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Holder, J.

Publications and source records attributed to Holder, J..

3 recordsLinked to original sources

Generalizable EEG encoding models with naturalistic audiovisual stimuli

In natural conversations, listeners must attend to what others are saying while ignoring extraneous background sounds. Recent studies have used encoding models to predict electroencephalography (EEG) responses to speech in noise-free listening situations, sometimes referred to as "speech tracking" in EEG. Researchers have analyzed how speech tracking changes with different types of background noise. It is unclear, however, whether neural responses from noisy and naturalistic environments can be generalized to more controlled stimuli. If encoding models for noisy, naturalistic stimuli are generalizable to other tasks, this could aid in data collection from populations who may not tolerate listening to more controlled, less-engaging stimuli for long periods of time. We recorded non-invasive scalp EEG while participants listened to speech without noise and audiovisual speech stimuli containing overlapping speakers and background sounds. We fit multivariate temporal receptive field (mTRF) encoding models to predict EEG responses to pitch, the acoustic envelope, phonological features, and visual cues in both noise-free and noisy stimulus conditions. Our results suggested that neural responses to naturalistic stimuli were generalizable to more controlled data sets. EEG responses to speech in isolation were predicted accurately using phonological features alone, while responses to noisy speech were more accurate when including both phonological and acoustic features. These findings may inform basic science research on speech-in-noise processing. Ultimately, they may also provide insight into auditory processing in people who are hard of hearing, who use a combination of audio and visual cues to understand speech in the presence of noise. Significance StatementUnderstanding spoken language in natural environments requires listeners to parse acoustic and linguistic information in the presence of other distracting stimuli. However, most studies of auditory processing rely on highly controlled stimuli with no background noise, or with background noise inserted at specific times. Here, we compare models where EEG data are predicted based on a combination of acoustic, phonetic, and visual features in highly disparate stimuli - sentences from a speech corpus, and speech embedded within movie trailers. We show that modeling neural responses to highly noisy, audiovisual movies can uncover tuning for acoustic and phonetic information that generalizes to simpler stimuli typically used in sensory neuroscience experiments.

neuroscience

PP1 promotes cyclin B destruction and the metaphase-anaphase transition by dephosphorylating CDC20

Ubiquitin-dependent proteolysis of cyclin B and securin initiates sister chromatid segregation and anaphase. The anaphase promoting complex/cyclosome (APC/C) and its co-activator CDC20 form the main ubiquitin E3 ligase for these proteins. APC/CCDC20 is regulated by CDK1-cyclin B and counteracting PP1 and PP2A family phosphatases through modulation of both activating and inhibitory phosphorylations. Here we report that PP1 promotes cyclin B destruction at the onset of anaphase by removing specific inhibitory phosphorylation in the N-terminus of CDC20. Depletion or chemical inhibition of PP1 stabilises cyclin B and results in a pronounced delay at the metaphase-to-anaphase transition after chromosome alignment. This requirement for PP1 is lost in cells expressing CDK1-phosphorylation defective CDC206A mutants. These CDC206A cells show a normal spindle checkpoint response, but once all chromosomes have aligned rapidly degrade cyclin B and enter into anaphase in the absence of PP1 activity. PP1 therefore facilitates the metaphase-to-anaphase by promoting APC/CCDC20-dependent destruction of cyclin B in human cells.

cell biology

Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit

APC/C-mediated proteolysis of cyclin B and securin promotes entry into anaphase, inactivating CDK1 and permitting chromosome segregation, respectively. Reduction of CDK1 activity relieves inhibition of the CDK1-opposing phosphatases PP1 and PP2A-B55 leading to dephosphorylation of substrates crucial for mitotic exit. Meanwhile, continued APC/C activity is required to target various proteins, including Aurora and Polo kinases, for degradation. Together, these activities orchestrate a complex series of events during mitotic exit. However, the relative importance of regulated proteolysis and dephosphorylation in dictating the order and timing of these events remains unclear. Using high temporal-resolution mass spectrometry, we compare the relative extent of proteolysis and protein dephosphorylation. This reveals highly-selective rapid ([~]5min half-life) proteolysis of cyclin B, securin and geminin at the metaphase to anaphase transition, followed by slow proteolysis (>60 min half-life) of other mitotic regulators. Protein dephosphorylation requires APC/C-dependent destruction of cyclin B and was resolved into PP1-dependent fast, intermediate and slow categories with unique sequence motifs. We conclude that dephosphorylation initiated by the selective proteolysis of cyclin B drives the bulk of changes observed during mitotic exit.

cell biology