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Activity of Genes with Functions in Human Williams-Beuren Syndrome Is Impacted by Mobile Element Insertions in the Gray Wolf Genome.
In canines, transposon dynamics have been associated with a hyper-social behavioral syndrome, although the functional mechanism has yet to be described. We investigate the epigenetic and transcriptional consequences of these behavior-associated mobile element insertions (MEIs) in dogs and Yellowstone gray wolves. We posit that the transposons themselves may not be the causative feature; rather, their transcriptional regulation may exert the functional impact. We survey four outlier transposons associated with hyper-sociability, with the expectation that they are targeted for epigenetic silencing. We predict hyper-methylation of MEIs, suggestive that the epigenetic silencing of and not the MEIs themselves may be driving dysregulation of nearby genes. We found that transposon-derived sequences are significantly hyper-methylated, regardless of their copy number or species. Further, we have assessed transcriptome sequence data and found evidence that MEIs impact the expression levels of six genes (WBSCR17, LIMK1, GTF2I, WBSCR27, BAZ1B, and BCL7B), all of which have known roles in human Williams-Beuren syndrome due to changes in copy number, typically hemizygosity. Although further evidence is needed, our results suggest that a few insertions alter local expression at multiple genes, likely through a cis-regulatory mechanism that excludes proximal methylation
Age-Specific Human Papillomavirus Antibody and Deoxyribonucleic Acid Prevalence: A Global Review
Global data on human papillomavirus serological and DNA prevalence are essential to optimize HPV prophylactic vaccination strategies
Identifying Mechanisms of Normal Cognitive Aging Using a Novel Mouse Genetic Reference Panel.
Developing strategies to maintain cognitive health is critical to quality of life during aging. The basis of healthy cognitive aging is poorly understood; thus, it is difficult to predict who will have normal cognition later in life. Individuals may have higher baseline functioning (cognitive reserve) and others may maintain or even improve with age (cognitive resilience). Understanding the mechanisms underlying cognitive reserve and resilience may hold the key to new therapeutic strategies for maintaining cognitive health. However, reserve and resilience have been inconsistently defined in human studies. Additionally, our understanding of the molecular and cellular bases of these phenomena is poor, compounded by a lack of longitudinal molecular and cognitive data that fully capture the dynamic trajectories of cognitive aging. Here, we used a genetically diverse mouse population (B6-BXDs) to characterize individual differences in cognitive abilities in adulthood and investigate evidence of cognitive reserve and/or resilience in middle-aged mice. We tested cognitive function at two ages (6 months and 14 months) using y-maze and contextual fear conditioning. We observed heritable variation in performance on these traits
Designing optoelectronic properties by on-surface synthesis: formation and electronic structure of an iron-terpyridine macromolecular complex
Supramolecular chemistry protocols applied on surfaces offer compelling
avenues for atomic scale control over organic-inorganic interface structures.
In this approach, adsorbate-surface interactions and two-dimensional
confinement can lead to morphologies and properties that differ dramatically
from those achieved via conventional synthetic approaches. Here, we describe
the bottom-up, on-surface synthesis of one-dimensional coordination
nanostructures based on an iron (Fe)-terpyridine (tpy) interaction borrowed
from functional metal-organic complexes used in photovoltaic and catalytic
applications. Thermally activated diffusion of sequentially deposited ligands
and metal atoms, and intra-ligand conformational changes, lead to Fe-tpy
coordination and formation of these nanochains. Low-temperature Scanning
Tunneling Microscopy and Density Functional Theory were used to elucidate the
atomic-scale morphology of the system, providing evidence of a linear tri-Fe
linkage between facing, coplanar tpy groups. Scanning Tunneling Spectroscopy
reveals highest occupied orbitals with dominant contributions from states
located at the Fe node, and ligand states that mostly contribute to the lowest
unoccupied orbitals. This electronic structure yields potential for hosting
photo-induced metal-to-ligand charge transfer in the visible/near-infrared. The
formation of this unusual tpy/tri-Fe/tpy coordination motif has not been
observed for wet chemistry synthesis methods, and is mediated by the bottom-up
on-surface approach used here
