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Henry, S.

Publications and source records attributed to Henry, S..

16 recordsLinked to original sources
bioRxiv2026

White matter cognition mapping in pediatric cancer survivors: a two-cohort NODDI-Bingham study

Childhood cancer survivors (CS) treated with chemotherapy frequently experience long-term cognitive impairments, commonly referred to as CRCI. Whether these deficits reflect disrupted white matter microstructure, altered relationships between microstructure and cognition, or both remains unclear. Here, we applied the NODDI-Bingham model, which quantifies neurite density (NDI), isotropic free water (ISO), and orientation dispersion along primary (ODIp), secondary (ODIs), and total (ODIt) fiber axes, to characterize biophysically specific white matter microstructure in CS and examine its relationship to cognition. Twenty-one pediatric cancer survivors and 21 age-matched healthy controls (HC) underwent multi-shell diffusion MRI. Voxel-wise NODDI-Bingham analyses were performed within JHU atlas regions. Group differences were tested by ANCOVA, and associations between microstructure and cognition were examined with the NIH Toolbox Crystallized, Fluid, and Early Childhood composites using group-specific regressions. Confirmatory analyses were performed in an age-matched subsample of the HCP (n = 679). Notably, CS showed reduced NDI in the corona radiata, cerebral peduncles, and corpus callosum, with elevated ODIt and ODIp in the middle cerebellar peduncle, pathways that subserve processing speed and interhemispheric integration, cognitive domains among the most vulnerable in CRCI. Group-specific regressions revealed qualitatively different relationships between microstructure and cognition: HC exhibited mixed positive and negative relationships across four of five metrics (138 clusters spanning approximately 305,000 voxels; peak Cohen's d up to 3.00), whereas CS showed a predominantly uniformly negative pattern (67 clusters across 57,000 voxels), with no positive clusters for ISO, ODIt, ODIp, or ODIs, thus highlighting that reduced dispersion and extracellular free water are linked to better cognitive performance in CS. HCP analyses reproduced the HC pattern across all five metrics at proportionally smaller effect sizes, ruling out sample-size effects. NODDI-Bingham identifies two aspects of chemotherapy-related white matter pathology that standard diffusion metrics cannot resolve. First, pediatric cancer survivors show selective elevation of ODIp and ODIt in the cerebellar peduncles and reduced NDI in the corona radiata and corpus callosum, localizing group-level injury to specific fanning and neurite density signatures. Second, whereas in healthy controls white matter shows mixed positive and negative relationships between microstructure and cognition, survivors retain only negative relationships for ODIp and ODIt and a diminished mixed pattern for NDI, such that in the chemotherapy-exposed brain, only reduced neurite density and increased primary-axis fanning relate to cognitive impairment. These findings implicate a biophysically specific restructuring of the relationships between white matter and cognition as a candidate mechanism for CRCI and support NODDI-Bingham as a targeted biomarker panel for monitoring and intervention trials.

neuroscience↗
bioRxiv2026

Intranasal adenovirus type 5 influenza vaccination enhances milk antibody responses and passive transfer to neonatal ferrets

Newborns and infants are particularly vulnerable to influenza, largely due to the immaturity of their immune systems. As such, maternal immunization is a valuable strategy to enhance influenza-neutralizing antibodies in both blood and breast milk, ensuring optimal passive immunity transfer to the infant. In our pregnant and lactating ferret maternal-neonatal model, we evaluated antibody responses to an adenovirus type 5-vectored H1N1 hemagglutinin vaccine delivered enterically, intranasally, or intramuscularly. While all three routes elicited a robust antibody response compared to saline-treated controls, intranasal vaccination significantly increased influenza-specific antibodies in dam serum, upper respiratory tract secretions, and milk, and subsequent transfer to suckling kits. Our results suggest that intranasal immunization was the most effective route for inducing functional influenza-specific antibodies in both dam serum and milk, with efficient passive transfer to suckling kits. Leveraging mucosal immune induction may enhance maternal antibody responses, transfer to offspring, and downstream neonatal protection.

microbiology↗
bioRxiv2026

Engineered mRNA nanostructures expand the design space of mRNA therapeutics through programmable protein expression and immune stimulation

