Biology subjects

Payne, J.

Publications and source records attributed to Payne, J..

6 recordsLinked to original sources

bioRxiv2024

Australian Culex annulirostris mosquitoes are competent vectors for Japanese encephalitis virus genotype IV

Japanese encephalitis virus (JEV) is transmitted by Culex species of mosquitoes. In 2022, JEV belonging to a previously unrecognised lineage of genotype IV (GIV) caused a major outbreak of JE in South-eastern Australia, resulting in human cases and affecting piggeries. Cx. annulirostris has previously been implicated as the major vector of JEV in northern Australia where the virus has circulated since its first detection in 1995. Here, we showed that experimental infection of a laboratory colony of Australian Cx. annulirostris with the isolate JEV NSW/22 resulted in a 100% mosquito infection rate, with 87% of mosquito saliva samples testing positive by RT-qPCR at 14 days post-infection. Immunohistochemistry confirmed the presence of a replicating virus in the mosquito midgut and dissemination throughout the body, including the salivary glands. Our results also showed evidence of transovarial transmission of this virus; however, transstadial transmission from the eggs to the adult stage was not found. Comparison with an Indonesian isolate of GIV JEV and previous Australian isolates belonging to genotypes I and II showed that infection with JEV NSW/22 resulted in higher viral titres in the early stage of infection and higher proportions of mosquitoes with JEV-positive saliva, indicating a greater transmission potential compared to other isolates. This study provides compelling experimental evidence that Australian Cx. annulirostris is a highly efficient vector for the 2022 Australian JEV GIV outbreak strain.

microbiology↗

bioRxiv2023

Experienced Meditators Show Multifaceted Attention-Related Differences in Neural Activity

ObjectivesMindfulness meditation (MM) is suggested to improve attention. Research has explored this using the attentional-blink (AB) task, where stimuli are rapidly presented, and a second target stimulus (T2) is often missed if presented [~]300ms after an initial target stimulus (T1). This research showed improved task-accuracy and altered neural activity after an intensive 3-month MM retreat. We tested whether these results replicated in a community sample of typical meditators. MethodsThirty-one mindfulness meditators and 30 non-meditators completed an AB task while electroencephalography (EEG) was recorded. Between-group comparisons were made for task-accuracy, event-related potential activity (posterior-N2 and P3b), theta and alpha oscillatory phase synchronisation to stimuli presentation, and alpha-power. Primary aims examined effects within time windows reported by previous research. Additional exploratory aims assessed effects across broader time windows. ResultsNo differences were detected in task-accuracy or neural activity within our primary hypotheses. However, exploratory analyses showed posterior-N2 and theta phase synchronisation effects indicating meditators prioritised attending to T2 stimuli (p < 0.01). Meditators also showed more alpha-phase synchronisation, and lower alpha-power when processing T2 stimuli (p < 0.025). ConclusionsOur results showed multiple differences in neural activity that suggested enhanced attention in meditators. The neural activity patterns in meditators aligned with theoretical perspectives on activity associated with enhanced cognitive performance. These include enhanced alpha gating mechanisms, increased oscillatory synchronisation to stimuli, and more equal allocation of neural activity across stimuli. However, meditators did not show higher task-accuracy, nor did effects align with our primary hypotheses or previous research. PreregistrationThis study was not preregistered.

neuroscience↗

bioRxiv2022

Meditators probably show increased behaviour-monitoring related neural activity

ObjectivesMindfulness meditation is associated with better attention function. Performance monitoring and error-processing are important aspects of attention. We investigated whether experienced meditators showed different neural activity related to performance monitoring and error-processing. Previous research has produced inconsistent results. This study used more rigorous analyses and a larger sample to resolve the inconsistencies. MethodsWe used electroencephalography (EEG) to measure the error-related negativity (ERN) and error positivity (Pe) following correct and incorrect responses to a Go/Nogo task from 27 experienced meditators and 27 non-meditators. ResultsNo differences were found in the ERN (all p > 0.05). Meditators showed larger global field potentials (GFP) in the Pe after both correct responses and errors, indicating stronger neural responses (p = 0.0190, FDR-p = 0.152, np2 = 0.0951, BFincl = 2.691). This effect did not pass multiple comparison controls. However, single electrode analysis of the Pe did pass multiple comparison controls (p = 0.002, FDR-p = 0.016, np2 = 0.133, BFincl = 220.659). Meditators also showed a significantly larger Pe GFP for errors only, which would have passed multiple comparison controls, but was not a primary analysis (p = 0.0028, np2 = 0.1493, BF10 = 9.999). ConclusionsMeditation may strengthen neural responses related to performance monitoring (measured by the Pe), but not specifically to error monitoring (although measurements of the Pe after errors may be more sensitive to group differences). However, only the single electrode analysis passed multiple comparison controls, while analysis including all electrodes did not, so this conclusion remains tentative.

