Biology subjects

Jones, B.

Publications and source records attributed to Jones, B..

At least 19 recordsLinked to original sources

bioRxiv2026

Comparative Distribution of α2,3- and α2,6-Linked Sialic Acid Receptors and Influenza A(H5N1) Virus Binding in Sheep, Goats, and Alpacas

Highly pathogenic avian influenza virus (HPAIV) H5N1 continues to pose a significant threat to animal and human health. Since 2022, an expanded host range has been observed, as illustrated by the H5N1 outbreak in dairy cows. Other minor livestock species, such as sheep, goats, and alpacas, have also tested positive for H5N1 for the first time, raising concerns about its impact on previously overlooked livestock species. In this study, we first characterized the distribution of sialic acid (SA) receptors across respiratory and non-respiratory tissues of sheep, goats, and alpacas using Maackia amurensis (SA 2,3) and Sambucus nigra (SA 2,6) lectins. We found that both SA receptors are present in all tissues across species, with notable differences in their distribution and abundance. Next, we developed recombinant LPAIV H5N1 viruses over a laboratory-adapted backbone to evaluate tissue-specific virus binding profiles. The results show that a representative H5N1 virus from clade 2.3.4.4b binds effectively to respiratory and non-respiratory tissues across all species. The strongest virus binding was observed in sheep, followed by goats and, lastly, alpacas. Similar binding patterns were observed with an LPAIV version of clade 2.3.4.4b and a Gs/Gd lineage precursor prototype virus. Finally, we show that H1N1 and H3N2 viruses also bind to respiratory tissues of sheep and goats. These findings provide important insights into the potential susceptibility of minor livestock species to HPAIV H5N1 and other influenza subtypes. Our results contribute to a better understanding of influenza tissue tropism across livestock species and its potential implications for zoonotic transmission.

microbiology↗

bioRxiv2026

Environmental drivers of soil virus diversity across UK habitats

Soil viruses are critical members of the soil microbiome, shaping terrestrial ecosystem processes and microbial dynamics. However, the environmental factors governing their landscape-scale biogeography remain poorly characterised. Here, we analysed bulk soil metagenomic data from the UKCEH Countryside Survey across broad habitat classes to identify the key drivers of viral diversity and community assembly in UK soils. We show that soil pH is the primary predictor of both viral species richness and overall community composition, alongside significant contributions from the co-related soil organic matter and broad habitat type. Viral species diversity exhibited a strongly non-linear relationship with pH, peaking in neutral to slightly acidic soils. Viral community dissimilarity strongly correlated with 16S rRNA bacterial community structure across all taxonomic ranks, with the strongest association at ASV-level resolution. Despite high spatial turnover among viral contigs, and significant habitat-specific enrichment of particular anti-phage defence systems, viral lifestyle proxies like integrase gene frequencies showed no habitat-specific variation. Together, our results demonstrate that UK soil viral communities are primarily structured by soil pH and habitat parameters and closely coupled to patterns of bacterial host distribution, providing a baseline for future investigations and monitoring of change.

microbiology↗

bioRxiv2026

Noncoding regulatory mutations contribute to the aberrant gene expression in neuroblastoma

