Publications

Abstract

Prion diseases are fatal neurodegenerative disorders that include Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy in animals. They are unique in terms of their biology because they are caused by the conformational re-arrangement of a normal host-encoded prion protein, PrPC, to an abnormal infectious isoform, PrPSc. Currently the precise mechanism behind prion-mediated neurodegeneration remains unclear. It is hypothesised than an unknown toxic gain of function of PrPSc, or an intermediate oligomeric form, underlies neuronal death. Increasing evidence suggests a role for the ubiquitin proteasome system (UPS) in prion disease. Both wild-type PrPC and disease-associated PrP isoforms accumulate in cells after proteasome inhibition leading to increased cell death, and abnormal beta-sheet-rich PrP isoforms have been shown to inhibit the catalytic activity of the proteasome. Here we review potential interactions between prions and the proteasome outlining how the UPS may be implicated in prion-mediated neurodegeneration.

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.

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

Retrieval of autobiographical memories is facilitated by activation of perceptuo-motor aspects of the experience, for example a congruent body position at the time of the experiencing and the time of retelling (Dijkstra, Kaschak, & Zwaan, 2007). The present study examined whether similar retrieval facilitation occurs when the direction of motor action is congruent with the valence of emotional memories. Consistent with evidence that people mentally represent emotions spatially (Casasanto, in press), participants moved marbles between vertically stacked boxes at a higher rate when the direction of movement was congruent with the valence of the memory they retrieved (e.g., upward for positive memories, downward for negative memories) than when direction and valence were incongruent (t(22)=4.24, p<.001). In addition, valence-congruent movements facilitated access to these memories, resulting in shorter retrieval times (t(22)=2.43, p<.05). Results demonstrate bidirectional influences between the emotional content of autobiographical memories and irrelevant motor actions.

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

In this paper we discuss the influence of semantically unexpected information on the prosodic realization of contrast.
For this purpose, we examine the interplay between unexpectedness and various discourse factors that have been claimed to enhance the accentuation of contrastive
information: contrast direction, syntactic status, and discourse distance. We conducted a production experiment in Dutch in which speakers described scenes consisting of moving fruits with unnatural colors. We found that a general cognitive factor such as the unexpectedness of a property has a strong impact on the intonational marking of contrast, over and above the influence of the immediate discourse context.

Abstract

The present dissertation investigates what neurocognitive processes are activated in the brain when listeners comprehend spoken language and in particular the melody and rhythm of speech, also referred to as prosody. The findings of several electrophysiological studies show that prosody influences the early and late stages of spoken language processing. When words are accented, listeners consider them important, and the brain responds to accentuation already 200 milliseconds after stimulus onset. The processing of prosodic prominence occurs whether or not a context is present and whether or not accent is congruent with context, although the responses to accentuation may be modified by either of these factors and by the focus particle only. Listeners are sensitive not only to the presence of prosodic prominence but also to the type of accents speakers use: corrective prosody activates additional interpretation mechanisms related to the construction of corrective meaning. The parallel between accents across clauses impacts the disambiguation of sentences with verb ellipsis. By interpreting prosodically parallel elements as syntactically parallel, listeners arrive at less preferred interpretations of conjoined clauses. The research indentifies early correlates of incongruous prosody in strongly predictive contexts as well as late integration processes for prosody comprehension, which are related to the processing of structural complexity in isolated and ambiguous sentences. The dissertation provides evidence that the brain is sensitive to differences in prosody even in the absence of prosodic judgment. However, by changing the task, one modulates the neural mechanisms of prosody processing.

Abstract

In this paper, we discuss the interplay of factors that influence the intonational marking of contrast in Dutch. In particular, we examine how prominence is expressed at the prosodic level when semantically abnormal information conflicts with contrastive information. For this purpose, we conducted a production experiment in Dutch in which speakers described scenes containing fruits with unnatural colors. We found that semantically abnormal information invokes cognitive prominence which corresponds to intonational prominence. Moreover, the results show that abnormality may overrule the accentual marking of information structural categories such as contrastive focus. If semantically abnormal information becomes integrated into the larger discourse context, its prosodic prominence decreases in favor of the signaling of information structural categories such as contrastive focus.