Messenger RNA (mRNA) therapeutics have transformed vaccination and protein replacement strategies, yet efforts to improve their performance have focused largely on sequence engineering, nucleotide modification, and delivery vehicles. Here we show that mRNA function can be controlled by rational design of higher-order RNA architectures. We develop self-assembling mRNA origami (mRNA-OG), a class of unimolecular RNA nanostructures that encode protein-coding sequences within higher-order, programmable, and compact nucleic acid architectures. Using computational design and experimental validation, we demonstrate that mRNA-OG folds into well-defined nanostructures while remaining translationally competent in mammalian cells. Although folded mRNA-OG recruits ribosomes comparably to unfolded constructs, it produces lower protein output, indicating that RNA architecture can directly influence translational efficiency. The compact geometry of mRNA-OG also enhances encapsulation by cationic lipid delivery systems, suggesting a structural route to improved cargo packaging. Beyond its effects on translation, mRNA architecture modulates innate immune recognition. In primary human dendritic cells, folded and unfolded mRNA-OG elicit distinct cytokine programs and differential activation of stress-response pathways, including a modest induction of the integrated stress response that is not fully explained by canonical PKR signaling. Our results establish programmable structure as a new design parameter for mRNA therapeutics that can affect its functionality, delivery properties, and immune sensing.

bioengineering↗
bioRxiv2026

Cognitive Control in Pediatric Cancer Survivors: A task-fMRI study

BackgroundChemotherapy-related cognitive impairment is a well-documented concern among cancer survivors, yet the neural mechanisms underlying deficits in cognitive control remain poorly understood. This study examined group differences in brain activation during a flanker task using functional MRI (fMRI) between chemotherapy-exposed participants and healthy controls. MethodsParticipants (21 survivors (24.9 years old; 71.4 % female; 15 years from diagnosis) and 21 healthy controls (26.7 years old; 61.9 % female) completed a flanker task during fMRI, with congruent and incongruent conditions. Reaction time, accuracy, and Flanker scores were collected. Whole-brain group comparisons were performed for congruent, incongruent, and incongruent > congruent contrasts. Associations between the incongruent > congruent contrast and cognitive performance were examined. ResultsCompared to controls, the Chemo group had longer reaction times in both congruent and incongruent conditions (p < .001) and lower NIH Flanker scores (p = .01), with no differences in accuracy. They showed reduced activation in the bilateral inferior frontal gyri, supplementary motor area, and bilateral caudate, but greater activation in the right inferior temporal and cerebellar regions. The incongruent > congruent contrast correlated with increased activation in the orbitofrontal cortex, inferior temporal gyri, and fusiform gyrus with cognitive performance. ConclusionsChemotherapy-exposed participants showed cognitive control deficits and altered neural activation during a flanker task, indicating disrupted recruitment of frontoparietal and subcortical regions key for conflict processing. These findings improve understanding of neural causes of chemotherapy-related cognitive impairment and may help identify at-risk survivors and guide personalized rehabilitation.

neuroscience↗
bioRxiv2026

Kaposi's Sarcoma-associated herpesvirus uses a novel protein fold to hijack RNA Polymerase II for viral late gene transcription

Herpesviruses, including the oncogenic human pathogen Kaposis Sarcoma-associated herpesvirus (KSHV), rely on cellular RNA Polymerase II (RNAPII) for expression of their protein-coding genes. Late in the lytic cycle, transcription initiation on a subset of KSHV genes depends on ORF24, a viral transcriptional activator that binds to viral late promoters through structural mimicry of a host transcription factor. Here, we present a structure of the N-terminal domain of ORF24, and show that it adopts a novel fold that facilitates direct binding of the RNAPII C-terminal domain (CTD). We further show that ORF24 is highly sensitive to the phosphorylation state of the RNAPII CTD, allowing for selective binding of the hypophosphorylated form to viral preinitiation complexes. By combining promoter binding and polymerase recruitment into a single protein, KSHV has streamlined essential steps in transcription complex assembly. Our work lays the groundwork for mechanistic dissection of a viral preinitiation complex.

microbiology↗
bioRxiv2025

FMO4 drives lung adenocarcinoma by stabilizing the MAT2A/MAT2B complex and hindering ferroptosis

Lung cancer is the leading cause of death by cancer in the world and finding new targets is a major medical need to tackle this disease. Here, upon proteomic analysis to identify common players in oncogenic EGFR- and KRAS-driven lung adenocarcinoma mouse models, we uncovered a largely unknown protein in cancer, flavin-containing monooxygenase 4 (FMO4), whose expression was increased in lung tumors compared with adjacent lung tissue. FMO4 expression was strongly increased also in lung cancer samples from patients compared with healthy lung, and its expression level was inversely correlated with overall survival. Remarkably, in vivo deletion of FMO4 greatly decreased tumor burden and increased survival in oncogenic KRAS-driven lung adenocarcinoma mice unveiling its crucial role in tumor biology. Mechanistically, we found that FMO4 loss of function promotes ferroptosis and cooperates with ferroptosis inducers in vitro and in vivo. Moreover, FMO4 facilitates the interaction between MAT2A and MAT2B, promoting the generation of cysteine from methionine, which in turn boosts the generation of glutathione, thus protecting lung adenocarcinoma against ferroptosis. In summary we identified a new target in lung adenocarcinoma with important implications in cancer biology.

