Why Don't Women Patent?

We investigate women's underrepresentation among holders of commercialized patents: only 5.5% of holders of such patents are female. Using the National Survey of College Graduates 2003, we find only 7% of the gap is accounted for by women's lower probability of holding any science or engineering degree, because women with such a degree are scarcely more likely to patent than women without. Differences among those without a science or engineering degree account for 15%, while 78% is accounted for by differences among those with a science or engineering degree. For the latter group, we find that women's underrepresentation in engineering and in jobs involving development and design explain much of the gap; closing it would increase U.S. GDP per capita by 2.7%.

Why Don't Women Patent?

We investigate women's underrepresentation among holders of commercialized patents: only 5.5% of holders of such patents are female. Using the National Survey of College Graduates 2003, we find only 7% of the gap in patenting rates is accounted for by women's lower probability of holding any science or engineering degree, because women with such a degree are scarcely more likely to patent than women without. Differences among those without a science or engineering degree account for 15%, while 78% is accounted for by differences among those with a science or engineering degree. For the latter group, we find that women's underrepresentation in engineering and in jobs involving development and design explain much of the gap

Global Profiling of the Cellular Alternative RNA Splicing Landscape during Virus-Host Interactions.

Alternative splicing (AS) is a central mechanism of genetic regulation which modifies the sequence of RNA transcripts in higher eukaryotes. AS has been shown to increase both the variability and diversity of the cellular proteome by changing the composition of resulting proteins through differential choice of exons to be included in mature mRNAs. In the present study, alterations to the global RNA splicing landscape of cellular genes upon viral infection were investigated using mammalian reovirus as a model. Our study provides the first comprehensive portrait of global changes in the RNA splicing signatures that occur in eukaryotic cells following infection with a human virus. We identify 240 modified alternative splicing events upon infection which belong to transcripts frequently involved in the regulation of gene expression and RNA metabolism. Using mass spectrometry, we also confirm modifications to transcript-specific peptides resulting from AS in virus-infected cells. These findings provide additional insights into the complexity of virus-host interactions as these splice variants expand proteome diversity and function during viral infection

Validation of ASEs dysregulated in infected cells.

<p>(A) Overview of two isoforms encoded by the <i>ABI1</i> gene. Exons are depicted in red and the intervening introns are shown as thin black lines (not to scale). The primers used to detect the ASE by RT-PCR assays are shown in gray and the sizes of the expected amplicons (306 nt and 393 nt) are also indicated. The genomic coordinates of these two representative isoforms are also indicated. (B) Cellular mRNAs isolated from both uninfected and infected cells were analyzed by RT-PCR using specific primers to detect both forms of the modified ASE encoded by the <i>ABI1</i> gene. The amplified products were analyzed by automated chip-based microcapillary electrophoresis. Capillary electropherograms of the PCR reactions are shown. The positions and the amplitude of the detected amplicons are highlighted by red boxes. The positions of the internal markers are also indicated. The data shows the increase in the relative abundance of the short form (306 nt) and a decrease in the abundance of the long form (393 nt) upon viral infection. (C) Correlation between PSI values obtained from RNA-Seq and RT-PCR data. The analysis was performed on 16 selected ASEs (Abi1, Cwc22, Eif4a2, Hnrnpa2b1, Il34, Srsf3, Srsf5, Alkbh1, Cdkn2aip, Cflar, Hif1a, Mdm2, Serbp1, Sfswap, Smc2, Tbp). In all cases, the changes in AS levels detected by RT-PCR and the ones revealed through transcriptome sequencing displayed high levels of correlation (r >0.77). Sanger sequencing was also realized on several ASEs to confirm that RT-PCR reaction is specific and amplifies predicted ASE.</p

Transcriptomic studies of cells infected with reovirus.

<p>(A) Overview of the strategy used to identify the changes in both the cellular transcriptome and alternative splicing landscape upon reovirus infection. RNA-seq analysis was performed on infected cells at 14 hours post-infection. (B) MA-plot of cellular gene expression levels upon viral infection as compared to uninfected cells. The graph shows the fold-change (FC) in base 2 logarithm between infected and mock cells according to the mean expression of the gene in transcripts per million (TPM, also presented in log₂). A cluster of over-expressed genes during viral infections with high TPM value can be seen on the upper right corner. (C) Gene ontology analyses of the 569 genes for which the expression was the most significantly modified following viral infection. Up- and down-regulated genes were imported into the DAVID gene ontology suite of programs at the NIAID. Ontological functions were determined for biological processes, and background of all detected genes was used.</p

Protein families found in the 240 transcripts that are differentially spliced upon viral infection.

<p>Protein families found in the 240 transcripts that are differentially spliced upon viral infection.</p

Global profiling of the cellular alternative splicing landscape and identification of differentially spliced ASEs during virus-host interactions.

<p>(A) Heatmap representation of isoform ratios for cellular transcripts in both infected and uninfected (mock) cells. RNA sequencing was done in triplicate for each condition. The map represents the percent-spliced-in (PSI) values based on isoform expression for the long and the short ASEs (see Materials and methods). Blue indicates high PSI values and red indicates low PSI values. (B) Alternative splicing events (ASEs) in cells infected with reovirus. ASEs were detected and quantified using the percent-spliced-in (PSI) metric. The graph shows an analysis of the difference in PSI values (Delta PSI) of the cellular genes following viral infection. Black triangles indicate Delta PSI values between -10 and 10, red squares indicate Delta PSI values greater than 10 or less than -10 with a Q value under 0.05, and green circles indicate same Delta PSI values but with a Q value above 0.05. (C) Heatmap representation of the 240 ASEs that are differentially spliced upon viral infection. RNA sequencing was done in triplicate for both the uninfected (mock) and infected cells. Blue indicates high absolute PSI values and red indicates low absolute PSI values. (D) PSI distribution of the 40 primary ASEs for which AS is the most significantly altered upon viral infection. The PSI values for the respective ASEs are indicated both for the uninfected and infected cells. Error bars indicate standard deviation.</p

Proteins involved in RNA splicing.

<p>(A) Iris graph displaying the expression profile of proteins involved in RNA splicing. Differences in gene expression levels are shown on a logarithmic color scale (Log2). The expression of only 10 proteins involved in splicing was modulated by more than 2-fold upon infection (indicated by an asterisk). (B) Modifications to the splicing profiles of proteins involved in RNA splicing upon viral infection. Nine splicing factors were differentially spliced following viral infection. The changes in PSI values are indicated in red (negative delta PSI) or green (positive delta PSI).</p