Publications

Abstract

Neurodevelopmental disorders have a strong genetic component, but despite widespread efforts, the specific genetic factors underlying these disorders remain undefined for a large proportion of affected individuals. Given the accessibility of exome-sequencing, this problem has thus far been addressed from a protein-centric standpoint; however, protein-coding regions only make up ∼1-2% of the human genome. With the advent of whole-genome sequencing we are in the midst of a paradigm shift as it is now possible to interrogate the entire sequence of the human genome (coding and non-coding) to fill in the missing heritability of complex disorders. These new technologies bring new challenges, as the number of non-coding variants identified per individual can be overwhelming, making it prudent to focus on non-coding regions of known function, for which the effects of variation can be predicted and directly tested to assess pathogenicity. The 3’UTRome is a region of the non-coding genome that perfectly fulfils these criteria and is of high interest when searching for pathogenic variation related to complex neurodevelopmental disorders. Herein, we review the regulatory roles of the 3’UTRome as binding sites for microRNAs, RNA binding proteins or during alternative polyadenylation. We detail existing evidence that these regions contribute to neurodevelopmental disorders and outline strategies for identification and validation of novel putatively pathogenic variation in these regions. This evidence suggests that studying the 3’UTRome will lead to the identification of new risk factors, new candidate disease genes and a better understanding of the molecular mechanisms contributing to NDDs.

Abstract

While listeners are recognizing words from the connected speech stream, they are also parsing information from the intonational contour. This contour may contain cues to word boundaries, particularly if a language has boundary tones that occur at a large proportion of word onsets. We investigate how useful the pitch rise at the beginning of an accentual phrase (APR) would be as a potential word-boundary cue for Japanese listeners. A corpus study shows that it should allow listeners to locate approximately 40–60% of word onsets, while causing less than 1% false positives. We then present a word-spotting study which shows that Japanese listeners can, indeed, use accentual phrase boundary cues during segmentation. This work shows that the prosodic patterns that have been found in the production of Japanese also impact listeners’ processing.

Abstract

The establishment of a reliable model for the study of Purkinje cells in vitro is of particular importance, given their central role in cerebellar function and pathology. Recent advances in induced pluripotent stem cell (iPSC) technology offer the opportunity to generate multiple neuronal subtypes for study in vitro. However, to date, only a handful of studies have generated Purkinje cells from human pluripotent stem cells, with most of these protocols proving challenging to reproduce. Here, we describe a simplified method for the reproducible generation of Purkinje cells from human iPSCs. After 21 days of treatment with factors selected to mimic the self-inductive properties of the isthmic organiser—insulin, fibroblast growth factor 2 (FGF2), and the transforming growth factor β (TGFβ)-receptor blocker SB431542—hiPSCs could be induced to form En1-positive cerebellar progenitors at efficiencies of up to 90%. By day 35 of differentiation, subpopulations of cells representative of the two cerebellar germinal zones, the rhombic lip (Atoh1-positive) and ventricular zone (Ptf1a-positive), could be identified, with the latter giving rise to cells positive for Purkinje cell progenitor-specific markers, including Lhx5, Kirrel2, Olig2 and Skor2. Further maturation was observed following dissociation and co-culture of these cerebellar progenitors with mouse cerebellar cells, with 10% of human cells staining positive for the Purkinje cell marker calbindin by day 70 of differentiation. This protocol, which incorporates modifications designed to enhance cell survival and maturation and improve the ease of handling, should serve to make existing models more accessible, in order to enable future advances in the field.

Abstract

Two cross-modal priming studies investigated the recognition of English words spoken with a foreign accent. Auditory English primes were either typical of a Dutch accent or typical of a Japanese accent in English and were presented to both Dutch and Japanese L2 listeners. Lexical-decision times to subsequent visual target words revealed that foreign-accented words can facilitate word recognition for L2 listeners if at least one of two requirements is met: the foreign-accented production is in accordance with the language background of the L2 listener, or the foreign accent is perceptually confusable with the standard pronunciation for the L2 listener. If neither one of the requirements is met, no facilitatory effect of foreign accents on L2 word recognition is found. Taken together, these findings suggest that linguistic experience with a foreign accent affects the ability to recognize words carrying this accent, and there is furthermore a general benefit for L2 listeners for recognizing foreign-accented words that are perceptually confusable with the standard pronunciation.