cancer biology↗
bioRxiv2025

Transient Acute Neuronal Activation Response Caused by High Concentrations of Oligonucleotides in the Cerebral Spinal Fluid

Oligonucleotide (ON) therapeutics are promising as a disease-modifying therapy for central nervous system disorders. Intrathecal ON administration into the cerebral spinal fluid is a safe and effective delivery mode to the CNS. However, preclinical studies have shown acute toxicities following high-dose central ON delivery. Here we characterize a transient neurobehavioral change peaking 15 minutes after ON dosing and resolving after 120 minutes. Symptoms include shaking, muscle twitching, cramping, hyperactivity, stereotypic movements, hyperreactivity, vocalizations, tremors, convulsions, and seizures. These are collectively referred here as the acute neuronal activation response. Acute neuronal activation is observed in rats, mice, and non-human primates and is quantifiable using a simple scoring system. It is distinct from acute sedation seen with some phosphorothioate-modified antisense oligonucleotides, characterized by loss of spinal reflexes, ataxia, and sedation. The acute neuronal activation response is largely sequence-independent and is driven by ON chelation of divalent cations, particularly influenced by the divalent cations-to-ON ratio in the dosing solution. Acute neuronal activation can be safely mitigated by adjusting this ratio through magnesium supplementation in the ON formulation. We provide a comprehensive framework for quantifying and mitigating the acute neuronal activation response caused by high concentrations of centrally delivered ON therapeutics in preclinical species. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/638138v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@b18796org.highwire.dtl.DTLVardef@13c9898org.highwire.dtl.DTLVardef@1463019org.highwire.dtl.DTLVardef@ffe719_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗
bioRxiv2024

Host response during unresolved urinary tract infection alters mammary tissue homeostasis through collagen deposition and TIMP1

Exposure to pathogens throughout a lifetime influences immunity and organ function. Here, we explored how the systemic host-response to bacterial urinary tract infection (UTI) induces tissue-specific alterations to the mammary gland. Utilizing a combination of histological tissue analysis, single cell RNA sequencing and flow cytometry, we identified that mammary tissue from UTI-bearing mice display collagen deposition, enlarged ductal structures, ductal hyperplasia with atypical epithelial transcriptomes and altered immune composition. Bacterial cells were absent in the mammary tissue and blood of UTI-bearing mice, therefore, alterations to the distal mammary tissue were mediated by the systemic host response to local infection. Furthermore, broad spectrum antibiotic treatment resolved the infection and restored mammary cellular and tissue homeostasis. Systemically, unresolved UTI correlated with increased plasma levels of the metalloproteinase inhibitor, TIMP1, which controls extracellular matrix (ECM) remodeling and neutrophil function. Treatment of nulliparous and post-lactation UTI-bearing female mice with a TIMP1 neutralizing antibody, or broad-spectrum antibiotic, prevented mammary collagen deposition, thus providing evidence for an unexpected link between the systemic host response during UTI and mammary alterations. SummaryThe systemic response during urinary tract infection induces TIMP1-driven collagen deposition specifically into the mammary gland.

developmental biology↗
bioRxiv2024

Background food influences rate of encounter and efficacy of rodenticides in wild house mice

