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"Cook, Peter"
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Local introduction and heterogeneous spatial spread of dengue-suppressing Wolbachia through an urban population of Aedes aegypti
Dengue-suppressing Wolbachia strains are promising tools for arbovirus control, particularly as they have the potential to self-spread following local introductions. To test this, we followed the frequency of the transinfected Wolbachia strain wMel through Ae. aegypti in Cairns, Australia, following releases at 3 nonisolated locations within the city in early 2013. Spatial spread was analysed graphically using interpolation and by fitting a statistical model describing the position and width of the wave. For the larger 2 of the 3 releases (covering 0.97 km2 and 0.52 km2), we observed slow but steady spatial spread, at about 100-200 m per year, roughly consistent with theoretical predictions. In contrast, the smallest release (0.11 km2) produced erratic temporal and spatial dynamics, with little evidence of spread after 2 years. This is consistent with the prediction concerning fitness-decreasing Wolbachia transinfections that a minimum release area is needed to achieve stable local establishment and spread in continuous habitats. Our graphical and likelihood analyses produced broadly consistent estimates of wave speed and wave width. Spread at all sites was spatially heterogeneous, suggesting that environmental heterogeneity will affect large-scale Wolbachia transformations of urban mosquito populations. The persistence and spread of Wolbachia in release areas meeting minimum area requirements indicates the promise of successful large-scale population transformation.
Journal Article
Rhythmic entrainment: Why humans want to, fireflies can’t help it, pet birds try, and sea lions have to be bribed
Until recently, the literature on rhythmic ability took for granted that only humans are able to synchronize body movements to an external beat—to
entrain
. This assumption has been undercut by findings of beat-matching in various species of parrots and, more recently, in a sea lion, several species of primates, and possibly horses. This throws open the question of how widespread beat-matching ability is in the animal kingdom. Here we reassess the arguments and evidence for an absence of beat-matching in animals, and conclude that in fact no convincing case against beat-matching in animals has been made. Instead, such evidence as there is suggests that this capacity could be quite widespread. Furthermore, mutual entrainment of oscillations is a general principle of physical systems, both biological and nonbiological, suggesting that entrainment of motor systems by sensory systems may be a default rather than an oddity. The question then becomes, not why a few privileged species are able to beat-match, but why species do not always do so—why they vary in both spontaneous and learned beat-matching. We propose that when entrainment is not driven by fixed, mandatory connections between input and output (as in the case of, e.g., fireflies entraining to each others’ flashes), it depends on voluntary control over, and voluntary or learned coupling of, sensory and motor systems, which can paradoxically lead to apparent failures of entrainment. Among the factors that affect whether an animal will entrain are sufficient control over the motor behavior to be entrained, sufficient perceptual sophistication to extract the entraining beat from the overall sensory environment, and the current cognitive state of the animal, including attention and motivation. The extent of entrainment in the animal kingdom potentially has widespread implications, not only for understanding the roots of human dance, but also for understanding the neural and cognitive architectures of animals.
Journal Article
Nonspecific bridging-induced attraction drives clustering of DNA-binding proteins and genome organization
Molecular dynamics simulations are used to model proteins that diffuse to DNA, bind, and dissociate; in the absence of any explicit interaction between proteins, or between templates, binding spontaneously induces local DNA compaction and protein aggregation. Small bivalent proteins form into rows [as on binding of the bacterial histone-like nucleoid-structuring protein (H-NS)], large proteins into quasi-spherical aggregates (as on nanoparticle binding), and cylinders with eight binding sites (representing octameric nucleosomal cores) into irregularly folded clusters (like those seen in nucleosomal strings). Binding of RNA polymerase II and a transcription factor (NFκB) to the appropriate sites on four human chromosomes generates protein clusters analogous to transcription factories, multiscale loops, and intrachromosomal contacts that mimic those found in vivo. We suggest that this emergent behavior of clustering is driven by an entropic bridging-induced attraction that minimizes bending and looping penalties in the template.
Journal Article
Conceptual uncertainties in groundwater and porewater fluxes estimated by radon and radium mass balances
Radium isotopes and radon are routinely used as tracers to quantify groundwater and porewater fluxes into coastal and freshwater systems. However, uncertainties associated with the determination of the tracer flux are often poorly addressed and often neglect all the potential errors associated with the conceptualization of the system (i.e., conceptual uncertainties). In this study, we assess the magnitude of some of the key uncertainties related to the determination of the radium and radon inputs supplied by groundwater and porewater fluxes into a waterbody (La Palme Lagoon, France). This uncertainty assessment is addressed through a single model ensemble approach, where a tracer mass balance is run multiple times with variable sets of assumptions and approaches for the key parameters determined through a sensitivity test. In particular, conceptual uncertainties linked to tracer concentration, diffusive fluxes, radon evasion to the atmosphere, and change of tracer inventory over time were considered. The magnitude of porewater fluxes is further constrained using a comparison of independent methods: (1) 224 Ra and (2) 222 Rn mass balances in overlying waters, (3) a model of 222 Rn deficit in sediments, and (4) a fluid-salt numerical transport model. We demonstrate that conceptual uncertainties are commonly a major source of uncertainty on the estimation of groundwater or porewater fluxes and they need to be taken into account when using tracer mass balances. In the absence of a general framework for assessing these uncertainties, this study provides a practical approach to evaluate key uncertainties associated to radon and radium mass balances.
