748 research outputs found
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Integrated Genome Analysis Suggests that Most Conserved Non-Coding Sequences are Regulatory Factor Binding Sites
More than 98% of a typical vertebrate genome does not code for proteins. Although non-coding regions are sprinkled with short (<200 bp) islands of evolutionarily conserved sequences, the function of most of these unannotated conserved islands remains unknown. One possibility is that unannotated conserved islands could encode non-coding RNAs (ncRNAs); alternatively, unannotated conserved islands could serve as promoter-distal regulatory factor binding sites (RFBSs) like enhancers. Here we assess these possibilities by comparing unannotated conserved islands in the human and mouse genomes to transcribed regions and to RFBSs, relying on a detailed case study of one human and one mouse cell type. We define transcribed regions by applying a novel transcript-calling algorithm to RNA-Seq data obtained from total cellular RNA, and we define RFBSs using ChIP-Seq and DNAse-hypersensitivity assays. We find that unannotated conserved islands are four times more likely to coincide with RFBSs than with unannotated ncRNAs. Thousands of conserved RFBSs can be categorized as insulators based on the presence of CTCF or as enhancers based on the presence of p300/CBP and H3K4me1. While many unannotated conserved RFBSs are transcriptionally active to some extent, the transcripts produced tend to be unspliced, non-polyadenylated and expressed at levels 10 to 100-fold lower than annotated coding or ncRNAs. Extending these findings across multiple cell types and tissues, we propose that most conserved non-coding genomic DNA in vertebrate genomes corresponds to promoter-distal regulatory elements
From What We Eat, We Define Ourselves: The Creative Fictions and Nonfictions of Contemporary Food
This panel, made up of current and former Winthrop writing students and of current Winthrop faculty seeks to look creatively at the myriad of ways in which the food we eat might offer another helpful entrance point into defining our identity
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Expression divergence measured by transcriptome sequencing of four yeast species
<p>Abstract</p> <p>Background</p> <p>The evolution of gene expression is a challenging problem in evolutionary biology, for which accurate, well-calibrated measurements and methods are crucial.</p> <p>Results</p> <p>We quantified gene expression with whole-transcriptome sequencing in four diploid, prototrophic strains of <it>Saccharomyces </it>species grown under the same condition to investigate the evolution of gene expression. We found that variation in expression is gene-dependent with large variations in each gene's expression between replicates of the same species. This confounds the identification of genes differentially expressed across species. To address this, we developed a statistical approach to establish significance bounds for inter-species differential expression in RNA-Seq data based on the variance measured across biological replicates. This metric estimates the combined effects of technical and environmental variance, as well as Poisson sampling noise by isolating each component. Despite a paucity of large expression changes, we found a strong correlation between the variance of gene expression change and species divergence (R<sup>2 </sup>= 0.90).</p> <p>Conclusion</p> <p>We provide an improved methodology for measuring gene expression changes in evolutionary diverged species using RNA Seq, where experimental artifacts can mimic evolutionary effects.</p> <p>GEO Accession Number: GSE32679</p
Genome-Wide Analysis of MEF2 Transcriptional Program Reveals Synaptic Target Genes and Neuronal Activity-Dependent Polyadenylation Site Selection
Although many transcription factors are known to control important aspects of neural development, the genome-wide programs that are directly regulated by these factors are not known. We have characterized the genetic program that is activated by MEF2, a key regulator of activity-dependent synapse development. These MEF2 target genes have diverse functions at synapses, revealing a broad role for MEF2 in synapse development. Several of the MEF2 targets are mutated in human neurological disorders including epilepsy and autism spectrum disorders, suggesting that these disorders may be caused by disruption of an activity-dependent gene program that controls synapse development. Our analyses also reveal that neuronal activity promotes alternative polyadenylation site usage at many of the MEF2 target genes, leading to the production of truncated mRNAs that may have different functions than their full-length counterparts. Taken together, these analyses suggest that the ubiquitously expressed transcription factor MEF2 regulates an intricate transcriptional program in neurons that controls synapse development
Thiol-Anchored TIPS-Tetracene Ligands with Quantitative Triplet Energy Transfer to PbS Quantum Dots and Improved Thermal Stability.
Triplet energy transfer between inorganic quantum dots (QDs) and organic materials plays a fundamental role in many optoelectronic applications based on these nanocomposites. Attaching organic molecules to the QD as transmitter ligands has been shown to facilitate transfer both to and from QDs. Here we show that the often disregarded thiol anchoring group can achieve quantitative triplet energy transfer yields in a PbS QD system with 6,11-bis[(triisopropylsilyl)ethynyl]tetracene-2-methylthiol (TET-SH) ligands. We demonstrate efficient triplet transfer in a singlet fission-based photon multiplication system with 5,12-bis[(triisopropylsilyl)ethynyl]tetracene generating triplets in solution that transfer to the PbS QDs via the thiol ligand TET-SH. Importantly, we demonstrate the increased thermal stability of the PbS/TET-SH system, compared to the traditional carboxylic acid counterpart, allowing for higher photoluminescence quantum yields
Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin
One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution
Swift follow-up observations of candidate gravitational-wave transient events
We present the first multi-wavelength follow-up observations of two candidate
gravitational-wave (GW) transient events recorded by LIGO and Virgo in their
2009-2010 science run. The events were selected with low latency by the network
of GW detectors and their candidate sky locations were observed by the Swift
observatory. Image transient detection was used to analyze the collected
electromagnetic data, which were found to be consistent with background.
Off-line analysis of the GW data alone has also established that the selected
GW events show no evidence of an astrophysical origin; one of them is
consistent with background and the other one was a test, part of a "blind
injection challenge". With this work we demonstrate the feasibility of rapid
follow-ups of GW transients and establish the sensitivity improvement joint
electromagnetic and GW observations could bring. This is a first step toward an
electromagnetic follow-up program in the regime of routine detections with the
advanced GW instruments expected within this decade. In that regime
multi-wavelength observations will play a significant role in completing the
astrophysical identification of GW sources. We present the methods and results
from this first combined analysis and discuss its implications in terms of
sensitivity for the present and future instruments.Comment: Submitted for publication 2012 May 25, accepted 2012 October 25,
published 2012 November 21, in ApJS, 203, 28 (
http://stacks.iop.org/0067-0049/203/28 ); 14 pages, 3 figures, 6 tables;
LIGO-P1100038; Science summary at
http://www.ligo.org/science/Publication-S6LVSwift/index.php ; Public access
area to figures, tables at
https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p110003
Search for gravitational waves associated with the InterPlanetary Network short gamma ray bursts
We outline the scientific motivation behind a search for gravitational waves
associated with short gamma ray bursts detected by the InterPlanetary Network
(IPN) during LIGO's fifth science run and Virgo's first science run. The IPN
localisation of short gamma ray bursts is limited to extended error boxes of
different shapes and sizes and a search on these error boxes poses a series of
challenges for data analysis. We will discuss these challenges and outline the
methods to optimise the search over these error boxes.Comment: Methods paper; Proceedings for Eduardo Amaldi 9 Conference on
Gravitational Waves, July 2011, Cardiff, U
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