O_LIBaiting is widely used in wildlife management for various purposes, including lethal control, fertility control, disease and parasite control, and conditioned aversion programs for many invasive vertebrate species. The efficacy of baiting programs relies on the likelihood that target animals will encounter the bait, consume it, and receive an appropriate dose of the active ingredient. However, there has been little focus on encounter rate of toxic baits combined with behavioural aversion, which are likely to be significant factors affecting efficacy. C_LIO_LIThe likelihood of an animal encountering and consuming a toxic grain bait should theoretically increase in proportion to its availability relative to background food quantity if it is neither more or less detectable or palatable. Furthermore, the probability of consuming toxic baits might also be influenced by bait aversion following ingestion of a non-lethal dose of toxin. C_LIO_LIUsing a model system of wild house mice (Mus musculus L.) in mouse-proof enclosures in Australia, we manipulated background food, applied zinc phosphide (ZnP) baits and measured the mortality of mice. When background food was scarce, mouse mortality was high, whereas an increasing abundance of background food led to reduced mortality. A scenario modelling random encounters and including bait aversion explained 78% of the variation in observed mortality outcomes and achieved a closer fit to the data. Mortality rates were predicted to be higher with a higher strength bait which overcomes behavioural aversion. C_LIO_LIEnsuring that animals locate and consume a lethal dose of toxic bait is a critical factor for successful bait delivery and efficacy. This is particularly significant in toxic baiting programs, where sublethal doses can make animals feel sick, leading to a negative association with the bait, and the development of aversion. C_LIO_LISynthesis and applications: Our findings explain why some toxic baiting programs might fail. To achieve successful control, efforts should be directed at reducing the availability of background food to increase the probability of encounter and uptake of toxic baits. It is important to measure and understand the role of background food on toxic baiting programs to explain variable outcomes and inform strategies for successful bait delivery. C_LI Graphical abstractOur findings explain why some toxic baiting programs might fail. To achieve successful control, efforts should be directed at reducing the availability of background food to increase the probability of encounter and uptake of toxic baits. It is important to measure and understand the role of background food on toxic baiting programs to explain variable outcomes and inform strategies for successful bait delivery. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/573962v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@df4b66org.highwire.dtl.DTLVardef@1cf1910org.highwire.dtl.DTLVardef@17680eeorg.highwire.dtl.DTLVardef@10ac688_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗
bioRxiv2023

Tuft cell-derived acetylcholine is an effector of type 2 immunity and directly targets helminth parasites in the gut lumen

Upon parasitic helminth infection, activated intestinal tuft cells secrete IL-25, which initiates a type 2 immune response during which lamina propria ILC2s produce IL-13. This causes epithelial remodelling, including tuft cell hyperplasia with an unknown function. We describe a novel cholinergic effector function of tuft cells, which we show are the only epithelial cells expressing Choline Acetyltransferase (ChAT). During parasite infections, mice with epithelial-specific deletion of ChAT have increased worm burden and faecal egg counts although they are able to mount a comparable type 2 immune response. Mechanistically, IL-13-amplified tuft cells release acetylcholine (ACh) into the gut lumen. We demonstrate a direct effect of ACh on worms, reducing their viability and fecundity via helminth muscarinic ACh receptors, with effects promoted by inhibition of acetylcholinesterase, an helminth-secreted enzyme. Thus, tuft cells are sentinels in naive mice, and their amplification upon helminth infections serves an additional type 2 immune response effector function.

immunology↗
bioRxiv2023

Single-cell transcription mapping of murine and human mammary organoids responses to female hormones

During female adolescence and pregnancy, rising levels of hormones result in a cyclic source of signals that control the development of mammary tissue. While such alterations are well understood from a whole-gland perspective, the alterations that such hormones bring to organoid cultures derived from mammary glands have yet to be fully mapped. This is of special importance given that organoids are considered suitable systems to understand cross species breast development. Here we utilized single-cell transcriptional profiling to delineate responses of murine and human normal breast organoid systems to female hormones across evolutionary distinct species. Collectively, our study represents a molecular atlas of epithelial dynamics in response to estrogen and pregnancy hormones.

developmental biology↗
bioRxiv2023

Improving radio transmitter attachment methods for small mammals through captive trials and field studies

Radio tracking can be used to collect information about animal movement, home range, behaviour and habitat use. Many field studies have fitted radio transmitters to small rodents using permanent nylon cable tie collars and successfully collected movement and fate data. The approach to animal welfare within the context of scientific research prioritises minimising adverse effects on the research animals. While a range of electronically activated release mechanisms exist in radio tracking collars for larger mammals, weight and size restrictions make these unsuitable for smaller animals (< 30 g). Our aim was to identify a radio transmitter model and attachment method of an appropriate size and weight, which would remain attached to a house mouse (Mus musculus) for >20 days to collect movement data and then detach or show signs of detaching after 30 days. Laboratory and field trials established that cable ties with a cotton thread weak-link, using heat shrink to attach a customised radio transmitter worked for wild house mice in agricultural fields. Glue-on methods did not stay attached for long enough to obtain more than a few days tracking data. Short summaryCollecting meaningful radio tracking data for small mammals weighing <30 grams relies on selecting radio transmitter attachment methods suitable for the target species while prioritising animal welfare. Developing a non-permanent radio transmitter attachment for house mice is challenging due to size and weight constraints however, by trialling methods in the laboratory and field we developed a suitable radio collar with an in-built weak-link. Our non-permanent weak-link radio collar is an important improvement on existing permanent radio collars for small mammals.

