Publications

Displaying 201 - 300 of 1218
  • Cutler, A. (2004). On spoken-word recognition in a second language. Newsletter, American Association of Teachers of Slavic and East European Languages, 47, 15-15.
  • Cutler, A. (1985). Cross-language psycholinguistics. Linguistics, 23, 659-667.
  • Cutler, A. (1982). Idioms: the older the colder. Linguistic Inquiry, 13(2), 317-320. Retrieved from http://www.jstor.org/stable/4178278?origin=JSTOR-pdf.
  • Cutler, A. (2014). In thrall to the vocabulary. Acoustics Australia, 42, 84-89.

    Abstract

    Vocabularies contain hundreds of thousands of words built from only a handful of phonemes; longer words inevitably tend to contain shorter ones. Recognising speech thus requires distinguishing intended words from accidentally present ones. Acoustic information in speech is used wherever it contributes significantly to this process; but as this review shows, its contribution differs across languages, with the consequences of this including: identical and equivalently present information distinguishing the same phonemes being used in Polish but not in German, or in English but not in Italian; identical stress cues being used in Dutch but not in English; expectations about likely embedding patterns differing across English, French, Japanese.
  • Cutler, A., Howard, D., & Patterson, K. E. (1989). Misplaced stress on prosody: A reply to Black and Byng. Cognitive Neuropsychology, 6, 67-83.

    Abstract

    The recent claim by Black and Byng (1986) that lexical access in reading is subject to prosodic constraints is examined and found to be unsupported. The evidence from impaired reading which Black and Byng report is based on poorly controlled stimulus materials and is inadequately analysed and reported. An alternative explanation of their findings is proposed, and new data are reported for which this alternative explanation can account but their model cannot. Finally, their proposal is shown to be theoretically unmotivated and in conflict with evidence from normal reading.
  • Cutler, A., Norris, D., & McQueen, J. M. (1994). Modelling lexical access from continuous speech input. Dokkyo International Review, 7, 193-215.

    Abstract

    The recognition of speech involves the segmentation of continuous utterances into their component words. Cross-linguistic evidence is briefly reviewed which suggests that although there are language-specific solutions to this segmentation problem, they have one thing in common: they are all based on language rhythm. In English, segmentation is stress-based: strong syllables are postulated to be the onsets of words. Segmentation, however, can also be achieved by a process of competition between activated lexical hypotheses, as in the Shortlist model. A series of experiments is summarised showing that segmentation of continuous speech depends on both lexical competition and a metrically-guided procedure. In the final section, the implementation of metrical segmentation in the Shortlist model is described: the activation of lexical hypotheses matching strong syllables in the input is boosted and that of hypotheses mismatching strong syllables in the input is penalised.
  • Cutler, A., & Otake, T. (1994). Mora or phoneme? Further evidence for language-specific listening. Journal of Memory and Language, 33, 824-844. doi:10.1006/jmla.1994.1039.

    Abstract

    Japanese listeners detect speech sound targets which correspond precisely to a mora (a phonological unit which is the unit of rhythm in Japanese) more easily than targets which do not. English listeners detect medial vowel targets more slowly than consonants. Six phoneme detection experiments investigated these effects in both subject populations, presented with native- and foreign-language input. Japanese listeners produced faster and more accurate responses to moraic than to nonmoraic targets both in Japanese and, where possible, in English; English listeners responded differently. The detection disadvantage for medial vowels appeared with English listeners both in English and in Japanese; again, Japanese listeners responded differently. Some processing operations which listeners apply to speech input are language-specific; these language-specific procedures, appropriate for listening to input in the native language, may be applied to foreign-language input irrespective of whether they remain appropriate.
  • Cutler, A. (2011). Listening to REAL second language. AATSEEL Newsletter, 54(3), 14.
  • Cutler, A., & Fay, D. A. (1982). One mental lexicon, phonologically arranged: Comments on Hurford’s comments. Linguistic Inquiry, 13, 107-113. Retrieved from http://www.jstor.org/stable/4178262.
  • Cutler, A. (1991). Proceed with caution. New Scientist, (1799), 53-54.
  • Cutler, A. (1989). Straw modules [Commentary/Massaro: Speech perception]. Behavioral and Brain Sciences, 12, 760-762.
  • Cutler, A. (1989). The new Victorians. New Scientist, (1663), 66.
  • Cutler, A. (1994). The perception of rhythm in language. Cognition, 50, 79-81. doi:10.1016/0010-0277(94)90021-3.
  • Cutler, A., Hawkins, J. A., & Gilligan, G. (1985). The suffixing preference: A processing explanation. Linguistics, 23, 723-758.
  • Cutler, A., & Butterfield, S. (1991). Word boundary cues in clear speech: A supplementary report. Speech Communication, 10, 335-353. doi:10.1016/0167-6393(91)90002-B.

    Abstract

    One of a listener's major tasks in understanding continuous speech is segmenting the speech signal into separate words. When listening conditions are difficult, speakers can help listeners by deliberately speaking more clearly. In four experiments, we examined how word boundaries are produced in deliberately clear speech. In an earlier report we showed that speakers do indeed mark word boundaries in clear speech, by pausing at the boundary and lengthening pre-boundary syllables; moreover, these effects are applied particularly to boundaries preceding weak syllables. In English, listeners use segmentation procedures which make word boundaries before strong syllables easier to perceive; thus marking word boundaries before weak syllables in clear speech will make clear precisely those boundaries which are otherwise hard to perceive. The present report presents supplementary data, namely prosodic analyses of the syllable following a critical word boundary. More lengthening and greater increases in intensity were applied in clear speech to weak syllables than to strong. Mean F0 was also increased to a greater extent on weak syllables than on strong. Pitch movement, however, increased to a greater extent on strong syllables than on weak. The effects were, however, very small in comparison to the durational effects we observed earlier for syllables preceding the boundary and for pauses at the boundary.
  • Dahan, D., & Tanenhaus, M. K. (2004). Continuous mapping from sound to meaning in spoken-language comprehension: Immediate effects of verb-based thematic constraints. Journal of Experimental Psychology: Learning, Memory, and Cognition, 30(2), 498-513. doi:10.1037/0278-7393.30.2.498.

    Abstract

    The authors used 2 “visual-world” eye-tracking experiments to examine lexical access using Dutch constructions in which the verb did or did not place semantic constraints on its subsequent subject noun phrase. In Experiment 1, fixations to the picture of a cohort competitor (overlapping with the onset of the referent’s name, the subject) did not differ from fixations to a distractor in the constraining-verb condition. In Experiment 2, cross-splicing introduced phonetic information that temporarily biased the input toward the cohort competitor. Fixations to the cohort competitor temporarily increased in both the neutral and constraining conditions. These results favor models in which mapping from the input onto meaning is continuous over models in which contextual effects follow access of an initial form-based competitor set.
  • D'Alessandra, Y., Carena, M. C., Spazzafumo, L., Martinelli, F., Bassetti, B., Devanna, P., Rubino, M., Marenzi, G., Colombo, G. I., Achilli, F., Maggiolini, S., Capogrossi, M. C., & Pompilio, G. (2013). Diagnostic Potential of Plasmatic MicroRNA Signatures in Stable and Unstable Angina. PLoS ONE, 8(11), e80345. doi:10.1371/journal.pone.0080345.

    Abstract

    PURPOSE: We examined circulating miRNA expression profiles in plasma of patients with coronary artery disease (CAD) vs. matched controls, with the aim of identifying novel discriminating biomarkers of Stable (SA) and Unstable (UA) angina. METHODS: An exploratory analysis of plasmatic expression profile of 367 miRNAs was conducted in a group of SA and UA patients and control donors, using TaqMan microRNA Arrays. Screening confirmation and expression analysis were performed by qRT-PCR: all miRNAs found dysregulated were examined in the plasma of troponin-negative UA (n=19) and SA (n=34) patients and control subjects (n=20), matched for sex, age, and cardiovascular risk factors. In addition, the expression of 14 known CAD-associated miRNAs was also investigated. RESULTS: Out of 178 miRNAs consistently detected in plasma samples, 3 showed positive modulation by CAD when compared to controls: miR-337-5p, miR-433, and miR-485-3p. Further, miR-1, -122, -126, -133a, -133b, and miR-199a were positively modulated in both UA and SA patients, while miR-337-5p and miR-145 showed a positive modulation only in SA or UA patients, respectively. ROC curve analyses showed a good diagnostic potential (AUC ≥ 0.85) for miR-1, -126, and -483-5p in SA and for miR-1, -126, and -133a in UA patients vs. controls, respectively. No discriminating AUC values were observed comparing SA vs. UA patients. Hierarchical cluster analysis showed that the combination of miR-1, -133a, and -126 in UA and of miR-1, -126, and -485-3p in SA correctly classified patients vs. controls with an efficiency ≥ 87%. No combination of miRNAs was able to reliably discriminate patients with UA from patients with SA. CONCLUSIONS: This work showed that specific plasmatic miRNA signatures have the potential to accurately discriminate patients with angiographically documented CAD from matched controls. We failed to identify a plasmatic miRNA expression pattern capable to differentiate SA from UA patients.
  • Dalla Bella, S., Janaqi, S., Benoit, C.-E., Farrugia, N., Bégel, V., Verga, L., Harding, E. E., & Kotz, S. A. (2024). Unravelling individual rhythmic abilities using machine learning. Scientific Reports, 14(1): 1135. doi:10.1038/s41598-024-51257-7.

    Abstract

    Humans can easily extract the rhythm of a complex sound, like music, and move to its regular beat, like in dance. These abilities are modulated by musical training and vary significantly in untrained individuals. The causes of this variability are multidimensional and typically hard to grasp in single tasks. To date we lack a comprehensive model capturing the rhythmic fingerprints of both musicians and non-musicians. Here we harnessed machine learning to extract a parsimonious model of rhythmic abilities, based on behavioral testing (with perceptual and motor tasks) of individuals with and without formal musical training (n = 79). We demonstrate that variability in rhythmic abilities and their link with formal and informal music experience can be successfully captured by profiles including a minimal set of behavioral measures. These findings highlight that machine learning techniques can be employed successfully to distill profiles of rhythmic abilities, and ultimately shed light on individual variability and its relationship with both formal musical training and informal musical experiences.

    Additional information

    supplementary materials
  • Daller, M. H., Treffers-Daller, J., & Furman, R. (2011). Transfer of conceptualization patterns in bilinguals: The construal of motion events in Turkish and German. Bilingualism: Language and Cognition, 14(1), 95-119. doi:10.1017/S1366728910000106.

    Abstract

    In the present article we provide evidence for the occurrence of transfer of conceptualization patterns in narratives of two German-Turkish bilingual groups. All bilingual participants grew up in Germany, but only one group is still resident in Germany (n = 49). The other, the returnees, moved back to Turkey after having lived in Germany for thirteen years (n = 35). The study is based on the theoretical framework for conceptual transfer outlined in Jarvis and Pavlenko (2008) and on the typology of satellite-framed and verb-framed languages developed by Talmy (1985, 1991, 2000a, b) and Slobin (1987, 1996, 2003, 2004, 2005, 2006). In the present study we provide evidence for the hypothesis that language structure affects the organization of information structure at the level of the Conceptualizer, and show that bilingual speakers’ conceptualization of motion events is influenced by the dominant linguistic environment in both languages (German for the group in Germany and Turkish for the returnees). The returnees follow the Turkish blueprints for the conceptualization of motion, in both Turkish and German event construals, whereas the German-resident bilinguals follow the German blueprints, when speaking German as well as Turkish. We argue that most of the patterns found are the result of transfer of conceptualization patterns from the dominant language of the environment.
  • Dastjerdi, M., Ozker, M., Foster, B. L., Rangarajan, V., & Parvizi, J. (2013). Numerical processing in the human parietal cortex during experimental and natural conditions. Nature Communications, 4: 2528. doi:10.1038/ncomms3528.

    Abstract

    Human cognition is traditionally studied in experimental conditions wherein confounding complexities of the natural environment are intentionally eliminated. Thus, it remains unknown how a brain region involved in a particular experimental condition is engaged in natural conditions. Here we use electrocorticography to address this uncertainty in three participants implanted with intracranial electrodes and identify activations of neuronal populations within the intraparietal sulcus region during an experimental arithmetic condition. In a subsequent analysis, we report that the same intraparietal sulcus neural populations are activated when participants, engaged in social conversations, refer to objects with numerical content. Our prototype approach provides a means for both exploring human brain dynamics as they unfold in complex social settings and reconstructing natural experiences from recorded brain signals.
  • Dautriche, I., Cristia, A., Brusini, P., Yuan, S., Fisher, C., & Christophe, A. (2014). Toddlers default to canonical surface-to-meaning mapping when learning verbs. Child Development, 85(3), 1168-1180. doi:10.1111/cdev.12183.

