Connexin 43 phosphorylation by casein kinase 1 is essential for the cardioprotection by ischemic preconditioning

Myocardial connexin 43 (Cx43) forms gap junctions and hemichannels, and is also present within subsarcolemmal mitochondria. The protein is phosphorylated by several kinases including mitogen-activated protein kinase (MAPK), protein kinase C (PKC), and casein kinase 1 (CK1). A reduction in Cx43 content abrogates myocardial infarct size reduction by ischemic preconditioning (IPC). The present study characterizes the contribution of Cx43 phosphorylation towards mitochondrial function, hemichannel activity, and the cardioprotection by IPC in wild-type (WT) mice and in mice in which Cx43-phosphorylation sites targeted by above kinases are mutated to non-phosphorylatable residues (Cx43(MAPKmut), Cx43(PKCmut), and Cx43(CK1mut) mice). The amount of Cx43 in the left ventricle and in mitochondria was reduced in all mutant strains compared to WT mice and Cx43 phosphorylation was altered at residues not directly targeted by the mutations. Whereas complex 1 respiration was reduced in all strains, complex 2 respiration was decreased in Cx43(CK1mut) mice only. In Cx43 epitope-mutated mice, formation of reactive oxygen species and opening of the mitochondrial permeability transition pore were not affected. The hemichannel open probability was reduced in Cx43(PKCmut) and Cx43(CK1mut) but not in Cx43(MAPKmut) cardiomyocytes. Infarct size in isolated saline-perfused hearts after ischemia/reperfusion (45 min/120 min) was comparable between genotypes and was significantly reduced by IPC (3 x 3 min ischemia/5 min reperfusion) in WT, Cx43(MAPKmut), and Cx43(PKCmut), but not in Cx43(CK1mut) mice, an effect independent from the amount of Cx43 and the probability of hemichannel opening. Taken together, our study shows that alterations of Cx43 phosphorylation affect specific cellular functions and highlights the importance of Cx43 phosphorylation by CK1 for IPC's cardioprotection

Cortical tracking of speech in noise accounts for reading strategies in children

Humans’ propensity to acquire literacy relates to several factors, including the ability to understand speech in noise (SiN). Still, the nature of the relation between reading and SiN perception abilities remains poorly understood. Here, we dissect the interplay between (1) reading abilities, (2) classical behavioral predictors of reading (phonological awareness, phonological memory, and rapid automatized naming), and (3) electrophysiological markers of SiN perception in 99 elementary school children (26 with dyslexia). We demonstrate that, in typical readers, cortical representation of the phrasal content of SiN relates to the degree of development of the lexical (but not sublexical) reading strategy. In contrast, classical behavioral predictors of reading abilities and the ability to benefit from visual speech to represent the syllabic content of SiN account for global reading performance (i.e., speed and accuracy of lexical and sublexical reading). In individuals with dyslexia, we found preserved integration of visual speech information to optimize processing of syntactic information but not to sustain acoustic/phonemic processing. Finally, within children with dyslexia, measures of cortical representation of the phrasal content of SiN were negatively related to reading speed and positively related to the compromise between reading precision and reading speed, potentially owing to compensatory attentional mechanisms. These results clarify the nature of the relation between SiN perception and reading abilities in typical child readers and children with dyslexia and identify novel electrophysiological markers of emergent literacy

Audiovisual Segregation in Cochlear Implant Users

It has traditionally been assumed that cochlear implant users de facto perform atypically in audiovisual tasks. However, a recent study that combined an auditory task with visual distractors suggests that only those cochlear implant users that are not proficient at recognizing speech sounds might show abnormal audiovisual interactions. The present study aims at reinforcing this notion by investigating the audiovisual segregation abilities of cochlear implant users in a visual task with auditory distractors. Speechreading was assessed in two groups of cochlear implant users (proficient and non-proficient at sound recognition), as well as in normal controls. A visual speech recognition task (i.e. speechreading) was administered either in silence or in combination with three types of auditory distractors: i) noise ii) reverse speech sound and iii) non-altered speech sound. Cochlear implant users proficient at speech recognition performed like normal controls in all conditions, whereas non-proficient users showed significantly different audiovisual segregation patterns in both speech conditions. These results confirm that normal-like audiovisual segregation is possible in highly skilled cochlear implant users and, consequently, that proficient and non-proficient CI users cannot be lumped into a single group. This important feature must be taken into account in further studies of audiovisual interactions in cochlear implant users

The effect of phonetically augmented lipspeech on the development of phonological representations in deaf children

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Avant-Propos

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Hearing the hands: The case of deaf children educated with Cued-Speech

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Représentations phonologiques, Implants cochléaires et L.P.C.

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