Influence of Egr-1 in cardiac tissue-derived mesenchymal stem cells in response to glucose variations

Mesenchymal stem cells (MSCs) represent a promising cell population for cell therapy and regenerative medicine applications. However, how variations in glucose are perceived by MSC pool is still unclear. Since, glucose metabolism is cell type and tissue dependent, this must be considered when MSCs are derived from alternative sources such as the heart. The zinc finger transcription factor Egr-1 is an important early response gene, likely to play a key role in the glucose-induced response. Our aim was to investigate how short-term changes in in vitro glucose concentrations affect multipotent cardiac tissue-derived MSCs (cMSCs) in a mouse model of Egr-1 KO (Egr-1-/-). Results showed that loss of Egr-1 does not significantly influence cMSC proliferation. In contrast, responses to glucose variations were observed in wt but not in Egr-1 -/- cMSCs by clonogenic assay. Phenotype analysis by RT-PCR showed that cMSCs Egr-1-/- lost the ability to regulate the glucose transporters GLUT-1 and GLUT-4 and, as expected, the Egr-1 target genes VEGF, TGFβ-1, and p300. Acetylated protein levels of H3 histone were impaired in Egr-1-/- compared to wt cMSCs. We propose that Egr-1 acts as immediate glucose biological sensor in cMSCs after a short period of stimuli, likely inducing epigenetic modifications. © 2014 Daniela Bastianelli et al.

Acoustic source characteristics, across-formant integration, and speech intelligibility under competitive conditions

An important aspect of speech perception is the ability to group or select formants using cues in the acoustic source characteristics-for example, fundamental frequency (F0) differences between formants promote their segregation. This study explored the role of more radical differences in source characteristics. Three-formant (F1+F2+F3) synthetic speech analogues were derived from natural sentences. In Experiment 1, F1+F3 were generated by passing a harmonic glottal source (F0 = 140 Hz) through second-order resonators (H1+H3); in Experiment 2, F1+F3 were tonal (sine-wave) analogues (T1+T3). F2 could take either form (H2 or T2). In some conditions, the target formants were presented alone, either monaurally or dichotically (left ear = F1+F3; right ear = F2). In others, they were accompanied by a competitor for F2 (F1+F2C+F3; F2), which listeners must reject to optimize recognition. Competitors (H2C or T2C) were created using the time-reversed frequency and amplitude contours of F2. Dichotic presentation of F2 and F2C ensured that the impact of the competitor arose primarily through informational masking. In the absence of F2C, the effect of a source mismatch between F1+F3 and F2 was relatively modest. When F2C was present, intelligibility was lowest when F2 was tonal and F2C was harmonic, irrespective of which type matched F1+F3. This finding suggests that source type and context, rather than similarity, govern the phonetic contribution of a formant. It is proposed that wideband harmonic analogues are more effective informational maskers than narrowband tonal analogues, and so become dominant in across-frequency integration of phonetic information when placed in competition.

Across-formant integration and speech intelligibility:effects of acoustic source properties in the presence and absence of a contralateral interferer

The role of source properties in across-formant integration was explored using three-formant (F1+F2+F3) analogues of natural sentences (targets). In experiment 1, F1+F3 were harmonic analogues (H1+H3) generated using a monotonous buzz source and second-order resonators; in experiment 2, F1+F3 were tonal analogues (T1+T3). F2 could take either form (H2 or T2). Target formants were always presented monaurally; the receiving ear was assigned randomly on each trial. In some conditions, only the target was present; in others, a competitor for F2 (F2C) was presented contralaterally. Buzz-excited or tonal competitors were created using the time-reversed frequency and amplitude contours of F2. Listeners must reject F2C to optimize keyword recognition. Whether or not a competitor was present, there was no effect of source mismatch between F1+F3 and F2. The impact of adding F2C was modest when it was tonal but large when it was harmonic, irrespective of whether F2C matched F1+F3. This pattern was maintained when harmonic and tonal counterparts were loudness-matched (experiment 3). Source type and competition, rather than acoustic similarity, governed the phonetic contribution of a formant. Contrary to earlier research using dichotic targets, requiring across-ear integration to optimize intelligibility, H2C was an equally effective informational masker for H2 as for T2.