Abstract

Empirical studies addressing the age factor in second language acquisition have mainly been concerned with a comparison of end state data (from learners before and after the closure of a putative Critical Period for language acquisition) to the native speaker norm. Based on longitudinal corpus data, this paper investigates the affect of age on end state, rate and the process of acquisition and addresses the question of whether different grammatical domains are equally affected. To this end, the paper presents summarized findings from the acquisition of word order and inflectional morphology in L2 German by Russian learners of different ages and discusses theoretical implications that can be drawn from this evidence.

Abstract

It is widely assumed that ultimate attainment in adult second language (L2) learners often differs quite radically from ultimate attainment in child L2 learners. This article addresses the question of whether learners at different ages also show qualitative differences in the process of L2 acquisition. Longitudinal production data from two untutored Russian beginners (ages 8 and 14) acquiring German under roughly similar conditions are compared to published results on the acquisition of German by adult immigrants. The study focuses on the acquisition of negation and finiteness as core domains of German sentence grammar. Adult learners have been shown to produce an early nonfinite learner variety in which utterance organization relies on principles of information structure rather than on target language grammar. They then go through a couple of intermediate steps in which, first, semantically empty verbs (auxiliaries) serve as isolated carriers of finiteness before lexical verbs become finite. Whereas the 14-year-old learner of this case study basically shows a developmental pattern similar to that of adults, the 8-year-old child produces a different order of acquisition: Not only is the development of finite morphology faster, but finite lexical verbs are acquired before auxiliary constructions (Perfekt). Results suggest a stronger tendency for young learners to incrementally assimilate input patterns without relying on analytic steps guided by principles of information organization to the same extent as older learners.

Abstract

Words evolve not as blobs of ink on paper but in face to face interaction. The nature of language as fundamentally interactive and multimodal is shown by the study of ideophones, vivid sensory words that thrive in conversations around the world. The ways in which these Lautbilder enable precise communication about sensory knowledge has for the first time been studied in detail. It turns out that we can paint with language, and that the onomatopoeia we sometimes classify as childish might be a subset of a much richer toolkit for depiction in speech, available to us all.

Abstract

We present a new transcription mode for the annotation tool ELAN. This mode is designed to speed up the process of creating transcriptions of primary linguistic data (video and/or audio recordings of linguistic behaviour). We survey the basic transcription workflow of some commonly used tools (Transcriber, BlitzScribe, and ELAN) and describe how the new transcription interface improves on these existing implementations. We describe the design of the transcription interface and explore some further possibilities for improvement in the areas of segmentation and computational enrichment of annotations.

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

This entry provides some orientation and task suggestions on how to explore the perceptual world of your field site and the interaction between the cultural world and the sensory lexicon in your community. The material consists of procedural texts; soundscapes; other documentary and observational tasks. The goal of this task is to explore the perceptual world of your field site and the interaction between the cultural world and the sensory lexicon in your community.

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

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

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.

Abstract

The widespread occurrence of ideophones, large classes of words specialized in evoking sensory imagery, is little known outside linguistics and anthropology. Ideophones are a common feature in many of the world’s languages but are underdeveloped in English and other Indo-European languages. Here we study the meanings of ideophones in Siwu (a Kwa language from Ghana) using a pile-sorting task. The goal was to uncover the underlying structure of the lexical space and to examine the claimed link between ideophones and perception. We found that Siwu ideophones are principally organized around fine-grained aspects of sensory perception, and map onto salient psychophysical dimensions identified in sensory science. The results ratify ideophones as dedicated sensory vocabulary and underline the relevance of ideophones for research on language and perception.

Abstract

This thesis examines the semantic structures underlying the encoding of space in Chintang, a Kiranti (Sino-Tibetan) language of Nepal. It provides a short general introduction to the history of thinking and speaking about space as well as to the notions of deixis and transposition, and sketches a state-of-the-art theory for categorizing spatial semantics (Levinson 2003). Drawing on targeted elicitation with native speakers, the empirical part then relates linguistic items of Chintang to the theoretical framework, with a focus on the nominal domain. After an analysis of deictic, topological, intrinsic and absolute spatial relations and their reflections in the language, the investigation concludes by comparing sets of Chintang deictics to those found in neighbouring Belhare (Bickel 2001). Despite striking formal resemblances, the semantic differences found indicate that even across closely related languages, meaning does not generalize easily.

