Genome-wide association studies (GWASs) implicate the PHACTR1 locus (6p24) in risk for five vascular diseases, including coronary artery disease, migraine headache, cervical artery dissection, ...fibromuscular dysplasia, and hypertension. Through genetic fine mapping, we prioritized rs9349379, a common SNP in the third intron of the PHACTR1 gene, as the putative causal variant. Epigenomic data from human tissue revealed an enhancer signature at rs9349379 exclusively in aorta, suggesting a regulatory function for this SNP in the vasculature. CRISPR-edited stem cell-derived endothelial cells demonstrate rs9349379 regulates expression of endothelin 1 (EDN1), a gene located 600 kb upstream of PHACTR1. The known physiologic effects of EDN1 on the vasculature may explain the pattern of risk for the five associated diseases. Overall, these data illustrate the integration of genetic, phenotypic, and epigenetic analysis to identify the biologic mechanism by which a common, non-coding variant can distally regulate a gene and contribute to the pathogenesis of multiple vascular diseases.
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•A non-coding variant on chromosome 6 associates with five vascular diseases•Histone acetylation shows a vascular-specific regulatory element at the causal SNP•Genome editing at the SNP demonstrates distal regulatory effect on endothelin-1•Endothelin-1 signaling in blood vessels may explain pattern of vascular disease risk
A common sequence variant that perturbs long-range enhancer interactions mediates risk for different vascular diseases.
Natural photosystems use protein scaffolds to control intermolecular interactions that enable exciton flow, charge generation, and long-range charge separation. In contrast, there is limited ...structural control in current organic electronic devices such as OLEDs and solar cells. We report here the DNA-encoded assembly of π-conjugated perylene diimides (PDIs) with deterministic control over the number of electronically coupled molecules. The PDIs are integrated within DNA chains using phosphoramidite coupling chemistry, allowing selection of the DNA sequence to either side, and specification of intermolecular DNA hybridization. In this way, we have developed a “toolbox” for construction of any stacking sequence of these semiconducting molecules. We have discovered that we need to use a full hierarchy of interactions: DNA guides the semiconductors into specified close proximity, hydrophobic–hydrophilic differentiation drives aggregation of the semiconductor moieties, and local geometry and electrostatic interactions define intermolecular positioning. As a result, the PDIs pack to give substantial intermolecular π wave function overlap, leading to an evolution of singlet excited states from localized excitons in the PDI monomer to excimers with wave functions delocalized over all five PDIs in the pentamer. This is accompanied by a change in the dominant triplet forming mechanism from localized spin–orbit charge transfer mediated intersystem crossing for the monomer toward a delocalized excimer process for the pentamer. Our modular DNA-based assembly reveals real opportunities for the rapid development of bespoke semiconductor architectures with molecule-by-molecule precision.
ABSTRACT We study the stellar population properties of the IRAC-detected 6 z 10 galaxy candidates from the Spitzer UltRa Faint SUrvey Program. Using the Lyman Break selection technique, we find a ...total of 17 galaxy candidates at 6 z 10 from Hubble Space Telescope images (including the full-depth images from the Hubble Frontier Fields program for MACS 1149 and MACS 0717) that have detections at signal-to-noise ratios ≥ 3 in at least one of the IRAC 3.6 and 4.5 m channels. According to the best mass models available for the surveyed galaxy clusters, these IRAC-detected galaxy candidates are magnified by factors of ∼1.2-5.5. Due to the magnification of the foreground galaxy clusters, the rest-frame UV absolute magnitudes M1600 are between −21.2 and −18.9 mag, while their intrinsic stellar masses are between 2 × 108M and 2.9 × 109M . We identify two Ly emitters in our sample from the Keck DEIMOS spectra, one at zLy = 6.76 (in RXJ 1347) and one at zLy = 6.32 (in MACS 0454). We find that 4 out of 17 z 6 galaxy candidates are favored by z 1 solutions when IRAC fluxes are included in photometric redshift fitting. We also show that IRAC 3.6-4.5 color, when combined with photometric redshift, can be used to identify galaxies which likely have strong nebular emission lines or obscured active galactic nucleus contributions within certain redshift windows.
