Biology subjects

Cleary, M.

Publications and source records attributed to Cleary, M..

7 recordsLinked to original sources

bioRxiv2026

Environmental Frass Remodels the Larval Gut Microbiome to Enable Black Soldier Fly (Hermetia illucens) Bioconversion of Livestock Manure

Black Soldier Fly larvae (BSFL) consume nearly any organic material and show promise for the remediation of agricultural waste, including livestock manure. BSFL feeding generates frass, a mixture of unconsumed substrate, larval feces, and microorganisms. We identified a wild population of BSFL (Yuba strain) thriving on rabbit manure, a challenging substrate due to its high lignocellulose content. We investigated if frass extract from this source was necessary and sufficient to support bioconversion of manure and if such effects are altered by captive husbandry. Larvae supplemented with domestic frass failed to grow on rabbit manure but grew well when supplemented with wild-sourced frass. Microbiome analysis revealed that wild-sourced frass contributes a cohort of lignocellulose-degrading microorganisms to the BSFL gut, particularly Rummeliibacillus bacteria and Scedosporium fungi. These growth-promoting effects extended to cattle manure. Following initial seeding with wild-sourced frass, lab-cultured frass ultimately failed to support growth on rabbit manure and the gut microbiome shifted toward bacteria commonly found in domestic BSFL. This study reveals that frass extract derived from environmental sources can improve the bioconversion ability of BSFL and that beneficial microbes are lost during captive-rearing.

microbiology↗

bioRxiv2023

Multiple, single trait GWAS and supervised machine learning reveal the genetic architecture of Fraxinus excelsior tolerance to ash dieback in Europe

Common ash (Fraxinus excelsior) is under intensive attack from the invasive alien pathogenic fungus Hymenoscyphus fraxineus, causing ash dieback at epidemic levels throughout Europe. Previous studies have found significant genetic variation among clones in ash dieback susceptibility and that host phenology, such as autumn yellowing, is correlated with susceptibility of ash trees to H. fraxineus; however, the genomic basis of ash dieback tolerance in F. excelsior remains poorly understood. Here, we integrate quantitative genetics and genome-wide association analyses with machine learning to reveal the genetic architecture of ash dieback tolerance and its relationship to phenological traits in F. excelsior populations in six European countries (Austria, Denmark, Germany, Ireland, Lithuania, Sweden). We use whole-genome sequencing of 486 F. excelsior genotypes to confirm the genotypic correlation between crown damage caused by ash dieback and intensity of autumn leaf yellowing within multiple sampling sites. Although, our results suggest that the examined traits are polygenic, a relatively small number of single nucleotide polymorphisms (SNPs) explained a large proportion of the variation in both disease tolerance and autumn leaf yellowing. We could explain up to 63% (based on 9155 unlinked SNPs) of variation in individual response to ash dieback crown damage and up to 72% (based on 3740 unlinked SNPs) of variation in autumn yellowing. We identified eight SNPs encoding non-synonymous substitutions, of which those with the highest predictive power were located within genes related to plant defence (pattern triggered immunity, pathogen detection) and phenology (regulation of flowering and seed maturation, auxin transport). Overall, our results provide insights of a multifaceted defence response, according to which a combination of direct defence mechanisms and phenological avoidance of pathogen spread constitute tolerance to ash dieback.

plant biology↗

bioRxiv2023

The incidence of movement disorders increases with age and contrasts with subtle and limited neuroimaging abnormalities in argininosuccinic aciduria.

Argininosuccinate lyase is integral to the urea cycle detoxifying neurotoxic ammonia and the nitric oxide biosynthesis cycle. Inherited argininosuccinate lyase deficiency causes argininosuccinic aciduria (ASA), a rare disease with hyperammonaemia and nitric oxide deficiency. Patients present with developmental delay, epilepsy and movement disorders, associated with nitric oxide-mediated downregulation of central catecholamine biosynthesis. A neurodegenerative phenotype has been proposed in ASA. To better characterise this neurodegenerative phenotype in ASA, we conducted a retrospective study in six paediatric and adult metabolic centres in the UK in 2022. We identified 60 patients and specifically looked for movement disorders-related symptoms: movement disorders such as ataxia, tremor and dystonia, hypotonia and abnormal behaviour. We analysed neuroimaging with diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) in an ASA patient with movement disorders. We assessed conventional and DTI MRI alongside single photon emission computer tomography (SPECT) with dopamine analogue radionuclide 123I-ioflupane, in Asl-deficient mice treated by hASL mRNA with normalised ureagenesis. Movement disorders in ASA appears in the 2nd and 3rd decades of life, becoming more prevalent with ageing and independent from the age of onset of hyperammonaemia. Neuroimaging can show abnormal DTI features affecting both grey and white matter, preferentially basal ganglia. ASA mouse model with normalised ureagenesis did not recapitulate these DTI findings and showed normal 123I-ioflupane SPECT and cerebral dopamine metabolomics. Altogether these findings support the pathophysiology of a late-onset movement disorders with functional central catecholamine dysregulation but without or limited neurodegeneration of dopaminergic neurons, making these symptoms amenable to targeted therapy. SynopsisMovement disorders-related symptoms in ASA appear in the 2nd and 3rd decades of life, becoming more prevalent with age and shows abnormal neuroimaging features of basal ganglia in ASA patients, not recapitulated in ASA mice.