neuroscience↗

bioRxiv2021

Hepatocyte-specific activity of TSC22D4 triggers progressive NAFLD by impairing mitochondrial function

ObjectiveFibrotic organ responses have recently been identified as long-term complication in diabetes. Indeed, insulin resistance and aberrant hepatic lipid accumulation represent driving features of progressive non-alcoholic fatty liver disease (NAFLD), ranging from simple steatosis and non-alcoholic steatohepatitis (NASH) to fibrosis. Effective pharmacological regimens to stop progressive liver disease are still lacking to-date. MethodsBased on our previous discovery of transforming growth factor beta-like stimulated clone (TSC)22D4 as a key driver of insulin resistance and glucose intolerance in obesity and type 2 diabetes, we generated a TSC22D4-hepatocyte specific knockout line (TSC22D4-HepaKO) and exposed mice to control or NASH diet models. Mechanistic insights were generated by metabolic phenotyping and single cell liver sequencing. ResultsHepatic TSC22D4 expression was significantly correlated with markers of liver disease progression and fibrosis in both murine and human livers. Indeed, hepatic TSC22D4 levels were elevated in human NASH patients as well as in several murine NASH models. Specific genetic deletion of TSC22D4 in hepatocytes led to reduced liver lipid accumulation, improvements in steatosis and inflammation scores and decreased apoptosis in mice. Single cell RNA sequencing revealed a distinct gene signature identifying an upregulation of mitochondrial-related processes. An enrichment of genes involved in the TCA cycle, mitochondrial organization, and triglyceride metabolism underscored the hepatocyte-protective phenotype and overall decreased liver damage as seen in mouse models. ConclusionsTogether, our data uncover a new connection between targeted depletion of TSC22D4 and intrinsic metabolic processes in progressive liver disease. Cell-specific reduction of TSC22D4 improves hepatic steatosis, inflammation and promotes hepatocyte survival thus paving the way for further preclinical therapy developments.

physiology↗

bioRxiv2019

Capillary morphogenesis gene 2 mediates multiple pathways of growth factor-induced angiogenesis by regulating endothelial cell chemotaxis

Pathological angiogenesis contributes to diseases as varied as cancer and corneal neovascularization. The vascular endothelial growth factor (VEGF) - VEGF receptor 2 (KDR/VEGFR2) axis has been the major target for treating pathological angiogenesis. However, VEGF-targeted therapies exhibit reduced efficacy over time, indicating that new therapeutic strategies are needed. Therefore, identifying new targets that mediate angiogenesis is of great importance. Here, we report that one of the anthrax toxin receptors, capillary morphogenesis gene 2 (ANTXR2/CMG2), plays an important role in mediating angiogenesis induced by both bFGF and VEGF. Inhibiting physiological ligand binding to CMG2 results in significant reduction of corneal neovascularization, endothelial tube formation and cell migration. We also report the novel finding that CMG2 mediates angiogenesis by regulating the direction of endothelial chemotactic migration without affecting overall cell motility.

biochemistry↗

bioRxiv2019

Enhancers facilitate the birth of de novo genes and their functional integration into regulatory networks

Regulatory networks control the spatiotemporal gene expression patterns that give rise to and define the individual cell types of multicellular organisms. In eumetazoa, distal regulatory elements called enhancers play a key role in determining the structure of such networks, particularly the wiring diagram of \"who regulates whom.\" Mutations that affect enhancer activity can therefore rewire regulatory networks, potentially causing changes in gene expression that are adaptive. Here, we use whole-tissue and single-cell transcriptomic and chromatin accessibility data from mouse to show that enhancers play an additional role in the evolution of regulatory networks: They facilitate network growth by creating transcriptionally active regions of open chromatin that are conducive to de novo gene evolution. Specifically, our comparative transcriptomic analysis with three other mammalian species shows that young, mouse-specific intergenic open reading frames are preferentially located near enhancers, whereas older open reading frames are not. Mouse-specific intergenic open reading frames that are proximal to enhancers are more highly and stably transcribed than those that are not proximal to enhancers or promoters, and they are transcribed in a limited diversity of cellular contexts. Furthermore, we report several instances of mouse-specific intergenic open reading frames that are proximal to promoters that show evidence of being repurposed enhancers. We also show that open reading frames gradually acquire specific interactions with enhancers over macro-evolutionary timescales, helping integrate new genes into existing regulatory networks. Taken together, our results highlight a dual role of enhancers in expanding and rewiring gene regulatory networks.

evolutionary biology↗