Biology subjects

Tucker, M.

Publications and source records attributed to Tucker, M..

8 recordsLinked to original sources

bioRxiv2026

The scents of summer: Plant-diversity and vegetation-height drive health-relevant scent exposure in urban greenspaces

Urban green infrastructure is increasingly promoted as a public-health intervention, yet the biological features that determine exposure to potentially beneficial plant-derived volatile compounds remain poorly understood. Here we quantified airborne terpenes and terpenoids across five contrasting urban greenspaces in Oxford, UK, and related chemical profiles to plant diversity, vegetation structure and surrounding habitat characteristics. Ambient air samples collected across spring and summer were analysed by thermal-desorption gas chromatography-mass spectrometry, alongside field surveys of taxonomic richness, canopy cover, vegetation volume and ground composition. Terpene and terpenoid scentscapes differed strongly among sites and through time, with monoterpenes dominating detected profiles. Sites with greater plant richness and greater vegetation volume below 1.5 m consistently showed higher terpene/terpenoid abundance, whereas total vegetation volume, canopy cover and tree abundance were weaker and less consistent predictors. These relationships were specific to plant-associated chemical classes and were not observed for predominantly anthropogenic volatile compounds. These patterns were resolved across only five independent sampling sites, and the relationships reported here should therefore be considered exploratory. Our findings suggest that human exposure to plant-derived volatiles in cities may be maximised not simply by increasing tree cover, but by designing biodiverse, structurally complex lower-to-mid-storey vegetation within the breathing zone. These results provide an empirical basis for incorporating scentscape ecology into health-oriented urban greenspace design.

ecology↗

bioRxiv2026

Middle-aged mice treated with GHK-Cu peptide administered intraperitoneally or intranasally show behavioral rescue but divergent hippocampal aging programs

Age-related cognitive decline (ARCD) is driven by conserved biological mechanisms of aging, yet no gerotherapeutic directly targets these processes in the brain. Glycyl-L-histidyl-L-lysine complexed with copper (GHK-Cu) is an endogenous peptide with regenerative and anti-inflammatory properties that declines with age. Whether its effects on cognitive aging depend on delivery route or exposure duration remains unclear. Aged C57BL/6J mice (20-21 months) received GHK-Cu (15 mg/kg) via short-term intraperitoneal (IP; 5 days) or longer-term intranasal (IN; 8 weeks) administration. Hippocampal-dependent escape learning was assessed using a spatial navigation task. Molecular effects were evaluated using hippocampal immunohistochemistry and bulk RNA sequencing. Differential gene expression was analyzed using DESeq2 with false discovery rate (FDR) correction, and pathway-level changes were assessed via gene set enrichment analysis (GSEA). IN GHK-Cu improved escape latency across Trials 2-4 in both sexes (P < 0.05), whereas IP dosing produced a transient improvement in males during Trial 2 (P < 0.05) without sustained effects or improvement in females. IN treatment increased synaptophysin in females (P < 0.001) and decreased GFAP in both sexes (P < 0.01), while IP treatment reduced TGF-{beta}, GFAP, and MCP-1 in males (P < 0.05) and decreased p21 in females (P < 0.0001). Transcriptomic analysis revealed distinct molecular programs. IN GHK-Cu induced coordinated suppression of oxidative phosphorylation (male NES -5.44, female NES -4.20; FDR < 0.0001) and MYC target pathways (female NES -4.31, FDR < 0.0001), with additional attenuation of PI3K-AKT-mTOR signaling in females (NES -3.15, FDR = 0.062). In contrast, IP treatment activated oxidative phosphorylation (female NES 4.97, FDR < 0.001), DNA repair (NES 5.58, FDR < 0.001), and MYC targets (NES 4.34, FDR = 0.002), indicating engagement of acute stress-response and repair pathways. GHK-Cu improves hippocampal-dependent learning in aged mice through distinct biological modes: IP exposure activates repair and stress-response pathways, whereas IN delivery induces sustained suppression of growth and mitochondrial metabolic signaling associated with aging biology. These findings demonstrate that functional cognitive improvement can arise from divergent molecular states and identify administrative route and exposure duration as key determinants of gerotherapeutic response.

