bluuebunny/crossref_metadata_2025_split huggingface dataset:
I was going to say / j’allais dire as discourse markers in contemporary English and French
Authors: Lansari Laure 
Published: May 2017

Abstract
This paper investigates two emerging discourse markers based on verbs of saying in English and French – I was going to say and j’allais dire. Relying on various comparable corpora, the author shows that the markers under scrutiny have developed a similar use as “reduced parenthetical clauses” mitigating discourse. The corpus study also reveals an interesting difference, namely that I was going to say stands as a topical transition marker in some of its uses. It is thus hypothesized that the two markers do not exactly follow the same pragmaticalisation path.
Applied Language Typology
Authors: Filipović Luna 
Published: May 2017

AbstractIn this paper we introduce and outline a new research area, Applied Language Typology (ALT). ALT builds on fundamental typological findings in morphology, syntax and semantics. ALT examines the attested and potential practical consequences of these contrasts for different professional contexts of communication, such as translation, the law and second language learning and teaching. We propose three general organising principles that underlie ALT, illustrating how these principles enable us to identify exact points of language contrasts that result in significant practical difficulty, and we suggest future directions in ALT research for the benefit of academics and language practitioners.
Silencing of transposable elements may not be a major driver of regulatory evolution in primate induced pluripotent stem cells
Authors: Ward Michelle C. , Zhao Siming , Luo Kaixuan , Pavlovic Bryan J. , Karimi Mohammad M. , Stephens Matthew , Gilad Yoav 
Published: May 2017

AbstractTransposable elements (TEs) comprise a substantial proportion of primate genomes. The regulatory potential of TEs can result in deleterious effects, especially during development. It has been suggested that, in pluripotent stem cells, TEs are targeted for silencing by KRAB-ZNF proteins, which recruit the TRIM28-SETDB1 complex, to deposit the repressive histone modification H3K9me3. TEs, in turn, can acquire mutations that allow them to evade detection by the host, and hence KRAB-ZNF proteins need to rapidly evolve to counteract them. To investigate the short-term evolution of TE silencing, we profiled the genome-wide distribution of H3K9me3 in induced pluripotent stem cells from ten human and seven chimpanzee individuals. We performed chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) for H3K9me3, as well as total RNA sequencing. We focused specifically on cross-species H3K9me3 ChIP-seq data that mapped to four million orthologous TEs. We found that, depending on the TE class, 10-60% of elements are marked by H3K9me3, with SVA, LTR and LINE elements marked most frequently. We found little evidence of inter-species differences in TE silencing, with as many as 80% of orthologous, putatively silenced, TEs marked at similar levels in humans and chimpanzees. Our data suggest limited species-specificity of TE silencing across six million years of primate evolution. Interestingly, the minority of TEs enriched for H3K9me3 in one species are not more likely to be associated with gene expression divergence of nearby orthologous genes. We conclude that orthologous TEs may not play a major role in driving gene regulatory divergence between humans and chimpanzees.
Mechanical and tactile incompatibilities cause reproductive isolation between two young damselfly species
Authors: Barnard Alexandra A. , Fincke Ola M. , McPeek Mark A. , Masly John P. 
Published: May 2017

AbstractExternal male reproductive structures have received considerable attention as an early-acting cause of reproductive isolation (RI), because the morphology of these structures often evolves rapidly between populations. This presents the potential for mechanical incompatibilities with heterospecific female structures during mating and could thus prevent interbreeding between nascent species. Although such mechanical incompatibilities have received little empirical support as a common cause of RI, the potential for mismatch of reproductive structures to cause RI due to incompatible species-specific tactile cues has not been tested. We tested the importance of mechanical and tactile incompatibilities in RI betweenEnallagma annaandE. carunculatum,two damselfly species that diverged within the past ~250,000 years and currently hybridize in a sympatric region. We quantified 19 prezygotic and postzygotic RI barriers using both naturally occurring and lab-reared damselflies. We found incomplete mechanical isolation between the two pure species and between hybrid males and pure species females. Interestingly, where mechanical isolation was incomplete, females showed greater resistance and refusal to mate with hybrid or heterospecific males compared to conspecific males, which suggests that tactile incompatibilities involving male reproductive structures can influence female mating decisions and form a strong barrier to gene flow in early stages of speciation.
High-resolution mapping of cis-regulatory variation in budding yeast
Authors: Kita Ryosuke , Venkataram Sandeep , Zhou Yiqi , Fraser Hunter B. 
Published: May 2017

