Biology subjects

Cunningham, A.

Publications and source records attributed to Cunningham, A..

11 recordsLinked to original sources

bioRxiv2026

Feasibility of Using Functional Near-Infrared Spectroscopy for Characterizing Misophonia-Related Brain Activity

Significance: Misophonia is characterized by decreased tolerance to specific sounds ("triggers") that evoke negative emotional, physiological, and behavioral responses. To understand the neural mechanisms underlying misophonia, functional neuroimaging has been proposed such as functional magnetic resonance imaging (fMRI). However, the fMRI environment introduces substantial noise that increases anxiety, which is one of the comorbidities of misophonia, confounds auditory stimuli, and is costly. We therefore propose an alternative, functional near-infrared spectroscopy (fNIRS) to detect misophonia-related responses. Aim: We evaluated the feasibility of fNIRS to detect misophonia-related sound-evoked responses. Approach: We measured fNIRS, electrodermal activity (EDA), and photoplethysmography (PPG) data from ten adults with minimal to mild misophonia symptoms while they listened to trigger, unpleasant, and neutral sounds. Participants rated their annoyance and antisociality after each sound. Results: Compared with neutral sounds, trigger and unpleasant sounds received higher subjective ratings and evoked greater neural response in the orofacial area. Neural responses tended to increase with annoyance ratings. Significantly lower heart rate (HR) was observed during unpleasant sounds than during neutral and trigger sounds, with no significant difference in EDA features. Conclusions: fNIRS can measure misophonia responses in a quiet setting. Both brain and physiological responses have the same trend observed in prior fMRI studies, verifying its feasibility.

neuroscience↗

bioRxiv2026

Integrated phenotypic and metabolomic analyses identify elite chickpeahaplotypes under water limitation

Chickpea (Cicer arietinum) is a globally important legume crop whose productivity is frequently constrained by terminal drought, particularly in rainfed systems. We used high-throughput phenotyping of 35 diverse chickpea haplotypes at contrasting watering regimes (80% and 40% field capacity) to identify superior haplotypes. Significant haplotype:watering interactions were observed for water-use dynamics, growth rates, biomass accumulation and nodulation, indicating strong genetic control over drought responses. Certain haplotypes (e.g., ICC2210 and ICC18839) maintained relatively high water-use efficiency and growth under stress, while others exhibited pronounced reductions in biomass and nodulation. Principal Component Analyses (PCA) were used to identify haplotypes associated with tolerant and sensitive stress phenotypes. Metabolomic profiling revealed widespread reprogramming of metabolism under water limitation, with 57 of 82 metabolites significantly affected by treatment. A consistent decrease in tricarboxylic acid intermediates, including succinic acid, indicated altered energy metabolism, while accumulation of osmoprotectants such as proline and sucrose reflected adaptive responses to osmotic stress. Multivariate and ANOVA Simultaneous Component Analyses (ASCA) identified key metabolites as major contributors to haplotype-specific drought responses. These metabolites are linked to nitrogen metabolism, stress signalling and cellular protection mechanisms. These results demonstrate substantial variation in drought adaptation among chickpea haplotypes and confirm that the integration of phenotypic and metabolomic traits is a powerful approach to identify drought-resilient genotypes.

plant biology↗

bioRxiv2026

Emergent Biological Realism in RL-Trained DNA Language Models

We compare the efficacy and distributional effects of supervised fine-tuning (SFT) and reinforcement learning (RL) post-training for PlasmidGPT, a foundation model for whole-plasmid generation, using Group Relative Policy Optimization (GRPO) for the RL model. Using a biologically motivated reward function encoding functional annotations, length constraints, and repeat penalties, the RL model achieves a 71.6% quality-control pass rate across 8 prompts on 4,000 sequences, compared to 4.3% for the pretrained baseline and 11.0% for SFT. A five-model reward ablation identifies the cassette arrangement bonus, which rewards correct promoter [->] CDS [->] terminator ordering, as the critical reward component. Rejection-sampling baselines indicate that the gain is not recovered by sampling more heavily from the base model. Beyond directly optimized features, RL-generated sequences converge toward real plasmid distributions in 3-mer composition and minimum free energy density, neither of which is directly optimized by the reward function. Minimum free energy density independently converges to the real-plasmid regime under both SFT and RL despite these being parallel post-training paths. On a small curated hold-out set, RL improves continuation log-likelihood over the pretrained baseline on all 29 held-out sequences (mean {Delta} = +0.83 nats).

