K-antigens is critical to understanding the rapid changes in these polysaccharides seen in pandemic <it>V. parahaemolyticus. </it>This report confirms the genetic location of K-antigen synthesis in <it>V. parahaemolyticus </it>O3:K6 allowing us to focus future studies of the evolution of serotypes to this region.</p
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