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Biology subjects

Hunt, H.

Publications and source records attributed to Hunt, H..

6 recordsLinked to original sources

Disease investigation in a New Zealand high-health pig herd reveals a divergent porcine adenovirus

Porcine adenoviruses are common in domestic pigs and are generally regarded as low-pathogenicity viruses associated with mild or subclinical infections. However, their diversity, host associations and disease potential remain poorly understood. Here, we investigated a disease outbreak in an immunologically naive 320-sow high-health hysterectomy-derived pig herd in New Zealand. The outbreak was characterised by anorexia, lethargy, diffuse cutaneous erythema, death in neonatal piglets, and an increased occurrence of mummified fetuses. Histopathological examination of a piglet revealed widespread intranuclear inclusion bodies within endothelial cells, indicative of systemic viral infection. Total RNA sequencing was performed on tissues from an affected piglet and mummified fetuses. Metatranscriptomic analysis identified an abundant adenovirus in multiple piglet and aborted fetus tissues, and de novo assembly recovered a 27,685-nucleotide genome. Phylogenetic analysis placed the virus within the genus Mastadenovirus but it formed a divergent lineage distinct from all previously characterised porcine adenoviruses. Despite sequence divergence, the genome retained the characteristic organisation of mastadenoviruses. Aside from a single detection of porcine kobuvirus identified at low abundance in the small intestine and colon from the piglet, no other viral pathogens were identified. The high viral abundance and systemic tissue distribution observed in both the piglet and fetus, together with the presence of widespread adenoviral inclusion bodies in the piglet, support an association between this novel adenovirus and the disease outbreak. These findings expand the diversity of porcine adenoviruses and suggest that previously unrecognised adenovirus lineages may contribute to reproductive and neonatal disease when introduced into immunologically naive high-health herds.

microbiology↗

TMPRSS2-ERG confers resistance to antiandrogens: mechanism and therapeutic implications

Approximately 50% of prostate cancer (PCa) patients harbor fusions involving the TMPRSS2 and ERG genes. Despite this, tailored therapies targeting the fused gene, tERG, remain undeveloped. Our study analyzed biopsy samples from two clinical trials assessing the efficacies of androgen receptor (AR) signaling inhibitors (ARSIs). The results revealed that tERG promotes resistance to ARSIs and is associated with elevated levels of the glucocorticoid receptor (GR). Subsequent assays showed that GR directly interacts with tERG, alleviates allosteric autoinhibition and prevents chemotherapy-induced tERG degradation. In PCa models, either inhibiting GR or lowering cortisol levels suppressed tumor growth in tERG-positive models, but not in fusion-negative models. In addition, patient-derived fusion-positive xenografts displayed enhanced sensitivity to combined GR and AR inhibitors. Collectively, these findings highlight TMPRSS2-ERG as a new biomarker and propose that simultaneous inhibition of GR and AR may specifically benefit tERG-positine patients. However, GR stimulatory corticosteroid therapies may not be advisable for this patient subgroup.

cancer biology↗

Oral and faecal viromes of New Zealand calves on pasture with an idiopathic ill-thrift syndrome

Since 2015, an idiopathic ill-thrift syndrome featuring diarrhoea and, in some cases, gastrointestinal ulceration has been reported in weaned New Zealand dairy calves. Similar syndromes have been described in the British Isles and Australia, but investigations in New Zealand have yet to identify a specific cause. Notably, the viromes of affected calves remain understudied. We conducted metatranscriptomic analyses of oral and faecal viromes in 11 calves from a dairy farm in Taranaki, New Zealand experiencing an outbreak of this syndrome. This included nine symptomatic calves. Our analysis identified 18 bovine-associated viruses across two DNA and three RNA viral families, including five novel species. Oral viromes were dominated by Pseudocowpox virus, detected in all calves with oral lesions. Faecal viromes were more diverse, featuring adenoviruses, caliciviruses, astroviruses, and picornaviruses. Bovine bopivirus, from the Picornaviridae family and previously unreported in New Zealand, was significantly associated with calves showing oral lesions and diarrhoea, indicating a possible link to disease, though its role remains unclear. The diverse viral communities in the calves complicates identifying a single causative agent. Importantly, no novel viruses were significantly associated with the syndrome, and the viromes closely resembled those found in cattle globally. These findings suggest the syndrome likely has a multifactorial origin involving nutritional, management, and environmental factors rather than being driven primarily by known or novel viruses. Further research across regions and seasons is recommended to clarify the role of viruses in idiopathic ill-thrift among New Zealand calves.

