Search bioRxiv⌕ Search

Biology subjects

Cross, J. L.

Publications and source records attributed to Cross, J. L..

2 recordsLinked to original sources

BrainLM: A foundation model for brain activity recordings

AO_SCPLOWBSTRACTC_SCPLOWWe introduce the Brain Language Model (BrainLM), a foundation model for brain activity dynamics trained on 6,700 hours of fMRI recordings. Utilizing self-supervised masked-prediction training, BrainLM demonstrates proficiency in both fine-tuning and zero-shot inference tasks. Fine-tuning allows for the accurate prediction of clinical variables like age, anxiety, and PTSD as well as forecasting of future brain states. Critically, the model generalizes well to entirely new external cohorts not seen during training. In zero-shot inference mode, BrainLM can identify intrinsic functional networks directly from raw fMRI data without any network-based supervision during training. The model also generates interpretable latent representations that reveal relationships between brain activity patterns and cognitive states. Overall, BrainLM offers a versatile and interpretable framework for elucidating the complex spatiotemporal dynamics of human brain activity. It serves as a powerful "lens" through which massive repositories of fMRI data can be analyzed in new ways, enabling more effective interpretation and utilization at scale. The work demonstrates the potential of foundation models to advance computational neuroscience research.

neuroscience↗

Tacrolimus, but not voclosporin, inhibits insulin secretion from human islets at a clinical trough dose

ContextThe incidence of new onset diabetes after transplant (NODAT) has increased over the past decade, likely due to calcineurin inhibitor-based immunosuppressants, including tacrolimus (TAC) and cyclosporin (CsA). Voclosporin (VCS), a next generation calcineurin inhibitor is reported to cause fewer incidences of NODAT but the reason is unclear. ObjectiveWhilst calcineurin signaling plays important roles in pancreatic {beta}-cell survival, proliferation, and function, its effects on human {beta}-cells remain understudied. In particular, we do not understand why some calcineurin inhibitors have more profound effects on the incidence of NODAT. MethodsWe compared the effects of TAC and VCS on the dynamics of insulin secretory function, programmed cell death rate, and the transcriptomic profile of human islets. We studied two clinically relevant doses of TAC (10 ng/ml, 30 ng/ml) and VCS (20 ng/ml, 60 ng/ml), meant to approximate the clinical trough and peak concentrations. ResultsTAC, but not VCS, caused a significant impairment of 15 mM glucose-stimulated and 30 mM KCl-stimulated insulin secretion. This points to molecular defects in the distal stages of exocytosis after voltage-gated Ca2+ entry. No significant effects on islet cell survival or total insulin content were identified. RNA sequencing showed that TAC significantly decreased the expression of 17 genes, including direct and indirect regulators of exocytosis (SYT16, TBC1D30, PCK1, SMOC1, SYT5, PDK4, and CREM), whereas VCS has less broad and milder effects on gene expression. ConclusionsClinically relevant doses of TAC, but not VCS, directly inhibit insulin secretion from human islets, likely via transcriptional control of exocytosis machinery.

cell biology↗