Methylation of the imprinted GNAS1 gene in cell-free plasma DNA : equal steady-state quantities of methylated and unmethylated DNA in plasma

Background Genomic DNA sequences in cell-free plasma are biomarkers of cancer prognosis, where characteristic changes in methylation of tumour suppressor or oncogene DNA regions are indicative of changes in gene activity. Also, cell-free fetal DNA can be distinguished, by its methylation status, from the maternal DNA in the plasma of pregnant women, hence providing DNA biomarkers for the proposed minimally-invasive diagnosis of fetal aneuploidies, including Down's syndrome. However, the production and clearance of cell-free DNA from plasma in relation to its methylation status, are poorly understood processes. Methods We studied the methylation status of DNA derived from the imprinted GNAS1 locus, in cell-free plasma DNA of healthy adults. Heterozygotes were identified that carried the SNP rs1800905 in the imprinted region. The parent-of-origin-dependent DNA methylation was analysed by bisulfite conversion, followed by cloning and sequencing. Results Genomic DNA molecules derived from both the methylated, maternal, allele and the unmethylated, paternal, allele were found in plasma. Methylated and unmethylated DNA molecules were present in equal numbers. Conclusions Our data indicate that the methylation status of a DNA sequence has no effect on its steady state concentration in the cell-free DNA component of plasma, in healthy adults

Exploring the progenitors of brightest cluster galaxies at z ∼ 2

We present a new method for tracing the evolution of brightest cluster galaxies (BCGs) from z ∼ 2 to z ∼ 0. We conclude on the basis of semi-analytical models that the best method to select BCG progenitors at z ∼ 2 is a hybrid environmental density and stellar mass ranking approach. Ultimately, we are able to retrieve 45 per cent of BCG progenitors. We apply this method on the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey, Ultra Deep Survey data to construct a progenitor sample at high redshift. We furthermore populate the comparisons in local Universe by using Sloan Digital Sky Survey data with statistically likely contamination to ensure a fair comparison between high and low redshifts. Using these samples we demonstrate that the BCG sizes have grown by a factor of ∼3.2 since z ∼ 2, and BCG progenitors are mainly late-type galaxies, exhibiting less concentrated profiles than their early type local counterparts. We find that BCG progenitors have more disturbed morphologies. In contrast, local BCGs have much smoother profiles. Moreover, we find that the stellar masses of BCGs have grown by a factor of ∼2.5 since z ∼ 2, and the star formation rate of BCG progenitors has a median value of 13.5 Mʘ yr‾¹, much higher than their quiescent local descendants. We demonstrate that over z = 1–2 star formation and merging contribute equally to BCG mass growth. However, merging plays a dominant role in BCG assembly at z ≲ 1. We also find that BCG progenitors at high z are not significantly different from other galaxies of similar mass at the same epoch. This suggests that the processes which differentiate BCGs from normal massive elliptical galaxies must occur at z ≲ 2

Puritan Expedition.

38 p. : ill. ; 24 cm.Includes bibliographical references (p. 30-38)

The TORC1 phosphoproteome in C. elegans reveals roles in transcription and autophagy

The protein kinase complex target of rapamycin complex 1 (TORC1) is a critical mediator of nutrient sensing that has been widely studied in cultured cells and yeast, yet our understanding of the regulatory activities of TORC1 in the context of a whole, multi-cellular organism is still very limited. Using Caenorhabditis elegans, we analyzed the DAF-15/Raptor-dependent phosphoproteome by quantitative mass spectrometry and characterized direct kinase targets by in&nbsp;vitro kinase assays. Here, we show new targets of TORC1 that indicate previously unknown regulation of transcription and autophagy. Our results further show that DAF-15/Raptor is differentially expressed during postembryonic development, suggesting a dynamic role for TORC1 signaling throughout the life span. This study provides a comprehensive view of the TORC1 phosphoproteome, reveals more than 100 DAF-15/Raptor-dependent phosphosites that reflect the complex function of TORC1 in a whole, multi-cellular organism, and serves as a rich resource to the field. &nbsp;</p