microbiology↗

Differentiating wild and domesticated enset (Musaceae) using phytolith analysis

Enset (Ensete ventricosum, Musaceae) is an important economic crop from Ethiopia which accounts for 20% of the staple diet in Ethiopia today. However, its evolutionary history and spread is poorly understood. Archaeology could provide evidence of past use and contribute to our understanding of its early history, but so far, this has not transpired. Cultivated enset is clonally reproduced and seed production rarely occurs, therefore, looking for seed remains is futile and instead archaeobotanical research should focus on microfossils such as phytoliths. Phytoliths have been shown to be diagnostic for the presence of banana (Musa) and are expected to be similarly useful for identifying enset, but we need a better understanding of phytolith production and variability, and the extent to which this may be used to track domestication. The current study provides a fundamental baseline for the identification of Ensete phytoliths through the examination of phytoliths from leaves and other plant parts based on their size and shape. We consider the differentiation of phytoliths across a single plant, based on location in the leaf, the age of the leaf, and different organs of the plant. We also compare phytoliths in the Musaceae Family, and between the enset cultivar and wild samples. HIGHLIGHTSWe provide the first identification baseline to differentiate wild from domesticated enset by looking at variation across an individual enset plant and comparing these results to phytoliths from wild plants.

plant biology↗

Analysis of companion cell and phloem metabolism using a transcriptome-guided model of Arabidopsis metabolism

Companion cells and sieve elements play an essential role in vascular plants and yet the details of the metabolism that underpins their function remain largely unknown. Here we construct a tissue-scale flux balance analysis (FBA) model to describe the metabolism of phloem loading in a mature Arabidopsis leaf. We explore the potential metabolic interactions between mesophyll cells, companion cells, and sieve elements based on current understanding of the physiology of phloem tissue and through the use of cell-type-specific transcriptome data as a weighting in our model. We find that companion cell chloroplasts likely play a very different role to mesophyll chloroplasts. Our model suggests that, rather than carbon capture, the most crucial function of companion cell chloroplasts is to provide photosynthetically-generated ATP to the cytosol. Additionally, our model predicts that the metabolites imported into the companion cell are not necessarily the same metabolites that are exported in phloem sap; phloem loading is more efficient if certain amino acids are synthesised in the phloem tissue. Surprisingly, in our model predictions the H+-PPiase is the more important contributor than the H+ ATPase to the energisation of the companion cell plasma membrane.

plant biology↗

Ca2+ release via IP3Rs increases RyR mediated Ca2+ spark frequency in ventricular cardiomyocytes without altering spark amplitude and duration

Calcium (Ca2+) plays a critical role in the excitation contraction coupling (ECC) process that governs the contraction of cardiomyocytes during each heartbeat. While ryanodine receptors (RyRs) are the primary Ca2+ channels responsible for mediating cell-wide Ca2+ transients during ECC, Ca2+ release via inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) have been reported to elicit ECC-modulating effects. Recent studies suggest that the proximal localization of IP3Rs at dyads grants their ability to modify the occurrence of Ca2+ sparks (elementary Ca2+ release events that constitute ECC-associated Ca2+ transients) which may underlie the modulatory effects on ECC. Here, we aim to uncover the mechanism by which IP3Rs affect Ca2+ spark dynamics. To this end, we developed a mathematical model of the dyad that incorporates IP3Rs to reveal their impact on local Ca2+ handling and corresponding Ca2+ spark formation. Consistent with published experimental data, our model predicts that the propensity for Ca2+ spark formation increases with IP3R activity. Our simulations support the hypothesis that IP3R activity elevates Ca2+ within the dyad, sensitizing proximal RyRs for future release. However, this lowers Ca2+ in the JSR available for release and thus results in Ca2+ sparks with the same duration but lower amplitudes.

biophysics↗