Publications

Abstract

A number of researchers have claimed that questions and other constructions with long distance dependencies (LDDs) are acquired relatively early, by age 4 or even earlier, in spite of their complexity. Analysis of LDD questions in the input available to children suggests that they are extremely stereotypical, raising the possibility that children learn lexically specific templates such as WH do you think S-GAP? rather than general rules of the kind postulated in traditional linguistic accounts of this construction. We describe three elicited imitation experiments with children aged from 4;6 to 6;9 and adult controls. Participants were asked to repeat prototypical questions (i.e., questions which match the hypothesised template), unprototypical questions (which depart from it in several respects) and declarative counterparts of both types of interrogative sentences. The children performed significantly better on the prototypical variants of both constructions, even when both variants contained exactly the same lexical material, while adults showed prototypicality e¤ects for LDD questions only. These results suggest that a general declarative complementation construction emerges quite late in development (after age 6), and that even adults rely on lexically specific templates for LDD questions.

Abstract

Evidence from certain geographical areas links lymphomas of the ocular adnexa marginal zone B-cell lymphomas (OAMZL) with Chlamydophila psittaci (Cp) infection, suggesting that lymphoma development is dependent upon chronic stimulation by persistent infections. Notwithstanding that, the actual immunopathogenetical mechanisms have not yet been elucidated. As in other B-cell lymphomas, insight into this issue, especially with regard to potential selecting ligands, could be provided by analysis of the immunoglobulin (IG) receptors of the malignant clones. To this end, we studied the molecular features of IGs in 44 patients with OAMZL (40% Cp-positive), identifying features suggestive of a pathogenic mechanism of autoreactivity. Herein, we show that lymphoma cells express a distinctive IG repertoire, with electropositive antigen (Ag)-binding sites, reminiscent of autoantibodies (auto-Abs) recognizing DNA. Additionally, five (11%) cases of OAMZL expressed IGs homologous with autoreactive Abs or IGs of patients with chronic lymphocytic leukemia, a disease known for the expression of autoreactive IGs by neoplastic cells. In contrast, no similarity with known anti-Chlamydophila Abs was found. Taken together, these results strongly indicate that OAMZL may originate from B cells selected for their capability to bind Ags and, in particular, auto-Ags. In OAMZL associated with Cp infection, the pathogen likely acts indirectly on the malignant B cells, promoting the development of an inflammatory milieu, where auto-Ags could be exposed and presented, driving proliferation and expansion of self-reactive B cells.

Abstract

Researchers interested in face processing have recently debated whether access to the name of a known person occurs in parallel with retrieval of semantic-biographical codes, rather than in a sequential fashion. Recently, Schweinberger, Burton, and Kelly (2001) took a failure to obtain a semantic context effect in a manual syllable judgment task on names of famous faces as support for this position. In two experiments, we compared the effects of visually presented categorically related prime words with either objects (e.g. prime: animal; target: dog) or faces of celebrities (e.g. prime: actor; target: Bruce Willis) as targets. Targets were either manually categorized with regard to the number of syllables (as in Schweinberger et al.), or they were overtly named. For neither objects nor faces was semantic priming obtained in syllable decisions; crucially, however, priming was obtained when objects and faces were overtly named. These results suggest that both face and object naming are susceptible to semantic context effects

Abstract

This study focusses on the optimal paradigm for simultaneous assessment of auditory and phonemic discrimination in clinical populations. We investigated (a) whether pitch and phonemic deviants presented together in one sequence are able to elicit mismatch negativities (MMNs) in healthy adults and (b) whether MMN elicited by a change in pitch is modulated by the presence of the phonemic deviants.

Abstract

The morphosyntactic paradigm of an inflected word can influence isolated word recognition, but its role in multiple-word phrasal integration is less clear. We examined the electrophysiological response to adjectives in short German prepositional phrases to evaluate whether strong and weak forms of the adjective show a differential response, and whether paradigm variables are related to this response. Twenty native German speakers classified serially presented phrases as grammatically correct or not while the electroencephalogram (EEG) was recorded. A functional mixed effects model of the response to grammatically correct trials revealed a differential response to strong and weak forms of the adjectives. This response difference depended on whether the preceding preposition imposed accusative or dative case. The lexically conditioned information content of the adjectives modulated a later interval of the response. The results indicate that grammatical context modulates the response to morphosyntactic information content, and lends support to the role of paradigm structure in integrative phrasal processing.

Abstract

Based on recent findings showing electrophysiological changes in adult language learners after relatively short periods of training, we hypothesized that adult Dutch learners of German would show responses to German gender and adjective declension violations after brief instruction. Adjective declension in German differs from previously studied morphosyntactic regularities in that the required suffixes depend not only on the syntactic case, gender, and number features to be expressed, but also on whether or not these features are already expressed on linearly preceding elements in the noun phrase. Violation phrases and matched controls were presented over three test phases (pretest and training on the first day, and a posttest one week later). During the pretest, no electrophysiological differences were observed between violation and control conditions, and participants’ classification performance was near chance. During the training and posttest phases, classification improved, and there was a P600-like violation response to declension but not gender violations. An error-related response during training was associated with improvement in grammatical discrimination from pretest to posttest. The results show that rapid changes in neuronal responses can be observed in adult learners of a complex morphosyntactic rule, and also that error-related electrophysiological responses may relate to grammar acquisition.

Abstract

Previous studies have examined cross-serial and embedded complement clauses in West Germanic in order to distinguish between different types of working memory models of human sentence processing, as well as different formal language models. Here, adult plasticity in the use of these constructions is investigated by examining the response of German-speaking learners of Dutch using magnetoencephalography (MEG). In three experimental sessions spanning their initial acquisition of Dutch, participants performed a sentence-scene matching task with Dutch sentences including two different verb constituent orders (Dutch verb order, German verb order), and in addition rated similar constructions in a separate rating task. The average planar gradient of the evoked field to the initial verb within the cluster revealed a larger evoked response for the German order relative to the Dutch order between 0.2 to 0.4 s over frontal sensors after 2 weeks, but not initially. The rating data showed that constructions consistent with Dutch grammar, but inconsistent with the German grammar were initially rated as unacceptable, but this preference reversed after 3 months. The behavioural and electrophysiological results suggest that cortical responses to verb order preferences in complement clauses can change within 3 months after the onset of adult language learning, implying that this aspect of grammatical processing remains plastic into adulthood.