bioinformatics↗

bioRxiv2025

Maternal type 2 immunity promotes a microchimeric transfer of systemic type 2 immunity to offspring.

During maternity mothers undergo an immune pivot to a type 2 immune phenotype which is independent of any antigen experience. In this study we present this maternal Type 2 immunity as a key enabler of optimal maternally-driven microchimeric transfer of immunity to helminth infection in offspring. To demonstrate that maternal type 2 immunity dictates offspring immunity we nursed wildtype (WT) offspring on WT or IL-4R-/- foster mothers. WT offspring nursed on IL-4Ra-/- mothers acquired a reduced type 2 immune signature compared to WT offspring nursed on WT mothers. This demonstrated maternal IL-4R imprints type 2 immunity in offspring. This increased type 2 immunity in offspring related to a maternal IL-4R dependent increased frequency of maternal microchimeric cells (MMc) being detected in offspring. Higher worm burdens were detected in offspring nursed on IL-4R-/- mothers, demonstrating that an antigen independent promotion of maternal type 2 immunity provides offspring with protective immunity against a helminth infection. To establish the contribution of increased MMc in offspring nursed on WT mothers in the control of infection, we undertook an antibody mediated depletion of MMc cells in WT offspring. This MMc depletion impaired the control of infection and reduced the magnitude of offspring type 2 immune response against a helminth infection. These findings present antigen independent maternal IL-4R driven type 2 immunity during pregnancy as critical for imparting a profound immune influence via MMc on offspring immunity to infection.

immunology↗

bioRxiv2024

Counting on AR: EEG responses to incongruent information with real-world context

Augmented Reality (AR) technologies enhance the real world by integrating contextual digital information about physical entities. However, inconsistencies between physical reality and digital augmentations, which may arise from errors in the visualized information or the users mental context, can considerably impact user experience. This study characterizes the brain dynamics associated with processing incongruent information within an AR environment. We designed an interactive paradigm featuring the manipulation of a Rubiks cube serving as a physical referent. Congruent and incongruent information regarding the cubes current status was presented via symbolic (digits) and non-symbolic (graphs) stimuli, thus examining the impact of different means of data representation. The analysis of electroencephalographic (EEG) signals from 19 participants revealed the presence of centro-parietal N400 and P600 components following the processing of incongruent information, with significantly increased latencies for non-symbolic stimuli. Additionally, we explored the feasibility of exploiting incongruency effects for brain-computer interfaces. Hence, we implemented decoders using linear discriminant analysis, support vector machines, and EEGNet, achieving comparable performances with all methods. The successful decoding of incongruency-induced modulations can inform systems about the current mental state of users without making it explicit, aiming for more coherent and contextually appropriate AR interactions.

neuroscience↗

bioRxiv2021

Crosstalk between AML and stromal cells triggers acetate secretion through the metabolic rewiring of stromal cells

Acute myeloid leukaemia (AML) cells interact and modulate components of their surrounding microenvironment into their own benefit. Stromal cells have been shown to support AML survival and progression through various mechanisms. Nonetheless, it is unclear whether AML cells could establish beneficial metabolic interactions with stromal cells. Here, we identify a novel metabolic crosstalk between AML and stromal cells where AML cells prompt stromal cells to secrete acetate for their own consumption to feed the tricarboxylic acid cycle (TCA). By performing transcriptome analysis, tracer-based metabolic NMR analysis and ROS measurements, we observe that stromal cells present a higher rate of glycolysis. We also find that acetate in stromal cells is derived from pyruvate via chemical conversion under the influence of reactive oxygen species (ROS) following ROS transfer from AML to stromal cells via gap junctions. Overall, we present a unique metabolic communication between AML and stromal cells that could potentially be exploited for adjuvant therapy.