Comprehensive analyses of whole-genome and exome sequencing data from high-risk neuroblastoma tumors have identified relatively few recurrent and clinically actionable protein-coding driver mutations at initial diagnosis. This suggests that noncoding genetic variations that alter regulatory sequences and impact gene expression are important drivers of neuroblastoma tumorigenesis. Allele-specific expression (ASE), which quantifies differences in expression between the two alleles of a gene, is a powerful approach for identifying genes with altered dosage resulting from cis-regulatory variation. In this study, we compared ASE profiles of 156 neuroblastoma patients with 220 adrenal gland tissues from the Genotype-Tissue Expression (GTEx) Project to identify 1,363 neuroblastoma-specific ASE genes. We demonstrated that these genes were enriched for biological processes relevant to neuroblastoma pathogenesis including chromatin remodeling, protein ubiquitination, and sympathetic nervous system development, and were preferentially associated with the adrenergic transcriptional program. To elucidate the genetic mechanism underlying aberrant expression of neuroblastoma-specific ASE genes we integrated our ASE data with somatic copy number alterations (SCNA) and somatic mutation profiles. We observed that although many neuroblastoma specific ASE genes were associated with chromosomal gains and losses, a substantial subset was located within copy-number-neutral genomic regions. These genes showed significant enrichment for noncoding somatic single-nucleotide variants (SNVs) within intronic and distal intergenic neuroblastoma-specific open chromatin regions. Furthermore, functional analyses revealed that many of these SNVs disrupt transcription factor binding sites for GATA3, a core component of the regulatory circuitry that maintains the adrenergic identity of neuroblastoma cells, and neuroblastoma-specific ASE genes harboring such mutations were significantly more likely to belong to the GATA3 regulon than expected by chance. Together, our findings identify novel molecular targets of noncoding regulatory mutations in neuroblastoma and highlight the important yet underappreciated contribution of noncoding genetic variation to neuroblastoma tumorigenesis.

bioinformatics↗

bioRxiv2026

Identification and functional assessment of GPCRs across human adipogenesis

Clinical obesity, defined as the presence of excess adiposity in conjunction with the presence of at least one clinical presentation of disease, remains a significant social and economic burden. Pharmacological weight loss agents based on glucagon-like peptide-1 receptor (GLP-1R) targeting are effective but exhibit significant side-effects leading to cessation of treatment, weight regain and, importantly, re-development of co-morbidities. Adipose tissue, now established as a central mediator of energy balance, endocrine signalling and inflammation, plays a significant role in the protection against metabolic disease onset. Loss of adipose tissue expandability, insulin sensitivity and function is thought to be a pivotal event in the transition to clinical obesity. Targeting adipose tissue dysfunction prior to or following development of metabolic disease remains a key therapeutic strategy either in conjunction with incretin-based weight loss therapy, or as a stand-alone therapy. The recent confirmation of functional glucose-dependent insulinotropic polypeptide receptor (GIPR) in mature adipocytes has led to a significant shift in our mechanistic understanding of dual GLP-1R/GIPR agonists such as tirzepatide, with the addition of adipocyte-specific targeting thought to underpin its clinical superiority to GLP-1R agonism alone. However, the expression, regulation and mechanistic targets of GIPR, and indeed many G protein-coupled receptors (GPCRs), in human adipocytes remains unclear, with adipocyte development being particularly under-studied in this regard. Here we use unbiased transcriptomic analyses of human adipocyte development with high temporal resolution to identify the onset of human GPCR expression, uncovering a previously undocumented surge in expression following adipogenic induction and elegant gene waves throughout adipocyte development that may provide attractive pharmacological targets for adipose tissue dysfunction with or without weight loss. We functionally characterise GIPR, GLP-1 and CALCR/RAMP (Amylin) receptor activation at key differentiation timepoints, and identify a novel amylin response in early adipogenesis, presenting committed adipogenic precursors as a primary target of amylin signalling. HighlightsO_LIComprehensive transcriptomic analysis of human adipogenesis with improved temporal resolution and depth C_LIO_LIIdentification and classification of >150 GPCRs differentially regulated across adipocyte differentiation C_LIO_LIFunctional validation highlighting targeting of adipose stem cells and adipocytes using clinically approved receptor agonists C_LIO_LIGeneration of novel human adipocyte stem cell lines from healthy and obese individuals to drive early target validation and exploration of adipocyte biology with increased pre-clinical power. C_LI SummaryComprehensive temporal RNA sequencing across human adipocyte development with a focus on G-protein coupled receptor expression and activity.

