Biology subjects

Arthur, C.

Publications and source records attributed to Arthur, C..

7 recordsLinked to original sources

bioRxiv2026

A custom two-in-one HIST and line-scanning confocal excitation module

Fluorescence microscopy applications often require specialized instruments that are optimized for different experimental goals. Here, we present a reconfigurable microscopy module that integrates highly inclined swept tile (HIST) illumination for high-sensitivity single-molecule imaging and line-scanning confocal microscopy for rapid and optically sectioned volumetric acquisition. The system shares major hardware components, including lasers, scanning optics, and detection hardware, while employing unique beam shaping pathways to enable rapid switching between modalities without realignment. We characterize the module performance by measuring the excitation beam profiles, the point spread functions (PSF), and the optical transfer functions (OTF) across 40x, 60x, and 100x magnifications and demonstrate imaging applications including diffraction-limited fixed and live-cell volumetric imaging, fluorescence recovery after photobleaching, and super-resolution DNA-PAINT and single particle tracking (SPT). We also demonstrate the capability to execute multimodal imaging workflows by performing confocal imaging for chromatin density classification correlated with SPT data of nuclear proteins with diverse functions. Together, these results demonstrate a versatile imaging platform capable of supporting complementary fluorescence imaging modalities within a single instrument.

bioengineering↗

bioRxiv2026

Cross-Modal Scaffolding: Music Enhances Hippocampal Binding and Separation for Visual Sequential Memory

The human brain continuously segments experience into meaningful episodes while also encoding temporal relationships between events, yet the mechanisms that optimize this dual challenge remain poorly understood. Here we tested a theoretical framework in which structured temporal context from one modality (music) can organize such memory computations in another (visual) through coordinated modulation of the hippocampus. Using fMRI and a sequence learning paradigm, we show that musical accompaniment enhanced both boundary detection and sequential organization of visual event memory. Mechanistically, musical context accelerated development of neural responses to boundaries in hippocampus and prefrontal cortex while simultaneously optimizing hippocampal representational patterns for learning: strengthening pattern similarity for within-sequence items while reducing computational demands for discriminating representations of different sequences. Critically, musical context created conditions where contextual similarity became a stronger predictor of memory success than before, transforming similarity from an interference signal into a beneficial learning mechanism. Multivariate analysis further revealed that musical scaffolding enhanced hippocampal encoding of the sequential position of visual stimuli, demonstrating cross-modal transfer of temporal structure to visual sequence learning. Finally, we demonstrate functional specificity across hippocampal subfields, revealing how temporal structure cues can coordinate distinct computational processes within the memory circuit. These findings establish a framework for understanding how structured context signals like music can simultaneously optimize multiple aspects of memory organization, and provide mechanistic insight for educational and clinical interventions that have leveraged cross-modal temporal enhancement to improve human cognitive function.

neuroscience↗

bioRxiv2025

Allosteric Disordering of eIF2B Regulates the Integrated Stress Response

The ternary complex (TC), composed of translation initiation factor eIF2, GTP, and initiator methionyl tRNA, delivers the first amino acid to the ribosome to initiate protein synthesis. The activity of the decameric eukaryotic initiation factor 2B complex (eIF2B) initiates TC assembly by catalyzing GDP to GTP exchange on eIF2, thereby setting the TC levels in the cell. Stress-induced phosphorylation converts eIF2 from the substrate of the GDP/GTP exchange reaction into an inhibitor (eIF2-P) of eIF2B. This conversion reduces the cells TC levels and induces the widespread reprogramming of translation known as the Integrated Stress Response (ISR). Here, we chart an allosteric axis running through eIF2B, revealing the importance of a protrusive -helix in its {beta}-subunit, the latch-helix, that locks onto the -subunit to induce eIF2B activity. eIF2-P binding unhooks the latch-helix, opening eIF2B, which inhibits its GDP/GTP exchange activity. Distinct viral proteins have convergently evolved to bind to eIF2B and stabilize the latch-helix-bound active state. Using these insights, we generated ISR-ACTivating compounds, ISRACTs, that stabilize eIF2B in its inhibited, unlatched state. Our study thus highlights how state-transitions in eIF2B are regulated via long-range allostery.

biochemistry↗

bioRxiv2025

Music Scaffolds Visual Statistical Sequence Learning Through Network-Level Reorganization in the Brain

