Articulatory Rate and Stuttering

The effect of speech rate on stuttering frequency was investigated with 20 stutterers. Subjects read two different 300 syllable passages at a normal and fast speech rate. Stuttering counts and articulatory rate was determined for each speech sample. Articulatory rates were derived from portions of the passages which were perceptually fluent. No statistically significant difference in stuttering frequency was found between the two speech rate conditions (p = .16) while a significant difference was observed for articulatory rate (p = .0007). These findings suggest that increased articulatory rate does not determine stuttering frequency with the same consistency as does decreased articulatory rate. It was concluded that a single explanation of the relationship between speech rate and stuttering frequency in terms of speech timing complexity is inadequate

The kinases MSK1 and MSK2 act as negative regulators of Toll-like receptor signaling

The kinases MSK1 and MSK2 are activated 'downstream' of the p38 and Erk1/2 mitogen-activated protein kinases. Here we found that MSK1 and MSK2 were needed to limit the production of proinflammatory cytokines in response to stimulation of primary macrophages with lipopolysaccharide. By inducing transcription of the mitogen-activated protein kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10, MSK1 and MSK2 exerted many negative feedback mechanisms. Deficiency in MSK1 and MSK2 prevented the binding of phosphorylated transcription factors CREB and ATF1 to the promoters of the genes encoding interleukin 10 and DUSP1. Mice doubly deficient in MSK1 and MSK2 were hypersensitive to lipopolysaccharide-induced endotoxic shock and showed prolonged inflammation in a model of toxic contact eczema induced by phorbol 12-myristate 13-acetate. Our results establish MSK1 and MSK2 as key components of negative feedback mechanisms needed to limit Toll-like receptor-driven inflammation.</p

miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity

miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles in both immune and neuronal function. We describe here the generation and initial characterisation of a miR-132/212 double knockout mouse. These mice were viable and fertile with no overt adverse phenotype. Analysis of innate immune responses, including TLR-induced cytokine production and IFNβ induction in response to viral infection of primary fibroblasts did not reveal any phenotype in the knockouts. In contrast, the loss of miR-132 and miR-212, while not overtly affecting neuronal morphology, did affect synaptic function. In both hippocampal and neocortical slices miR-132/212 knockout reduced basal synaptic transmission, without affecting paired-pulse facilitation. Hippocampal long-term potentiation (LTP) induced by tetanic stimulation was not affected by miR-132/212 deletion, whilst theta burst LTP was enhanced. In contrast, neocortical theta burst-induced LTP was inhibited by loss of miR-132/212. Together these results indicate that miR-132 and/or miR-212 play a significant role in synaptic function, possibly by regulating the number of postsynaptic AMPA receptors under basal conditions and during activity-dependent synaptic plasticity

Altered Auditory Feedback

The purpose of the study was to determine if combining delayed auditory feedback (DAF) and frequency altered feedback (FAF) would be more fluency enhancing than either DAF or FAF alone. Ten stutterers read at normal and fast speech rates under nonaltered auditory feedback (NAF), DAF (i.e., a 50 ms delay), FAF (i.e., a one half octave downward shift), and a combination of DAF and FAF [(COMBO), i.e., a 50 ms delay plus a one half octave downward shift]. Results indicated that stuttering frequency was significantly reduced under all altered auditory conditions at both speech rates relative to the NAF condition. There was, however, no significant differences between the altered auditory feedback conditions (i.e., DAF, FAF, and COMBO). It is suggested that further studies be undertaken to explore the combination of altered auditory feedback conditions, as it may be the case that a floor effect was demonstrated with the singular presentations of DAF and FAF and further improvements in fluency enhancement could not be exhibited in the combined condition. Finally, these findings support the notion that a slowed rate of speech is not necessary for fluency enhancement under conditions of altered auditory feedback

Common polymorphic variation in the genetically diverse African insulin gene and its association with size at birth.

The insulin variable number of tandem repeats (INS VNTR) has been variably associated with size at birth in non-African populations. Small size at birth is a major determinant of neonatal mortality, so the INS VNTR may influence survival. We tested the hypothesis, therefore, that genetic variation around the INS VNTR in a rural Gambian population, who experience seasonal variation in nutrition and subsequently birth weight, may be associated with foetal and early growth. Six polymorphisms flanking the INS VNTR were genotyped in over 2,500 people. Significant associations were detected between the maternally inherited SNP 27 (rs689) allele and birth length [effect size 17.5 (5.2-29.8) mm; P = 0.004; n = 361]. Significant associations were also found between the maternally inherited African-specific SNP 28 (rs5506) allele and post-natal weight gain [effect size 0.19 (0.05-0.32) z score points/year; P = 0.005; n = 728). These results suggest that in the Gambian population studied there are associations between polymorphic variation in the genetically diverse INS gene and foetal and early growth characteristics, which contribute to overall polygenic associations with these traits