Biology subjects

Smith, D. W.

Publications and source records attributed to Smith, D. W..

12 recordsLinked to original sources

bioRxiv2024

Aging disrupts blood-brain and blood-spinal cord barrier homeostasis, but does not increase paracellular permeability

3Blood-CNS barriers protect the CNS from circulating immune cells and damaging molecules. It is thought barrier integrity becomes disrupted with aging, contributing to impaired CNS function. Using genome-wide and targeted molecular approaches, we found aging affected expression of predominantly immune invasion and pericyte-related genes in most CNS regions investigated, especially after middle age, with spinal cord being most impacted. We did not find significant perturbation of tight junction genes, nor were vascular density or pericyte coverage affected by aging. We evaluated barrier paracellular permeability using small molecular weight tracers, serum protein extravasation, CNS water content, and iron labelling measures. We found no evidence for age-related increased barrier permeability in any of these tests. We conclude that blood-brain (BBB) and blood-spinal cord barrier (BSCB) paracellular permeability does not increase with normal aging in mouse. Whilst expression changes were not associated with increased permeability, they may represent an age-related primed state whereby additional insults cause increased leakiness.

neuroscience↗

bioRxiv2022

Host network-based discovery of critical regulators of innate immunity, virus growth, and pathogenesis in influenza virus infection

Innate immunity is protective against viruses, but also can facilitate pathological infection responses. Despite intensive research, our understanding of the mechanisms that regulate innate immunity in virus infection remains incomplete. Systems biology-based data-driven modeling approaches hold substantial promise toward discovery of crucial innate immune signaling regulators, yet model-derived predictions are almost completely unexplored. Here, we carried out systematic experimental validation of candidate regulators predicted by a transcriptional association network model of influenza virus-infected cells. We identified dozens of novel innate immune signaling regulators with potent effects on the replication of influenza and other viruses, and importantly, we established the biological relevance of a validated regulator in vivo. Collectively, these findings aid in clarifying mechanisms of influenza virus pathogenicity and might lead to innovative approaches for treating influenza virus disease. Similar data-driven modeling strategies may be applicable for the study of other pathogen systems or immunological disorders.

microbiology↗

bioRxiv2022

Density-dependent habitat selection alters drivers of population distribution in northern Yellowstone elk

Although it is well established that density dependence drives changes in organismal abundance over time, relatively little is known about how density dependence affects variation in abundance over space. We tested the hypothesis that spatial tradeoffs between food and safety can change the drivers of population distribution, caused by opposing patterns of density-dependent habitat selection (DDHS) that are predicted by the multidimensional ideal free distribution. We addressed this using winter aerial survey data of northern Yellowstone elk (Cervus canadensis) spanning four decades. Supporting our hypothesis, we found positive DDHS for food (herbaceous biomass) and negative DDHS for safety (openness and roughness), such that the primary driver of habitat selection switched from food to safety as elk density decreased from 9.3 to 2.0 elk/km2. Our results demonstrate how population density can drive landscape-level shifts in population distribution, confounding habitat selection inference and prediction, and potentially affecting community-level interactions.

ecology↗

bioRxiv2022

Investigating tri-trophic interactions using bio-energetic demographic models

A central debate in ecology has been the long running discussion on the role of apex predators in affecting the abundance and dynamics of their prey. In terrestrial systems, research has primarily relied on correlational approaches, due to the challenge of implementing robust experiments with replication and appropriate controls. A consequence of this is that we largely suffer from a lack of mechanistic understanding of the population dynamics of interacting species that can be surprisingly complex. Mechanistic models offer an opportunity to examine the causes and consequences of some of this complexity. We present a bioenergetic mechanistic model of a tri-trophic system where the primary vegetation resource follows a seasonal growth function, and the herbivore and carnivore species are modelled using two integral projection models (IPMs) with body mass as the phenotypic trait. Within each IPM, the demographic functions are structured according to bioenergetic principles, describing how animals acquire and transform resources into body mass, energy reserves and breeding potential. We parameterise this model to reproduce the population dynamics of grass, elk and wolves in northern Yellowstone (USA), and investigate the impact of wolf reintroduction on the system. Our model generated predictions that closely matched the observed population sizes of elk and wolf in Yellowstone prior to and post wolf reintroduction. The introduction of wolves into our basal grass-elk bioenergetic model resulted in a population of 99 wolves, and a reduction in elk numbers by 61% (from 14,948 to 5,823) at equilibrium. In turn, vegetation biomass increased by approximately 25% in the growing season and more than 3-fold in the non-growing season. The addition of wolves to the model caused the elk population to shift from being food-limited to being predator-limited, and had a stabilising effect on elk numbers across different years. Wolf predation also led to a shift in the phenotypic composition of the elk population, via a small increase in elk average body mass. Our model represents a novel approach to the study of predator-prey interactions. Explicitly considering and linking bioenergetics, population demography and body mass phenotypes can provide novel insights into the mechanisms behind complex ecosystem processes.

