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Lowe, C.

Publications and source records attributed to Lowe, C..

14 recordsLinked to original sources

Evolutionary principles underlying neuron subtype encoding and diversification in animals

Animals harbor a diversity of terminally differentiated cell types. This cell type diversity is particularly spectacular in the nervous system. While the shared evolutionary origin of the bilaterian neuron has been increasingly supported, it remains poorly understood when the first neuron diversified into the many types present in extant lineages and what molecular mechanisms accompanied this neuron diversification. Existing models of neuronal evolution are based on select observations from flies, nematodes, and humans, rather than systems-level comparisons across whole nervous systems and diverse species. Applying single-cell RNA-sequencing in the acorn worm Saccoglossus kowalevskii and performing cell type comparisons across protostome and deuterostome species, we show that neuronal subtypes in one species bear little resemblance to those found in different phyla. Previously identified cross-phyletic transcriptional similarities represent exceptions to a global pattern of divergence. Specifically, we observe that all neurons share the expression of genes associated with general features such as the presynapse and axon cytoskeleton, but distantly related species have evolved distinct usage of subtype-defining genes: they co-express unique combinations of neurotransmitter pathways, ion channels, postsynaptic receptors, and transcription factors. Additionally, we recover signal for an ancient neuronal regulatory code characterized by a strong enrichment for homeodomain transcription factors. Overall, these results suggest that while neurons largely share a core set of transcriptional features, a great deal of reshuffling of gene expression has occurred, supporting large-scale turnover in neuron subtype identities amongst major animal lineages.

evolutionary biology↗

SELECT 2.0: Refined and open access SELection Endpoints in Communities of bacTeria (SELECT) method to determine concentrations of antibiotics that may select for antimicrobial resistance in the environment

Antimicrobial resistance (AMR) is a significant and growing threat to human, plant and animal health, the global economy, and food security. The One Health approach to AMR recognises the role of the environment in the evolution, emergence, and dissemination of AMR. In part, this is due to anthropogenic pollution that releases AMR organisms alongside cocktails of compounds that may select for AMR in situ, which then pose an exposure risk to humans and animals. This has spurred growing interest from cross-sectoral stakeholders in environmental risk assessment (ERA) of antibiotics, with regards to their selective potential. Many different experimental and modelling approaches have been used to determine the lowest concentration of an antibiotic that may select for AMR. Debates continue regarding which individual approach, if any, may be best for determining concentrations of antibiotics that may select for AMR, for ERA purposes. This paper contributes to this ongoing discourse by refining and using a previously published method SELECT (SELection Endpoints in Communities of bacTeria) to rapidly generate predicted no effect concentrations for resistance (PNECRs) for 32 antibiotics on the premise that reduction in growth of complex community of bacteria correlates with selection for AMR resistance genes. The database of PNECRs of antibiotics presented here is the largest generated using a single experimental, empirical approach that will aid future efforts towards creating a standardised test. PNECR data were used to conduct ERAs using measured environmental concentrations of antibiotics to rank antibiotics by potential selection risk in different environments. The experimental approach and statistical code have been made open access, with online tutorials available to facilitate other laboratories using the SELECT 2.0 method. Finally, we discuss the limitations of this approach and how these could be addressed in future studies.

microbiology↗

Major cell type differences between larval and adult hemichordate body plans

A major gap in our understanding of animal development is how adult body plans arise in animals with indirect development, where adults emerge from the transformation of a distinct larval form during metamorphosis. We address this question by examining cellular changes in the enteropneust hemichordate Schizocardium californicum, a species with a complex lifecycle and dramatic metamorphosis. Employing whole-body single-cell RNA sequencing, we chart the cellular composition and transcriptional dynamics of larval, metamorphosis, and adult stages. Our tissue level atlas reveals that ectodermal and endodermal cell types in larvae and adults occupy distinct transcriptional spaces, showing greater similarity to other cell types within the same life stage than to their counterparts in the opposite stage. In contrast, mesodermal cell types from both larvae and adults cluster closely together, indicating conserved transcriptional profiles. These findings demonstrate that the extensive morphological reorganization during metamorphosis is paralleled by profound shifts in cell-type specific transcriptional programs, highlighting the complexity of the larva-to-adult transition.

