Publications

Abstract

Dent disease, an X-linked familial renal tubular disorder, is a form of Fanconi syndrome associated with proteinuria, hypercalciuria, nephrocalcinosis, kidney stones, and eventual renal failure. We have previously used positional cloning to identify the 3' part of a novel kidney-specific gene (initially termed hClC-K2, but now referred to as CLCN5), which is deleted in patients from one pedigree segregating Dent disease. Mutations that disrupt this gene have been identified in other patients with this disorder. Here we describe the isolation and characterization of the complete open reading frame of the human CLCN5 gene, which is predicted to encode a protein of 746 amino acids, with significant homology to all known members of the ClC family of voltage-gated chloride channels. CLCN5 belongs to a distinct branch of this family, which also includes the recently identified genes CLCN3 and CLCN4. We have shown that the coding region of CLCN5 is organized into 12 exons, spanning 25-30 kb of genomic DNA, and have determined the sequence of each exon-intron boundary. The elucidation of the coding sequence and exon-intron organization of CLCN5 will both expedite the evaluation of structure/function relationships of these ion channels and facilitate the screening of other patients with renal tubular dysfunction for mutations at this locus.

Abstract

Dent's disease, an X-linked renal tubular disorder, is a form of Fanconi syndrome which is characterized by proteinuria, hypercalciuria, nephrocalcinosis, kidney stones and renal failure. Previous studies localised the gene responsible to Xp11.22, within a microdeletion involving the hypervariable locus DXS255. Further analysis using new probes which flank this locus indicate that the deletion is less than 515 kb. A 185 kb YAC containing DXS255 was used to screen a cDNA library from adult kidney in order to isolate coding sequences falling within the deleted region which may be implicated in the disease aetiology. We identified two clones which are evolutionarily conserved, and detect a 9.5 kb transcript which is expressed predominantly in the kidney. Sequence analysis of 780 bp of ORF from the clones suggests that the identified gene, termed hCIC-K2, encodes a new member of the CIC family of voltage-gated chloride channels. Genomic fragments detected by the cDNA clones are completely absent in patients who have an associated microdeletion. On the basis of the expression pattern, proposed function and deletion mapping, hCIC-K2 is a strong candidate for Dent's disease.

Abstract

The human Xp11.23-p11.22 interval has been implicated in several inherited diseases including Wiskott-Aldrich syndrome; three forms of X-linked hypercalciuric nephrolithiaisis; and the eye disorders retinitis pigmentosa 2, congenital stationary night blindness, and Aland Island eye disease. In constructing YAC contigs spanning Xp11. 23-p11.22, we have previously shown that the region around the synaptophysin (SYP) gene is refractory to cloning in YACs, but highly stable in cosmids. Preliminary analysis of the latter suggested that this might reflect a high density of coding sequences and we therefore undertook the complete sequencing of a SYP-containing cosmid. Sequence data were extensively analyzed using computer programs such as CENSOR (to mask repeats), BLAST (for homology searches), and GRAIL and GENE-ID (to predict exons). This revealed the presence of 29 putative exons, organized into three genes, in addition to the 7 exons of the complete SYP coding region, all mapping within a 44-kb interval. Two genes are novel, one (CACNA1F) showing high homology to alpha1 subunits of calcium channels, the other (LMO6) encoding a product with significant similarity to LIM-domain proteins. RT-PCR and Northern blot studies confirmed that these loci are indeed transcribed. The third locus is the previously described, but not previously localized, A4 differentiation-dependent gene. Given that the intron-exon boundaries predicted by the analysis are consistent with previous information where available, we have been able to suggest the genomic organization of the novel genes with some confidence. The region has an elevated GC content (>53%), and we identified CpG islands associated with the 5' ends of SYP, A4, and LMO6. The order of loci was Xpter-A4-LMO6-SYP-CACNA1F-Xcen, with intergenic distances ranging from approximately 300 bp to approximately 5 kb. The density of transcribed sequences in this area (>80%) is comparable to that found in the highly gene-rich chromosomal band Xq28. Further studies may aid our understanding of the long-range organization surrounding such gene-enriched regions.

Abstract

All accounts of communicative behaviour in general, and communicative strategies in particular, mention gesture1 in relation to language acquisition (cf. Faerch & Kasper 1983 for an overview). However, few attempts have been made to investigate how spoken language and spontaneous gesture combine to determine discourse referents. Referential gesture and referential discourse will be of particular interest, since communicative strategies in second language discourse often involve labelling problems.

This paper will focus on two issues:

1) Within a cognitive account of communicative strategies, gesture will be seen to be part of conceptual or analysis-based strategies, in that relational features in the referents are exploited;

2) It will be argued that communication strategies can be seen in terms of cue manipulation in the same sense as sentence processing has been analysed in terms of competing cues. Strategic behaviour, and indeed the process of referring in general, are seen in terms of cues, combining or competing to determine discourse referents. Gesture can then be regarded as being such a cue at the discourse level, and as a cue-based communicative strategy, in that gesture functions by exploiting physically based cues which can be recognised as being part of the referent. The question of iconicity and motivation vs. the arbitrary qualities of gesture as a strategic cue will be addressed in connection with this.

Abstract

This study tests the recent claim that Broca’s aphasics are impaired in automatic lexical access, including the retrieval of word meaning. Subjects are required to perform a lexical decision on visually presented prime target pairs. Half of the word targets are preceded by a related word, half by an unrelated word. Primes and targets are presented with a long stimulus-onset-asynchrony (SOA) of 1400 msec and with a short SOA of 300 msec. Normal priming effects are observed in Broca’s aphasics for both SOAs. This result is discussed in the context of the claim that Broca’s aphasics suffer from an impairment in the automatic access of lexical–semantic information. It is argued that none of the current priming studies provides evidence supporting this claim, since with short SOAs priming effects have been reliably obtained in Broca’s aphasics. The results are more compatible with the claim that in many Broca’s aphasics the functional locus of their comprehension deficit is at the level of postlexical integration processes.