ecology↗

bioRxiv2022

High retention of genomic variation and fitness-related traits in the effective population of reintroduced wolves in Yellowstone National Park

Cooperatively breeding species exhibit numerous strategies to avoid mating with close relatives, inherently reducing effective population size. For species of management concern, accurate estimates of inbreeding and trait depression are crucial for the species future. We utilized genomic and pedigree data for Yellowstone National Park gray wolves to investigate the contributions of foundation stock lineages, genetic architecture of the effective population, and putative fitness consequences of inbreeding. Our dataset spans 25 years and seven generations since reintroduction, encompassing 152 nuclear families and 329 litters. We found over 87% of the pedigree foundation genomes persisted and report influxes of allelic diversity from two translocated wolves from a divergent source in Montana. As expected for group-living species, mean kinship significantly increased over time, although we found high retention of genetic variation. Strikingly, the effective population carried a significantly lower level of genome-wide inbreeding coefficients and autozygosity with shorter decays for linkage disequilibrium relative to the non-breeding population. Lifespan and heterozygosity were higher in the effective population, although individuals who had their first litter at an older age also had higher inbreeding coefficients. Our findings highlight genetic contributions to fitness, and the importance of effective population size and gene flow to counteract loss of genetic variation in a wild, free-ranging social carnivore. It is crucial for managers to mitigate factors that significantly reduce effective population size and genetic connectivity, which supports the dispersion of genetic variation that aids in rapid evolutionary responses to environmental challenges.

evolutionary biology↗

bioRxiv2021

Breeding displacement in gray wolves (Canis lupus): Three males usurp breeding position and pup rearing from a neighboring pack in Yellowstone National Park

Gray Wolves (Canis lupus) are territorial, group living carnivores that live in packs typically consisting of a dominant breeding pair and their offspring. Breeding tenures are relatively short and competitive, with vacancies usually occurring following a breeders death, and are often filled by unrelated immigrants or by relatives of the previous breeder. The frequency and conditions of active breeder displacements are poorly understood. Position changes in the dominance hierarchy are common yet rarely documented in detail. We describe a turnover in male breeding position in a wolf pack by males from a neighboring pack in mid-summer 2016 in Yellowstone National Park. Over the course of two months, three males from the Mollies pack displaced the breeding male of the neighboring Wapiti Lake pack, joined the packs two adult females, and subsequently raised the previous males four approximately three-month old pups. In the four years following the displacement (2017 to 2020), at least one of the intruding males has successfully bred with the dominant female and most years with a subordinate female (who was one of the pups at the time of displacement). The pack reared pups to adulthood each year. Male breeding displacements are likely influenced by male-male competition and female mate choice. These changes are the result of individuals competing to improve breeding position and may lead to increased pack stability and greater reproductive success. We report in detail on the behavior of a closely observed breeding displacement and we discuss the adaptive benefits of the change.

animal behavior and cognition↗

bioRxiv2020

The spatial-temporal dynamics of respiratory syncytial virus infections across the east-west coasts of Australia during 2016-17