developmental biology↗

Intrinsic Gestational Timing Governs Human Cerebellar Development After Preterm Birth

Intrinsic programs shape brain maturation, yet which are perturbed by prematurity, and the molecular pathways involved remain unknown. The human cerebellum serves as a paradigm of extrauterine development; its accelerated growth and circuit formation align with the third trimester, a period disrupted by preterm delivery. Through multimodal datasets encompassing in vivo neuroimaging and neurodevelopmental outcomes with postmortem spatial-transcriptomic and histopathological profiling, we show that prematurity diverts the cerebellar developmental trajectory. Cerebellar growth and functional outcomes scaled with gestational age, despite modifying perinatal exposures. Spatially resolved developmental programs underlying macroscopic trajectories were marked by incomplete granule cell maturation and impaired Purkinje cell structural refinement, indicating lineage-specific developmental asynchrony. Thus, prematurity constitutes biologically displaced maturation, in which infants of equivalent post-menstrual age occupy divergent developmental states.

neuroscience↗

Prematurity Reprograms Cerebellar Development and Long-Term Behavior

Preterm survivors often develop motor and socio-cognitive impairments that implicate altered cerebellar development, yet the underlying mechanisms remain poorly understood. A key challenge is that prematurity involves overlapping perinatal insults that converge on the developing brain, making their individual effects difficult to disentangle. Here, we model two major prematurity-associated insults, maternal immune activation (MIA) and neonatal hypoxia (Hx), in mice. By controlling timing and sequence, we define how these insults shape cerebellar assembly during rapid maturation. Comparative analysis with human tissue confirmed that these insults recapitulate key features of the human preterm cerebellum, establishing the translational validity of this model for dissecting insult-specific outcomes. Behavioral and kinematic profiling revealed divergent motor and social phenotypes, which we traced to insult-specific cerebellar remodelling. Hypoxia compromised both granule cell maturation in the internal granule layer and the principal excitatory afferents to Purkinje cells, a circuit state that manifested as impaired motor execution and stereotyped, sensory-disengaged social investigation. Maternal immune activation, by contrast, expanded the granule cell progenitor layer and reduced Purkinje cell dendritic complexity, a phenotype that preserved social preference but reorganized the kinematic structure of social investigation. When hypoxia followed maternal immune activation, it acted on this primed substrate to produce a distinct state in which the features established by prior inflammation were compounded by granule cell proliferative arrest, progressive mitochondrial dysfunction, and aberrant, hyper-interactive social investigation. Together, these findings reframe prematurity-associated insults as cerebellar reprogramming events shaped by both the identity and sequence of insults, linking distinct mechanistic substrates to divergent neurodevelopmental outcomes.

neuroscience↗

Habitat use of juvenile green turtles along the North Pacific coast of Costa Rica

Understanding how threatened marine species use coastal areas and the extent of connectivity across different spatial and temporal scales is important for identifying critical habitats that can enhance conservation efforts in other regions of their distribution. In this study, we investigated the site fidelity and habitat use of juvenile yellow morphotype green sea turtles (Chelonia mydas) in the Gulf of Santa Elena, north Pacific coast of Costa Rica. Fifteen juvenile green sea turtles (49 - 83 cm curved carapace length; CCL) were monitored for 19 - 629 days with an array of 11 acoustic receivers placed within 5 main habitat types: muddy areas, reef patches, macroalgae, rocky reefs, and mangroves. Daily and seasonal locations of the turtles were estimated using a positioning estimation algorithm to determine the site fidelity and habitat use within the study area. Large juveniles ([&ge;] 65 CCL) were detected disproportionally in the macroalgae habitat during the upwelling season (43.9% detections) from December - April, and in the reef patch habitat during the non-upwelling season (36.0%) from May to November. Small juveniles (< 65 cm CCL) had more detections in the reef patch habitat during both seasons (Upwelling: 35.4%, non-upwelling: 45.4%) relative to other habitats sampled. More than half of the turtles monitored (67%) showed strong site fidelity to the study area, ranging from 68.9 to 100% from October 2020 to September 2022. Our results suggest that juvenile green sea turtles, particularly larger individuals, have a strong association with coral / rocky reef patches and macroalgae habitats, similar to adults. Our finding suggested that protecting similar habitats in other areas along the Central American coast will help rebuild the Eastern Pacific Ocean green sea turtle population.