    Abstract

    This work was supported by grants from the French Agence Nationale de la Recherche (ANR-2010-BLAN-1901) and from French Fondation de France to Anne Christophe, from the National Institute of Child Health and Human Development (HD054448) to Cynthia Fisher, Fondation Fyssen and Ecole de Neurosciences de Paris to Alex Cristia, and a PhD fellowship from the Direction Générale de l'Armement (DGA, France) supported by the PhD program FdV (Frontières du Vivant) to Isabelle Dautriche. We thank Isabelle Brunet for the recruitment, Michel Dutat for the technical support, and Hernan Anllo for his puppet mastery skill. We are grateful to the families that participated in this study. We also thank two anonymous reviewers for their comments on an earlier draft of this manuscript.
  • Davids, N., Segers, E., Van den Brink, D., Mitterer, H., van Balkom, H., Hagoort, P., & Verhoeven, L. (2011). The nature of auditory discrimination problems in children with specific language impairment: An MMN study. Neuropsychologia, 49, 19-28. doi:10.1016/j.neuropsychologia.2010.11.001.

    Abstract

    Many children with Specific Language Impairment (SLI) show impairments in discriminating auditorily presented stimuli. The present study investigates whether these discrimination problems are speech specific or of a general auditory nature. This was studied by using a linguistic and nonlinguistic contrast that were matched for acoustic complexity in an active behavioral task and a passive ERP paradigm, known to elicit the mismatch negativity (MMN). In addition, attention skills and a variety of language skills were measured. Participants were 25 five-year-old Dutch children with SLI having receptive as well as productive language problems and 25 control children with typical speechand language development. At the behavioral level, the SLI group was impaired in discriminating the linguistic contrast as compared to the control group, while both groups were unable to distinguish the non-linguistic contrast. Moreover, the SLI group tended to have impaired attention skills which correlated with performance on most of the language tests. At the neural level, the SLI group, in contrast to the control group, did not show an MMN in response to either the linguistic or nonlinguistic contrast. The MMN data are consistent with an account that relates the symptoms in children with SLI to non-speech processing difficulties.
  • Davidson, D., & Indefrey, P. (2011). Error-related activity and correlates of grammatical plasticity. Frontiers in Psychology, 2: 219. doi:10.3389/fpsyg.2011.00219.

    Abstract

    Cognitive control involves not only the ability to manage competing task demands, but also the ability to adapt task performance during learning. This study investigated how violation-, response-, and feedback-related electrophysiological (EEG) activity changes over time during language learning. Twenty-two Dutch learners of German classified short prepositional phrases presented serially as text. The phrases were initially presented without feedback during a pre-test phase, and then with feedback in a training phase on two separate days spaced 1 week apart. The stimuli included grammatically correct phrases, as well as grammatical violations of gender and declension. Without feedback, participants' classification was near chance and did not improve over trials. During training with feedback, behavioral classification improved and violation responses appeared to both types of violation in the form of a P600. Feedback-related negative and positive components were also present from the first day of training. The results show changes in the electrophysiological responses in concert with improving behavioral discrimination, suggesting that the activity is related to grammar learning.
  • Davidson, D., & Martin, A. E. (2013). Modeling accuracy as a function of response time with the generalized linear mixed effects model. Acta Psychologica, 144(1), 83-96. doi:10.1016/j.actpsy.2013.04.016.

    Abstract

    In psycholinguistic studies using error rates as a response measure, response times (RT) are most often analyzed independently of the error rate, although it is widely recognized that they are related. In this paper we present a mixed effects logistic regression model for the error rate that uses RT as a trial-level fixed- and random-effect regression input. Production data from a translation–recall experiment are analyzed as an example. Several model comparisons reveal that RT improves the fit of the regression model for the error rate. Two simulation studies then show how the mixed effects regression model can identify individual participants for whom (a) faster responses are more accurate, (b) faster responses are less accurate, or (c) there is no relation between speed and accuracy. These results show that this type of model can serve as a useful adjunct to traditional techniques, allowing psycholinguistic researchers to examine more closely the relationship between RT and accuracy in individual subjects and better account for the variability which may be present, as well as a preliminary step to more advanced RT–accuracy modeling.
  • Debreslioska, S., Ozyurek, A., Gullberg, M., & Perniss, P. M. (2013). Gestural viewpoint signals referent accessibility. Discourse Processes, 50(7), 431-456. doi:10.1080/0163853x.2013.824286.

    Abstract

    The tracking of entities in discourse is known to be a bimodal phenomenon. Speakers achieve cohesion in speech by alternating between full lexical forms, pronouns, and zero anaphora as they track referents. They also track referents in co-speech gestures. In this study, we explored how viewpoint is deployed in reference tracking, focusing on representations of animate entities in German narrative discourse. We found that gestural viewpoint systematically varies depending on discourse context. Speakers predominantly use character viewpoint in maintained contexts and observer viewpoint in reintroduced contexts. Thus, gestural viewpoint seems to function as a cohesive device in narrative discourse. The findings expand on and provide further evidence for the coordination between speech and gesture on the discourse level that is crucial to understanding the tight link between the two modalities.
  • Dediu, D. (2011). Are languages really independent from genes? If not, what would a genetic bias affecting language diversity look like? Human Biology, 83, 279-296. doi:10.3378/027.083.0208.

    Abstract

    It is generally accepted that the relationship between human genes
    and language is very complex and multifaceted. This has its roots in the
    “regular” complexity governing the interplay among genes and between genes
    and environment for most phenotypes, but with the added layer of supraontogenetic
    and supra-individual processes defining culture. At the coarsest
    level, focusing on the species, it is clear that human-specific—but not necessarily
    faculty-specific—genetic factors subtend our capacity for language and a
    currently very productive research program is aiming at uncovering them. At the
    other end of the spectrum, it is uncontroversial that individual-level variations in
    different aspects related to speech and language have an important genetic
    component and their discovery and detailed characterization have already started
    to revolutionize the way we think about human nature. However, at the
    intermediate, glossogenetic/population level, the relationship becomes controversial,
    partly due to deeply ingrained beliefs about language acquisition and
    universality and partly because of confusions with a different type of genelanguages
    correlation due to shared history. Nevertheless, conceptual, mathematical
    and computational models—and, recently, experimental evidence from
    artificial languages and songbirds—have repeatedly shown that genetic biases
    affecting the acquisition or processing of aspects of language and speech can be
    amplified by population-level intergenerational cultural processes and made
    manifest either as fixed “universal” properties of language or as structured
    linguistic diversity. Here, I review several such models as well as the recently
    proposed case of a causal relationship between the distribution of tone languages
    and two genes related to brain growth and development, ASPM and Microcephalin,
    and I discuss the relevance of such genetic biasing for language
    evolution, change, and diversity.
  • Dediu, D. (2011). A Bayesian phylogenetic approach to estimating the stability of linguistic features and the genetic biasing of tone. Proceedings of the Royal Society of London/B, 278(1704), 474-479. doi:10.1098/rspb.2010.1595.

    Abstract

    Language is a hallmark of our species and understanding linguistic diversity is an area of major interest. Genetic factors influencing the cultural transmission of language provide a powerful and elegant explanation for aspects of the present day linguistic diversity and a window into the emergence and evolution of language. In particular, it has recently been proposed that linguistic tone—the usage of voice pitch to convey lexical and grammatical meaning—is biased by two genes involved in brain growth and development, ASPM and Microcephalin. This hypothesis predicts that tone is a stable characteristic of language because of its ‘genetic anchoring’. The present paper tests this prediction using a Bayesian phylogenetic framework applied to a large set of linguistic features and language families, using multiple software implementations, data codings, stability estimations, linguistic classifications and outgroup choices. The results of these different methods and datasets show a large agreement, suggesting that this approach produces reliable estimates of the stability of linguistic data. Moreover, linguistic tone is found to be stable across methods and datasets, providing suggestive support for the hypothesis of genetic influences on its distribution.
  • Dediu, D., & Levinson, S. C. (2013). On the antiquity of language: The reinterpretation of Neandertal linguistic capacities and its consequences. Frontiers in Language Sciences, 4: 397. doi:10.3389/fpsyg.2013.00397.

    Abstract

    It is usually assumed that modern language is a recent phenomenon, coinciding with the emergence of modern humans themselves. Many assume as well that this is the result of a single, sudden mutation giving rise to the full “modern package”. However, we argue here that recognizably modern language is likely an ancient feature of our genus pre-dating at least the common ancestor of modern humans and Neandertals about half a million years ago. To this end, we adduce a broad range of evidence from linguistics, genetics, palaeontology and archaeology clearly suggesting that Neandertals shared with us something like modern speech and language. This reassessment of the antiquity of modern language, from the usually quoted 50,000-100,000 years to half a million years, has profound consequences for our understanding of our own evolution in general and especially for the sciences of speech and language. As such, it argues against a saltationist scenario for the evolution of language, and towards a gradual process of culture-gene co-evolution extending to the present day. Another consequence is that the present-day linguistic diversity might better reflect the properties of the design space for language and not just the vagaries of history, and could also contain traces of the languages spoken by other human forms such as the Neandertals.
  • Dediu, D., & Cysouw, M. A. (2013). Some structural aspects of language are more stable than others: A comparison of seven methods. PLoS One, 8: e55009. doi:10.1371/journal.pone.0055009.

