Biology subjects

Neal, M.

Publications and source records attributed to Neal, M..

8 recordsLinked to original sources

bioRxiv2026

AberTrap: an open-source, lightweight, programmable sampler of airborne biological particles

1. Context. Capturing and identifying airborne biological matter (bioaerosols) enables detailed characterisation of ecological communities, but the cost and weight of existing commercially available active air samplers limits the deployment of multiple devices needed to realise this potential. 2. Method. We present the AberTrap, a lightweight (~50g), open-source (CC-BY-SA), programmable rotating-arm bioaerosol sampler that can be self-built from common laboratory components and makerspace equipment at low cost (ca {pound}20 per unit, exc. power supply). To characterise the device's performance, we first explored the influence of rotational speed and paddle design on aerosol capture under controlled conditions, using fluorescein and a range of biological aerosols (4.5-33 m). To demonstrate its utility for ecological applications, we then validated field performance in a species-rich broadleaf woodland (England, UK), deploying eight samplers over five days and identifying captured fungal aerosols by ITS2 metabarcoding. 3. Key results. Modifying paddle design allowed us to influence particle selection and capture efficiency. Slotted paddles captured significantly more aerosols than plain paddles despite sampling less air, which we traced to the concentration of aerosols at the paddle leading edges. This effect was most pronounced for the smallest particles and outweighs the influence of rotational speed. In the field, 20 daily samples (four samplers over five days) detected 2,431 fungal taxa, 78.9% of the Chao2-estimated total fungal richness. A single sampler captured only 59% of this richness. Continuous 5-day sampling recovered 78% of the taxa detected by daily sampling, indicating only modest paddle saturation over this period. Our time segregated design allowed us to infer dispersal dynamics; 35% of taxa were recorded only on one day, and 19% recorded across all five days. Overall, replicate AberTraps provided high sampling completeness. 4. Implications. The AberTrap provides a low-cost, lightweight and programmable alternative to commercial rotating-arm samplers, enabling levels of spatial and temporal replication impractical with existing devices. Low cost and portability facilitate deployment in remote or resource-limited contexts. Its open-source, adaptable design allows the device to be tailored for applications in biodiversity assessment, pathogen surveillance and ecological monitoring.

ecology↗

bioRxiv2026

Multi-model Segmentation and Morphometric Quantification of Cerebral Amyloid Angiopathy in Alzheimer's Disease Whole Slide Histopathology Images

IntroductionCerebral amyloid angiopathy (CAA) is characterized by amyloid-beta deposition in cortical and leptomeningeal vessels and associated with cognitive impairment and hemorrhage. Current neuropathological assessments rely on semiquantitative grading and lack vessel-level resolution and scalability. Existing computational pathology approaches also fail to capture individual vessel morphology and spatial amyloid distribution across whole-slide images (WSIs). To address this gap, we developed a deep learning framework for reproducible, quantitative analysis of CAA in WSIs. MethodsWe analyzed 20 postmortem brain tissue sections from the frontal (n = 10) and occipital cortices (n = 10) of 10 individuals with Alzheimers disease pathology obtained from the University of Pittsburgh Alzheimers Disease Research Center, which served as the internal development cohort. An independent external cohort consisted of 10 sections (5 frontal and 5 occipital samples) from 5 individuals obtained from the University of Kentucky Alzheimers Disease Research Center. We trained and compared three semantic segmentation architectures, a standard U-Net, a dual-attention residual U-Net (DA-ResUNet), and a Swin Transformer-based U-Net (Swin-UNet), using the internal development cohort with slide-level five-fold cross-validation. All models were evaluated on the independent external cohort to assess generalization under domain shift. Based on segmentation performance and computational efficiency, we selected one architecture to generate whole-slide composite segmentation masks for vessel walls, amyloid deposits, and tissue compartments. These masks were subsequently used for deterministic vessel detection, morphometric measurements, and quantification of vascular and perivascular amyloid features through post-processing analysis. ResultsAll three architectures achieved high segmentation accuracy on the internal cohort, with Dice scores above 90% across vessel walls, amyloid deposits, gray matter, and leptomeninges. The Swin-UNet showed marginally higher performance for vessel segmentation, whereas the DA-ResUNet provided more balanced accuracy and computational efficiency and was selected for downstream analysis. External cohort evaluation demonstrated robust generalization, with attention-enhanced models outperforming the standard U-Net under domain shift. Using the selected model, the pipeline reliably detected valid vessels, excluded non-vascular artifacts, and enabled deterministic extraction of vessel morphometry, vascular and perivascular amyloid burden, and identification of circumferential CAA involvement at the vessel level. DiscussionThis framework provides a scalable, interpretable solution for vessel-level CAA analysis, supporting robust geometric and spatial characterization of cerebrovascular pathology and enabling future integration with clinical and genetic studies. Beyond CAA, the modular design allows extension to other vascular pathologies, including arteriolosclerosis, in WSIs, facilitating broader investigation of cerebrovascular disease mechanisms.

