Biology subjects

Spencer, M.

Publications and source records attributed to Spencer, M..

9 recordsLinked to original sources

bioRxiv2026

The algebra of community temperature indices

The Community Temperature Index (CTI) was developed as a way to measure changes in a community over time in a way that reflects the temperature preferences of species. Several different forms of CTI are in widespread use, but their properties have not been systematically investigated. We argue that a CTI should preserve the algebraic structure of relative abundances given by the Aitchison geometry used in compositional data analysis. We show that this requirement leads to a new Aitchison CTI. The CTI has been used to classify species as warm- or cold-affinity, depending on whether an increase in their relative abundance increases or decreases the CTI. However, such classifications depend on relative abundances as well as on temperature preferences, which is undesirable. We show that the Aitchison CTI leads to a classification of species as relative warm- or cold-affinity that does not depend on relative abundances, with species contributions to changes in CTI that are consistent with the principles of population dynamics. We show that the Aitchison CTI is approximately linearly related to the most popular CTI in current use if relative abundances are approximately equal and temperature preferences for all species are close to their geometric mean. We provide a quantity analogous to an R2 for the Aitchison CTI, that tells us whether the CTI contains useful information. We illustrate our approach using data from a hard-substrate macrobenthos community.

ecology↗

bioRxiv2026

Cannabis Use by People with HIV is Associated with an Anti-Inflammatory Immunometabolic Phenotype in Monocyte-Derived Macrophages

Chronic neuroinflammation is associated with comorbidities in people with HIV (PWH) on antiretroviral therapy (ART). While cannabis use is associated with reduced neuroinflammation and neurocognitive impairment (NCI) in PWH, the underlying mechanisms are unknown. To address this gap in knowledge, we analyzed monocyte-derived macrophages (MDMs) from a cohort of 50 PWH and 33 people without HIV (mean age: 61.9 years), categorized by frequency of cannabis use (naive/low, moderate, daily). We performed immunocytochemistry, RNA sequencing, and qPCR on MDMs and quantified related biomarkers in donor plasma. In this cohort study, daily cannabis use in PWH was associated with less global neurocognitive deficits, and with an anti-inflammatory immunometabolic-phenotype in MDMs characterized by (1) a metabolic shift from glycolysis to oxidative phosphorylation, (2) higher mitochondrial numbers, (3) altered cytokine profiles (pro-inflammatory downregulation, anti-inflammatory upregulation), and (4) higher brain-derived neurotrophic factor (BDNF) expression. These cellular changes were corroborated by a plasma biomarker profile in PWH including (1) lower levels of growth differentiation factor 15 and soluble triggering receptor expressed on myeloid cells 2, and (2) higher mature BDNF/precursor BDNF ratios that correlated with better cognition. Thus, cannabis use may mitigate NCI in PWH by immunometabolically reprogramming MDM function towards an anti-inflammatory and neuroprotective state. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/709579v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@15fb1adorg.highwire.dtl.DTLVardef@189d79corg.highwire.dtl.DTLVardef@aa6a89org.highwire.dtl.DTLVardef@3852f8_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Axiomatic Community Ecology, Topology, and Dynamic Distance

The super-organismal view of ecosystems has largely been superseded by the individualistic view. One consequence of the dominance of the individualistic view is that many modern ecologists treat ecosystems as nothing more than vectors of relative abundances, ignoring the potentially important idea that an understanding of ecosystems should be based on dynamics rather than abundances or species identities. We develop a mathematical framework in which we compare dynamical properties of ecosystems with different sets of species, using ideas from functional analysis, metric spaces, and topology. We give two proof-of-principle applications of our framework to marine sessile communities and to a large database of ecosystem models. We show that under a set of biologically-motivated axioms designed to capture the properties of predator-prey systems, there is only one natural kind of ecosystem.

ecology↗

bioRxiv2023

Single-cell and spatial transcriptomics identify a macrophage population associated with skeletal muscle fibrosis