Abstract

Background: Previous research has found that newborn infants can match phonetic information in the lips and voice from as young as ten weeks old. There is evidence that access to visual speech is necessary for normal speech development. Although we have an understanding of this early sensitivity, very little research has investigated older children's ability to speechread whole words. Aims: The aim of this study was to identify aspects of preschool children's linguistic knowledge and processing ability that may contribute to speechreading ability. We predicted a significant correlation between receptive vocabulary and speechreading, as well as phonological working memory to be a predictor of speechreading performance. Methods & Procedures: Seventy-six children (n = 76) aged between 2;10 and 4;11 years participated. Children were given three pictures and were asked to point to the picture that they thought that the experimenter had silently mouthed (ten trials). Receptive vocabulary and phonological working memory were also assessed. The results were analysed using Pearson correlations and multiple regressions. Outcomes & Results: The results demonstrated that the children could speechread at a rate greater than chance. Pearson correlations revealed significant, positive correlations between receptive vocabulary and speechreading score, phonological error rate and age. Further correlations revealed significant, positive relationships between The Children's Test of Non-Word Repetition (CNRep) and speechreading score, phonological error rate and age. Multiple regression analyses showed that receptive vocabulary best predicts speechreading ability over and above phonological working memory. Conclusions & Implications: The results suggest that preschool children are capable of speechreading, and that this ability is related to vocabulary size. This suggests that children aged between 2;10 and 4;11 are sensitive to visual information in the form of audio-visual mappings. We suggest that current and future therapies are correct to include visual feedback as a therapeutic tool; however, future research needs to be conducted in order to elucidate further the role of speechreading in development.

Abstract

A response to Moving Beyond Nature-Nurture: a Problem of Science or Communication? by John Spencer, Mark Blumberg and David Shenk

Abstract

Language is the best example of a cultural evolutionary system, able to retain a phylogenetic signal over many thousands of years. The temporal stability (conservatism) of basic vocabulary is relatively well understood, but the stability of the structural properties of language (phonology, morphology, syntax) is still unclear. Here we report an extensive Bayesian phylogenetic investigation of the structural stability of numerous features across many language families and we introduce a novel method for analyzing the relationships between the “stability profiles” of language families. We found that there is a strong universal component across language families, suggesting the existence of universal linguistic, cognitive and genetic constraints. Against this background, however, each language family has a distinct stability profile, and these profiles cluster by geographic area and likely deep genealogical relationships. These stability profiles reveal, for example, the ancient historical relationships between the Siberian and American language families, presumed to be separated by at least 12,000 years. Thus, such higher-level properties of language seen as an evolutionary system might allow the investigation of ancient connections between languages and shed light on the peopling of the world.

Abstract

The recent Bayesian approaches to language evolution and change seem to suggest that genetic biases can impact on the characteristics of language, but, at the same time, that its cultural transmission can partially free it from these same genetic constraints. One of the current debates centres on the striking differences between sampling and a posteriori maximising Bayesian learners, with the first converging on the prior bias while the latter allows a certain freedom to language evolution. The present paper shows that this difference disappears if populations more complex than a single teacher and a single learner are considered, with the resulting behaviours more similar to the sampler. This suggests that generalisations based on the language produced by Bayesian agents in such homogeneous single agent chains are not warranted. It is not clear which of the assumptions in such models are responsible, but these findings seem to support the rising concerns on the validity of the “acquisitionist” assumption, whereby the locus of language change and evolution is taken to be the first language acquirers (children) as opposed to the competent language users (the adults).

Abstract

Commentary on Cohen, E. (2012). The evolution of tag-based cooperation in humans: The case for accent. Current Anthropology, 53, 588-616. doi:10.1086/667654.

Abstract

Interest in the origins and evolution of language has been around for as long as language has been around. However, only recently has the empirical study of language come of age. We argue that the field has sufficiently advanced that it now needs its own journal—the Journal of Language Evolution.

Abstract

Our understanding of language, its origins and subsequent evolution (including language change) is shaped not only by data and theories from the language sciences, but also fundamentally by the biological sciences. Recent developments in genetics and evolutionary theory offer both very strong constraints on what scenarios of language evolution are possible and probable but also offer exciting opportunities for understanding otherwise puzzling phenomena. Due to the intrinsic breathtaking rate of advancement in these fields, the complexity, subtlety and sometimes apparent non-intuitiveness of the phenomena discovered, some of these recent developments have either being completely missed by language scientists, or misperceived and misrepresented. In this short paper, we offer an update on some of these findings and theoretical developments through a selection of illustrative examples and discussions that cast new light on current debates in the language sciences. The main message of our paper is that life is much more complex and nuanced than anybody could have predicted even a few decades ago, and that we need to be flexible in our theorizing instead of embracing a priori dogmas and trying to patch paradigms that are no longer satisfactory.

Abstract

Serial verb constructions have often been said to refer to single conceptual events. However, evidence to support this claim has been elusive. This article introduces co-speech gestures as a new way of investigating the relationship. The alignment patterns of gestures with serial verb constructions and other complex clauses were compared in Avatime (Ka-Togo, Kwa, Niger-Congo). Serial verb constructions tended to occur with single gestures overlapping the entire construction. In contrast, other complex clauses were more likely to be accompanied by distinct gestures overlapping individual verbs. This pattern of alignment suggests that serial verb constructions are in fact used to describe single events.

Abstract

Speakers choose a particular expression based on many factors, including availability of the referent in the perceptual context. We examined whether, when expressing referents, monolingual English- and Turkish-speaking children: (1) are sensitive to perceptual context, (2) express this sensitivity in language-specific ways, and (3) use co-speech gestures to specify referents that are underspecified. We also explored the mechanisms underlying children's sensitivity to perceptual context. Children described short vignettes to an experimenter under two conditions: The characters in the vignettes were present in the perceptual context (perceptual context); the characters were absent (no perceptual context). Children routinely used nouns in the no perceptual context condition, but shifted to pronouns (English-speaking children) or omitted arguments (Turkish-speaking children) in the perceptual context condition. Turkish-speaking children used underspecified referents more frequently than English-speaking children in the perceptual context condition; however, they compensated for the difference by using gesture to specify the forms. Gesture thus gives children learning structurally different languages a way to achieve comparable levels of specification while at the same time adhering to the referential expressions dictated by their language.

