The Callosal Relay Model of Interhemispheric Communication: New Evidence from Effective Connectivity Analysis.

Interhemispheric auditory connectivity via the corpus callosum has been demonstrated to be important for normal speech processing. According to the callosal relay model, directed information flow from the right to the left auditory cortex has been suggested, but this has not yet been proven. For this purpose, 33 healthy participants were investigated with 64-channel EEG while performing the dichotic listening task in which two different consonant-vowel syllables were presented simultaneously to the left (LE) and right ear (RE). eLORETA source estimation was used to investigate the functional (lagged phase synchronization/LPS) and effective (isolated effective coherence/ICoh) connectivity between right and left primary (PAC) and secondary auditory cortices (SAC) in the gamma-band (30-100 Hz) during right and left ear reports. The major finding was a significantly increased effective connectivity in the gamma-band from the right to the left SAC during conscious perception of LE stimuli. In addition, effective and functional connectivity was significantly enhanced during LE as compared to RE reports. These findings give novel insight into transcallosal information transfer during auditory perception by showing that LE performance requires causal interhemispheric inputs from the right to the left auditory cortices, and that this interaction is mediated by synchronized gamma-band oscillations.

Comparison of effects of OSA treatment by MAD and by CPAP on cardiac autonomic function during daytime.

PURPOSE: The present study compared the effects of mandibular advancement therapy (MAD) with continuous positive airway pressure therapy (CPAP) on daytime cardiac autonomic modulation in a wide range of obstructive sleep apnea (OSA) patients under controlled conditions in a randomized, two-period crossover trial. METHODS: Forty OSA patients underwent treatment with MAD and with CPAP for 12 weeks each. At baseline and after each treatment period, patients were assessed by polysomnography as well as by a daytime cardiac autonomic function test that measured heart rate variability (HRV), continuous blood pressure (BP), and baroreceptor sensitivity (BRS) under conditions of spontaneous breathing, with breathing at 6, 12, and 15/min. RESULTS: Both CPAP and MAD therapy substantially eliminated apneas and hypopneas. CPAP had a greater effect. During daytime with all four conditions of controlled breathing, three-minute mean values of continuous diastolic BP were significantly reduced for both MAD and CPAP therapy. At the same time, selective increases due to therapy with MAD were found for HRV high frequency (HF) values. No changes were observed for BRS in either therapy mode. CONCLUSIONS: These findings indicate that both MAD and CPAP result in similar beneficial changes in cardiac autonomic function during daytime, especially in blood pressure. CPAP is more effective than MAD in eliminating respiratory events.

Genome-wide identification of translationally inhibited and degraded miR-155 targets using RNA-interacting protein-IP.

MicroRNAs (miRNAs) are single-stranded, small, non-coding RNAs, which fine-tune protein expression by degrading and/or translationally inhibiting mRNAs. Manipulation of miRNA expression in animal models frequently results in severe phenotypes indicating their relevance in controlling cellular functions, most likely by interacting with multiple targets. To better understand the effect of miRNA activities, genome-wide analysis of their targets are required. MicroRNA profiling as well as transcriptome analysis upon enforced miRNA expression were frequently used to investigate their relevance. However, these approaches often fail to identify relevant miRNAs targets. Therefore, we tested the precision of RNA-interacting protein immunoprecipitation (RIP) using AGO2-specific antibodies, a core component of the "RNA-induced silencing complex" (RISC), followed by RNA sequencing (Seq) in a defined cellular system, the HEK293T cells with stable, ectopic expression of miR-155. Thereby, we identified 100 AGO2-associated mRNAs in miR-155-expressing cells, of which 67 were in silico predicted miR-155 target genes. An integrated analysis of the corresponding expression profiles indicated that these targets were either regulated by mRNA decay or by translational repression. Of the identified miR-155 targets, 17 were related to cell cycle control, suggesting their involvement in the observed increase in cell proliferation of HEK293T cells upon miR-155 expression. Additional, secondary changes within the gene expression profile were detected and might contribute to this phenotype as well. Interestingly, by analyzing RIP-Seq data of HEK-293T cells and two B-cell lines we identified a recurrent disproportional enrichment of several miRNAs, including miR-155 and miRNAs of the miR-17-92 cluster, in the AGO2-associated precipitates, suggesting discrepancies in miRNA expression and activity.

Intrinsic 40Hz-phase asymmetries predict tACS effects during conscious auditory perception.

Synchronized oscillatory gamma-band activity (30-100Hz) has been suggested to constitute a key mechanism to dynamically orchestrate sensory information integration across multiple spatio-temporal scales. We here tested whether interhemispheric functional connectivity and ensuing auditory perception can selectively be modulated by high-density transcranial alternating current stimulation (HD-tACS). For this purpose, we applied multi-site HD-tACS at 40Hz bilaterally with a phase lag of 180° and recorded a 64-channel EEG to study the oscillatory phase dynamics at the source-space level during a dichotic listening (DL) task in twenty-six healthy participants. In this study, we revealed an oscillatory phase signature at 40Hz which reflects different temporal profiles of the phase asymmetries during left and right ear percept. Here we report that 180°-tACS did not affect the right ear advantage during DL at group level. However, a follow-up analysis revealed that the intrinsic phase asymmetries during sham-tACS determined the directionality of the behavioral modulations: While a shift to left ear percept was associated with augmented interhemispheric asymmetry (closer to 180°), a shift to right ear processing was elicited in subjects with lower asymmetry (closer to 0°). Crucially, the modulation of the interhemispheric network dynamics depended on the deviation of the tACS-induced phase-lag from the intrinsic phase asymmetry. Our characterization of the oscillatory network trends is giving rise to the importance of phase-specific gamma-band coupling during ambiguous auditory perception, and emphasizes the necessity to address the inter-individual variability of phase asymmetries in future studies by tailored stimulation protocols.

Quantitative proteomics identify novel miR-155 target proteins.

BACKGROUND: MicroRNAs are 22 nucleotides long non-coding RNAs and exert their function either by transcriptional or translational inhibition. Although many microRNA profiles in different tissues and disease states have already been discovered, only little is known about their target proteins. The microRNA miR-155 is deregulated in many diseases, including cancer, where it might function as an oncoMir. METHODOLOGY/PRINCIPAL FINDINGS: We employed a proteomics technique called "stable isotope labelling by amino acids in cell culture" (SILAC) allowing relative quantification to reliably identify target proteins of miR-155. Using SILAC, we identified 46 putative miR-155 target proteins, some of which were previously reported. With luciferase reporter assays, CKAP5 was confirmed as a new target of miR-155. Functional annotation of miR-155 target proteins pointed to a role in cell cycle regulation. CONCLUSIONS/SIGNIFICANCE: To the best of our knowledge we have investigated for the first time miR-155 target proteins in the HEK293T cell line in large scale. In addition, by comparing our results to previously identified miR-155 target proteins in other cell lines, we provided further evidence for the cell line specificity of microRNAs.