cell biology↗

bioRxiv2026

Opposing GIPR brainstem circuits differentially control feeding behaviour

Central glucose-dependent insulinotropic polypeptide receptor (GIPR) signalling is required for the efficacy of GIP-based obesity therapeutics, yet how distinct subpopulations of GIPR neurons shape appetite remains undefined. Here we show that GIPR neurons in adjacent brainstem nuclei, the area postrema (AP) and nucleus tractus solitarius (NTS), exert opposing control over ingestion. We find GIPRAP neurons dampen post-ingestive satiation, permitting hyperphagia, whereas GIPRNTS neurons are anorectic. In line with this model, we show Gipr expression in AP, but not NTS, neurons is necessary for appetite suppression following GIPR antagonism. Additionally, we reveal that GIPR neurons in the AP and NTS occupy distinct gut-brain circuits, and are differentially sensitive to obesity-driven circuit remodelling. These data offer a framework for understanding how current GIPR agonist and antagonist strategies elicit weight loss.

neuroscience↗

bioRxiv2026

Ontological Analysis of Brain Proteostasis Highlights the Sex-Dependent Trajectory of ApoE Isoform-Specific Regulation

Apolipoprotein E (ApoE) is the strongest genetic predictor of Alzheimers disease (AD) risk, with ApoE4 increasing and ApoE2 decreasing risk relative to ApoE3. Using a global LC-MS proteomic approach, we integrated protein abundance and kinetics in Human-APOE knock-in mice for young (3-month) and aged (18-month) cohorts to quantify the changes in steady-state proteostasis. By mapping 6,052 identified proteins and 3,986 associated turnover rates into ontological groups, we observed that vesicle trafficking and mitochondrial dysregulation occur as early as 3 months in ApoE4 mice accompanied by hyperactive metabolism that eventually reduces with age. In contrast, young and old ApoE2 mice retain similar signatures to ApoE3 mice in metabolic, mitochondrial, cellular regulation, and membrane trafficking ontologies. We found that females had more isoform-induced ontological changes relative to ApoE3, providing insight into sex-dependent vulnerabilities. Our global proteomic approach for ApoE proteostasis crucially unifies independent literature observations while providing turnover kinetics to uncover the underlying mechanism behind abundance changes. Data are available via ProteomeXchange with identifier PXD079261. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=189 SRC="FIGDIR/small/735293v1_ufig2.gif" ALT="Figure 1000"> View larger version (45K): org.highwire.dtl.DTLVardef@28ebfforg.highwire.dtl.DTLVardef@9dc6f2org.highwire.dtl.DTLVardef@704577org.highwire.dtl.DTLVardef@e0b0e2_HPS_FORMAT_FIGEXP M_FIG C_FIG O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/735293v1_ufig1.gif" ALT="Figure 1001"> View larger version (48K): org.highwire.dtl.DTLVardef@17d0474org.highwire.dtl.DTLVardef@af771borg.highwire.dtl.DTLVardef@1b49f67org.highwire.dtl.DTLVardef@14d3aa2_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2026

Coral settlement module designs for scalable reef restoration

The global coral reef crisis has prompted restoration initiatives worldwide. Targeting the coral larval stage is among the most scalable approaches as recruitment operates over large spatial scales. It thus represents one of the best levers for coral population recovery. Active coral larval seeding has shown considerable success, and passive substrate engineering has emerged as a promising complementary strategy. Coral settlement modules featuring helix recesses have increased settlement and survival by up to 80-fold on small experimental units, but whether these results translate to tools deployable at the scale of thousands of units, remains yet an open question. Here, we transferred structural features from successful experimental coral settlement designs into production-ready concrete modules to (i) evaluate coral recruitment on five designs at four reef sites differing in flow regime and coral cover over one year; (ii) compare production-scale performance against experimental clay modules and natural reef substrate; and (iii) identify key parameters for large-scale production. The helix recess geometry of coral settlement modules outperformed the featureless control design approximately 20-fold and exceeded natural reef recruitment at least 3- to 32-fold. The helix features were successfully transferred from experimental clay to production-scale concrete modules, yielding comparable settlement densities when standardized to crevice length, which proved to be the biologically relevant unit of available habitat. Production feasibility was demonstrated by producing 690 modules for deployment on a hybrid reef on the west side of Oahu, Hawaii. The passive coral larval recruitment approach presented here could substantially improve the logistical and economic feasibility of large-scale coral reef restoration. This approach requires neither coral larval rearing, handling, nor coral fragmenting, and is compatible with active larval seeding where genetic diversity or larvae supply are limiting factors. The coral settlement modules can be cast in standardized concrete molds at precast facilities. Modules have demonstrated consistent coral recruitment enhancement across reef environments with contrasting flow and coral cover. Deploying mixed arrays of helix-recess structures with designs offering multi-level complexity and three-dimensional rugosity maximizes outcomes for coral, fish, and invertebrate communities simultaneously. Site selection is the most critical deployment decision and should consider larval supply, hydrodynamics, and substrate stability which drive recruitment outcomes more than design choice alone. The modules offer a range of application potential, ranging from integration into existing coastal infrastructure over stand-alone reef restoration approaches, to substrate-consolidating interconnected arrangements.