Journal Article
Lateralized cerebellar connectivity differentiates auditory pathways in echolocating and non-echolocating whales
We report the first application of diffusion tractography to a mysticete, which was analyzed alongside three odontocete brains, allowing the first direct comparison of strength and laterality of auditory pathways in echolocating and non-echolocating whales. Brains were imaged post-mortem at high resolution with a specialized steady state free precession diffusion sequence optimized for dead tissue. We conducted probabilistic tractography to compare the qualitative features, tract strength, and lateralization of potential ascending and descending auditory paths in the mysticete versus odontocetes. Tracts were seeded in the inferior colliculi (IC), a nexus for ascending auditory information, and the cerebellum, a center for sensorimotor integration. Direct IC to temporal lobe pathways were found in all animals, replicating previous cetacean tractography and suggesting conservation of the primary auditory projection path in the cetacean clade. Additionally, odontocete IC-cerebellum pathways exhibited higher overall tract strength than in the mysticete, suggesting they may play a role in supporting the rapid sensorimotor integration demands of echolocation. Further, in the mysticete, contralateral right IC to left cerebellum pathways were 17x stronger than those between left IC and right cerebellum, while in odontocetes, the laterality was reversed, and left IC to right cerebellum pathways were 2-4x stronger than those between right IC and left cerebellum. This lateralization may also relate to echolocation. Right cerebellum is responsible for integrating sensory and motor signals from the left cortical hemisphere, and in odontocetes, this hemisphere likely controls the contralateral right-side phonic lips, which have been empirically implicated in the production of echolocation clicks. We also found differences in the specific subregions of cerebellum targeted by the IC between the mysticete and odontocetes, some of which may also bear on hearing and vocal production. This study establishes foundational knowledge on mysticete brain connectivity and extends knowledge on pathways supporting hearing and auditory-motor integration across the order Cetacea.
Journal Article
Fungal-mediated lung allergic airway disease: The critical role of macrophages and dendritic cells
Fungi are abundant in the environment, causing our lungs to be constantly exposed to a diverse range of species. While the majority of these are cleared effectively in healthy individuals, constant exposure to spores (especially Aspergillus spp.) can lead to the development of allergic inflammation that underpins and worsen diseases such as asthma. Despite this, the precise mechanisms that underpin the development of fungal allergic disease are poorly understood. Innate immune cells, such as macrophages (MΦs) and dendritic cells (DCs), have been shown to be critical for mediating allergic inflammation to a range of different allergens. This review will focus on the crucial role of MΦ and DCs in mediating antifungal immunity, evaluating how these immune cells mediate allergic inflammation within the context of the lung environment. Ultimately, we aim to highlight important future research questions that will lead to novel therapeutic strategies for fungal allergic diseases.
Journal Article
Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation
A defining feature of inflammation is the accumulation of innate immune cells in the tissue that are thought to be recruited from the blood. We reveal that a distinct process exists in which tissue macrophages undergo rapid in situ proliferation in order to increase population density. This inflammatory mechanism occurred during T helper 2 (T(H)2)-related pathologies under the control of the archetypal T(H)2 cytokine interleukin-4 (IL-4) and was a fundamental component of T(H)2 inflammation because exogenous IL-4 was sufficient to drive accumulation of tissue macrophages through self-renewal. Thus, expansion of innate cells necessary for pathogen control or wound repair can occur without recruitment of potentially tissue-destructive inflammatory cells.
Journal Article
DNA replication timing reveals genome-wide features of transcription and fragility
DNA replication in humans requires precise regulation to ensure accurate genome duplication and maintain genome integrity. A key indicator of this regulation is replication timing, which reflects the interplay between origin firing and fork dynamics. We present a high-resolution (1-kilobase) mathematical model that infers firing rate distributions from Repli-seq timing data across multiple cell lines, enabling a genome-wide comparison between predicted and observed replication. Notably, regions where the model and data diverge often overlap fragile sites and long genes, highlighting the influence of genomic architecture on replication dynamics. Conversely, regions of strong concordance are associated with open chromatin and active promoters, where elevated firing rates facilitate timely fork progression and reduce replication stress. In this work, we provide a valuable framework for exploring the structural interplay between replication timing, transcription, and chromatin organisation, offering insights into the mechanisms underlying replication stress and its implications for genome stability and disease.
Replication timing reflects the coordination of origin firing and fork progression to preserve genome integrity. Here, the authors show that a high-resolution model of replication timing captures genomic features linked to replication stress and chromatin structure.
Journal Article
Sensorimotor synchronization to rhythm in an experienced sea lion rivals that of humans
Is human beat keeping unique among vertebrates? The only non-human data showing consistent and lagless beat matching to novel stimuli, including music, come from
Ronan
, a trained sea lion [Cook et al.,
J. Comp. Psychol.
, 127(4):412–427].
Ronan’s
convincing demonstration of adaptive auditory-motoric entrainment at age 3 years showed stronger tempo-phase relationships and higher variability than reported in similar studies of human subjects. This apparent performance mismatch has been used to suggest the mechanisms underlying her beat keeping ability are not isomorphic with those of humans. However, in the twelve years since our original report,
Ronan
has continued intermittent beat-keeping practice. Comparative arguments should consider her improved performance with increased experience and evaluate her ability against human subjects performing similar rhythmic tasks. Here, we report
Ronan’s
contemporary ability to synchronize head movements with novel metronomic sounds presented at novel tempos. We also provide data for ten humans moving in time to the same stimuli using a comfortable arm motion with similar amplitude. This sea lion’s sensorimotor synchronization was precise, consistent, and indistinguishable from or superior to that of typical adults. These findings challenge claims of unique neurobiological adaptations for beat keeping in humans.
Journal Article