Biology subjects

Power, L.

Publications and source records attributed to Power, L..

4 recordsLinked to original sources

bioRxiv2026

Dissociable Anterior and Posterior Beta-Burst Dynamics Track Thought Disorder in Schizophrenia

BackgroundThought disorder in schizophrenia reflects disrupted internal model maintenance in predictive processing. Beta oscillations have been proposed to index top-down predictive signalling, but prior resting-state studies have focused on spectral power, overlooking transient burst dynamics that enable the stabilization and reinstatement of internal representations, especially in the default mode network (DMN). MethodsResting-state MEG was acquired from 25 patients (7 females) with schizophrenia and 25 matched controls (8 females) between May 2024 and October 2025. Beta bursts (15-30 Hz) were extracted from source-localized cortical time series, and burst rate, duration, power, and inter-regional synchrony were quantified. Associations with computationally-derived semantic and syntactic speech features were assessed using principal-component regression within patients. ResultsConventional beta power did not differ between groups after correction. In contrast, beta-burst dynamics showed significant group-by-anterior-posterior-position interactions for burst rate (p = 0.018), power (p = 0.0014) and duration (p < 0.001). Within the DMN, patients showed shorter inferior parietal burst duration (t(46.0) = -2.74, FDR-p = 0.0343) and increased burst synchrony within left prefrontal cortex (t(31.0) = 2.81, FDR-p = 0.0343) and between prefrontal cortices (t(29.8) = 2.73, FDR-p = 0.0423). Within patients, burst components predicted speech organization (R{superscript 2} = 0.47, F(3,19) = 5.66, p = 0.006), driven by the inferior parietal burst-duration component ({beta} = -0.55, p = 0.0036), but did not predict overall clinical severity. LimitationsThe modest patient sample, short resting-state recording, cross-sectional design, and lack of laminar specificity limit causal and mechanistic inference; burst-speech associations require replication. ConclusionSchizophrenia was associated with dissociable anterior and posterior beta-burst abnormalities that tracked objective speech markers of thought disorder. These findings suggest impaired hierarchical coordination of predictive beta signalling as a candidate mechanism linking intrinsic network dysfunction to disorganized thought.

neuroscience↗

bioRxiv2026

Mitochondrial cytochrome c accumulation accompanies reduced electron flux through complex IV without enhancing cell sensitivity to apoptosis

We show that chronic impairment of mitochondrial respiration is associated with marked accumulation of cytochrome c (Cytc) protein. Using SCO2-deficient HCT116 cells lacking functional cytochrome c oxidase and wild-type cells exposed to sustained hypoxia, we found that substantial mitochondrial Cytc accumulation parallels reduced electron flux through Cytc. SCO2-deficient cells exhibited equally elevated Cytc levels under normoxia (19% O2) and hypoxia (0.1-3% O2). Wild-type cells under sustained hypoxia accumulated Cytc, reaching levels comparable to those in SCO2-deficient cells. This effect was reversible upon reoxygenation. Increased Cytc protein levels were also observed in other cell models, including primary cortical neurons cultured under chronic hypoxia and in cerebral cortex tissue from hypoxia-exposed mice. Cytc accumulation occurred independently of CYCS transcription, mRNA translation, HIF activation, ROS production and changes in mitochondrial network. Pharmacological inhibition of complex III was likewise accompanied by increased Cytc levels, whereas mitochondrial uncoupling had no effect, suggesting that impaired electron transfer rather than membrane depolarisation per se underlies this association. Raman spectroscopy revealed enrichment of reduced Cytc and an increased Cytc-to-cytochrome b ratio in respiration-deficient cells. Further supporting a stabilisation-based mechanism, the fraction of membrane-unbound ferro-Cytc was decreased in SCO2-deficient cells, consistent with moderate cardiolipin enrichment, which is known to enhance retention of Cytc at the inner mitochondrial membrane. Despite elevated mitochondrial Cytc content, SCO2-deficient cells were less susceptible to apoptosis induced by intermittent hypoxia or dichloroacetate. Together, these findings indicate that reduced electron flux through complex IV is associated with Cytc accumulation through increased protein stability and membrane retention without enhancing apoptotic sensitivity.

Cell Biology↗

bioRxiv2026

Decoding the Mechanism of Action of a Parasite TGFβAntagonist Inspires the Creation of Cell-type-specific TGFβ Modulators

Heligmosomoides polygyrus, a mouse parasite, modulates host immunity by secreting modular transforming growth factor-{beta} (TGF{beta}) mimics (TGMs). The agonist TGM1 interacts with TGFBR1, TGFBR2, and the co-receptor CD44 through domains D1/2, D3, and D4/5, respectively. In contrast, the antagonist TGM6, which lacks D1/2, but retains TGFBR2 binding through D3, targets different subsets of cells compared to TGM1. The TGM6 co-receptor is unknown. Using X-ray crystallography and binding studies, we show that TGM6 preferentially binds mouse TGFBR2 over human TGFBR2, and that this is essential for its antagonistic function. We identified low-density lipoprotein receptor-related protein 1 (LRP1) and betaglycan (TGFBR3) as co-receptors for TGM6. LRP1 enhances TGM6 efficacy and is vital for its specific antagonistic effects by promoting TGFBR2 degradation, while betaglycan counteracts TGM6 in a TGFBR2-dependent manner. The modular organization of TGMs enabled us to rationally design TGM1/6 chimeras or TGM-D3 fusion with an affibody that recognizes a specific cell-surface receptor, thereby altering cell-type specificity and functionality. Furthermore, we developed a TGFBR2 nanobody that, on its own, has no inhibitory effect but, when fused to a receptor antibody, antagonizes TGF{beta} signaling in a cell-selective manner. Thus, we designed programmable agents that modulate TGF{beta} signaling only in target co-receptor-expressing cells.

biochemistry↗

bioRxiv2025

The Cortical Temporal Axis: MEG-Based Cross-Frequency Gradients with Biological Anchors

Neural oscillations have long been used to characterize the temporal dynamics of individual brain regions, yet a parsimonious, system-level representation that integrates multi-rhythmic activity has been lacking. Using source-localized resting-state magnetoencephalography (MEG) data, we computed regional power spectra and assessed spectral similarity, then applied diffusion map embedding to construct cross-frequency neurophysiological gradients that place whole-brain oscillations within a unified, low-dimensional coordinate system. We found the first three gradients accounted for over 40% of the variance, remained stable across individuals, and aligned with established functional, structural, and geometric cortical axes. Computational modeling showed that these gradients reflect local excitation-inhibition balance, while multimodal analyses revealed strong associations with neurotransmitter receptor distributions, cytoarchitecture, and cell-type-specific gene expression. Lifespan analyses further demonstrated systematic gradient reorganization, with distinct cognitive mappings onto functions such as language, memory, and multisensory integration. Clinically, Parkinsons disease patients displayed disrupted gradients, particularly in regions linked to language and social cognition. Finally, these gradient patterns exhibited high test-retest reliability. These findings establish MEG-derived neurophysiological gradients as robust, low-dimensional representations of cortical organization, offering a biologically grounded framework for studying brain aging and disease.

neuroscience↗