Biology subjects

Doan, N.

Publications and source records attributed to Doan, N..

5 recordsLinked to original sources

bioRxiv2026

An improved Stentor coeruleus genome and time-resolved transcriptomics link cyclic nucleotide-dependent kinase signaling to single-cell habituation

The giant ciliate Stentor coeruleus is a single cell capable of modifying its behavior through experience. When repeatedly disturbed, it undergoes habituation, a simple and widely conserved form of non-associative learning, despite lacking a nervous system. How a single cell achieves such behavioral plasticity at the molecular level remains poorly understood. Here, we report a compact, contiguous macronuclear reference genome for S. coeruleus, substantially improving genome continuity and annotation quality while resolving two successive rounds of whole-genome duplication and extensive lineage-specific gene-family expansion. Anchoring time-resolved transcriptomics to this reference, we profiled pooled RNA from behaviorally tracked cells collected at defined points during a mechanical stimulation paradigm and identified 341 genes with significant temporal expression dynamics during habituation. The dominant transcriptional signature of habituation was the coordinated, sustained up-regulation of a conserved cyclic nucleotide, calcium, and phosphatase signaling module centered on five cGMP-dependent protein kinase (PKG) paralogs together with a voltage-gated calcium channel and a protein phosphatase 2A regulatory subunit, representing conserved intracellular components of the neuronal long-term depression (LTD) pathway. By integrating an improved genome with time-resolved transcriptomics of habituation, this work provides a community resource for Stentor and identifies a conserved signaling program as a candidate molecular framework underlying single-cell habituation.

molecular biology↗

bioRxiv2026

A quantitative portrait of habituation in Stentor coeruleus

Habituation--the decrement in response to a series of stimuli--is a widespread form of learning observed across many organisms, including the unicellular organism Stentor coeruleus. A lesser-known feature of Stentor habituation, shared with animals, is potentiation: faster habituation to a second stimulus series despite partial or complete recovery of responsiveness before that series begins. This suggests that although the first-order habituation memory can decay during the recovery period between the two series, a persistent second-order memory mediates faster relearning. We investigate the response profile of Stentor across a range of stimulation frequencies and recovery periods to identify the timescales at which these memory traces operate. We introduce a statistical framework to infer both population and single-cell learning parameters, allowing us to quantify prior qualitative findings and examine relationships among parameters across cells. Two key findings are that potentiation is frequency-sensitive, and that recovery and potentiation are decoupled, consistent with a serial and hierarchical cascade of leaky integrator units underlying these processes. This quantitative portrait provides a foundation for mechanistic modeling of intracellular memory in Stentor.

cell biology↗

bioRxiv2026

Associative learning in the protozoan Stentor coeruleus

The capacity for associative learning in protozoa has been a matter of longstanding controversy. In a series of Pavlovian conditioning experiments with the ciliate Stentor coeruleus, we show that temporally pairing weak and strong mechanical stimuli results in a transiently enhanced contraction response to the weak stimulus. Control experiments rule out several alternative explanations, such as non-associative sensitization or arousal. Parametric manipulation of the conditioning protocol's temporal structure revealed a systematic dependence of learning on the inter-trial and inter-stimulus intervals, though not in the form classically observed in animals. A simple mathematical model, combining associative learning with habituation, can explain why enhancement is transient, and accurately fits the learning curve at the aggregate level. We conclude that Stentor coeruleus appears capable of associative learning, suggesting an ancient evolutionary origin that preceded the emergence of multicellular nervous systems.

cell biology↗

bioRxiv2025

Rational Design of Immunogenic Nanoparticles as a Platform for Enhanced Ovarian Cancer Immunotherapy in Mice

Ovarian cancer immunotherapy remains a challenge based on the "cold" tumor microenvironment. Herein we present a rational design to create immunogenic nanoparticles as a multi-agent platform that promotes immune response in a mouse model of ovarian cancer. The hybrid lipid-silica nanosystem is capable of co-loading four types of cargo molecules including a model antigen, nucleic acid-based adjuvant Cytosine-p-linked to Guanine (CpG, TLR3/9 agonist), lipid-based adjuvant (MPLA, TLR4 agonist) integrated into the lipid coat, and optionally a small molecule drug, such as the chemotherapeutic agent oxaliplatin, a well-established treatment for ovarian cancer. The optimization of the nanoplatform in terms of lipid composition, functionalized silica dendritic core formation, and final charge, as well as their compatibility with the complex loading profile highlights an opportunity for enhanced survival of mice with advanced ovarian cancer compared to monotherapy. Furthermore, intraperitoneal administration led to preferential accumulation within tumor-burdened tissues with selective accumulation in myeloid cells. High myeloid cell cytotoxicity negated the benefits of oxaliplatin. The inclusion of CpG in the nanoparticle formulation enhanced the survival of mice with ovarian cancer. To interpret these outcomes and guide future design, we also developed a mathematical model of nanoparticle-driven immune activation, which quantified treatment efficacy and identified key parameters governing tumor response. The presented hybrid nanoparticle i tunable, enabling delivery of alternative molecules therefore, thereby highlighting a promising platform for the treatment of peritoneal cancers. Graphical TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=69 SRC="FIGDIR/small/657862v1_ufig1.gif" ALT="Figure 1000"> View larger version (26K): org.highwire.dtl.DTLVardef@1434599org.highwire.dtl.DTLVardef@18e79e6org.highwire.dtl.DTLVardef@e5285corg.highwire.dtl.DTLVardef@bcc604_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2021

Neutrophil-epithelial interactions augment infectivity and pro-inflammatory responses to SARS-CoV-2 infection

In response to viral infection, neutrophils release inflammatory mediators as part of the innate immune response, contributing to pathogen clearance through virus internalization and killing. Pre-existing co- morbidities correlating to incidence of severe COVID-19 are associated with chronic airway neutrophilia. Furthermore, examination of COVID-19 explanted lung tissue revealed a series of epithelial pathologies associated with the infiltration and activation of neutrophils, indicating neutrophil activity in response to SARS- CoV-2 infection. To determine the impact of neutrophil-epithelial interactions on the infectivity and inflammatory responses to SARS-CoV-2 infection, we developed a co-culture model of airway neutrophilia. SARS-CoV-2 infection of the airway epithelium alone does not result in a notable pro-inflammatory response from the epithelium. The addition of neutrophils induces the release of proinflammatory cytokines and stimulates a significantly augmented pro-inflammatory response subsequent SARS-CoV-2 infection. The resulting inflammatory response is polarized with differential release from the apical and basolateral side of the epithelium. Additionally, the integrity of the epithelial barrier is impaired with notable epithelial damage and infection of basal stem cells. This study reveals a key role for neutrophil-epithelial interactions in determining inflammation and infectivity in response to SARS-CoV-2 infection.

cell biology↗