Abstract

Spatial congruity effects have often been interpreted as evidence for metaphorical thinking, but an alternative markedness-based account challenges this view. In two experiments, we directly compared metaphor and markedness explanations for spatial congruity effects, using musical pitch as a testbed. English speakers who talk about pitch in terms of spatial height were tested in speeded space-pitch compatibility tasks. To determine whether space-pitch congruency effects could be elicited by any marked spatial continuum, participants were asked to classify high- and low-frequency pitches as 'high' and 'low' or as 'front' and 'back' (both pairs of terms constitute cases of marked continuums). We found congruency effects in high/low conditions but not in front/back conditions, indicating that markedness is not sufficient to account for congruity effects (Experiment 1). A second experiment showed that congruency effects were specific to spatial words that cued a vertical schema (tall/short), and that congruity effects were not an artifact of polysemy (e.g., 'high' referring both to space and pitch). Together, these results suggest that congruency effects reveal metaphorical uses of spatial schemas, not markedness effects.

Abstract

People often talk about musical pitch in terms of spatial metaphors. In English, for instance, pitches can be high or low, whereas in other languages pitches are described as thick or thin. According to psychophysical studies, metaphors in language can also shape people’s nonlinguistic space-pitch representations. But does language establish mappings between space and pitch in the first place or does it modify preexisting associations? Here we tested 4-month-old Dutch infants’ sensitivity to height-pitch and thickness-pitch mappings in two preferential looking tasks. Dutch infants looked significantly longer at cross-modally congruent stimuli in both experiments, indicating that infants are sensitive to space-pitch associations prior to language. This early presence of space-pitch mappings suggests that these associations do not originate from language. Rather, language may build upon pre-existing mappings and change them gradually via some form of competitive associative learning.

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.

Abstract

The Levelt, Noort and Drenth Committees make their sole and final rejoinder to criticisms of their report on the Stapel fraud

Abstract

This paper summarizes the results of a descriptive syntactic category analysis of child English no which reveals that young children use and represent no as a determiner and negatives like no pen as NPs, contra standard analyses.

Abstract

Der vorliegende Beitrag zum Kieler Symposium1 stellt die Resultate eines Teilbereichs meiner Arbeit zum Guarani vor, nämlich einen Vorschlag zur Analyse der Personenpräfixe dieser Sprache und der mit ihnen verbundenen grammatischen Kategorien. Die im Titel angedeutete lexikographische Fragestellung bedarf einer näheren Erläuterung, die ich im Zusammenhang mit einer kurzen Darstellung der Motivation für meine Untersuchungen geben will

Abstract

With the present essay I pursue a threefold aim as will be explained in the following paragraphs. Since I cannot expect my readers to be familiar with the language studied, Guaran´ı, more information about this language will be given in the next subsection.

Abstract

Overview Since the early nineties, the on-going dramatic loss of the world’s linguistic diversity has gained attention, first by the linguists and increasingly also by the general public. As a response, the new field of language documentation emerged from around 2000 on, starting with the funding initiative ‘Dokumentation Bedrohter Sprachen’ (DoBeS, funded by the Volkswagen foundation, Germany), soon to be followed by others such as the ‘Endangered Languages Documentation Programme’ (ELDP, at SOAS, London), or, in the USA, ‘Electronic Meta-structure for Endangered Languages Documentation’ (EMELD, led by the LinguistList) and ‘Documenting Endangered Languages’ (DEL, by the NSF). From its very beginning, the new field focused on digital technologies not only for recording in audio and video, but also for annotation, lexical databases, corpus building and archiving, among others. This development not just coincides but is intrinsically interconnected with the increasing focus on digital data, technology and methods in all sciences, in particular in the humanities.

