Biology subjects

Jackson, A. L.

Publications and source records attributed to Jackson, A. L..

8 recordsLinked to original sources

bioRxiv2026

Critical flicker fusion thresholds predict attentional blink magnitude

The critical flicker fusion (CFF) threshold is a psychophysical measure used to quantify the temporal resolution of the visual system and is known to vary across individuals. However, it is unclear if this measure is stimulus-specific, or if it may represent a more fundamental processing rate for visual perception in general. Here, we assess if individual variation in CFF is predictive of two features of visual processing that are dependent on temporal perception: the attentional blink and global motion sensitivity. In a non-clinical sample of 84 individuals, flicker fusion thresholds were predictive of the magnitude of the attentional blink. In contrast, we found no link between flicker fusion and global motion sensitivity in a sample of 79 individuals. Our results suggest that CFF reflects a visual processing rate that impacts other, more complex perceptual tasks.

neuroscience↗

bioRxiv2024

Divalent siRNA for prion disease

Prion protein (PrP) lowering is effective in animal models of prion disease and is being tested clinically in prion disease patients, but there remains a need for more potent PrP-lowering drug candidates. Inspired by the reported potency and duration of action of divalent short interfering RNA (siRNA), a new oligonucleotide drug modality for the central nervous system, we sought to discover and develop a new PrP-lowering drug candidate. Herein we identify a mouse Prnp-targeting divalent siRNA molecule, 1682-s4, that lowers PrP to 49% residual brain expression in wild-type mice, and, in the context of intracerebral infection with Rocky Mountain Laboratory (RML) prions, achieves a 2.7-fold increase in survival time with pre-symptomatic chronic treatment and 64% increase in survival time with a single dose after symptom onset. We describe the generation of two transgenic mouse lines, Tg25109 and Tg26372, expressing the full human PRNP gene and its non-coding sequence, and demonstrate their utility for in vivo discovery of potent human PRNP-targeting oligonucleotides. We discover siRNA sequence 2439 against human PRNP and compare its potency in different divalent siRNA chemical scaffolds. We determine that both the fixed UU tail and extended nucleic acid linkages of scaffold s4 contribute to superior potency compared to other scaffolds tested, offering 9.4 and 15.9 percentage points respectively of additional PrP knockdown. A single dose of 348 {micro}g of 2439-s4 lowered whole brain hemisphere human PrP in transgenic mice to 17% residual after 30 days, while 52 {micro}g lowered PrP to 49% residual. 1-2% of the dose of 2439-s4 delivered into cerebrospinal fluid is retained in the brain, and the median effective tissue concentration is estimated at 1.2 micrograms per gram of tissue. Good Laboratory Practices toxicology studies identified no significant liabilities, and the U.S. FDA has cleared an Investigational New Drug application to bring 2439-s4 into clinical trials.

neuroscience↗

bioRxiv2023

The speed of sight: individual variation in critical flicker fusion thresholds

The critical flicker fusion threshold is a psychophysical measure commonly used to quantify visual temporal resolution; the fastest rate at which a visual system can discriminate visual signals. Critical flicker fusion thresholds vary substantially among species, reflecting different ecological niches and demands. However, it is unclear how much variation exists in flicker fusion thresholds between healthy individuals of the same species, or how stable this attribute is over time within individuals. In this study, we assessed both inter- and intra-individual variation in critical flicker fusion thresholds in a cohort of healthy human participants within a specific age range, using two common psychophysical methods and three different measurements during each session. The resulting thresholds for each method were highly correlated. We found a between-participant maximum difference of roughly 30 Hz in flicker fusion thresholds and we estimated a 95% prediction interval of 21 Hz. We used random-effects models to compare between- and within-participant variance and found that approximately 80% of variance was due to between-individual differences, and about 10% of the variance originated from within-individual differences over three sessions. Within-individual thresholds did not differ significantly between the three sessions in males, but did in females (P<0.001 for two methods and P<0.05 for one method), indicating that critical flicker fusion thresholds may be more variable in females than in males.

ecology↗

bioRxiv2023

Identifying the limits where variation in consumer stable isotope values reflect variation in diet

O_LIAnalysis of stable isotopes in cosumbers is used commonly to study their ecological and/or environmental niche. There is, however, considerable debate regarding how isotopic values relate to diet and how other sources of variation confound this link, which can undermine the utility. C_LIO_LIFrom the analysis of a simple, but general, model of isotopic incorporation in consumer organisms, we examine the relationship between isotopic variance among individuals, and diet variability within a consumer population. C_LIO_LIWe show that variance in consumer isotope values is directly proportional to variation in diet (through Simpson indices), to the number of isotopically distinct food sources in the diet, and to the baseline variation within and among the isotope values of the food sources. Additionally, when considering temporal diet variation within a consumer we identify the interplay between diet turnover rates and tissue turnover rates that controls the sensitivity of stable isotopes to detect diet variation. C_LIO_LIOur work demonstrates that variation in the stable isotope values of consumers reflect variation in their diet. This relationship, however, can be confounded with other factors to the extent that they may mask the signal coming from diet. We show how simple quantitative corrections can recover a direct 1:1 correlation in some situations, and in others we can adjust our interpretation in light of the new understanding arising from our models. Our framework provides guidance for the design and analysis of empirical studies where the goal is to infer niche width from stable isotope data. C_LI

ecology↗

bioRxiv2022

Heating tolerance of ectotherms is explained by temperature's non-linear influence on biological rates

