Biology subjects

Turner, B.

Publications and source records attributed to Turner, B..

7 recordsLinked to original sources

bioRxiv2025

Nighttime and daytime scenarios in Darwinian liposome evolution under UV-driven natural selection

Previously, we presented a hypothesis on Darwinian evolution of liposomes that relies solely on natural and ever-present phenomena: the day-night cycle of solar UV radiation, gravity, and the release of amphiphiles in aqueous media. We demonstrated the protective ability of certain ferric salts typical for Archean waters, notably iron trichloride and ferric ammonium citrate, against liposome destruction by short-wavelength UV by shielding the liposomes with cuvettes filled with ferric salts. In the present study, we investigate the interaction with UV for the liposomes with negative buoyancy that sink naturally in ferric salt solutions. We examined two scenarios: 1) liposomes submerged in the FeCl3 solution prior to the UV exposure, a scenario mimicking the nighttime submergence; and 2) submergence under UV exposure, a relevant daytime scenario. We use custom-designed micron-sized, negative-buoyant (heavy), UV-sensitive liposomes. The results showed that for the nighttime scenario, all liposomes were free from UV damage when given sufficient time to submerge in a protective ferric salt solution. Given that larger and heavier liposomes submerge faster, we hypothesize that simple sugar molecules, such as ribose, which is a vital component of RNA, can serve as the proposed heavy molecules in Origin of Life scenarios. Conversely, the daytime scenario results indicate that liposomes slowly submerging under UV exposure sustain some damage. The results of these experiments, which aim to simulate natural events, showed that negative buoyancy and short-wavelength UV radiation could serve as natural drivers in the novel scenario of Darwinian liposome evolution.

evolutionary biology↗

bioRxiv2025

Synthetic Mucins as Glycan-Defined Prebiotics

The human microbiome contains at least as many bacterial cells as human cells. The mucosal layer that lines all epithelial cells organizes, cultivates, and regulates these bacterial inhabitants. Some commensal bacteria offer benefits, like improving gut barrier function, suppressing pathobiont growth, and modulating host immunity. These health benefits have fueled the popularity of probiotics, but their retention is often hindered by their low colonization efficiency and mucosal adhesion. Mucins, the primary structural components of the mucosal layer, are essential for the organization and regulation of microbial populations, promoting growth and offering sites for adhesion through their multivalent presentation of O-glycosylation. The molecular mechanisms of mucin- probiotic interactions remain understudied due, in part, to the inability to incisively manipulate native mucin sequences or the glycans they bear. In this investigation, we developed synthetic mucins with defined glycan presentations to interrogate glycan-dependent interactions between mucus and probiotic Lactobacillus species. Though synthetic mucins can dampen the effects of pathogens, toxins, and viruses, their impact on probiotic bacteria as prebiotics or binding sites is unclear. We synthesized mucin surrogates that bind to three investigated Lactobacillus species. The nutrient conditions under which bacteria were cultured influenced glycan binding preferences, suggesting mucin-probiotic interactions change with nutrient availability. The addition of synthetic mucins to native mucin increased Lactobacillus fermentum adherence. Additionally, an increase in Lactobacillus glycosidase activity indicated that native and synthetic mucins both function as prebiotics, as probiotic bacteria can cleave the displayed O-glycans. Thus, synthetic mucins can cultivate target probiotic bacteria and increase adhesion as binding sites, highlighting their value as tools for elucidating native mucin functions and as promising agents for promoting human health.

biochemistry↗

bioRxiv2024

Solutions of ferrous salts protect liposomes from UV damage: implications for Life Origin