ABSTRACTGenetic variants affecting gene expression levels are a major source of phenotypic variation. The approximate locations of these variants can be mapped as expression quantitative trait loci (eQTLs); however a major limitation of eQTLs is their low resolution, which precludes investigation of the causal variants and their molecular mechanisms. Here we report RNA-seq and full genome sequences for 85 diverse isolates of the yeastSaccharomyces cerevisiae—including wild, domesticated, and human clinical strains—which allowed us to perform eQTL mapping with 50-fold higher resolution than previously possible. In addition to variants in promoters, we uncovered an important role for variants in 3’ untranslated regions, especially those affecting binding of the PUF family of RNA-binding proteins. The eQTLs are predominantly under purifying selection, particularly those affecting essential genes and conserved genes. However, applying the sign test for lineage-specific selection revealed the polygenic up-regulation of dozens of biofilm suppressor genes in strains isolated from human patients, consistent with the key role of biofilms in fungal pathogenicity. In addition, a single variant in the promoter of a biofilm suppressor,NIT3,showed the strongest genome-wide association with clinical origin. Altogether our results demonstrate the power of high-resolution eQTL mapping in understanding the molecular mechanisms of regulatory variation, as well as the natural selection acting on this variation that drives adaptation to environments ranging from laboratories to vineyards to the human body.
Repurposing tofacitinib as an anti-myeloma therapeutic to reverse growth-promoting effects of the bone marrow microenvironment
Authors: Lam Christine , Murnane Megan , Liu Hui , Smith Geoffrey A. , Wong Sandy , Taunton Jack , Liu Jun O. , Mitsiades Constantine S. , Hann Byron C. , Aftab Blake T. , Wiita Arun P. 
Published: May 2017

AbstractThe myeloma bone marrow microenvironment promotes proliferation of malignant plasma cells and resistance to therapy. Interleukin-6 (IL-6) and downstream JAK/STAT signaling are thought to be central components of these microenvironment-induced phenotypes. In a prior drug repurposing screen, we identified tofacitinib, a pan-JAK inhibitor FDA-approved for rheumatoid arthritis, as an agent that may reverse the tumor-stimulating effects of bone marrow mesenchymal stromal cells. Here, we validated bothin vitro, in stromal-responsive human myeloma cell lines, andin vivo, in orthotopic disseminated murine xenograft models of myeloma, that tofacitinib showed both single-agent and combination therapeutic efficacy in myeloma models. Surprisingly, we found that ruxolitinib, an FDA-approved agent targeting JAK1 and JAK2, did not lead to the same anti-myeloma effects. Combination with a novel irreversible JAK3-selective inhibitor also did not enhance ruxolitinib effects. RNA-seq and unbiased phosphoproteomics revealed that marrow stromal cells stimulate a JAK/STAT-mediated proliferative program in myeloma plasma cells, and tofacitinib reversed the large majority of these pro-growth signals. Taken together, our results suggest that tofacitinib specifically reverses the growth-promoting effects of the tumor microenvironment through blocking an IL-6-mediated signaling axis. As tofacitinib is already FDA-approved, these results can be rapidly translated into potential clinical benefits for myeloma patients.
Characterization of imprinted genes in rice reveals post-fertilization regulation and conservation at some loci of imprinting in plant species
Authors: Chen Chen , Li Tingting , Zhu Shan , Liu Zehou , Shi Zhenyuan , Zheng Xiaoming , Chen Rui , Huang Jianfeng , Shen Yi , Luo Shiyou , Wang Lei , Liu Qiao-Quan , Zhiguo E 
Published: May 2017

