Biology subjects

Guerin, B.

Publications and source records attributed to Guerin, B..

6 recordsLinked to original sources

bioRxiv2026

SARS-CoV-2 maturation driven by a mechano-active nucleocapsid-RNA condensate

The nucleocapsid (N) protein, the core component of the SARS-CoV-2 virus, binds to the 30-kb viral genomic RNA (vgRNA) to form ribonucleoprotein assemblies that are packaged into ~100 nm membrane-enclosed virions. In addition to viral assembly, the N protein performs other functions, including roles in viral mRNA transcription, replication, and immune regulation, making it a key target for developing diagnostics and vaccines. Recent studies show that N protein and RNA undergo phase separation to form a biomolecular condensate that constitutes the viral core. However, how this condensate becomes selectively enveloped by a membrane remains unclear. Here, using a minimal reconstituted system, we demonstrate that N protein-vgRNA condensates are spontaneously enveloped by lipid bilayer membranes, whereas condensates formed by N protein alone or with genomic RNA fragments fail to undergo envelopment and instead adhere to or weakly deform membranes. We show that RNA length tunes the material properties of N protein condensates, with vgRNA imparting enhanced elasticity. We propose a physical model for SARS-CoV-2 maturation in which adhesion between the membrane and the N protein-vgRNA condensate drives membrane bending, while condensate elasticity preserves core geometry. These results identify RNA-dependent material properties as an underlying physical principle for selective SARS-CoV-2 maturation.

biophysics↗

bioRxiv2026

Peripheral Nerve Stimulation Optimized Pulses for EPI (POPE) allows high-resolution fMRI

PurposeRecent improvements in MRI gradient design and amplifiers, advanced MRI scanners are now routinely utilizing slew rates of several hundred T/m/s. However, full gradient performance cannot be exploited in high-resolution EPI due to peripheral nerve stimulation (PNS) limits. We aim to characterize and mitigate these PNS constraints using a simple sequence modification: PNS-optimized EPI gradient pulse shapes. MethodsPNS-Optimized Pulses for EPI (POPE): we selectively reduce the slew rate of gradient pulses at periods of high predicted PNS spikes, while leaving the rest of the waveform unchanged. PNS sensation was evaluated. ResultsPOPE allows 7%-35% faster imaging of EPI protocols resolutions of 1mm-0.3mm resolutions without exceeding predicted PNS. With such improvements, POPE allows robust 0.3 mm isotropic fMRI protocols that would have exceeded safety limits without it. ConclusionPOPE facilitates locally precise fMRI activation mapping on clinical 7T scanners at spatial resolution that were previously unattainable due to PNS limitations.

neuroscience↗

bioRxiv2025

Shivering, but not adipose tissue thermogenesis, increases as a function of mean skin temperature in cold-exposed men and women

Skin cooling results in the activation of heat generating mechanisms to counteract heat lost to the environment. Here, we aim to understand the extent that variations in cold-stimulated heat production may be driven by differences in the contribution of shivering and non-shivering thermogenesis (NST) and the interaction with biological sex. Using a novel mean skin temperature clamping technique in healthy men and women, our data shows that cold-stimulated heat production rises with increasing shivering and myocardial oxidative metabolism in a skin temperature-dependent fashion. Shivering and myocardial thermogenesis were also moderately associated. In contrast, adipose tissue NST did not increase in a linear manner to reductions in skin temperature. Men and women displayed similar thermoregulatory responses, although women presented more pronounced shivering through a greater recruitment of lower-body muscles and greater number of motor units recruited. Thus, shivering contributes proportionally to cold-induced thermogenesis whereas adipose tissue thermogenesis displays an all-or-none response.

physiology↗

bioRxiv2025

Endogenously generated Dutch-type Aβ nonfibrillar aggregates dysregulate presynaptic neurotransmission in the absence of detectable inflammation

Structured AbstractO_ST_ABSBackgroundC_ST_ABSAPPE693Q ("Dutch") transgenic mice develop aging-related learning deficits and accumulate endogenously generated nonfibrillar aggregates of A{beta} (NFA-A{beta}) and APP -carboxy terminal fragments. NFA-A{beta} correlates with synaptic loss and memory deficits more closely than does fibrillar A{beta}. MethodsWe assessed the physiological, transcriptomic, ultrastructural, histological, and metabolic changes associated with the accumulation of NFA of Dutch A{beta} in brains of APPE693Q mice. ResultsAging-related accumulation of NFA-A{beta} in APPE693Q mice was revealed by A11 immunohistochemistry and cyclic D,L--peptide-FITC microscopy. Presynaptic termini of APPE693Q mice developed physiological abnormalities in post-tetanic potentiation, synaptic fatigue, synaptic vesicle replenishment, and an aging-related reduction in mitochondrial complex I activity. Single-cell RNA sequencing showed that excitatory neurons exhibited an altered transcriptomic profile involving "protein translation" and "oxidative phosphorylation". DiscussionAccumulation of NFA-A{beta} alters neuronal metabolism but does not activate inflammation. Depletion of all forms of A{beta} may be required to eliminate A{beta} toxicity with anti-amyloid antibodies.