Previously, we presented a hypothesis on the Darwinian evolution of liposomes that relies only on natural and ever-present phenomena: solar UV radiation, day/night cycle, gravity, and the formation of amphiphiles, e.g., fatty acids and phospholipids, in aqueous media. The hypothesis further suggests that liposomes, formed at the air-water interface, will be inevitably destroyed by Sun UV unless they are submerged and shielded by primordial water. The hypothesis makes two testable predictions. First, certain ingredients of the Archean waters, e.g., ferric salts, can completely attenuate UV; and second, such ferric salts solution can protect the submerged liposomes from the solar UV damage. In our previous experiments (Subbotin and Fiksel 2023a), we tested the prediction of UV attenuation by ferrous salt solutions. We have demonstrated that out of several tested iron salt solutions, two salts demonstrated very strong UV attenuation: at a concentration of 2.5 g/L of (NH4)5[Fe(C6H4O7)2] and FeCl3, the UV intensity drops by a factor of 1000 at a submersion depth of 7.4 mm and 6.3 mm, respectively. In the present study, we tested the second prediction: we investigated whether the above ferrous salt solutions can protect UV-sensitive liposomes from UV damage. The results demonstrated that 10 mm of solutions, the ferric ammonium citrate or iron trichoride, completely protected UV-sensitive liposomes from UV damage. These results supplement and reinforce the proposed hypothesis.

systems biology↗

bioRxiv2020

Frontoparietal dynamics and value accumulation in intertemporal choice

Intertemporal choice requires choosing between a smaller reward available after a shorter time delay and a larger reward available after a longer time delay. Previous studies suggest that intertemporal preferences are formed by generating a subjective value of the monetary rewards that depends on reward amount and the associated time delay. Neuroimaging results indicate that this subjective value is tracked by ventral medial prefrontal cortex (vmPFC) and ventral striatum. Subsequently, an accumulation process, subserved by a network including dorsal medial frontal cortex (dmFC), dorsal lateral prefrontal cortex (dlPFC) and posterior parietal cortex (pPC), selects a choice based on the subjective values. The mechanisms of how value accumulation interacts with subjective valuation to make a choice, and how brain regions communicate during decision making are undetermined. We developed and performed an EEG experiment that parametrically manipulated the probability of preferring delayed larger rewards. A computational model equipped with time and reward information transformation, selective attention, and stochastic value accumulation mechanisms was constructed and fit to choice and response time data using a hierarchical Bayesian approach. Phase-based functional connectivity between putative dmFC and pPC was found to be associated with stimulus processing and to resemble the reconstructed accumulation dynamics from the best performing computational model across experimental conditions. By combining computational modeling and phase-based functional connectivity, our results suggest an association between value accumulation, choice competition, and frontoparietal connectivity in intertemporal choice. Author summaryIntertemporal choice is a prominent experimental assay for impulsivity. Behavior in the task involves several cognitive functions including valuation, action selection and self-control. It is unknown how these different functions are temporally implemented during the course of decision making. In the current study, we combined formal computational models of intertemporal choice with a phase-based EEG measure of activity across brain regions to show that functional connectivity between dmFC and pPC reflects cognitive mechanisms of both visual stimulus processing and choice value accumulation. The result supports the notion that dynamic interaction between frontopatietal regions instantiates the critical value accumulation process in intertemporal choice.

neuroscience↗

bioRxiv2020

Comparison of motility of H. pylori in broth and mucin reveals the interplay of effect of acid on bacterium and the rheology of the medium it swims in.

To colonize on the gastric epithelium Helicobacter pylori bacteria have to swim across a gradient of pH from 2-7 in the mucus layer. Previous studies of H. pylori motility have shown that at pH below 4 do not swim in porcine gastric mucin (PGM) gels. To separately assess the influence of gelation of PGM and that of pH on motors and pH sensitive receptors of H. pylori, we used phase contrast microscopy to compare the translational and rotational motion of H. pylori in PGM versus Brucella broth (BB10) at different pHs. We observed that decreasing pH leads to decreased fraction of motile swimmers with a decrease in the contribution of fast swimmers to the distributions of swimming speeds and length of trajectories. At all pHs the bacteria swam faster with longer net displacement over the trajectory in BB10 as compared to PGM. While bacteria are stuck in PGM gels at low pH, they swim at low pH in broth, albeit with reduced speed. The body rotation rate and estimated cell body torque are weakly dependent on pH in BB10, whereas in PGM the torque increases with increasing viscosity and bacteria stuck in the low pH gel rotate faster than the motile bacteria. Our results show that H. pylori has optimal swimming under slightly acidic conditions, and exhibits mechanosensing when stuck in low pH mucin gels.