Abstract

Abnormal prosody is a striking feature of the speech of those with Autism Spectrum Disorder (ASD), but previous reports suggest large variability among those with ASD. Here we show that part of this heterogeneity can be explained by level of language functioning. We recorded semi-spontaneous but controlled conversations in adults with and without Autism Spectrum Disorder and measured features related to pitch and duration to determine (1) general use of prosodic features, (2) prosodic use in relation to marking information structure, specifically, the emphasis of new information in a sentence (focus) as opposed to information already given in the conversational context (topic), and (3) the relation between prosodic use and level of language function. We found that, compared to typical adults, those with ASD with high language functioning generally used a larger pitch range than controls but did not mark information structure, whereas those with moderate language functioning generally used a smaller pitch range than controls but marked information structure appropriately to a large extent. Both impaired general prosodic use and impaired marking of information structure would be expected to seriously impact social communication and thereby lead to increased difficulty in personal domains, such as making and keeping friendships, and in professional domains, such as competing for employment opportunities.

Abstract

Intellectual disability (ID) is a common condition with considerable genetic heterogeneity. Next-generation sequencing of large cohorts has identified an increasing number of genes implicated in ID, but their roles in neurodevelopment remain largely unexplored. Here we report an ID syndrome caused by de novo heterozygous missense, nonsense, and frameshift mutations in BCL11A, encoding a transcription factor that is a putative member of the BAF swi/snf chromatin-remodeling complex. Using a comprehensive integrated approach to ID disease modeling, involving human cellular analyses coupled to mouse behavioral, neuroanatomical, and molecular phenotyping, we provide multiple lines of functional evidence for phenotypic effects. The etiological missense variants cluster in the amino-terminal region of human BCL11A, and we demonstrate that they all disrupt its localization, dimerization, and transcriptional regulatory activity, consistent with a loss of function. We show that Bcl11a haploinsufficiency in mice causes impaired cognition, abnormal social behavior, and microcephaly in accordance with the human phenotype. Furthermore, we identify shared aberrant transcriptional profiles in the cortex and hippocampus of these mouse models. Thus, our work implicates BCL11A haploinsufficiency in neurodevelopmental disorders and defines additional targets regulated by this gene, with broad relevance for our understanding of ID and related syndromes

Abstract

Developmental dyslexia, a severe and persistent reading and spelling impairment, is characterized by difficulties in processing speech sounds (i.e., phonemes). Here, we test the hypothesis that these phonological difficulties are associated with a dysfunction of the auditory sensory thalamus, the medial geniculate body (MGB). By using functional MRI, we found that, in dyslexic adults, the MGB responded abnormally when the task required attending to phonemes compared with other speech features. No other structure in the auditory pathway showed distinct functional neural patterns between the two tasks for dyslexic and control participants. Furthermore, MGB activity correlated with dyslexia diagnostic scores, indicating that the task modulation of the MGB is critical for performance in dyslexics. These results suggest that deficits in dyslexia are associated with a failure of the neural mechanism that dynamically tunes MGB according to predictions from cortical areas to optimize speech processing. This view on task-related MGB dysfunction in dyslexics has the potential to reconcile influential theories of dyslexia within a predictive coding framework of brain function.

Abstract

The extent to which the phonetic system of a second language is mastered varies across individuals. The present study evaluates the pattern of individual differences in late bilinguals across different phonological processes. Fifty-five late Dutch-English bilinguals were tested on their ability to perceive a difficult L2 speech contrast (the English /æ/-/ε/ contrast) in three different tasks: A categorization task, a word identification task and a lexical decision task. As a group, L2 listeners were less accurate than native listeners. However, at the individual level, almost half of the L2 listeners scored within the native range in the categorization task whereas a small percentage scored within the native range in the identification and lexical decision tasks. These results show that L2 listeners' performance crucially depends on the nature of the task, with higher L2 listener accuracy on an acoustic-phonetic analysis task than on tasks involving lexical processes. These findings parallel previous results for early bilinguals, where the pattern of performance was consistent with the processing hierarchy proposed by different models of speech perception. The results indicate that the analysis of patterns of non-native performance can provide important insights concerning the architecture of the speech perception system and the issue of language learnability.

Abstract

People differ in their ability to perceive second language (L2) sounds. In early bilinguals the variability in learning L2 phonemes stems from speech-specific capabilities (Díaz, Baus, Escera, Costa & Sebastián-Gallés, 2008). The present study addresses whether speech-specific capabilities similarly explain variability in late bilinguals. Event-related potentials were recorded (using a design similar to Díaz et al., 2008) in two groups of late Dutch–English bilinguals who were good or poor in overtly discriminating the L2 English vowels /ε-æ/. The mismatch negativity, an index of discrimination sensitivity, was similar between the groups in conditions involving pure tones (of different length, frequency, and presentation order) but was attenuated in poor L2 perceivers for native, unknown, and L2 phonemes. These results suggest that variability in L2 phonemic learning originates from speech-specific capabilities and imply a continuity of L2 phonemic learning mechanisms throughout the lifespan

Abstract

Adherence to medications is an important indicator of the quality of medication management and impacts on health outcomes and cost-effectiveness of healthcare delivery. Electronic healthcare data (EHD) are increasingly used to estimate adherence in research and clinical practice, yet standardization and transparency of data processing are still a concern. Comprehensive and flexible open-source algorithms can facilitate the development of high-quality, consistent, and reproducible evidence in this field. Some EHD-based clinical decision support systems (CDSS) include visualization of medication histories, but this is rarely integrated in adherence analyses and not easily accessible for data exploration or implementation in new clinical settings. We introduce AdhereR, a package for the widely used open-source statistical environment R, designed to support researchers in computing EHD-based adherence estimates and in visualizing individual medication histories and adherence patterns. AdhereR implements a set of functions that are consistent with current adherence guidelines, definitions and operationalizations. We illustrate the use of AdhereR with an example dataset of 2-year records of 100 patients and describe the various analysis choices possible and how they can be adapted to different health conditions and types of medications. The package is freely available for use and its implementation facilitates the integration of medication history visualizations in open-source CDSS platforms.

Abstract

Communication is facilitated when listeners allocate their attention to important information (focus) in the message, a process called "information structure." Linguistic cues like the preceding context and pitch accent help listeners to identify focused information. In multimodal communication, relevant information can be emphasized by nonverbal cues like beat gestures, which represent rhythmic nonmeaningful hand movements. Recent studies have found that linguistic and nonverbal attention cues are integrated independently in single sentences. However, it is possible that these two cues interact when information is embedded in context, because context allows listeners to predict what information is important. In an ERP study, we tested this hypothesis and asked listeners to view videos capturing a dialogue. In the critical sentence, focused and nonfocused words were accompanied by beat gestures, grooming hand movements, or no gestures. ERP results showed that focused words are processed more attentively than nonfocused words as reflected in an N1 and P300 component. Hand movements also captured attention and elicited a P300 component. Importantly, beat gesture and focus interacted in a late time window of 600-900 msec relative to target word onset, giving rise to a late positivity when nonfocused words were accompanied by beat gestures. Our results show that listeners integrate beat gesture with the focus of the message and that integration costs arise when beat gesture falls on nonfocused information. This suggests that beat gestures fulfill a unique focusing function in multimodal discourse processing and that they have to be integrated with the information structure of the message.