    Abstract

    Understanding the patterns and causes of differential structural stability is an area of major interest for the study of language change and evolution. It is still debated whether structural features have intrinsic stabilities across language families and geographic areas, or if the processes governing their rate of change are completely dependent upon the specific context of a given language or language family. We conducted an extensive literature review and selected seven different approaches to conceptualising and estimating the stability of structural linguistic features, aiming at comparing them using the same dataset, the World Atlas of Language Structures. We found that, despite profound conceptual and empirical differences between these methods, they tend to agree in classifying some structural linguistic features as being more stable than others. This suggests that there are intrinsic properties of such structural features influencing their stability across methods, language families and geographic areas. This finding is a major step towards understanding the nature of structural linguistic features and their interaction with idiosyncratic, lineage- and area-specific factors during language change and evolution.
  • Defina, R. (2014). Arbil: Free tool for creating, editing and searching metadata. Language Documentation and Conservation, 8, 307-314.
  • den Hoed, M., Eijgelsheim, M., Esko, T., Brundel, B. J. J. M., Peal, D. S., Evans, D. M., Nolte, I. M., Segrè, A. V., Holm, H., Handsaker, R. E., Westra, H.-J., Johnson, T., Isaacs, A., Yang, J., Lundby, A., Zhao, J. H., Kim, Y. J., Go, M. J., Almgren, P., Bochud, M. and 249 moreden Hoed, M., Eijgelsheim, M., Esko, T., Brundel, B. J. J. M., Peal, D. S., Evans, D. M., Nolte, I. M., Segrè, A. V., Holm, H., Handsaker, R. E., Westra, H.-J., Johnson, T., Isaacs, A., Yang, J., Lundby, A., Zhao, J. H., Kim, Y. J., Go, M. J., Almgren, P., Bochud, M., Boucher, G., Cornelis, M. C., Gudbjartsson, D., Hadley, D., van der Harst, P., Hayward, C., den Heijer, M., Igl, W., Jackson, A. U., Kutalik, Z., Luan, J., Kemp, J. P., Kristiansson, K., Ladenvall, C., Lorentzon, M., Montasser, M. E., Njajou, O. T., O'Reilly, P. F., Padmanabhan, S., St Pourcain, B., Rankinen, T., Salo, P., Tanaka, T., Timpson, N. J., Vitart, V., Waite, L., Wheeler, W., Zhang, W., Draisma, H. H. M., Feitosa, M. F., Kerr, K. F., Lind, P. A., Mihailov, E., Onland-Moret, N. C., Song, C., Weedon, M. N., Xie, W., Yengo, L., Absher, D., Albert, C. M., Alonso, A., Arking, D. E., de Bakker, P. I. W., Balkau, B., Barlassina, C., Benaglio, P., Bis, J. C., Bouatia-Naji, N., Brage, S., Chanock, S. J., Chines, P. S., Chung, M., Darbar, D., Dina, C., Dörr, M., Elliott, P., Felix, S. B., Fischer, K., Fuchsberger, C., de Geus, E. J. C., Goyette, P., Gudnason, V., Harris, T. B., Hartikainen, A.-L., Havulinna, A. S., Heckbert, S. R., Hicks, A. A., Hofman, A., Holewijn, S., Hoogstra-Berends, F., Hottenga, J.-J., Jensen, M. K., Johansson, A., Junttila, J., Kääb, S., Kanon, B., Ketkar, S., Khaw, K.-T., Knowles, J. W., Kooner, A. S., Kors, J. A., Kumari, M., Milani, L., Laiho, P., Lakatta, E. G., Langenberg, C., Leusink, M., Liu, Y., Luben, R. N., Lunetta, K. L., Lynch, S. N., Markus, M. R. P., Marques-Vidal, P., Mateo Leach, I., McArdle, W. L., McCarroll, S. A., Medland, S. E., Miller, K. A., Montgomery, G. W., Morrison, A. C., Müller-Nurasyid, M., Navarro, P., Nelis, M., O'Connell, J. R., O'Donnell, C. J., Ong, K. K., Newman, A. B., Peters, A., Polasek, O., Pouta, A., Pramstaller, P. P., Psaty, B. M., Rao, D. C., Ring, S. M., Rossin, E. J., Rudan, D., Sanna, S., Scott, R. A., Sehmi, J. S., Sharp, S., Shin, J. T., Singleton, A. B., Smith, A. V., Soranzo, N., Spector, T. D., Stewart, C., Stringham, H. M., Tarasov, K. V., Uitterlinden, A. G., Vandenput, L., Hwang, S.-J., Whitfield, J. B., Wijmenga, C., Wild, S. H., Willemsen, G., Wilson, J. F., Witteman, J. C. M., Wong, A., Wong, Q., Jamshidi, Y., Zitting, P., Boer, J. M. A., Boomsma, D. I., Borecki, I. B., van Duijn, C. M., Ekelund, U., Forouhi, N. G., Froguel, P., Hingorani, A., Ingelsson, E., Kivimaki, M., Kronmal, R. A., Kuh, D., Lind, L., Martin, N. G., Oostra, B. A., Pedersen, N. L., Quertermous, T., Rotter, J. I., van der Schouw, Y. T., Verschuren, W. M. M., Walker, M., Albanes, D., Arnar, D. O., Assimes, T. L., Bandinelli, S., Boehnke, M., de Boer, R. A., Bouchard, C., Caulfield, W. L. M., Chambers, J. C., Curhan, G., Cusi, D., Eriksson, J., Ferrucci, L., van Gilst, W. H., Glorioso, N., de Graaf, J., Groop, L., Gyllensten, U., Hsueh, W.-C., Hu, F. B., Huikuri, H. V., Hunter, D. J., Iribarren, C., Isomaa, B., Jarvelin, M.-R., Jula, A., Kähönen, M., Kiemeney, L. A., van der Klauw, M. M., Kooner, J. S., Kraft, P., Iacoviello, L., Lehtimäki, T., Lokki, M.-L.-L., Mitchell, B. D., Navis, G., Nieminen, M. S., Ohlsson, C., Poulter, N. R., Qi, L., Raitakari, O. T., Rimm, E. B., Rioux, J. D., Rizzi, F., Rudan, I., Salomaa, V., Sever, P. S., Shields, D. C., Shuldiner, A. R., Sinisalo, J., Stanton, A. V., Stolk, R. P., Strachan, D. P., Tardif, J.-C., Thorsteinsdottir, U., Tuomilehto, J., van Veldhuisen, D. J., Virtamo, J., Viikari, J., Vollenweider, P., Waeber, G., Widen, E., Cho, Y. S., Olsen, J. V., Visscher, P. M., Willer, C., Franke, L., Erdmann, J., Thompson, J. R., Pfeufer, A., Sotoodehnia, N., Newton-Cheh, C., Ellinor, P. T., Stricker, B. H. C., Metspalu, A., Perola, M., Beckmann, J. S., Smith, G. D., Stefansson, K., Wareham, N. J., Munroe, P. B., Sibon, O. C. M., Milan, D. J., Snieder, H., Samani, N. J., Loos, R. J. F., Global BPgen Consortium, CARDIoGRAM Consortium, PR GWAS Consortium, QRS GWAS Consortium, QT-IGC Consortium, & CHARGE-AF Consortium (2013). Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. Nature Genetics, 45(6), 621-631. doi:10.1038/ng.2610.

    Abstract

    Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.
  • Deriziotis, P., O'Roak, B. J., Graham, S. A., Estruch, S. B., Dimitropoulou, D., Bernier, R. A., Gerdts, J., Shendure, J., Eichler, E. E., & Fisher, S. E. (2014). De novo TBR1 mutations in sporadic autism disrupt protein functions. Nature Communications, 5: 4954. doi:10.1038/ncomms5954.

    Abstract

    Next-generation sequencing recently revealed that recurrent disruptive mutations in a few genes may account for 1% of sporadic autism cases. Coupling these novel genetic data to empirical assays of protein function can illuminate crucial molecular networks. Here we demonstrate the power of the approach, performing the first functional analyses of TBR1 variants identified in sporadic autism. De novo truncating and missense mutations disrupt multiple aspects of TBR1 function, including subcellular localization, interactions with co-regulators and transcriptional repression. Missense mutations inherited from unaffected parents did not disturb function in our assays. We show that TBR1 homodimerizes, that it interacts with FOXP2, a transcription factor implicated in speech/language disorders, and that this interaction is disrupted by pathogenic mutations affecting either protein. These findings support the hypothesis that de novo mutations in sporadic autism have severe functional consequences. Moreover, they uncover neurogenetic mechanisms that bridge different neurodevelopmental disorders involving language deficits.
  • Deriziotis, P., André, R., Smith, D. M., Goold, R., Kinghorn, K. J., Kristiansen, M., Nathan, J. A., Rosenzweig, R., Krutauz, D., Glickman, M. H., Collinge, J., Goldberg, A. L., & Tabrizi, S. J. (2011). Misfolded PrP impairs the UPS by interaction with the 20S proteasome and inhibition of substrate entry. EMBO Journal, 30(15), 3065-3077. doi:10.1038/emboj.2011.224.

    Abstract

    * Deriziotis, P., André, R., and Smith. D.M. contributed equally to this work * - Prion diseases are associated with the conversion of cellular prion protein (PrP(C)) to toxic β-sheet isoforms (PrP(Sc)), which are reported to inhibit the ubiquitin-proteasome system (UPS). Accordingly, UPS substrates accumulate in prion-infected mouse brains, suggesting impairment of the 26S proteasome. A direct interaction between its 20S core particle and PrP isoforms was demonstrated by immunoprecipitation. β-PrP aggregates associated with the 20S particle, but did not impede binding of the PA26 complex, suggesting that the aggregates do not bind to its ends. Aggregated β-PrP reduced the 20S proteasome's basal peptidase activity, and the enhanced activity induced by C-terminal peptides from the 19S ATPases or by the 19S regulator itself, including when stimulated by polyubiquitin conjugates. However, the 20S proteasome was not inhibited when the gate in the α-ring was open due to a truncation mutation or by association with PA26/PA28. These PrP aggregates inhibit by stabilising the closed conformation of the substrate entry channel. A similar inhibition of substrate entry into the proteasome may occur in other neurodegenerative diseases where misfolded β-sheet-rich proteins accumulate.

    Additional information

    EMBOsup.pdf
  • Deriziotis, P., Graham, S. A., Estruch, S. B., & Fisher, S. E. (2014). Investigating protein-protein interactions in live cells using Bioluminescence Resonance Energy Transfer. Journal of visualized experiments, 87: e51438. doi:10.3791/51438.

    Abstract

    Assays based on Bioluminescence Resonance Energy Transfer (BRET) provide a sensitive and reliable means to monitor protein-protein interactions in live cells. BRET is the non-radiative transfer of energy from a ‘donor’ luciferase enzyme to an ‘acceptor’ fluorescent protein. In the most common configuration of this assay, the donor is Renilla reniformis luciferase and the acceptor is Yellow Fluorescent Protein (YFP). Because the efficiency of energy transfer is strongly distance-dependent, observation of the BRET phenomenon requires that the donor and acceptor be in close proximity. To test for an interaction between two proteins of interest in cultured mammalian cells, one protein is expressed as a fusion with luciferase and the second as a fusion with YFP. An interaction between the two proteins of interest may bring the donor and acceptor sufficiently close for energy transfer to occur. Compared to other techniques for investigating protein-protein interactions, the BRET assay is sensitive, requires little hands-on time and few reagents, and is able to detect interactions which are weak, transient, or dependent on the biochemical environment found within a live cell. It is therefore an ideal approach for confirming putative interactions suggested by yeast two-hybrid or mass spectrometry proteomics studies, and in addition it is well-suited for mapping interacting regions, assessing the effect of post-translational modifications on protein-protein interactions, and evaluating the impact of mutations identified in patient DNA.

    Additional information

    video
  • Deriziotis, P., & Fisher, S. E. (2013). Neurogenomics of speech and language disorders: The road ahead. Genome Biology, 14: 204. doi:10.1186/gb-2013-14-4-204.

    Abstract

    Next-generation sequencing is set to transform the discovery of genes underlying neurodevelopmental disorders, and so off er important insights into the biological bases of spoken language. Success will depend on functional assessments in neuronal cell lines, animal models and humans themselves.
  • Devanna, P., & Vernes, S. C. (2014). A direct molecular link between the autism candidate gene RORa and the schizophrenia candidate MIR137. Scientific Reports, 4: 3994. doi:10.1038/srep03994.

    Abstract

    Retinoic acid-related orphan receptor alpha gene (RORa) and the microRNA MIR137 have both recently been identified as novel candidate genes for neuropsychiatric disorders. RORa encodes a ligand-dependent orphan nuclear receptor that acts as a transcriptional regulator and miR-137 is a brain enriched small non-coding RNA that interacts with gene transcripts to control protein levels. Given the mounting evidence for RORa in autism spectrum disorders (ASD) and MIR137 in schizophrenia and ASD, we investigated if there was a functional biological relationship between these two genes. Herein, we demonstrate that miR-137 targets the 3'UTR of RORa in a site specific manner. We also provide further support for MIR137 as an autism candidate by showing that a large number of previously implicated autism genes are also putatively targeted by miR-137. This work supports the role of MIR137 as an ASD candidate and demonstrates a direct biological link between these previously unrelated autism candidate genes
  • Devanna, P., Middelbeek, J., & Vernes, S. C. (2014). FOXP2 drives neuronal differentiation by interacting with retinoic acid signaling pathways. Frontiers in Cellular Neuroscience, 8: 305. doi:10.3389/fncel.2014.00305.

    Abstract

    FOXP2 was the first gene shown to cause a Mendelian form of speech and language disorder. Although developmentally expressed in many organs, loss of a single copy of FOXP2 leads to a phenotype that is largely restricted to orofacial impairment during articulation and linguistic processing deficits. Why perturbed FOXP2 function affects specific aspects of the developing brain remains elusive. We investigated the role of FOXP2 in neuronal differentiation and found that FOXP2 drives molecular changes consistent with neuronal differentiation in a human model system. We identified a network of FOXP2 regulated genes related to retinoic acid signaling and neuronal differentiation. FOXP2 also produced phenotypic changes associated with neuronal differentiation including increased neurite outgrowth and reduced migration. Crucially, cells expressing FOXP2 displayed increased sensitivity to retinoic acid exposure. This suggests a mechanism by which FOXP2 may be able to increase the cellular differentiation response to environmental retinoic acid cues for specific subsets of neurons in the brain. These data demonstrate that FOXP2 promotes neuronal differentiation by interacting with the retinoic acid signaling pathway and regulates key processes required for normal circuit formation such as neuronal migration and neurite outgrowth. In this way, FOXP2, which is found only in specific subpopulations of neurons in the brain, may drive precise neuronal differentiation patterns and/or control localization and connectivity of these FOXP2 positive cells
  • Devaraju, K., Barnabé-Heider, F., Kokaia, Z., & Lindvall, O. (2013). FoxJ1-expressing cells contribute to neurogenesis in forebrain of adult rats: Evidence from in vivo electroporation combined with piggyBac transposon. ScienceDirect, 319(18), 2790-2800. doi:10.1016/j.yexcr.2013.08.028.

    Abstract

    Ependymal cells in the lateral ventricular wall are considered to be post-mitotic but can give rise to neuroblasts and astrocytes after stroke in adult mice due to insult-induced suppression of Notch signaling. The transcription factor FoxJ1, which has been used to characterize mouse ependymal cells, is also expressed by a subset of astrocytes. Cells expressing FoxJ1, which drives the expression of motile cilia, contribute to early postnatal neurogenesis in mouse olfactory bulb. The distribution and progeny of FoxJ1-expressing cells in rat forebrain are unknown. Here we show using immunohistochemistry that the overall majority of FoxJ1-expressing cells in the lateral ventricular wall of adult rats are ependymal cells with a minor population being astrocytes. To allow for long-term fate mapping of FoxJ1-derived cells, we used the piggyBac system for in vivo gene transfer with electroporation. Using this method, we found that FoxJ1-expressing cells, presumably the astrocytes, give rise to neuroblasts and mature neurons in the olfactory bulb both in intact and stroke-damaged brain of adult rats. No significant contribution of FoxJ1-derived cells to stroke-induced striatal neurogenesis was detected. These data indicate that in the adult rat brain, FoxJ1-expressing cells contribute to the formation of new neurons in the olfactory bulb but are not involved in the cellular repair after stroke.
  • Dikshit, A. P., Das, D., Samal, R. R., Parashar, K., Mishra, C., & Parashar, S. (2024). Optimization of (Ba1-xCax)(Ti0.9Sn0.1)O3 ceramics in X-band using Machine Learning. Journal of Alloys and Compounds, 982: 173797. doi:10.1016/j.jallcom.2024.173797.

