Biology subjects

Burns, S.

Publications and source records attributed to Burns, S..

5 recordsLinked to original sources

bioRxiv2025

In utero lipid nanoparticle delivery achieves robust editing in hematopoietic stem cells.

Efficient delivery of genome editing reagents to hematopoietic stem cells (HSCs) has limited the development of in vivo gene editing therapies for hematologic disease. Here, we exploit developmental hematopoiesis to enable HSC targeting using clinically scalable lipid nanoparticles (LNPs). During fetal development, HSCs reside in the liver, a tissue that is efficiently accessed by LNPs. We show that in utero delivery of LNPs carrying Cre recombinase or CRISPR-Cas9 components results in transfection and genome editing of bona fide long-term repopulating HSCs. Edited HSCs maintain multilineage reconstitution capacity following transplantation, demonstrating preserved stem cell function. Comparative studies reveal that both fetal and early neonatal delivery permit HSC editing, with greater efficiency during fetal liver hematopoiesis. We further identify an LNP formulation that enhance HSC targeting and enable robust neonatal HSC editing without antibody-mediated targeting. Finally, combined delivery of Cas9 via LNPs and a repair template via adeno-associated virus in neonatal mice enables in vivo homology-directed repair in multiple tissues. Together, these findings establish the perinatal period as a therapeutic window for in vivo HSC genome editing and provide a scalable strategy for treating severe early-onset hematologic diseases.

cell biology↗

bioRxiv2025

Linguistic coupling between neural systems for speech production and comprehension during real-time dyadic conversations

The core use of human language is communicating complex ideas from one mind to another in everyday conversations. In conversations, comprehension and production processes are intertwined, as speakers soon become listeners, and listeners become speakers. Nonetheless, the neural systems underlying these faculties are typically studied in isolation, using paradigms that cannot fully engage our capacity for interactive communication, and with indirect measures of similarity. Here, we used an fMRI hyperscanning paradigm to measure neural activity simultaneously in pairs of subjects engaged in real-time, interactive conversations. We used contextual word embeddings from a large language model to quantify the linguistic coupling between production and comprehension systems within and across individual brains. We found a highly overlapping network of regions involved in both production and comprehension spanning much of the cortical language network. Our findings reveal that shared representations for both processes extend beyond the language network into areas associated with social cognition. Together, these results suggest that the specialized neural systems for speech perception and production align on a common set of linguistic features encoded in a broad cortical network for language and communication.

neuroscience↗

bioRxiv2024

Predicting whole-brain neural dynamics from prefrontal cortex fNIRS signal during movie-watching

Functional near-infrared spectroscopy (fNIRS) offers a portable, cost-effective alternative to functional magnetic resonance imaging (fMRI) for non-invasively measuring neural activity. However, fNIRS measurements are limited to cortical regions near the scalp, missing important medial and deeper brain areas. We introduce a predictive model that maps prefrontal fNIRS signals to whole-brain fMRI activity during movie-watching. By aligning neural responses to a common audiovisual stimulus, our approach leverages shared dynamics across imaging modalities to map fNIRS signals to broader neural activity patterns. We scanned participants with fNIRS and utilized a publicly available fMRI dataset of participants watching the same TV episode. The model was trained on the first half of the episode and tested on a held-out participant watching the second half to assess cross-individual and cross-stimulus generalizability. The model significantly predicted fMRI time courses in 66 out of 122 brain regions, including in areas otherwise inaccessible to fNIRS. The predicted fMRI time course also replicated intersubject functional connectivity patterns and retained semantic information about the movie content. Our publicly available model enables researchers to infer broader neural dynamics from localized fNIRS data, offering new opportunities for studying the neural basis of complex cognitive processes during naturalistic tasks.

neuroscience↗

bioRxiv2024

Finding Agreement: fMRI-hyperscanning reveals that dyads explore in mental state space to align opinions.

Many prize synchrony as the ingredient that turns a discordant conversation into a delightful duet. Although failure to align is sometimes associated with discord, exploring divergent opinions can also foster understanding and agreement, satisfy curiosity, and spur imagination. Using fMRI hyperscanning and natural language processing, we tested if dyadic alignment or exploration during decision-making conversations was a more effective route to agreement. Dyads (N = 60) discussed pressing societal problems while being instructed to either persuade or compromise with their partner. Our analysis uncovered four key insights: First, individuals instructed to compromise rather than persuade tended to agree more at the end of the conversation. Second, hyperscanning and linguistic analyses revealed that encouraging compromise resulted in increased exploration during conversations; dyads given compromise instructions traversed more diverse mental states and topics. Third, heightened exploration was linked to greater agreement at the end of the conversation. Fourth, the effect of the compromise instructions on agreement was entirely mediated by the degree of exploration. Together, these results suggest that finding agreement may be spurred by exploration, something that happens spontaneously when people are motivated to compromise. Significance StatementSuccessful conflict resolution is not just about syncing perfectly--it sometimes means leaning into differences. Our study employed fMRI hyperscanning to examine if exploratory conversation strategies promote consensus. We paired participants to discuss societal issues with either a persuasion or compromise mindset. We found that dyads aiming to compromise reached more agreement because they delved deeper into each others minds and covered more topics; in contrast, dyads aiming to persuade their partner covered a narrower scope of topics and mental states and ended up disagreeing more as a result. The finding that exploration rather than simple alignment facilitates agreement could sharpen communication strategies in fields from politics to education and economics.

neuroscience↗

bioRxiv2024

Identification and characterization of a temperature sensitive chlorotic soybean mutant

Screening a transposon-mutagenized soybean population led to the discovery of a recessively inherited chlorotic phenotype. This "vir1" phenotype results in smaller stature, weaker stems, and a smaller root system with smaller nodules. Genome sequencing identified 15 candidate genes with mutations likely to result in a loss of function. Amplicon sequencing of a segregating population was then used to narrow the list to a single candidate mutation, a single-base change in Glyma.07G102300 that disrupts splicing of the second intron. Single cell transcriptomic profiling indicates that this gene is expressed primarily in mesophyll cells and RNA sequencing data indicates it is upregulated in germinating seedlings by cold stress. Previous studies have shown that mutations to Os05g34040, the rice homolog of Glyma.07G102300, produced a chlorotic phenotype that was more pronounced in cool temperatures. Growing soybean vir1 mutants at lower temperatures also resulted in a more severe phenotype. In addition, transgenic expression of wild type Glyma.07G102300 in the knockout mutant of the Arabidopsis homolog At4930720 rescues the chlorotic phenotype, further supporting the hypothesis that the mutation in Glyma.07G102300 is causal of the vir1 phenotype.

plant biology↗