The capacity of ectotherms to adjust their thermal tolerance limits through evolution or acclimation seems relatively modest and highly variable, and we lack satisfying explanations for both findings given a limited understanding of what ultimately determines an organisms thermal tolerance. Here, we test if the amount of heating an ectotherm tolerates throughout a heating event until organismal failure scales with temperatures non-linear influence on biological rates. To account for the non-linear influence of temperature on biological rates on heating tolerance, we rescaled the duration of heating events of 316 ectothermic taxa acclimated to different temperatures and describe the biological rate-corrected heating duration. This rescaling reveals that the capacity of an organism to resist a heating event is in fact remarkably constant across any acclimation temperature, enabling high-precision estimates of how organismal thermal tolerance limits vary under different thermal regimes. We also find that faster heating consistently reduces biological rate-corrected heating durations, which helps further explain why thermal tolerance limits seem so variable on absolute temperature scales. Existing paradigms are that heating tolerances and thermal tolerance limits reflect incomplete metabolic compensatory responses, are constrained by evolutionary conservatism, or index failure of systems such as membrane function; our data provide a different perspective and show that an organisms thermal tolerance emerges from the interaction between the non-linear thermal dependence of biological rates and heating durations, which is an approximately-fixed property of a species.

ecology↗

bioRxiv2022

Stressor interactions at the community level: explaining qualitative mismatches between observations

Perturbations such as climate change, invasive species and pollution, impact the functioning and diversity of ecosystems. But because there is no unique way to measure functioning and diversity, this leads to a ubiquitous and overwhelming variability in community-level responses, that is often seen as a barrier to prediction in ecology. Here, we show that this variability can instead provide insights into hidden features of a communitys functions and responses to perturbations. By first analysing a dataset of global change experiments in microbial soil systems we show that variability of functional and diversity responses to a given perturbation is not random: aggregate properties that are thought to be mechanistically similar tend to respond similarly. We then formalise this intuitive observation to demonstrate that the variability of community-level responses to perturbations is not only predictable, but that it can also be used to access hidden and useful information about population-level responses to perturbations (i.e., response diversity and scaling by species biomass). Our theory offers a baseline expectation for the variability of community-level responses to perturbations and helps to explain the complexity of ecological responses to global change. Significance StatementMeasures of biodiversity and ecosystem functioning show highly variable responses to a given perturbation. This variability is traditionally thought of as reflecting our inability to predict ecological responses to global change. Our work, however, finds that variability of community-level responses is itself predictable and can even be used to gain insights about how species respond to perturbations and collectively contribute to ecosystem functions.

ecology↗

bioRxiv2021

Alternate patterns of temperature variation bring about very different disease outcomes at different mean temperatures

The dynamics of host-parasite interactions are highly temperature-dependent and may be modified by increasing frequency and intensity of climate-driven heat events. Here, we show that altered patterns of temperature variance lead to an almost order-of-magnitude shift in thermal performance of host and pathogen life history traits over and above the effects of mean temperature and, moreover, that different temperature regimes affect these traits differently. We found that diurnal fluctuations of {+/-}3{degrees}C lowered infection rates and reduced spore burden compared to constant temperatures in our focal host Daphnia magna exposed to the microsporidium parasite Ordospora colligata. In contrast, a three-day heatwave (+6{degrees}C) did not affect infection rates, but increased spore burden (relative to constant temperatures with the same mean) at 16{degrees}C, while reducing burden at higher temperatures. We conclude that changing patterns of climate variation, superimposed on shifts in mean temperatures due to global warming, may have profound and unanticipated effects on disease dynamics.

ecology↗

bioRxiv2019

How indirect interactions shape long-term invasion dynamics in complex ecological communities

Many facets of ecological theory rely on the analysis of invasion processes, and general approaches exist to understand the early stages of an invasion. However, predicting the long-term transformations of communities following an invasion remains a challenging endeavour. We propose an analytical method that uses community structure and invader dynamical features to predict when these impacts can be large, and show it to be applicable across a wide class of dynamical models. Our approach reveals that short-term invasion success and long-term consequences are two distinct axes of variation controlled by different properties of both invader and resident community. Whether a species can invade is controlled by its invasion fitness, which depends on environmental conditions and direct interactions with resident species. But whether this invasion will cause significant transformations, such as extinctions or a regime shift, depends on a specific measure of indirect feedbacks that may involve the entire resident community. Our approach applies to arbitrarily complex communities, from few competing phenotypes in adaptive dynamics to large nonlinear food webs. It hints at new questions to ask as part of any invasion analysis, and suggests that long-term indirect interactions are key determinants of invasion outcomes.

ecology↗