ecology↗

bioRxiv2026

A Polymeric Nanoparticle System for the Delivery of CRISPR/Cas9 Components into Arabidopsis Pollen

Efficient and heritable genome editing in plants remains constrained by transformation bottlenecks and reliance on tissue culture-based regeneration. Targeting the male germline offers a promising alternative for DNA-free genome modification. Here, we report a polymeric nanoparticle platform for the delivery of RNA-based CRISPR/Cas9 components into Arabidopsis thaliana pollen, establishing a foundation for sperm transfection-assisted genome editing (STAGE)-like approaches in plants. Poly(2-dimethylaminoethyl methacrylate) (PDMAEMA)-based polyplexes were designed to independently encapsulate Cas9 mRNA and ATTO 550-labeled guide RNA, forming nanoparticles with hydrodynamic diameters of [~]146 nm and condensed cores of 20-30 nm. Following internalization and cytosolic release, Cas9 mRNA translation enabled the nuclear localization of ATTO 550-labeled gRNA, as confirmed by confocal imaging and fluorescence lifetime (TauSense) analysis. Fluorescent signals corresponding to the CRISPR RNPs were detected in both vegetative and sperm cell nuclei, with higher accumulation in the vegetative nucleus. Together, these results demonstrate the feasibility of RNA-mediated delivery and intracellular assembly of CRISPR/Cas9 RNPs in plant male gametophytes. By bypassing tissue culture and DNA integration, this nanoparticle-based approach establishes a framework for a more efficient mechanism for introducing heritable genome modifications in plants. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=91 SRC="FIGDIR/small/733037v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@170f7a5org.highwire.dtl.DTLVardef@1929c6forg.highwire.dtl.DTLVardef@5c4a94org.highwire.dtl.DTLVardef@1243cc8_HPS_FORMAT_FIGEXP M_FIG C_FIG

Plant Biology↗

bioRxiv2026

First Usutu virus detections in wild birds in Scotland, 2025

In summer 2025, several Eurasian Blackbird (Turdus merula) deaths were reported on the Isle of Arran in Scotland. Initial investigation included post-mortem examination, where no diagnosis was achieved. Following Orthoflavivirus and avian paramyxovirus testing, Usutu virus RNA was detected in two Blackbirds by reverse transcription-PCR. Phylogenetic analysis identified Usutu virus Africa 3.2 lineage which clustered closely with existing UK detections, indicating geographic expansion rather than a new incursion. Subsequent surveillance confirmed the presence of several potential mosquito vector species.