ecology↗

Algorithmic construction of topologically complex biomineral lattices via cellular syncytia

Biomineralization is ubiquitous in both unicellular and multicellular living systems [1, 2] and has remained elusive due to a limited understanding of physicochemical and biomolecular processes [3]. Echinoderms, identified with diverse architectures of calcite-based structures in the dermis[4], present an enigma of how cellular processes control shape and form of individual structures. Specifically, in holothurians (sea cucumbers), multi-cellular clusters construct discrete single-crystal calcite ossicles ([~] 100 {micro}m length scale), with diverse morphologies both across species and even within an individual animal [5]. The local rules that might encode these unique morphologies in calcite ossicles in holothurians remain largely unknown. Here we show how transport processes in a cellular syncytium impart a top-down control on ossicle geometry via symmetry breaking, branching, and fusion in finite cellular clusters. As a unique example of cellular masonary, we show how coordination within a small cluster of cells builds calcite structures about an order of magnitude larger than any individual participating cell. We establish live imaging of ossicle growth in Apostichopus parvimensis juveniles revealing how individual crystalline seeds ([~] 1 - 2 {micro}m) grow inside a multi-cellular syncytial complex with the biomineral completely wrapped within a membrane-bound cytoplasmic sheath. Constructing a topological description of ossicle geometries from 3D micro-CT (computational tomography) data reveals the hidden growth history and conserved patterns across ossicle types. We further demonstrate vesicle transport on the surface of the ossicle, rather than cell motility, regulates material transport to the ossicle tips via a unique cytoskeletal architecture. Finally, using reduced order models of conserved transport on self-closing active branching networks, we highlight the hidden universality in the growth process of distinct ossicles. The system presented here serves as a unique playground merging top-down cellular physiology and classical branching morphogenesis [6] with bottom-up non-equilibrium mineralization [7] processes at the interface of living and non-living matter [8].

biophysics↗

The effects of brief heat during early booting on reproductive, developmental and physiological performance in common wheat (Triticum aestivum L.)

Rising temperatures due to climate change threaten agricultural crop productivity. As a cool-season crop wheat is heat sensitive, but often exposed to high temperatures during cultivation. In the current study, a bread wheat panel of spring wheat genotypes, including putatively heat-tolerant Australian and CIMMYT genotypes, was exposed to a 5-day mild (34{degrees}C/28{degrees}C, day/night) or extreme (37{degrees}C/27{degrees}C) heat stress during the sensitive pollen developmental stage. Worsening effects on anther morphology were observed as heat stress increased from mild to extreme. Even under mild heat a significant decrease in pollen viability and grain number per spike from primary spike was observed compared with the control (21{degrees}C/15{degrees}C), with Sunstar and two CIMMYT breeding lines performing well. A heat-specific positive correlation between the two traits indicates the important role of pollen fertility for grain setting. Interestingly, both mild and extreme heat induced development of new tillers after the heat stress, providing an alternative sink for accumulated photosynthates and significantly contributing to the final yield. Measurements of flag leaf maximum potential quantum efficiency of Photosystem II (Fv/Fm) showed an initial inhibition after the heat treatment, followed by a full recovery within a few days. Despite this, model fitting using chlorophyll SPAD measurements showed an earlier onset or faster senescence rate under heat stress. The data presented here provide interesting entry points for further research into pollen fertility, tillering dynamics and leaf senescence under heat. The identified tolerant wheat genotypes can be used to dissect the underlying mechanisms and breed climate-resilient wheat.

plant biology↗

The blackgrass genome reveals patterns of divergent evolution of non-target site resistance to herbicides.

