Reordering contigs of draft genomes using the Mauve Aligner

Summary: Mauve Contig Mover provides a new method for proposing the relative order of contigs that make up a draft genome based on comparison to a complete or draft reference genome. A novel application of the Mauve aligner and viewer provides an automated reordering algorithm coupled with a powerful drill-down display allowing detailed exploration of results

Priming Picture Naming with a Semantic Task: An fMRI Investigation

Prior semantic processing can enhance subsequent picture naming performance, yet the neurocognitive mechanisms underlying this effect and its longevity are unknown. This functional magnetic resonance imaging study examined whether different neurological mechanisms underlie short-term (within minutes) and long-term (within days) facilitation effects from a semantic task in healthy older adults. Both short- and long-term facilitated items were named significantly faster than unfacilitated items, with short-term items significantly faster than long-term items. Region of interest results identified decreased activity for long-term facilitated items compared to unfacilitated and short-term facilitated items in the mid-portion of the middle temporal gyrus, indicating lexical-semantic priming. Additionally, in the whole brain results, increased activity for short-term facilitated items was identified in regions previously linked to episodic memory and object recognition, including the right lingual gyrus (extending to the precuneus region) and the left inferior occipital gyrus (extending to the left fusiform region). These findings suggest that distinct neurocognitive mechanisms underlie short- and long-term facilitation of picture naming by a semantic task, with long-term effects driven by lexical-semantic priming and short-term effects by episodic memory and visual object recognition mechanisms

The neural correlates of picture naming facilitated by auditory repetition

Background: Overt repetition of auditorily presented words can facilitate picture naming performance in both unimpaired speakers and individuals with word retrieval difficulties, but the underlying neurocognitive mechanisms and longevity of such effects remain unclear. This study used functional magnetic resonance imaging to examine whether different neurological mechanisms underlie short-term (within minutes) and long-term (within days) facilitation effects from an auditory repetition task in healthy older adults

The gene desert mammary carcinoma susceptibility locus Mcs1a regulates Nr2f1 modifying mammary epithelial cell differentiation and proliferation.

Genome-wide association studies have revealed that many low-penetrance breast cancer susceptibility loci are located in non-protein coding genomic regions; however, few have been characterized. In a comparative genetics approach to model such loci in a rat breast cancer model, we previously identified the mammary carcinoma susceptibility locus Mcs1a. We now localize Mcs1a to a critical interval (277 Kb) within a gene desert. Mcs1a reduces mammary carcinoma multiplicity by 50% and acts in a mammary cell-autonomous manner. We developed a megadeletion mouse model, which lacks 535 Kb of sequence containing the Mcs1a ortholog. Global gene expression analysis by RNA-seq revealed that in the mouse mammary gland, the orphan nuclear receptor gene Nr2f1/Coup-tf1 is regulated by Mcs1a. In resistant Mcs1a congenic rats, as compared with susceptible congenic control rats, we found Nr2f1 transcript levels to be elevated in mammary gland, epithelial cells, and carcinoma samples. Chromatin looping over ∼820 Kb of sequence from the Nr2f1 promoter to a strongly conserved element within the Mcs1a critical interval was identified. This element contains a 14 bp indel polymorphism that affects a human-rat-mouse conserved COUP-TF binding motif and is a functional Mcs1a candidate. In both the rat and mouse models, higher Nr2f1 transcript levels are associated with higher abundance of luminal mammary epithelial cells. In both the mouse mammary gland and a human breast cancer global gene expression data set, we found Nr2f1 transcript levels to be strongly anti-correlated to a gene cluster enriched in cell cycle-related genes. We queried 12 large publicly available human breast cancer gene expression studies and found that the median NR2F1 transcript level is consistently lower in 'triple-negative' (ER-PR-HER2-) breast cancers as compared with 'receptor-positive' breast cancers. Our data suggest that the non-protein coding locus Mcs1a regulates Nr2f1, which is a candidate modifier of differentiation, proliferation, and mammary cancer risk

on biodefense-relevant enterobacteria

(ERIC): bioinformatics support for researc

<i>Mcs1a</i> affects rat mammary epithelial cell (RMEC) growth and differentiation.