Tetra-methoxystilbene modulates ductal growth of the developing murine mammary gland
Extensive data suggest that estradiol contributes to the development of breast cancer by acting as a mitogen and exerting direct genotoxic effects after enzymatic conversion to 4-hydroxyestradiol (4-OHE2) via cytochrome P450 1B1 (CYP1B1). The mammary gland, ovary, and uterus all express CYP1B1. Overexpression of this enzyme has been associated with an increased risk of breast cancer and blockade might reduce this carcinogenic effect. For this reason, we conducted systematic in vitro and in vivo studies of a CYP1B1 inhibitor, TMS (2,3',4,5'-tetramethoxystilbene). We found that TMS blocked the enzymatic conversion of radiolabeled estradiol to both 2-hydroxyestradiol (2-OHE2) and 4-OHE2, but did not inhibit Cyp1b1 message formation. In vivo studies using mass spectrometry showed that TMS inhibited formation of 2-OHE2 and 4-OHE2 and the resulting estrogen-DNA adducts. To examine its biologic actions in vivo, we investigated whether TMS could block the hyperplastic changes that occur in the developing breast of aromatase-transfected mice. We found that TMS induced a significant reduction of ductal structures in mice less than 6 months in age. In older mice, no reduction in breast morphology occurred. These latter studies uncovered unexpected estrogen agonistic actions of TMS at high doses, including a paradoxical stimulation of breast ductal structures and the endometrium. These studies suggest that the enzyme inhibitory properties of TMS, as well as the effects on developing breast, could implicate a role for TMS in breast cancer prevention, but only in low doses and on developing breast
: Probing the Milky Way and Magellanic Clouds potentials with the 6-D map of the Orphan-Chenab stream
We present a 6-D map of the Orphan-Chenab (OC) stream by combining the data
from 5 years of Southern Stellar Stream Spectroscopic Survey observations
with Gaia EDR3 data. We reconstruct the proper motion, radial velocity,
distance and on-sky track of stream stars with spline models and extract the
stellar density along the stream. The stream has a total luminosity of
and an average metallicity of , similar to classical MW
satellites like Draco. The stream shows drastic changes in its physical width
varying from 200 pc to 1 kpc, a constant line of sight velocity dispersion of 5
km/s, but an increase in the velocity dispersion along the stream near
pericenter to 10 km/s. Despite the large apparent variation in the
stellar number density along the stream, the flow rate of stars along the
stream is remarkably constant. We model the 6-D stream track by a
Lagrange-point stripping method with a flexible MW potential in the presence of
a moving extended LMC potential. This allows us to constrain the mass profile
of the MW within the distance range 15.6 < r < 55.5 kpc, with the best measured
enclosed mass of within 32.4 kpc. With
the OC stream's closest approach distance to the LMC of kpc, our
stream measurements are highly sensitive to the LMC mass profile with the most
precise measurement of the LMC's enclosed mass being at 32.8 kpc with
. We confidently detect that the LMC
DM halo extends to at least 53 kpc. The fitting of the OC stream allows us to
constrain the past LMC trajectory and the degree of dynamical friction it
experienced. We demonstrate that the stars on the OC stream show large energy
and angular momentum spreads caused by the LMC perturbation and revealing the
limitations of orbital invariants for substructure identification in the MW
halo.Comment: submitted to MNRAS; comments welcome; data released with the paper is
available on Zenodo https://zenodo.org/record/722265
OPENMENDEL: A Cooperative Programming Project for Statistical Genetics
Statistical methods for genomewide association studies (GWAS) continue to
improve. However, the increasing volume and variety of genetic and genomic data
make computational speed and ease of data manipulation mandatory in future
software. In our view, a collaborative effort of statistical geneticists is
required to develop open source software targeted to genetic epidemiology. Our
attempt to meet this need is called the OPENMENDELproject
(https://openmendel.github.io). It aims to (1) enable interactive and
reproducible analyses with informative intermediate results, (2) scale to big
data analytics, (3) embrace parallel and distributed computing, (4) adapt to
rapid hardware evolution, (5) allow cloud computing, (6) allow integration of
varied genetic data types, and (7) foster easy communication between
clinicians, geneticists, statisticians, and computer scientists. This article
reviews and makes recommendations to the genetic epidemiology community in the
context of the OPENMENDEL project.Comment: 16 pages, 2 figures, 2 table
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