Biology subjects

Bai, A.

Publications and source records attributed to Bai, A..

3 recordsLinked to original sources

bioRxiv2026

Scientific computing in the age of agentic AI: an exploratory field report

Scientific computing has become a central component of modern scientific discovery. Yet many computational tools are developed by small, specialized teams under incentives that encourage the release of rapidly prototyped tooling without commensurate attention to engineering concerns, including performance and maintainability. These gaps are particularly visible in the life sciences, where the advent of high-throughput sequencing and molecular profiling has made the production and processing of datasets routine at scales that strain reliability and cost. Recently, LLM-based agents have become increasingly capable, with publicly available systems possessing both significant domain knowledge in many scientific fields and the ability to autonomously operate over complex and specialized codebases in pursuit of well-defined goals. Together, these developments create a practical opportunity for scientific computing. Many of the persistent weaknesses of the scientific computing ecosystem stem from technical debt and a shortage of sustained engineering labor and expertise. Here, we examine coding agents as a potential way to address these weaknesses: we present an exploratory field report of eight early case studies in the application of LLM agents to scientific computing across a range of project scopes, from lightweight maintenance tasks to full performance-oriented rewrites of scientific libraries, with a focus on the life sciences. Each of these case studies is accompanied by reflections from the individual or group responsible for the work, including lessons from the process. Overall, we find that the use of coding agents in scientific computing holds great promise for accelerating scientific research and increasing the reliability of critical systems, but that outstanding concerns remain, including responsibility and ownership for such projects, and we suggest collaboration and stewardship with existing maintainers when feasible.

bioinformatics↗

bioRxiv2026

Molecular mechanics of smooth muscle contraction and relaxation modulated by caldesmon

Smooth muscle (SM) contraction is well known to be regulated by the reversible phosphorylation of the myosin regulatory light chain. However, SM force generation and relaxation are often uncoupled from myosin phosphorylation levels (e.g. the latch-state), indicating that additional regulatory mechanisms must be at play. The precise effects of the actin binding protein caldesmon (CaD) on SM force production and relaxation remain ambiguous, largely due to contradictory findings in experiments performed at the tissue level. To date, there are no studies that have measured the effects of CaD on force and relaxation at the molecular level. Here, we use a laser-trap assay to measure the force produced by SM myosin molecules in the presence and absence of CaD. Measurements were performed before and during myosin dephosphorylation, thus simulating SM contraction and relaxation in-vitro. We demonstrate that CaD inhibits force generation, most likely through competitive inhibition of actomyosin binding while simultaneously introducing a resistive load via tethering of actin and myosin. We also establish CaD as a potentiator of relaxation, increasing force decay rate during myosin dephosphorylation. Finally, we show that CaD directly modulates the dependence of myosin-actin mechanics on myosin phosphorylation levels. These findings refine our understanding of SM regulation, highlighting CaD not merely as a passive structural stabilizer, but as a critical regulatory component of force development and relaxation. Ultimately, understanding these mechanical functions offers new perspectives on pathophysiologies involving SM, such as asthma, hypertension, and gastrointestinal disorders, potentially guiding targeted therapeutic strategies. SIGNIFICANCE STATEMENTSmooth muscle (SM) is responsible for controlling the internal diameter of blood vessels and viscera. Understanding the precise regulation of SM relaxation by actin-binding proteins remains a fundamental lacuna in physiology. Using a molecular mechanics chamber to manipulate the biochemical milieu during active measurements, we demonstrate, for the first time at the molecular level, that caldesmon (CaD) acts as a mechanical modulator that inhibits force generation and accelerates relaxation of SM myosin ensembles. Our results provide a molecular basis for resolving previous contradictory findings reported in tissue-level experiments. Ultimately, understanding the role of contractile and regulatory proteins of SM will provide the basis for understanding SM disorders, such as hypertension and asthma, and guide the development of targeted therapeutic strategies.

biophysics↗

bioRxiv2022

Alpha-1-antitrypsin binds to the glucocorticoid receptor with biological significance in macrophages

Alpha-1-antitrypsin (AAT), a serine protease inhibitor produced mainly by the liver, is the third most abundant protein in plasma. While a canonical receptor for AAT has not been identified, AAT can be internalized into the cytoplasm and is known to affect gene regulation. Since AAT has significant anti-inflammatory properties affecting many cell types including macrophages, we examined whether AAT binds the cytoplasmic glucocorticoid receptor (GR) in macrophages. We report the novel finding that AAT binds to GR in macrophages using several approaches, including co-immunoprecipitation, mass spectrometry, microscale thermophoresis, and molecular modeling. The mass spectrometry data are available via ProteomeXchange with identifier PXD030989. We further demonstrate that AAT induction of angiopoietin-like 4 protein and AAT inhibition of lipopolysaccharide-induced nuclear factor-kappa B activation and interleukin-8 production are mediated, in part, through AAT-GR interaction. Furthermore, this interaction contributes to a host-protective role against mycobacteria in macrophages. The interaction of AAT and GR described in this study identifies a mechanism for the antiinflammatory and host-defense properties of AAT.

immunology↗