Abstract

We advance the hypothesis here that the higher-than-average vocal pitch (FO) found for speech of Broca's aphasics in experimental settings is due, in part, to increased psychological stress. Two experiments were conducted which manipulated conversational constraints and the sentence forms to be produced by aphasic patients. Our study revealed significant differences between changes in vocal pitch of agrammatic Broca's aphasics versus those of Wernicke's aphasics and normal controls. It is suggested that the greater psychological stress experienced by the Broca's aphasics, but not by the Wernicke's aphasics, accounts for these observed differences.

Abstract

Stimulus-related changes in cerebral blood oxygenation were measured using high-resolution functional magnetic resonance imaging sequentially covering visual occipital areas in contiguous sections. During dynamic imaging, healthy subjects silently viewed pseudowords, single false fonts, or length-matched strings of the same false fonts. The paradigm consisted of a sixfold alternation of an activation and a control task. With pseudowords as activation vs single false fonts as control, responses were seen mainly in medial occipital cortex. These responses disappeared when pseudowords were alternated with false font strings as the control and reappeared when false font strings instead of pseudowords served as activation and were alternated with single false fonts. The string-length contrast alone, therefore, is sufficient to account for the activation pattern observed in medial visual cortex when word-like stimuli are contrasted with single characters.

Abstract

The aim of this paper is to discuss an inherent difficulty of PET (and fMRI) research in language production. On the one hand, language production presupposes some degree of freedom for the subject, on the other hand, interpretability of results presupposes restrictions of this freedom. This difficulty is reflected in the existing PET literature in some neglect of the general principle to design experiments in such a way that the results do not allow for alternative interpretations. It is argued that by narrowing down the scope of experiments a gain in interpretability can be achieved.

Abstract

In 7 experiments the authors investigated the locus of word frequency effects in speech production. Experiment 1 demonstrated a frequency effect in picture naming that was robust over repetitions. Experiments 2, 3, and 7 excluded contributions from object identification and initiation of articulation. Experiments 4 and 5 investigated whether the effect arises in accessing the syntactic word (lemma) by using a grammatical gender decision task. Although a frequency effect was found, it dissipated under repeated access to word's gender. Experiment 6 tested whether the robust frequency effect arises in accessing the phonological form (lexeme) by having Ss translate words that produced homophones. Low-frequent homophones behaved like high-frequent controls, inheriting the accessing speed of their high-frequent homophone twins. Because homophones share the lexeme, not the lemma, this suggests a lexeme-level origin of the robust effect.

Abstract

Day-to-day interpretations of “space” are enmeshed in specific cultural and linguistic practices. For example, many cultures have an association between vertical height and social standing; more powerful people may be placed literally higher than others at social gatherings, and be spoken of as having higher status. This questionnaire is a guide for exploring relationships between space, language, and social structure. The goal is to better understand how space is organised in the focus community, and to investigate the extent to which space is used as a model for reproducing social forms.

Abstract

Essays van psychologen en linguı̈sten over de relatie hersens-computers.

Abstract

Comments on a study by Frazier and others on Dutch-language lexical processing. Claims that the control condition in the experiment was inadequate and that an assumption made by Frazier about closed class verbal items is inaccurate, and proposes an alternative account of a subset of the data from the experiment

Abstract

Raises objections to L. Frazier et al's (see record 1994-32229-001) report of an experimental study intended to test Schreuder's (1990) Morphological Integration (MI) model concerning the processing of separable and inseparable verbs and shows that the logic of the experiment is flawed. The problem is rooted in the notion of a separable complex verb. The conclusion is drawn that Frazier et al's experimental data cannot be taken as evidence for the theoretical propositions they develop about the MI model.

Abstract

[Seven one-page psycholinguistic sketches]

Abstract

This task investigates the expression of “enter” and “exit” events, and is a supplement to the Motion Elicitation task (https://doi.org/10.17617/2.3003391). Consultants are asked to describe a series of animated clips where a man moves into or out of a house. The clips focus on contrasts to do with perspective (e.g., whether the man appears to move away or towards the viewer) and transitional movement (e.g., whether the man walks or “teleports” into his new location).

Abstract

Do our hands 'speak the same language' across cultures? Gesture is the silent partner of spoken languages in face-to-face interaction, but we still have a lot to learn about gesture practices in different speech communities. The primary purpose of this task is to collect data in naturalistic settings that can be used to investigate the linguistic and cultural relativity of gesture performance, especially spatially indicative gestures. It involves video-recording pairs of speakers in both free conversation and more structured communication tasks (e.g., describing film plots).

Please note: the stimuli mentioned in this entry are available elsewhere: 'The Pear Story', a short film made at the University of California at Berkeley; "Frog, where are you?" from the original Mayer (1969) book, as published in the Appendix of Berman & Slobin (1994).

Abstract

Nobel's legacy, or the metamorphosis of what is idealistic Ever since the first Nobel prize in literature was awarded to Prudhomme in 1901, the decisions of the Swedish Academy have been subject to criticism. What is surprising in the changing decision policy as well as in its criticism is the fact that Alfred Nobel's original intentions are hardly ever taken into account: the Nobel prize is a philanthropic prize, it is not meant to select and honour the most eminent literary work but the work with maximal benefit to human beings. What is even more surprising is the fact that no one seems to care that the donator's Last Will is regularly broken.