microbiology↗

bioRxiv2026

Somatic CRISPR editing of Msh3 mitigates Huntington's disease pathology in mice

Huntingtons disease (HD) is a fatal, dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in Huntingtin (HTT) exon 1. Further progressive CAG repeat expansion occurs in somatic cells, particularly in neurons, and drives the timing of clinical onset. Therefore, therapeutic strategies to slow somatic expansion are predicted to be disease-modifying. Somatic CAG expansion is driven by mismatch repair protein MSH3, a leading therapeutic target supported by human genetic data. To gain insight into the impact of targeting MSH3 at different stages of the disease process we used somatic CRISPR-Cas9 editing to knock out Msh3 in HttQ111 mice at ages of 6, 16, 24 weeks exhibiting progressively increasing somatic expansion. Intervention at all three ages slowed striatal CAG expansion, reduced nuclear huntingtin pathology and suppressed transcriptional dysregulation, with earlier intervention having greater impact. Msh3 knockout also suppressed the production of the exon 1 Htt1a transcript. The results of our study provide important preclinical information relevant to an MSH3 therapeutic in humans that would be expected to impact a subset of cells in the brain, provide insight into the influence of timing of intervention on therapeutic effectiveness and deepen our understanding of how targeting MSH3 could alter the trajectory of HD.

genetics↗

bioRxiv2026

Serum proteomic atlas reveals distinct molecular signatures of lupus nephritis activity, chronicity, and treatment response

Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus (SLE), features heterogeneous renal pathology and reliance on invasive biopsies for diagnosis, prognosis, and treatment selection. Current peripheral clinical markers inadequately capture disease activity and progression. Here, we performed comprehensive serum proteomic profiling of over 5,000 proteins in the large, longitudinal Accelerating Medicines Partnership Rheumatoid Arthritis/SLE cohort of 270 LN patients and 63 healthy controls. Machine learning identified distinct molecular signatures that classified LN versus controls, differentiated histological classes, and delineated activity- and chronicity-associated pathways, including inflammatory cytokine, PI3K/AKT, TGFb, and complement/coagulation pathways. An increase in VSIG4, CD27, HAVCR1, and LAIR1 consistently emerged as top biomarkers across multiple clinical contexts, and early decreases in these markers at 3 months were associated with complete treatment response at 1 year. By resolving coordinated serum protein modules linked to key inflammatory, PI3K/AKT, TGFb, and complement pathways, these signatures mechanistically connect circulating proteomic perturbations to intrarenal immune activation, tissue injury, and repair in LN. These findings demonstrate that serum proteomics reflect complex intrarenal immunopathology and offer a promising noninvasive "liquid biopsy" approach to refine LN classification and guide personalized management, potentially reducing the need for repeated invasive biopsies and improving therapeutic decision-making.

immunology↗

bioRxiv2026

Taxonomic filtering accompanies functional expansion during long-term soil restoration

The restoration of species-rich calcareous grasslands is a critical conservation objective, yet the recovery of the invisible below-ground microbiome remains poorly quantified compared to above-ground vegetation. Using a unique 143-year land-use chronosequence on Salisbury Plain, UK, we investigated the trajectory of ecosystem reassembly across arable, regenerating (23 and 67 years), and ancient grasslands. By integrating vegetation surveys with soil physiochemistry, microbial profiling, and shotgun metagenomics, we identified a profound functional decoupling between floral and edaphic recovery. While vegetation diversity recovered relatively rapidly, approaching saturation within 23-67 years, soil properties exhibited persistent legacy effects and slow convergence. Bacterial richness decreased with restoration age, reflecting a transition from disturbance-adapted copiotrophs in arable soils to a specialised, oligotrophic community in ancient sites. This taxonomic contraction was conversely matched by an expansion in functional potential, driven by the emergence of specific taxa (e.g., Microthrixaceae, Aquihabitans sp.) and metabolic pathways associated with complex carbon cycling and stress tolerance. Crucially, the soil ecosystem did not reach equilibrium even after 67 years, characterised by persistent legacy phosphorus and a slow accumulation of soil organic matter. These findings suggest that passive regeneration alone may be insufficient for full soil functional recovery, and that strategies targeting microbial assembly and long-term carbon dynamics warrant further evaluation.