pathology↗

bioRxiv2026

Rational engineering of facultative anaerobiosis enables commensal survival in the oxygenated gut

Life originated in the absence of oxygen. Despite its substantial energetic advantages, many modern microbes remain obligate anaerobes, confined to anoxic niches such as the mammalian gut. Why these organisms cannot tolerate oxygen has remained unresolved for more than two centuries. Here, using integrated multi-omics analyses, we identify a network of interlocking vulnerabilities in central metabolism, biosynthetic pathways, and redox homeostasis that together impose an aerobic growth barrier in the obligate anaerobic commensal Bacteroides thetaiotaomicron. Rational repair of these vulnerabilities restores metabolic integrity and progressively enhances oxygen tolerance, yielding engineered strains capable of robust growth at 10% O2 and markedly improved resilience in the oxygenated, inflamed gut. These findings define a molecular basis for obligate anaerobiosis and establish a framework for engineering commensal bacteria to function in oxidative environments, expanding their ecological range and therapeutic potential.

microbiology↗

bioRxiv2025

Prokineticin-2 Upregulates GDNF in Astrocytes and Pharmacological Modulation of PK2 Receptors offers Neuroprotection in Experimental Models of Parkinson's Disease

Despite a wealth of preclinical studies establishing neuroprotective and neurorestorative properties of glial cell-line-derived neurotrophic factor (GDNF) in animal models of Parkinsons disease (PD), clinical trials utilizing direct intracranial infusion of GDNF protein, or adeno-associated virus (AAV)-mediated GDNF gene transfer has not achieved the desired efficacy, largely due to challenges in delivery methods. Given GDNFs strong potential for neuroprotection, alternative strategies to elevate its expression by beyond invasive injection or genetic manipulation remain a promising therapeutic avenue for PD. We previously reported that prokineticin signaling provides a compensatory protective response against dopaminergic neuronal degeneration in cell and animal models of PD. Herein, we report a novel finding that PK2 regulates GDNF gene expression in astrocytes, suggesting that PK2 signaling can be harnessed for neuroprotection in PD. Treatment of cultured astrocytes with the PK2 protein, PK2 gene overexpression or prokineticin receptor 1 (PKR1) agonist IS20 significantly induced the GDNF gene expression and the protein secretion, resulting in enhanced dopaminergic cell survival in cell culture models of PD. Importantly, systemic administration of IS20 through intraperitoneal or intranasal routes elevated GDNF levels in the mouse brain, including the nigrostriatal system. Furthermore, IS20 treatment conferred significant neuroprotective effects in both 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced and MitoPark transgenic mouse models of PD. Collectively, our translational findings suggest that pharmacological modulation PK2 signaling may unlock the full clinical benefit of GDNF, offering a novel and non-invasive therapeutic strategy for Parkinsons disease.

pharmacology and toxicology↗

bioRxiv2025

An Anaerobic Pathogen Rewires Host Metabolism to Fuel Oxidative Growth in the Inflamed Gut

To colonize their host and cause disease, enteric pathogens must deploy their virulence factors to establish distinct nutrient niches. How obligate anaerobic pathogens construct nutrient niches in the densely populated large intestine remains poorly understood. Enterotoxigenic Bacteroides fragilis (ETBF) is considered an obligate anaerobic bacterium and has been implicated in inflammation-associated diseases, including colitis and colorectal cancer. Here we show that ETBF uses its virulence factor, Bacteroides fragilis toxin, to reprogram colonic epithelial cell metabolism to colonize the inflamed gut. Bacteroides fragilis toxin activates colonic epithelial signaling and hijacks the host bile acid recycling pathway, inducing a metabolic shift in the epithelium from oxidative phosphorylation to glycolysis. This shift increases local concentrations of lactate and oxygen, nutrients that support an oxidative metabolism in ETBF. These findings reveal an unexpected strategy by which a pathogenic organism, previously considered to be an obligate anaerobic bacterium, generates and exploits an oxidative niche in the inflamed gut.