Abstract

Prosody, particularly accent, aids comprehension by drawing attention to important elements such as the information that answers a question. A study using ERP registration investigated how the brain deals with the interpretation of prosodic prominence. Sentences were embedded in short dialogues and contained accented elements that were congruous or incongruous with respect to a preceding question. In contrast to previous studies, no explicit prosodic judgment task was added. Robust effects of accentuation were evident in the form of an “accent positivity” (200–500 msec) for accented elements irrespective of their congruity. Our results show that incongruously accented elements, that is, superfluous accents, activate a specific set of neural systems that is inactive in case of incongruously unaccented elements, that is, missing accents. Superfluous accents triggered an early positivity around 100 msec poststimulus, followed by a right-lateralized negative effect (N400). This response suggests that redundant information is identified immediately and leads to the activation of a neural system that is associated with semantic processing (N400). No such effects were found when contextually expected accents were missing. In a later time window, both missing and superfluous accents triggered a late positivity on midline electrodes, presumably related to making sense of both kinds of mismatching stimuli. These results challenge previous findings of greater processing for missing accents and suggest that the natural processing of prosody involves a set of distinct, temporally organized neural systems.

Abstract

Ultimate attainment in adult second language learners often differs tremendously from the end state typically achieved by young children learning their first language (L1) or a second language (L2). The research summarized in this article concentrates on developmental steps and orders of acquisition attested in learners of different ages. Findings from a longitudinal study concerned with the acquisition of verbal morpho-syntax in German as an L2 by two young Russian learners (8 and 14 years old) are compared to findings from the acquisition of the same target language by younger children and by untutored adult learners. The study focuses on the acquisition of verbal morphology, the role of auxiliary verbs and the position of finite and non finite verbs in relation to negation and additive scope particles.

Abstract

Ideophones are marked words that depict sensory imagery found in many of the world’s languages. They are noted for their special forms, distinct grammatical behaviour, rich sensory meanings, and interactional uses related to experience and evidentiality. This review surveys recent developments in ideophone research. Work on the semiotics of ideophones helps explain why they are marked and how they realise the depictive potential of speech. A true semantic typology of ideophone systems is coming within reach through a combination of language-internal analyses and language-independent elicitation tools. Documentation of ideophones in a wide variety of genres as well as sequential analysis of ideophone use in natural discourse leads to new insights about their interactional uses and about their relation to other linguistic devices like reported speech and grammatical evidentials. As the study of ideophones is coming of age, it sheds new light on what is possible and probable in human language.

Abstract

We provide an annotated coding scheme for other-initiated repair, along with guidelines for building collections and aggregating cases based on interactionally relevant similarities and differences. The questions and categories of the scheme are grounded in inductive observations of conversational data and connected to a rich body of work on other-initiated repair in conversation analysis. The scheme is developed and tested in a 12-language comparative project and can serve as a stepping stone for future work on other-initiated repair and the systematic comparative study of conversational structures.

Abstract

Kyeei Yao, an age group leader, oversees a festival in Akpafu-Mempeasem, Volta Region, Ghana. The expensive draped cloth, Ashanti-inspired wreath, strings of beads that are handed down through the generations, and digital wristwatch work together to remind us that culture is a moving target, always renewing and reshaping itself. Kããã is a Siwu ideophone for "looking attentively".

Abstract

Mensen groeien op in verschillende omgevingen, met verschillende ervaringen en verschillende talen. Betekent dat ook dat ze verschillend denken? En als er invloed is van taal op denken, hoe ver reikt die dan? Wordt ons denken begrensd door woorden, of is de invloed meer gematigd en kunnen we er soms zelfs aan ontkomen?

Abstract

This paper addresses the question why body-part terms are so often used to talk about other things than body parts. It is argued that the strategy of falling back on stable common ground to maximize the chances of successful communication is the driving force behind the selective advantage of body-part terms. The many different ways in which languages may implement this universal strategy suggest that, in order to properly understand the privileged role of the body in the evolution of linguistic signs, we have to look beyond the body to language in its socio-cultural context. A theory which acknowledges the interacting influences of stable common ground and diversified cultural practices on the evolution of linguistic signs will offer the most explanatory power for both universal patterns and language-specific variation.

Abstract

Sound symbolism is a phenomenon with broad relevance to the study of language and mind, but there has been a disconnect between its investigations in linguistics and psychology. This study tests the sound-symbolic potential of ideophones—words described as iconic—in an experimental task that improves over prior work in terms of ecological validity and experimental control. We presented 203 ideophones from five languages to eighty-two Dutch listeners in a binary-choice task, in four versions: original recording, full diphone resynthesis, segments-only resynthesis, and prosody-only resynthesis. Listeners guessed the meaning of all four versions above chance, confirming the iconicity of ideophones and showing the viability of speech synthesis as a way of controlling for segmental and suprasegmental properties in experimental studies of sound symbolism. The success rate was more modest than prior studies using pseudowords like bouba/kiki, implying that assumptions based on such words cannot simply be transferred to natural languages. Prosody and segments together drive the effect: neither alone is sufficient, showing that segments and prosody work together as cues supporting iconic interpretations. The findings cast doubt on attempts to ascribe iconic meanings to segments alone and support a view of ideophones as words that combine arbitrariness and iconicity.We discuss the implications for theory and methods in the empirical study of sound symbolism and iconicity.

Abstract

Background Sanger sequencing, still the standard technique for genetic testing in most diagnostic laboratories and until recently widely used in research, is gradually being complemented by next-generation sequencing (NGS). No single mutation detection technique is however perfect in identifying all mutations. Therefore, we wondered to what extent inconsistencies between Sanger sequencing and NGS affect the molecular diagnosis of patients. Since mutations in SCN1A, the major gene implicated in epilepsy, are found in the majority of Dravet syndrome (DS) patients, we focused on missed SCN1A mutations. Methods We sent out a survey to 16 genetic centers performing SCN1A testing. Results We collected data on 28 mutations initially missed using Sanger sequencing. All patients were falsely reported as SCN1A mutation-negative, both due to technical limitations and human errors. Conclusion We illustrate the pitfalls of Sanger sequencing and most importantly provide evidence that SCN1A mutations are an even more frequent cause of DS than already anticipated.

