51 research outputs found
Whole-genome bisulfite sequencing of cell-free DNA identifies signature associated with metastatic breast cancer
The stellar and sub-stellar IMF of simple and composite populations
The current knowledge on the stellar IMF is documented. It appears to become
top-heavy when the star-formation rate density surpasses about 0.1Msun/(yr
pc^3) on a pc scale and it may become increasingly bottom-heavy with increasing
metallicity and in increasingly massive early-type galaxies. It declines quite
steeply below about 0.07Msun with brown dwarfs (BDs) and very low mass stars
having their own IMF. The most massive star of mass mmax formed in an embedded
cluster with stellar mass Mecl correlates strongly with Mecl being a result of
gravitation-driven but resource-limited growth and fragmentation induced
starvation. There is no convincing evidence whatsoever that massive stars do
form in isolation. Various methods of discretising a stellar population are
introduced: optimal sampling leads to a mass distribution that perfectly
represents the exact form of the desired IMF and the mmax-to-Mecl relation,
while random sampling results in statistical variations of the shape of the
IMF. The observed mmax-to-Mecl correlation and the small spread of IMF
power-law indices together suggest that optimally sampling the IMF may be the
more realistic description of star formation than random sampling from a
universal IMF with a constant upper mass limit. Composite populations on galaxy
scales, which are formed from many pc scale star formation events, need to be
described by the integrated galactic IMF. This IGIMF varies systematically from
top-light to top-heavy in dependence of galaxy type and star formation rate,
with dramatic implications for theories of galaxy formation and evolution.Comment: 167 pages, 37 figures, 3 tables, published in Stellar Systems and
Galactic Structure, Vol.5, Springer. This revised version is consistent with
the published version and includes additional references and minor additions
to the text as well as a recomputed Table 1. ISBN 978-90-481-8817-
The G1613A Mutation in the HBV Genome Affects HBeAg Expression and Viral Replication through Altered Core Promoter Activity
Infection of hepatitis B virus (HBV) causes acute and chronic hepatitis and is closely associated with the development of cirrhosis and hepatocellular carcinoma (HCC). Previously, we demonstrated that the G1613A mutation in the HBV negative regulatory element (NRE) is a hotspot mutation in HCC patients. In this study, we further investigated the functional consequences of this mutation in the context of the full length HBV genome and its replication. We showed that the G1613A mutation significantly suppresses the secretion of e antigen (HBeAg) and enhances the synthesis of viral DNA, which is in consistence to our clinical result that the G1613A mutation associates with high viral load in chronic HBV carriers. To further investigate the molecular mechanism of the mutation, we performed the electrophoretic mobility shift assay with the recombinant RFX1 protein, a trans-activator that was shown to interact with the NRE of HBV. Intriguingly, RFX1 binds to the G1613A mutant with higher affinity than the wild-type sequence, indicating that the mutation possesses the trans-activating effect to the core promoter via NRE. The trans-activating effect was further validated by the enhancement of the core promoter activity after overexpression of RFX1 in liver cell line. In summary, our results suggest the functional consequences of the hotspot G1613A mutation found in HBV. We also provide a possible molecular mechanism of this hotspot mutation to the increased viral load of HBV carriers, which increases the risk to HCC
Modulation of the peripheral blood transcriptome by the ingestion of probiotic yoghurt and acidified milk in healthy, young men
The metabolic health benefits of fermented milks have already been investigated using clinical biomarkers but the development of transcriptomic analytics in blood offers an alternative approach that may help to sensitively characterise such effects. We aimed to assess the effects of probiotic yoghurt intake, compared to non-fermented, acidified milk intake, on clinical biomarkers and gene expression in peripheral blood. To this end, a randomised, crossover study was conducted in fourteen healthy, young men to test the two dairy products. For a subset of seven subjects, RNA sequencing was used to measure gene expression in blood collected during postprandial tests and after two weeks daily intake. We found that the postprandial response in insulin was different for probiotic yoghurt as compared to that of acidified milk. Moreover changes in several clinical biomarkers were associated with changes in the expression of genes representing six metabolic genesets. Assessment of the postprandial effects of each dairy product on gene expression by geneset enrichment analysis revealed significant, similar modulation of inflammatory and glycolytic genes after both probiotic yoghurt and acidified milk intake, although distinct kinetic characteristics of the modulation differentiated the dairy products. The aryl hydrocarbon receptor was a major contributor to the down-regulation of the inflammatory genesets and was also positively associated with changes in circulating insulin at 2h after yoghurt intake (p = 0.05). Daily intake of the dairy products showed little effect on the fasting blood transcriptome. Probiotic yoghurt and acidified milk appear to affect similar gene pathways during the postprandial phase but differences in the timing and the extent of this modulation may lead to different physiological consequences. The functional relevance of these differences in gene expression is supported by their associations with circulating biomarkers
Zebrafish: a vertebrate tool for studying basal body biogenesis, structure, and function.