AbstractGenomic imprinting is an epigenetic phenomenon by which certain genes display monoallelic expression in a parent-of-origin-dependent manner. Hundreds of imprinted genes have been identified from several plant species. Here we identified, with a high level of confidence, 208 imprinted candidates from rice. Imprinted genes of rice showed limited association to the transposable elements, which is contrast to the findings inArabidopsis. Generally, imprinting of rice is conserved within species, but intraspecific variations were confirmed here. Imprinting between cultivated rice and wild rice are likely similar. The imprinted genes of rice do not show significant selective signatures overall, which suggests that domestication imposes limited evolutionary effects on genomic imprinting of rice. Though the conservation of imprinting in plants is limited, here we prove that some loci tend to be imprinted in different species. In addition, our results suggest that differential epigenetic regulation between parental alleles can be established either prior to or post-fertilization. The imprinted 24-nt small RNAs, but not the 21-nt ones, likely involve the regulation of imprinting in an opposite parental-allele targeting manner. Together, our findings suggest that regulation of imprinting can be very diverse, and genomic imprinting as well as imprinted genes have essential evolutionary and biological significance.
SRGAP2and the gradual evolution of the modern human language faculty
Authors: Martins Pedro Tiago , Marí Maties , Boeckx Cedric 
Published: May 2017

AbstractIn this paper we examine a new source of evidence that draws on data from archaic human genomes to support the hypothesis that vocal learning inHomopreceded the emergence of Anatomically Modern Humans. We build our claim on the evolutionary history of the SLITROBO GTPase 2 gene (SRGAP2). The SLIT-ROBO molecular pathway has been shown to have an important role in the context of vocal learning. Though the relevance of theSRGAP2gene duplication in the emergence of some aspect of language has not gone completely unnoticed, recent results now allow us to articulate a mechanistic hypothesis of its role in the context of axon guidance. Specifically,SRGAP2C, a duplication ofSRGAP2crucially also found in Neanderthals and Denisovans, but not in extant mammals, inhibits the ancestralSRGAP2A, which in turn modulates the axon guidance function of the SLIT-ROBO molecular pathway. This, we claim, could have contributed to the establishment of the critical cortico-laryngeal connection of the vocal learning circuit. Our conclusions support the idea that complex vocal learning could already have been part of the arsenal of some of our extinct ancestors.
CAM: a quality control pipeline for MNase-seq data
Authors: Hu Sheng’en , Chen Xiaolan , Liao Ji , Chen Yiqing , Zhao Chengchen , Zhang Yong 
Published: May 2017

AbstractNucleosome organization affects the accessibility of cis-elements to trans-acting factors. Micrococcal nuclease digestion followed by high-throughput sequencing (MNase-seq) is the most popular technology used to profile nucleosome organization on a genome-wide scale. Evaluating the data quality of MNase-seq data remains challenging, especially in mammalian. There is a strong need for a convenient and comprehensive approach to obtain dedicated quality control (QC) for MNase-seq data analysis. Here we developed CAM, which is a comprehensive QC pipeline for MNase-seq data. The CAM pipeline provides multiple informative QC measurements and nucleosome organization profiles on different potentially functional regions for given MNase-seq data. CAM also includes 268 historical MNase-seq datasets from human and mouse as a reference atlas for unbiased assessment. CAM is freely available at:http://www.tongji.edu.cn/~zhanglab/CAM
Dr.seq2: a quality control and analysis pipeline for parallel single cell transcriptome and epigenome data
Authors: Zhao Chengchen , Hu Sheng’en , Huo Xiao , Zhang Yong 
Published: May 2017