Abstract

1. Object: Awetí and the ‘Mawetí-Guaraní’ subfamily “Mawetí-Guaraní” is a shorter designation of a branch of the large Tupí language family, alongside with eight other branches or subfamilies. This branch in turn consists internally of the languages (Sateré-) Mawé and Awetí and the large Tupí-Guaraní subfamily, and so its explicit but longish name could be “Mawé-Awetí-Tupí-Guaraní” (MTAG). This genetic grouping has already been suggested (without any specific designation) by A. D. Rodrigues (e.g., 1984/85; Rodrigues and Dietrich 1997), and, more recently, it has been confirmed by comparative studies (Corrêa da Silva 2007; Drude 2006; Meira and Drude in prep.), which also more reliably establish the most probable internal ramification, according to which Mawé separated first, whereas the differentiation between Awetí, on the one hand, and the precursor of the Tupí-Guaraní (TG) subfamily, proto-Tupí-Guaraní (pTG), on the other, would have been more recent. The intermediate branch could be named “Awetí-Tupí-Guaraní” (“Awetí-TG” or “ATG”). Figure 1 shows the internal grouping of the Tupí family according to results of the Tupí Comparative Project under D. Moore at the Museu Goeldi (2000–2006).

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

This paper describes the verbal Tense-Aspect-Mood system of Awetí (Tupian, Central Brazil) in a Word-and-Paradigm approach. One classification of Awetí verb forms contains clear aspect categories. A second set of independent classifications renders at least four moods and contains a third major TAM classification, factuality, that has one mainly temporal category Future, while others are partially or wholly modal. Structural categories reflect the formal composition of the forms. Some forms are synthetic, ‘marked’ only by means of affixes, but many are analytic, containing auxiliary particles. With selected sample forms we demonstrate in detail the interplay of structural and functional categories in Awetí verb paradigms.

Abstract

This contribution presents “The Language Archive” (TLA), a new unit at the MPI for Psycholinguistics, discussing the current developments in management of scientific data, considering the need for new data research infrastructures. Although several initiatives worldwide in the realm of language resources aim at the integration, preservation and mobilization of research data, the state of such scientific data is still often problematic. Data are often not well organized and archived and not described by metadata ― even unique data such as field-work observational data on endangered languages is still mostly on perishable carriers. New data centres are needed that provide trusted, quality-reviewed, persistent services and suitable tools and that take legal and ethical issues seriously. The CLARIN initiative has established criteria for suitable centres. TLA is in a good position to be one of such centres. It is based on three essential pillars: (1) A data archive; (2) management, access and annotation tools; (3) archiving and software expertise for collaborative projects. The archive hosts mostly observational data on small languages worldwide and language acquisition data, but also data resulting from experiments

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

Using various methods derived from evolutionary biology, including maximum parsimony and Bayesian phylogenetic analysis, we tackle the question of the relationships among a group of Papuan isolate languages that have hitherto resisted accepted attempts at demonstration of interrelatedness. Instead of using existing vocabulary-based methods, which cannot be applied to these languages due to the paucity of shared lexemes, we created a database of STRUCTURAL FEATURES—abstract phonological and grammatical features apart from their form. The methods are first tested on the closely related Oceanic languages spoken in the same region as the Papuan languages in question. We find that using biological methods on structural features can recapitulate the results of the comparative method tree for the Oceanic languages, thus showing that structural features can be a valid way of extracting linguistic history. Application of the same methods to the otherwise unrelatable Papuan languages is therefore likely to be similarly valid. Because languages that have been in contact for protracted periods may also converge, we outline additional methods for distinguishing convergence from inherited relatedness.

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

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 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.

Abstract

In recent years, large scale initiatives like CLARIN set out to overcome the notorious heterogeneity of metadata formats in the domain of language resource. The CLARIN Component Metadata Infrastructure established means for flexible resouce descriptions for the domain of language resources. The Data Category Registry ISOcat and the accompanying Relation Registry foster semantic interoperability within the growing heterogeneous collection of metadata records. This paper describes the CMD Infrastructure focusing on the facilities for semantic mapping, and gives also an overview of the current status in the joint component metadata domain.

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

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.

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.

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.