Globally, weedy plants result in more crop yield loss than plant pathogens and insect pests combined. Much of the success of weeds rests with their ability to rapidly adapt in the face of human-mediated environmental management and change. The evolution of resistance to herbicides is an emblematic example of this rapid adaptation. Here, we focus on Alopecurus myosuroides (blackgrass), the most impactful agricultural weed in Europe. To gain insights into the evolutionary history and genomic mechanisms underlying adaptation in blackgrass, we assembled and annotated its large, complex genome. We show that non-target site herbicide resistance is oligogenic and likely evolves from standing genetic variation. We present evidence for divergent selection of resistance at the level of the genome in wild, evolved populations, though at the transcriptional level, resistance mechanisms are underpinned by similar patterns of up-regulation of stress- and defence-responsive gene families. These gene families are expanded in the blackgrass genome, suggesting that the large, duplicated, and dynamic genome plays a role in enabling rapid adaptation in blackgrass. These observations have wide significance for understanding rapid plant adaptation in novel stressful environments.

genomics↗

Investigating cortical buffering effects of acute moderate and light intensity exercise: a cTBS study targeting the left dorsolateral prefrontal cortex

BackgroundThe beneficial effects of both single-session bouts of aerobic exercise and therapeutic exercise interventions on the cortical regions associated with executive functions (i.e., prefrontal cortex (PFC)) have been well documented. However, it remains unclear whether aerobic exercise can be used to offset temporary fluctuations in cortical activity. ObjectiveThe current study sought to determine whether a single session of moderate intensity aerobic exercise can offset the attenuating effects of continuous theta burst stimulation (cTBS) targeting the dorsolateral prefrontal cortex (dlPFC). MethodsTwenty-two right-handed participants between 18-30 years completed a 20 minute session of light intensity (10% heart rate reserve (HRR)) and moderate intensity (50% HRR) exercise in a counterbalanced order. Following each exercise session, participants received active cTBS to the left dlPFC. Changes in executive functions were quantified using a flanker paradigm employed at baseline, post-exercise and post-cTBS time points. Additionally, EEG methodologies were used to measure changes in inhibitory control specific event-related potential components (i.e., P3 and N2) in response to the flanker task. ResultsBehavioural results from the flanker task revealed a significant improvement in task performance following an acute bout of moderate intensity exercise. Furthermore, the effect of cTBS in both light and moderate intensity conditions were non significant Similarly, EEG data from P3 and N2 ERP components revealed no changes to amplitude across time and condition. P3 latency data revealed a significant effect of time in the light intensity condition, such that latency was faster following cTBS. Similarly, latency data within the N2 ERP component revealed a significant effect of time on congruent trials in the light intensity condition; N2 latency was faster following cTBS. ConclusionThe current study revealed that light and moderate intensity exercise may provide a buffer to cTBS-induced attenuation of the dlPFC. This study provides empirical and theoretical implications on the potential for exercise to promote cognitive control.

neuroscience↗

Pseudogenization, genome streamlining and specific gene repertoire landmark the genomes of Carnobacterium maltaromaticum isolated from diseased sharks

Carnobacterium maltaromaticum is a well-known pathogen of bony fish. More recently, C. maltaromaticum have been isolated from the brain and inner ear of disorientated and stranded common thresher (Alopias vulpinus) and salmon shark (Lamna ditropis). While thresher shark strandings are recent, salmon sharks have been stranding for decades, suggesting a long-term association between C. maltaromaticum and sharks. Interestingly, some strains of C. maltaromaticum are used by the food industry for their probiotic and antimicrobial activity. Here, we sequenced the genome of 9 C. maltaromaticum strains (SK-isolates) from diseased common thresher and salmon sharks and compared them to other C. maltaromaticum strains in order to identify the genomic signatures that differentiate the disease-associated from the innocuous C. maltaromaticum isolates. SK strains formed a monophyletic clade, with a conserved gene repertoire, and shared a high degree of pseudogenization even though isolates were from different shark species, locations, and across years. In addition, these strains displayed few virulence associated genes and unique genomic regions, some resulting from horizontal gene transfer. The association of diseased sharks and SK strains suggests their role as potential pathogens. Although the high degree of pseudogenization suggests a transition to a host-adapted lifestyle, a set of conserved functional genes highlights the need of essential functions required for a host-independent life style. Globally, this work identifies specific genomic signatures of C. maltaromaticum strains isolated from infected sharks, provides the framework to elucidate the role of SK strains in the development of the disease in sharks, and further investigate the dissemination of SK strains in populations of wild fish.

