Biology subjects

Ross, O.

Publications and source records attributed to Ross, O..

8 recordsLinked to original sources

bioRxiv2026

Matching in the wild: promise and pitfalls of propensity score matching for field ecology

Field ecologists often rely on observational data to understand the impact of environmental stressors and management interventions on natural systems. Natural and anthropogenic events (e.g. wildfires, protected areas, nutrient deposition) do not occur randomly in space, however, which can introduce bias into observational studies--which we refer to as causal selection bias. Field study designs that ignore the non-random occurrence of stressors may yield biased estimates of stressor effects on ecosystems. Matching methods commonly used in economics, political science and epidemiology offer a powerful framework for controlling for causal selection bias by identifying more comparable treatment and control sites. Although these methods are increasingly used in conservation, they are rarely used in ecological field-based studies. Here we review how Propensity Score Matching (PSM) can improve field sampling designs in ecology and strengthen causal identification of stressor effects. Then we apply this approach to a case study examining wildfire effects on forest recovery in California. We conclude with practical recommendations for implementing PSM to improve causal identification of ecological change, which is particularly important for developing effective management interventions.

ecology↗

bioRxiv2026

PINK1 loss in astrocytes triggers inflammatory dysfunction and neuronal death

Genetic loss of the mitochondrial control enzyme PINK1 leads to Parkinsons disease, characterized by dopaminergic neuron degeneration and neuroinflammation, yet its role in glia remains poorly understood. To address this gap, we investigated how the function of astrocytes and their ability to support neurons is influenced by PINK1 deficiency. For the first time, we demonstrate that human astrocytes exhibit robust PINK1 activity. Next, the first bulk transcriptomic study of human PINK1 mutant astrocytes was performed followed by biochemical validation at the protein level, uncovering homeostatic collapse. Co-culture experiments demonstrated that this astrocyte dysfunction drives neuronal damage through non-cell-autonomous mechanisms. Notably, pharmacological enhancement of autophagy successfully mitigated this inflammatory secretome, indicating that mitochondrial quality control deficits are reversible. These findings establish an unexpected role for PINK1 in glial biology, reveal that astrocytes are vulnerable to mitophagy deficits, and highlight a novel mechanistic link connecting mitochondrial dysfunction, neuroinflammation, and neurodegeneration.

neuroscience↗

bioRxiv2025

Cryptococcus neoformans responds to presence of mycobacterium by diversifying its morphologies and remodelling its capsular material

Cryptococcus neoformans and Mycobacterium tuberculosis are opportunistic pathogens that share overlapping geographical distributions and physiological niches within the human body. Both are recognised by the World Health Organization as high-priority pathogens. Although clinical reports of co-infections with cryptococcosis and tuberculosis are increasing, experimental studies exploring their interactions remain scarce. Here, we demonstrate that C. neoformans can grow in physiologically relevant human plasma-like medium in the presence of either heat-killed M. tuberculosis antigen or the live vaccine strain, M. bovis BCG. In response to presence of mycobacteria, C. neoformans increased in number and exhibited enhanced virulence-associated traits, including titan cell formation, capsule enlargement and increased survival from phagocytosis. This work provides proof-of-principle for a dynamic, inter-pathogen interaction that may contribute to exacerbation disease outcomes in settings of a co-infection.

microbiology↗

bioRxiv2025

Copper Driven Mutualism of Candida albicans and Staphylococcus aureus Interkingdom Biofilms

Although fungi and bacteria commonly coexist within polymicrobial communities, the molecular mechanisms underlying their interactions are still not well understood. Here, we show that the fungus Candida albicans forms biofilms with the bacterium Staphylococcus aureus along a nutritional axis of mutualism and propose that "a copper economy" shapes fungal-bacterial biofilm interactions. Using in vitro biofilms formed on plastic, we found that dual species biofilms are consistently larger than single-species counterparts, indicating a cooperative interaction. Dual species proteomic analysis revealed non-reciprocal copper handling: C. albicans increased copper uptake via transporter Ctr1, while S. aureus enhanced copper export via regulator CsoR and export chaperone CopZ. Dual species biofilms exhibited specific sensitivity to both copper depletion and supplementation, with corresponding reductions in biomass. We identified fungal copper import as the crucial element in mutualistic interactions between C. albicans and staphylococcal species. Moreover, fungal hyphae served as a critical scaffold for biofilm architecture, a role that was compromised under copper-replete conditions. Notably, copper nanoparticles disrupted these dual species biofilms, highlighting a potential therapeutic avenue. Furthermore, we extend the role of C. albicans copper import to mutualistic interactions with additional bacterial species. Our findings establish copper as a central mediator of C. albicans and S. aureus cooperation and suggest that a "copper economy" underpins mutualistic interactions in biofilms.