Abstract

Reports of an advantage of bilingualism on brain structure in young adult participants
are inconsistent. Abutalebi et al. (2012) reported more efficient monitoring of conflict during the
Flanker task in young bilinguals compared to young monolingual speakers. The present study
compared young adult (mean age = 24) Cantonese-English bilinguals in Hong Kong and young
adult monolingual speakers. We expected (a) differences in metabolites in neural tissue to result
from bilingual experience, as measured by 1H-MRS at 3T, (b) correlations between metabolic
levels and Flanker conflict and interference effects (c) different associations in bilingual and
monolingual speakers. We found evidence of metabolic differences in the ACC due to bilingualism,
specifically in metabolites Cho, Cr, Glx and NAA. However, we found no significant correlations
between metabolic levels and conflict and interference effects and no significant evidence of
differential relationships between bilingual and monolingual speakers. Furthermore, we found no
evidence of significant differences in the mean size of conflict and interference effects between
groups i.e. no bilingual advantage. Lower levels of Cho, Cr, Glx and NAA in bilingual adults
compared to monolingual adults suggest that the brains of bilinguals develop greater adaptive
control during conflict monitoring because of their extensive bilingual experience.

Abstract

Three experiments examined the time course of phonological encoding in speech production. A new methodology is introduced in which subjects are required to monitor their internal speech production for prespecified target segments and syllables. Experiment 1 demonstrated that word initial target segments are monitored significantly faster than second syllable initial target segments. The addition of a concurrent articulation task (Experiment 1b) had a limited effect on performance, excluding the possibility that subjects are monitoring a subvocal articulation of the carrier word. Moreover, no relationship was observed between the pattern of monitoring latencies and the timing of the targets in subjects′ overt speech. Subjects are not, therefore, monitoring an internal phonetic representation of the carrier word. Experiment 2 used the production monitoring task to replicate the syllable monitoring effect observed in speech perception experiments: responses to targets were faster when they corresponded to the initial syllable of the carrier word than when they did not. We conclude that subjects are monitoring their internal generation of a syllabified phonological representation. Experiment 3 provides more detailed evidence concerning the time course of the generation of this representation by comparing monitoring latencies to targets within, as well as between, syllables. Some amendments to current models of phonological encoding are suggested in light of these results.

Abstract

Early language development is known to be under genetic influence, but the genes affecting normal variation in the general population remain largely elusive. Recent studies of disorder reported that variants of the CNTNAP2 gene are associated both with language deficits in specific language impairment (SLI) and with language delays in autism. We tested the hypothesis that these CNTNAP2 variants affect communicative behavior, measured at 2 years of age in a large epidemiological sample, the Western Australian Pregnancy Cohort (Raine) Study. Singlepoint analyses of 1149 children (606 males, 543 emales) revealed patterns of association which were strikingly reminiscent of those observed in previous investigations of impaired language, centered on the same genetic markers, and with a consistent direction of effect (rs2710102, p = .0239; rs759178, p = .0248). Based on these findings we performed analyses of four-marker haplotypes of rs2710102- s759178-rs17236239-rs2538976, and identified significant association (haplotype TTAA, p = .049; haplotype GCAG, p = .0014). Our study suggests that common variants in the exon 13-15 region of CNTNAP2 influence early language acquisition, as assessed at age 2, in the general population. We propose that these CNTNAP2 variants increase susceptibility to SLI or autism when they occur together with other risk factors.

