Biology subjects

Bolton, J.

Publications and source records attributed to Bolton, J..

5 recordsLinked to original sources

bioRxiv2026

Life-cycle plasticity enables conditional asexual reproduction in a kelp

Many organisms alternate between distinct life stages and can reproduce either sexually or asexually, yet the mechanisms coordinating these developmental and reproductive transitions remain poorly understood. Here, we investigate the molecular basis of life stage identity and reproductive mode in the kelp Laminaria pallida, a multicellular organism with a complex life cycle. By combining gene expression analyses with developmental experiments and natural population-level approaches, we identify the genetic networks that govern developmental state transitions in both sexual and asexual contexts. We show that the capacity for asexual reproduction is broadly retained but rarely expressed in natural populations and is associated with reduced fitness. Moreover, we find that the presence of potential mating partners suppresses asexual development, revealing that reproductive mode is actively adjusted in response to reproductive opportunities. Together, these findings suggest that asexual reproduction functions as a conditional alternative to sex, promoting persistence when sexual reproduction is constrained while preserving the long-term benefits of sexual reproduction when mates are available. More broadly, our results reveal how organisms integrate developmental, environmental, and reproductive cues to balance alternative reproductive strategies across complex life cycles.

Developmental Biology↗

bioRxiv2025

Rats Exposed to a Low Resource Environment in Early Life Display Sex Differences in Blood Pressure, Autonomic Activity, and Brain and Kidney Pro-inflammatory Markers During Adulthood

Introduction: Poverty, a low resource state, is a common adverse childhood experience (ACE) and early life stress (ELS). People who experienced childhood poverty are at greater risk for developing hypertension during adulthood, with sex differences. To determine the possible mechanisms of these sex differences, we investigated the alterations in blood pressure (BP), autonomic activity, and inflammation in the brain and kidneys of rats exposed to an impoverished environment during the early postnatal period, by using the limited bedding and nesting (LBN) model. Methods: The LBN model mimics childhood poverty by creating a low resource environment on postnatal days 2-9. After weaning, offspring were separated by sex and LBN exposure and were evaluated at 16-18 weeks of age (Adulthood). Results: LBN males displayed an increase in BP compared to the control (CON), whereas LBN females showed no changes. Sympathetic nerve activity (SNA) was increased in LBN males and females compared to the CON, while only parasympathetic nerve activity (PNA) was increased in LBN vs. CON females. Pro-inflammatory cytokines, IL-17 and TNF-, were decreased in the brains of LBN vs. CON males, with no alterations in females. Conclusion: Adult LBN males have elevated BP, due to increased SNA, while LBN females may be protected from increased BP due to a simultaneous increase in SNA and PNA. The reduction in IL-17 and TNF- in LBN males may serve as a compensatory mechanism to lower BP. This study provides insights into sex differences in BP for adults who experienced childhood poverty.

physiology↗

bioRxiv2025

High-resolution imaging reveals a cascade of interconnected cellular bioeffects differentiating the long-term fates of sonoporated cells

Low-intensity ultrasound combined with microbubbles is a promising, non-invasive treatment strategy for enhancing vascular permeability and targeted intracellular drug or gene delivery. After ultrasound insonification, cells can undergo reversible sonoporation, involving adaptation and recovery, or irreversible sonoporation, marked by a loss of cell viability. To design effective sonoporation-based therapeutic delivery strategies, it is therefore critical to identify the biological responses that determine these distinct cell fates. Here, we developed a custom-built high-resolution multicolour imaging device and applied a single pulse of ultrasound (267 kHz frequency, 20 s duration, and [~]110 kPa peak-negative pressure) to trigger targeted microbubble-mediated reversible and irreversible sonoporation events within a confluent monolayer of cultured Madin-Darby canine kidney (MDCK) II cells. We found that intracellular calcium levels rose rapidly and peaked within 10 s in both types of sonoporated cells, although the levels declined differently. In reversibly sonoporated cells, these levels gradually returned to baseline, whereas in irreversibly sonoporated cells, they dropped rapidly, falling well below baseline within 7.9 {+/-} 3.0 min (mean {+/-} s.d.). Using single-vesicle imaging, we further found that vesicles containing the tight junction protein claudin-5 remained mobile with subtly reduced movement in reversibly sonoporated cells, whereas they almost stalled in irreversibly sonoporated cells. The underlying microtubule network was partially disrupted in the reversibly sonoporated cells, recovering fully within 3.2 {+/-} 2.9 min (mean {+/-} s.d.). In contrast, in irreversibly sonoporated cells, the entire microtubule network collapsed within 4.0 {+/-} 2.4 min (mean {+/-} s.d.). Whilst in reversibly sonoporated cells, the uptake of the model drug propidium iodide was mild-to-moderate, without drastic cell size changes up to about 1 h post-sonication, irreversibly sonoporated cells presented with substantially higher propidium iodide uptake and shrunk completely within 43.2 {+/-} 10.5 min (mean {+/-} s.d.). Together, our study identified distinct spatiotemporal sequences of interconnected biological responses underlying different fates of sonoporated cells, providing a framework for identifying processes that could be manipulated for safe and effective sonoporation-based drug delivery.