AbstractAn increasing number of single cell transcriptome and epigenome technologies, including single cell ATAC-seq (scATAC-seq), have been recently developed as powerful tools to analyze the features of many individual cells simultaneously. However, the methods and software were designed for one certain data type and only for single cell transcriptome data. A systematic approach for epigenome data and multiple types of transcriptome data is needed to control data quality and to perform cell-to-cell heterogeneity analysis on these ultra-high-dimensional transcriptome and epigenome datasets. Here we developed Dr.seq2, a Quality Control (QC) and analysis pipeline for multiple types of single cell transcriptome and epigenome data, including scATAC-seq and Drop-ChIP data. Application of this pipeline provides four groups of QC measurements and different analyses, including cell heterogeneity analysis. Dr.seq2 produced reliable results on published single cell transcriptome and epigenome datasets. Overall, Dr.seq2 is a systematic and comprehensive QC and analysis pipeline designed for parallel single cell transcriptome and epigenome data. Dr.seq2 is freely available at:http://www.tongji.edu.cn/~zhanglab/drseq2/andhttps://github.com/ChengchenZhao/DrSeq2.
Bias, robustness and scalability in differential expression analysis of single-cell RNA-seq data
Authors: Soneson Charlotte , Robinson Mark D. 
Published: May 2017

AbstractBackgroundAs single-cell RNA-seq (scRNA-seq) is becoming increasingly common, the amount of publicly available data grows rapidly, generating a useful resource for computational method development and extension of published results. Although processed data matrices are typically made available in public repositories, the procedure to obtain these varies widely between data sets, which may complicate reuse and cross-data set comparison. Moreover, while many statistical methods for performing differential expression analysis of scRNA-seq data are becoming available, their relative merits and the performance compared to methods developed for bulk RNA-seq data are not sufficiently well understood.ResultsWe presentconquer, a collection of consistently processed, analysis-ready public single-cell RNA-seq data sets. Each data set has count and transcripts per million (TPM) estimates for genes and transcripts, as well as quality control and exploratory analysis reports. We use a subset of the data sets available inconquerto perform an extensive evaluation of the performance and characteristics of statistical methods for differential gene expression analysis, evaluating a total of 30 statistical approaches on both experimental and simulated scRNA-seq data.ConclusionsConsiderable differences are found between the methods in terms of the number and characteristics of the genes that are called differentially expressed. Pre-filtering of lowly expressed genes can have important effects on the results, particularly for some of the methods originally developed for analysis of bulk RNA-seq data. Generally, however, methods developed for bulk RNA-seq analysis do not perform notably worse than those developed specifically for scRNA-seq.
Improving tauG-control of action in PD
Authors: Schögler Benjaman , Polokoff Rachel , Pepping Gert-Jan , Perkins Jon , Lee David N 
Published: May 2017

AbstractA theory of action control (General Tau Theory) is applied to analyzing normal and abnormal movements in PD; and to designing and testing the efficacy of a sonic aid for PD. A central aspect of the theory, which is supported by experimental evidence across a variety of actions and species, is that the trajectories of competent skilled actions follow a particular temporal pattern, which is described by the mathematical function, tauG. Since tauG-control of actions can be largely deficient in PD, we designed a device that generates whoop-like sounds, where the fundamental frequency of the sound follows the tauG pattern. Our hypothesis was that by listening to these sounds the nervous system of someone with PD might be helped subsequently to self-generate tauG patterns in their nervous system, which might facilitate movement control in different situations. Five adults with PD, and five age-matched controls, took part in the study. They each listened to the sounds under two conditions: (a) experimental - turning a handle for 5 minutes while the sounds were played (b) control - turning the handle without the sounds. Before and after each condition, the tauG-control of lateral body sway while standing was measured (without the sounds playing), using force-plates, on two tasks: (i) keeping the feet down, (ii) lifting the trailing foot. The number of participants out of five, who showed greater ratio improvement following practice with whoop sounds compared to without sounds, was, on each task, high for the PDs compared with the age-matched controls (4 vs 2 or 3). Thus, for the PDs, listening to the tauG whoop-like sounds while performing one action (handle turning) improved subsequent tauG-control on a different task (body-swaying).
SpatialDE - Identification of spatially variable genes
Authors: Svensson Valentine , Teichmann Sarah A , Stegle Oliver 
Published: May 2017