The monocytic/macrophage system is essential for skeletal muscle homeostasis, but its dysregulation contributes to the pathogenesis of muscle degenerative disorders. Despite our increasing knowledge of the role of macrophages in degenerative disease, it still remains unclear how macrophages contribute to muscle fibrosis. Here, we used single-cell transcriptomics to determine the molecular attributes of dystrophic and healthy muscle macrophages. We identified six novel clusters. Unexpectedly, none corresponded to traditional definitions of M1 or M2 macrophage activation. Rather, the predominant macrophage signature in dystrophic muscle was characterized by high expression of fibrotic factors, galectin-3 and spp1. Spatial transcriptomics and computational inferences of intercellular communication indicated that spp1 regulates stromal progenitor and macrophage interactions during muscular dystrophy. Galectin-3+ macrophages were chronically activated in dystrophic muscle and adoptive transfer assays showed that the galectin-3+ phenotype was the dominant molecular program induced within the dystrophic milieu. Histological examination of human muscle biopsies revealed that galectin-3+ macrophages were also elevated in multiple myopathies. These studies advance our understanding of macrophages in muscular dystrophy by defining the transcriptional programs induced in muscle macrophages, and reveal spp1 as a major regulator of macrophage and stromal progenitor interactions.

immunology↗

bioRxiv2022

High-latitude marginal reefs support fewer but bigger corals than their tropical counterparts

AimDespite the awareness that climate change impacts are typically detrimental to tropical coral reefs, the effect of increasing environmental stress and variability on the population size structure of coral species remains poorly understood. This gap in knowledge limits our ability to effectively conserve coral reef ecosystems because size specific dynamics are rarely incorporated. Our aim is to quantify variation in the size structure of coral populations along a tropical-to-subtropical environmental gradient. Location20 coral populations along a latitudinal gradient on the east coast of Australia ([~]23{degrees}S to 30{degrees}S). Time PeriodBetween 2010 and 2018. Major taxa studiedScleractinian corals. MethodsWe apply two methods to quantify the relationship between environmental covariates and coral population size structure along a latitudinal environmental gradient. First, we use linear regression with summary statistics, such as median size as response variables; a method frequently favoured by ecologists. The second method is compositional functional regression, a novel method using entire size-frequency distributions as response variables. We then predict coral population size structure with increasing environmental stress and variability. ResultsCompared to tropical reefs, we find fewer but larger coral colonies in marginal reefs, where environmental conditions are more variable and stressful for corals in the former. Our model predicts that coral populations may become gradually dominated by larger colonies (> 148 cm2) with increasing environmental stress. Main conclusionsWith increasing environmental stress and variability, we can expect shifts in coral population size structure towards more larger colonies. Fewer but bigger corals suggest low survival, slow growth, and poor recruitment. This finding is concerning for the future of coral reefs as it implies populations may have low recovery potential from disturbances. We highlight the importance and usefulness of continuously monitoring changes to population structure over large spatial scales. Data availabilityData is supplied in the supplementary information, or upon request. Once accepted for publication it will be made openly available on Dryad.

ecology↗

bioRxiv2022

Negative and positive interspecific interactions involving jellyfish polyps in marine sessile communities

O_LISessile marine invertebrates on hard substrates are one of the two canonical examples of communities structured by competition, but some aspects of their dynamics remain poorly understood. Jellyfish polyps are an important but under-studied component of these communities. C_LIO_LIWe determined how jellyfish polyps interact with their potential competitors in sessile marine hard-substrate communities, using a combination of experiments and modelling. C_LIO_LIWe carried out an experimental study of the interaction between polyps of the moon jellyfish Aurelia aurita and potential competitors on settlement panels, in which we determined the effects of reduction in relative abundance of either A. aurita or potential competitors at two depths. We predicted that removal of potential competitors would result in a relative increase in A. aurita that would not depend on depth, and that removal of A. aurita would result in a relative increase in potential competitors that would be stronger at shallower depths, where oxygen is less likely to be limiting. C_LIO_LIRemoval of potential competitors resulted in a relative increase in A. aurita at both depths, as predicted. Unexpectedly, removal of A. aurita resulted in a relative decrease in potential competitors at both depths. We investigated a range of models of competition for space, of which the most successful involved enhanced overgrowth of A. aurita by potential competitors, but none of these models was completely able to reproduce the observed pattern. C_LIO_LIOur results suggest that interspecific interactions in this canonical example of a competitive system are more complex than is generally believed. C_LI