ecology↗

bioRxiv2026

A multi-omics atlas of human hindbrain development

The human hindbrain controls essential motor and autonomic functions and is the site of neurodevelopmental diseases. Yet, its cellular diversity, developmental trajectories and underlying regulatory logic remain poorly understood. We present a comprehensive multi-omics atlas of human hindbrain development spanning embryonic to adult stages, encompassing 594,817 transcriptomic and 422,568 chromatin-accessibility single-nucleus profiles. This dataset resolved the cellular architecture of hindbrain cellular lineages, and delineated coordinated gene expression, cis-regulatory programs and regulatory grammar guiding their developmental trajectories. By integrating multi-omics data, we discovered context-specific roles of transcription factors across cell types and deciphered the role of HOX genes in driving divergent cellular identity in related lineages. We further leveraged the atlas to contextualize pediatric gliomas to decode how subtle yet coordinated shifts in gene expression context can define oncogenic transformation. Together, this atlas provides a foundational resource for hindbrain biology and establishes a gene-regulatory framework linking development and disease.

neuroscience↗

bioRxiv2026

Trophoblast ferroptosis restricts SARS-CoV-2 spread in the placenta

Prenatal SARS-CoV-2 infection is associated with adverse pregnancy outcomes, but placental mechanisms that restrict viral spread remain unclear. Here we show that SARS-CoV-2 exposure induces ferroptosis-linked iron dysregulation in the placenta as a host defense. Human placentas from early gestation SARS-CoV-2-exposed pregnancies exhibited persistent viral protein expression at term, iron accumulation, disrupted localization of iron transport proteins, and reduced expression of the ferroptosis inhibitor, GPX4. In trophoblast cells and newly generated stem cell-derived trophoblast organoids (SC-TOs) with physiological apical-out polarity, infection with live SARS-CoV-2 Delta variant suppressed expression of iron efflux transporter, ferroportin and ferroptosis inhibitors, GPX4 and PLA2G6, promoting lipid peroxidation and ferroptotic signaling. Sub-lethal pharmacological activation of ferroptosis reduced viral titers in trophoblasts, indicating an antiviral function. Together, these results uncover a new mechanism through which the placenta attempts to restrict SARS-CoV-2 replication. However, this protective response is accompanied by placental iron sequestration, which may compromise maternal-fetal iron transfer and help explain iron deficiency and anemia reported in infants born after prenatal SARS-CoV-2 exposure, highlighting a delicate balance between iron and ferroptosis-mediated protection and damage with implications for pregnancy outcomes.

cell biology↗

bioRxiv2025

The microbial tryptophan metabolite indole acts on the gastrointestinal tract to improve glucose homeostasis by enhancing GLP-1 secretion and L-cell differentiation

Aims/hypothesisGrowing evidence implicates gut microbiota-derived metabolites in metabolic homeostasis. Indole, a microbial tryptophan metabolite, has been reported to enhance Glucagon-like peptide-1 (GLP-1) secretion in vitro, and its derivatives have been inversely associated with risk of type 2 diabetes (T2D). We hypothesised that indole acts via the gastrointestinal tract to modulate glucose homeostasis, and aimed to test this hypothesis using in vitro and in vivo models. MethodsThe acute effects of indole on GLP-1 secretion in vitro, and on glucose tolerance and hormone secretion in mice, were determined. Subsequently, the effects of indole on intestinal epithelial cell fate and L-cell differentiation in murine ileal organoids and in vivo were studied. Finally, the utility of chronic indole administration in a murine model of T2D was explored. ResultsIndole stimulated in vitro GLP-1 secretion in a concentration-dependent manner, and improved acute glucose control in vivo. Additionally, we demonstrate that indole drives enteroendocrine L-cell differentiation in murine ileal organoids, resulting in increased L-cell density and longer-term glucoregulatory benefits in vivo. Finally, sub-chronic indole administration improved glucose tolerance and insulin sensitivity in diabetic mice. Conclusions/interpretationOur findings identify indole as an anti-diabetic molecule that acts on the gut, and raise the possibility of incorporating indole into nutraceutical supplements to aid in the treatment or prevention of T2D. This highlights the importance of gut microbiota-derived metabolites in metabolic health and opens new avenues for developing novel strategies to combat T2D. Research in ContextO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIGut microbiota-derived metabolites play a role in metabolic homeostasis. C_LIO_LIIndole, a microbial tryptophan metabolite, enhances GLP-1 secretion in vitro. C_LIO_LIIndole derivatives are inversely associated with type 2 diabetes (T2D) risk. C_LI What is the key question?O_LIDoes indole act on the gut to modulate glucose homeostasis? C_LI What are the new findings?O_LIIndole stimulates GLP-1 secretion and improves acute glucose control in vivo. C_LIO_LIIndole drives enteroendocrine L-cell differentiation in murine ileal organoids, increasing L-cell density and long-term glucoregulatory benefits. C_LIO_LISub-chronic indole administration improves glucose tolerance and insulin sensitivity in mice with type 2 diabetes, showing the potential of gut microbiota-derived metabolites as therapeutic targets. C_LI How might this impact clinical practice in the foreseeable future?O_LIIndole could be incorporated into nutraceutical supplements for T2D prevention or treatment. C_LI

