Biology subjects

Hawkins, K.

Publications and source records attributed to Hawkins, K..

7 recordsLinked to original sources

bioRxiv2026

Chromosome-scale genome assembly of diploid halophyte Thinopyrum bessarabicum excludes J genome from polyploid Thinopyrum ancestry

Wild relatives of wheat harbour genetic diversity essential for improving resilience to climate-driven stresses, yet their deployment is hampered by unresolved evolutionary relationships and the absence of reference genomes. Here we present a chromosome-scale reference genome for Thinopyrum bessarabicum, a diploid halophyte and high-priority donor for wheat salt tolerance breeding. A key unresolved question is whether the diploid J genome contributed directly to the subgenome composition of extant polyploid Thinopyrum species, and which genomic features underpin its exceptional salt tolerance. Using this resource, we show that the diploid J genome of Th. bessarabicum is not represented among the subgenomes of polyploid Thinopyrum species, resolving a long-standing ambiguity in Triticeae genomics. Gene-level resolution of the reciprocal 4/5 chromosomal translocation across six related Triticeae species identifies conserved breakpoint gene pairs, supporting a single ancestral rearrangement. Genome-wide gene content analysis shows that halophytic capacity is underpinned by quantitative expansion of conserved stress-response gene families. Salt tolerance phenotyping validates chromosome 5J as a tolerance locus in both Th. bessarabicum and wheat introgression lines. A physically anchored marker framework and dual-reference skim-sequencing pipeline enable precise megabase-resolution characterisation of Th. bessarabicum introgressions in wheat, providing a genomic foundation for deploying J-genome diversity in crop improvement.

plant biology↗

bioRxiv2025

microRNA-21 promotes dysregulated lipid metabolism and hepatocellular carcinoma

Backgrounds and AimsThe prevalence of hepatocellular carcinoma (HCC) is rising in parallel with increasing obesity and metabolic dysfunction-associated steatohepatitis (MASH). MicroRNAs are key post-transcriptional regulators of gene expression and are attractive targets for HCC therapy. Here we sought to identify and characterize dysregulated microRNAs in MASH-driven HCC (MASH-HCC). Approach and ResultsWe profiled microRNA expression in liver tissue from patients with MASH and/or MASH-HCC and in zebrafish HCC driven by activated {beta}-catenin (ABC), one of the most commonly mutated oncogenes in MASH-HCC. We found significant overlap between dysregulated human and zebrafish miRNAs, including miR-21, which was increasingly upregulated from normal liver to MASH to MASH-HCC. We generated transgenic zebrafish that overexpress or sponge (downregulate) miR-21. We found that miR-21 overexpression caused larval liver overgrowth and increased HCC while miR-21 sponge suppressed {beta}-catenin-driven larval liver overgrowth. By performing histologic and lipidomic analysis, we found that overexpression of miR-21, like ABC, suppressed lipid accumulation in response to a high cholesterol diet and increased accumulation of acylcarnitines. ConclusionsHere we characterize microRNA dysregulation in MASH and MASH-HCC in patients, identify miR-21 as increasingly dysregulated from MASH to MASH-HCC, and delineate the impacts of miR-21 overexpression on lipid metabolism and hepatocarcinogenesis in zebrafish {beta}-catenin-driven HCC. This study shows that miR-21, which is similarly dysregulated in human and zebrafish HCC, promotes lipid metabolic changes that may help drive hepatocarcinogenesis.

cancer biology↗

bioRxiv2025

Multi-year study on the effects of elevated CO2 in mature oaks unravels subtle metabolic adjustments but stable biotic stress resistance

O_LIRising atmospheric CO2 levels are predicted to influence forest health directly and indirectly, yet the long-term effects of elevated CO2 (eCO2) on mature trees in natural ecosystems remain poorly understood. Understanding how eCO2 affects susceptibility to biotic stress and alters leaf metabolism is critical for predicting forest responses to climate change. C_LIO_LIWe examined the effects of eCO2 (+150 ppm) on 180-year-old Quercus robur at the Birmingham Institute of Forest Research (BIFoR) Free Air CO2 Enrichment (FACE) facility. From 2016 (pre-treatment) to 2024 (year 8 of enrichment), we monitored natural powdery mildew infection and insect herbivory, alongside targeted and untargeted metabolomic profiling of leaf material collected across the growing season. C_LIO_LIWhile seasonal patterns and an overall decline in PM and herbivory were observed, no consistent differences in biotic stress incidence emerged due to eCO2. Metabolomic data revealed subtle but widespread shifts, especially in amino acid, CoenzymeA, and redox pathways. C_LIO_LIThese results suggest that although eCO2 drives extensive metabolic changes, it does not alter biotic stress resistance in mature oaks. Instead, eCO2 appears to promote physiological plasticity that may shape future responses to combined environmental stressors. These insights offer a valuable reference point for interpreting long-term ecosystem dynamics. C_LI

plant biology↗

bioRxiv2025

Rejuvenated human amniotic fluid stem cells: a superior source of standardized induced mesenchymal stem cells for enhanced therapeutic applications