microbiology↗

bioRxiv2023

Human Plasma-Like Medium (HPLM) induces Cryptococcus neoformans in vivo cell morphologies

The fungal pathogen Cryptococcus neoformans (C. neoformans) forms yeast cells of different sizes and morphological characteristics during infection. These features are usually not seen in standard laboratory in vitro conditions. Here, we describe in vivo cell morphologies when C. neoformans is grown in human plasma-like medium at 37{degrees}C-5% CO2. We observed mixed-size populations of cells less than 1 m up to 16.8 m cell diameter, increased capsule size, high chitin and DNA content in larger cells. Our findings show serum is not required for HPLM-induced C. neoformans cellular heterogeneity. Thus, this new method offers an opportunity to investigate factors of C. neoformans that mediate pathogenesis or host-pathogen interactions in a physiologically relevant setting. IMPORTANCEDescription of new in vitro culture condition using the human plasma-like medium that supports the formation of the full range of in vivo cell morphologies of C. neoformans.

microbiology↗

bioRxiv2022

A high-throughput COPD bronchosphere model for disease-relevant phenotypic compound screening

COPD is the third leading cause of death worldwide, but current therapies for COPD are only effective at treating the symptoms of the disease rather than targeting the underlying pathways that are driving the pathogenic changes. The lack of targeted therapies for COPD is in part due to a lack of knowledge about drivers of disease progression and the difficulty in building relevant and high throughput models that can recapitulate the phenotypic and transcriptomic changes associated with pathogenesis of COPD. To identify these drivers, we have developed a cigarette smoke extract (CSE)-treated bronchosphere assay in 384-well plate format that exhibits CSE-induced decreases in size and increase in luminal secretion of MUC5AC. Transcriptomic changes in CSE-treated bronchospheres resemble changes that occur in human smokers both with and without COPD compared to healthy groups, indicating that this model can capture human smoking signature. To identify new targets, we ran a small molecule compound deck screening with diversity in target mechanisms of action and identified hit compounds that attenuated CSE induced changes, either decreasing spheroid size or increasing secreted mucus. This work provides insight into the utility of this bronchosphere model in examining human respiratory diseases, the pathways implicated by CSE, and compounds with known mechanisms of action for therapeutic development.

cell biology↗

bioRxiv2022

A high-throughput 3D cantilever array to model airway smooth muscle hypercontractility in asthma

Asthma is often characterized by tissue-level mechanical phenotypes that include remodeling of the airway and an increase in airway tightening driven by the underlying smooth muscle. Existing therapies only provide symptom relief and do not improve the baseline narrowing of the airway or halt progression of the disease. To investigate such targeted therapeutics, there is a need for models that can recapitulate the 3D environment present in this tissue, provide phenotypic readouts of contractility, and be easily integrated into existing assay plate designs and laboratory automation used in drug discovery campaigns. To address this, we have developed DEFLCT, a high-throughput plate insert that can be paired with standard labware to easily generate high volumes of microscale tissues in vitro for screening applications. Using this platform, we exposed primary human airway smooth muscle cell-derived microtissues to a panel of six of inflammatory cytokines present in the asthmatic niche, identifying TGF-{beta}1 and IL-13 as strong contractile modulators. RNAseq analysis further demonstrated enrichment of contractile and remodeling-relevant pathways in TGF-{beta}1 and IL-13 treated tissues as well as pathways generally associated with asthma. Taken together, these data establish a disease relevant, 3D tissue model for the asthmatic airway which combines niche specific inflammatory cues and complex mechanical readouts that can be utilized in drug discovery efforts.

bioengineering↗

bioRxiv2018

Heritability and genetic variance of dementia with Lewy bodies

Recent large-scale genetic studies have allowed for the first glimpse of the effects of common genetic variability in dementia with Lewy bodies (DLB), identifying risk variants with appreciable effect sizes. However, it is currently well established that a substantial portion of the genetic heritable component of complex traits is not captured by genome-wide significant SNPs. To overcome this issue, we have estimated the proportion of phenotypic variance explained by genetic variability (SNP heritability) in DLB using a method that is unbiased by allele frequency or linkage disequilibrium properties of the underlying variants. This shows that the heritability of DLB is nearly twice as high as previous estimates based on common variants only (31% vs 59.9%). We also determine the amount of phenotypic variance in DLB that can be explained by recent polygenic risk scores from either Parkinsons disease (PD) or Alzheimers disease (AD), and show that, despite being highly significant, they explain a low amount of variance. Additionally, to identify pleiotropic events that might improve our understanding of the disease, we performed genetic correlation analyses of DLB with over 200 diseases and biomedically relevant traits. Our data shows that DLB has a positive correlation with education phenotypes, which is opposite to what occurs in AD. Overall, our data suggests that novel genetic risk factors for DLB should be identified by larger GWAS and these are likely to be independent from known AD and PD risk variants.

neuroscience↗