Biology subjects

Burns, E.

Publications and source records attributed to Burns, E..

9 recordsLinked to original sources

bioRxiv2026

Live-cell, single-molecule imaging resolves the dual nature of mRNA silencing by SARS-CoV-2 Nsp1

SARS-CoV-2 nonstructural protein 1 (Nsp1) is a conserved viral factor that potently silences host transcripts by binding ribosomes. Yet how it acts at the level of individual mRNAs remains unclear, with competing models arguing that Nsp1 blocks translation initiation, stalls ribosome elongation, cleaves mRNA, or does all three. Here, we use Nascent Chain Tracking to quantify in living cells how Nsp1 reshapes mRNA abundance and translation dynamics with single-molecule resolution. Using reporter transcripts that vary in UTR architecture, initiation mode, and open reading frame length, we find that Nsp1 mainly silences our reporter transcripts by reducing their numbers rather than inhibiting initiation. Two routes to Nsp1-mediated mRNA loss are identified, both requiring cap-dependent initiation: an early route acting during or shortly after initiation and a later route associated with downstream translation that depends in part on ZNF598. Together, these two mechanisms make Nsp1 an efficient and robust suppressor of host gene expression. We further find that reporters containing the SARS-CoV-2 UTRs remain susceptible to Nsp1-mediated mRNA loss, but the 5' and 3' UTRs cooperate to increase translation output. Neither viral UTR alone increased translation beyond the host reporter, whereas combining both UTRs substantially enhanced translation in the absence of Nsp1. Together, our results reveal that Nsp1 uses dual, cap-dependent routes to promote mRNA loss across the translation cycle, while the SARS-CoV-2 UTRs provide a cooperative translational advantage rather than robust protection from Nsp1.

molecular biology↗

bioRxiv2026

Why woodiness repeatedly evolves--and disappears

Derived woodiness--the evolution of woody growth from herbaceous ancestors--has arisen hundreds of times across flowering plants, yet the environmental conditions associated with its repeated evolution remain poorly understood. Here, we analyse woodiness evolution in the mustard family (Brassicaceae; ~4,150 species) using a time-calibrated phylogeny of 2,927 species, including 374 of the 385 known woody species, together with global growth-form and climatic niche data. We infer 231 independent origins of woodiness alongside 176 reversals to herbaceousness, indicating that woodiness evolves repeatedly but remains evolutionarily unstable. Although woody species are enriched on islands, most occur on the mainland, where woodiness is consistently associated with drought and reduced frost. Correlated-evolution analyses reveal that drought is associated primarily with the persistence of woodiness, whereas reduced frost is associated with gains of woodiness and increased frost with its loss. These findings identify distinct climatic associations with the gain, persistence, and loss of woody growth forms.

evolutionary biology↗

bioRxiv2026

Tumor context determines ARID1A effects on gastric cancer immunity

The role of ARID1A in cancer immune evasion remains uncertain, with prior studies reaching opposing conclusions. In addition, previous work has shown that the role of ARID1A in cell-autonomous tumorigenesis is context-dependent. Using isogenic murine gastric cancer models, we found that in vivo Arid1a loss in an autochthonous genetically engineered mouse model of gastric cancer conferred T cell-dependent immune evasion, while in vitro deletion did not. Mechanistically, tumor Arid1a loss reprogrammed the tumor microenvironment into an immune desert through suppression of GM-CSF secretion and interferon-{gamma} responsiveness. These changes were not observed when Arid1a was deleted in vitro. In human gastric cancer, an immune-cold phenotype was restricted to ARID1A mutants in the genomically stable subtype, while ARID1A loss in the chromosomal instability subtype was associated with variable immune profiles. These results demonstrate that tumor ARID1A loss does not intrinsically confer pro- or anti-tumor immune properties and instead is determined by tissue context.

cancer biology↗

bioRxiv2025

CISH, a novel intracellular immune checkpoint, in comparison and combination to existing and emerging cancer immune checkpoints

Over the past decade, Immuno-Oncology has largely focused on blocking inhibitory surface receptors like PD-1 to enhance T cell anti-tumor activity. However, intracellular immune checkpoints such as CISH, which function independently of tumor-expressed ligands, offer powerful and previously untapped therapeutic potential. As a downstream regulator of TCR signaling, CISH controls T cell activation, expansion, and neoantigen reactivity. Though historically considered undruggable, recent advances in CRISPR engineering have enabled functional interrogation of these targets. We demonstrate that CISH deletion enhances T cell activation and anti-cancer functions more effectively than other emerging intracellular checkpoints. In CAR-T cells, CISH inactivation significantly increased sensitivity to tumor antigen, enabling robust recognition and killing even at low antigen levels, conditions that often lead to treatment failure with conventional T cell therapies, mirroring antigen escape scenarios seen in solid tumors. Our findings further validate CISH as a potent and druggable intracellular checkpoint capable of boosting anti-tumor T cell responses across diverse cancer types, independent of PD-L1 status. The underlying mechanisms of CISH inhibition may help explain the positive outcomes reported in recent clinical studies of this approach in solid tumor immunotherapy.

cancer biology↗

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

Barley variety Quest exhibits broad-spectrum, moderate quantitative resistance against diverse Xanthomonas translucens pathovar translucens