    Abstract

    Developing efficient electromagnetic interference shielding materials has become significantly important in present times. This paper reports a series of (Ba1-xCax)(Ti0.9Sn0.1)O3 (BCTS) ((x =0, 0.01, 0.05, & 0.1)ceramics synthesized by conventional method which were studied for electromagnetic interference shielding (EMI) applications in X-band (8-12.4 GHz). EMI shielding properties and all S parameters (S11 & S12) of BCTS ceramic pellets were measured in the frequency range (8-12.4 GHz) using a Vector Network Analyser (VNA). The BCTS ceramic pellets for x = 0.05 showed maximum total effective shielding of 46 dB indicating good shielding behaviour for high-frequency applications. However, the development of lead-free ceramics with different concentrations usually requires iterative experiments resulting in, longer development cycles and higher costs. To address this, we used a machine learning (ML) strategy to predict the EMI shielding for different concentrations and experimentally verify the concentration predicted to give the best EMI shielding. The ML model predicted BCTS ceramics with concentration (x = 0.06, 0.07, 0.08, and 0.09) to have higher shielding values. On experimental verification, a shielding value of 58 dB was obtained for x = 0.08, which was significantly higher than what was obtained experimentally before applying the ML approach. Our results show the potential of using ML in accelerating the process of optimal material development, reducing the need for repeated experimental measures significantly.
  • Dimroth, C. (1998). Indiquer la portée en allemand L2: Une étude longitudinale de l'acquisition des particules de portée. AILE (Acquisition et Interaction en Langue étrangère), 11, 11-34.
  • Dingemanse, M., & Enfield, N. J. (2014). Ongeschreven regels van de taal. Psyche en Brein, 6, 6-11.

    Abstract

    Als je wereldwijd gesprekken beluistert, merk je dat de menselijke dialoog universele regels volgt. Die sturen en verrijken onze sociale interactie.
  • Dingemanse, M., Blythe, J., & Dirksmeyer, T. (2014). Formats for other-initiation of repair across languages: An exercise in pragmatic typology. Studies in Language, 38, 5-43. doi:10.1075/sl.38.1.01din.

    Abstract

    In conversation, people have to deal with problems of speaking, hearing, and understanding. We report on a cross-linguistic investigation of the conversational structure of other-initiated repair (also known as collaborative repair, feedback, requests for clarification, or grounding sequences). We take stock of formats for initiating repair across languages (comparable to English huh?, who?, y’mean X?, etc.) and find that different languages make available a wide but remarkably similar range of linguistic resources for this function. We exploit the patterned variation as evidence for several underlying concerns addressed by repair initiation: characterising trouble, managing responsibility, and handling knowledge. The concerns do not always point in the same direction and thus provide participants in interaction with alternative principles for selecting one format over possible others. By comparing conversational structures across languages, this paper contributes to pragmatic typology: the typology of systems of language use and the principles that shape them
  • Dingemanse, M. (2013). Ideophones and gesture in everyday speech. Gesture, 13, 143-165. doi:10.1075/gest.13.2.02din.

    Abstract

    This article examines the relation between ideophones and gestures in a corpus of everyday discourse in Siwu, a richly ideophonic language spoken in Ghana. The overall frequency of ideophone-gesture couplings in everyday speech is lower than previously suggested, but two findings shed new light on the relation between ideophones and gesture. First, discourse type makes a difference: ideophone-gesture couplings are more frequent in narrative contexts, a finding that explains earlier claims, which were based not on everyday language use but on elicited narratives. Second, there is a particularly strong coupling between ideophones and one type of gesture: iconic gestures. This coupling allows us to better understand iconicity in relation to the affordances of meaning and modality. Ultimately, the connection between ideophones and iconic gestures is explained by reference to the depictive nature of both. Ideophone and iconic gesture are two aspects of the process of depiction
  • Dingemanse, M. (2011). Ideophones and the aesthetics of everyday language in a West-African society. The Senses & Society, 6(1), 77-85. doi:10.2752/174589311X12893982233830.

    Abstract

    This article explores language, culture, and the perceptual world as reflected in a particular linguistic device: ideophones, marked words that depict sensory imagery. Data from a range of elicitation tasks shows that ideophones are a key resource in talking about sensory perception in Siwu. Their use in everyday conversations underlines their communicative versatility while at the same time showing that people delight in their expressiveness. In ideophones, we have an expressive resource that combines sheer playfulness with extraordinary precision
  • Dingemanse, M. (2014). Making new ideophones in Siwu: Creative depiction in conversation. Pragmatics and Society, 5(3), 384-405. doi:10.1075/ps.5.3.04din.

    Abstract

    Ideophones are found in many of the world’s languages. Though they are a major word class on a par with nouns and verbs, their origins are ill-understood, and the question of ideophone creation has been a source of controversy. This paper studies ideophone creation in naturally occurring speech. New, unconventionalised ideophones are identified using native speaker judgements, and are studied in context to understand the rules and regularities underlying their production and interpretation. People produce and interpret new ideophones with the help of the semiotic infrastructure that underlies the use of existing ideophones: foregrounding frames certain stretches of speech as depictive enactments of sensory imagery, and various types of iconicity link forms and meanings. As with any creative use of linguistic resources, context and common ground also play an important role in supporting rapid ‘good enough’ interpretations of new material. The making of new ideophones is a special case of a more general phenomenon of creative depiction: the art of presenting verbal material in such a way that the interlocutor recognises and interprets it as a depiction.
  • Dingemanse, M., & Enfield, N. J. (2014). Let's talk: Universal social rules underlie languages. Scientific American Mind, 25, 64-69. doi:10.1038/scientificamericanmind0914-64.

    Abstract

    Recent developments in the science of language signal the emergence of a new paradigm for language study: a social approach to the fundamental questions of what language is like, how much languages really have in common, and why only our species has it. The key to these developments is a new appreciation of the need to study everyday spoken language, with all its complications and ‘imperfections’, in a systematic way. The work reviewed in this article —on turn-taking, timing, and other-initiated repair in languages around the world— has important implications for our understanding of human sociality and sheds new light on the social shape of language. For the first time in the history of linguistics, we are no longer tied to what can be written down or thought up. Rather, we look at language as a biologist would: as it occurs in nature.
  • Dingemanse, M., Torreira, F., & Enfield, N. J. (2013). Is “Huh?” a universal word? Conversational infrastructure and the convergent evolution of linguistic items. PLoS One, 8(11): e78273. doi:10.1371/journal.pone.0078273.

    Abstract

    A word like Huh?–used as a repair initiator when, for example, one has not clearly heard what someone just said– is found in roughly the same form and function in spoken languages across the globe. We investigate it in naturally occurring conversations in ten languages and present evidence and arguments for two distinct claims: that Huh? is universal, and that it is a word. In support of the first, we show that the similarities in form and function of this interjection across languages are much greater than expected by chance. In support of the second claim we show that it is a lexical, conventionalised form that has to be learnt, unlike grunts or emotional cries. We discuss possible reasons for the cross-linguistic similarity and propose an account in terms of convergent evolution. Huh? is a universal word not because it is innate but because it is shaped by selective pressures in an interactional environment that all languages share: that of other-initiated repair. Our proposal enhances evolutionary models of language change by suggesting that conversational infrastructure can drive the convergent cultural evolution of linguistic items.
  • Dingemanse, M., & Enfield, N. J. (2024). Interactive repair and the foundations of language. Trends in Cognitive Sciences, 28(1), 30-42. doi:10.1016/j.tics.2023.09.003.

    Abstract

    The robustness and flexibility of human language is underpinned by a machinery of interactive repair. Repair is deeply intertwined with two core properties of human language: reflexivity (it can communicate about itself) and accountability (it is used to publicly enforce social norms). We review empirical and theoretical advances from across the cognitive sciences that mark interactive repair as a domain of pragmatic universals, a key place to study metacognition in interaction, and a system that enables collective computation. This provides novel insights on the role of repair in comparative cognition, language development and human-computer interaction. As an always-available fallback option and an infrastructure for negotiating social commitments, interactive repair is foundational to the resilience, complexity, and flexibility of human language.
  • Dingemanse, M. (2024). Interjections at the heart of language. Annual Review of Linguistics, 10, 257-277. doi:10.1146/annurev-linguistics-031422-124743.
  • Doherty, M., & Klein, W. (Eds.). (1991). Übersetzung [Special Issue]. Zeitschrift für Literaturwissenschaft und Linguistik, (84).
  • Dolscheid, S., Hunnius, S., Casasanto, D., & Majid, A. (2014). Prelinguistic infants are sensitive to space-pitch associations found across cultures. Psychological Science, 25(6), 1256-1261. doi:10.1177/0956797614528521.

    Abstract

    People often talk about musical pitch using spatial metaphors. In English, for instance, pitches can be “high” or “low” (i.e., height-pitch association), whereas in other languages, pitches are described as “thin” or “thick” (i.e., thickness-pitch association). According to results from psychophysical studies, metaphors in language can shape people’s nonlinguistic space-pitch representations. But does language establish mappings between space and pitch in the first place, or does it only modify preexisting associations? To find out, we tested 4-month-old Dutch infants’ sensitivity to height-pitch and thickness-pitch mappings using a preferential-looking paradigm. The infants looked significantly longer at cross-modally congruent stimuli for both space-pitch mappings, which indicates that infants are sensitive to these associations before language acquisition. The early presence of space-pitch mappings means that these associations do not originate from language. Instead, language builds on preexisting mappings, changing them gradually via competitive associative learning. Space-pitch mappings that are language-specific in adults develop from mappings that may be universal in infants.
  • Dolscheid, S., Shayan, S., Majid, A., & Casasanto, D. (2013). The thickness of musical pitch: Psychophysical evidence for linguistic relativity. Psychological Science, 24, 613-621. doi:10.1177/0956797612457374.

    Abstract

    Do people who speak different languages think differently, even when they are not using language? To find out, we used nonlinguistic psychophysical tasks to compare mental representations of musical pitch in native speakers of Dutch and Farsi. Dutch speakers describe pitches as high (hoog) or low (laag), whereas Farsi speakers describe pitches as thin (na-zok) or thick (koloft). Differences in language were reflected in differences in performance on two pitch-reproduction tasks, even though the tasks used simple, nonlinguistic stimuli and responses. To test whether experience using language influences mental representations of pitch, we trained native Dutch speakers to describe pitch in terms of thickness, as Farsi speakers do. After the training, Dutch speakers’ performance on a nonlinguistic psychophysical task resembled the performance of native Farsi speakers. People who use different linguistic space-pitch metaphors also think about pitch differently. Language can play a causal role in shaping nonlinguistic representations of musical pitch.

    Additional information

    DS_10.1177_0956797612457374.pdf
  • Donnelly, S., Rowland, C. F., Chang, F., & Kidd, E. (2024). A comprehensive examination of prediction‐based error as a mechanism for syntactic development: Evidence from syntactic priming. Cognitive Science, 48(4): e13431. doi:10.1111/cogs.13431.

    Abstract

    Prediction-based accounts of language acquisition have the potential to explain several different effects in child language acquisition and adult language processing. However, evidence regarding the developmental predictions of such accounts is mixed. Here, we consider several predictions of these accounts in two large-scale developmental studies of syntactic priming of the English dative alternation. Study 1 was a cross-sectional study (N = 140) of children aged 3−9 years, in which we found strong evidence of abstract priming and the lexical boost, but little evidence that either effect was moderated by age. We found weak evidence for a prime surprisal effect; however, exploratory analyses revealed a protracted developmental trajectory for verb-structure biases, providing an explanation as for why prime surprisal effects are more elusive in developmental populations. In a longitudinal study (N = 102) of children in tightly controlled age bands at 42, 48, and 54 months, we found priming effects emerged on trials with verb overlap early but did not observe clear evidence of priming on trials without verb overlap until 54 months. There was no evidence of a prime surprisal effect at any time point and none of the effects were moderated by age. The results relating to the emergence of the abstract priming and lexical boost effects are consistent with prediction-based models, while the absence of age-related effects appears to reflect the structure-specific challenges the dative presents to English-acquiring children. Overall, our complex pattern of findings demonstrates the value of developmental data sets in testing psycholinguistic theory.

