UCVMRESEARCH
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University of Calgary · Veterinary Medicine

This week in research.

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Characterization of subpleural lung tissue patterns in dogs with respiratory distress and myxomatous mitral valve disease — Journal: Unknown — Date: 2026-10-17 — Cohort author: Soren R Boysen Abstract not provided in the data; unable to summarize findings. SCN1A haploinsufficiency disrupts neural progenitor networks and accelerates neurogenesis in human Dravet syndrome forebrain assembloids — Journal: bioRxiv (Cold Spring Harbor Laboratory) — Date: 2026-10-16 — Cohort author: Jeff A. Biernaskie SCN1A expression in ventricular zone progenitors; haploinsufficiency reduces progenitor proliferation and disrupts ventricular zone organization; accelerated maturation increases excitatory neuron production and network hyperexcitability. Germinal center dynamics in the mediastinal lymph node distinguish time-dependent and variant-specific immunity during SARS-CoV-2 secondary exposure — Journal: Research Square — Date: 2026-10-16 — Cohort author: Alyson A. Kelvin Germinal center responses show time- and variant-specific patterns during SARS-CoV-2 secondary exposure; findings illuminate recall-immunity dynamics in mediastinal lymph nodes. Distinct roles of Hsp110 proteins in regulating prion propagation — Journal: bioRxiv (Cold Spring Harbor Laboratory) — Date: 2026-10-16 — Cohort author: Hermann M. Schätzl Apg-1, Apg-2, and Hsp105 have distinct effects on PrPSc propagation; Apg-1 loss reduces PrPSc broadly, Apg-2 loss increases prion seeding, Hsp105 promotes early replication; highlights specialized chaperone roles in mammalian prion dynamics. On the emergence of in silico biology for intervention in living systems — Journal: Research Square — Date: 2026-10-14 — Cohort author: Jeff A. Biernaskie Conceptual framing of in silico biology for designing interventions in living systems; discusses theoretical foundations, model-to-phenotype integration, and translational considerations. Optimized approaches to profile low biomass DNA and RNA virome in the upper respiratory tract of beef cattle — Journal: Animal Microbiome — Date: 2026-10-13 — Cohort author: Nilusha Malmuthuge Preservation and extraction optimization (RNAlater; NucleoSpin Virus kit) yields higher viral DNA/RNA recovery; Kaiju-based classification provides higher-resolution viral taxonomy than Kraken2; method advances URT virome profiling in low-biomass samples. Additional file 1 of Optimized approaches to profile low biomass DNA and RNA virome in the upper respiratory tract of beef cattle — Journal: Figshare — Date: 2026-10-13 — Cohort author: Nilusha Malmuthuge Supplementary material accompanying the beef cattle URT virome study; supports methodological and analytical details. Host-mediated filtering and interspecific associations structure strongyle parasite communities in Sable Island horses — Journal: Journal of Animal Ecology — Date: 2026-10-12 — Cohort author: Jocelyn Poissant Host factors (age, individual identity) explain the majority of variation in parasite prevalence and intensity; environmental factors play a minor role; positive interspecific associations prevail, with negative ties involving Strongylus equinus; end-to-end joint species modeling clarifies host-driven structuring. By the numbers - Journals/venues represented: bioRxiv (2), Research Square (2), Animal Microbiome (1), Figshare (1), Journal of Animal Ecology (1), Unknown (1) - Total works: 8

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Publications this week

8
bioRxiv (Cold Spring Harbor Laboratory)

SCN1A haploinsufficiency disrupts neural progenitor networks and accelerates neurogenesis in human Dravet syndrome forebrain assembloids · doi/link

UCVM authors Jeff A. Biernaskie

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Dravet syndrome is a severe childhood neurological disorder caused mostly due to mutations in the sodium channel gene SCN1A. Although the disorder is widely attributed to dysfunction of inhibitory neurons, growing evidence suggests that disease mechanisms may begin much earlier during brain development. To investigate the developmental consequences of SCN1A haploinsufficiency, we generated patient-derived dorsal-ventral forebrain assembloids that model key features of human corticogenesis. We found that SCN1A was expressed in ventricular zone neural progenitors and that its reduced expression was associated with impaired growth, disrupted ventricular zone organization, and progressive depletion of progenitor populations. We further demonstrated reduced progenitor proliferation and self-renewal, accelerated cell-cycle exit, and premature neuronal differentiation, leading to increased production of excitatory neurons and enhanced network excitability. Single cell transcriptomic analyses revealed reduced cycling radial glial cells, accelerated progenitor maturation, and dysregulation of gap junction and calcium signaling pathways. Following these findings, we examined progenitor calcium activity and found that SCN1A haploinsufficiency disrupted coordinated functional network organization, resulting in reduced recurrent connectivity and fragmentation of functional cellular assemblies. These abnormalities occurred despite preserved intrinsic electrophysiological properties of individual progenitors, indicating a defect in population-level coordination rather than single cell electrophysiology. Together, our findings identify disrupted progenitor communication as an early developmental consequence of SCN1A haploinsufficiency and suggest that abnormalities within neural progenitor populations contribute to altered corticogenesis, excitatory neurogenesis, and circuit hyperexcitability in Dravet syndrome. This work expands current disease models beyond interneuron dysfunction and highlights the developing ventricular zone as a potential therapeutic target.
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bioRxiv (Cold Spring Harbor Laboratory)