genetics↗

bioRxiv2023

Climate, host and geography shape insect and fungal communities of trees

Non-native pests, climate change, and their interactions are likely to alter relationships between trees and tree-associated organisms with consequences for forest health. To understand and predict such changes, factors structuring tree-associated communities need to be determined. Here, we analysed the data consisting of records of insects and fungi collected from dormant twigs from 155 tree species at 51 botanical gardens or arboreta in 32 countries. Generalized dissimilarity models revealed similar relative importance of studied climatic, host-related and geographic factors on differences in tree-associated communities. Mean annual temperature, phylogenetic distance between hosts and geographic distance between locations were the major drivers of dissimilarities. The increasing importance of high temperatures on differences in studied communities indicate that climate change could affect tree-associated organisms directly and indirectly through host range shifts. Insect and fungal communities were more similar between closely related vs. distant hosts suggesting that host range shifts may facilitate the emergence of new pests. Moreover, dissimilarities among tree-associated communities increased with geographic distance suggesting that human-mediated transport may facilitate the introductions of new pests. The results of this study highlight the need to limit the establishment of tree pests and increase the resilience of forest ecosystems to changes in climate.

ecology↗

bioRxiv2020

Aspen leaves as a "chemical landscape" for fungal endophyte diversity - Can nitrogen and herbivory shape the community composition in controlled conditions?

AO_SCPLOWBSTRACTC_SCPLOWThe endophytic microbiome may influence the ecological performance of plants, including forest trees. Various abiotic and biotic factors may shape the endophyte communities directly but also indirectly, by modifying the quality of host plants as a substrate. We hypothesized that potentially antifungal or fungistatic condensed tannins (CTs) would determine the quality of aspen (Populus tremula) leaves as a substrate for endophytic fungi. By subjecting the plants to nitrogen fertilization (N) or herbivory (H; leaf beetles) we aimed to change the internal "chemical landscape", especially the CT levels, in aspen leaves. We expected that this would lead to changes in the fungal community composition, in line with the predictions of heterogeneity-diversity relationship hypothesis. To test this we conducted a greenhouse study where aspen plants were subjected to N and H treatments, individually or in combination. The chemical status of the leaves was analysed using GC/MS (114 metabolites), LC/MS (11 phenolics) and UV-spectrometry (CTs) and the endophytic communities were characterized using culture-dependent sequencing. Nitrogen treatment, alone or in combination with herbivory had a suppressing effect on the concentration and within-treatment variation in the CT precursors, catechins, and resulted in similar trend also in CTs. Nitrogen increased the concentration of certain amino acids, and it also tended to increase most of the analysed sugars sugars. Herbivory had a negligible effect on chemical traits. In N-treated plants, the endophyte richness and abundance were higher than in plants exposed to H, but in general, the diversity of the culturable endophytes remaind stable despite the subtle changes in leaf chemistry.

plant biology↗

bioRxiv2020

Identification of novel regulators of dendrite arborization using cell type-specific RNA metabolic labeling

Obtaining neuron transcriptomes is challenging; their complex morphology and interconnected microenvironments make it difficult to isolate neurons without potentially altering gene expression. Multidendritic sensory neurons (md neurons) of Drosophila larvae are commonly used to study peripheral nervous system biology, particularly dendrite arborization. We sought to test if EC-tagging, a biosynthetic RNA tagging and purification method that avoids the caveats of physical isolation, would enable discovery of novel regulators of md neuron dendrite arborization. RNAs were biosynthetically tagged by expressing CD:UPRT (a nucleobase-converting fusion enzyme) in md neurons and feeding 5-ethynylcytosine (EC) to larvae. Tagged RNAs were subsequently purified and used for RNA-sequencing. Reference RNA was prepared in a similar manner using 5-ethynyluridine (EUd) to tag RNA in all cells and negative control RNA-seq was performed on "mock tagged" samples to identify non-specifically purified transcripts. Differential expression analysis identified md neuron enriched and depleted transcripts. Three candidate genes encoding RNA-binding proteins (RBPs) were tested for a role in md neuron dendrite arborization. Loss-of-function for the m6A-binding factor Ythdc1 did not cause any dendrite arborization defects while RNAi of the other two candidates, the poly(A) polymerase Hiiragi and the translation regulator Hephaestus, caused significant defects in dendrite arborization. This work provides an expanded view of transcription in md neurons and a technical framework for combining EC-tagging with RNA-seq to profile transcription in cells that may not be amenable to physical isolation.

molecular biology↗

bioRxiv2019

Efficacy of the MEK1/2 inhibitor trametinib in combination with clinically-investigated γ-secretase inhibitors in rhabdomyosarcoma

The childhood muscle cancer rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. In the last 40 years, outcomes for low and intermediate risk patients have improved; however, high risk patients with metastatic disease still have poor overall survival. Differentiation therapy for RMS has been considered a potential clinical approach to halting tumor progression by inducing the terminal myogenic differentiation program, and thus reducing the need for cytotoxic chemotherapy. Both the NOTCH and MEK pathway have been shown to play varying roles in inducing differentiation in RMS cells. Here, we tested several different RMS cell lines harboring varying genetic abnormalities with the MEK inhibitor trametinib alone, and in combination with {gamma}-secretase inhibitors and found no significant effect on cell viability when used together.

cancer biology↗