    Additional information

    table S1 and S2 appendix A, B, C and D
  • Dow, D. J., Huxley-Jones, J., Hall, J. M., Francks, C., Maycox, P. R., Kew, J. N., Gloger, I. S., Mehta, N. A., Kelly, F. M., Muglia, P., Breen, G., Jugurnauth, S., Pederoso, I., St.Clair, D., Rujescu, D., & Barnes, M. R. (2011). ADAMTSL3 as a candidate gene for schizophrenia: Gene sequencing and ultra-high density association analysis by imputation. Schizophrenia Research, 127(1-3), 28-34. doi:10.1016/j.schres.2010.12.009.

    Abstract

    We previously reported an association with a putative functional variant in the ADAMTSL3 gene, just below genome-wide significance in a genome-wide association study of schizophrenia. As variants impacting the function of ADAMTSL3 (a disintegrin-like and metalloprotease domain with thrombospondin type I motifs-like-3) could illuminate a novel disease mechanism and a potentially specific target, we have used complementary approaches to further evaluate the association. We imputed genotypes and performed high density association analysis using data from the HapMap and 1000 genomes projects. To review all variants that could potentially cause the association, and to identify additional possible pathogenic rare variants, we sequenced ADAMTSL3 in 92 schizophrenics. A total of 71 ADAMTSL3 variants were identified by sequencing, many were also seen in the 1000 genomes data, but 26 were novel. None of the variants identified by re-sequencing was in strong linkage disequilibrium (LD) with the associated markers. Imputation analysis refined association between ADAMTSL3 and schizophrenia, and highlighted additional common variants with similar levels of association. We evaluated the functional consequences of all variants identified by sequencing, or showing direct or imputed association. The strongest evidence for function remained with the originally associated variant, rs950169, suggesting that this variant may be causal of the association. Rare variants were also identified with possible functional impact. Our study confirms ADAMTSL3 as a candidate for further investigation in schizophrenia, using the variants identified here. The utility of imputation analysis is demonstrated, and we recommend wider use of this method to re-evaluate the existing canon of suggestive schizophrenia associations.
  • Drenth, P., Levelt, W. J. M., & Noort, E. (2013). Rejoinder to commentary on the Stapel-fraud report. The Psychologist, 26(2), 81.

    Abstract

    The Levelt, Noort and Drenth Committees make their sole and final rejoinder to criticisms of their report on the Stapel fraud
  • Drolet, M., & Kempen, G. (1985). IPG: A cognitive approach to sentence generation. CCAI: The Journal for the Integrated Study of Artificial Intelligence, Cognitive Science and Applied Epistemology, 2, 37-61.
  • Dronkers, N. F., Wilkins, D. P., Van Valin Jr., R. D., Redfern, B. B., & Jaeger, J. J. (2004). Lesion analysis of the brain areas involved in language comprehension. Cognition, 92, 145-177. doi:10.1016/j.cognition.2003.11.002.

    Abstract

    The cortical regions of the brain traditionally associated with the comprehension of language are Wernicke's area and Broca's area. However, recent evidence suggests that other brain regions might also be involved in this complex process. This paper describes the opportunity to evaluate a large number of brain-injured patients to determine which lesioned brain areas might affect language comprehension. Sixty-four chronic left hemisphere stroke patients were evaluated on 11 subtests of the Curtiss–Yamada Comprehensive Language Evaluation – Receptive (CYCLE-R; Curtiss, S., & Yamada, J. (1988). Curtiss–Yamada Comprehensive Language Evaluation. Unpublished test, UCLA). Eight right hemisphere stroke patients and 15 neurologically normal older controls also participated. Patients were required to select a single line drawing from an array of three or four choices that best depicted the content of an auditorily-presented sentence. Patients' lesions obtained from structural neuroimaging were reconstructed onto templates and entered into a voxel-based lesion-symptom mapping (VLSM; Bates, E., Wilson, S., Saygin, A. P., Dick, F., Sereno, M., Knight, R. T., & Dronkers, N. F. (2003). Voxel-based lesion-symptom mapping. Nature Neuroscience, 6(5), 448–450.) analysis along with the behavioral data. VLSM is a brain–behavior mapping technique that evaluates the relationships between areas of injury and behavioral performance in all patients on a voxel-by-voxel basis, similar to the analysis of functional neuroimaging data. Results indicated that lesions to five left hemisphere brain regions affected performance on the CYCLE-R, including the posterior middle temporal gyrus and underlying white matter, the anterior superior temporal gyrus, the superior temporal sulcus and angular gyrus, mid-frontal cortex in Brodmann's area 46, and Brodmann's area 47 of the inferior frontal gyrus. Lesions to Broca's and Wernicke's areas were not found to significantly alter language comprehension on this particular measure. Further analysis suggested that the middle temporal gyrus may be more important for comprehension at the word level, while the other regions may play a greater role at the level of the sentence. These results are consistent with those seen in recent functional neuroimaging studies and offer complementary data in the effort to understand the brain areas underlying language comprehension.
  • Drude, S. (2011). Nominalization and subordination in Awetí. Amerindia, 35, 189-218.

    Abstract

    This paper describes the different kinds of nominalizations and the main forms used in subordination in Awetí, a Tupian language spoken by ca. 150 people in central Bra-zil in the Upper Xingu area. Awetí does not belong to, but is arguably the closest rela-tive of the well-known Tupí-Guaraní subfamily, the largest branch of the Tupí stock. In our analysis, subordination in Awetí is achieved by means of forms which may have developed from nominalizations, but which are synchronously possibly best classified as verbal moods, belonging into the verbal paradigm. On the other hand, nouns (and in particular nouns derived from verbs) often appear as predicates, especially in equality and cleft sentences.
  • Drude, S., Broeder, D., & Trilsbeek, P. (2014). The Language Archive and its solutions for sustainable endangered languages corpora. Book 2.0, 4, 5-20. doi:10.1386/btwo.4.1-2.5_1.

    Abstract

    Since the late 1990s, the technical group at the Max-Planck-Institute for Psycholinguistics has worked on solutions for important challenges in building sustainable data archives, in particular, how to guarantee long-time-availability of digital research data for future research. The support for the well-known DOBES (Documentation of Endangered Languages) programme has greatly inspired and advanced this work, and lead to the ongoing development of a whole suite of tools for annotating, cataloguing and archiving multi-media data. At the core of the LAT (Language Archiving Technology) tools is the IMDI metadata schema, now being integrated into a larger network of digital resources in the European CLARIN project. The multi-media annotator ELAN (with its web-based cousin ANNEX) is now well known not only among documentary linguists. We aim at presenting an overview of the solutions, both achieved and in development, for creating and exploiting sustainable digital data, in particular in the area of documenting languages and cultures, and their interfaces with related other developments
  • Drude, S. (2011). Word accent and its manifestation in Awetí. Amerindia, 35, 7-40.

    Abstract

    This paper describes the distribution and phonetic properties of accentuation of word forms in Awetí, a Tupian language spoken by ca. 150 people in central Brazil in the Upper Xingu area. Awetí does not belong to, but is arguably the closest relative of the better known Tupí-Guaraní subfamily, the largest branch of the Tupí stock. After a short overview over the word classes and general phonotactics of Awetí (sec-tion 2), we briefly discuss the notion ‘word accent’ and show that, in Awetí, it is generally located on the last syllable of the stem in morphologically simple forms (section 3). We then discuss regular and isolated exceptions to this rule (section 4). In section 5, we describe the distribution of the word accent when inflectional or deriva-tional suffixes are present – usually, the word accent of the word form with suffixes continues to be on the last syllable of the stem. After this descriptive part, we present a preliminary study of the acoustic-phonetic details of the manifestation of the word accent, observing word forms in isolation (section 6) and in different syntactic con-texts (section 7). The results are briefly summarized in the conclusion (section 8)
  • Dufau, S., Duñabeitia, J. A., Moret-Tatay, C., McGonigal, A., Peeters, D., Alario, F.-X., Balota, D. A., Brysbaert, M., Carreiras, M., Ferrand, L., Ktori, M., Perea, M., Rastle, K., Sasburg, O., Yap, M. J., Ziegler, J. C., & Grainger, J. (2011). Smart phone, smart science: How the use of smartphones can revolutionize research in cognitive science. PLoS One, 6(9), e24974. doi:10.1371/journal.pone.0024974.

    Abstract

    Investigating human cognitive faculties such as language, attention, and memory most often relies on testing small and homogeneous groups of volunteers coming to research facilities where they are asked to participate in behavioral experiments. We show that this limitation and sampling bias can be overcome by using smartphone technology to collect data in cognitive science experiments from thousands of subjects from all over the world. This mass coordinated use of smartphones creates a novel and powerful scientific ‘‘instrument’’ that yields the data necessary to test universal theories of cognition. This increase in power represents a potential revolution in cognitive science
  • Dunn, M., Burenhult, N., Kruspe, N., Tufvesson, S., & Becker, N. (2011). Aslian linguistic prehistory: A case study in computational phylogenetics. Diachronica, 28, 291-323. doi:10.1075/dia.28.3.01dun.

    Abstract

    This paper analyzes newly collected lexical data from 26 languages of the Aslian subgroup of the Austroasiatic language family using computational phylogenetic methods. We show the most likely topology of the Aslian family tree, discuss rooting and external relationships to other Austroasiatic languages, and investigate differences in the rates of diversification of different branches. Evidence is given supporting the classification of Jah Hut as a fourth top level subgroup of the family. The phylogenetic positions of known geographic and linguistic outlier languages are clarified, and the relationships of the little studied Aslian languages of Southern Thailand to the rest of the family are explored.
  • Dunn, M. (2014). [Review of the book Evolutionary Linguistics by April McMahon and Robert McMahon]. American Anthropologist, 116(3), 690-691.
  • Dunn, M., Greenhill, S. J., Levinson, S. C., & Gray, R. D. (2011). Evolved structure of language shows lineage-specific trends in word-order universals. Nature, 473, 79-82. doi:10.1038/nature09923.

    Abstract

    Languages vary widely but not without limit. The central goal of linguistics is to describe the diversity of human languages and explain the constraints on that diversity. Generative linguists following Chomsky have claimed that linguistic diversity must be constrained by innate parameters that are set as a child learns a language1, 2. In contrast, other linguists following Greenberg have claimed that there are statistical tendencies for co-occurrence of traits reflecting universal systems biases3, 4, 5, rather than absolute constraints or parametric variation. Here we use computational phylogenetic methods to address the nature of constraints on linguistic diversity in an evolutionary framework6. First, contrary to the generative account of parameter setting, we show that the evolution of only a few word-order features of languages are strongly correlated. Second, contrary to the Greenbergian generalizations, we show that most observed functional dependencies between traits are lineage-specific rather than universal tendencies. These findings support the view that—at least with respect to word order—cultural evolution is the primary factor that determines linguistic structure, with the current state of a linguistic system shaping and constraining future states.

    Additional information

    Supplementary information
  • Dunn, M., Kruspe, N., & Burenhult, N. (2013). Time and place in the prehistory of the Aslian languages. Human Biology, 85, 383-399.

    Abstract

    The Aslian branch of Austroasiatic is recognised as the oldest recoverable language family in the Malay Peninsula, predating the now dominant Austronesian languages present today. In this paper we address the dynamics of the prehistoric spread of Aslian languages across the peninsula, including the languages spoken by Semang foragers, traditionally associated with the 'Negrito' phenotype. The received view of an early and uniform tripartite break-up of proto-Aslian in the Early Neolithic period, and subsequent differentiation driven by societal modes is challenged. We present a Bayesian phylogeographic analysis of our dataset of vocabulary from 28 Aslian varieties. An explicit geographic model of diffusion is combined with a cognate birth-word death model of lexical evolution to infer the location of the major events of Aslian cladogenesis. The resultant phylogenetic trees are calibrated against dates in the historical and archaeological record to extrapolate a detailed picture of Aslian language history. We conclude that a binary split between Southern Aslian and the rest of Aslian took place in the Early Neolithic (4000 BP). This was followed much later in the Late Neolithic (2000-3000 BP) by a tripartite branching into Central Aslian, Jah Hut and Northern Aslian. Subsequent internal divisions within these sub-clades took place in the Early Metal Phase (post-2000 BP). Significantly, a split in Northern Aslian between Ceq Wong and the languages of the Semang was a late development and is proposed here to coincide with the adoption of Aslian by the Semang foragers. Given the difficulties involved in associating archaeologically recorded activities with linguistic events, as well as the lack of historical sources, our results remain preliminary. However, they provide sufficient evidence to prompt a rethinking of previous models of both clado- and ethno-genesis within the Malay Peninsula.
  • Eaves, L. J., St Pourcain, B., Smith, G. D., York, T. P., & Evans, D. M. (2014). Resolving the Effects of Maternal and Offspring Genotype on Dyadic Outcomes in Genome Wide Complex Trait Analysis (“M-GCTA”). Behavior Genetics, 44(5), 445-455. doi:10.1007/s10519-014-9666-6.

