154 research outputs found

    Discourse markers activate their, <i>like</i>, cohort competitors

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    Speech in everyday conversations is riddled with discourse markers (DMs), such as well, you know, and like. However, in many lab-based studies of speech comprehension, such DMs are typically absent from the carefully articulated and highly controlled speech stimuli. As such, little is known about how these DMs influence online word recognition. The present study specifically investigated the online processing of DM like and how it influences the activation of words in the mental lexicon. We specifically targeted the cohort competitor (CC) effect in the Visual World Paradigm: Upon hearing spoken instructions to “pick up the beaker,” human listeners also typically fixate—next to the target object—referents that overlap phonologically with the target word (cohort competitors such as beetle; CCs). However, several studies have argued that CC effects are constrained by syntactic, semantic, pragmatic, and discourse constraints. Therefore, the present study investigated whether DM like influences online word recognition by activating its cohort competitors (e.g., lightbulb). In an eye-tracking experiment using the Visual World Paradigm, we demonstrate that when participants heard spoken instructions such as “Now press the button for the, like … unicycle,” they showed anticipatory looks to the CC referent (lightbulb)well before hearing the target. This CC effect was sustained for a relatively long period of time, even despite hearing disambiguating information (i.e., the /k/ in like). Analysis of the reaction times also showed that participants were significantly faster to select CC targets (lightbulb) when preceded by DM like. These findings suggest that seemingly trivial DMs, such as like, activate their CCs, impacting online word recognition. Thus, we advocate a more holistic perspective on spoken language comprehension in naturalistic communication, including the processing of DMs

    Efficient Non-viral Gene Delivery into Human Hematopoietic Stem Cells by Minicircle Sleeping Beauty Transposon Vectors

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    The Sleeping Beauty (SB) transposon system is a non-viral gene delivery platform that combines simplicity, inexpensive manufacture, and favorable safety features in the context of human applications. However, efficient correction of hematopoietic stem and progenitor cells (HSPCs) with non-viral vector systems, including SB, demands further refinement of gene delivery techniques. We set out to improve SB gene transfer into hard-to-transfect human CD34 + cells by vectorizing the SB system components in the form of minicircles that are devoid of plasmid backbone sequences and are, therefore, significantly reduced in size. As compared to conventional plasmids, delivery of the SB transposon system as minicircle DNA is 3c20 times more efficient, and it is associated with up to a 50% reduction in cellular toxicity in human CD34 + cells. Moreover, providing the SB transposase in the form of synthetic mRNA enabled us to further increase the efficacy and biosafety of stable gene delivery into hematopoietic progenitors ex vivo. Genome-wide insertion site profiling revealed a close-to-random distribution of SB transposon integrants, which is characteristically different from gammaretroviral and lentiviral integrations in HSPCs. Transplantation of gene-marked CD34 + cells in immunodeficient mice resulted in long-term engraftment and hematopoietic reconstitution, which was most efficient when the SB transposase was supplied as mRNA and nucleofected cells were maintained for 4\u20138 days in culture before transplantation. Collectively, implementation of minicircle and mRNA technologies allowed us to further refine the SB transposon system in the context of HSPC gene delivery to ultimately meet clinical demands of an efficient and safe non-viral gene therapy protocol. Ivics and collegues refined the Sleeping Beauty transposon system for gene transfer in human hematopoietic stem and progenitor cells by vectorizing the transposon components as minicircle DNA and synthetic mRNA. The advanced vector system enables efficient and safe non-viral engineering of hematopoietic cells that can be transplanted into immunodeficient mice

    Heritage language anxiety and majority language anxiety among Turkish immigrants in the Netherlands

