Biology subjects

Johnstone, M.

Publications and source records attributed to Johnstone, M..

8 recordsLinked to original sources

bioRxiv2026

Sublethal exposure to the insecticide chlorantraniliprole does not alter antipredator behaviour in wild field crickets

Pesticide exposure has been proposed as a major driver of global insect declines. Sublethal effects occur when non-fatal pesticide exposure disrupts behaviour or physiology in ways that may reduce survival or reproductive success. However, most evidence for sublethal effects comes from laboratory studies under controlled conditions. We tested whether exposure to a sublethal dose of chlorantraniliprole, a widely used diamide insecticide known for its long environmental persistence, affects antipredator escape behaviours in wild field crickets (Gryllus campestris). Adult crickets were treated with either pesticide or a sham control. They then underwent behavioural tests in the wild. Following a simulated predator attack, we measured two key behaviours: escape speed and subsequent latency to re-emerge from their burrow. We found no consistent effects of pesticide exposure on either behaviour. Re-emergence latency increased over successive days across both groups, while escape speed did not change. Re-emergence latency showed greater individual variability than escape speed. This likely reflects its role as a risk-assessment behaviour, which is more context-dependent than escape speed. Our findings challenge the assumption, largely derived from laboratory assays, that sublethal pesticide exposure universally impairs insect behaviour. Overall, our results underscore the need to integrate environmental context when evaluating pesticide impacts on insect behaviour.

animal behavior and cognition↗

bioRxiv2024

A CONTRIBUTION TO THE ANATOMY OF TWO RARE CETACEAN SPECIES: THE HOURGLASS DOLPHIN (Lagenorhynchus cruciger) AND THE SPECTACLED PORPOISE (Phocoena dioptrica)

The anatomical description of the hourglass dolphin (Lagenorhynchus cruciger) and the spectacled porpoise (Phocoena dioptrica) remains largely unexplored, due to limited specimen availability and preservation challenges. This study employed digital imaging techniques, conventional histology and computed tomography to provide visualisation of anatomical structures for a detailed analysis. We present a comprehensive analysis of the gross macroscopical and microscopical morphology of two hourglass dolphins and four spectacled porpoises. The hourglass dolphins were characterised by their distinctive black and white pigmentation and a hooked dorsal fin, while the spectacled porpoises were defined by their large dorsal fin, lack of a visible rostrum and unique eye markings. Morphometric measurements and skeletal characteristics aligned with the literature, while internal anatomy (organs and systems) were similar to other odontocetes. Although precise lung measurements were challenging, qualitative assessments indicated relatively large lungs for their body size, supporting the "short dive, big lung" hypothesis and suggesting that these species are not deep divers. The spectacled porpoise dorsal fin was uniquely large with a well-developed blood supply; this is hypothesised to act as a thermoregulatory window, helping to manage body heat. Overall, this study provides new data on the anatomy of the hourglass dolphin and spectacled porpoise, contributing insights that may influence future research on these rare species. The findings highlight the importance of anatomical studies in explaining evolutionary relationships within cetaceans and their ecological roles in the Southern Ocean ecosystems.

evolutionary biology↗

bioRxiv2024

The chromatin remodeler DEK promotes proliferation of mammary epithelium and is associated with H3K27me3 epigenetic modifications

The DEK chromatin remodeling protein was previously shown to confer oncogenic phenotypes to human and mouse mammary epithelial cells using in vitro and knockout mouse models. However, its functional role in normal mammary gland epithelium remained unexplored. We developed two novel mouse models to study the role of Dek in normal mammary gland biology in vivo. Mammary gland-specific Dek over-expression in mice resulted in hyperproliferation of cells that visually resembled alveolar cells, and a transcriptional profile that indicated increased expression of cell cycle, mammary stem/progenitor, and lactation-associated genes. Conversely, Dek knockout mice exhibited an alveologenesis or lactation defect, resulting in dramatically reduced pup survival. Analysis of previously published single-cell RNA-sequencing of mouse mammary glands revealed that Dek is most highly expressed in mammary stem cells and alveolar progenitor cells, and to a lesser extent in basal epithelial cells, supporting the observed phenotypes. Mechanistically, we discovered that Dek is a modifier of Ezh2 methyltransferase activity, upregulating the levels of histone H3 trimethylation on lysine 27 (H3K27me3) to control gene transcription. Combined, this work indicates that Dek promotes proliferation of mammary epithelial cells via cell cycle deregulation. Furthermore, we report a novel function for Dek in alveologenesis and histone H3 K27 trimethylation.

