The social aetiology of essentialist beliefs

This commentary highlights the importance of attending to the sociocultural contexts that foster essentialist ideas. It contends that Cimpian & Salomon's (C&S's) model undervalues the extent to which the development of essentialist beliefs is contingent on social experience. The result is a restriction of the model's applicability to real-world instances of essentialism-fuelled prejudice and discrimination

A model for calculating mRNA dynamics from an RNA-Seq snapshot.

<p>(<b>A</b>) The decrease in expression from 5′ to 3′ along an intron, shown as the height of the green “guillotine” blade, is a product of the rate of intron synthesis (<i>S</i>) and the time required to transcribe the intron (<i>T</i>_t). The abundance of the fully transcribed intron at steady state, shown as the height of the black guillotine base, is a product of <i>S</i> and the intron processing time (<i>T</i>_p). <i>T</i>_p consists of the two steps of splicing and intron degradation. Changes in <i>S</i> and <i>T_p</i> both affect <i>total</i> intron expression level; however, only changes in <i>S</i> affect the <i>difference</i> in RNA-Seq read density across an intron. The conversion factor <i>c</i>₀ has units of RNA-Seq read density per initiated RNA transcript per cell. (<b>B</b>) A detailed timeline of pre-mRNA maturation indicating the four lifetimes (<i>T</i>_t, <i>T</i>₅, <i>T</i>₃, <i>T</i>_γ) that can be inferred from RNA-Seq read densities across three genomic features (INT, 5′SS, 3′SS). (<b>C</b>) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0089673#pone.0089673.e002" target="_blank">Equations (2a</a>) – (4) relating the times of lariat formation, exon ligation, and intron degradation to total RNA-Seq read densities. Additional details are provided in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0089673#s4" target="_blank">Materials and Methods</a> section.</p

SnapShot-Seq-derived timescales for ten human tissues and technical controls.

<p>(<b>A</b>) Lifetimes obtained from total RNA-Seq performed on ten human tissues, using the SOLiD Whole Transcriptome Sequencing method <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0089673#pone.0089673-Tumor1" target="_blank">[23]</a> with RiboMinus rRNA-depletion. <i>T</i>₅, <i>T</i>₃, and <i>T</i>_γ are as defined as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0089673#pone-0089673-g001" target="_blank">Fig. 1</a>. (<b>B</b>) A comparison of lifetimes across different sequencing methodologies. We performed sequencing on SOLiD (S) or Illumina (I); hybridization-based rRNA depletion with RiboMinus (M) or RiboZero (Z); and compared RNA samples isolated and prepared into libraries on several different days. We performed Illumina total RNA-Seq using the dUTP method <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0089673#pone.0089673-Levin1" target="_blank">[19]</a>. Error bars indicate 95% confidence from Monte Carlo simulations from individual biological samples.</p

Bimodality of mRNA synthesis rates reflects genome organization.

<p>(<b>A</b>) Distributions of gene expression levels (D_EXN), mRNA synthesis rates (D_3′INT), and mRNA stability (D_EXN/D_3′INT) reveal two modes of gene expression. D_EXN and D_3′INT refer to the RNA-Seq read densities across exons and the 3′-most 10 kb of introns respectively. (<b>B</b>) Compared to genes that are not expressed, low and high expressors are found closer to highly expressed genes. The <i>x</i>-axis indicates the distance from a gene's transcription start site (TSS) to the TSS of the nearest high expressor; * indicates <i>p</i><10⁻³ by a two-sample K-S test. (<b>C</b>) Genes adjacent to high mode genes are disproportionately more likely to be in the low mode and less likely to be in the off mode of gene expression, for both head-to-tail and tail-to-tail gene pair architectures (* indicates <i>p</i><10⁻⁶ from a bootstrap simulation with one million iterations, in which expression classes were permuted). (<b>D</b>) Between tissues, when genes transition from low expressors to non-expressors, their average distance to the nearest high expressor increases (<i>p</i><2.2×10⁻¹⁶, based on a chi-square test). The ∼15% difference between the data and the randomized control suggests that at least 15% of the changes from low to off are due to a nearby gene being up-regulated. RNA-Seq data is from mouse cortical neurons sequenced using SOLiD <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0089673#pone.0089673-Kim1" target="_blank">[53]</a> (A–C) and ten human tissues (D).</p

Average expression of the 3′ ends of introns across a gene is an accurate measure of mRNA synthesis rate.