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    Aims and objectives: This study examines the language anxiety that occurs in immigrants’ daily lives when speaking the heritage language and the majority language, both in their host country and during visits to their home country. It compares the levels of heritage language anxiety and majority language anxiety across three generations of the Turkish immigrant community in the Netherlands and explores the link between immigrants’ language anxiety, and sociobiographical (i.e. generation, gender, education) and language background variables (i.e. age of acquisition, self-perceived proficiency, frequency of language use). Design: A Likert scale-based questionnaire was administered to 116 participants across three generations who reported their language anxiety levels when speaking the heritage language and the majority language in three social contexts (i.e. family, friendship and speaking with native speakers). Findings: Statistical analyses revealed that heritage language anxiety and majority language anxiety were prevalent in immigrants’ daily life, and that levels of both forms of anxiety differed across generations, and in different daily life situations. First- and second-generation immigrants typically experienced majority language anxiety, while second- and predominantly third-generation immigrants suffered from heritage language anxiety. Relationships emerged between language background variables and both forms of anxiety, but only in certain situations. These findings suggest that language background variables on their own may be insufficient to explain immigrant language anxiety in certain social contexts (i.e. within family). Rather than merely language background factors, a variety of other issues within social, cultural and national currents must be considered when examining language anxiety in the immigrant context. Implications: Taking an interdisciplinary approach that combines language contact and foreign language anxiety/second language anxiety research, this study suggests that the concept of foreign language anxiety/second language anxiety should be expanded beyond the confines of the classroom in order to include daily interactions immigrant or minority communities. Originality: This study contributes to the limited body of evidence on the topic of language anxiety in immigrant contexts and presents a new construct ‘majority language anxiety’

    Ebf factors and MyoD cooperate to regulate muscle relaxation via Atp2a1

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    Jin, Saihong et al.Myogenic regulatory factors such as MyoD and Myf5 lie at the core of vertebrate muscle differentiation. However, E-boxes, the cognate binding sites for these transcription factors, are not restricted to the promoters/enhancers of muscle cell-specific genes. Thus, the specificity in myogenic transcription is poorly defined. Here we describe the transcription factor Ebf3 as a new determinant of muscle cell-specific transcription. In the absence of Ebf3 the lung does not unfold at birth, resulting in respiratory failure and perinatal death. This is due to a hypercontractile diaphragm with impaired Ca2+ efflux-related muscle functions. Expression of the Ca2+ pump Serca1 (Atp2a1) is downregulated in the absence of Ebf3, and its transgenic expression rescues this phenotype. Ebf3 binds directly to the promoter of Atp2a1 and synergises with MyoD in the induction of Atp2a1. In skeletal muscle, the homologous family member Ebf1 is strongly expressed and together with MyoD induces Atp2a1. Thus, Ebf3 is a new regulator of terminal muscle differentiation in the diaphragm, and Ebf factors cooperate with MyoD in the induction of muscle-specific genes. © 2014 Macmillan Publishers Limited.This work was supported by grants from the German Research Foundation (DFG, TRR54; FOR1586; FOR2033) and by a stipend of the Max Planck SocietyPeer Reviewe

    Molecular structure and developmental expression of zebrafish atp2a genes

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    [[abstract]]We isolated two atp2a genes, atp2a1 and atp2a2a, from embryonic zebrafish. Amino acid sequences deduced from zebrafish atp2a genes are aligned with orthologue proteins from other species, the results showed that they share high percentage of identities (82%–94%) and acidic pIs (5.03–5.33). Whole mount in situ hybridization experiments showed that atp2a1 and atp2a2a are maternal inherited genes which can be detected at 1-cell stage embryos and express in the entire animal pole from 6 hours post-fertilization (hpf) to 12 hpf. At the later stages (48–96 hpf), expression of atp2a1 was restricted in head and trunk muscles as well as in some neurons. In contrast to the strongly expression of atp2a1 in head muscle, expression of atp2a2a was detected in head muscle in a fainter manner. In addition, transcripts of atp2a2a were observed in the developing heart during early cardiogenesis. The present studies not only help us to comparatively analyze atp2a genes across species, but also provide useful information about expressions during early embryogenesis that will help in further investigations of functional studies of Atp2a in the future.[[incitationindex]]SCI[[booktype]]紙
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