neuroscience↗

bioRxiv2023

8-channel Tx dipole and 20-channel Rx loop coil array for MRI of the cervical spinal cord at 7 Tesla

The quality of cervical spinal cord images can be improved by the use of tailored radiofrequency coil solutions for ultra-high field imaging; however, very few commercial and research 7 Tesla radiofrequency coils currently exist for the spinal cord, and in particular those with parallel transmit capabilities. This work presents the design, testing and validation of a pTx/Rx coil for the human neck and cervical/upper-thoracic spinal cord. The pTx portion is composed of 8 dipoles to ensure high homogeneity over this large region of the spinal cord. The Rx portion is made of 20 semi-adaptable overlapping loops to produce high Signal-to-noise ratio (SNR) across the patient population. The coil housing is designed to facilitate patient positioning and comfort, while being tight fitting to ensure high sensitivity. We demonstrate RF shimming capabilities to optimize B1+ uniformity, power efficiency and/or specific absorption rate (SAR) efficiency. B1+ homogeneity, SNR and g-factor was evaluated in adult volunteers and demonstrated excellent performance from the occipital lobe down to the T4-T5 level. We compared the proposed coil with two state-of-the-art head and head/neck coils, confirming its superiority in the cervical and upper-thoracic regions of the spinal cord. This coil solution therefore provides a convincing platform for producing the high image quality necessary for clinical and research scanning of the upper spinal cord.

bioengineering↗

bioRxiv2021

Mapping the subcortical connectivity of the human default mode network

The default mode network (DMN) mediates self-awareness and introspection, core components of human consciousness. Therapies to restore consciousness in patients with severe brain injuries have historically targeted subcortical sites in the brainstem, thalamus, hypothalamus, basal forebrain, and basal ganglia, with the goal of reactivating cortical DMN nodes. However, the subcortical connectivity of the DMN has not been fully mapped and optimal subcortical targets for therapeutic neuromodulation of consciousness have not been identified. In this work, we created a comprehensive map of DMN subcortical connectivity by combining high-resolution functional and structural datasets with advanced signal processing methods. We analyzed 7 Tesla resting-state functional MRI (rs-fMRI) data from 168 healthy volunteers acquired in the Human Connectome Project. The rs-fMRI blood-oxygen-level-dependent (BOLD) data were temporally synchronized across subjects using the BrainSync algorithm. Cortical and subcortical DMN nodes were jointly analyzed and identified at the group level by applying a novel Nadam-Accelerated SCAlable and Robust (NASCAR) tensor decomposition method to the synchronized dataset. The subcortical connectivity map was then overlaid on a 7 Tesla 100 micron ex vivo MRI dataset for neuroanatomic analysis using automated segmentation of nuclei within the brainstem, thalamus, hypothalamus, basal forebrain, and basal ganglia. We further compared the NASCAR subcortical connectivity map with its counterpart generated from canonical seed-based correlation analyses. The NASCAR method revealed that BOLD signal in the central lateral nucleus of the thalamus and ventral tegmental area of the midbrain is strongly correlated with that of the DMN. In an exploratory analysis, additional subcortical sites in the median and dorsal raphe, lateral hypothalamus, and caudate nuclei were correlated with the cortical DMN. We also found that the putamen and globus pallidus are negatively correlated (i.e., anti-correlated) with the DMN, providing rs-fMRI evidence for the mesocircuit hypothesis of human consciousness, whereby a striatopallidal feedback system modulates anterior forebrain function via disinhibition of the central thalamus. Seed-based analyses yielded similar subcortical DMN connectivity, but the NASCAR result showed stronger contrast and better spatial alignment with dopamine immunostaining data. The DMN subcortical connectivity map identified here advances understanding of the subcortical regions that contribute to human consciousness and can be used to inform the selection of therapeutic targets in clinical trials for patients with disorders of consciousness.

neuroscience↗