283 research outputs found
Conserved substitution patterns around nucleosome footprints in eukaryotes and Archaea derive from frequent nucleosome repositioning through evolution.
Nucleosomes, the basic repeat units of eukaryotic chromatin, have been suggested to influence the evolution of eukaryotic genomes, both by altering the propensity of DNA to mutate and by selection acting to maintain or exclude nucleosomes in particular locations. Contrary to the popular idea that nucleosomes are unique to eukaryotes, histone proteins have also been discovered in some archaeal genomes. Archaeal nucleosomes, however, are quite unlike their eukaryotic counterparts in many respects, including their assembly into tetramers (rather than octamers) from histone proteins that lack N- and C-terminal tails. Here, we show that despite these fundamental differences the association between nucleosome footprints and sequence evolution is strikingly conserved between humans and the model archaeon Haloferax volcanii. In light of this finding we examine whether selection or mutation can explain concordant substitution patterns in the two kingdoms. Unexpectedly, we find that neither the mutation nor the selection model are sufficient to explain the observed association between nucleosomes and sequence divergence. Instead, we demonstrate that nucleosome-associated substitution patterns are more consistent with a third model where sequence divergence results in frequent repositioning of nucleosomes during evolution. Indeed, we show that nucleosome repositioning is both necessary and largely sufficient to explain the association between current nucleosome positions and biased substitution patterns. This finding highlights the importance of considering the direction of causality between genetic and epigenetic change
DASH: Dynamic Attention-Based Substructure Hierarchy for Partial Charge Assignment
We present a robust and computationally efficient approach for assigning
partial charges of atoms in molecules. The method is based on a hierarchical
tree constructed from attention values extracted from a graph neural network
(GNN), which was trained to predict atomic partial charges from accurate
quantum-mechanical (QM) calculations. The resulting dynamic attention-based
substructure hierarchy (DASH) approach provides fast assignment of partial
charges with the same accuracy as the GNN itself, is software-independent, and
can easily be integrated in existing parametrization pipelines as shown for the
Open force field (OpenFF). The implementation of the DASH workflow, the final
DASH tree, and the training set are available as open source / open data from
public repositories
Col-OSSOS: The Colours of the Outer Solar System Origins Survey
The Colours of the Outer Solar System Origins Survey (Col-OSSOS) is acquiring
near-simultaneous , , and photometry of unprecedented precision with
the Gemini North Telescope, targeting nearly a hundred trans-Neptunian objects
(TNOs) brighter than mag discovered in the Outer Solar System
Origins Survey. Combining the optical and near-infrared photometry with the
well-characterized detection efficiency of the Col-OSSOS target sample will
provide the first flux-limited compositional dynamical map of the outer Solar
System. In this paper, we describe our observing strategy and detail the data
reduction processes we employ, including techniques to mitigate the impact of
rotational variability. We present optical and near-infrared colors for 35
TNOs. We find two taxonomic groups for the dynamically excited TNOs, the
neutral and red classes, which divide at . Based on simple
albedo and orbital distribution assumptions, we find that the neutral class
outnumbers the red class, with a ratio of 4:1 and potentially as high as 11:1.
Including in our analysis constraints from the cold classical objects, which
are known to exhibit unique albedos and colors, we find that within our
measurement uncertainty, our observations are consistent with the primordial
Solar System protoplanetesimal disk being neutral-class-dominated, with two
major compositional divisions in color space.Comment: Accepted to ApJS; on-line supplemental files will be available with
the AJS published version of the pape
Early outcomes of percutaneous pulmonary valve implantation using the Edwards SAPIEN XT transcatheter heart valve system
BACKGROUND: Patients with congenital or acquired heart defects affecting the pulmonary valve and right ventricular outflow tract (RVOT) commonly require multiple surgical interventions, resulting in significant morbidity. A less invasive alternative is percutaneous pulmonary valve implantation (PPVI). Though studies have previously reported the safety and efficacy of the early generation transcatheter heart valves (THVs), data on more recent devices are severely lacking.
METHODS AND RESULTS: We performed a multinational, multicentre, retrospective, observational registry analysis of patients who underwent PPVI using the Edwards SAPIEN XT THV. Of the 46 patients that were enrolled, the majority had tetralogy of Fallot as the underlying diagnosis (58.7%), and stentless xenograft as the most common RVOT anatomy (34.8%). Procedural success rate was high (93.5%), with a low frequency of periprocedural complications and adverse events (6.5% and 10.9%, respectively). At 30days post-procedure, NYHA class had improved significantly (90.6% were at NYHA I or II). The rate of moderate/severe pulmonary regurgitation had decreased from 76.1% at baseline to 5.0% at 30days, and the calculated peak systolic gradient had decreased from 45.2 (SD±21.3) mmHg to 16.4 (SD±8.0) mmHg, with these values remaining low up to 2years.
CONCLUSIONS: The data suggest the efficacy and safety of the SAPIEN XT THV in PPVI in common anatomies in patients with conduits, as well as those with native pulmonary valves or transannular patches. Continued data collection is necessary to verify long-term findings
Col-OSSOS: Z-Band Photometry Reveals Three Distinct TNO Surface Types
Several different classes of trans-Neptunian objects (TNOs) have been
identified based on their optical and near-infrared colors. As part of the
Colours of the Outer Solar System Origins Survey, we have obtained , ,
and band photometry of 26 TNOs using Subaru and Gemini Observatories.
Previous color surveys have not utilized band reflectance, and the
inclusion of this band reveals significant surface reflectance variations
between sub-populations. The colors of TNOs in and show obvious
structure, and appear consistent with the previously measured bi-modality in
. The distribution of colors of the two dynamically excited surface types
can be modeled using the two-component mixing models from Fraser \& Brown
(2012). With the combination of and , the dynamically excited
classes can be separated cleanly into red and neutral surface classes. In and , the two dynamically excited surface groups are also clearly
distinct from the cold classical TNO surfaces, which are red, with
0.85 and 0.6, while all dynamically excited objects
with similar colors exhibit redder colors. The band photometry
makes it possible for the first time to differentiate the red excited TNO
surfaces from the red cold classical TNO surfaces. The discovery of different
colors for these cold classical TNOs makes it possible to search for cold
classical surfaces in other regions of the Kuiper belt and to completely
separate cold classical TNOs from the dynamically excited population, which
overlaps in orbital parameter space.Comment: 11 pages, 2 figures, Accepted to A
Positron emission tomography imaging of coronary atherosclerosis
Inflammation has a central role in the progression of coronary atherosclerosis. Recent developments in cardiovascular imaging with the advent of hybrid positron emission tomography have provided a window into the molecular pathophysiology underlying coronary plaque inflammation. Using novel radiotracers targeted at specific cellular pathways, the potential exists to observe inflammation, apoptosis, cellular hypoxia, microcalcification and angiogenesis in vivo. Several clinical studies are now underway assessing the ability of this hybrid imaging modality to inform about atherosclerotic disease activity and the prediction of future cardiovascular risk. A better understanding of the molecular mechanisms governing coronary atherosclerosis may be the first step toward offering patients a more stratified, personalized approach to treatment
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