ecology↗
bioRxiv2021

Acute oral toxicity of zinc phosphide: an assessment for wild house mice in Australia

BACKGROUNDThe efficacy of zinc phosphide (ZnP) for broadacre control of wild house mice in Australia is being reported by growers as increasingly variable. Have mice become less sensitive over time or are they taking a sub-lethal dose and developing aversion? In this laboratory study the sensitivity of groups of wild caught and an outbred laboratory strain of mice was assessed using oral gavage of a range of ZnP concentrations. The willingness of mice to consume ZnP-coated grains was then determined. RESULTSEach mouse group had very similar LD50 values (72 to 79 mg ZnP per kg body weight) which are significantly higher than previously reported. Time to death post-gavage ranged between 2.5 to 48 h. ZnP coated grains (50 g ZnP per kg grain) presented in the absence of alternative food were consumed and 94 percent of wild mice died. Mice provided with alternative food and ZnP coated wheat grains (either 25 or 50 g ZnP per kg grain) consumed toxic and non-toxic grains, and mortality was lower (33 to 55 percent). If a sublethal amount of ZnP coated grain was consumed, aversion occurred mostly in the presence of alternative food. CONCLUSIONSThe sensitivity of wild house mice to ZnP in Australia is significantly lower than previously assumed. Under laboratory conditions ZnP coated grains coated with a new higher dose (50 g ZnP per kg grain) were readily consumed. Consumption of toxic grain occurred when alternative food was available but was decreased. It is important to assess the efficacy of the higher ZnP dose per grain under natural field conditions, especially when background food is low.

ecology↗
bioRxiv2021

Effects of background food on alternative grain uptake and zinc phosphide efficacy in wild house mice

BACKGROUNDHouse mice (Mus musculus) cause significant, ongoing losses to grain crops in Australia, particularly during mouse plagues. Zinc phosphide (ZnP) coated grain is used for control, but with variable success. In a laboratory setting, we tested if mice would (1) switch from consumption of one grain type to another when presented with an alternative, and (2) consume ZnP-treated grains when presented as a choice with a different grain. RESULTSMice readily switched from their background grain to an alternative grain, preferring cereals (wheat or barley) over lentils. Mice readily consumed ZnP-coated barley grains. Their mortality rate was significantly higher (86%, n=30) in the presence of a less-favoured grain (lentils) compared to their mortality rate (47%, n=29; and 53%, n=30) in the presence of a more-favoured grain (wheat and barley, respectively). Mice died between 4-112 h (median = 18 h) after consuming one or more toxic grains. Independent analysis of ZnP-coated grains showed variable toxin loading indicating that consumption of a single grain would not guarantee intake of a lethal dose. There was also a strong and rapid behavioural aversion if mice did not consume a lethal dose on the first night. CONCLUSIONSThe registered dose rate of 25 g ZnP/kg wheat; [~] 1 mg ZnP/grain in Australia needs to be re-evaluated to determine what factors may be contributing to variation in efficacy. Further field research is also required to understand the complex association between ZnP dose, and quantity and quality of background food on efficacy of ZnP baits.

ecology↗
bioRxiv2018

Sexual isolation with and without ecological isolation between sympatric isopods Jaera albifrons and J. praehirsuta

Sexual isolation is often coupled with other barriers, and sexual isolation mechanisms can be intrinsically tied to ecological conditions or natural selection against heterospecific gene flow. The independence and relative strength of sexual isolation are thus difficult to assess. Here we take advantage of a pair of isopod species (Jaera albifrons and J. praehirsuta) that show sexual isolation and coexist in populations where they share the same habitat or not (i.e. without or with ecological isolation). Using no-choice trials and a free-choice experimental population, we estimated the strength of sexual isolation between J. albifrons and J. praehirsuta individuals originating from these different ecological contexts. We found that sexual isolation is strong in presence and absence of ecological isolation, but that it is asymmetric and fails to prevent gene flow entirely. Post-zygotic barriers were low, and there was no sexual isolation within J. praehirsuta across habitats. The J. albifrons / J. praehirsuta species pair thus provides an example where the role of sexual isolation as a barrier to gene flow i) does not depend upon current ecological isolation, ii) seems to have evolved independently of local ecological conditions and hybridization costs, but iii) is unable to complete speciation entirely on its own.

evolutionary biology↗