“<i>Hama</i>”? Reduced pronunciations in non-native natural speech obstruct high-school students’ comprehension at lower processing levels

Native speakers ‘reduce’ their pronunciations, i.e., they shorten and merge words. For instance, German native speakers may say “hama” for “haben wir” (‘have-we’). We examined to what extent such reductions are problematic for adolescent learners of a second language, after four years of high-school training; and whether the problems can be related to inadequate bottom-up and top-down processing. For this, 39 Dutch and 38 German adolescents heard either reduced or unreduced German full phrases and part-phrases (phrase-intelligibility task) and words (lexical decision task). The results show that (1) Learners perceive non-native reduced speech less accurately than unreduced speech and also judge it as less intelligible; (2) This reduced-form disadvantage occurs separately from factors such as speech rate, orthography and voice; (3) The disadvantage for non-native listeners is substantial and larger than that in native listeners. Therefore, it probably reflects a lack of experience with reduced (i.e., real-life) speech; and (4) Non-native reductions induce at least inadequate bottom-up processing in learners, and may make top-down processing less accessible. We interpret the findings as supporting the idea that experience with variants (here: reduced variants) is necessary to strengthen linguistic (word) representations

Improved Horizontal Directional Hearing in Bone Conduction Device Users with Acquired Unilateral Conductive Hearing Loss

We examined horizontal directional hearing in patients with acquired severe unilateral conductive hearing loss (UCHL). All patients (n = 12) had been fitted with a bone conduction device (BCD) to restore bilateral hearing. The patients were tested in the unaided (monaural) and aided (binaural) hearing condition. Five listeners without hearing loss were tested as a control group while listening with a monaural plug and earmuff, or with both ears (binaural). We randomly varied stimulus presentation levels to assess whether listeners relied on the acoustic head-shadow effect (HSE) for horizontal (azimuth) localization. Moreover, to prevent sound localization on the basis of monaural spectral shape cues from head and pinna, subjects were exposed to narrow band (1/3 octave) noises. We demonstrate that the BCD significantly improved sound localization in 8/12 of the UCHL patients. Interestingly, under monaural hearing (BCD off), we observed fairly good unaided azimuth localization performance in 4/12 of the patients. Our multiple regression analysis shows that all patients relied on the ambiguous HSE for localization. In contrast, acutely plugged control listeners did not employ the HSE. Our data confirm and further extend results of recent studies on the use of sound localization cues in chronic and acute monaural listening

The mitochondrial transcription termination factor mTERF modulates replication pausing in human mitochondrial DNA.

The mammalian mitochondrial transcription termination factor mTERF binds with high affinity to a site within the tRNA(Leu(UUR)) gene and regulates the amount of read through transcription from the ribosomal DNA into the remaining genes of the major coding strand of mitochondrial DNA (mtDNA). Electrophoretic mobility shift assays (EMSA) and SELEX, using mitochondrial protein extracts from cells induced to overexpress mTERF, revealed novel, weaker mTERF-binding sites, clustered in several regions of mtDNA, notably in the major non-coding region (NCR). Such binding in vivo was supported by mtDNA immunoprecipitation. Two-dimensional neutral agarose gel electrophoresis (2DNAGE) and 5' end mapping by ligation-mediated PCR (LM-PCR) identified the region of the canonical mTERF-binding site as a replication pause site. The strength of pausing was modulated by the expression level of mTERF. mTERF overexpression also affected replication pausing in other regions of the genome in which mTERF binding was found. These results indicate a role for TERF in mtDNA replication, in addition to its role in transcription. We suggest that mTERF could provide a system for coordinating the passage of replication and transcription complexes, analogous with replication pause-region binding proteins in other systems, whose main role is to safeguard the integrity of the genome whilst facilitating its efficient expression

Effect of Audiovisual Training on Monaural Spatial Hearing in Horizontal Plane

The article aims to test the hypothesis that audiovisual integration can improve spatial hearing in monaural conditions when interaural difference cues are not available. We trained one group of subjects with an audiovisual task, where a flash was presented in parallel with the sound and another group in an auditory task, where only sound from different spatial locations was presented. To check whether the observed audiovisual effect was similar to feedback, the third group was trained using the visual feedback paradigm. Training sessions were administered once per day, for 5 days. The performance level in each group was compared for auditory only stimulation on the first and the last day of practice. Improvement after audiovisual training was several times higher than after auditory practice. The group trained with visual feedback demonstrated a different effect of training with the improvement smaller than the group with audiovisual training. We conclude that cross-modal facilitation is highly important to improve spatial hearing in monaural conditions and may be applied to the rehabilitation of patients with unilateral deafness and after unilateral cochlear implantation

A Common Polymorphism in the Promoter Region of the TNFSF4 Gene Is Associated with Lower Allele-Specific Expression and Risk of Myocardial Infarction

BACKGROUND: The TNFSF4/TNFRSF4 system, along with several other receptor-ligand pairs, is involved in the recruitment and activation of T-cells and is therefore tentatively implicated in atherosclerosis and acute coronary syndromes. We have previously shown that genetic variants in TNFSF4 are associated with myocardial infarction (MI) in women. This prompted functional studies of TNFSF4 expression. METHODS AND RESULTS: Based on a screening of the TNFSF4 genomic region, a promoter polymorphism (rs45454293) and a haplotype were identified, conceivably involved in gene regulation. The rs45454293T-allele, in agreement with the linked rs3850641G-allele, proved to be associated with increased risk of MI in women. Haplotype-specific chromatin immunoprecipitation of activated polymerase II, as a measure of transcriptional activity in vivo, suggested that the haplotype including the rs45454293 and rs3850641 polymorphisms is functionally important, the rs45454293T- and rs3850641G-alleles being associated with lower transcriptional activity in cells heterozygous for both polymorphisms. The functional role of rs45454293 on transcriptional levels of TNFSF4 was clarified by luciferase reporter assays, where the rs45454293T-allele decreased gene expression when compared with the rs45454293C-allele, while the rs3850641 SNP did not have any effect on TNFSF4 promoter activity. Electromobility shift assay showed that the rs45454293 polymorphism, but not rs3850641, affects the binding of nuclear factors, thus suggesting that the lower transcriptional activity is attributed to binding of one or more transcriptional repressor(s) to the T-allele. CONCLUSIONS: Our data indicate that the TNFSF4 rs45454293T-allele is associated with lower TNFSF4 expression and increased risk of MI