cell biology↗

bioRxiv2018

Mammalian Cell Entry domains are required for bile resistance and virulence in Salmonella

MCE domains were first reported in Mycobacteria as having a role in Mammalian Cell Entry, with subsequent studies showing their importance during infection. Here, we have examined the function of MCE proteins in Salmonella Typhimurium during mammalian infection. We report that MCE proteins are required for Salmonella virulence, but that this is not related to decreased adherence, entry or survival in mammalian cells. Instead, we reveal that MCE proteins are required for Salmonella bile resistance, in particular to withstand bile salts such as cholate and deoxycholate. Based on our previous work in Escherichia coli, and other studies that have reported roles for MCE proteins in membrane biogenesis, we propose that Salmonella lacking MCE domains have a defective outer membrane that results in bile sensitivity and decreased virulence in vivo. These results suggest that MCE domains mediate fundamental aspects of bacterial membrane physiology as opposed to a proposed direct role in mammalian cell entry, explaining their conservation across both pathogenic and non-pathogenic bacteria.

microbiology↗

bioRxiv2018

Development and worldwide use of a non-lethal and minimal population-level impact protocols for the isolation of chytrids from amphibians

Parasitic chytrid fungi have emerged as a significant threat to amphibian species worldwide, necessitating the development of techniques to isolate these pathogens into sterile culture for research purposes. However, early methods of isolating chytrids from their hosts relied on killing amphibians. We modified a pre-existing protocol for isolating chytrids from infected animals to use toe clips and biopsies from toe webbing rather than euthanizing hosts, and distributed the protocol to interested researchers worldwide as part of the BiodivERsA project RACE - here called the RML protocol. In tandem, we developed a lethal procedure for isolating chytrids from tadpole mouthparts. Reviewing a database of use a decade after their inception, we find that these methods have been widely applied across at least 5 continents, 23 countries and in 62 amphibian species, and have been successfully used to isolate chytrids in remote field locations. Isolation of chytrids by the non-lethal RML protocol occured in 18% of attempts with 207 fungal isolates and three species of chytrid being recovered. Isolation of chytrids from tadpoles occured in 43% of attempts with 334 fungal isolates of one species (Batrachochytrium dendrobatidis) being recovered. Together, these methods have resulted in a significant reduction and refinement of our use of threatened amphibian species and have improved our ability to work with this important group of emerging fungal pathogens.

ecology↗

bioRxiv2017

The essential genome of Escherichia coli K-12

Transposon-Directed Insertion-site Sequencing (TraDIS) is a high-throughput method coupling transposon mutagenesis with short-fragment DNA sequencing. It is commonly used to identify essential genes. Single gene deletion libraries are considered the gold standard for identifying essential genes. Currently, the TraDIS method has not been benchmarked against such libraries and therefore it remains unclear whether the two methodologies are comparable. To address this, a high density transposon library was constructed in Escherichia coli K-12. Essential genes predicted from sequencing of this library were compared to existing essential gene databases. To decrease false positive identification of essential gene candidates, statistical data analysis included corrections for both gene length and genome length. Through this analysis new essential genes and genes previously incorrectly designated as essential were identified. We show that manual analysis of TraDIS data reveals novel features that would not have been detected by statistical analysis alone. Examples include short essential regions within genes, orientation-dependent effects and fine resolution identification of genome and protein features. Recognition of these insertion profiles in transposon mutagenesis datasets will assist genome annotation of less well characterized genomes and provides new insights into bacterial physiology and biochemistry.\n\nIMPORTANCEIncentives to define lists of genes that are essential for bacterial survival include the identification of potential targets for antibacterial drug development, genes required for rapid growth for exploitation in biotechnology, and discovery of new biochemical pathways. To identify essential genes in E. coli, we constructed a very high density transposon mutant library. Initial automated analysis of the resulting data revealed many discrepancies when compared to the literature. We now report more extensive statistical analysis supported by both literature searches and detailed inspection of high density TraDIS sequencing data for each putative essential gene for the model laboratory organism, Escherichia coli. This paper is important because it provides a better understanding of the essential genes of E. coli, reveals the limitations of relying on automated analysis alone and a provides new standard for the analysis of TraDIS data.