Ecologists have long sought to understand the factors controlling the structure of savanna vegetation. Using data from 2154 sites in savannas across Africa, Australia, and South America, we found ...that increasing moisture availability drives increases in fire and tree basal area, whereas fire reduces tree basal area. However, among continents, the magnitude of these effects varied substantially, so that a single model cannot adequately represent savanna woody biomass across these regions. Historical and environmental differences drive the regional variation in the functional relationships between woody vegetation, fire, and climate. These same differences will determine the regional responses of vegetation to future climates, with implications for global carbon stocks.
Thermal inertia and surface roughness are proxies for the physical characteristics of planetary surfaces. Global maps of these two propertiesdistinguish the boulder population on near-Earth asteroid ...(NEA) (101955)Bennuinto two typesthat differ in strength,andboth havelower thermal inertiathan expectedfor boulders and meteorites. Neither has strongly temperature-dependent thermal properties. The weakerbouldertypeprobably would not survive atmospheric entry and thus may not berepresented in the meteorite collection. The maps also show ahigh-thermal-inertia band at Bennu’s equator, which might be explained by processes such as compaction or strength sorting during mass movement, but these explanations are not wholly consistent with other data. Our findings imply that other C-complex NEAs likely have boulderssimilar to those on Bennu,rather than finer-particulate regoliths.A tentative correlation between albedo and thermal inertia of C-complex NEAs may be due to relative abundances of boulder types.
Hybridization between wild and escaped cultured Atlantic salmon (Salmo salar) can threaten the stability and persistence of locally adapted wild populations. Here we describe the development and ...validation of a genomic-based approach to quantify recent hybridization between escapee and wild salmon in the western Atlantic. Based on genome-wide single nucleotide polymorphism (SNP) scans of wild and cultured salmon, collectively diagnostic panels were created for Newfoundland and the Canadian Maritimes. These panels were capable of both discriminating hybrids from nonhybrids and of correctly assigning individuals to hybrid class (i.e., pure wild, pure farm, F
1
, F
2
, and backcrosses) with a high degree of accuracy (Newfoundland 96 SNPs > 90%, Maritimes 720 SNPs > 80%). These genomic panels permit the assessment of the impacts of past and future farmed salmon escape events on wild populations and can inform the protection and conservation of wild Atlantic salmon genetic integrity in the western Atlantic.
The first
James Webb
Space Telescope (JWST) data on the massive colliding cluster
El Gordo
allow for 23 known families of multiply lensed images to be confirmed and for eight new members of these ...families to be identified. Based on these families, which have been confirmed spectroscopically by MUSE, we derived an initial lens model. This model guided the identification of 37 additional families of multiply lensed galaxies, among which 28 are entirely new systems, and nine were previously known. The initial lens model determined geometric redshifts for the 37 new systems. The geometric redshifts agree reasonably well with spectroscopic or photometric redshifts when those are available. The geometric redshifts enable two additional models that include all 60 families of multiply lensed galaxies spanning a redshift range 2 <
z
< 6. The derived dark-matter distribution confirms the double-peak configuration of mass found by earlier work with the southern and northern clumps having similar masses. We confirm that El Gordo is the most massive known cluster at
z
> 0.8 and has an estimated virial mass close the maximum mass allowed by standard cosmological models. The JWST images also reveal the presence of small-mass perturbers that produce small lensing distortions. The smallest of these is consistent with being a dwarf galaxy at
z
= 0.87 and has an estimated mass of 3.8 × 10
9
M
⊙
, making it the smallest substructure found at
z
> 0.5. The JWST images also show several candidate caustic-crossing events. One of them is detected at high significance at the expected position of the critical curve and is likely a red supergiant star at
z
= 2.1878. This would be the first red supergiant found at cosmological distances. The cluster lensing should magnify background objects at
z
> 6, making more of them visible than in blank fields of a similar size, but there appears to be a deficiency of such objects.