Distinct roles of Hsp110 proteins in regulating prion propagation · doi/link

UCVM authors Hermann M. Schätzl

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Prion diseases are fatal, transmissible neurodegenerative disorders characterized by the conformational conversion of the cellular prion protein (PrPC) into its pathogenic isoform PrPSc. Propagation of prions depends on the fragmentation of PrPSc aggregates to generate new seeds. However, the factors regulating this process remain incompletely understood. For yeast prions, Hsp104 that has no mammalian homologue, is firmly established as a disaggregase. Hsp110 has emerged as a potential mediator of protein disaggregation and aggregate remodeling in mammalian cells. Although Hsp110 proteins have been implicated in several protein misfolding disorders, their individual contributions to mammalian prion propagation have not been characterized. In this study, we examined the roles of the three Hsp110 proteins -Apg-1, Apg-2, and Hsp105- in cellular prion infection. CRISPR-generated knockout cell lines were established for each Hsp110 and evaluated for their effect on de novo prion infection. PrPSc accumulation was assessed by immunoblot across serial passages and up to 40 days, and prion seeding activity was quantified using real-time quaking-induced conversion (RT-QuIC). Loss of individual Hsp110s produced distinct effects on prion propagation. Apg-1-deficient cells exhibited strongly reduced levels of PrPSc over all passages analyzed, suggesting a role for Apg-1 in establishing persistent prion infection. Interestingly, prion seeding activity was detectable in later passages. Hsp105-deficient cells displayed reduced PrPSc levels during the early stages, indicating that Hsp105 contributes to early prion replication. In contrast, Apg-2 knockout resulted in high prion seeding activity over all passages analyzed and only slightly reduced PrPSc levels in early passages. Collectively, these findings demonstrate that Hsp110 family members perform distinct functions during early phases of prion infection and establishment of persistent infection. This work provides new insight into the role of molecular chaperones in prion biology and identifies Hsp110 proteins as potential modulators of prion replication and potentially therapeutic targets for protein misfolding diseases.
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Animal Microbiome

Optimized approaches to profile low biomass DNA and RNA virome in the upper respiratory tract of beef cattle · doi/link

UCVM authors Nilusha Malmuthuge

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BACKGROUND: Viruses play a key role in cattle respiratory tract (RT) health, yet, profiling the upper respiratory tract (URT) virome (DNA and RNA viruses) from deep nasopharyngeal swabs (DNS) remains challenging due to their low biomass, lack of well-defined enrichment approaches, and a high proportion of unclassified viral sequences. This study aimed to optimize DNS preservation, nucleic acid extraction, and bioinformatics pipelines to enhance URT virome characterization in beef calves. RESULTS: Three DNS preservation methods were tested (RNAlater, brain heart infusion (BHI) medium/glycerol at -80 °C, and BHI medium/glycerol followed by RNAlater). Three nucleic acid extraction kits (QIAamp Fast DNA Stool Mini Kit, GeneJET Genomic DNA Purification Kit, and mirVana™ miRNA Isolation Kit) were evaluated to compare total nucleic acid yields. Viral DNA and RNA were extracted separately using the NucleoSpin Virus Kit, which was optimized for viral nucleic acid recovery. The DNS samples that preserved in RNAlater and extracted using the NucleoSpin Virus kit generated highest viral DNA (1.35 ± 0.12 µg) and RNA (1.57 ± 0.09 µg) (mean ± SEM) yields for metagenomics sequencing. Metagenomic sequencing and viral taxonomic assignment using Kraken2 and Kaiju, respectively showed that Kaiju allowed maximum exact matches for viral taxonomy assignment and provided high-resolution outputs for the profiling of cattle URT viromes. CONCLUSION: The use of an optimized nucleic acid extraction method and Kaiju-based classification enhanced viral nucleic acid recovery and taxonomic classification from low-biomass DNS samples. The findings highlighted the importance of effective storage conditions and extraction methods in maximizing viral nucleic acid yield, while demonstrating that Kaiju provided more reliable viral taxonomic assignments than Kraken2. These advancements provide a framework for more accurate assessment of the URT virome in cattle and other farm animals, enabling deeper investigation into the roles of viruses in RT health.
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Journal of Animal Ecology

Host‐mediated filtering and interspecific associations structure strongyle parasite communities in Sable Island horses · doi/link

UCVM authors Jocelyn Poissant

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Mixed-species parasite infections are common in wildlife, yet the ecological processes that structure these communities remain poorly understood. We hypothesized that host-mediated and extrinsic environmental filtering, alongside biotic interactions, act concurrently to shape parasite community composition, and that these structuring patterns would depend on parasite traits or evolutionary history. We applied nemabiome DNA metabarcoding to 3147 faecal samples from 916 feral horses with no history of anthelmintic treatment, collected over 10 years as part of a long-term individual-based study on Sable Island, Canada. Using joint species distribution models, we tested whether strongyle parasite communities were structured by host-associated factors, extrinsic environmental variables or interspecific interactions. Host factors, particularly age and individual identity, explained the greatest proportion of variation in both parasite prevalence and infection intensity, indicating strong host-mediated environmental filtering. In contrast, spatial location and year explained minimal variation, suggesting weaker effects of extrinsically mediated environmental filtering. Parasite traits such as body size and gut site preference had limited associations with species' environmental responses. Positive species associations were common, particularly among species occupying the same gut region, suggesting that strong, consistent competitive interactions were not prominently reflected in the residual covariance structure. Negative associations were less frequent but consistently involved Strongylus equinus, indicating potential context-dependent biotic interactions involving this species. By integrating species-level molecular data with hierarchical joint species models, this study quantifies patterns of host-related filtering and species co-variation within a natural parasite community and provides a framework for examining mixed infections in wild systems.
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