microbiology↗

bioRxiv2017

Impact of global change on future Ebola emergence and epidemic potential in Africa

Animal-borne or zoonotic human diseases (e.g., SARS, Rabies) represent major health and economic burdens throughout the world, disproportionately impacting poor communities. In 2013-2016, an outbreak of the Ebola virus disease (EVD), a zoonotic disease spread from animal reservoirs caused by the Zaire Ebola virus (EBOV), infected approximately 30,000 people, causing considerable negative social and economic impacts in an unexpected geographical location(Sierra Leone, Guinea, and Liberia). It is not known whether the spatial distribution of this outbreak and unprecedented severity was precipitated by environmental changes and, if so, which areas might be at risk in the future. To better address the major health and economic impacts of zoonotic diseases we develop a system-dynamics approach to capture the impact of future climate, land use and human population change on Ebola (EVD). We create future risk maps for affected areas and predict between a 1.75-3.2 fold increase in EVD outbreaks per year by 2070. While the best case future scenarios we test saw a reduction in the likelihood of epidemics, other future scenarios with high human population growth and low rates of socioeconomic development saw a fourfold increase in the risk of epidemics occurring and almost 50% increase in the risk of catastrophic epidemics. As well as helping to target where health infrastructure might be further developed or vaccines best deployed, our modelling framework can be used to target global interventions and forecast risk for many other zoonotic diseases.\n\nSignificance StatementDespite the severe health and economic impacts of outbreaks of diseases like SARS or Zika, there has been surprisingly little progress in predicting where and when human infectious disease outbreaks will occur next. By modelling the impacts of future climate, land use and human population change on one particular disease Ebola, we develop future risk maps for the affected areas and predict 1.7-3.2 times as many human Ebola outbreaks per year by 2070, and a 50% increase in the chance that these outbreaks will become epidemics. As well as helping to target where health infrastructure might be further developed or vaccines deployed, our approach can also be used to target actions and predict risk hotspots for many other infectious diseases.

epidemiology↗

bioRxiv2017

MCE domain proteins: conserved inner membrane lipid-binding proteins required for outer membrane homeostasis

Bacterial proteins with MCE domains were first described as being important for Mammalian Cell Entry. More recent evidence suggests they are components of lipid ABC transporters. In Escherichia coli, the single-domain protein MlaD is known to be part of an inner membrane transporter that is important for maintenance of outer membrane lipid asymmetry. Here we describe two multi MCE domain-containing proteins in Escherichia coli, PqiB and YebT, the latter of which is an orthologue of MAM-7 that was previously reported to be an outer membrane protein. We show that all three MCE domain-containing proteins localise to the inner membrane. Bioinformatic analyses revealed that MCE domains are widely distributed across bacterial phyla but multi MCE domain-containing proteins evolved in Proteobacteria from single-domain proteins. Mutants defective in mlaD, pqiAB and yebST were shown to have distinct but partially overlapping phenotypes, but the primary functions of PqiB and YebT differ from MlaD. Complementing our previous findings that all three proteins bind phospholipids, results presented here indicate that multi-domain proteins evolved in Proteobacteria for specific functions in maintaining cell envelope homeostasis.

microbiology↗