Respiratory syncytial virus (RSV) is an important human respiratory pathogen. In temperate regions a distinct seasonality is observed, where peaks of infections typically occur in early winter, often preceding the annual influenza season. Infections are associated with high rates of morbidity and mortality, and in some populations exceeds that of influenza. Two subtypes, RSV-A and RSV-B, have been described, and molecular epidemiological studies have shown that both viruses mostly co-circulate. This trend also appears to be the case for Australia, however previous genomic studies have been limited to cases from one Eastern state - New South Wales. As such, the broader spatial patterns and viral traffic networks across the continent are not known. Here, we conducted a whole genome study of RSV comparing strains across eastern and western Australia during the period January 2016 to June 2017. In total, 96 new RSV genomes were sequenced, compiled with previously generated data, and examined using a phylodynamic approach. This analysis revealed that both RSV-A and RSV-B strains were circulating, and each subtype was dominated by a single genotype, RSV-A/ON1-like and RSV-B/BA10-like viruses. Some geographical clustering was evident in strains from both states with multiple distinct sub-lineages observed and relatively low mixing across jurisdictions suggesting that endemic transmission was likely seeded from imported, unsampled locations. Overall, the RSV phylogenies reflected a complex pattern of interactions across multiple epidemiological scales from fluid virus traffic across global and regional networks to fine-scale local transmission events.

microbiology↗

bioRxiv2019

Tooth fracture frequency in gray wolves reflects prey availability

Exceptionally high rates of tooth fracture in large Pleistocene carnivorans imply intensified interspecific competition, given that tooth fracture rises with increased bone consumption, a behavior that likely occurs when prey are difficult to acquire. To assess the link between prey availability and dental attrition, we documented dental fracture rates over decades among three well-studied populations of extant gray wolves that differed in prey:predator ratio and levels of carcass utilization. When prey:predator ratios declined, kills were more fully consumed, and rates of tooth fracture more than doubled. This supports tooth fracture frequency as a relative measure of the difficulty of acquiring prey, and reveals a rapid response to diminished food levels in large carnivores despite risks of infection and reduced fitness due to dental injuries. More broadly, large carnivore tooth fracture frequency likely reflects energetic stress, an aspect of predator success that is challenging to quantify in wild populations.

ecology↗

bioRxiv2017

Diel predator activity drives a dynamic landscape of fear

AO_SCPLOWBSTRACTC_SCPLOWA landscape of fear (LOF) is a map that describes continuous spatial variation in an animals perception of predation risk. The relief on this map reflects, for example, places that an animal avoids to minimize risk. Although the LOF concept is a potential unifying theme in ecology that is often invoked to explain the ecological and conservation significance of fear, quantified examples of a LOF over large spatial scales are lacking as is knowledge about the daily dynamics of a LOF. Despite theory and data to the contrary, investigators often assume, implicitly or explicitly, that a LOF is a static consequence of a predators mere presence. We tested the prediction that a LOF in a large-scale, free-living system is a highly-dynamic map with peaks and valleys that alternate across the diel (24-hour) cycle in response to daily lulls in predator activity. We did so with extensive data from the case study of Yellowstone elk (Cervus elaphus) and wolves (Canis lupus) that was the original basis for the LOF concept. We quantified the elk LOF, defined here as spatial allocation of time away from risky places and times, across nearly 1000-km2 of northern Yellowstone National Park and found that it fluctuated with the crepuscular activity pattern of wolves, enabling elk to use risky places during wolf downtimes. This may help explain evidence that wolf predation risk has no effect on elk stress levels, body condition, pregnancy, or herbivory. The ability of free-living animals to adaptively allocate habitat use across periods of high and low predator activity within the diel cycle is an underappreciated aspect of animal behavior that helps explain why strong antipredator responses may trigger weak ecological effects, and why a LOF may have less conceptual and practical importance than direct killing.

ecology↗

bioRxiv2017

Limited evidence for proactive and reactive spatial responses of prey to an active predator