Barley (Hordeum vulgare subspp. vulgare) is the fourth most widely produced cereal today and is valuable for both animal and human consumption. Bacterial leaf streak (BLS) of barley is caused primarily by X. translucens pv. translucens (Xtt) and can lead to significant yield losses. There are currently no available control methods for BLS pathogens, but there are ongoing efforts to identify and characterize sources of resistance to Xtt in available barley germplasm. These screening projects require field trials which are time-consuming and challenged due to variables introduced by environmental and weather conditions, field conditions and other organisms that may be present. Reliable greenhouse phenotyping techniques are needed to accelerate screening of barley germplasm against more Xtt strains. In this study, we established a rapid greenhouse spray inoculation protocol for pathogen-plant phenotyping. This provides a framework for rapid germplasm screening before time-consuming and limited field nursery trials. Our method confirmed the moderate quantitative resistance phenotype discovered in field trials for the cultivars Quest and Tradition against the Xtt strain CIX95. One week old seedlings of the previously characterized resistant line PI329000 were not resistant relative to the susceptible check line MW14-5371-013. The cultivar Quest then demonstrated moderate quantitative resistance against a diverse panel of Xtt strains. Xtt subgroup did not influence BLS outcomes on tested barley lines. We found evidence to support the hypothesis that the virulence of modern strains is increasing, though this does not improve their ability to cause disease on Quest.

microbiology↗

bioRxiv2020

Global cognitive performance is not influenced by diurnal rhythm

ObjectiveThe human brain is influenced by different biological rhythms, including the daily 24-hour (diurnal) cycle. Past studies have reported evidence of variation in cognitive performance over the course of the day, and of differences in the peak time for cognition in older age. Here, we investigated these questions using two existing longitudinal studies of healthy adults. MethodsTime of neuropsychological battery testing was extracted from study records, and we analyzed cognitive performance measures from 4 domains (Vocabulary, Processing Speed, Fluid Reasoning, and Episodic Memory) in 543 healthy adults between the ages of 20 and 80. Time of day was dichotomized as morning (281 tested before noon), and afternoon (242 tested after noon). ResultsMultivariate analyses controlling for both gender and years of education revealed no significant effect of time of testing (or its interaction with participant age) on cognitive performance. These results suggest that diurnal effects during time periods typically used to test human subjects are unlikely to have a meaningful effect on performance on the neuropsychological tests that are used for standard cognitive assessment. ConclusionThis suggests that the effect of time of day on cognition in the context of aging may not be as ubiquitous as previously suggested, and thus is unlikely to represent a large confound in existing studies of cognition across the adult lifespan.

neuroscience↗

bioRxiv2020

The giant sequoia genome and proliferation of disease resistance genes

The giant sequoia (Sequoiadendron giganteum) of California are massive, long-lived trees that grow along the U.S. Sierra Nevada mountains. As they grow primarily in isolated groves within a narrow range, conservation of existing trees has been a national goal for over 150 years. Genomic data are limited in giant sequoia, and the assembly and annotation of the first giant sequoia genome has been an important goal to allow marker development for restoration and management. Using Illumina and Oxford Nanopore sequencing combined with Dovetail chromosome conformation capture libraries, 8.125 Gbp of sequence was assembled into eleven chromosome-scale scaffolds. This giant sequoia assembly represents the first genome sequenced in the Cupressaceae family, and lays a foundation for using genomic tools to aid in giant sequoia conservation and management. Beyond conservation and management applications, the giant sequoia assembly is a resource for answering questions about the life history of this enigmatic and robust species. Here we provide an example by taking an inventory of the large and complex family of NLR type disease resistance genes.

genomics↗

bioRxiv2019

Reorganisation of complex ciliary flows around regenerating Stentor coeruleus

The phenomenon of ciliary coordination has garnered increasing attention in recent decades, with multiple theories accounting for its emergence in different contexts. The heterotrich ciliate Stentor coeruleus is a unicellular organism which boasts a number of features which present unrivalled opportunities for biophysical studies of cilia coordination. With their cerulean colour and distinctive morphology, these large protists possess a characteristic differentiation between cortical rows of short body cilia used for swimming, and an anterior ring structure of fused oral cilia forming a membranellar band. The oral cilia beat metachronously to produce strong feeding currents. In addition to this complex body plan, Stentor have remarkable regenerative capabilities. Minute fragments of single cells can over the period of hours or days, regenerate independently into new, proportional individuals. Certain environmental perturbations elicit a unique programmed response known as oral regeneration wherein only the membranellar band is shed and a new, ciliated oral primordium formed on the side of the body. Here, we target oral regeneration induced by sucrose-shock to reveal the complex interplay between ciliary restructuring and hydrodynamics in Stentor, which accompanies the complete developmental sequence from band formation, elongation, curling, and migration toward the cell anterior.\n\n\"When the anterior part is open, one may perceive about its Edges a very lively Motion; and when the Polyps presents itself in a certain manner, it discovers, on either side of these edges of its anterior part, somewhat very much resembling the wheels of a little Mill, that move with great velocity.\"\n\nA. Trembley F.R.S describing the membranellar band of Stentor, Phil. Soc. Trans. Royal Society (London), 1744.

biophysics↗