Transcriptional regulation of mammalian autophagy at a glance.

Macroautophagy, hereafter referred to as autophagy, is a catabolic process that results in the lysosomal degradation of cytoplasmic contents ranging from abnormal proteins to damaged cell organelles. It is activated  under diverse conditions, including nutrient deprivation and hypoxia. During autophagy, members of the core autophagy-related (ATG) family of proteins mediate membrane rearrangements, which lead to the engulfment and degradation of cytoplasmic cargo. Recently, the nuclear regulation of autophagy, especially by transcription factors and histone modifiers, has gained increased attention. These factors are not only involved in rapid responses to autophagic stimuli, but also regulate the long-term outcome of autophagy. Now there are more than 20 transcription factors that have been shown to be linked to the autophagic process. However, their interplay and timing appear enigmatic as several have been individually shown to act as major regulators of autophagy. This Cell Science at a Glance article and the accompanying poster highlights the main cellular regulators of transcription involved in mammalian autophagy and their target genes

Evaluation of a method for determining binaural sensitivity to temporal fine structure (TFS-AF test) for older listeners with normal and impaired low-frequency hearing

The ability to process binaural temporal fine structure (TFS) information was assessed using the TFS-AF test (where AF stands for adaptive frequency) for 26 listeners aged 60 years or more with normal or elevated low-frequency audiometric thresholds. The test estimates the highest frequency at which a fixed interaural phase difference (IPD) of ϕ (varied here between 30° and 180°) can be discriminated from an IPD of 0°, with higher thresholds indicating better performance. A sensation level of 30 dB was used. All listeners were able to perform the task reliably, giving thresholds well above the lowest allowed frequency of 30 Hz. The duration of a run averaged 5 min. Repeated testing of the normal-hearing listeners showed no significant practice effects. Thresholds varied markedly across listeners, but their ranking was fairly consistent across values of ϕ. Thresholds decreased (worsened) with decreasing ϕ and were lower than for a group of young listeners tested in an earlier study. There were weak to moderate, negative correlations between TFS-AF thresholds and audiometric thresholds at low frequencies (125–1000 Hz) but not at high frequencies (4000–8000 Hz). In conclusion, the TFS-AF test yielded a graded measure of binaural TFS sensitivity for all listeners. This contrasts with the TFS-LF (low-frequency) test, which measures the smallest detectable shift in IPD for a fixed frequency. The absence of practice effects and a reasonably short administration time make the TFS-AF test a good candidate for the assessment of sensitivity to changes in binaural TFS for older listeners without or with hearing loss

Envelope regularity discrimination

The ability to discriminate irregular from regular amplitude modulation was assessed using the "envelope regularity discrimination" test. The amount of irregularity was parametrically varied and quantified by an "irregularity index." Normative data were gathered for young subjects with normal audiometric thresholds. Parameters varied were the carrier and modulation frequencies, f c and f m , and the baseline modulation index, m. All tests were performed using a background threshold-equalizing noise. The main findings were (1) using f c = 4000 Hz, f m = 8 Hz, and m = 0.3, performance improved over the first two threshold runs and then remained roughly stable, and there was a high correlation between thresholds obtained at 80 dB sound pressure level (SPL) and at 20 dB sensation level; (2) using f m = 8 Hz and m = 0.3 with a level of 80 dB SPL, thresholds did not vary significantly across f c = 1000, 2000, and 4000 Hz; (3) using f m = 8 Hz and f c = 4000 Hz with a level of 80 dB SPL, thresholds did not vary significantly for m from 0.2 to 0.5; and (4) using m = 0.3 and f c = 4000 Hz with a level of 80 dB SPL, thresholds improved with increasing f m from 2 to 16 Hz. For all conditions, there was substantial individual variability, probably resulting from differences in "processing efficiency."This work was supported by the Engineering and Physical Sciences Research Council (UK, Grant No. RG78536)

Does training with amplitude modulated tones affect tone-vocoded speech perception?

Temporal-envelope cues are essential for successful speech perception. We asked here whether training on stimuli containing temporal-envelope cues without speech content can improve the perception of spectrally-degraded (vocoded) speech in which the temporal-envelope (but not the temporal fine structure) is mainly preserved. Two groups of listeners were trained on different amplitude-modulation (AM) based tasks, either AM detection or AM-rate discrimination (21 blocks of 60 trials during two days, 1260 trials; frequency range: 4Hz, 8Hz, and 16Hz), while an additional control group did not undertake any training. Consonant identification in vocoded vowel-consonant-vowel stimuli was tested before and after training on the AM tasks (or at an equivalent time interval for the control group). Following training, only the trained groups showed a significant improvement in the perception of vocoded speech, but the improvement did not significantly differ from that observed for controls. Thus, we do not find convincing evidence that this amount of training with temporal-envelope cues without speech content provide significant benefit for vocoded speech intelligibility. Alternative training regimens using vocoded speech along the linguistic hierarchy should be explored

Teologija na tržištu

One task intended to measure sensitivity to temporal fine structure (TFS) involves the discrimination of a harmonic complex tone from a tone in which all harmonics are shifted upwards by the same amount in hertz. Both tones are passed through a fixed bandpass filter centered on the high harmonics to reduce the availability of excitation-pattern cues and a background noise is used to mask combination tones. The role of frequency selectivity in this "TFS1" task was investigated by varying level. Experiment 1 showed that listeners performed more poorly at a high level than at a low level. Experiment 2 included intermediate levels and showed that performance deteriorated for levels above about 57 dB sound pressure level. Experiment 3 estimated the magnitude of excitation-pattern cues from the variation in forward masking of a pure tone as a function of frequency shift in the complex tones. There was negligible variation, except for the lowest level used. The results indicate that the changes in excitation level at threshold for the TFS1 task would be too small to be usable. The results are consistent with the TFS1 task being performed using TFS cues, and with frequency selectivity having an indirect effect on performance via its influence on TFS cues. (C) 2015 Acoustical Society of America

Common and distinct transcriptional signatures of mammalian embryonic lethality

Abstract: The Deciphering the Mechanisms of Developmental Disorders programme has analysed the morphological and molecular phenotypes of embryonic and perinatal lethal mouse mutant lines in order to investigate the causes of embryonic lethality. Here we show that individual whole-embryo RNA-seq of 73 mouse mutant lines (>1000 transcriptomes) identifies transcriptional events underlying embryonic lethality and associates previously uncharacterised genes with specific pathways and tissues. For example, our data suggest that Hmgxb3 is involved in DNA-damage repair and cell-cycle regulation. Further, we separate embryonic delay signatures from mutant line-specific transcriptional changes by developing a baseline mRNA expression catalogue of wild-type mice during early embryogenesis (4–36 somites). Analysis of transcription outside coding sequence identifies deregulation of repetitive elements in Morc2a mutants and a gene involved in gene-specific splicing. Collectively, this work provides a large scale resource to further our understanding of early embryonic developmental disorders