pharmacology and toxicology↗

bioRxiv2023

Behavioral and neuropathological features of Alzheimer's disease are attenuated in 5xFAD mice treated with intranasal GHK peptide

Efforts to find disease modifying treatments for Alzheimers disease (AD) have met with limited success in part because the focus has been on testing drugs that target a specific pathogenic mechanism. Multiple pathways have been implicated in the pathogenesis of AD. Hence, the probability of more effective treatment for AD is likely increased by using an intervention that targets more than one pathway. The naturally occurring peptide GHK (glycyl-L-histidyl-L-lysine), as a GHK-Cu complex, supports angiogenesis, remodeling, and tissue repair, has anti-inflammatory and antioxidant properties, and has been shown to improve cognitive performance in aging mice. In order to test GHK-Cu as a neurotherapeutic for AD, male and female 5xFAD transgenic mice on the C57BL/6 background at 4 months of age were given 15 mg/kg GHK-Cu intranasally 3 times per week for 3 months until 7 months of age. Results showed that intranasal GHK-Cu treatment delayed cognitive impairment, reduced amyloid plaques, and lowered inflammation levels in the frontal cortex and hippocampus. These observations suggest additional studies are warranted to investigate the potential of GHK-Cu peptide as a promising treatment for AD.

neuroscience↗

bioRxiv2023

Intranasal GHK peptide enhances resilience to cognitive decline in aging mice

Brain aging and cognitive decline are aspects of growing old. Age-related cognitive impairment entails the early stages of cognitive decline, and is extremely common, affecting millions of older people. Investigation into early cognitive decline as a treatable condition is relevant to a wide range of cognitive impairment conditions, since mild age-related neuropathology increases risk for more severe neuropathology and dementia associated with Alzheimers Disease. Recent studies suggest that the naturally occurring peptide GHK (glycyl-L-histidyl-L-lysine) in its Cu-bound form, has the potential to treat cognitive decline associated with aging. In order to test this concept, male and female C57BL/6 mice, 20 months of age, were given intranasal GHK-Cu, 15 mg/kg daily, for two months. Results showed that mice treated with intranasal GHK-Cu had an enhanced level of cognitive performance in spatial memory and learning navigation tasks, and expressed decreased neuroinflammatory and axonal damage markers compared to mice treated with intranasal saline. These observations suggest that GHK-Cu can enhance resilience to brain aging, and has translational implications for further testing in both preclinical and clinical studies using an atomizer device for intranasal delivery.

neuroscience↗

bioRxiv2021

Membrane Constriction by ESCRT-III Proteins Induces Structural Lipid Bilayer Asymmetries

Lipids in biological membranes are thought to be functionally organized, but few experimental tools can probe nanoscale membrane structure. Using brominated lipids as contrast probes for cryo-EM and a model ESCRT-III membrane remodeling system, we observed leaflet-level and protein-localized lipid structural patterns within highly constricted and thinned membrane nanotubes. These nanotubes differed markedly from protein-free, flat bilayers in leaflet thickness, lipid diffusion rates, and lipid compositional and conformational asymmetries. Simulations and cryo-EM imaging of brominated SDPC showed how a pair of phenylalanine residues scored the outer leaflet with a helical hydrophobic defect where polyunsaturated docosahexaenoyl (DHA) tails accumulated at the bilayer surface. Combining cryo-EM of halogenated lipids with molecular dynamics thus enables new characterizations of the composition and structure of membranes on molecular length scales. One-Sentence SummaryCryo-EM imaging of halogenated lipids and MD simulations provide molecular-scale insight into constricted bilayer structure.

biophysics↗

bioRxiv2021

Transcriptomic Analysis of the Innate Immune Response to in vitro Transfection of Plasmid DNA