Abstract

The purpose of this paper is to question some of the basic assumpiions concerning motion verbs. In particular, it examines the assumption that "come" and "go" are lexical universals which manifest a universal deictic Opposition. Against the background offive working hypotheses about the nature of'come" and ''go", this study presents a comparative investigation of t wo unrelated languages—Mparntwe Arrernte (Pama-Nyungan, Australian) and Longgu (Oceanic, Austronesian). Although the pragmatic and deictic "suppositional" complexity of"come" and "go" expressions has long been recognized, we argue that in any given language the analysis of these expressions is much more semantically and systemically complex than has been assumed in the literature. Languages vary at the lexical semantic level äs t o what is entailed by these expressions, äs well äs differing äs t o what constitutes the prototype and categorial structure for such expressions. The data also strongly suggest that, ifthere is a lexical universal "go", then this cannof be an inherently deictic expression. However, due to systemic Opposition with "come", non-deictic "go" expressions often take on a deictic Interpretation through pragmatic attribution. Thus, this crosslinguistic investigation of "come" and "go" highlights the need to consider semantics and pragmatics äs modularly separate.

Abstract

According to theories of embodied cognition, understanding a verb like throw involves unconsciously simulating the action of throwing, using areas of the brain that support motor planning. If understanding action words involves mentally simulating one’s own actions, then the neurocognitive representation of word meanings should differ for people with different kinds of bodies, who perform actions in systematically different ways. In a test of the body-specificity hypothesis, we used functional magnetic resonance imaging to compare premotor activity correlated with action verb understanding in right- and left-handers. Righthanders preferentially activated the left premotor cortex during lexical decisions on manual-action verbs (compared with nonmanual-action verbs), whereas left-handers preferentially activated right premotor areas. This finding helps refine theories of embodied semantics, suggesting that implicit mental simulation during language processing is body specific: Right- and lefthanders, who perform actions differently, use correspondingly different areas of the brain for representing action verb meanings.

Abstract

The left-hemisphere dominance for language is a core example of the functional specialization of the cerebral hemispheres. The degree of left-hemisphere dominance for language depends on hand preference: Whereas the majority of right-handers show left-hemispheric language lateralization, this number is reduced in left-handers. Here, we assessed whether handedness analogously has an influence upon lateralization in the visual system. Using functional magnetic resonance imaging, we localized 4 more or less specialized extrastriate areas in left- and right-handers, namely fusiform face area (FFA), extrastriate body area (EBA), fusiform body area (FBA), and human motion area (human middle temporal [hMT]). We found that lateralization of FFA and EBA depends on handedness: These areas were right lateralized in right-handers but not in left-handers. A similar tendency was observed in FBA but not in hMT. We conclude that the relationship between handedness and hemispheric lateralization extends to functionally lateralized parts of visual cortex, indicating a general coupling between cerebral lateralization and handedness. Our findings indicate that hemispheric specialization is not fixed but can vary considerably across individuals even in areas engaged relatively early in the visual system.

Abstract

Although language is an effective vehicle for communication, it is unclear how linguistic and communicative abilities relate to each other. Some researchers have argued that communicative message generation involves perspective taking (mentalizing), and—crucially—that mentalizing depends on language. We employed a verbal communication paradigm to directly test whether the generation of a communicative action relies on mentalizing and whether the cerebral bases of communicative message generation are distinct from parts of cortex sensitive to linguistic variables. We found that dorsomedial prefrontal cortex, a brain area consistently associated with mentalizing, was sensitive to the communicative intent of utterances, irrespective of linguistic difficulty. In contrast, left inferior frontal cortex, an area known to be involved in language, was sensitive to the linguistic demands of utterances, but not to communicative intent. These findings show that communicative and linguistic abilities rely on cerebrally (and computationally) distinct mechanisms

Abstract

Does language comprehension depend, in part, on neural systems for action? In previous studies, motor areas of the brain were activated when people read or listened to action verbs, but it remains unclear whether such activation is functionally relevant for comprehension. In the experiments reported here, we used off-line theta-burst transcranial magnetic stimulation to investigate whether a causal relationship exists between activity in premotor cortex and action-language understanding. Right-handed participants completed a lexical decision task, in which they read verbs describing manual actions typically performed with the dominant hand (e.g., “to throw,” “to write”) and verbs describing nonmanual actions (e.g., “to earn,” “to wander”). Responses to manual-action verbs (but not to nonmanual-action verbs) were faster after stimulation of the hand area in left premotor cortex than after stimulation of the hand area in right premotor cortex. These results suggest that premotor cortex has a functional role in action-language understanding.