    Abstract

    Genome wide complex trait analysis (GCTA) is extended to include environmental effects of the maternal genotype on offspring phenotype (“maternal effects”, M-GCTA). The model includes parameters for the direct effects of the offspring genotype, maternal effects and the covariance between direct and maternal effects. Analysis of simulated data, conducted in OpenMx, confirmed that model parameters could be recovered by full information maximum likelihood (FIML) and evaluated the biases that arise in conventional GCTA when indirect genetic effects are ignored. Estimates derived from FIML in OpenMx showed very close agreement to those obtained by restricted maximum likelihood using the published algorithm for GCTA. The method was also applied to illustrative perinatal phenotypes from ~4,000 mother-offspring pairs from the Avon Longitudinal Study of Parents and Children. The relative merits of extended GCTA in contrast to quantitative genetic approaches based on analyzing the phenotypic covariance structure of kinships are considered.
  • Ebisch, S. J., Gallese, V., Willems, R. M., Mantini, D., Groen, W. B., Romani, G. L., Buitelaar, J. K., & Bekkering, H. (2011). Altered intrinsic functional connectivity of anterior and posterior insular regions in high-functioning participants with autism spectrum disorder. Human Brain Mapping, 32, 1013-1028. doi:10.1002/hbm.21085.

    Abstract

    Impaired understanding of others' sensations and emotions as well as abnormal experience of their own emotions and sensations is frequently reported in individuals with Autism Spectrum Disorder (ASD). It is hypothesized that these abnormalities are based on altered connectivity within “shared” neural networks involved in emotional awareness of self and others. The insula is considered a central brain region in a network underlying these functions, being located at the transition of information about bodily arousal and the physiological state of the body to subjective feelings. The present study investigated the intrinsic functional connectivity properties of the insula in 14 high-functioning participants with ASD (HF-ASD) and 15 typically developing (TD) participants in the age range between 12 and 20 years by means of “resting state” or “nontask” functional magnetic resonance imaging. Essentially, a distinction was made between anterior and posterior regions of the insular cortex. The results show a reduced functional connectivity in the HF-ASD group, compared with the TD group, between anterior as well as posterior insula and specific brain regions involved in emotional and sensory processing. It is suggested that functional abnormalities in a network involved in emotional and interoceptive awareness might be at the basis of altered emotional experiences and impaired social abilities in ASD, and that these abnormalities are partly based on the intrinsic functional connectivity properties of such a network.
  • Eekhof, L. S., & Mar, R. A. (2024). Does reading about fictional minds make us more curious about real ones? Language and Cognition, 16(1), 176-196. doi:10.1017/langcog.2023.30.

    Abstract

    Although there is a large body of research assessing whether exposure to narratives boosts social cognition immediately afterward, not much research has investigated the underlying mechanism of this putative effect. This experiment investigates the possibility that reading a narrative increases social curiosity directly afterward, which might explain the short-term boosts in social cognition reported by some others. We developed a novel measure of state social curiosity and collected data from participants (N = 222) who were randomly assigned to read an excerpt of narrative fiction or expository nonfiction. Contrary to our expectations, we found that those who read a narrative exhibited less social curiosity afterward than those who read an expository text. This result was not moderated by trait social curiosity. An exploratory analysis uncovered that the degree to which texts present readers with social targets predicted less social curiosity. Our experiment demonstrates that reading narratives, or possibly texts with social content in general, may engage and fatigue social-cognitive abilities, causing a temporary decrease in social curiosity. Such texts might also temporarily satisfy the need for social connection, temporarily reducing social curiosity. Both accounts are in line with theories describing how narratives result in better social cognition over the long term.
  • Eerland, A., Guadalupe, T. M., & Zwaan, R. A. (2011). Leaning to the left makes the Eiffel Tower seem smaller: Posture-modulated estimation. Psychological Science, 22, 1511-1514. doi:10.1177/0956797611420731.

    Abstract

    In two experiments, we investigated whether body posture influences people’s estimation of quantities. According to the mental-number-line theory, people mentally represent numbers along a line with smaller numbers on the left and larger numbers on the right. We hypothesized that surreptitiously making people lean to the right or to the left would affect their quantitative estimates. Participants answered estimation questions while standing on a Wii Balance Board. Posture was manipulated within subjects so that participants answered some questions while they leaned slightly to the left, some questions while they leaned slightly to the right, and some questions while they stood upright. Crucially, participants were not aware of this manipulation. Estimates were significantly smaller when participants leaned to the left than when they leaned to the right.

    Additional information

    Eerland_2011_Suppl_mat.pdf
  • Eibl-Eibesfeldt, I., & Senft, G. (1991). Trobriander (Papua-Neu-guinea, Trobriand -Inseln, Kaile'una) Tänze zur Einleitung des Erntefeier-Rituals. Film E 3129. Trobriander (Papua-Neuguinea, Trobriand-Inseln, Kiriwina); Ausschnitte aus einem Erntefesttanz. Film E3130. Publikationen zu wissenschaftlichen Filmen. Sektion Ethnologie, 17, 1-17.
  • Eicher, J. D., Powers, N. R., Miller, L. L., Akshoomoff, N., Amaral, D. G., Bloss, C. S., Libiger, O., Schork, N. J., Darst, B. F., Casey, B. J., Chang, L., Ernst, T., Frazier, J., Kaufmann, W. E., Keating, B., Kenet, T., Kennedy, D., Mostofsky, S., Murray, S. S., Sowell, E. R. and 11 moreEicher, J. D., Powers, N. R., Miller, L. L., Akshoomoff, N., Amaral, D. G., Bloss, C. S., Libiger, O., Schork, N. J., Darst, B. F., Casey, B. J., Chang, L., Ernst, T., Frazier, J., Kaufmann, W. E., Keating, B., Kenet, T., Kennedy, D., Mostofsky, S., Murray, S. S., Sowell, E. R., Bartsch, H., Kuperman, J. M., Brown, T. T., Hagler, D. J., Dale, A. M., Jernigan, T. L., St Pourcain, B., Davey Smith, G., Ring, S. M., Gruen, J. R., & Pediatric Imaging, Neurocognition, and Genetics Study (2013). Genome-wide association study of shared components of reading disability and language impairment. Genes, Brain and Behavior, 12(8), 792-801. doi:10.1111/gbb.12085.

    Abstract

    Written and verbal languages are neurobehavioral traits vital to the development of communication skills. Unfortunately, disorders involving these traits-specifically reading disability (RD) and language impairment (LI)-are common and prevent affected individuals from developing adequate communication skills, leaving them at risk for adverse academic, socioeconomic and psychiatric outcomes. Both RD and LI are complex traits that frequently co-occur, leading us to hypothesize that these disorders share genetic etiologies. To test this, we performed a genome-wide association study on individuals affected with both RD and LI in the Avon Longitudinal Study of Parents and Children. The strongest associations were seen with markers in ZNF385D (OR = 1.81, P = 5.45 × 10(-7) ) and COL4A2 (OR = 1.71, P = 7.59 × 10(-7) ). Markers within NDST4 showed the strongest associations with LI individually (OR = 1.827, P = 1.40 × 10(-7) ). We replicated association of ZNF385D using receptive vocabulary measures in the Pediatric Imaging Neurocognitive Genetics study (P = 0.00245). We then used diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine the implications of replicated markers. ZNF385D was a predictor of overall fiber tract volumes in both hemispheres, as well as global brain volume. Here, we present evidence for ZNF385D as a candidate gene for RD and LI. The implication of transcription factor ZNF385D in RD and LI underscores the importance of transcriptional regulation in the development of higher order neurocognitive traits. Further study is necessary to discern target genes of ZNF385D and how it functions within neural development of fluent language.
  • Eisenbeiß, S., Bartke, S., Weyerts, H., & Clahsen, H. (1994). Elizitationsverfahren in der Spracherwerbsforschung: Nominalphrasen, Kasus, Plural, Partizipien. Theorie des Lexikons, 57.
  • Eising, E., A Datson, N., van den Maagdenberg, A. M., & Ferrari, M. D. (2013). Epigenetic mechanisms in migraine: a promising avenue? BMC Medicine, 11(1): 26. doi:10.1186/1741-7015-11-26.

    Abstract

    Migraine is a disabling common brain disorder typically characterized by attacks of severe headache and associated with autonomic and neurological symptoms. Its etiology is far from resolved. This review will focus on evidence that epigenetic mechanisms play an important role in disease etiology. Epigenetics comprise both DNA methylation and post-translational modifications of the tails of histone proteins, affecting chromatin structure and gene expression. Besides playing a role in establishing cellular and developmental stage-specific regulation of gene expression, epigenetic processes are also important for programming lasting cellular responses to environmental signals. Epigenetic mechanisms may explain how non-genetic endogenous and exogenous factors such as female sex hormones, stress hormones and inflammation trigger may modulate attack frequency. Developing drugs that specifically target epigenetic mechanisms may open up exciting new avenues for the prophylactic treatment of migraine.
  • Eising, E., De Vries, B., Ferrari, M. D., Terwindt, G. M., & Van Den Maagdenberg, A. M. J. M. (2013). Pearls and pitfalls in genetic studies of migraine. Cephalalgia, 33(8), 614-625. doi:10.1177/0333102413484988.

    Abstract

    Purpose of review: Migraine is a prevalent neurovascular brain disorder with a strong genetic component, and different methodological approaches have been implemented to identify the genes involved. This review focuses on pearls and pitfalls of these approaches and genetic findings in migraine. Summary: Common forms of migraine (i.e. migraine with and without aura) are thought to have a polygenic make-up, whereas rare familial hemiplegic migraine (FHM) presents with a monogenic pattern of inheritance. Until a few years ago only studies in FHM yielded causal genes, which were identified by a classical linkage analysis approach. Functional analyses of FHM gene mutations in cellular and transgenic animal models suggest abnormal glutamatergic neurotransmission as a possible key disease mechanism. Recently, a number of genes were discovered for the common forms of migraine using a genome-wide association (GWA) approach, which sheds first light on the pathophysiological mechanisms involved. Conclusions: Novel technological strategies such as next-generation sequencing, which can be implemented in future genetic migraine research, may aid the identification of novel FHM genes and promote the search for the missing heritability of common migraine.
  • Eising, E., Vino, A., Mabie, H. L., Campbell, T. F., Shriberg, L. D., & Fisher, S. E. (2024). Genome sequencing of idiopathic speech delay. Human Mutation, 2024: 9692863. doi:10.1155/2024/9692863.

    Abstract

    Genetic investigations of people with speech and language disorders can provide windows into key aspects of human biology. Most genomic research into impaired speech development has so far focused on childhood apraxia of speech (CAS), a rare neurodevelopmental disorder characterized by difficulties with coordinating rapid fine motor sequences that underlie proficient speech. In 2001, pathogenic variants of FOXP2 provided the first molecular genetic accounts of CAS aetiology. Since then, disruptions in several other genes have been implicated in CAS, with a substantial proportion of cases being explained by high-penetrance variants. However, the genetic architecture underlying other speech-related disorders remains less well understood. Thus, in the present study, we used systematic DNA sequencing methods to investigate idiopathic speech delay, as characterized by delayed speech development in the absence of a motor speech diagnosis (such as CAS), a language/reading disorder, or intellectual disability. We performed genome sequencing in a cohort of 23 children with a rigorous diagnosis of idiopathic speech delay. For roughly half of the sample (ten probands), sufficient DNA was also available for genome sequencing in both parents, allowing discovery of de novo variants. In the thirteen singleton probands, we focused on identifying loss-of-function and likely damaging missense variants in genes intolerant to such mutations. We found that one speech delay proband carried a pathogenic frameshift deletion in SETD1A, a gene previously implicated in a broader variable monogenic syndrome characterized by global developmental problems including delayed speech and/or language development, mild intellectual disability, facial dysmorphisms, and behavioural and psychiatric symptoms. Of note, pathogenic SETD1A variants have been independently reported in children with CAS in two separate studies. In other probands in our speech delay cohort, likely pathogenic missense variants were identified affecting highly conserved amino acids in key functional domains of SPTBN1 and ARF3. Overall, this study expands the phenotype spectrum associated with pathogenic SETD1A variants, to also include idiopathic speech delay without CAS or intellectual disability, and suggests additional novel potential candidate genes that may harbour high-penetrance variants that can disrupt speech development.

    Additional information

    supplemental table
  • Eisner, F., Melinger, A., & Weber, A. (2013). Constraints on the transfer of perceptual learning in accented speech. Frontiers in Psychology, 4: 148. doi:10.3389/fpsyg.2013.00148.