The innate immune response to cytosolic DNA is intended to protect the host from viral infections, but it can also inhibit the delivery and expression of therapeutic transgenes in gene and cell therapies. The goal of this work was to use mRNA-sequencing to reveal correlations between the transfection efficiencies of four cell types (PC-3, Jurkat, HEK-293T, and primary CD3+ T cells) and their innate immune responses to nonviral gene delivery. Overall, the highest transfection efficiency was observed in HEK-293T cells (87%), which upregulated only 142 genes with no known anti-viral functions. Lipofection upregulated a much larger number (n = 1,057) of cytokine-stimulated genes (CSGs) in PC-3 cells, which also exhibited a significantly lower transfection efficiency. However, the addition of serum during Lipofection and electroporation significantly increased transfection efficiencies and decreased the number of upregulated genes in PC-3 cells. Finally, while Lipofection of Jurkat and Primary T cells only upregulated a few genes, several anti-viral CSGs that were absent in HEK and upregulated in PC-3 cells were observed to be constitutively expressed in T cells, which may explain their relatively low Lipofection efficiencies (8-21%). Indeed, overexpression of one such CSG (IFI16) significantly decreased transfection efficiency in HEK cells to 33%.

bioengineering↗

bioRxiv2019

Analysis of mutations in West Australian populations of Blumeria graminis f. sp. hordei CYP51 conferring resistance to DMI fungicides

Powdery mildew caused by Blumeria graminis f. sp. hordei (Bgh) is a constant threat to barley production but is generally well controlled through combinations of host genetics and fungicides. An epidemic of barley powdery mildew was observed from 2007 to 2013 in the West Australian wheatbelt (WA). We collected isolates, examined their sensitivity to demethylation inhibitor (DMI) fungicides and sequenced the Cyp51B target gene. Five amino acid substitutions were found of which four were novel. A clear association was established between combinations of mutations and altered levels of resistance to DMIs. The most resistant genotypes increased in prevalence from 0 in 2009 to 16% in 2010 and 90% in 2011. Yeast strains expressing the Bgh Cyp51 genotypes replicated the altered sensitivity to various DMIs and these results were confirmed by in silico protein docking studies.

plant biology↗

bioRxiv2019

Generating real-world tumor burden endpoints from electronic health record data: Comparison of RECIST, radiology-anchored, and clinician-anchored approaches for abstracting real-world progression in non-small cell lung cancer

Real-world evidence derived from electronic health records (EHRs) is increasingly recognized as a supplement to evidence generated from traditional clinical trials. In oncology, tumor-based Response Evaluation Criteria in Solid Tumors (RECIST) endpoints are collected in clinical trials. The best approach for collecting similar endpoints from EHRs remains unknown. We evaluated the feasibility of a traditional RECIST-based methodology to assess EHR-derived real-world progression (rwP) and explored non-RECIST-based approaches. In this retrospective study, cohorts were randomly selected from Flatiron Healths database of patient-level EHR data in advanced non-small cell lung cancer. A RECIST-based approach was tested for feasibility (N=26). Three non-RECIST abstraction approaches were tested for feasibility, reliability, and validity (N=200): (1) radiology-anchored, (2) clinician-anchored, and (3) combined. RECIST-based cancer progression could be ascertained from the EHRs of 23% of patients (6/26). In 87% of patients (173/200), at least one rwP event was identified using both the radiology- and clinician-anchored approaches. rwP dates matched 90% of the time. In 72% of patients (124/173), the first clinician-anchored rwP event was accompanied by a downstream event (e.g., treatment change); the association was slightly lower for the radiology-anchored approach (67%; 121/180). Median overall survival (OS) was 17 months (95% confidence interval [CI]: 14, 19). Median real-world progression-free survival (rwPFS) was 5.5 (95% CI: 4.6, 6.3) and 4.9 months (95% CI: 4.2, 5.6) for clinician-anchored and radiology-anchored approaches, respectively. Correlations between rwPFS and OS were similar across approaches (Spearmans rho: 0.65-0.66). Abstractors preferred the clinician-anchored approach as it provided more comprehensive context. RECIST cannot adequately assess cancer progression in EHR-derived data due to missing data and lack of clarity in radiology reports. We found a clinician-anchored approach supported by radiology report data to be the optimal, and most practical, method for characterizing tumor-based endpoints from EHR-sourced data.

bioinformatics↗