Abstract

We investigated how visual and linguistic information interact in the perception of emotion. We borrowed a phenomenon from film theory which states that presentation of an as such neutral visual scene intensifies the percept of fear or suspense induced by a different channel of information, such as language. Our main aim was to investigate how neutral visual scenes can enhance responses to fearful language content in parts of the brain involved in the perception of emotion. Healthy participants’ brain activity was measured (using functional magnetic resonance imaging) while they read fearful and less fearful sentences presented with or without a neutral visual scene. The main idea is that the visual scenes intensify the fearful content of the language by subtly implying and concretizing what is described in the sentence. Activation levels in the right anterior temporal pole were selectively increased when a neutral visual scene was paired with a fearful sentence, compared to reading the sentence alone, as well as to reading of non-fearful sentences presented with the same neutral scene. We conclude that the right anterior temporal pole serves a binding function of emotional information across domains such as visual and linguistic information.

Abstract

A debated issue in the relationship between language and thought is how our linguistic abilities are involved in understanding the intentions of others (‘mentalizing’). The results of both theoretical and empirical work have been used to argue that linguistic, and more specifically, grammatical, abilities are crucial in representing the mental states of others. Here we contribute to this debate by investigating how damage to the language system influences the generation and understanding of intentional communicative behaviors. Four patients with pervasive language difficulties (severe global or agrammatic aphasia) engaged in an experimentally controlled non-verbal communication paradigm, which required signaling and understanding a communicative message. Despite their profound language problems they were able to engage in recipient design as well as intention recognition, showing similar indicators of mentalizing as have been observed in the neurologically healthy population. Our results show that aspects of the ability to communicate remain present even when core capacities of the language system are dysfunctional

Abstract

Do people use sensori-motor cortices to understand language? Here we review neurocognitive studies of language comprehension in healthy adults and evaluate their possible contributions to theories of language in the brain. We start by sketching the minimal predictions that an embodied theory of language understanding makes for empirical research, and then survey studies that have been offered as evidence for embodied semantic representations. We explore four debated issues: first, does activation of sensori-motor cortices during action language understanding imply that action semantics relies on mirror neurons? Second, what is the evidence that activity in sensori-motor cortices plays a functional role in understanding language? Third, to what extent do responses in perceptual and motor areas depend on the linguistic and extra-linguistic context? And finally, can embodied theories accommodate language about abstract concepts? Based on the available evidence, we conclude that sensori-motor cortices are activated during a variety of language comprehension tasks, for both concrete and abstract language. Yet, this activity depends on the context in which perception and action words are encountered. Although modality-specific cortical activity is not a sine qua non of language processing even for language about perception and action, sensori-motor regions of the brain appear to make functional contributions to the construction of meaning, and should therefore be incorporated into models of the neurocognitive architecture of language.

Abstract

According to embodied theories of language, people understand a verb like throw, at least in part, by mentally simulating throwing. This implicit simulation is often assumed to be similar or identical to motor imagery. Here we used fMRI totest whether implicit simulations of actions during language understanding involve the same cortical motor regions as explicit motor imagery Healthy participants were presented with verbs related to hand actions (e.g., to throw) and nonmanual actions (e.g., to kneel). They either read these verbs (lexical decision task) or actively imagined performing the actions named by the verbs (imagery task). Primary motor cortex showd effector-specific activation during imagery, but not during lexical decision. Parts of premotor cortex distinguished manual from nonmanual actions during both lexical decision and imagery, but there was no overlap or correlation between regions activated during the two tasks. These dissociations suggest that implicit simulation and explicit imagery cued by action verbs may involve different types of motor representations and that the construct of “mental simulation” should be distinguished from “mental imagery” in embodied theories of language.