ATpase-deficient mitochondrial inner membrane protein ATAD3a disturbs mitochondrial dynamics in dominant hereditary spastic paraplegia

© The Author 2017. Published by Oxford University Press. All rights reserved.De novo mutations in ATAD3A (ATPase family AAA-domain containing protein 3A) were recently found to cause a neurological syndrome with developmental delay, hypotonia, spasticity, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy. Using whole-exome sequencing, we identified a dominantly inherited heterozygous variant c.1064G>A (p. G355D) in ATAD3A in a mother presenting with hereditary spastic paraplegia (HSP) and axonal neuropathy and her son with dyskinetic cerebral palsy, both with disease onset in childhood. HSP is a clinically and genetically heterogeneous disorder of the upper motor neurons. Symptoms beginning in early childhood may resemble spastic cerebral palsy. The function of ATAD3A, a mitochondrial inner membrane AAA ATPase, is yet undefined. AAA ATPases form hexameric rings, which are catalytically dependent on the co-operation of the subunits. The dominant-negative patient mutation affects the Walker A motif, which is responsible for ATP binding in the AAA module of ATAD3A, and we show that the recombinant mutant ATAD3A protein has a markedly reduced ATPase activity. We further show that overexpression of the mutant ATAD3A fragments the mitochondrial network and induces lysosome mass. Similarly, we observed altered dynamics of the mitochondrial network and increased lysosomes in patient fibroblasts and neurons derived through differentiation of patient-specific induced pluripotent stem cells. These alterations were verified in patient fibroblasts to associate with upregulated basal autophagy through mTOR inactivation, resembling starvation. Mutations in ATAD3A can thus be dominantly inherited and underlie variable neurological phenotypes, including HSP, with intrafamiliar variability. This finding extends the group of mitochondrial inner membrane AAA proteins associated with spasticity

Acoustic Cues for Sound Source Distance and Azimuth in Rabbits, a Racquetball and a Rigid Spherical Model

There are numerous studies measuring the transfer functions representing signal transformation between a source and each ear canal, i.e., the head-related transfer functions (HRTFs), for various species. However, only a handful of these address the effects of sound source distance on HRTFs. This is the first study of HRTFs in the rabbit where the emphasis is on the effects of sound source distance and azimuth on HRTFs. With the rabbit placed in an anechoic chamber, we made acoustic measurements with miniature microphones placed deep in each ear canal to a sound source at different positions (10–160 cm distance, ±150° azimuth). The sound was a logarithmically swept broadband chirp. For comparisons, we also obtained the HRTFs from a racquetball and a computational model for a rigid sphere. We found that (1) the spectral shape of the HRTF in each ear changed with sound source location; (2) interaural level difference (ILD) increased with decreasing distance and with increasing frequency. Furthermore, ILDs can be substantial even at low frequencies when distance is close; and (3) interaural time difference (ITD) decreased with decreasing distance and generally increased with decreasing frequency. The observations in the rabbit were reproduced, in general, by those in the racquetball, albeit greater in magnitude in the rabbit. In the sphere model, the results were partly similar and partly different than those in the racquetball and the rabbit. These findings refute the common notions that ILD is negligible at low frequencies and that ITD is constant across frequency. These misconceptions became evident when distance-dependent changes were examined

The effect of long-term unilateral deafness on the activation pattern in the auditory cortices of French-native speakers: influence of deafness side

<p>Abstract</p> <p>Background</p> <p>In normal-hearing subjects, monaural stimulation produces a normal pattern of asynchrony and asymmetry over the auditory cortices in favour of the contralateral temporal lobe. While late onset unilateral deafness has been reported to change this pattern, the exact influence of the side of deafness on central auditory plasticity still remains unclear. The present study aimed at assessing whether left-sided and right-sided deafness had differential effects on the characteristics of neurophysiological responses over auditory areas. Eighteen unilaterally deaf and 16 normal hearing right-handed subjects participated. All unilaterally deaf subjects had post-lingual deafness. Long latency auditory evoked potentials (late-AEPs) were elicited by two types of stimuli, non-speech (1 kHz tone-burst) and speech-sounds (voiceless syllable/pa/) delivered to the intact ear at 50 dB SL. The latencies and amplitudes of the early exogenous components (N100 and P150) were measured using temporal scalp electrodes.</p> <p>Results</p> <p>Subjects with left-sided deafness showed major neurophysiological changes, in the form of a more symmetrical activation pattern over auditory areas in response to non-speech sound and even a significant reversal of the activation pattern in favour of the cortex ipsilateral to the stimulation in response to speech sound. This was observed not only for AEP amplitudes but also for AEP time course. In contrast, no significant changes were reported for late-AEP responses in subjects with right-sided deafness.</p> <p>Conclusion</p> <p>The results show that cortical reorganization induced by unilateral deafness mainly occurs in subjects with left-sided deafness. This suggests that anatomical and functional plastic changes are more likely to occur in the right than in the left auditory cortex. The possible perceptual correlates of such neurophysiological changes are discussed.</p