<p>(<b>A</b>) Equations relating the mRNA synthesis rate <i>S</i> to RNA-Seq density across introns (D_INT) or across the 3′ ends of introns (D_3′INT). <i>T_p</i> is intron processing time, and c₀ is a constant relating RNA-Seq read density to transcript number per cell. In Eq. (7), subscripts 1-2 and superscripts 1-2 refer to separate genes. (<b>B</b>) The expression levels of the 3′ ends of introns are a useful proxy for mRNA synthesis rates, assuming that the variation in intron processing times among introns is smaller than the variation in mRNA synthesis rates among genes. The schematic shows the contributions of mRNA synthesis and intron processing to expression at the 3′ ends of introns across two hypothetical genes, each with three introns. The second gene is transcribed at a higher rate. (<b>C</b>) The assumption stated in (B) holds true: the within-gene standard error of intron densities at the 3′ ends of the (D_3′INT, red) is much smaller than the range of average D_3′INT among genes (blue). For clarity, the distribution of standard errors of D_3′INT is shown for the subset of genes with mean intron log-densities within 10% of -5 on the <i>x-</i>axis. Data is from mouse neuron RNA-Seq using SOLiD. (<b>D</b>) Quantification of mRNA synthesis using RNA labeling with 4-thiouridine (4SU, vertical axis) versus total RNA-Seq (D_3′INT, horizontal axis). The two methods are correlated with a Spearman's ρ of 0.87. Each point represents one gene and is an average of three total RNA-Seq and three 4SU RNA-Seq samples (biological replicates) from a lymphocyte cell line. Cells were exposed to 4SU for five minutes before cell lysis. Sequencing was performed using the dUTP/Illumina method (total RNA) or standard Illumina RNA-Seq (4SU).</p

The rate of lariat formation is decreased two-fold by isoginkgetin treatment.

<p>(<b>A</b>) Genome-wide expression of 5′ splice sites, 3′ splice sites, and introns are increased relative to exons upon treatment of HeLa cells with isoginkgetin (30 µM, 18 hours), based on total RNA-Seq (dUTP method <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0089673#pone.0089673-Parkhomchuk1" target="_blank">[18]</a>, Illumina). The height of each bar indicates the fold change, from vehicle- to isoginkgetin-treated cells, in the mean fraction of reads aligning to each genic feature (<i>p</i><0.02 from two-tailed <i>t</i>-tests for all ratios). (<b>B</b>) Isoginkgetin treatment increases the “guillotine” base height (<i>p</i> = 10⁻¹²) of intronic expression without increasing the blade height (<i>p</i> = 0.5), consistent with a splicing defect (compare to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0089673#pone-0089673-g001" target="_blank">Fig. 1A</a>). Only introns longer than 50 kb from genes with at least 10 introns are included in these meta-intron profiles, which show the last 50 kb of each aggregated intron. Introns of different lengths are aligned at their 3′ ends. RNA-Seq density is normalized as read counts per 10M uniquely aligning reads. The indicated values are from an average of three biological replicates, and <i>p</i>-values are from two-tailed <i>t</i>-tests based on mean values for aggregated introns 2–10 (n = 9). (<b>C</b>) Isoginkgetin treatment leads to a decreased rate of lariat formation (* indicates <i>p</i> = 0.02) without affecting exon ligation or excised lariat degradation (<i>p</i> = 0.22, 0.08), with calculations as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0089673#pone-0089673-g001" target="_blank">Fig. 1</a>. <i>p-</i>values are from two-tailed <i>t</i>-tests with n = 3 biological replicates. Error bars in (A, C) represent s.e.m. from three biological replicates.</p