biophysics↗

bioRxiv2019

A novel resistance pathway for calcineurin inhibitors in the human pathogenic Mucorales Mucor circinelloides

Mucormycosis is an emerging lethal fungal infection in immunocompromised patients. Mucor circinelloides is a causal agent of mucormycosis and serves as a model system to understand genetics in Mucorales. Calcineurin is a conserved virulence factor in many pathogenic fungi and calcineurin inhibition or deletion of the calcineurin regulatory subunit (CnbR) in Mucor results in a shift from hyphal to yeast growth. We analyzed thirty-six calcineurin inhibitor resistant or bypass mutants that exhibited hyphal growth in the presence of calcineurin inhibitors or in the yeast-locked cnbR{Delta} mutant background without carrying any mutations in known calcineurin components. We found that a majority of the mutants had altered sequence in a gene, named here bycA (bypass of calcineurin A). bycA encodes an amino acid permease. We verified that both bycA{Delta}, and the bycA{Delta} cnbR{Delta} double mutant are resistant to the calcineurin inhibitor FK506, thereby demonstrating a novel resistance mechanism against calcineurin inhibitors. We also found that the expression of bycA was significantly higher in the wild type strain treated with FK506 and in the cnbR{Delta} mutants, but significantly lower in the wild type without FK506. These findings suggest that bycA is a negative regulator of hyphal growth and/or a positive regulator of yeast growth in Mucor and calcineurin suppresses the bycA gene at the mRNA level to promote hyphal growth. BycA is involved in the Mucor hyphal-yeast transition as our data demonstrates a positive correlation between bycA expression, protein kinase A activity, and Mucor yeast-growth. Also calcineurin, independent of its role in morphogenesis, contributes to virulence traits including phagosome maturation blockade, host cell damages, and pro-angiogenic growth factor induction during interactions with hosts. ImportanceMucor is intrinsically resistant to most known antifungals, which makes mucormycosis treatment challenging. Calcineurin is a serine/threonine phosphatase widely conserved across eukaryotes. When calcineurin function is inhibited in Mucor, growth shifts to a less-virulent yeast growth form which makes calcineurin an attractive target for development of new antifungal drugs. Previously we identified two distinct mechanisms through which Mucor can become resistant to calcineurin inhibitors involving Mendelian mutations in the gene for FKBP12, calcineurin A or B subunits and epimutations silencing the FKBP12 gene. Here, we identified a third novel mechanism where loss of function mutations in the amino acid permease encoding the bycA gene contribute to resistance against calcineurin inhibitors. When calcineurin activity is absent, BycA can activate PKA to promote yeast growth via a cAMP-independent pathway. Our data also shows that calcineurin activity, primarily contributes to host - pathogen interactions in the pathogenesis of Mucor.

microbiology↗

bioRxiv2017

How Sample Size Influences The Reproducibility Of Task-Based fMRI

Despite a growing body of research suggesting that task-based functional magnetic resonance imaging (fMRI) studies often suffer from a lack of statistical power due to too-small samples, the proliferation of such underpowered studies continues unabated. Using large independent samples across eleven distinct tasks, we demonstrate the impact of sample size on replicability, assessed at different levels of analysis relevant to fMRI researchers. We find that the degree of replicability for typical sample sizes is modest and that sample sizes much larger than typical (e.g., N = 100) produce results that fall well short of perfectly replicable. Thus, our results join the existing line of work advocating for larger sample sizes. Moreover, because we test sample sizes over a fairly large range and use intuitive metrics of replicability, our hope is that our results are more understandable and convincing to researchers who may have found previous results advocating for larger samples inaccessible.

neuroscience↗