<p>A) Results of the limiting-dilution RMEC transplantation assay. Graphed is the percentage of transplant sites with an outgrowth versus the number of RMECs transplanted. Vertical bars represent lower and upper limits of a 95%-confidence interval for a proportion. Outgrowth potential of RMECs from the susceptible congenic control (susc.; light grey) and <i>Mcs1a</i> resistant congenic (res.; dark grey) line (lines W4 and W5 combined) is not significantly different. B) Pseudocolor dot plots from a susceptible congenic control sample, representing the gating strategy used to enrich for clonogenic luminal RMECs using cell sorting on the BD FACS Aria. CD31–CD45− RMECs were divided into luminal and basal cells based on CD24 and CD29 expression (left panel). Based on staining with anti-CD61 and peanut lectin (PNL), the clonogenic luminal cell population (CD45–CD31-CD24hiCD29medCD61+PNLhi; <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003549#pgen.1003549.s003" target="_blank">Figure S3</a>) was selected for Matrigel assays (right panel). C) Graphed is the average (+/− sem) number of spherical mammary colonies formed in Matrigel assays plating 10,000 clonogenic RMECs sorted from the susceptible congenic control (n = 12) and <i>Mcs1a</i> resistant congenic line (n = 10; line W4 only). In the lower panel, a representative picture of a spherical mammary colony in a methylene blue-stained Matrigel is shown. Significantly different colony-forming ability (P<0.05) is indicated by an asterisk.</p

Proposed model for the <i>Mcs1a</i> breast cancer risk-affecting mechanism.

<p>The <i>Mcs1a</i> resistance allele displays increased mammary <i>Nr2f1</i> transcript levels as compared with the susceptible allele. Lower <i>Nr2f1</i> transcript levels in the mammary gland are associated with susceptibility, a lower percentage of luminal rat mammary epithelial cells (RMEC), a higher percentage of basal RMECs and increased colony-forming ability of the clonogenic luminal RMEC population, indicative of increased proliferation.</p

FACS analysis of rat and mouse MEC populations.

<p>A) Quantification of luminal and basal RMEC populations derived from susceptible congenic control (susc.; open bars; n = 6; WF.Cop) and <i>Mcs1a</i> resistant congenic (res.; filled bars; n = 7; Line W4) rats. B) Quantification of the CD61hi and PNLhi gates in RMEC populations derived from susc. (open bars; n = 11; WF.Cop) and res. (filled bars; n = 24; Lines W4 and W5). These gates were quantified in all CD31–CD45− RMECs as well as in the luminal RMECs. PNL = peanut lectin. C) Quantification of luminal and basal MMEC populations derived from wild type (WT; filled bars; n = 30) and megadeletion (MD; open bars; n = 27) mice (FVB and B6 pooled). D) Quantification of mature luminal (ML), luminal progenitor (LP) and mammary stem cell (MaSc) populations derived from WT (filled bars; n = 30) and MD (open bars; n = 27) mice (FVB and B6 pooled). FACS pseudocolor dot plot or histograms in each panel's upper figure illustrate the gating strategies used to quantify specific MEC populations. These dot plots were taken from a susc. sample (RMEC), or from a WT (FVB) sample (MMEC). Graphed in panels A–C are the average (+/−sem) percentages of populations among CD45–CD31− MECs. Graphed in panel D is the average (+/− sem) percentage of population among CD45–CD31− MECs, expressed relative to the WT run on the same day. In all graphs, significantly different (P<0.05) percentages of cells between susc. and <i>Mcs1a</i> or between WT and MD are indicated with an asterisk.</p

Global gene expression analysis reveals potential processes associated with <i>Nr2f1/NR2F1</i> transcript levels.

<p>A) Heatmap of expression correlation clustering analysis of 412 genes (which have 1-1-1 mouse-rat-human orthologues) that are differentially expressed between mammary gland samples from megadeletion (MD) and wild type mice (WT), both FVB. B) Heatmap of expression correlation clustering analysis of the same 412 genes in 243 human breast cancers from GSE3494, downloaded from the Gene Expression Omnibus. For both panels, strong correlation is indicated in blue, strong anti-correlation is indicated in yellow. The position of <i>Nr2f1/NR2F1</i> in group 1 is indicated by a dark blue vertical line. Below the panels, a summary of the gene ontology enrichment analysis is given. Smaller print indicates weak enrichment, larger print indicates strong enrichment (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003549#pgen.1003549.s009" target="_blank">Tables S5</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003549#pgen.1003549.s010" target="_blank">S6</a>).</p