Technological advances have enabled low-input RNA-sequencing, paving the way for assaying transcriptome variation in spatial contexts, including in tissues. While the generation of spatially resolved transcriptome maps is increasingly feasible, computational methods for analysing the resulting data are not established. Existing analysis strategies either ignore the spatial component of gene expression variation, or require discretization of the cells into coarse grained groups.To address this, we have developed SpatialDE, a computational framework for identifying and characterizing spatially variable genes. Our method generalizes variable gene selection, as used in population-and single-cell studies, to spatial expression profiles. To illustrate the broad utility of our approach, we apply SpatialDE to spatial transcriptomics data, and to data from single cell methods based on multiplexedin situhybridisation (SeqFISH and MERFISH). SpatialDE enables the statistically robust identification of spatially variable genes, thereby identifying genes with known disease implications, several of which are missed by conventional variable gene selection. Additionally, to enable gene-expressed based histology, SpatialDE implements a spatial gene clustering model which we call “automatic expression histology,” allowing to classify genes into groups with distinct spatial patterns.
Post‐Fordist reconfigurations of gender, work and life: theory and practice
Authors: Gray Breda , Ciolfi Luigina , de Carvalho Aparecido Fabiano Pinatti , D'Andrea Anthony , Wixted Lisa 
Published: May 2017

AbstractBased on an in‐depth study with 56 informants (25 women and 31 men), across the ICT (information and communication technology), creative and academic sectors in one city/regional hub in Ireland, this article investigates the so‐called revolution in work/life practices associated with the post‐Fordist labour processes of the Knowledge Economy from the perspectives of workers themselves. Recent theorizations of post‐Fordist work patterns emphasize a rearranging of work and life place boundaries; a reconfiguring of work and life time boundaries; and a dissolving of the gendered boundaries of work and life (production and social reproduction) (Adkins and Dever ; Morini and Fumagalli ; Gill and Pratt ; Weeks ; Hardt and Negri ). Our findings suggest that, instead of dissolving boundaries, workers constantly struggle to draw boundaries between what counts as work and as life, and that this varies primarily in relation to gender and stage in a gendered life trajectory. Work extensification is compensated for via a perceived freedom to shape one's own life, which is articulated in terms of individualized boundary‐drawing. While younger men embraced ‘always on’ work, they also articulated anxieties about how these work habits might interfere with family aspirations. This was also true for younger women who also struggled to make time for life in the present. For mothers, boundary drawing was articulated as a necessity but was framed more in terms of personal choice by fathers. Although all participants distinguished between paid work and life as distinct sites of value, boundaries were individually drawn and resist any easy mapping of masculinity and femininity onto the domains of work and life. Instead, we argue that it is the process of boundary drawing that reveals gendered patterns. The personalized struggles of these relatively privileged middle‐class workers centre on improving the quality of their lives, but raise important questions about the political possibilities within and beyond the world of post‐Fordist labour.
Mind the gap: financial London and the regional class pay gap
Authors: Friedman Sam , Laurison Daniel 
Published: May 2017

AbstractThe hidden barriers, or ‘gender pay gap’, preventing women from earning equivalent incomes to men is well documented. Yet recent research has uncovered that, in Britain, there is also a comparable class‐origin pay gap in higher professional and managerial occupations. So far this analysis has only been conducted at the national level and it is not known whether there are regional differences within the UK. This paper uses pooled data from the 2014 and 2015 Labour Force Survey (N = 7,534) to stage a more spatially sensitive analysis that examines regional variation in the class pay gap. We find that this ‘class ceiling’ is not evenly spatially distributed. Instead it is particularly marked in Central London, where those in high‐status occupations who are from working‐class backgrounds earn, on average, £10,660 less per year than those whose parents were in higher professional and managerial employment. Finally, we inspect the Capital further to reveal that the class pay gap is largest within Central London's banking and finance sector. Challenging policy conceptions of London as the ‘engine room’ of social mobility, these findings suggest that class disadvantage within high‐status occupations is particularly acute in the Capital. The findings also underline the value of investigating regional differences in social mobility, and demonstrate how such analysis can unravel important and previously unrecognized spatial dimensions of class inequality.