Delisle-Houde, P, Reid, RER, Insogna, JA, Chiarlitti, NA, and Andersen, RE. Seasonal changes in physiological responses and body composition during a competitive season in male and female elite ...collegiate ice hockey players. J Strength Cond Res 33(8): 2162-2169, 2019-Ice hockey continually overloads athletes with limited time for recovery, which may affect several physiological responses and alter body composition. The purpose of this study was to identify changes in physiological parameters and body composition profiles over the competitive season in elite collegiate ice hockey players. Forty-four players, 24 males (age = 22.7 ± 1.3 years, height = 1.82 ± 0.6 m, and body mass = 86.87 ± 6.44 kg) and 20 females (age = 19.9 ± 1.8 years, height = 1.66 ± 0.7 m, and body mass = 68.76 ± 5.91 kg) participated in 4-minute submaximal exercise tests and body composition assessments at pre-season, mid-season, and end-season. Changes in physiological parameters and body composition were analyzed using repeated-measures analysis of covariance controlling for age. Males' postexercise blood lactate concentration decreased (p ≤ 0.05) from pre- to mid-season (9.3 vs. 6.2 mmol·L) and increased (p ≤ 0.05) from mid- to end-season (6.2 vs. 8.0 mmol·L). Heart rate increased (p ≤ 0.05) after the third and fourth minute of the submaximal test in both sexes from pre- to end-season and from mid- to end-season. Males' body fat percentage decreased (p ≤ 0.05) from mid-season (17.4 vs. 16.1%), whereas increases were observed (p ≤ 0.05) in both sexes from mid- to end-season. This study produced evidence that male and female collegiate hockey athletes' physiological responses and body composition profiles change over the season. Sport scientists working with collegiate hockey teams, may need to revise annual training programs to attenuate reductions in fitness and hopefully prevent injuries.
Advances in genetic sequencing technologies and techniques have made large, genome‐wide data sets comprised of hundreds or even thousands of individuals and loci the norm rather than the exception ...even for nonmodel organisms. While such data present new opportunities for evaluating population structure and demographic processes, the large size of these genomic data sets brings new computational challenges for researchers needing to parse, convert and manipulate data often into a variety of software‐specific formats required of genomic analyses. We developed genepopedit as a flexible tool for the manipulation of multilocus molecular data sets. Functionality can be divided among diagnostic‐, manipulation‐, sampling‐, simulation‐, and transformation‐based tools. Metadata from large genomic data sets can be efficiently extracted, without the need to view data in a text‐editing program. genepopedit provides tools to manipulate loci, individual samples and populations included in genomic data sets, in addition to the ability to convert directly to a variety of software formats. Functions are compiled as an R package, which can integrate into existing analysis workflows. Importantly, genepopedit provides a simple yet robust code‐based tool for repeatable genomic data manipulation, which has been proven to be stable for data sets in excess of 200 000 SNPs. The latest version of the package and associated documentation are available on Github (github.com/rystanley/genepopedit).
Intermittent energy restriction (IER) is an eating pattern of regular daily periods of restricted energy intake followed by periods of unrestricted energy intake. This is gaining prominence as an ...alternative weight-loss strategy to daily energy restriction (DER). The aim of this systematic review was to determine the effectiveness of IER on weight loss in overweight and obese adults and compare this with DER.
A systematic literature search was conducted using the CINAHL, Embase, Medline, PsycINFO, Cochrane and Scopus databases. Eight studies that assigned overweight or obese adults to IER or to a DER 'control' were deemed eligible for inclusion.
All studies reported significant weight loss for IER groups. Average weight loss was approximately 0.2-0.8 kg per week. IER resulted in comparable weight loss to DER when overall energy restriction remained similar between diets. The majority of studies that reported body composition outcomes have shown equal efficacy for fat mass, fat-free mass and waist circumference.
Weight loss was achieved in overweight and obese adults following IER and this loss was comparable to a DER diet. IER may be an effective alternative strategy for health practitioners to promote weight loss for selected overweight and obese people.
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