Abstract

Reduced forms like yeshay for yesterday often occur in conversations. Previous behavioral research reported a processing advantage for full over reduced forms. The present study investigated whether this processing advantage is reflected in a modulation of alpha (8–12 Hz) and gamma (30+ Hz) band activity. In three electrophysiological experiments, participants listened to full and reduced forms in isolation (Experiment 1), sentence-final position (Experiment 2), or mid-sentence position (Experiment 3). Alpha power was larger in response to reduced forms than to full forms, but only in Experiments 1 and 2. We interpret these increases in alpha power as reflections of higher auditory cognitive load. In all experiments, gamma power only increased in response to full forms, which we interpret as showing that lexical activation spreads more quickly through the semantic network for full than for reduced forms. These results confirm a processing advantage for full forms, especially in non-medial sentence position.

Abstract

There is ample evidence that native and non-native listeners use lexical knowledge to retune their native phonetic categories following ambiguous pronunciations. The present study investigates whether a non-native ambiguous sound can retune non-native phonetic categories. After a brief exposure to an ambiguous British English [l/ɹ] sound, Dutch listeners demonstrated retuning. This retuning was, however, asymmetrical: the non-native listeners seemed to show (more) retuning of the /ɹ/ category than of the /l/ category, suggesting that non-native listeners can retune non-native phonetic categories. This asymmetry is argued to be related to the large phonetic variability of /r/ in both Dutch and English.

Abstract

This article describes and analyses nasal harmony (or spreading of nasality) in Awetí. It first shows generally how sounds in prefixes adapt to nasality or orality of stems, and how nasality in stems also ‘extends’ to the left. With abstract templates we show which phonetically nasal or oral sequences are possible in Awetí (focusing on stops, pre-nasalized stops and nasals) and which phonological analysis is appropriate for account for this regularities. In Awetí, there are intrinsically nasal and oral vowels and ‘neutral’ vowels which adapt phonetically to a following vowel or consonant, as is the case of sonorant consonants. Pre-nasalized stops such as “nt” are nasalized variants of stops, not post-oralized variants of nasals as in Tupí-Guaranian languages. For nasals and stops in syllable coda (end of morphemes), we postulate arqui-phonemes which adapt to the preceding vowel or a following consonant. Finally, using a declarative approach, the analysis formulates ‘rules’ (statements) which account for the ‘behavior’ of nasality in Awetí words, making use of “structured sequences” on both the phonetic and phonological levels. So, each unit (syllable, morpheme, word etc.) on any level has three components, a sequence of segments, a constituent structure (where pre-nasalized stops, like diphthongs, correspond to two segments), and an intonation structure. The statements describe which phonetic variants can be combined (concatenated) with which other variants, depending on their nasality or orality.

Abstract

This contribution explores the potentials of combining corpora of language use data with language description in e-grammars (or digital grammars). We present three directions of ongoing research and discuss the advantages of combining these and similar approaches, arguing that the technological possibilities have barely begun to be explored.

Abstract

Previous studies, including Duffield and Matsuo (2001; 2002; 2009), have demonstrated second language learners’ overall sensitivity to a parallelism constraint governing English VP-ellipsis constructions: like native speakers (NS), advanced Dutch, Spanish and Japanese learners of English reliably prefer ellipsis clauses with structurally parallel antecedents over those with non-parallel antecedents. However, these studies also suggest that, in contrast to English native speakers, L2 learners’ sensitivity to parallelism is strongly influenced by other non-syntactic formal factors, such that the constraint applies in a comparatively restricted range of construction-specific contexts. This article reports a set of follow-up experiments — from both computer-based as well as more traditional acceptability judgement tasks — that systematically manipulates these other factors. Convergent results from these tasks confirm a qualitative difference in the judgement patterns of the two groups, as well as important differences between theoreticians’ judgements and those of typical native speakers. We consider the implications of these findings for theories of ultimate attainment in second language acquisition (SLA), as well as for current theoretical accounts of ellipsis.

Abstract

Although laughter forms an important part of human non-verbal communication, it has received rather less attention than it deserves in both the experimental and the observational literatures. Relaxed social (Duchenne) laughter is associated with feelings of wellbeing and heightened affect, a proximate expla- nation for which might be the release of endorphins. We tested this hypothesis in a series of six experimental studies in both the laboratory (watching videos) and naturalistic contexts (watching stage performances), using change in pain threshold as an assay for endorphin release. The results show that pain thresholds are significantly higher after laughter than in the control condition. This pain-tolerance effect is due to laughter itself and not simply due to a change in positive affect. We suggest that laughter, through an endorphin-mediated opiate effect, may play a crucial role in social bonding.

Abstract

In the absence of comparative method reconstruction, high rate of lexical cognate candidates is often used as evidence for relationships between languages. This paper uses the Oswalt Monte Carlo Shift test (a variant of Oswalt 1970) to explore the statistical basis of the claim that the four Papuan languages of the Solomon Islands have greater than chance levels of lexical similarity. The results of this test initially appear to show that the lexical similarities between the Central Solomons Papuan languages are statistically significant, but the effect disappears when known Oceanic loanwords are removed. The Oswalt Monte Carlo test is a useful technique to test a claim of greater than chance similarity between any two word lists — with the proviso that undetected loanwords strongly increase the chance of spurious identification.

Abstract

This paper shows that despite evidence of structural convergence between some of the Austronesian and non-Austronesian (Papuan) languages of Island Melanesia, statistical methods can detect two independent genealogical signals derived from linguistic structural features. Earlier work by the author and others has presented a maximum parsimony analysis which gave evidence for a genealogical connection between the non-Austronesian languages of island Melanesia. Using the same data set, this paper demonstrates for the non-statistician the application of more sophisticated statistical techniques—including Bayesian methods of phylogenetic inference, and shows that the evidence for common ancestry is if anything stronger than originally supposed.

Abstract

A review of "Anthropological papers of the University of Alaska: The Dene-Yeniseian connection." Ed. by JAMES KARI and BEN A. POTTER Fairbanks, AK: University of Alaska, Fairbanks. 2010. Pp. vi, 363.