Abstract

1. Introduction Speech conveys not only linguistic meaning but also paralinguistic information, such as features of the speaker’s social background, physiology, and emotional state. Linguistic and paralinguistic information is encoded in speech by using largely the same vocal apparatus and both are transmitted simultaneously in the acoustic signal, drawing on a limited set of acoustic cues. How this simultaneous encoding is achieved, how the different types of information are disentangled by the listener, and how much they interfere with one another is presently not well understood. Previous research has highlighted the importance of acoustic source and filter cues for emotion and linguistic encoding respectively, which may suggest that the two types of information are encoded independently of each other. However, those lines of investigation have been almost completely disconnected (Murray & Arnott, 1993).

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.

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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.

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Language resource centers allow researchers to reliably deposit their structured data together with associated meta data and run services operating on this deposited data. We are looking into possibilities to create long-term persistency of both the deposited data and the services operating on this data. Challenges, both technical and non-technical, that need to be solved are the need to replicate more than just the data, proper identification of the digital objects in a distributed environment by making use of persistent identifiers and the set-up of a proper authentication and authorization domain including the management of the authorization information on the digital objects. We acknowledge the investment that most language resource centers have made in their current infrastructure. Therefore one of the most important requirements is the loose coupling with existing infrastructures without the need to make many changes. This shift from a single language resource center into a federated environment of many language resource centers is discussed in the context of a real world center: The Language Archive supported by the Max Planck Institute for Psycholinguistics.

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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.

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To develop a nuanced account for selection within an epidemiological, population-based model of language contact and change, it is useful to consider possible conduits and filters on linguistic transmission and distribution. Richerson & Boyd (2005) describe a number of candidate biases in their evolutionary analysis of culture as a biological phenomenon (cf. Cavalli-Sforza & Feldman 1981, Sperber 1985, 1999, Boyd & Richerson 2005). This paper explores some of these biases with reference to language, exploring a set of analytic distinctions for a proper understanding of population-level linguistic processes. In putting forward these ideas, this paper echoes recent attempts to combine linguistic and biological concepts in the analysis of language diversity and change.

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This field guide is for eliciting information about grammatical resources used in describing perceptual events and perception-based properties and states. A list of leading questions outlines an underlying semantic space for events/states of perception, against which language-specific constructions may be defined. It should be used as an entry point into a flexible exploration of the structures and constraints which are specific to the language you are working on. The goal is to provide a cross-linguistically comparable description of the constructions of a language used in describing perceptual events and states. The core focus is to discover any sensory asymmetries, i.e., ways in which different sensory modalities are treated differently with respect to these constructions.

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Different domains of concrete referential semantics have provided testing grounds for investigation of the differential roles of perception, cognition, language, and culture in human categorization. A vast literature on semantics of biological classification, color, shape and topological relations, artifacts, and more, raises a range of theoretical and analytical debates. This article uses landscape terms to address a key debate from within research on ethnobiological classification: the opposition between so-called utilitarian and intellectualist accounts for patterns of lexicalization of the natural world [Berlin, B., 1992. Ethnobiological Classification: Principles of Categorization of Plants and Animals in Traditional Societies. Princeton University Press, Princeton, NJ]. ‘Utilitarianists’ argue that lexical categories reflect practical consequences of knowing certain category distinctions, related to cultural practice and functional affordances of referents. ‘Intellectualists’ argue that lexical categories reflect people’s innate interest in the natural world, combined with the perceptual discontinuities supplied by ‘Nature’s Plan’. The debate is generalizable to other domains, including landscape terminology, the topic of this special issue. This article brings landscape terminology into this larger debate, arguing in favor of a utilitarian account of linguistic categories in the domain of landscape, but proposing a significant revision to the concept of utility in linguistic categorization. The proposal is that for linguistic categorization, what is at issue is not (primarily) the utility of the referent (e.g. a river), but the utility of the word (e.g. the English word river). By considering how landscape terms are actually used in conversation, we see that they are deployed in communicative contexts which fit a rich, ‘functionalist’ semantics. A landscape term is not employed for mere referring, but functions to bring particular associated ideas into social discourse. In turn, language use reveals a range of evidence for the semantic content of any such term, of utility both to the language learner and to the semanticist. This kind of evidence can be argued to underlie the acquisition of semantic categories in language learning. The arguments are illustrated with examples from Lao, a Tai language of mainland Southeast Asia.

