Biology subjects

Chang, J. L.

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

3 recordsLinked to original sources

bioRxiv2025

Sex Based Differences in Active Avoidance and Approach Strategy in the Platform Mediated Avoidance Task

Sex differences have been documented in threat conditioning, but research into potential sex differences in avoidance paradigms, particularly active avoidance, remains limited. This research gap is particularly concerning given that women are disproportionately affected by stress- and anxiety-related disorders, characterized by maladaptive avoidance. Yet, preclinical research has historically focused on male subjects, limiting our understanding of the neurobiological mechanisms underlying sex differences in threat responses. To address this, we investigated sex-specific strategies in adult Long Evans rats (10 female, 9 male) using a modified platform-mediated avoidance (PMA) task that created a high-conflict choice between reward-seeking and safety. Behavior was tracked over 25 days, with analyses focusing on a stable performance phase (days 20-25) objectively defined using change point analysis. The study design included an initial cohort and a replication cohort to ensure the findings robustness. Females consistently prioritized safety, spending significantly more time foregoing reward to avoid foot shock, while males engaged in more persistent reward-seeking despite the risk of shock. This difference was not driven by differential reward motivation. Furthermore, female strategies were not significantly modulated by the estrous cycle. Thus, male and female rats employ fundamentally different strategies to resolve approach-avoidance conflict: females adopt a robust, safety-first strategy, while males demonstrate a risk-prone, reward-oriented approach. These findings highlight the importance of considering biological factors underlying threat responses, suggesting that characterizing these neural mechanisms may guide more targeted interventions for anxiety and trauma-related disorders.

animal behavior and cognition↗

bioRxiv2025

An embryonic artery-forming niche reactivates in pulmonary arterial hypertension

Developmental programs that orchestrate cell fate and tissue architecture during organogenesis can cause disease when reactivated in adults. Here we identify a population of endothelial cells (ECs) defined by the pioneer factor early B cell factor 1 (EBF1) that controls both pulmonary artery (PA) morphogenesis and pulmonary arterial hypertension (PAH). During embryonic development, the PA emerges from an endothelial niche harbored within the vascular plexus, where Aplnr+ endothelial progenitors give rise to both arterial ECs and EBF1+ ECs. Rather than directly incorporating into the PA intima, EBF1+ ECs control the branching and maturation of the PA tree through paracrine vasculotrophic signals that direct plexus expansion, arterialization, and mural cell recruitment. Although essential for development, most EBF1+ ECs disappear upon completion of PA morphogenesis. In adult PAH, vascular injury reactivates this developmental program: normally quiescent general capillary ECs re-enter the cell cycle and differentiate into arterial ECs and EBF1+ ECs, reconstituting this artery-forming niche in a maladaptive reprise. Unlike their transient embryonic counterparts, EBF1+ ECs persist within neointimal lesions and express vasculotrophic signals associated with pathological PA remodeling. Capillary-restricted Ebf1 induction combined with endothelial injury recapitulates this program, driving neo-arterialization, neointimal formation, and severe PAH. Conversely, endothelial-targeted AAV-mediated Ebf1 knockdown achieves complete protection in a preclinical model of disease, demonstrating that endothelial EBF1 is necessary for PAH pathogenesis. These findings demonstrate that reactivation and persistence of a transient embryonic artery-forming niche in adulthood can promote pathological vascular remodeling and PAH.

developmental biology↗

bioRxiv2018

Poly-Target Selection Identifies RNA Broad-Spectrum Inhibitors of HIV Reverse Transcriptases

Aptamer selections often yield distinct subpopulations, each with unique phenotypes that can be leveraged for specialized applications. RNA aptamers that bind HIV-1 reverse transcriptase (RT) exhibit potent RT inhibition and suppress viral replication when targeting the strain-specific RT that they were originally selected to bind, but some of these same aptamers fail against single-point mutant and phylogenetically-diverse RTs. We hypothesized that a subset of the total aptamer population in libraries pre-enriched against a single RT may exhibit broad-spectrum RT binding and inhibition, and we devised a multiplexed Poly-Target selection approach to elicit those phenotypes against a panel of diverse primate lentiviral RTs. High-throughput sequencing of starting, negative, and final libraries, followed by analysis of coenrichment and codepletion in parallel and duplicate selection trajectories, narrowed the list of candidate aptamers by orders of magnitude. Biochemical characterization of candidates identified a novel aptamer motif and several rare and unobserved variants of previously-known motifs that inhibited recombinant RTs from HIV-1, HIV-2 and SIV to varying degrees. These broad-spectrum aptamers also suppressed replication of viral constructs carrying phylogenetically-diverse RTs. The Poly-Target selection and coenrichment approach described herein is a generalizable strategy for identifying broad-spectrum behavior and cross-reactivity among related targets from combinatorial libraries.

molecular biology↗