Statistical learning--the ability to extract patterns from noisy continuous experiences--is fundamental to human cognition. Yet, how contextual factors shape this process remains poorly understood. Music is an important example of such contextual factors, because it is ubiquitous in human experience and provides a rich temporally-structured stimulus that can co-occur with other learning processes. Here we demonstrate that pairing music fundamentally enhances visual statistical learning, and this is correlated with systematic reorganization of large-scale brain networks. Using fMRI and a novel probabilistic sequence learning paradigm, we show that familiar melodies significantly improved participants ability to segment continuous visual streams into events and learn sequential relationships. Neuroimaging analyses revealed that the presence of music fundamentally altered the neural network organization that coordinates learning mechanisms: while sequence learning in silence engaged frontal-parietal networks associated with explicit pattern extraction, providing musical temporal structure as a context shifted learning toward MTL-vmPFC circuits recently implicated in schema-guided memory processing. Machine learning analyses confirmed these architectural differences, with the music condition achieving optimal neural prediction of behavioral performance through distributed connectivity patterns while control condition relied on concentrated processing. Our findings support a Cross-Modal Temporal Scaffolding Theory, demonstrating that structured temporal context signals from one modality (here, music) can create more efficient neural states for sequence processing in another through dual mechanisms: enhanced memory integration through schema-guided learning and reduced demands on explicit control resources. These results identify network-level principles for optimizing statistical learning, with broad implications for understanding how environmental context shapes human learning capacity.

neuroscience↗

bioRxiv2025

Harnessing the Evolution of Proteostasis Networks to Reverse Cognitive Dysfunction

The integrated stress response (ISR) is a highly conserved network essential for maintaining cellular homeostasis and cognitive function. Here, we investigated how persistent ISR activation impacts cognitive performance, primarily focusing on a PPP1R15BR658C genetic variant associated with intellectual disability. By generating a novel mouse model that mimics this human condition, we revealed that this variant destabilizes the PPP1R15B*PP1 phosphatase complex, resulting in chronic ISR activation, impaired protein synthesis, and deficits in long-term memory. Importantly, we found that the cognitive and synaptic deficits in Ppp1r15bR658C mice are directly due to ISR activation. Leveraging insights from evolutionary biology, we characterized DP71L, a viral orthologue of PPP1R15B, through detailed molecular and structural analyses, uncovering its mechanism of action as a potent pan-ISR inhibitor. Remarkably, we found that DP71L not only buffers cognitive decline associated with a wide array of conditions--including Down syndrome, Alzheimers disease and aging--but also enhances long-term synaptic plasticity and memory in healthy mice. These findings highlight the promise of utilizing evolutionary insight to inform innovative therapeutic strategies.

neuroscience↗

bioRxiv2024

Mapping the nuclear landscape with multiplexed super-resolution fluorescence microscopy

The nucleus coordinates many different processes. Visualizing how these are spatially organized requires imaging protein complexes, epigenetic marks, and DNA across scales from single molecules to the whole nucleus. To accomplish this, we developed a multiplexed imaging protocol to localize 13 different nuclear targets with nanometer precision in single cells. We show that nuclear specification into active and repressive states exists along a spectrum of length scales, emerging below one micron and becoming strengthened at the nanoscale with unique organizational principles in both heterochromatin and euchromatin. HP1- was positively correlated with DNA at the microscale but uncorrelated at the nanoscale. RNA Polymerase II, p300, and CDK9 were positively correlated at the microscale but became partitioned below 300 nm. Perturbing histone acetylation or transcription disrupted nanoscale organization but had less effect at the microscale. We envision that our imaging and analysis pipeline will be useful to reveal the organizational principles not only of the cell nucleus but also other cellular compartments.

cell biology↗

bioRxiv2020

De Novo Designed Peptide and Protein Hairpins that Self-assemble into Sheets and Nanoparticles.

The design and assembly of peptide based materials has advanced considerably, leading to a variety of fibrous, sheet and nanoparticle structures. A remaining challenge is to account for and control different possible supramolecular outcomes accessible to the same or similar peptide building blocks. Here we present a de novo peptide system that forms nanoparticles or sheets depending on the strategic placement of a disulfide pin between two elements of secondary structure that drive self-assembly. Specifically, we join homodimerizing and homotrimerizing de novo coiled-coil -helices with a flexible linker to generate a series of linear peptides. The helices are pinned back-to-back, constraining them as hairpins by a disulfide bond placed either proximal or distal to the linker. Computational modeling and advanced microscopy show that the proximally pinned hairpins self-assemble into nanoparticles, whereas the distally pinned constructs form sheets. These peptides can be made synthetically or recombinantly to allow both chemical modifications and the introduction of whole protein cargoes as required.

synthetic biology↗