Abstract

The human capacity to communicate has been hypothesized to be causally dependent upon language. Intuitively this seems plausible since most communication relies on language. Moreover, intention recognition abilities (as a necessary prerequisite for communication) and language development seem to co-develop. Here we review evidence from neuroimaging as well as from neuropsychology to evaluate the relationship between communicative and linguistic abilities. Our review indicates that communicative abilities are best considered as neurally distinct from language abilities. This conclusion is based upon evidence showing that humans rely on different cortical systems when designing a communicative message for someone else as compared to when performing core linguistic tasks, as well as upon observations of individuals with severe language loss after extensive lesions to the language system, who are still able to perform tasks involving intention understanding

Abstract

Marr and Poggio’s levels of description are one of the most well-known theoretical constructs of twentieth century cognitive science. It entails that behavior can and should be considered at three different levels: computation, algorithm, and implementation. In this contribution focus is on the computational level of description, the level that describes the “why” of cognition. I argue that the computational level should be taken as a starting point in devising experiments in cognitive (neuro)science. Instead, the starting point in empirical practice often is a focus on the stimulus or on some capacity of the cognitive system. The “why” of cognition tends to be ignored when designing research, and is not considered in subsequent inference from experimental results. The overall aim of this manuscript is to show how re-appreciation of the computational level of description as a starting point for experiments can lead to more informative experimentation.

Abstract

Background

The biological mechanisms of headache chronification are poorly understood. We aimed to identify changes in DNA methylation associated with the transformation from episodic to chronic headache.
Methods

Participants were recruited from the population-based Norwegian HUNT Study. Thirty-six female headache patients who transformed from episodic to chronic headache between baseline and follow-up 11 years later were matched against 35 controls with episodic headache. DNA methylation was quantified at 485,000 CpG sites, and changes in methylation level at these sites were compared between cases and controls by linear regression analysis. Data were analyzed in two stages (Stages 1 and 2) and in a combined meta-analysis.
Results

None of the top 20 CpG sites identified in Stage 1 replicated in Stage 2 after multiple testing correction. In the combined meta-analysis the strongest associated CpG sites were related to SH2D5 and NPTX2, two brain-expressed genes involved in the regulation of synaptic plasticity. Functional enrichment analysis pointed to processes including calcium ion binding and estrogen receptor pathways.
Conclusion

In this first genome-wide study of DNA methylation in headache chronification several potentially implicated loci and processes were identified. The study exemplifies the use of prospectively collected population cohorts to search for epigenetic mechanisms of disease

Abstract

Researchers have suggested that the vocabularies of languages are oriented towards the communicative needs of language users. Here, we provide evidence demonstrating that the higher frequency of visual words in a large variety of English corpora is reflected in greater lexical differentiation—a greater number of unique words—for the visual domain in the English lexicon. In comparison, sensory modalities that are less frequently talked about, particularly taste and smell, show less lexical differentiation. In addition, we show that even though sensory language can be expected to change across historical time and between contexts of use (e.g., spoken language versus fiction), the pattern of visual dominance is a stable property of the English language. Thus, we show that across the board, precisely those semantic domains that are more frequently talked about are also more lexically differentiated, for perceptual experiences. This correlation between type and token frequencies suggests that the sensory lexicon of English is geared towards communicative efficiency.

Abstract

The modality learning effect, according to Mayer (2001), proposes that learning is enhanced when information is presented in both the visual and auditory domain (e.g., pictures and spoken information), compared to presenting information solely in the visual channel (e.g., pictures and written text). Most of the evidence for this effect comes from adults in a laboratory setting. Therefore, we tested the modality effect with 80 children in the highest grade of elementary school, in a naturalistic setting. In a between-subjects design children either saw representational pictures with speech or representational pictures with text. Retention and transfer knowledge was tested at three moments: immediately after the intervention, one day after, and after one week. The present study did not find any evidence for a modality effect in children when the lesson is learner-paced. Instead, we found a reversed modality effect directly after the intervention for retention. A reversed modality effect was also found for the transfer questions one day later. This effect was robust, even when controlling for individual differences.