    Abstract

    The perception of speech sounds can be re-tuned rapidly through a mechanism of lexically-driven learning (Norris et al 2003, Cogn.Psych. 47). Here we investigated this type of learning for English voiced stop consonants which are commonly de-voiced in word final position by Dutch learners of English . Specifically, this study asked under which conditions the change in pre-lexical representation encodes phonological information about the position of the critical sound within a word. After exposure to a Dutch learner’s productions of de-voiced stops in word-final position (but not in any other positions), British English listeners showed evidence of perceptual learning in a subsequent cross-modal priming task, where auditory primes with voiceless final stops (e.g., ‘seat’), facilitated recognition of visual targets with voiced final stops (e.g., SEED). This learning generalized to test pairs where the critical contrast was in word-initial position, e.g. auditory primes such as ‘town’ facilitated recognition of visual targets like DOWN (Experiment 1). Control listeners, who had not heard any stops by the speaker during exposure, showed no learning effects. The generalization to word-initial position did not occur when participants had also heard correctly voiced, word-initial stops during exposure (Experiment 2), and when the speaker was a native BE speaker who mimicked the word-final devoicing (Experiment 3). These results suggest that word position can be encoded in the pre-lexical adjustment to the accented phoneme contrast. Lexcially-guided feedback, distributional properties of the input, and long-term representations of accents all appear to modulate the pre-lexical re-tuning of phoneme categories.
  • Enfield, N. J. (2004). On linear segmentation and combinatorics in co-speech gesture: A symmetry-dominance construction in Lao fish trap descriptions. Semiotica, 149(1/4), 57-123. doi:10.1515/semi.2004.038.
  • Enfield, N. J. (2011). Books that live and die [Book review]. Current Anthropology, 52(1), 129-131. doi:10.1086/657928.

    Abstract

    Reviewed work(s): Dying Words: Endangered Languages and What They Have to Tell Us. By Nicholas Evans. Indianapolis: Wiley-Blackwell, 2010. On the Death and Life of Languages. By Claude Hagège, translated by Jody Gladding. New Haven, CT: Yale University Press, 2009.
  • Enfield, N. J. (2011). Credit tests [Review of the book You are not a gadget by Jaron Lanier]. The Times Literary Supplement, February 18, 2011, 12.
  • Enfield, N. J. (2004). Nominal classification in Lao: A sketch. Sprachtypologie und Universalienforschung, 57(2/3), 117-143.
  • Enfield, N. J. (2013). Language, culture, and mind: Trends and standards in the latest pendulum swing. Journal of the Royal Anthropological Institute, 19, 155-169. doi:10.1111/1467-9655.12008.

    Abstract

    The study of language in relation to anthropological questions has deep and varied roots, from Humboldt and Boas, Malinowski and Vygotsky, Sapir and Whorf, Wittgenstein and Austin, through to the linguistic anthropologists of now. A recent book by the linguist Daniel Everett, language: the cultural tool (2012), aims to bring some of the issues to a popular audience, with a focus on the idea that language is a tool for social action. I argue in this essay that the book does not represent the state of the art in this field, falling short on three central desiderata of a good account for the social functions of language and its relation to culture. I frame these desiderata in terms of three questions, here termed the cognition question, the causality question, and the culture question. I look at the relevance of this work for socio-cultural anthropology, in the context of a major interdisciplinary pendulum swing that is incipient in the study of language today, a swing away from formalist, innatist perspectives, and towards functionalist, empiricist perspectives. The role of human diversity and culture is foregrounded in all of this work. To that extent, Everett’s book is representative, but the quality of his argument is neither strong in itself nor representative of a movement that ought to be of special interest to socio-cultural anthropologists.
  • Enfield, N. J. (2011). Hidden delights [Review of the book How pleasure works by Paul Bloom]. The Times Literary Supplement, January 21, 2011, 30-30.
  • Enfield, N. J. (2013). Rejoinder to Daniel Everett [Comment]. Journal of the Royal Anthropological Institute, 19(3), 649. doi:10.1111/1467-9655.12056.
  • Enfield, N. J. (2011). Taste in two tongues: A Southeast Asian study of semantic convergence. The Senses & Society, 6(1), 30-37. doi:10.2752/174589311X12893982233632.

    Abstract

    This article examines vocabulary for taste and flavor in two neighboring but unrelated languages (Lao and Kri) spoken in Laos, Southeast Asia. There are very close similarities in underlying semantic distinctions made in the taste/flavor domain in these two languages, not just in the set of basic tastes distinguished (sweet, salty, bitter, sour, umami or glutamate), but in a series of further basic terms for flavors, specifying texture and other sensations in the mouth apart from pure taste (e.g. starchy, dry in the mouth, minty, tingly, spicy). After presenting sets of taste/flavor vocabulary in the two languages and showing their high degree of convergence, the article discusses some methodological and theoretical issues that arise from the observation of close convergence in semantic structure across languages, in particular the issue of how much inter-speaker variation is possible not only across apparently highly convergent systems, but also within languages. The final section raises possible causes for the close convergence of semantic structure in the two languages. The conclusion is that the likely cause of this convergence is historical social contact between speech communities in the area, although the precise mode of influence (e.g. direction of transmission) is unknown.
  • Enfield, N. J. (2013). The virtual you and the real you [Book review]. The Times Literary Supplement, April 12, 2013(5741), 31-32.

    Abstract

    Review of the books "Virtually you. The dangerous powers of the e-personality", by Elias Aboujaoude; "The big disconnect. The story of technology and loneliness", by Giles Slade; and "Net smart. How to thrive online", by Howard Rheingold.
  • Engelen, M. M., Franken, M.-C.-J.-P., Stipdonk, L. W., Horton, S. E., Jackson, V. E., Reilly, S., Morgan, A. T., Fisher, S. E., Van Dulmen, S., & Eising, E. (2024). The association between stuttering burden and psychosocial aspects of life in adults. Journal of Speech, Language, and Hearing Research, 67(5), 1385-1399. doi:10.1044/2024_JSLHR-23-00562.

    Abstract

    Purpose:
    Stuttering is a speech condition that can have a major impact on a person's quality of life. This descriptive study aimed to identify subgroups of people who stutter (PWS) based on stuttering burden and to investigate differences between these subgroups on psychosocial aspects of life.

    Method:
    The study included 618 adult participants who stutter. They completed a detailed survey examining stuttering symptomatology, impact of stuttering on anxiety, education and employment, experience of stuttering, and levels of depression, anxiety, and stress. A two-step cluster analytic procedure was performed to identify subgroups of PWS, based on self-report of stuttering frequency, severity, affect, and anxiety, four measures that together inform about stuttering burden.

    Results:
    We identified a high- (n = 230) and a low-burden subgroup (n = 372). The high-burden subgroup reported a significantly higher impact of stuttering on education and employment, and higher levels of general depression, anxiety, stress, and overall impact of stuttering. These participants also reported that they trialed more different stuttering therapies than those with lower burden.

    Conclusions:
    Our results emphasize the need to be attentive to the diverse experiences and needs of PWS, rather than treating them as a homogeneous group. Our findings also stress the importance of personalized therapeutic strategies for individuals with stuttering, considering all aspects that could influence their stuttering burden. People with high-burden stuttering might, for example, have a higher need for psychological therapy to reduce stuttering-related anxiety. People with less emotional reactions but severe speech distortions may also have a moderate to high burden, but they may have a higher need for speech techniques to communicate with more ease. Future research should give more insights into the therapeutic needs of people highly burdened by their stuttering.
  • Erb, J., Henry, M. J., Eisner, F., & Obleser, J. (2013). The brain dynamics of rapid perceptual adaptation to adverse listening conditions. The Journal of Neuroscience, 33, 10688-10697. doi:10.1523/​JNEUROSCI.4596-12.2013.

    Abstract

    Listeners show a remarkable ability to quickly adjust to degraded speech input. Here, we aimed to identify the neural mechanisms of such short-term perceptual adaptation. In a sparse-sampling, cardiac-gated functional magnetic resonance imaging (fMRI) acquisition, human listeners heard and repeated back 4-band-vocoded sentences (in which the temporal envelope of the acoustic signal is preserved, while spectral information is highly degraded). Clear-speech trials were included as baseline. An additional fMRI experiment on amplitude modulation rate discrimination quantified the convergence of neural mechanisms that subserve coping with challenging listening conditions for speech and non-speech. First, the degraded speech task revealed an “executive” network (comprising the anterior insula and anterior cingulate cortex), parts of which were also activated in the non-speech discrimination task. Second, trial-by-trial fluctuations in successful comprehension of degraded speech drove hemodynamic signal change in classic “language” areas (bilateral temporal cortices). Third, as listeners perceptually adapted to degraded speech, downregulation in a cortico-striato-thalamo-cortical circuit was observable. The present data highlight differential upregulation and downregulation in auditory–language and executive networks, respectively, with important subcortical contributions when successfully adapting to a challenging listening situation.
  • Ernestus, M. (2014). Acoustic reduction and the roles of abstractions and exemplars in speech processing. Lingua, 142, 27-41. doi:10.1016/j.lingua.2012.12.006.

    Abstract

    Acoustic reduction refers to the frequent phenomenon in conversational speech that words are produced with fewer or lenited segments compared to their citation forms. The few published studies on the production and comprehension of acoustic reduction have important implications for the debate on the relevance of abstractions and exemplars in speech processing. This article discusses these implications. It first briefly introduces the key assumptions of simple abstractionist and simple exemplar-based models. It then discusses the literature on acoustic reduction and draws the conclusion that both types of models need to be extended to explain all findings. The ultimate model should allow for the storage of different pronunciation variants, but also reserve an important role for phonetic implementation. Furthermore, the recognition of a highly reduced pronunciation variant requires top down information and leads to activation of the corresponding unreduced variant, the variant that reaches listeners’ consciousness. These findings are best accounted for in hybrids models, assuming both abstract representations and exemplars. None of the hybrid models formulated so far can account for all data on reduced speech and we need further research for obtaining detailed insight into how speakers produce and listeners comprehend reduced speech.
  • Ernestus, M., & Warner, N. (2011). An introduction to reduced pronunciation variants [Editorial]. Journal of Phonetics, 39(SI), 253-260. doi:10.1016/S0095-4470(11)00055-6.

    Abstract

    Words are often pronounced very differently in formal speech than in everyday conversations. In conversational speech, they may contain weaker segments, fewer sounds, and even fewer syllables. The English word yesterday, for instance, may be pronounced as [j epsilon integral eI]. This article forms an introduction to the phenomenon of reduced pronunciation variants and to the eight research articles in this issue on the characteristics, production, and comprehension of these variants. We provide a description of the phenomenon, addressing its high frequency of occurrence in casual conversations in various languages, the gradient nature of many reduction processes, and the intelligibility of reduced variants to native listeners. We also describe the relevance of research on reduced variants for linguistic and psychological theories as well as for applications in speech technology and foreign language acquisition. Since reduced variants occur more often in spontaneous than in formal speech, they are hard to study in the laboratory under well controlled conditions. We discuss the advantages and disadvantages of possible solutions, including the research methods employed in the articles in this special issue, based on corpora and experiments. This article ends with a short overview of the articles in this issue.
  • Ernestus, M., & Mak, W. M. (2004). Distinctive phonological features differ in relevance for both spoken and written word recognition. Brain and Language, 90(1-3), 378-392. doi:10.1016/S0093-934X(03)00449-8.

    Abstract

    This paper discusses four experiments on Dutch which show that distinctive phonological features differ in their relevance for word recognition. The relevance of a feature for word recognition depends on its phonological stability, that is, the extent to which that feature is generally realized in accordance with its lexical specification in the relevant word position. If one feature value is uninformative, all values of that feature are less relevant for word recognition, with the least informative feature being the least relevant. Features differ in their relevance both in spoken and written word recognition, though the differences are more pronounced in auditory lexical decision than in self-paced reading.
  • Ernestus, M., & Baayen, R. H. (2004). Analogical effects in regular past tense production in Dutch. Linguistics, 42(5), 873-903. doi:10.1515/ling.2004.031.

    Abstract

    This study addresses the question to what extent the production of regular past tense forms in Dutch is a¤ected by analogical processes. We report an experiment in which native speakers of Dutch listened to existing regular verbs over headphones, and had to indicate which of the past tense allomorphs, te or de, was appropriate for these verbs. According to generative analyses, the choice between the two su‰xes is completely regular and governed by the underlying [voice]-specification of the stem-final segment. In this approach, no analogical e¤ects are expected. In connectionist and analogical approaches, by contrast, the phonological similarity structure in the lexicon is expected to a¤ect lexical processing. Our experimental results support the latter approach: all participants created more nonstandard past tense forms, produced more inconsistency errors, and responded more slowly for verbs with stronger analogical support for the nonstandard form.
  • Ernestus, M., & Baayen, R. H. (2004). Kuchde, tobte, en turfte: Lekkage in 't kofschip. Onze Taal, 73(12), 360-361.
  • Ernestus, M., & Warner, N. (Eds.). (2011). Speech reduction [Special Issue]. Journal of Phonetics, 39(SI).
  • Escudero, P., Broersma, M., & Simon, E. (2013). Learning words in a third language: Effects of vowel inventory and language proficiency. Language and Cognitive Processes, 28, 746-761. doi:10.1080/01690965.2012.662279.