physiology↗

bioRxiv2025

Enteropancreatic neurons drive the glucoregulatory response to ingested lipid

Enteropancreatic neurons project from the small intestinal wall to the pancreas. Though well positioned to mediate the effects of ingested nutrients on pancreatic function, the metabolic role of these neurons is unclear. Diets rich in olive oil promote weight loss and improve remission rates in patients with T2DM. Here, we show that olive oil improves acute glucose tolerance by stimulating insulin release via neurotensin receptor type 1 (NTSR1)-expressing enteropancreatic neurons. These neurons are necessary for the effects of olive and neurotensin on glucose tolerance, and their activation is sufficient to improve glucose tolerance. These findings suggest a mechanism by which dietary olive oil regulates blood glucose levels and present a novel functional role for enteropancreatic neurons in regulating glucose homeostasis.

physiology↗

bioRxiv2025

Exploring influenza A virus receptor distribution in the lactating mammary gland of domesticated livestock and in human breast tissue.

The spread of the highly pathogenic avian influenza (HPAI) H5N1 virus among dairy cattle illustrates the adaptability of influenza A viruses (IAV) to infect non-traditional species. While IAV-specific sialic acid (SA) receptors have been identified in the mammary glands of dairy cattle, their presence in pigs, sheep, goats, and alpacas has not been studied until now. The zoonotic transmission of HPAI H5N1 to dairy and poultry farm workers during outbreaks raises public health concerns. This study employed lectin histochemistry to examine the mammary glands of livestock and humans. We found that these tissues were rich in SA 2,6-Gal receptors, followed by SA 2,3-Gal receptors, essential for IAV binding. Notably, the A(H5N1) clade 2.3.4.4b virus could bind to mammary tissue from both cattle and pigs. These findings highlight the potential for HPAI H5N1 to infect and spread within the mammary glands of production animals and humans.

immunology↗

bioRxiv2025

HIV-Induced Sialoglycans on Infected Cells Promote Immune Evasion from Myeloid Cell-Mediated Killing

Sialic acid-containing glycans (sialoglycans) on pathological cells interact with Siglecs, glyco-immune checkpoint receptors expressed on myeloid cells such as monocytes and neutrophils. This interaction suppresses the cytotoxic functions of these immune cells. We show that HIV infection reprograms the glycosylation machinery of infected cells to increase the expression of specific sialoglycan ligands for Siglecs-3, -7, and -9. These ligands engage Siglecs on myeloid cells, impairing their ability to target HIV-infected cells. Selective disruption of these interactions using 10-1074-Sia, an HIV-specific antibody conjugated to sialidase--an enzyme that removes sialic acids--significantly enhances monocyte- and neutrophil-mediated killing of HIV-infected cells in autologous assays. Treatment with 10-1074-Sia in humanized mice infected with HIV reduces viral load and decreases inflammation. These findings reveal a novel immune evasion mechanism exploited by HIV to evade myeloid cell immune surveillance and highlight the potential of targeting sialoglycan-Siglec interactions to improve immune clearance of HIV-infected cells.

immunology↗