genomics↗

Effect of Live Attenuated Influenza Vaccine on Pneumococcal Carriage

The widely used nasally-administered Live Attenuated Influenza Vaccine (LAIV) alters the dynamics of naturally occurring nasopharyngeal carriage of Streptococcus pneumoniae in animal models. Using a human experimental model (serotype 6B) we tested two hypotheses: 1) LAIV increased the density of S. pneumoniae in those already colonised; 2) LAIV administration promoted colonisation. Randomised, blinded administration of LAIV or nasal placebo either preceded bacterial inoculation or followed it, separated by a 3-day interval. The presence and density of S. pneumoniae was determined from nasal washes by bacterial culture and PCR. Overall acquisition for bacterial carriage were not altered by prior LAIV administration vs. controls (25/55 [45.5%] vs 24/62 [38.7%] respectively, p=0.46). Transient increase in acquisition was detected in LAIV recipients at day 2 (33/55 [60.0%] vs 25/62 [40.3%] in controls, p=0.03). Bacterial carriage densities were increased approximately 10-fold by day 9 in the LAIV recipients (2.82 vs 1.81 log10 titers, p=0.03). When immunisation followed bacterial acquisition (n=163), LAIV did not change area under the bacterial density-time curve (AUC) at day 14 by conventional microbiology (primary endpoint), but significantly reduced AUC to day 27 by PCR (p=0.03). These studies suggest that LAIV may transiently increase nasopharyngeal density of S. pneumoniae. Transmission effects should therefore be considered in the timing design of vaccine schedules.\n\nTrial registrationThe study was registered on EudraCT (2014-004634-26)\n\nFundingThe study was funded by the Bill and Melinda Gates Foundation and the UK Medical Research Council.

immunology↗

Thermal adaptation constrains the temperature dependence of ecosystem metabolism

Gross primary production (GPP) is the largest flux in the carbon cycle, yet its response to global warming is highly uncertain. The temperature sensitivity of GPP is directly linked to photosynthetic physiology, but the response of GPP to warming over longer timescales could also be shaped by ecological and evolutionary processes that drive variation community structure and functional trait distributions. Here, we show that selection on photosynthetic traits within and across taxa dampen the effects of temperature on GPP across a catchment of geothermally heated streams. Autotrophs from cold streams had higher photosynthetic rates and after accounting for differences in biomass among sites, rates of ecosystem-level GPP were independent of temperature, despite a 20 {o}C thermal gradient. Our results suggest that thermal adaptation constrains the long-term temperature dependence of GPP, and highlights the importance of considering physiological, ecological and evolutionary mechanisms when predicting how ecosystem-level processes respond to warming.

ecology↗

Adaptation to warming increases the strength of an algal-grazer interaction in naturally heated streams

Trophic interactions are important determinants of the structure and functioning of ecosystems. As the metabolism and consumption rates of ectotherms increase sharply with temperature, there are major concerns that global warming will increase the strength of trophic interactions, destabilizing food webs, and altering ecosystem structure and function. We used geothermally warmed streams that span a [~]10{degrees}C temperature gradient to investigate the interplay between temperature-driven selection on traits related to metabolism and resource acquisition, and the interaction strength between the keystone gastropod grazer, the wandering snail Radix balthica, and a common algal resource. Populations from a warm stream ([~]28{degrees}C) had higher maximal metabolic rates and optimal temperatures than their counterparts from a cold stream ([~]17{degrees}C). We found that metabolic rates of the population originating from a warmer stream were higher across all measurement temperatures. A reciprocal transplant experiment demonstrated that the interaction strengths between the grazer and its algal resource were highest for both populations when transplanted into the warm stream. In line with the thermal dependence of respiration, interaction strengths of grazers from the warm stream were always higher than those of grazers from the cold stream. These findings suggest that warming can increase the strength of algal-grazer interactions through the thermodynamic effects of higher temperatures on physiological rates as well as through correlated increases in per capita metabolism and consumption.

ecology↗