Biology subjects

Bullock, T.

Publications and source records attributed to Bullock, T..

3 recordsLinked to original sources

bioRxiv2024

UBA1-CDK16: A Sex-Specific Chimeric RNA and Its Role in Immune Sexual Dimorphism

RNA processing mechanisms, such as alternative splicing and RNA editing, have been recognized as critical means to expand the transcriptome. Chimeric RNAs formed by intergenic splicing provide another potential layer of RNA diversification. By analyzing a large set of RNA-Seq data and validating results in over 1,200 blood samples, we identified UBA1-CDK16, a female-specific chimeric transcript. Intriguingly, both parental genes, are expressed in males and females. Mechanistically, UBA1-CDK16 is produced by cis-splicing between the two adjacent X-linked genes, originating from the inactive X chromosome. A female-specific chromatin loop, formed between the junction sites, facilitates the alternative splicing of its readthrough precursor. This unique chimeric transcript exhibits evolutionary conservation, evolving to be female-specific from non-human primates to humans. Furthermore, our investigation reveals that UBA1-CDK16 is enriched in the myeloid lineage and plays a regulatory role in myeloid differentiation. Notably, female COVID-19 patients who tested negative for this chimeric transcript displayed higher counts of neutrophils, highlighting its potential role in disease pathogenesis. These findings support the notion that chimeric RNAs represent a new repertoire of transcripts that can be regulated independently from the parental genes, and a new class of RNA variance with potential implications in sexual dimorphism and immune responses.

genomics↗

bioRxiv2023

Cardiac-sympathetic contractility and neural alpha-band power: cross-modal collaboration during approach-avoidance conflict

As evidence mounts that the cardiac-sympathetic system reacts to challenging cognitive settings, we ask if these responses are passive companions or if they are instead fundamentally intertwined with cognitive function. Healthy human participants performed an approach-avoidance paradigm, trading off monetary reward for painful electric shock, while we recorded simultaneous neural and cardiac signals. Participants were reward-sensitive, but also experienced approach-avoidance "conflict" when the subjective appeal of the reward was near equivalent to the revulsion of the cost. Drift-diffusion model parameters revealed that participants managed conflict in part by integrating larger volumes of evidence into choices (wider decision boundaries). Late alpha-band (neural) dynamics suggested that widening decision boundaries served to combat reward-sensitivity and spread attention more fairly to all dimensions of available information. Independently, wider boundaries were also associated with cardiac "contractility" (an index of sympathetically-mediated positive inotropy). We also saw evidence of conflict-specific collaboration between the neural and cardiac-sympathetic signals. Specific to states of conflict, the alignment (i.e., product) of alpha dynamics and contractility were associated with a further widening of the boundary, independent of either signals singular influence. Cross-trial coherence analyses provided additional support for a direct role of cardiac-sympathetics in nurturing fair assessment of information streams during conflict by disrupting the prepotent reward signals. We conclude that cardiac-sympathetic activity is not a mere companion, rather it is a critical component collaborating with cognitive processes to combat reward-sensitivity during the approach-avoidance conflict.

physiology↗

bioRxiv2018

Dual process coding of recalled location in human oscillatory brain activity

A mental representation of the location of an object can be constructed using sensory information selected from the environment and information stored internally. Human electrophysiological evidence indicates that behaviorally relevant locations, regardless of the source of sensory information, are represented in alpha-band oscillations suggesting a shared process. Here we present evidence from human subjects of either sex for two distinct alpha-band based processes that separately support the representation of location, exploiting sensory evidence sampled either externally or internally.\n\nSignificance StatementOur sensory environment and our internal trains of thought are coded in patterns of brain activity and are used to guide coherent behavior. Oscillations in the alpha frequency band are a predominant feature of human brain activity. This oscillation plays a central role in both selective attention and working memory, suggesting that these important cognitive functions are mediated by a unitary mechanism. We show that the alpha oscillation reflects two distinct processes, one that is supported by continuous sampling of the external sensory environment, and one that is based on sampling from internal representations coded in visual short-term memory. This represents a significant change in our understanding of the nature of alpha oscillations and their relationship to attention and memory.

neuroscience↗