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Biology subjects

Baker, P.

Publications and source records attributed to Baker, P..

10 recordsLinked to original sources
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

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↗
bioRxiv2025

A Rapid and Scalable Subcutaneously Administered Murine Thymus Micro-organoid for Generating Functional T cells

Thymic function can decline due to age-related involution, congenital disorders, acute infections, or chemo/radiation therapy. Decline in thymic function leads to decreased T cell production and weakened immunity. To address these thymic insufficiencies, we aimed to develop a transplantable and scalable micro-organoid system utilizing fibroblasts and thymic cells. We have developed a reliable and rapid method to generate thymic micro-organoids using selectively screened fibroblasts and murine thymic cells. The thymic micro-organoids are cryo-preservable, injectable, and give rise to T cells both in vitro and in vivo. Thymic organoids expressed key genes required to sustain T cell development and maturation: ccl25, dll-1, dll-4, foxn-1, il-7, scf. When injected into T cell-deficient Prkdcscid mice, the organoids gave rise to functional {beta}, {psi}8, natural killer T (NKT) cells, and FoxP3+ regulatory T cells. Organoid-derived T cells expressed a diverse T cell receptor (TCR) repertoire in vivo and responded to stimulation with anti-CD3/28, Concanavalin-A, or Phytohemagglutinin. Thymic organoids derived from pmel-1 thymocytes gave rise to V{beta}13+ T cells that delayed the growth of B16 melanoma and enhanced activation of T and NK cells. This approach presents a valuable tool for mechanistic studies and addressing current therapeutic gaps in diseases associated with thymic decline and insufficiencies.

immunology↗
bioRxiv2025

Susceptibility of bovine respiratory and mammary epithelial cells to avian and mammalian derived clade 2.3.4.4b H5N1 highly pathogenic avian influenza viruses

Zoonotic transmission of avian influenza viruses into mammals is relatively rare due to anatomical differences in the respiratory tract between species. Recently, clade 2.3.4.4b highly pathogenic H5N1 avian influenza viruses were detected circulating in North American cattle. Sporadic transmission between cattle, humans, and other animals proximal to cattle or after consuming products from infected cattle has occurred, but thus far there is no evidence of human-to-human transmission. However, the virus has the potential to adapt to the mammalian respiratory tract with every transmission event that occurs, making it crucial to understand cellular and species tropism of the H5N1 2.3.4.4b viruses. We compared viral kinetics of clade 2.3.4.4b viruses isolated from birds and mammals in respiratory epithelial cells derived from cattle, human, swine, and ferret. We found that avian derived viruses could replicate in swine cells only, yet mammalian derived strains could replicate efficiently in all tracheal and nasal epithelial cells tested. Interestingly, only bovine mammary epithelial cells (MEC) and swine respiratory epithelial cells were permissive to both avian and mammalian derived strains, possibly due to increased sialic acid expression on bovine MEC compared to bovine tracheal epithelial cells (TEC). However, sialic acid expression differed between dairy and beef cows: TEC derived from a dairy cow had increased expression of 2,3 sialic acid receptors compared to TEC from a beef-dairy cow cross. This study highlights the ability of clade 2.3.4.4b H5N1 viruses derived from mammals but not wild birds to infect the respiratory epithelium of other mammalian hosts.

microbiology↗
bioRxiv2024

Urban effects on timing and variability of diel activity differ across passerine species and seasons

