A core difficulty in developmental dyslexia is the accurate specification and neural representation of speech. We argue that a likely perceptual cause of this difficulty is a deficit in the perceptual experience of rhythmic timing. Speech rhythm is one of the earliest cues used by infants to discriminate syllables and is determined principally by the acoustic structure of amplitude modulation at relatively low rates in the signal. We show significant differences between dyslexic and normally reading children, and between young early readers and normal developers, in amplitude envelope onset detection. We further show that individual differences in sensitivity to the shape of amplitude modulation account for 25% of the variance in reading and spelling acquisition even after controlling for individual differences in age, nonverbal IQ, and vocabulary. A possible causal explanation dependent on perceptual-center detection and the onset-rime representation of syllables is discussed.

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It is now well-established that there is a causal connection between children's phonological skills and their acquisition of reading and spelling. Here we study low-level auditory processes that may underpin the development of phonological representations in children. Dyslexic and control children were given a battery of phonological tasks, reading and spelling tasks and auditory processing tasks. Potential relations between deficits in dyslexic performance in the auditory processing tasks and phonological awareness were explored. It was found that individual differences in auditory tasks requiring amplitude envelope rise time processing explained significant variance in phonological processing. It is argued that developmentally, amplitude envelope cues may be primary in establishing well-specified phonological representations, as these cues should yield important rhythmic and syllable-level information about speech.

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TNF-stimulated gene/protein-6 (TSG-6) is expressed by many different cell types in response to pro-inflammatory cytokines and plays an important role in the protection of tissues from the damaging consequences of acute inflammation. Recently, TSG-6 was identified as being largely responsible for the beneficial effects of multipotent mesenchymal stem cells, for example in the treatment of animal models of myocardial infarction and corneal injury/allogenic transplant. The protective effect of TSG-6 is due in part to its inhibition of neutrophil migration, but the mechanism(s) underlying this activity remain(s) unknown. Here we have shown that TSG-6 inhibits chemokine-stimulated trans-endothelial migration of neutrophils via a direct interaction (KD ~25 nM) between TSG-6 and the glycosaminoglycan-binding site of CXCL8, which antagonizes the association of CXCL8 with heparin. Furthermore, we found that TSG-6 impairs the binding of CXCL8 to cell surface glycosaminoglycans and the transport of CXCL8 across an endothelial cell monolayer. In vivo this could limit the formation of haptotactic gradients on endothelial heparan sulfate proteoglycans and, hence, integrin-mediated tight adhesion and migration. We further observed that TSG-6 suppresses CXCL8-mediated chemotaxis of neutrophils; this lower potency effect might be important at sites where there is high local expression of TSG-6. Thus, we have identified TSG-6 as a CXCL8-binding protein, making it the first soluble mammalian chemokine-binding protein to be described to date. We have also revealed a potential mechanism whereby TSG-6 mediates its anti-inflammatory and protective effects. This could inform the development of new treatments for inflammation in the context of disease or post transplantation.

Children with developmental dyslexia appear to be insensitive to basic auditory cues to speech rhythm and stress. For example, they experience difficulties in processing duration and amplitude envelope onset cues. Here we explored the sensitivity of adults with developmental dyslexia to the same cues. In addition, relations with expressive and receptive rhythm tasks, such as tempi recognition and manual tapping to a metronome, were explored. Our goal was to investigate whether the auditory deficits seen in dyslexia are specific to cues to speech rhythm and stress, or are part of a wider rhythmic awareness problem. A group of 19 undergraduate students with dyslexia were compared with 20 age-and ability-matched controls. The findings confirmed a relationship between auditory rhythm sensitivity and literacy in adults, as well as showing an association with metronome inter-tap-interval variability.

Recent research has suggested a novel link between deficits in the perception of cues relevant to speech rhythm (i.e., deficits in amplitude envelope rise time processing, or beat perception) and the phonological deficits seen in most dyslexic children. In this research, we investigated whether these beat perception deficits were specific to a stress-timed language, such as English, or whether they would generalize to languages with different rhythmic properties, such as French. Eighteen dyslexics, 18 reading level controls, and 20 chronological age controls were tested on a battery of phonological tasks, reading tasks and psychoacoustic tests. The results suggest that deficits in the perception of cues important for speech rhythm may be universal in developmental dyslexia.