Abstract

The Core Trustworthy Data Repository Requirements were developed by the DSA–WDS Partnership Working Group on Repository Audit and Certification, a Working Group (WG) of the Research Data Alliance . The goal of the effort was to create a set of harmonized common requirements for certification of repositories at the core level, drawing from criteria already put in place by the Data Seal of Approval (DSA: www.datasealofapproval.org) and the ICSU World Data System (ICSU-WDS: https://www.icsu-wds.org/services/certification). An additional goal of the project was to develop common procedures to be implemented by both DSA and ICSU-WDS. Ultimately, the DSA and ICSU-WDS plan to collaborate on a global framework for repository certification that moves from the core to the extended (nestor-Seal DIN 31644), to the formal (ISO 16363) level.

Abstract

Approach and avoidance are two behavioral responses that make people tend to approach positive and avoid negative situations. This study examines whether postural behavior is influenced by the affective state of pictures. While standing on the Wii™ Balance Board, participants viewed pleasant, neutral, and unpleasant pictures (passively viewing phase). Then they had to move their body to the left or the right (lateral movement phase) to make the next picture appear. We recorded movements in the anterior-posterior direction to examine approach and avoidant behavior. During passively viewing, people approached pleasant pictures. They avoided unpleasant ones while they made a lateral movement. These findings provide support for the idea that we tend to approach positive and avoid negative situations.

Abstract

We investigated the roles of top-down task set and bottom-up stimulus salience for feature-specific attentional capture. ERPs and behavioural performance were measured in two experiments where spatially nonpredictive cues preceded visual search arrays that included a colour-defined target. When cue arrays contained a target-colour singleton, behavioural spatial cueing effects were accompanied by a cue-induced N2pc component, indicative of attentional capture. Behavioural cueing effects and N2pc components were only minimally attenuated for non-singleton relative to singleton target-colour cues, demonstrating that top-down task set has a much greater impact on attentional capture than bottom-up salience. For nontarget-colour singleton cues, no N2pc was triggered, but an anterior N2 component indicative of top-down inhibition was observed. In Experiment 2, these cues produced an inverted behavioural cueing effect, which was accompanied by a delayed N2pc to targets presented at cued locations. These results suggest that perceptually salient visual stimuli without task-relevant features trigger a transient location-specific inhibition process that prevents attentional capture, but delays the selection of subsequent target events.

Abstract

Migraine is a common disabling neurovascular brain disorder typically characterised by attacks of severe headache and associated with autonomic and neurological symptoms. Migraine is caused by an interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified over a dozen genetic loci associated with migraine. Here, we integrated migraine GWAS data with high-resolution spatial gene expression data of normal adult brains from the Allen Human Brain Atlas to identify specific brain regions and molecular pathways that are possibly involved in migraine pathophysiology. To this end, we used two complementary methods. In GWAS data from 23,285 migraine cases and 95,425 controls, we first studied modules of co-expressed genes that were calculated based on human brain expression data for enrichment of genes that showed association with migraine. Enrichment of a migraine GWAS signal was found for five modules that suggest involvement in migraine pathophysiology of: (i) neurotransmission, protein catabolism and mitochondria in the cortex; (ii) transcription regulation in the cortex and cerebellum; and (iii) oligodendrocytes and mitochondria in subcortical areas. Second, we used the high-confidence genes from the migraine GWAS as a basis to construct local migraine-related co-expression gene networks. Signatures of all brain regions and pathways that were prominent in the first method also surfaced in the second method, thus providing support that these brain regions and pathways are indeed involved in migraine pathophysiology.

Abstract

Migraine is a common episodic brain disorder characterized by recurrent attacks of severe unilateral headache and additional neurological symptoms. Two main migraine types can be distinguished based on the presence of aura symptoms that can accompany the headache: migraine with aura and migraine without aura. Multiple genetic and environmental factors confer disease susceptibility. Recent genome-wide association studies (GWAS) indicate that migraine susceptibility genes are involved in various pathways, including neurotransmission, which have already been implicated in genetic studies of monogenic familial hemiplegic migraine, a subtype of migraine with aura. Methods To further explore the genetic background of migraine, we performed a gene set analysis of migraine GWAS data of 4954 clinic-based patients with migraine, as well as 13,390 controls. Curated sets of synaptic genes and sets of genes predominantly expressed in three glial cell types (astrocytes, microglia and oligodendrocytes) were investigated. Discussion Our results show that gene sets containing astrocyte- and oligodendrocyte-related genes are associated with migraine, which is especially true for gene sets involved in protein modification and signal transduction. Observed differences between migraine with aura and migraine without aura indicate that both migraine types, at least in part, seem to have a different genetic background.

Abstract

Definition Perceptual learning in speech describes a change in the mapping from acoustic cues in the speech signal to abstract linguistic representations. Learning leads to a lasting benefit to the listener by improving speech comprehension. The change can occur as a response to a specific feature (such as a talker- or accent idiosyncrasy) or to a global degradation of the signal (such as in synthesized or compressed speech). In perceptual learning, a top-down process is involved in causing the change, whereas purely bottom-up, signal-driven phenomena are considered to be adaptation.

Abstract

In the present article, we introduce the continuous unified electronic (CUE) diary method, a longitudinal, event-based, electronic parent report method that allows real-time recording of infant and child behavior in natural contexts. Thirty-nine expectant mothers were trained to identify and record target behaviors into programmed handheld computers. From birth to 18 months, maternal reporters recorded the initial, second, and third occurrences of seven target motor behaviors: palmar grasp, rolls from side to back, reaching when sitting, pincer grip, crawling, walking, and climbing stairs. Compliance was assessed as two valid entries per behavior: 97 % of maternal reporters met compliance criteria. Reliability was assessed by comparing diary entries with researcher assessments for three of the motor behaviors: palmar grasp, pincer grip and walking. A total of 81 % of maternal reporters met reliability criteria. For those three target behaviors, age of emergence was compared across data from the CUE diary method and researcher assessments. The CUE diary method was found to detect behaviors earlier and with greater sensitivity to individual differences. The CUE diary method is shown to be a reliable methodological tool for studying processes of change in human development.

Abstract

It has been proposed that two amino acid substitutions in the transcription factor FOXP2 have been positively selected during human evolution due to effects on aspects of speech and language. Here, we introduce these substitutions into the endogenous Foxp2 gene of mice. Although these mice are generally healthy, they have qualitatively different ultrasonic vocalizations, decreased exploratory behavior and decreased dopamine concentrations in the brain suggesting that the humanized Foxp2 allele affects basal ganglia. In the striatum, a part of the basal ganglia affected in humans with a speech deficit due to a nonfunctional FOXP2 allele, we find that medium spiny neurons have increased dendrite lengths and increased synaptic plasticity. Since mice carrying one nonfunctional Foxp2 allele show opposite effects, this suggests that alterations in cortico-basal ganglia circuits might have been important for the evolution of speech and language in humans.