O_LIThe extent to which prey space use actively minimises predation risk continues to ignite controversy. Methodological reasons that have hindered consensus include inconsistent measurements of predation risk, biased spatiotemporal scales at which responses are measured, and lack of robust null expectations.\nC_LIO_LIWe addressed all three challenges in a comprehensive analysis of the spatiotemporal responses of adult female elk (Cervus elaphus) to the risk of predation by grey wolves (Canis lupus) during winter in northern Yellowstone, USA.\nC_LIO_LIWe quantified spatial overlap between the winter home ranges of GPS-collared elk and three measures of predation risk: the intensity of wolf space use, the distribution of wolf-killed elk and vegetation openness. We also assessed whether elk varied their use of areas characterised by more or less predation risk across hours of the day, and estimated encounter rates between simultaneous elk and wolf pack trajectories. We determined whether observed values were significantly lower than expected if elk movements were random with reference to predation risk using a null model approach.\nC_LIO_LIAlthough a small proportion of elk did show a tendency to minimise use of open vegetation at specific times of the day, overall we highlight a notable absence of spatiotemporal response by female elk to the risk of predation posed by wolves in northern Yellowstone.\nC_LIO_LIOur results suggest that predator-prey interactions may not always result in strong spatiotemporal patterns of avoidance.\nC_LI

ecology↗

bioRxiv2017

The eardrum moves when the eyes move: A multisensory effect on the mechanics of hearing

Interactions between sensory pathways such as the visual and auditory systems are known to occur in the brain, but where they first occur is uncertain. Here we show a novel multimodal interaction evident at the eardrum. Ear canal microphone measurements in humans (n=19 ears in 16 subjects) and monkeys (n=5 ears in 3 subjects) performing a saccadic eye movement task to visual targets indicated that the eardrum moves in conjunction with the eye movement. The eardrum motion was oscillatory and began as early as 10 ms before saccade onset in humans or with saccade onset in monkeys. These eardrum movements, which we dub Eye Movement Related Eardrum Oscillations (EMREOs), occurred in the absence of a sound stimulus. The EMREOs amplitude and phase depended on the direction and horizontal amplitude of the saccade. They lasted throughout the saccade and well into subsequent periods of steady fixation. We discuss the possibility that the mechanisms underlying EMREOs create eye movement-related binaural cues that may aid the brain in evaluating the relationship between visual and auditory stimulus locations as the eyes move.\n\nSIGNIFICANCE STATEMENTThe peripheral hearing system contains several motor mechanisms that allow the brain to modify the auditory transduction process. Movements or tensioning of either the middle-ear muscles or the outer hair cells modify eardrum motion, producing sounds that can be detected by a microphone placed in the ear canal (e.g. as otoacoustic emissions). Here, we report a novel form of eardrum motion produced by the brain via these systems -- oscillations synchronized with and covarying with the direction and amplitude of saccades. These observations suggest that a vision-related process modulates the first stage of hearing. In particular, these eye-movement related eardrum oscillations may help the brain connect sights and sounds despite changes in the spatial relationship between the eyes and the ears.

neuroscience↗

bioRxiv2017

Genomic And Transcriptomic Profiling Of Nematode Parasites Surviving After Vaccine Exposure

Some nematode species are economically important parasites of livestock, while others are important human pathogens causing some of the most important neglected tropical diseases. In both humans and animals, anthelmintic drug administration is the main control strategy, but the emergence of drug-resistant worms has stimulated the development of alternative control approaches. Among these, vaccination is considered to be a sustainable and cost effective strategy. Currently, Barbervax(R) for the ruminant strongylid Haemonchus contortus is the only registered subunit vaccine for a nematode parasite, although a vaccine for the human hookworm Necator americanus is undergoing clinical trials (HOOKVAC consortium). As both these vaccines comprise a limited number of proteins there is potential for selection of nematodes with altered sequence or expression of the vaccine antigens. Here we compared the transcriptome of H. contortus populations from sheep vaccinated with Barbervax(R) with worms from control animals. Barbervax(R) antigens are native integral membrane proteins isolated from the brush border of the intestinal cells of the adult parasite and many of them are proteases. Our findings provide no evidence for changes in expression of genes encoding Barbervax(R) antigens in the surviving parasite populations. However, surviving parasites from vaccinated animals showed increased expression of other proteases and regulators of lysosome trafficking, and displayed up-regulated lipid storage and defecation abilities that may have circumvented the vaccine effect. Implications for other potential vaccines for human and veterinary nematodes are discussed.

genomics↗