1. Life on Earth is adapted to rhythmic cycles in environmental conditions throughout the day and year via diel patterns of behavioural activity. 2. Urban conditions can disrupt such behavioural rhythms of activity. However, most studies so far have investigated urban effects on patterns of activity of single species in a single season. Additionally, we know little about the level of between and within-individual variation in urban and non-urban populations, and whether they differ. 3. Here, we use automated radio telemetry to record patterns of daily activity in six passerine species (blackbird, robin, great tit, blue tit, dunnock and chaffinch) across two urban and two forest populations during the pre-breeding and post-breeding season. We investigate urban effects on five activity-related traits: time of activity onset, time of activity end, duration of diurnal activity, level of diurnal activity and level of nocturnal activity. We employ statistical tools that allow us to estimate urban effects on mean phenotypic values, but also quantify urban versus forest differences in between-individual and within-individual phenotypic variation. 4. We found the strongest urban effects on time of activity onset in blackbirds and robins during the pre-breeding season: urban populations of blackbird and robin started their daily activity earlier than their forest counterparts. We did not find this effect in the other species. Urban populations of all species showed higher levels of nocturnal activity than forest populations, but this effect was not offset by lower diurnal activity, suggesting that urban birds may incur higher daily energetic demands. 5. Lastly, our analysis revealed large and consistent differences in variation in the investigated timing traits. Urban birds were more variable between individuals, implying lower population synchronization, and more variable within individuals, implying less consistent behaviour than their forest counterparts. Conversely, activity levels were more variable in forest birds. 6. We conclude that, for birds, urban life is associated with less rest, less consistency, and lower synchronicity, but that effect sizes depend on species and time of the year. Our results warn against generalising the effects of urbanisation on daily rhythms of birds, and call for future studies to understand the mechanisms behind species and seasonal differences.

animal behavior and cognition↗
bioRxiv2023

Dopamine neurons govern olfactory-gated infant begging behavior

Altricial young of many species beg parents for the nutrients required for healthy development. From human crying to begging chicks, young expend precious energy reserves to communicate their hunger. Despite repeated independent evolutionary origins, the neural basis of parent-directed communication by infants is unknown. Here, we examined the sensory and neural basis of begging behavior in tadpoles of the monogamous and biparental Mimetic poison frog (Ranitomeya imitator). In this species, tadpoles beg parents for egg meals by dancing. We used this robust motor display to determine that tadpoles use multimodal cues for caregiver recognition, where olfactory cues are necessary for caregiver recognition while visual cues provide an orientation goal. We found that dopamine related brain regions have higher neural activity in begging tadpoles and that dopamine signaling had opposing modulatory effects through D1 and D2 family receptors, similar to swimming behavior in other tadpole species. We then identified caudal posterior tuberculum dopamine neurons as more active during begging behavior and sensitive to caregiver olfactory cues. Projections of these dopaminergic neurons to the spinal accessory motor nucleus are required for begging displays. These findings support the idea that dopamine regulates olfactory-guided parental recognition in young and opens many avenues for studying how new communication behaviors can evolve from ancestral motor circuits.

neuroscience↗
bioRxiv2023

A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain

The mammalian brain is composed of millions to billions of cells that are organized into numerous cell types with specific spatial distribution patterns and structural and functional properties. An essential step towards understanding brain function is to obtain a parts list, i.e., a catalog of cell types, of the brain. Here, we report a comprehensive and high-resolution transcriptomic and spatial cell type atlas for the whole adult mouse brain. The cell type atlas was created based on the combination of two single-cell-level, whole-brain-scale datasets: a single- cell RNA-sequencing (scRNA-seq) dataset of [~]7 million cells profiled, and a spatially resolved transcriptomic dataset of [~]4.3 million cells using MERFISH. The atlas is hierarchically organized into five nested levels of classification: 7 divisions, 32 classes, 306 subclasses, 1,045 supertypes and 5,200 clusters. We systematically analyzed the neuronal, non-neuronal, and immature neuronal cell types across the brain and identified a high degree of correspondence between transcriptomic identity and spatial specificity for each cell type. The results reveal unique features of cell type organization in different brain regions, in particular, a dichotomy between the dorsal and ventral parts of the brain: the dorsal part contains relatively fewer yet highly divergent neuronal types, whereas the ventral part contains more numerous neuronal types that are more closely related to each other. We also systematically characterized cell-type specific expression of neurotransmitters, neuropeptides, and transcription factors. The study uncovered extraordinary diversity and heterogeneity in neurotransmitter and neuropeptide expression and co-expression patterns in different cell types across the brain, suggesting they mediate a myriad of modes of intercellular communications. Finally, we found that transcription factors are major determinants of cell type classification in the adult mouse brain and identified a combinatorial transcription factor code that defines cell types across all parts of the brain. The whole-mouse-brain transcriptomic and spatial cell type atlas establishes a benchmark reference atlas and a foundational resource for deep and integrative investigations of cell type and circuit function, development, and evolution of the mammalian brain.