developmental biology↗

bioRxiv2024

A High-quality Oxford Nanopore Assembly of the Hourglass Dolphin (Sagmatias cruciger) Genome

The hourglass dolphin (Lagenorhynchus cruciger) is a small cetacean species of the Southern Ocean, with significance to iwi M[a]ori (M[a]ori tribes) of Aotearoa New Zealand as taonga (treasured/valued). Due to the remoteness and difficulty of surveying Antarctic waters, it remains one of the least-studied dolphin species. A recent stranding of an hourglass dolphin represented a rare opportunity to generate a genome assembly as a resource for future study into the conservation and evolutionary biology of this species. In this study, we present a high-quality genome assembly of an hourglass dolphin individual using a single sequencing platform, Oxford Nanopore Technologies, coupled with computationally efficient assembly methods. Our assembly strategy yielded a genome of high contiguity (N50 of 8.07 Mbp) and quality (98.3% BUSCO completeness). Compared to other Delphinoidea reference genomes, this assembly has fewer missing BUSCOs than any except Orcinus orca, more single-copy complete BUSCOs than any except Phocoena sinus, and 20% fewer duplicated BUSCOs than the average Delphinoidea reference genome. This suggests that it is one of the most complete and accurate marine mammal genomes to date. This study showcases the feasibility of a cost-effective mammalian genome assembly method, allowing for genomic data generation outside the traditional confines of academia and/or resource-rich genome assembly hubs, and facilitating the ability to uphold Indigenous data sovereignty. In the future the genome assembly presented here will allow valuable insights into the past population size changes, adaptation, vulnerability to future climate change of the hourglass dolphin and related species.

genomics↗

bioRxiv2021

Long Noncoding RNA RROL Provides Chromatin Scaffold for MYC-WDR82 Interaction to Impact Lipid Metabolism and Tumor Cell Growth in Multiple Myeloma

Long noncoding RNAs (lncRNA) can drive the tumorigenesis and be susceptible to therapeutic intervention. To define the landscape of therapeutically actionable lncRNA dependencies in multiple myeloma (MM), we coupled our extensive lncRNA transcriptomic profile with lncRNA targeted CRISPR interference viability screen and identified RNA Regulator of Lipogenesis (RROL) as a leading lncRNA dependency in MM. RROL shares its origin with the microRNA locus MIR17HG, however supports the proliferation and survival of MM cells in a microRNA- and DROSHA- independent manner. We found that RROL provides a chromatin scaffold for the functional interaction between c-MYC and WDR82 to promote the regulation of the lipogenic pathways via the transcriptional control of the rate-limiting enzyme ACC1 in MM cells. Inhibition of RROL with clinically applicable antisense molecules disrupts its transcriptional and functional activities causing potent anti-tumor effects both in vitro and in vivo in two pre-clinical animal models. This study establishes lncRNA RROL as a therapeutically actionable dependency with a unique mechanism of action in support of myeloma cell growth.

cancer biology↗

bioRxiv2019

Familial t(1;11) translocation is associated with disruption of white matter structural integrity and oligodendrocyte-myelin dysfunction

Although the underlying neurobiology of major mental illness (MMI) remains unknown, emerging evidence implicates a role for oligodendrocyte-myelin abnormalities. Here, we took advantage of a large family carrying a balanced t(1;11) translocation, which substantially increases risk of MMI, to undertake both diffusion tensor imaging (DTI) and cellular studies to evaluate the consequences of the t(1;11) translocation on white matter structural integrity and oligodendrocyte-myelin biology. This translocation disrupts among others the DISC1 gene which plays a crucial role in brain development. We show that translocation-carrying patients display significant disruption in white matter integrity compared to familial controls. At a cellular level, we observe dysregulation of key pathways controlling oligodendrocyte development and morphogenesis in induced pluripotent stem cell (iPSC) case derived oligodendrocytes. This is associated with reduced proliferation and a stunted morphology in vitro. Further, myelin internodes in a humanized mouse model that recapitulates the human translocation as well as after transplantation of t(1;11) oligodendrocyte progenitors were significantly reduced compared to controls. Thus we provide evidence that the t(1;11) translocation has biological effects at both the systems and cellular level that together suggest oligodendrocyte-myelin dysfunction.