Abstract

This article presents a description of two sequences of talk by urban speakers of Lao (a southwestern Tai language spoken in Laos) in which co-speech gesture plays a central role in explanations of kinship relations and terminology. The speakers spontaneously use hand gestures and gaze to spatially diagram relationships that have no inherent spatial structure. The descriptive sections of the article are prefaced by a discussion of the semiotic complexity of illustrative gestures and gesture diagrams. Gestured signals feature iconic, indexical, and symbolic components, usually in combination, as well as using motion and three-dimensional space to convey meaning. Such diagrams show temporal persistence and structural integrity despite having been projected in midair by evanescent signals (i.e., handmovements anddirected gaze). Speakers sometimes need or want to revise these spatial representations without destroying their structural integrity. The need to "edit" gesture diagrams involves such techniques as hold-and-drag, hold-and-work-with-free-hand, reassignment-of-old-chunk-tonew-chunk, and move-body-into-new-space.

Abstract

Words such as what -d'you-call-it raise issues at the heart of the semantics/pragmatics interface. Expressions of this kind are conventionalised and have meanings which, while very general, are explicitly oriented to the interactional nature of the speech context, drawing attention to a speaker's assumption that the listener can figure out what the speaker is referring to. The details of such meanings can account for functional contrast among similar expressions, in a single language as well as cross-linguistically. The English expressions what -d'you-call-it and you-know-what are compared, along with a comparable Lao expression meaning, roughly, ‘that thing’. Proposed definitions of the meanings of these expressions account for their different patterns of use. These definitions include reference to the speech act participants, a point which supports the view that what -d'you-call-it words can be considered deictic. Issues arising from the descriptive section of this paper include the question of how such terms are derived, as well as their degree of conventionality.

Abstract

This task is designed to elicit virtual 3D ‘models’ created in gesture space using iconic and other representational gestures. This task has been piloted with Lao speakers, where two speakers were asked to explain the meaning of terms referring to different kinds of fish trap mechanisms. The task elicited complex performances involving a range of iconic gestures, and with especially interesting use of (a) the ‘model/diagram’ in gesture space as a virtual object, (b) the non-dominant hand as a prosodic/semiotic anchor, (c) a range of different techniques (indexical and iconic) for evoking meaning with the hand, and (d) the use of nearby objects and parts of the body as semiotic ‘props’.

Abstract

The semantics of simple (i.e. two-term) systems of demonstratives have in general hitherto been treated as inherently spatial and as marking a symmetrical opposition of distance (‘proximal’ versus ‘distal’), assuming the speaker as a point of origin. More complex systems are known to add further distinctions, such as visibility or elevation, but are assumed to build on basic distinctions of distance. Despite their inherently context-dependent nature, little previous work has based the analysis of demonstratives on evidence of their use in real interactional situations. In this article, video recordings of spontaneous interaction among speakers of Lao (Southwestern Tai, Laos) are examined in an analysis of the two Lao demonstrative determiners nii4 and nan4. A hypothesis of minimal encoded semantics is tested against rich contextual information, and the hypothesis is shown to be consistent with the data. Encoded conventional meanings must be kept distinct from contingent contextual information and context-dependent pragmatic implicatures. Based on examples of the two Lao demonstrative determiners in exophoric uses, the following claims are made. The term nii4 is a semantically general demonstrative, lacking specification of ANY spatial property (such as location or distance). The term nan4 specifies that the referent is ‘not here’ (encoding ‘location’ but NOT ‘distance’). Anchoring the semantic specification in a deictic primitive ‘here’ allows a strictly discrete intensional distinction to be mapped onto an extensional range of endless elasticity. A common ‘proximal’ spatial interpretation for the semantically more general term nii4 arises from the paradigmatic opposition of the two demonstrative determiners. This kind of analysis suggests a reappraisal of our general understanding of the semantics of demonstrative systems universally. To investigate the question in sufficient detail, however, rich contextual data (preferably collected on video) is necessary

Abstract

People of all cultures have some degree of concern with categorizing types of communicative social action. All languages have words with meanings like speak, say, talk, complain, curse, promise, accuse, nod, wink, point and chant. But the exact distinctions they make will differ in both quantity and quality. How is communicative social action categorised across languages and cultures? The goal of this task is to establish a basis for cross-linguistic comparison of native metalanguages for social action.

Abstract

Research on video- and audio-recordings of spontaneous naturally-occurring conversation in English has shown that conversation is a rule-guided, practice-oriented domain that can be investigated for its underlying mechanics or structure. Systematic study could yield something like a grammar for conversation. The goal of this task is to acquire a corpus of video-data, for investigating the underlying structure(s) of interaction cross-linguistically and cross-culturally

Abstract

We want to know how people think about their field of kin, on the supposition that it is quasi-spatial. To get some insights here, we need to video a discussion about kinship reckoning, the kinship system, marriage rules and so on, with a view to looking at both the linguistic expressions involved, and the gestures people use to indicate kinship groups and relations. Unlike the task in the 2001 manual, this task is a direct interview method.

Abstract

The approach to pragmatics explored in this article focuses on elements of social interaction which are of universal relevance, and which may provide bases for a comparative approach. The discussion is anchored by reference to a fragment of conversation from a video-recording of Lao speakers during a home visit in rural Laos. The following points are discussed. First, an understanding of the full richness of context is indispensable for a proper understanding of any interaction. Second, human relationships are a primary locus of social organization, and as such constitute a key focus for pragmatics. Third, human social intelligence forms a universal cognitive under-carriage for interaction, and requires careful cross-cultural study. Fourth, a neo-Peircean framework for a general understanding of semiotic processes gives us a way of stepping away from language as our basic analytical frame. It is argued that in order to get a grip on pragmatics across human groups, we need to take a comparative approach in the biological sense—i.e. with reference to other species as well. From this perspective, human pragmatics is about using semiotic resources to try to meet goals in the realm of social relationships.

Abstract

This task is a complement to the questionnaire ‘Multimodal interaction in your field site: a preliminary investigation’. The objective of the task is to obtain high quality video data on structured and symmetrical dyadic multimodal interaction. The features of interaction we are interested in include turn organization in speech and nonverbal behavior, eye-gaze behavior, use of composite signals (i.e. communicative units of speech-combined-with-gesture), and linguistic and other resources for ‘navigating’ interaction (e.g. words like okay, now, well, and um).