neuroscience↗
bioRxiv2022

Distinct types of multicellular aggregates in Pseudomonas aeruginosa liquid cultures

Pseudomonas aeruginosa forms suspended multicellular aggregates when cultured in liquid media. Such aggregates may be important in disease, and/or as a pathway to biofilm formation. The polysaccharide Psl and extracellular DNA (eDNA) have both been implicated in aggregation, but previous results depend strongly on the experimental conditions. Here we develop a quantitative microscopy-based method for assessing changes in the size distribution of suspended aggregates over time in growing cultures. For exponentially growing cultures of P. aeruginosa PAO1, we find that aggregation is mediated by cell-associated Psl, rather than by either eDNA or se-creted Psl. These aggregates arise de novo within the culture via a growth process that involves both collisions and clonal growth. They are "non-cheatable" since Psl non-producing cells do not aggregate with producers. In contrast, we find that stationary phase (overnight) cultures contain a different type of multicelullar aggregate, in which both eDNA and Psl mediate cohesion. Our findings suggest that the physical and bi-ological properties of multicellular aggregates may be very different in early-stage vs late-stage bacterial cultures.

microbiology↗
bioRxiv2017

Microbial glycoside hydrolases as antibiofilm agents with cross-kingdom activity

Galactosaminogalactan and Pel are cationic heteropolysaccharides produced by the opportunistic pathogens, Aspergillus fumigatus and Pseudomonas aeruginosa, respectively. These exopolysaccharides both contain 1,4-linked N-acetyl-D-galactosamine and play an important role in biofilm formation by these organisms. Proteins containing glycoside hydrolase domains have recently been identified within the biosynthetic pathway of each exopolysaccharide. Recombinant hydrolase domains from these proteins (Sph3h from A. fumigatus and PelAh from P. aeruginosa) were found to degrade their respective polysaccharides in vitro. We therefore hypothesized that these glycoside hydrolases could exhibit anti-biofilm activity, and further, given the chemical similarity between galactosaminogalactan and Pel, that they might display cross-species activity. Treatment of A. fumigatus with Sph3h disrupted A. fumigatus biofilms with an EC50 of 0.4 nM. PelAh treatment also disrupted pre-formed A. fumigatus biofilms with EC50 values similar to those obtained for Sph3h. In contrast, Sph3h was unable to disrupt P. aeruginosa Pel-based biofilms, despite being able to bind to the exopolysaccharide. Treatment of A. fumigatus hyphae with either Sph3h or PelAh significantly enhanced the activity of the antifungals posaconazole, amphotericin B and caspofungin, likely through increasing antifungal penetration of hyphae. Both enzymes were non-cytotoxic and protected A549 pulmonary epithelial cells from A. fumigatus-induced cell damage for up to 24 hours. Intratracheal administration of Sph3h was well tolerated, and reduced pulmonary fungal burden in a neutropenic mouse model of invasive aspergillosis. These findings suggest that glycoside hydrolases can exhibit activity against diverse microorganisms and may be useful as therapeutic agents by degrading biofilms and attenuating virulence.\n\nSignificanceThe production of biofilms is an important strategy used by both bacteria and fungi to colonize surfaces and to enhance resistance to killing by immune cells and antimicrobial agents. We demonstrate that glycoside hydrolases derived from the opportunistic fungus Aspergillus fumigatus and Gram-negative bacterium Pseudomonas aeruginosa can be exploited to disrupt pre-formed fungal biofilms and reduce virulence. Additionally, these glycoside hydrolases can be utilized to potentiate antifungal drugs by increasing their hyphal penetration, to protect human cells from fungal-induced injury and to attenuate virulence of A. fumigatus in a mouse model of invasive aspergillosis. The findings of this study identify recombinant microbial glycoside hydrolases as promising therapeutics with the potential for anti-biofilm activity against pathogens across different taxonomic kingdoms.

microbiology↗