Publications

Abstract

Over recent years small submicroscopic DNA copy-number variants (CNVs) have been highlighted as an important source of variation in the human genome, human phenotypic diversity and disease susceptibility. Consequently, there is a pressing need for the development of methods that allow the efficient, accurate and cheap measurement of genomic copy number polymorphisms in clinical cohorts. We have developed a simple competitive PCR based method to determine DNA copy number which uses the entire genome of a single chimpanzee as a competitor thus eliminating the requirement for competitive sequences to be synthesized for each assay. This results in the requirement for only a single reference sample for all assays and dramatically increases the potential for large numbers of loci to be analysed in multiplex. In this study we establish proof of concept by accurately detecting previously characterized mutations at the PARK2 locus and then demonstrating the potential of quantitative interspecies competitive PCR (qicPCR) to accurately genotype CNVs in association studies by analysing chromosome 22q11 deletions in a sample of previously characterized patients and normal controls.

Abstract

It is often assumed odors are associated with hot and cold temperature, since odor processing may trigger thermal sensations, such as coolness in the case of mint. It is unknown, however, whether people make consistent temperature associations for a variety of everyday odors, and, if so, what determines them. Previous work investigating the bases of cross-modal associations suggests a number of possibilities, including universal forces (e.g., perception), as well as culture-specific forces (e.g., language and cultural beliefs). In this study, we examined odor-temperature associations in three cultures—Maniq (N = 11), Thai (N = 24), and Dutch (N = 24)—who differ with respect to their cultural preoccupation with odors, their odor lexicons, and their beliefs about the relationship of odors (and odor objects) to temperature. Participants matched 15 odors to temperature by touching cups filled with hot or cold water, and described the odors in their native language. The results showed no consistent associations among the Maniq, and only a handful of consistent associations between odor and temperature among the Thai and Dutch. The consistent associations differed across the two groups, arguing against their universality. Further analysis revealed cross-modal associations could not be explained by language, but could be the result of cultural beliefs

Abstract

The cerebellar ataxias are a group of incurable brain disorders that are caused primarily by the progressive dysfunction and degeneration of cerebellar Purkinje cells. The lack of reliable disease models for the heterogeneous ataxias has hindered the understanding of the underlying pathogenic mechanisms as well as the development of effective therapies for these devastating diseases. Recent advances in the field of induced pluripotent stem cell (iPSC) technology offer new possibilities to better understand and potentially reverse disease pathology. Given the neurodevelopmental phenotypes observed in several types of ataxias, iPSC-based models have the potential to provide significant insights into disease progression, as well as opportunities for the development of early intervention therapies. To date, however, very few studies have successfully used iPSC-derived cells to cerebellar ataxias. In this review, we focus on recent breakthroughs in generating human iPSC-derived Purkinje cells. We also highlight the future challenges that will need to be addressed in order to fully exploit these models for the modelling of the molecular mechanisms underlying cerebellar ataxias and the development of effective therapeutics.

Abstract

Jedek is a previously unrecognized variety of the Northern Aslian subgroup of the Aslian branch of the Austroasiatic language family. It is spoken by c. 280 individuals in the resettlement area of Sungai Rual, near Jeli in Kelantan state, Peninsular Malaysia. The community originally consisted of several bands of foragers along the middle reaches of the Pergau river. Jedek’s distinct status first became known during a linguistic survey carried out in the DOBES project Tongues of the Semang (2005-2011). This paper describes the process leading up to its discovery and provides an overview of its typological characteristics.

Abstract

In the present study, event-related brain potentials (ERP) were recorded to investigate the role of pitch accent and lexical tone in spoken discourse comprehension. Chinese was used as material to explore the potential difference in the nature and time course of brain responses to sentence meaning as indicated by pitch accent and to lexical meaning as indicated by tone. In both cases, the pitch contour of critical words was varied. The results showed that both inconsistent pitch accent and inconsistent lexical tone yielded N400 effects, and there was no interaction between them. The negativity evoked by inconsistent pitch accent had the some topography as that evoked by inconsistent lexical tone violation, with a maximum over central–parietal electrodes. Furthermore, the effect for the combined violations was the sum of effects for pure pitch accent and pure lexical tone violation. However, the effect for the lexical tone violation appeared approximately 90 ms earlier than the effect of the pitch accent violation. It is suggested that there might be a correspondence between the neural mechanism underlying pitch accent and lexical meaning processing in context. They both reflect the integration of the current information into a discourse context, independent of whether the current information was sentence meaning indicated by accentuation, or lexical meaning indicated by tone. In addition, lexical meaning was processed earlier than sentence meaning conveyed by pitch accent during spoken language processing.

Abstract

Using the masked priming paradigm, we examined which phonological unit is used when naming Kanji compounds. Although the phonological unit in the Japanese language has been suggested to be the mora, Experiment 1 found no priming for mora-related Kanji prime-target pairs. In Experiment 2, significant priming was only found when Kanji pairs shared the whole sound of their initial Kanji characters. Nevertheless, when the same Kanji pairs used in Experiment 2 were transcribed into Kana, significant mora priming was observed in Experiment 3. In Experiment 4, matching the syllable structure and pitch-accent of the initial Kanji characters did not lead to mora priming, ruling out potential alternative explanations for the earlier absence of the effect. A significant mora priming effect was observed, however, when the shared initial mora constituted the whole sound of their initial Kanji characters in Experiments 5. Lastly, these results were replicated in Experiment 6. Overall, these results indicate that the phonological unit involved when naming Kanji compounds is not the mora but the whole sound of each Kanji character. We discuss how different phonological units may be involved when processing Kanji and Kana words as well as the implications for theories dealing with language production processes.

Abstract

Scene-selective regions (SSRs), including the parahippocampal place area (PPA), retrosplenial cortex (RSC), and transverse occipital sulcus (TOS), are among the most widely characterized functional regions in the human brain. However, previous studies have mostly focused on the commonality within each SSR, providing little information on different aspects of their variability. In a large group of healthy adults (N = 202), we used functional magnetic resonance imaging to investigate different aspects of topographical and functional variability within SSRs, including interindividual, interhemispheric, and sex differences. First, the PPA, RSC, and TOS were delineated manually for each individual. We then demonstrated that SSRs showed substantial interindividual variability in both spatial topography and functional selectivity. We further identified consistent interhemispheric differences in the spatial topography of all three SSRs, but distinct interhemispheric differences in scene selectivity. Moreover, we found that all three SSRs showed stronger scene selectivity in men than in women. In summary, our work thoroughly characterized the interindividual, interhemispheric, and sex variability of the SSRs and invites future work on the origin and functional significance of these variabilities. Additionally, we constructed the first probabilistic atlases for the SSRs, which provide the detailed anatomical reference for further investigations of the scene network.