ecology↗

bioRxiv2022

High Concentrations of floating life in the North Pacific Garbage Patch

Floating life (obligate neuston) is a core component of the ocean surface food web. However, only one region of high neustonic abundance is known so far, the Sargasso Sea in the Subtropical North Atlantic, where floating life provides critical habitat structure and ecosystem services. Here, we hypothesize that floating life is also concentrated in other gyres with converging surface currents. To test this hypothesis, we collected samples through the eastern North Pacific Subtropical Gyre in the area of the North Pacific "garbage patch" (NPGP) known to accumulate floating anthropogenic debris. We found that densities of floating life were significantly higher inside the central part of NPGP than on its periphery, and there was a significant positive relationship between neuston abundance and plastic abundance. This work has important implications for the ecology and human impact of subtropical oceanic gyre ecosystems.

ecology↗

bioRxiv2021

Long-Range Electrostatic Interactions Significantly Modulate the Affinity of Dynein for Microtubules

The dynein family of microtubule minus-end directed motor proteins drives diverse functions in eukaryotic cells, including cell division, intracellular transport, and flagellar beating. Motor protein processivity, which characterizes how far a motor walks before detaching from its filament, depends on the interaction between its microtubule-binding domain (MTBD) and the microtubule. Dyneins MTBD switches between high- and low-binding affinity states as it steps. Significant structural and functional data show that specific salt bridges within the MTBD and between the MTBD and the microtubule govern these affinity state shifts. However, recent computational work suggests that non-specific, long-range electrostatic interactions between the MTBD and the microtubule may also play a significant role in the processivity of dynein. To investigate this hypothesis, we mutated negatively charged amino acids remote from the dynein MTBD-microtubule-binding interface to neutral residues and measured the binding affinity using microscale thermophoresis and optical tweezers. We found a significant increase in the binding affinity of the mutated MTBDs for microtubules. Furthermore, we found that charge screening by free ions in solution differentially affected the binding and unbinding rates of MTBDs to microtubules. Together, these results demonstrate a significant role for long-range electrostatic interactions in regulating dynein-microtubule affinity. Moreover, these results provide insight into the principles that potentially underlie the biophysical differences between molecular motors with various processivities and protein-protein interactions more generally. Statement of SignificanceThe dynein family of motor proteins drives the motility of multiple cellular functions by walking toward the minus end of microtubules. The biophysical mechanisms of dynein rely on its ability to change affinity for the microtubule as it steps. Specific short-range electrostatic interactions acting at the microtubule-binding domain (MTBD)-microtubule interface are known to govern binding affinity. This study shows that non-specific longer-range electrostatic interactions due to charged amino acids remote from the binding interface also contribute significantly to the binding affinity mechanisms. Our results suggest that subtle differences in the electrostatic charge distribution within the MTBD significantly affect the molecular biophysical motility mechanisms in the dynein family of motors.

biophysics↗

bioRxiv2019

Disrupting HIV-1 capsid formation causes cGAS sensing of viral DNA

Detection of viral DNA by cyclic GMP-AMP synthase (cGAS) is a first line of defence leading to the production of type-I interferon (IFN). As HIV-1 is not a strong inducer of IFN we have hypothesised that its capsid cloaks viral DNA from cGAS. To test this we generated defective viral particles by treatment with HIV-1 protease inhibitors or by genetic manipulation of gag. These viruses had defective Gag cleavage, reduced infectivity and diminished capacity to saturate TRIM5. Importantly, unlike wild-type HIV-1, infection with cleavage defective HIV-1 triggered an IFN response in THP-1 cells and primary human macrophages that was dependent on viral DNA and cGAS. Infection in the presence of the capsid destabilising small molecule PF-74 also induced a cGAS-dependent IFN response. These data demonstrate a protective role for capsid and suggest that antiviral activity of capsid- and protease-targeting antivirals may benefit from enhanced innate and adaptive immunity in vivo.

microbiology↗