Abstract

Languages are among the most complex systems that evolution has created. With an unforeseen speed many of these unique results of evolution are currently disappearing: every two weeks one of the 6500 still spoken languages is dying and many are subject to extreme changes due to globalization. Experts understood the need to document the languages and preserve the cultural and linguistic treasures embedded in them for future generations. Also linguistic theory will need to consider the variation of the linguistic systems encoded in languages to improve our understanding of how human minds process language material, thus accessibility to all types of resources is increasingly crucial. Deeper insights into human language processing and a higher degree of integration and interoperability between resources will also improve our language processing technology. The DOBES programme is focussing on the documentation and preservation of language material. The Max Planck Institute developed the Language Archiving Technology to help researchers when creating, archiving and accessing language resources. The recently started CLARIN research infrastructure has as main goals to achieve a broad visibility and an easy
accessibility of language resources.

Abstract

Spinocerebellar ataxia type 14 (SCA14) is a subtype of the autosomal dominant cerebellar ataxias that is characterized by slowly progressive cerebellar dysfunction and neurodegeneration. SCA14 is caused by mutations in the PRKCG gene, encoding protein kinase C gamma (PKCγ). Despite the identification of 40 distinct disease-causing mutations in PRKCG, the pathological mechanisms underlying SCA14 remain poorly understood. Here we report the molecular neuropathology of SCA14 in post-mortem cerebellum and in human patient-derived induced pluripotent stem cells (iPSCs) carrying two distinct SCA14 mutations in the C1 domain of PKCγ, H36R and H101Q. We show that endogenous expression of these mutations results in the cytoplasmic mislocalization and aggregation of PKCγ in both patient iPSCs and cerebellum. PKCγ aggregates were not efficiently targeted for degradation. Moreover, mutant PKCγ was found to be hyper-activated, resulting in increased substrate phosphorylation. Together, our findings demonstrate that a combination of both, loss-of-function and gain-of-function mechanisms are likely to underlie the pathogenesis of SCA14, caused by mutations in the C1 domain of PKCγ. Importantly, SCA14 patient iPSCs were found to accurately recapitulate pathological features observed in post-mortem SCA14 cerebellum, underscoring their potential as relevant disease models and their promise as future drug discovery tools.

Abstract

We performed a resting-state functional connectivity study to investigate directly the functional correlations within the perisylvian language networks by seeding from 3 subregions of Broca's complex (pars opercularis, pars triangularis, and pars orbitalis) and their right hemisphere homologues. A clear topographical functional connectivity pattern in the left middle frontal, parietal, and temporal areas was revealed for the 3 left seeds. This is the first demonstration that a functional connectivity topology can be observed in the perisylvian language networks. The results support the assumption of the functional division for phonology, syntax, and semantics of Broca's complex as proposed by the memory, unification, and control (MUC) model and indicated a topographical functional organization in the perisylvian language networks, which suggests a possible division of labor for phonological, syntactic, and semantic function in the left frontal, parietal, and temporal areas.

Abstract

Electroencephalography (EEG) provides high temporal resolution cognitive information from non-invasive recordings. However, one of the common practices-using a subset of sensors in ERP analysis is hard to provide a holistic and precise dynamic results. Selecting or grouping subsets of sensors may also be subject to selection bias, multiple comparison, and further complicated by individual differences in the group-level analysis. More importantly, changes in neural generators and variations in response magnitude from the same neural sources are difficult to separate, which limit the capacity of testing different aspects of cognitive hypotheses. We introduce EasyEEG, a toolbox that includes several multivariate analysis methods to directly test cognitive hypotheses based on topographic responses that include data from all sensors. These multivariate methods can investigate effects in the dimensions of response magnitude and topographic patterns separately using data in the sensor space, therefore enable assessing neural response dynamics. The concise workflow and the modular design provide user-friendly and programmer-friendly features. Users of all levels can benefit from the open-sourced, free EasyEEG to obtain a straightforward solution for efficient processing of EEG data and a complete pipeline from raw data to final results for publication.

