Persistent Underrepresentation of Women’s Science in High Profile Journals, bioRxiv, 2018-03-03
AbstractYiqin Alicia Shen, Jason M. Webster, Yuichi Shoda, and Ione Fine Department of Psychology, University of Washington Past research has demonstrated an under-representation of female editors and reviewers in top scientific journals, but less is known about the representation of women authors within original research articles. We collected research article publication records from 15 high-profile multidisciplinary and neuroscience journals for 2005-2017 and analyzed the representation of women over time, as well as its relationship with journal impact factor. We find that women authors have been persistently underrepresented in high-profile journals. This under-representation has persisted over more than a decade, with glacial improvement over time. Even within our limited group of high profile journals, the percent of female first and last authors is negatively associated with journal impact factor. Since publishing in high-profile journals is a gateway to academic success, this underrepresentation of women may contribute to the lack of women at the top of the academic ladder.
biorxiv scientific-communication-and-education 500+-users 2018Transcriptional burst initiation and polymerase pause release are key control points of transcriptional regulation, bioRxiv, 2018-03-03
AbstractTranscriptional regulation occurs via changes to the rates of various biochemical processes. Sequencing-based approaches that average together many cells have suggested that polymerase binding and polymerase release from promoter-proximal pausing are two key regulated steps in the transcriptional process. However, single cell studies have revealed that transcription occurs in short, discontinuous bursts, suggesting that transcriptional burst initiation and termination might also be regulated steps. Here, we develop and apply a quantitative framework to connect changes in both Pol II ChIP-seq and single cell transcriptional measurements to changes in the rates of specific steps of transcription. Using a number of global and targeted transcriptional regulatory perturbations, we show that burst initiation rate is indeed a key regulated step, demonstrating that transcriptional activity can be frequency modulated. Polymerase pause release is a second key regulated step, but the rate of polymerase binding is not changed by any of the biological perturbations we examined. Our results establish an important role for transcriptional burst regulation in the control of gene expression.
biorxiv systems-biology 100-200-users 2018Unsupervised discovery of temporal sequences in high-dimensional datasets, with applications to neuroscience, bioRxiv, 2018-03-03
AbstractIdentifying low-dimensional features that describe large-scale neural recordings is a major challenge in neuroscience. Repeated temporal patterns (sequences) are thought to be a salient feature of neural dynamics, but are not succinctly captured by traditional dimensionality reduction techniques. Here we describe a software toolbox—called seqNMF—with new methods for extracting informative, non-redundant, sequences from high-dimensional neural data, testing the significance of these extracted patterns, and assessing the prevalence of sequential structure in data. We test these methods on simulated data under multiple noise conditions, and on several real neural and behavioral data sets. In hippocampal data, seqNMF identifies neural sequences that match those calculated manually by reference to behavioral events. In songbird data, seqNMF discovers neural sequences in untutored birds that lack stereotyped songs. Thus, by identifying temporal structure directly from neural data, seqNMF enables dissection of complex neural circuits without relying on temporal references from stimuli or behavioral outputs.
biorxiv neuroscience 100-200-users 2018An animal-actuated rotational head-fixation system for 2-photon imaging during 2-d navigation, bioRxiv, 2018-03-02
AbstractUnderstanding how the biology of the brain gives rise to the computations that drive behavior requires high fidelity, large scale, and subcellular measurements of neural activity. 2-photon microscopy is the primary tool that satisfies these requirements, particularly for measurements during behavior. However, this technique requires rigid head-fixation, constraining the behavioral repertoire of experimental subjects. Increasingly, complex task paradigms are being used to investigate the neural substrates of complex behaviors, including navigation of complex environments, resolving uncertainty between multiple outcomes, integrating unreliable information over time, andor building internal models of the world. In rodents, planning and decision making processes are often expressed via head and body motion. This produces a significant limitation for head-fixed two-photon imaging. We therefore developed a system that overcomes a major problem of head-fixation the lack of rotational vestibular input. The system measures rotational strain exerted by mice on the head restraint, which consequently drives a motor, rotating the constraint system and dissipating the strain. This permits mice to rotate their heads in the azimuthal plane with negligible inertia and friction. This stable rotating head-fixation system allows mice to explore physical or virtual 2-D environments. To demonstrate the performance of our system, we conducted 2-photon GCaMP6f imaging in somas and dendrites of pyramidal neurons in mouse retrosplenial cortex. We show that the subcellular resolution of the system’s 2-photon imaging is comparable to that of conventional head-fixed experiments. Additionally, this system allows the attachment of heavy instrumentation to the animal, making it possible to extend the approach to large-scale electrophysiology experiments in the future. Our method enables the use of state-of-the-art imaging techniques while animals perform more complex and naturalistic behaviors than currently possible, with broad potential applications in systems neuroscience.
biorxiv neuroscience 200-500-users 2018Efficient expression of genes in the Drosophila germline using a UAS-promoter free of interference by Hsp70 piRNAs, bioRxiv, 2018-03-02
ABSTRACTControlling the expression of genes using a binary system involving the yeast GAL4 transcription factor has been a mainstay of Drosophila melanogaster developmental genetics for twenty-five years. However, most existing GAL4 expression constructs only function effectively in somatic cells, but not in germ cells during oogenesis, for unknown reasons. A special UAS promoter, UASp was created that does express during oogenesis, but the need to use different constructs for somatic and female germline cells has remained a significant technical limitation. Here we show that the expression problem of UASt and many other Drosophila molecular tools in germline cells is caused by their core Hsp70 promoter sequences, which are targeted in female germ cells by Hsp70-directed piRNAs generated from endogenous Hsp70 gene sequences. In a genetic background lacking genomic Hsp70 genes and associated piRNAs, UASt-based constructs function effectively during oogenesis. By reducing Hsp70 sequences targeted by piRNAs, we created UASz, which functions better than UASp in the germline and like UASt in somatic cells.
biorxiv developmental-biology 0-100-users 2018fastp an ultra-fast all-in-one FASTQ preprocessor, bioRxiv, 2018-03-02
AbstractMotivationQuality control and preprocessing of FASTQ files are essential to providing clean data for downstream analysis. Traditionally, a different tool is used for each operation, such as quality control, adapter trimming, and quality filtering. These tools are often insufficiently fast as most are developed using high-level programming languages (e.g., Python and Java) and provide limited multi-threading support. Reading and loading data multiple times also renders preprocessing slow and IO inefficient.ResultsWe developed fastp as an ultra-fast FASTQ preprocessor with useful quality control and data-filtering features. It can perform quality control, adapter trimming, quality filtering, per-read quality cutting, and many other operations with a single scan of the FASTQ data. It also supports unique molecular identifier preprocessing, poly tail trimming, output splitting, and base correction for paired-end data. It can automatically detect adapters for single-end and paired-end FASTQ data. This tool is developed in C++ and has multi-threading support. Based on our evaluation, fastp is 2–5 times faster than other FASTQ preprocessing tools such as Trimmomatic or Cutadapt despite performing far more operations than similar tools.Availability and ImplementationThe open-source code and corresponding instructions are available at <jatsext-link xmlnsxlink=httpwww.w3.org1999xlink ext-link-type=uri xlinkhref=httpsgithub.comOpenGenefastp>httpsgithub.comOpenGenefastp<jatsext-link>Contactchen@haplox.com
biorxiv bioinformatics 100-200-users 2018