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Language is shaped by its environment, which includes not only the brain, but also the public context in which speech acts are effected. To fully account for why language has the shape it has, we need to examine the constraints imposed by language use as a sequentially organized joint activity, and as the very conduit for linguistic diffusion and change.

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Introduction

A comparison of conversation in twenty-one languages from around the world reveals commonalities and differences in the way that people do open-class other-initiation of repair (Schegloff, Jefferson, and Sacks, 1977; Drew, 1997). We find that speakers of all of the spoken languages in the sample make use of a primary interjection strategy (in English it is Huh?), where the phonetic form of the interjection is strikingly similar across the languages: a monosyllable featuring an open non-back vowel [a, æ, ə, ʌ], often nasalized, usually with rising intonation and sometimes an [h-] onset. We also find that most of the languages have another strategy for open-class other-initiation of repair, namely the use of a question word (usually “what”). Here we find significantly more variation across the languages. The phonetic form of the question word involved is completely different from language to language: e.g., English [wɑt] versus Cha'palaa [ti] versus Duna [aki]. Furthermore, the grammatical structure in which the repair-initiating question word can or must be expressed varies within and across languages. In this chapter we present data on these two strategies – primary interjections like Huh? and question words like What? – with discussion of possible reasons for the similarities and differences across the languages. We explore some implications for the notion of repair as a system, in the context of research on the typology of language use.

The general outline of this chapter is as follows. We first discuss repair as a system across languages and then introduce the focus of the chapter: open-class other-initiation of repair. A discussion of the main findings follows, where we identify two alternative strategies in the data: an interjection strategy (Huh?) and a question word strategy (What?). Formal features and possible motivations are discussed for the interjection strategy and the question word strategy in order. A final section discusses bodily behavior including posture, eyebrow movements and eye gaze, both in spoken languages and in a sign language.

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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.

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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.

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This chapter contains sections titled: Introduction Lexical Selection in Reference: Introductory Examples of Reference to Times Multiple “Preferences” Future Directions Conclusion

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This Field Manual entry has been superceded by the 2009 version: https://doi.org/10.17617/2.883564

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

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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.

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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.

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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.

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This study addresses the extent to which the location of primary stress in Dutch, German, and English monomorphemic words is affected by the syllables preceding the three final syllables. We present analyses of the monomorphemic words in the CELEX lexical database, which showed that penultimate primary stress is less frequent in Dutch and English trisyllabic than quadrisyllabic words. In addition, we discuss paper-and-pencil experiments in which native speakers assigned primary stress to pseudowords. These experiments provided evidence that in all three languages penultimate stress is more likely in quadrisyllabic than in trisyllabic words. We explain this length effect with the preferences in these languages for word-initial stress and for alternating patterns of stressed and unstressed syllables. The experimental data also showed important intra- and interspeaker variation, and they thus form a challenging test case for theories of language variation.

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Rede uitgesproken bij de aanvaarding van het ambt van hoogleraar Psycholinguïstiek aan de Faculteit der Letteren van de Radboud Universiteit Nijmegen op vrijdag 18 januari 2013

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The lexical and phonetic mapping of auditorily confusable L2 nonwords was examined by teaching L2 learners novel words and by later examining their word recognition using an eye-tracking paradigm. During word learning, two groups of highly proficient Dutch learners of English learned 20 English nonwords, of which 10 contained the English contrast /e/-æ/ (a confusable contrast for native Dutch speakers). One group of subjects learned the words by matching their auditory forms to pictured meanings, while a second group additionally saw the spelled forms of the words. We found that the group who received only auditory forms confused words containing /æ/ and /e/ symmetrically, i.e., both /æ/ and /e/ auditory tokens triggered looks to pictures containing both /æ/ and /e/. In contrast, the group who also had access to spelled forms showed the same asymmetric word recognition pattern found by previous studies, i.e., they only looked at pictures of words containing /e/ when presented with /e/ target tokens, but looked at pictures of words containing both /æ/ and /e/ when presented with /æ/ target tokens. The results demonstrate that L2 learners can form lexical contrasts for auditorily confusable novel L2 words. However, and most importantly, this study suggests that explicit information over the contrastive nature of two new sounds may be needed to build separate lexical representations for similar-sounding L2 words.

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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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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.

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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.

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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).

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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.