Abstract

Although bilingual speakers are very good at selectively using one language rather than another, sometimes language selection errors occur. To investigate how bilinguals monitor their speech errors and control their languages in use, we recorded event-related potentials (ERPs) in unbalanced Dutch-English bilingual speakers in a cued language-switching task. We tested the conflict-based monitoring model of Nozari and colleagues by investigating the error-related negativity (ERN) and comparing the effects of the two switching directions (i.e., to the first language, L1 vs. to the second language, L2). Results show that the speakers made more language selection errors when switching from their L2 to the L1 than vice versa. In the EEG, we observed a robust ERN effect following language selection errors compared to correct responses, reflecting monitoring of speech errors. Most interestingly, the ERN effect was enlarged when the speakers were switching to their L2 (less conflict) compared to switching to the L1 (more conflict). Our findings do not support the conflict-based monitoring model. We discuss an alternative account in terms of error prediction and reinforcement learning.

Abstract

Although bilingual speakers are very good at selectively using one language rather than another, sometimes language selection errors occur. We examined the relative contribution of top-down cognitive control and bottom-up language priming to these errors. Unbalanced Dutch-English bilinguals named pictures and were cued to switch between languages under time pressure. We also manipulated the number of same-language trials before a switch (long vs. short runs). Results show that speakers made more language selection errors when switching from their second language (L2) to the first language (L1) than vice versa. Furthermore, they made more errors when switching to the L1 after a short compared to a long run of L2 trials. In the reverse switching direction (L1 to L2), run length had no effect. These findings are most compatible with an account of language selection errors that assigns a strong role to top-down processes of cognitive control.

Abstract

Celiac disease (CD) is an intolerance to dietary proteins of wheat, barley, and rye. CD may have substantial morbidity, yet it is quite common with a prevalence of 1%-2% in Western populations. It is not clear why the CD phenotype is so prevalent despite its negative effects on human health, especially because appropriate treatment in the form of a gluten-free diet has only been available since the 1950s, when dietary gluten was discovered to be the triggering factor. The high prevalence of CD might suggest that genes underlying this disease may have been favored by the process of natural selection. We assessed signatures of selection for ten confirmed CD-associated loci in several genome-wide data sets, comprising 8154 controls from four European populations and 195 individuals from a North African population, by studying haplotype lengths via the integrated haplotype score (iHS) method. Consistent signs of positive selection for CD-associated derived alleles were observed in three loci: IL12A, IL18RAP, and SH2B3. For the SH2B3 risk allele, we also show a difference in allele frequency distribution (F(st)) between HapMap phase II populations. Functional investigation of the effect of the SH2B3 genotype in response to lipopolysaccharide and muramyl dipeptide revealed that carriers of the SH2B3 rs3184504*A risk allele showed stronger activation of the NOD2 recognition pathway. This suggests that SH2B3 plays a role in protection against bacteria infection, and it provides a possible explanation for the selective sweep on SH2B3, which occurred sometime between 1200 and 1700 years ago.

Abstract

It is undisputed that presenting a rhythmic stimulus leads to a measurable brain response that follows the rhythmic structure of this stimulus. What is still debated, however, is the question whether this brain response exclusively reflects a regular repetition of evoked responses, or whether it also includes entrained oscillatory activity. Here we systematically present evidence in favor of an involvement of entrained neural oscillations in the processing of rhythmic input while critically pointing out which questions still need to be addressed before this evidence could be considered conclusive. In this context, we also explicitly discuss the potential functional role of such entrained oscillations, suggesting that these stimulus-aligned oscillations reflect, and serve as, predictive processes, an idea often only implicitly assumed in the literature.

Abstract

Review: User friendliness of the first dictionary of Sign Language of the Netherlands can be improved

Abstract

(Needed: staff for residential care home with good eye-hand coordination. Measuring NGT-skills.)

Abstract

(The Corpus NGT and the daily practice of language teaching)

Abstract

(The Corpus NGT and teacher NGT/interpreter NGT training)

Abstract

Sign language lexicography has thus far been a relatively obscure area in the world of lexicography. Therefore, this article will contain background information on signed languages and the communities in which they are used, on the lexicography of sign languages, the situation in the Netherlands as well as a review of a sign language dictionary that has recently been published in the Netherlands.