Biology subjects

Murphy, J. W.

Publications and source records attributed to Murphy, J. W..

3 recordsLinked to original sources

bioRxiv2026

Dual recognition of negative charge by pleckstrin homology (PH) domains

Pleckstrin homology (PH) domains are typically assumed to be phosphoinositide-binding modules, although most lack strong lipid specificity and their broader ligand repertoire remains poorly defined. We find that many yeast PH domains bind Nsr1p, the ortholog of nucleolin, also identified as a PH domain ligand, suggesting widespread recognition of negatively charged protein regions. The phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)-binding PLC{delta}1 PH domain also binds a highly phosphorylated region of IRBIT through the same site that recognizes PtdIns(4,5)P2. Using high-throughput integrated phosphopeptide (Hi-P) screening, we surveyed 38,624 mammalian sequences containing three documented phosphoserines. PLC{delta}1-PH bound numerous phosphorylated and unphosphorylated acidic peptides, and phosphorylation generally strengthened pre-existing interactions rather than conferring strict specificity, without requiring a fixed phosphoserine spacing. Instead, favored phosphopeptides combined a key phosphoserine with upstream acidic residues. Structural modeling suggests that this phosphoserine occupies the canonical inositol phosphate binding pocket, while adjacent acidic residues make delocalized electrostatic contacts. Thus, PH domains can recognize various patterns of protein negative charge, expanding their potential regulatory roles beyond membrane targeting.

biochemistry↗

bioRxiv2024

It's all in the timing: Delayed feedback in autism may weaken predictive mechanisms during contour integration

Humans rely on predictive mechanisms during visual processing to efficiently resolve incomplete or ambiguous sensory signals. While initial low-level sensory data are conveyed by feedforward connections, feedback connections are believed to shape sensory processing through conveyance of statistical predictions based on prior exposure to stimulus configurations. Individuals with autism spectrum disorder (ASD) show biases in stimulus processing toward parts rather than wholes, suggesting their sensory processing may be less shaped by statistical predictions acquired through prior exposure to global stimulus properties. Investigations of illusory contour (IC) processing in neurotypical (NT) adults have established a well-tested marker of contour integration characterized by a robust modulation of the visually evoked potential (VEP) - the IC-effect - that occurs over lateral occipital scalp during the timeframe of the N1 component. Converging evidence strongly supports the notion that this IC-effect indexes a signal with significant feedback contributions. Using high-density VEPs, we compared the IC-effect in 6-17-year-old children with ASD (n=32) or NT development (n=53). Both groups of children generated an IC-effect that was equivalent in amplitude. However, the IC-effect notably onset 21ms later in ASD, even though timing of initial VEP afference was identical across groups. This suggests that feedforward information predominated during perceptual processing for 15% longer in ASD compared to NT children. This delay in the feedback dependent IC-effect, in the context of known developmental differences between feedforward and feedback fibers, suggests a potential pathophysiological mechanism of visual processing in ASD, whereby ongoing stimulus processing is less shaped by statistical prediction mechanisms. SIGNIFICANCE STATEMENTChildren with autism often present with an atypical visual perceptual style that emphasizes parts or details over the whole. Using electroencephalography (EEG), this study identifies delays in the visual feedback from higher order sensory brain areas to primary sensory regions. Because this type of visual feedback is thought to carry information about prior sensory experiences, individuals with autism may have difficulty efficiently using prior experience and predictions to help make sense of incoming new visual information. This provides empirical neural evidence to support theories of disrupted sensory perception mechanisms in autism.

neuroscience↗

bioRxiv2021

Envelope reconstruction of speech and music highlights unique tracking of speech at low frequencies

The human brain tracks amplitude fluctuations of both speech and music, which reflects acoustic processing in addition to the processing of higher-order features and ones cognitive state. Comparing neural tracking of speech and music envelopes can elucidate stimulus-general mechanisms, but direct comparisons are confounded by differences in their envelope spectra. Here, we use a novel method of frequency-constrained reconstruction of stimulus envelopes using EEG recorded during passive listening. We expected to see music reconstruction match speech in a narrow range of frequencies, but instead we found that speech was reconstructed better than music for all frequencies we examined. Additionally, speech envelope tracking at low frequencies, below 1 Hz, was uniquely associated with increased weighting over parietal channels. Our results highlight the importance of low-frequency speech tracking and its origin from speech-specific processing in the brain.

neuroscience↗