Understanding the role of basal bodies (BBs) during development and disease has been largely overshadowed by research into the function of the cilium. Although these two organelles are closely associated, they have specific roles to complete for successful cellular development. Appropriate development and function of the BB are fundamental for cilia function. Indeed, there are a growing number of human genetic diseases affecting ciliary development, known collectively as the ciliopathies. Accumulating evidence suggests that BBs establish cell polarity, direct ciliogenesis, and provide docking sites for proteins required within the ciliary axoneme. Major contributions to our knowledge of BB structure and function have been provided by studies in flagellated or ciliated unicellular eukaryotic organisms, specifically Tetrahymena and Chlamydomonas. Reproducing these and other findings in vertebrates has required animal in vivo models. Zebrafish have fast become one of the primary organisms of choice for modeling vertebrate functional genetics. Rapid ex-utero development, proficient egg laying, ease of genetic manipulation, and affordability make zebrafish an attractive vertebrate research tool. Furthermore, zebrafish share over 80 % of disease causing genes with humans. In this article, we discuss the merits of using zebrafish to study BB functional genetics, review current knowledge of zebrafish BB ultrastructure and mechanisms of function, and consider the outlook for future zebrafish-based BB studies
Low-mass and sub-stellar eclipsing binaries in stellar clusters
We highlight the importance of eclipsing double-line binaries in our
understanding on star formation and evolution. We review the recent discoveries
of low-mass and sub-stellar eclipsing binaries belonging to star-forming
regions, open clusters, and globular clusters identified by ground-based
surveys and space missions with high-resolution spectroscopic follow-up. These
discoveries provide benchmark systems with known distances, metallicities, and
ages to calibrate masses and radii predicted by state-of-the-art evolutionary
models to a few percent. We report their density and discuss current
limitations on the accuracy of the physical parameters. We discuss future
opportunities and highlight future guidelines to fill gaps in age and
metallicity to improve further our knowledge of low-mass stars and brown
dwarfs.Comment: 30 pages, 5 figures, no table. Review pape
Wnt signaling controls pro-regenerative Collagen XII in functional spinal cord regeneration in zebrafish
The inhibitory extracellular matrix in a spinal lesion site is a major impediment to axonal regeneration in mammals. In contrast, the extracellular matrix in zebrafish allows substantial axon re-growth, leading to recovery of movement. However, little is known about regulation and composition of the growth-promoting extracellular matrix. Here we demonstrate that activity of the Wnt/beta-catenin pathway in fibroblast-like cells in the lesion site is pivotal for axon re-growth and functional recovery. Wnt/beta-catenin signaling induces expression of col12a1a/b and deposition of Collagen XII, which is necessary for axons to actively navigate the non-neural lesion site environment. Overexpression of col12a1a rescues the effects of Wnt/beta-catenin pathway inhibition and is sufficient to accelerate regeneration. We demonstrate that in a vertebrate of high regenerative capacity, Wnt/beta-catenin signaling controls the composition of the lesion site extracellular matrix and we identify Collagen XII as a promoter of axonal regeneration. These findings imply that the Wnt/beta-catenin pathway and Collagen XII may be targets for extracellular matrix manipulations in non-regenerating species
Visual Orbits of Spectroscopic Binaries with the CHARA Array. IV. HD 61859, HD 89822, HD 109510, and HD 191692
This is the author accepted manuscript.We present the visual orbits of four spectroscopic binary stars, HD 61859, HD
89822, HD 109510, and HD 191692, using long baseline interferometry with the
CHARA Array. We also obtained new radial velocities from echelle spectra using
the APO 3.5 m, CTIO 1.5 m, and Fairborn Observatory 2.0 m telescopes. By
combining the astrometric and spectroscopic observations, we solve for the
full, three-dimensional orbits and determine the stellar masses to 1-12%
uncertainty and distances to 0.4-6% uncertainty. We then estimate the effective
temperature and radius of each component star through Doppler tomography and
spectral energy distribution analyses. We found masses of 1.4-3.5 Msun, radii
of 1.5-4.7 Rsun, and temperatures of 6400-10300K. We then compare the observed
stellar parameters to the predictions of the stellar evolution models, but
found that only one of our systems fits well with the evolutionary models.European Union Horizon 2020European Research Council (ERC)Science and Technology Facilities Council (STFC
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