pharmacology and toxicology↗

bioRxiv2022

The salivary, metal-binding peptide histatin-5 buffers extracellular copper availability

Antimicrobial peptides (AMPs) are key components of diverse host innate immune systems. The family of human salivary AMPs known as histatins bind Zn and Cu. Fluctuations in Zn and Cu availability play significant roles in the host innate immune response (so-called "nutritional immunity"). Thus, we hypothesised that histatins contribute to nutritional immunity by influencing host Zn and/or Cu availability. We posited that histatins limit Zn availability (promote bacterial Zn starvation) and/or raise Cu availability (promote bacterial Cu poisoning). To test this hypothesis, we examined the interactions between histatin-5 (Hst5) and Group A Streptococcus (GAS), which colonises the human oropharynx. Our results showed that Hst5 does not strongly influence Zn availability. Hst5 did not induce expression of Zn-responsive genes in GAS, nor did it suppress growth of mutant strains that are impaired in Zn transport. Biochemical examination of purified peptides confirmed that Hst5 binds Zn only weakly. By contrast, Hst5 bound Cu tightly and it strongly influenced Cu availability. However, Hst5 did not promote Cu toxicity. Instead, Hst5 suppressed expression of Cu-inducible genes, stopped intracellular accumulation of Cu, and rescued growth of a {Delta}copA mutant strain that is impaired in Cu efflux. We thus proposed a new role for salivary histatins as major Cu buffers in saliva that contribute to microbial homeostasis in the oral cavity and oropharynx by reducing the potential negative effects of Cu exposure (e.g. from food) to microbes. Our results raise broad questions regarding the physiological roles of diverse metal-binding AMPs and the management of host metal availability during host-microbe interactions.

microbiology↗

bioRxiv2021

A spike-ferritin nanoparticle vaccine induces robust innate immune activity and drives polyfunctional SARS-CoV-2-specific T cells

Potent cellular responses to viral infections are pivotal for long -lived protection. Evidence is growing that these responses are critical in SARS -CoV-2 immunity. Assessment of a SARS -CoV-2 spike ferritin nanoparticle (SpFN) immunogen paired with two distinct adjuvants, Alhydrogel(R) (AH) or Army Liposome Formulation containing QS-21 (ALFQ) demonstrated unique vaccine evoked immune signatures. SpFN+ALFQ enhanced recruitment of highly activated classical and non -classical antigen presenting cells (APCs) to the vaccine-draining lymph nodes of mice. The multifaceted APC response of SpFN+ALFQ vaccinated mice was associated with an increased frequency of polyfunctional spike -specific T cells with a bias towards TH1 responses and more robust SARS-CoV-2 spike-specific recall response. In addition, SpFN+ALFQ induced Kb spike(539-546)-specific memory CD8+ T cells with effective cytolytic function and distribution to the lungs. This epitope is also present in SARS-CoV, thus suggesting that generation of cross-reactive T cells may provide protection against other coronavirus strains. Our study reveals that a nanoparticle vaccine, combined with a potent adjuvant, generates effective SARS-CoV-2 specific innate and adaptive immune T cell responses that are key components to inducing long-lived immunity. One Sentence SummarySpFN vaccine generates multifactorial cellular immune responses.

immunology↗