neuroscience↗

bioRxiv2018

DISC1 regulates N-Methyl-D-Aspartate receptor dynamics: Abnormalities induced by a Disc1 mutation modelling a translocation linked to major mental illness

The neuromodulatory gene DISC1 is disrupted by a t(1;11) translocation that is highly penetrant for schizophrenia and affective disorders, but how this translocation affects DISC1 function is incompletely understood. N-Methyl-D-Aspartate receptors (NMDAR) play a central role in synaptic plasticity and cognition, and are implicated in the pathophysiology of schizophrenia through genetic and functional studies. We show that the NMDAR subunit GluN2B complexes with DISC1-associated trafficking factor TRAK1, while DISC1 interacts with the GluN1 subunit and regulates dendritic NMDAR motility in cultured mouse neurons. Moreover, in the first mutant mouse that models DISC1 disruption by the translocation, the pool of NMDAR transport vesicles and surface/synaptic NMDAR expression are increased. Since NMDAR cell surface/synaptic expression is tightly regulated to ensure correct function, these changes in the mutant mouse are likely to affect NMDAR signalling and synaptic plasticity. Consistent with these observations, RNASeq analysis of translocation carrier-derived human neurons indicates abnormalities of excitatory synapses and vesicle dynamics. RNASeq analysis of the human neurons also identifies many differentially expressed genes previously highlighted as putative schizophrenia and/or depression risk factors through large-scale genome-wide association and copy number variant studies, indicating that the translocation triggers common disease pathways that are shared with unrelated psychiatric patients. Altogether our findings suggest that translocation-induced disease mechanisms are likely to be relevant to mental illness in general, and that such disease mechanisms include altered NMDAR dynamics and excitatory synapse function. This could contribute to the cognitive disorders displayed by translocation carriers.

neuroscience↗

bioRxiv2018

Association of whole-genome and NETRIN1 signaling pathway-derived polygenic risk scores for Major Depressive Disorder and thalamic radiation white matter microstructure in UK Biobank

BackgroundMajor Depressive Disorder (MDD) is a clinically heterogeneous psychiatric disorder with a polygenic architecture. Genome-wide association studies have identified a number of risk-associated variants across the genome, and growing evidence of NETRIN1 pathway involvement. Stratifying disease risk by genetic variation within the NETRIN1 pathway may provide an important route for identification of disease mechanisms by focusing on a specific process excluding heterogeneous risk-associated variation in other pathways. Here, we sought to investigate whether MDD polygenic risk scores derived from the NETRIN1 signaling pathway (NETRIN1-PRS) and the whole genome excluding NETRIN1 pathway genes (genomic-PRS) were associated with white matter integrity.\n\nMethodsWe used two diffusion tensor imaging measures, fractional anisotropy (FA) and mean diffusivity (MD), in the most up-to-date UK Biobank neuroimaging data release (FA: N = 6,401; MD: N = 6,390).\n\nResultsWe found significantly lower FA in the superior longitudinal fasciculus ({beta} = -0.035, pcorrected = 0.029) and significantly higher MD in a global measure of thalamic radiations ({beta} = 0.029, pcorrected = 0.021), as well as higher MD in the superior ({beta} = 0.034, pcorrected = 0.039) and inferior ({beta} = 0.029, pcorrected = 0.043) longitudinal fasciculus and in the anterior ({beta} = 0.025, pcorrected = 0.046) and superior ({beta} = 0.027, pcorrected = 0.043) thalamic radiation associated with NETRIN1-PRS. Genomic-PRS was also associated with lower FA and higher MD in several tracts.\n\nConclusionsOur findings indicate that variation in the NETRIN1 signaling pathway may confer risk for MDD through effects on thalamic radiation white matter microstructure.

genetics↗