Publications

Abstract

To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E−8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E−07), TOX (rs7823467, P = 3.47E−07) and LINC00340 (rs12212674, P = 1.49E−06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = −0.59, P = 2.10E−04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.

Abstract

In het onderwijs wordt aangenomen dat hardop en stillezen dezelfde processen zijn. In dit onderzoek wordt gekeken naar het verschil tussen hardop en stillezen wat betreft leessnelheid en tekstbegrip bij 90 kinderen uit groep 4. Ook wordt de invloed van de cognitieve vaardigheden fonologisch bewustzijn, benoemsnelheid en visuele aandachtsspanne op de verschillende leesmodi onderzocht. De participanten lazen stil sneller, maar begrepen de tekst beter hardop. De cognitieve vaardigheden correleerden met hardop en stillezen wat betreft leessnelheid, maar hingen in beide leesmodi niet samen met tekstbegrip. Hoewel hardop en stillezen samenhangen, onderstrepen deze bevindingen dat het verschillende leesmodi zijn.

Abstract

Diffusion tensor imaging (DTI) and a longitudinal language learning approach were applied to investigate the relationship between the achieved second language (L2) proficiency during L2 learning and the reorganization of structural connectivity between core language areas. Language proficiency tests and DTI scans were obtained from German students before and after they completed an intensive 6-week course of the Dutch language. In the initial learning stage, with increasing L2 proficiency, the hemispheric dominance of the BA6-temporal pathway (mainly along the arcuate fasciculus) shifted from the left to the right hemisphere. With further increased proficiency, however, lateralization dominance was again found in the left BA6-temporal pathway. This result is consistent with reports in the literature that imply a stronger involvement of the right hemisphere in L2-processing especially for less proficient L2-speakers. This is the first time that a L2-proficiency-dependent laterality shift in structural connectivity of language pathways during L2 acquisition has been observed to shift from left to right, and back to left hemisphere dominance with increasing L2-proficiency. We additionally find that changes in fractional anisotropy values after the course are related to the time elapsed between the two scans. The results suggest that structural connectivity in (at least part of) the perisylvian language network may be subject to fast dynamic changes following language learning

Abstract

This article reports on results from a broad crosslinguistic study based on data from thirty-five signed languages around the world. The study is the first of its kind, and the typological generalizations presented here cover the domain of interrogative structures as they appear across a wide range of geographically and genetically distinct signed languages. Manual and nonmanual ways of marking basic types of questions in signed languages are investigated. As a result, it becomes clear that the range of crosslinguistic variation is extensive for some subparameters, such as the structure of question-word paradigms, while other parameters, such as the use of nonmanual expressions in questions, show more similarities across signed languages. Finally, it is instructive to compare the findings from signed language typology to relevant data from spoken languages at a more abstract, crossmodality level.

Abstract

This article presents a typology of negative constructions across a substantial number of sign languages from around the globe. After situating the topic within the wider context of linguistic typology, the main negation strategies found across sign languages are described. Nonmanual negation includes the use of head movements and facial expressions for negation and is of great importance in sign languages as well as particularly interesting from a typological point of view. As far as manual signs are concerned, independent negative particles represent the dominant strategy, but there are also instances of irregular negation in most sign languages. Irregular negatives may take the form of suppletion, cliticisation, affixing, or internal modification of a sign. The results of the study lead to interesting generalisations about similarities and differences between negatives in signed and spoken languages.

Abstract

In the word-learning domain, both adults and young children are able to find the correct referent of a word from highly ambiguous contexts that involve many words and objects by computing distributional statistics across the co-occurrences of words and referents at multiple naming moments (Yu & Smith, 2007; Smith & Yu, 2008). However, there is still debate regarding how learners accumulate distributional information to learn object labels in natural learning environments, and what underlying learning mechanism learners are most likely to adopt. Using the Human Simulation Paradigm (Gillette, Gleitman, Gleitman & Lederer, 1999), we found that participants’ learning performance gradually improved and that their ability to remember and carry over partial knowledge from past learning instances facilitated subsequent learning. These results support the statistical learning model that word learning is a continuous process.

Abstract

Osteoblast induction and differentiation in developing long bones is dynamically controlled by the opposing action of transcriptional activators and repressors. In contrast to the long list of activators that have been discovered over past decades, the network of repressors is not well-defined. Here we identify the expression of Foxp1/2/4 proteins, comprised of Forkhead-box (Fox) transcription factors of the Foxp subfamily, in both perichondrial skeletal progenitors and proliferating chondrocytes during endochondral ossification. Mice carrying loss-of-function and gain-of-function Foxp mutations had gross defects in appendicular skeleton formation. At the cellular level, over-expression of Foxp1/2/4 in chondroctyes abrogated osteoblast formation and chondrocyte hypertrophy. Conversely, single or compound deficiency of Foxp1/2/4 in skeletal progenitors or chondrocytes resulted in premature osteoblast differentiation in the perichondrium, coupled with impaired proliferation, survival, and hypertrophy of chondrocytes in the growth plate. Foxp1/2/4 and Runx2 proteins interacted in vitro and in vivo, and Foxp1/2/4 repressed Runx2 transactivation function in heterologous cells. This study establishes Foxp1/2/4 proteins as coordinators of osteogenesis and chondrocyte hypertrophy in developing long bones and suggests that a novel transcriptional repressor network involving Foxp1/2/4 may regulate Runx2 during endochondral ossification.

Abstract

Face-selective regions (FSRs) are among the most widely studied functional regions in the human brain. However, individual variability of the FSRs has not been well quantified. Here we use functional magnetic resonance imaging (fMRI) to localize the FSRs and quantify their spatial and functional variabilities in 202 healthy adults. The occipital face area (OFA), posterior and anterior fusiform face areas (pFFA and aFFA), posterior continuation of the superior temporal sulcus (pcSTS), and posterior and anterior STS (pSTS and aSTS) were delineated for each individual with a semi-automated procedure. A probabilistic atlas was constructed to characterize their interindividual variability, revealing that the FSRs were highly variable in location and extent across subjects. The variability of FSRs was further quantified on both functional (i.e., face selectivity) and spatial (i.e., volume, location of peak activation, and anatomical location) features. Considerable interindividual variability and rightward asymmetry were found in all FSRs on these features. Taken together, our work presents the first effort to characterize comprehensively the variability of FSRs in a large sample of healthy subjects, and invites future work on the origin of the variability and its relation to individual differences in behavioral performance. Moreover, the probabilistic functional atlas will provide an adequate spatial reference for mapping the face network.

Abstract

Neural correlates of lexical stress were studied using the mismatch negativity (MMN) component in event-related potentials. The MMN responses were expected to reveal the encoding of stress information into long-term memory and the contributions of prosodic features such as fundamental frequency (F0) and intensity toward lexical access. In a passive oddball paradigm, neural responses to changes in F0, intensity, and in both features together were recorded for words and pseudowords. The findings showed significant differences not only between words and pseudowords but also between prosodic features. Early processing of prosodic information in words was indexed by an intensity-related MMN and an F0-related P200. These effects were stable at right-anterior and mid-anterior regions. At a later latency, MMN responses were recorded for both words and pseudowords at the mid-anterior and posterior regions. The P200 effect observed for F0 at the early latency for words developed into an MMN response. Intensity elicited smaller MMN for pseudowords than for words. Moreover, a larger brain area was recruited for the processing of words than for the processing of pseudowords. These findings suggest earlier and higher sensitivity to prosodic changes in words than in pseudowords, reflecting a language-related process. The present study, therefore, not only establishes neural correlates of lexical stress but also confirms the presence of long-term memory traces for prosodic information in the brain.