    Abstract

    This study examines the effect of L2 and L3 proficiency on L3 word learning. Native speakers of Spanish with different proficiencies in L2 English and L3 Dutch and a control group of Dutch native speakers participated in a Dutch word learning task involving minimal and non-minimal word pairs. The minimal word pairs were divided into ‘minimal-easy’ and ‘minimal-difficult’ pairs on the basis of whether or not they are known to pose perceptual problems for L1 Spanish learners. Spanish speakers’ proficiency in Dutch and English was independently established by their scores on general language comprehension tests. All participants were trained and subsequently tested on the mapping between pseudo-words and non-objects. The results revealed that, first, both native and non-native speakers produced more errors and longer reaction times for minimal than for non-minimal word pairs, and secondly, Spanish learners had more errors and longer reaction times for minimal-difficult than for minimal-easy pairs. The latter finding suggests that there is a strong continuity between sound perception and L3 word recognition. With respect to proficiency, only the learner’s proficiency in their L2, namely English, predicted their accuracy on L3 minimal pairs. This shows that learning an L2 with a larger vowel inventory than the L1 is also beneficial for word learning in an L3 with a similarly large vowel inventory.

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  • Evans, D. M., Zhu, G., Dy, V., Heath, A. C., Madden, P. A. F., Kemp, J. P., McMahon, G., St Pourcain, B., Timpson, N. J., Golding, J., Lawlor, D. A., Steer, C., Montgomery, G. W., Martin, N. G., Smith, G. D., & Whitfield, J. B. (2013). Genome-wide association study identifies loci affecting blood copper, selenium and zinc. Human Molecular Genetics, 22(19), 3998-4006. doi:10.1093/hmg/ddt239.

    Abstract

    Genetic variation affecting absorption, distribution or excretion of essential trace elements may lead to health effects related to sub-clinical deficiency. We have tested for allelic effects of single-nucleotide polymorphisms (SNPs) on blood copper, selenium and zinc in a genome-wide association study using two adult cohorts from Australia and the UK. Participants were recruited in Australia from twins and their families and in the UK from pregnant women. We measured erythrocyte Cu, Se and Zn (Australian samples) or whole blood Se (UK samples) using inductively coupled plasma mass spectrometry. Genotyping was performed with Illumina chips and > 2.5 m SNPs were imputed from HapMap data. Genome-wide significant associations were found for each element. For Cu, there were two loci on chromosome 1 (most significant SNPs rs1175550, P = 5.03 × 10(-10), and rs2769264, P = 2.63 × 10(-20)); for Se, a locus on chromosome 5 was significant in both cohorts (combined P = 9.40 × 10(-28) at rs921943); and for Zn three loci on chromosomes 8, 15 and X showed significant results (rs1532423, P = 6.40 × 10(-12); rs2120019, P = 1.55 × 10(-18); and rs4826508, P = 1.40 × 10(-12), respectively). The Se locus covers three genes involved in metabolism of sulphur-containing amino acids and potentially of the analogous Se compounds; the chromosome 8 locus for Zn contains multiple genes for the Zn-containing enzyme carbonic anhydrase. Where potentially relevant genes were identified, they relate to metabolism of the element (Se) or to the presence at high concentration of a metal-containing protein (Cu).
  • Evans, D. M., Brion, M. J. A., Paternoster, L., Kemp, J. P., McMahon, G., Munafò, M., Whitfield, J. B., Medland, S. E., Montgomery, G. W., Timpson, N. J., St Pourcain, B., Lawlor, D. A., Martin, N. G., Dehghan, A., Hirschhorn, J., Davey Smith, G., The GIANT consortium, The CRP consortium, & The TAG Consortium (2013). Mining the Human Phenome Using Allelic Scores That Index Biological Intermediates. PLoS Genet, 9(10): e1003919. doi:10.1371/journal.pgen.1003919.

    Abstract

    Author SummaryThe standard approach in genome-wide association studies is to analyse the relationship between genetic variants and disease one marker at a time. Significant associations between markers and disease are then used as evidence to implicate biological intermediates and pathways likely to be involved in disease aetiology. However, single genetic variants typically only explain small amounts of disease risk. Our idea is to construct allelic scores that explain greater proportions of the variance in biological intermediates than single markers, and then use these scores to data mine genome-wide association studies. We show how allelic scores derived from known variants as well as allelic scores derived from hundreds of thousands of genetic markers across the genome explain significant portions of the variance in body mass index, levels of C-reactive protein, and LDLc cholesterol, and many of these scores show expected correlations with disease. Power calculations confirm the feasibility of scaling our strategy to the analysis of tens of thousands of molecular phenotypes in large genome-wide meta-analyses. Our method represents a simple way in which tens of thousands of molecular phenotypes could be screened for potential causal relationships with disease.
  • Evans, S., McGettigan, C., Agnew, Z., Rosen, S., Cesar, L., Boebinger, D., Ostarek, M., Chen, S. H., Richards, A., Meekins, S., & Scott, S. K. (2014). The neural basis of informational and energetic masking effects in the perception and production of speech [abstract]. The Journal of the Acoustical Society of America, 136(4), 2243. doi:10.1121/1.4900096.

    Abstract

    When we have spoken conversations, it is usually in the context of competing sounds within our environment. Speech can be masked by many different kinds of sounds, for example, machinery noise and the speech of others, and these different sounds place differing demands on cognitive resources. In this talk, I will present data from a series of functional magnetic resonance imaging (fMRI) studies in which the informational properties of background sounds have been manipulated to make them more or less similar to speech. I will demonstrate the neural effects associated with speaking over and listening to these sounds, and demonstrate how in perception these effects are modulated by the age of the listener. The results will be interpreted within a framework of auditory processing developed from primate neurophysiology and human functional imaging work (Rauschecker and Scott 2009).
  • Ge, R., Yu, Y., Qi, Y. X., Fan, Y.-n., Chen, S., Gao, C., Haas, S. S., New, F., Boomsma, D. I., Brodaty, H., Brouwer, R. M., Buckner, R., Caseras, X., Crivello, F., Crone, E. A., Erk, S., Fisher, S. E., Franke, B., Glahn, D. C., Dannlowski, U. Ge, R., Yu, Y., Qi, Y. X., Fan, Y.-n., Chen, S., Gao, C., Haas, S. S., New, F., Boomsma, D. I., Brodaty, H., Brouwer, R. M., Buckner, R., Caseras, X., Crivello, F., Crone, E. A., Erk, S., Fisher, S. E., Franke, B., Glahn, D. C., Dannlowski, U., Grotegerd, D., Gruber, O., Hulshoff Pol, H. E., Schumann, G., Tamnes, C. K., Walter, H., Wierenga, L. M., Jahanshad, N., Thompson, P. M., Frangou, S., & ENIGMA Lifespan Working Group (2024). Normative modelling of brain morphometry across the lifespan with CentileBrain: Algorithm benchmarking and model optimisation. The Lancet Digital Health, 6(3), e211-e221. doi:10.1016/S2589-7500(23)00250-9.

    Abstract

    The value of normative models in research and clinical practice relies on their robustness and a systematic comparison of different modelling algorithms and parameters; however, this has not been done to date. We aimed to identify the optimal approach for normative modelling of brain morphometric data through systematic empirical benchmarking, by quantifying the accuracy of different algorithms and identifying parameters that optimised model performance. We developed this framework with regional morphometric data from 37 407 healthy individuals (53% female and 47% male; aged 3–90 years) from 87 datasets from Europe, Australia, the USA, South Africa, and east Asia following a comparative evaluation of eight algorithms and multiple covariate combinations pertaining to image acquisition and quality, parcellation software versions, global neuroimaging measures, and longitudinal stability. The multivariate fractional polynomial regression (MFPR) emerged as the preferred algorithm, optimised with non-linear polynomials for age and linear effects of global measures as covariates. The MFPR models showed excellent accuracy across the lifespan and within distinct age-bins and longitudinal stability over a 2-year period. The performance of all MFPR models plateaued at sample sizes exceeding 3000 study participants. This model can inform about the biological and behavioural implications of deviations from typical age-related neuroanatomical changes and support future study designs. The model and scripts described here are freely available through CentileBrain.
  • Fatemifar, G., Hoggart, C. J., Paternoster, L., Kemp, J. P., Prokopenko, I., Horikoshi, M., Wright, V. J., Tobias, J. H., Richmond, S., Zhurov, A. I., Toma, A. M., Pouta, A., Taanila, A., Sipila, K., Lähdesmäki, R., Pillas, D., Geller, F., Feenstra, B., Melbye, M., Nohr, E. A. and 6 moreFatemifar, G., Hoggart, C. J., Paternoster, L., Kemp, J. P., Prokopenko, I., Horikoshi, M., Wright, V. J., Tobias, J. H., Richmond, S., Zhurov, A. I., Toma, A. M., Pouta, A., Taanila, A., Sipila, K., Lähdesmäki, R., Pillas, D., Geller, F., Feenstra, B., Melbye, M., Nohr, E. A., Ring, S. M., St Pourcain, B., Timpson, N. J., Davey Smith, G., Jarvelin, M.-R., & Evans, D. M. (2013). Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances. Human Molecular Genetics, 22(18), 3807-3817. doi:10.1093/hmg/ddt231.

    Abstract

    Twin and family studies indicate that the timing of primary tooth eruption is highly heritable, with estimates typically exceeding 80%. To identify variants involved in primary tooth eruption, we performed a population-based genome-wide association study of 'age at first tooth' and 'number of teeth' using 5998 and 6609 individuals, respectively, from the Avon Longitudinal Study of Parents and Children (ALSPAC) and 5403 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966). We tested 2 446 724 SNPs imputed in both studies. Analyses were controlled for the effect of gestational age, sex and age of measurement. Results from the two studies were combined using fixed effects inverse variance meta-analysis. We identified a total of 15 independent loci, with 10 loci reaching genome-wide significance (P < 5 × 10(-8)) for 'age at first tooth' and 11 loci for 'number of teeth'. Together, these associations explain 6.06% of the variation in 'age of first tooth' and 4.76% of the variation in 'number of teeth'. The identified loci included eight previously unidentified loci, some containing genes known to play a role in tooth and other developmental pathways, including an SNP in the protein-coding region of BMP4 (rs17563, P = 9.080 × 10(-17)). Three of these loci, containing the genes HMGA2, AJUBA and ADK, also showed evidence of association with craniofacial distances, particularly those indexing facial width. Our results suggest that the genome-wide association approach is a powerful strategy for detecting variants involved in tooth eruption, and potentially craniofacial growth and more generally organ development.
  • Feinberg, H., Taylor, M. E., Razi, N., McBride, R., Knirel, Y. A., Graham, S. A., Drickamer, K., & Weis, W. I. (2011). Structural basis for langerin recognition of diverse pathogen and mammalian glycans through a single binding site. Journal of Molecular Biology, 405, 1027-1039. doi:10.1016/j.jmb.2010.11.039.

    Abstract

    Langerin mediates the carbohydrate-dependent uptake of pathogens by Langerhans cells in the first step of antigen presentation to the adaptive immune system. Langerin binds to an unusually diverse number of endogenous and pathogenic cell surface carbohydrates, including mannose-containing O-specific polysaccharides derived from bacterial lipopolysaccharides identified here by probing a microarray of bacterial polysaccharides. Crystal structures of the carbohydrate-recognition domain from human langerin bound to a series of oligomannose compounds, the blood group B antigen, and a fragment of β-glucan reveal binding to mannose, fucose, and glucose residues by Ca(2+) coordination of vicinal hydroxyl groups with similar stereochemistry. Oligomannose compounds bind through a single mannose residue, with no other mannose residues contacting the protein directly. There is no evidence for a second Ca(2+)-independent binding site. Likewise, a β-glucan fragment, Glcβ1-3Glcβ1-3Glc, binds to langerin through the interaction of a single glucose residue with the Ca(2+) site. The fucose moiety of the blood group B trisaccharide Galα1-3(Fucα1-2)Gal also binds to the Ca(2+) site, and selective binding to this glycan compared to other fucose-containing oligosaccharides results from additional favorable interactions of the nonreducing terminal galactose, as well as of the fucose residue. Surprisingly, the equatorial 3-OH group and the axial 4-OH group of the galactose residue in 6SO(4)-Galβ1-4GlcNAc also coordinate Ca(2+), a heretofore unobserved mode of galactose binding in a C-type carbohydrate-recognition domain bearing the Glu-Pro-Asn signature motif characteristic of mannose binding sites. Salt bridges between the sulfate group and two lysine residues appear to compensate for the nonoptimal binding of galactose at this site.

    Additional information

    Feinberg_2011_Suppl_Table.pdf

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