Abstract

Human actions in the social world – like greeting, requesting, complaining, accusing, asking, confirming, etc. – are recognised through the interpretation of signs. Language is where much of the action is, but gesture, facial expression and other bodily actions matter as well. The goal of this task is to establish a maximally rich description of a representative, good quality piece of conversational interaction, which will serve as a reference point for comparative exploration of the status of social actions and their formulation across language

Abstract

Book review of James R. Hurford THE ORIGINS OF GRAMMAR 791pp. Oxford University Press. ISBN 978 0 19 920787 9

Abstract

Noise-vocoded speech is a spectrally highly degraded signal, but it preserves the temporal envelope of speech. Listeners vary considerably in their ability to adapt to this degraded speech signal. Here, we hypothesized that individual differences in adaptation to vocoded speech should be predictable by non-speech auditory, cognitive, and neuroanatomical factors. We tested eighteen normal-hearing participants in a short-term vocoded speech-learning paradigm (listening to 100 4-band-vocoded sentences). Non-speech auditory skills were assessed using amplitude modulation (AM) rate discrimination, where modulation rates were centered on the speech-relevant rate of 4 Hz. Working memory capacities were evaluated (digit span and nonword repetition), and structural MRI scans were examined for anatomical predictors of vocoded speech learning using voxel-based morphometry. Listeners who learned faster to understand degraded speech also showed smaller thresholds in the AM discrimination task. This ability to adjust to degraded speech is furthermore reflected anatomically in increased volume in an area of the left thalamus (pulvinar) that is strongly connected to the auditory and prefrontal cortices. Thus, individual non-speech auditory skills and left thalamus grey matter volume can predict how quickly a listener adapts to degraded speech.

Abstract

Among the most fascinating data for phonology are those showing how speakers incorporate new words and foreign words into their language system, since these data provide cues to the actual principles underlying language. In this article, we address how speakers deal with neutralized obstruents in new words. We formulate four hypotheses and test them on the basis of Dutch word-final obstruents, which are neutral for [voice]. Our experiments show that speakers predict the characteristics ofneutralized segments on the basis ofphonologically similar morphemes stored in the mental lexicon. This effect of the similar morphemes can be modeled in several ways. We compare five models, among them STOCHASTIC OPTIMALITY THEORY and ANALOGICAL MODELING OF LANGUAGE; all perform approximately equally well, but they differ in their complexity, with analogical modeling oflanguage providing the most economical explanation.

Abstract

Amsterdam klinkt in informele gesprekken vaak als Amsdam en Rotterdam als Rodam, zonder dat de meeste moedertaalsprekers zich daar bewust van zijn. In alledaagse situaties valt een aanzienlijk deel van de klanken weg. Daarnaast worden veel klanken zwakker gearticuleerd (bijvoorbeeld een d als een j, als de mond niet helemaal afgesloten wordt). Het lijkt waarschijnlijk dat deze half uitgesproken woorden een probleem vormen voor tweedetaalleerders. Gereduceerde vormen kunnen immers sterk afwijken van de vormen die deze leerders geleerd hebben. Of dit werkelijk zo is, hebben de auteurs onderzocht in twee studies. Voordat ze deze twee studies bespreken, vertellen ze eerst kort iets over de verschillende typen reducties die voorkomen.

Abstract

We investigated whether regional differences in the native language (L1) influence the perception of second language (L2) sounds. Many cross-language and L2 perception studies have assumed that the degree of acoustic similarity between L1 and L2 sounds predicts cross-linguistic and L2 performance. The present study tests this assumption by examining the perception of the English contrast between /e{open}/ and /æ/ in native speakers of Dutch spoken in North Holland (the Netherlands) and in East- and West-Flanders (Belgium). A Linear Discriminant Analysis on acoustic data from both dialects showed that their differences in vowel production, as reported in and Adank, van Hout, and Van de Velde (2007), should influence the perception of the L2 vowels if listeners focus on the vowels' acoustic/auditory properties. Indeed, the results of categorization tasks with Dutch or English vowels as response options showed that the two listener groups differed as predicted by the discriminant analysis. Moreover, the results of the English categorization task revealed that both groups of Dutch listeners displayed the asymmetric pattern found in previous word recognition studies, i.e. English /æ/ was more frequently confused with English /e{open}/ than the reverse. This suggests a strong link between previous L2 word learning results and the present L2 perceptual assimilation patterns.

Abstract

Nuclear orphan receptor TLX (NR2E1) functions primarily as a transcriptional repressor and its pivotal role in brain development, glioblastoma, mental retardation and retinopathologies make it an attractive drug target. TLX is expressed in the neural stem cells (NSCs) of the subventricular zone and the hippocampus subgranular zone, regions with persistent neurogenesis in the adult brain, and functions as an essential regulator of NSCs maintenance and self-renewal. Little is known about the TLX social network of interactors and only few TLX coregulators are described. To identify and characterize novel TLX-binders and possible coregulators, we performed yeast-two-hybrid (Y2H) screens of a human adult brain cDNA library using different TLX constructs as baits. Our screens identified multiple clones of Atrophin-1 (ATN1), a previously described TLX interactor. In addition, we identified an interaction with the oncoprotein and zinc finger transcription factor BCL11A (CTIP1/Evi9), a key player in the hematopoietic system and in major blood-related malignancies. This interaction was validated by expression and coimmunoprecipitation in human cells. BCL11A potentiated the transrepressive function of TLX in an in vitro reporter gene assay. Our work suggests that BCL11A is a novel TLX coregulator that might be involved in TLX-dependent gene regulation in the brain.

Abstract

Mutations affecting the transcription factor FOXP2 cause a rare form of severe speech and language disorder. Although it is clear that sufficient FOXP2 expression is crucial for normal brain development, little is known about how this transcription factor is regulated. To investigate post-translational mechanisms for FOXP2 regulation, we searched for protein interaction partners of FOXP2, and identified members of the PIAS family as novel FOXP2 interactors. PIAS proteins mediate post-translational modification of a range of target proteins with small ubiquitin-like modifiers (SUMOs). We found that FOXP2 can be modified with all three human SUMO proteins and that PIAS1 promotes this process. An aetiological FOXP2 mutation found in a family with speech and language disorder markedly reduced FOXP2 SUMOylation. We demonstrate that FOXP2 is SUMOylated at a single major site, which is conserved in all FOXP2 vertebrate orthologues and in the paralogues FOXP1 and FOXP4. Abolishing this site did not lead to detectable changes in FOXP2 subcellular localization, stability, dimerization or transcriptional repression in cellular assays, but the conservation of this site suggests a potential role for SUMOylation in regulating FOXP2 activity in vivo.