microbiology↗

bioRxiv2025

TOR and heat shock response pathways regulate peroxisome biogenesis during proteotoxic stress

Peroxisomes are versatile organelles mediating energy homeostasis and redox balance. While peroxisome dysfunction is linked to numerous diseases, the molecular mechanisms and signaling pathways regulating peroxisomes during cellular stress remain elusive. Using yeast, we show that perturbations disrupting protein homeostasis including loss of ER or cytosolic chaperone function, impairments in ER protein translocation, blocking ER N-glycosylation, or reductive stress, cause peroxisome proliferation. This proliferation is driven by increased de novo biogenesis from the ER as well as increased fission of pre-existing peroxisomes, rather than impaired pexophagy. Notably, peroxisome biogenesis is essential for cellular recovery from proteotoxic stress. Through comprehensive testing of major signaling pathways, we determine this response to be mediated by activation of the heat shock response and inhibition of Target of Rapamycin (TOR) signaling. Finally, the effects of proteotoxic stress and TOR inhibition on peroxisomes are also captured in human fibroblasts. Overall, our findings reveal a critical and conserved role of peroxisomes in cellular response to proteotoxic stress.

cell biology↗

bioRxiv2023

Altered Metabolism and DAM-signatures in Female Brains and Microglia with Aging

Despite Alzheimers disease (AD) disproportionately affecting women, the mechanisms remain elusive. In AD, microglia undergo metabolic reprogramming, which contributes to microglial dysfunction and AD pathology. However, how sex and age contribute to metabolic reprogramming in microglia is understudied. Here, we use metabolic imaging, transcriptomics, and metabolic assays to probe age-and sex-associated changes in brain and microglial metabolism. Glycolytic and oxidative metabolism in the whole brain was determined using Fluorescence Lifetime Imaging Microscopy (FLIM). Young female brains appeared less glycolytic than male brains, but with aging, the female brain became male-like. Transcriptomic analysis revealed increased expression of disease-associated microglia (DAM) genes (e.g., ApoE, Trem2, LPL), and genes involved in glycolysis and oxidative metabolism in microglia from aged females compared to males. To determine whether estrogen can alter the expression of these genes, BV-2 microglia-like cell lines, which abundantly express DAM genes, were supplemented with 17{beta}-estradiol (E2). E2 supplementation resulted in reduced expression of DAM genes, reduced lipid and cholesterol transport, and substrate-dependent changes in glycolysis and oxidative metabolism. Consistent with the notion that E2 may suppress DAM-associated factors, LPL activity was elevated in the brains of aged female mice. Similarly, DAM gene and protein expression was higher in monocyte-derived microglia-like (MDMi) cells derived from middle-aged females compared to age-matched males and was responsive to E2 supplementation. FLIM analysis of MDMi from young and middle-aged females revealed reduced oxidative metabolism and FAD+ with age. Overall, our findings show that altered metabolism defines age-associated changes in female microglia and suggest that estrogen may inhibit the expression and activity of DAM-associated factors, which may contribute to increased AD risk, especially in post-menopausal women.

neuroscience↗

bioRxiv2020

A synthetic lethal interaction with a viral-induced hypomorph of GBF1

Viruses co-opt host proteins to carry out their lifecycle. Repurposed host proteins may thus become functionally compromised; a situation analogous to a loss-of-function mutation. We term such host proteins viral-induced hypomorphs. Cells bearing cancer driver loss-of-function mutations have successfully been targeted with drugs perturbing proteins encoded by the synthetic lethal partners of cancer-specific mutations. Synthetic lethal interactions of viral-induced hypomorphs have the potential to be similarly targeted for the development of host-based antiviral therapeutics. Here, we use GBF1, which supports the infection of many RNA viruses, as a proof-of-concept. GBF1 becomes a hypomorph upon interaction with the poliovirus protein 3A. Screening for synthetic lethal partners of GBF1 revealed ARF1 as the top hit, disruption of which, selectively killed cells that synthesize poliovirus 3A. Thus, viral protein interactions can induce hypomorphs that render host cells vulnerable to perturbations that leave uninfected cells intact. Exploiting viral-induced vulnerabilities could lead to broad-spectrum antivirals for many viruses, including SARS-CoV-2. SummaryUsing a viral-induced hypomorph of GBF1, Navare et al., demonstrate that the principle of synthetic lethality is a mechanism to selectively kill virus-infected cells.

molecular biology↗