Human fetal mesenchymal stem cells (hfMSCs) present advantageous characteristics compared to their adult counterparts and have emerged as potent cells in the field of regenerative medicine. In the context of skeletal regeneration, human amniotic fluid stem cells (AFSCs) have been shown to improve the quality and structure of the bone extracellular matrix in an experimental model of severe osteogenesis imperfecta. However, primary hfMSCs undergo replicative senescence during in vitro expansion, along with a progressive decrease in plasticity and tissue repair potential. To overcome this challenge, we rejuvenated AFSC to pluripotency using non-integrative episomal reprogramming and subsequently re-derived the cells towards the mesoderm to obtain induced MSCs (iMSCs). We found that iMSCs have a slower proliferation rate compared to their parental cell line (40h{+/-}2h vs. 29h{+/-}5h) but retain the multipotency and differentiation potential characteristic of MSCs. Comparative genomic analysis revealed that iMSCs express higher levels of genes involved in maintaining stemness, cell signaling, adhesion and migration, as well as promoting osteoblast differentiation, whilst AFSC expressed higher levels of genes involved in cell proliferation. In addition, iMSCs secrete small extracellular vesicles (iEVs) that have the potential to stimulate fibroblast migration, a key process in tissue repair and wound healing. Together, these data suggest that resetting the epigenetic clock of primary hfMSCs may represent a promising strategy to address the limitations associated with primary cell use and enhance their therapeutic potential.

cell biology↗

bioRxiv2024

Mesoscale Modelling of Fibrin Clots: The Interplay between Rheology and Microstructure at the Gel Point

This study presents a numerical model for incipient fibrin-clot formation that captures characteristic rheological and microstructural features of the clot at the gel point. Using a mesoscale-clustering framework, we evaluate the effect of gel concentration or gel volume fraction and branching on the fractal dimension, the gel time, and the viscoelastic properties of the clots. We show that variations in the gel concentration of our model can reproduce the effect of thrombin in the formation of fibrin clots. In particular, the model reproduces the fractal dimensions dependency on gel concentration and the trends in elasticity and gelation time with varying thrombin concentrations. This approach allows us to accurately recreate the gelation point of fibrin-thrombin gels, highlighting the intricate process of fibrin polymerization and gel network formation. This is critical for applications in the clinical and bioengineering fields where precise control over the gelation process is required.

biophysics↗

bioRxiv2023

Disrupting the interaction between AMBRA1 and DLC1 is a promising therapeutic strategy for neurodegeneration that prevents apoptosis while enhancing autophagy and mitophagy

Activating molecule in Beclin1-regulated autophagy (AMBRA1) has critical roles in autophagy, mitophagy, cell cycle regulation, neurogenesis and apoptosis. Dysregulation of these processes are hallmarks of various neurodegenerative diseases and therefore AMBRA1 represents a potential therapeutic target. The flexibility of its intrinsically disordered regions allows AMBRA1 to undergo conformational changes and thus perform its function as an adaptor protein for various different complexes. Understanding the relevance of these multiple protein-protein interactions will allow us to gain information about which to target pharmacologically. To compare potential AMBRA1 activation strategies we have designed and validated several mutant constructs (ACTA, TAT, WD40 and S1014) in addition to characterising their effects on proliferation, apoptosis, autophagy and mitophagy in SHSY5Y cells. AMBRA1TAT, which is a mutant form of AMBRA1 that cant interact with dynein light chain (DLC)1 at the microtubules, produced the most promising results. Indeed, overexpression of this mutant protected cells against apoptosis and induced autophagy and mitophagy in SHSY5Y cells in addition to enhancing the switch from quiescence to proliferation in mouse neural stem cells. Future studies should focus on designing compounds that inhibit the protein-protein interaction between AMBRA1 and DLC1 and thus have potential to be used as a drug strategy to treat neurodegeneration.

cell biology↗

bioRxiv2018

Cross-fostering in rodents causes region-specific alterations in entorhinal cortical gamma rhythms associated with NMDA receptor dysfunction

There has recently been a large increase in the number of children placed in foster care in the United States and Europe. While this is the least worst scenario for those with a lack of appropriate biological care, it is recognised that these children are exposed to major stressors correlated with behavioural changes, particularly in the realm of social cognition into adulthood. Here we model foster care in rodents: rat pups are removed from their biological mother and placed with a non-genetically related dam. This prevented the entorhinal cortex from generating patterns of gamma rhythms required for normal parahippocampal function relevant to social interaction. These changes correlated with a reduction in NMDA receptor-mediated excitation, and changes in parvalbumin expression in interneurons. These data suggest that early life care delivered by a non-biological parent may disrupt social behaviour but, in contrast, generate neurobiological changes antagonistic to those currently associated with psychosis.\n\nSignificance StatementCross fostering is an effective approach for delineating the effect of environment from genetic influences upon behavior. This involves removal of pups from one mother and transfer to another lactating dam. This manipulation is considered as a mild form of early life stress, producing neurobehavioral changes such as alterations in social interaction. We demonstrate that cross fostering produces changes in the ability of cortical microcircuits to generate oscillatory rhythms, in particular the gamma rhythm, in brain regions important for social cognition. This reduction in gamma rhythmogenesis is related to a reduction in synaptic drive provided by the NMDA receptor. One implication of this work is that the modulation of NMDA receptors offers a potential therapeutic strategy for disorders involving impaired sociability.

neuroscience↗