Biology subjects

Butler, J.

Publications and source records attributed to Butler, J..

At least 19 recordsLinked to original sources

bioRxiv2026

First detected incursions of avian influenza H5N1 clade 2.3.4.4b into mainland Australia from the Southern Ocean

High pathogenicity avian influenza H5N1 clade 2.3.4.4b has caused a panzootic of devastating impact to poultry and wildlife globally. The Australian continent and broader Oceania until recently remained the last major region without confirmed detections. Here we report the first H5N1 clade 2.3.4.4b detections from two live seabirds - a brown skua and a southern giant petrel - found on the south coast of Western Australia in June 2026. Virus genome sequencing showed that both viruses were most closely related to H5N1 viruses detected recently on sub-Antarctic islands in the Southern Indian Ocean. In time-calibrated phylogeographic analyses, both viruses sampled in Western Australia clustered with viruses from Heard Island, a sub-Antarctic external territory of Australia. Ancestral location reconstruction also identified Heard Island as the most probable source location, although unsampled intermediate locations cannot be excluded. The two Western Australian detections were estimated to be independent incursions from Heard Island, rather than local transmission on mainland Australia. There was no evidence of reassortment with endemic avian influenza viruses in Australia, and both virus sequences retained key avian-like genetic markers and lacked known substitutions for reduced antiviral susceptibility. These detections revealed a Southern Ocean pathway of recurrent H5N1 incursions into Australia, highlighting the risk of potential establishment on the mainland and the need for heightened surveillance and rapid, nationally-coordinated, virus genomic characterisation.

microbiology↗

bioRxiv2026

The essential molecular components for cellular CO2 sensing via connexins

CO2 opens a subset of connexin hemichannels by binding to a site in the cytoplasmic domain of the channel. From outside the cell, CO2 must cross at least one membrane to reach this site. We have used Neuro-2A cells, which exhibit very low expression of CO2 permeable aquaporins (AQPs) and do not express any of the connexins (Cxs) known to be CO2 sensitive, to evaluate the minimal complement of molecular components required to recapitulate whole cell CO2 sensitivity mediated by connexins (assayed by either whole cell patch clamp recordings or real time recordings of ATP release via a co-expressed genetically encoded ATP sensor). Neuro-2A cells that expressed either Cx26, Cx32 or Cx43 on their own did not exhibit CO2-dependent connexin hemichannel gating. Expression of AQP1 or AQP5 either with or without carbonic anhydrase 2 (CA2) did not reveal any endogenous CO2 sensitivity of Neuro-2A cells. Only by expressing one of Cx26, Cx32 or Cx43 with either AQP1 or AQP5, plus CA2 were we able to reconstitute whole cell CO2 sensitivity. We found that expression of Cx26 with either AQP1 or AQP5 resulted in high levels of cell death. This was prevented by co-expression of CA2. Simulations of the influx and diffusion of CO2 show that CA2 prevents accumulation of intracellular CO2 and excessive activation of Cx26, thus protecting the cells from death. Surveying the transcriptome of cells that express CO2 sensitive connexins shows that many also express CO2 permeable aquaporins and CA2. We suggest that connexins, aquaporins and carbonic anhydrases represent the minimal trifecta of components required for cellular CO2 sensing.

cell biology↗

bioRxiv2026

Deep evolutionary origins of the connexin gene family

The vertebrate connexin family encodes a diverse repertoire of transmembrane channels that mediate both intercellular communication and cytosol to extracellular space exchange. Their apparent absence in non-chordates has led to the prevailing view that connexins arose during chordate evolution with analogous functions performed in non-chordates by the innexins, a structurally similar but non-homologous protein family. Here, using a combination of sequence and structural analyses, we discover the presence of connexins in anthozoan and protostome genomes despite widespread secondary gene loss in Bilateria. We show that these connexins can be present in up to 100 copies per genome and are often found as N-terminal domains of NOD-like receptors (NLRs) or other immune genes. We show that these invertebrate connexins localise at the cell membrane, function as either hemichannels (anthozoans and protostomes) or gap junctions (protostomes), and respond to depolarisation enabling the transfer of small molecules. Further, we demonstrate that a subset of the invertebrate connexin-like domains are sensitive to CO2 and mirroring findings in vertebrate connexins, the CO2-mediated gating stems from the formation of a carbamate bridge between neighbouring subunits. Taken together, we trace the evolution of this gene family to the cnidarian-bilaterian ancestor, demonstrate functional similarity between invertebrate and vertebrate connexins, and suggest an ancient role of connexins in innate immunity.

evolutionary biology↗

bioRxiv2026

Discovery, characterisation and optimisation of bicyclic peptide inhibitors that disarm Staphylococcus aureus a-hemolysin

-Hemolysin (Ahly) is a major Staphylococcus aureus virulence determinant implicated in tissue injury and immune dysregulation; antibody inhibitors have reached clinical trials but alternatives with improved ease of manufacture and tissue penetration are desirable. Here we demonstrate that phage-derived bicyclic peptides can serve as compact, chemically tractable Ahly neutralisers. Using TATB-scaffolded M13 phage libraries we identified WNP-motif containing bicyclic binders, with a lead hit of Peptide 14 (KD = 1792nM) and progressed the lead by iterative affinity maturation to Peptide 20 (KD = 609 nM) and by incorporation of strategically chosen non-canonical amino acids to yield Peptide 88 (KD = 96 nM). A 2.2 [A] co-crystal structure with AhlyH35A locates the binding footprint on the rim domain and explains the critical role of the WNP motif in target engagement. Functional assays show that the Peptide 88 blocks Ahly mediated hemolysis, inhibits Ahly driven ADAM10 activation, and elucidate its inhibitory mechanism of preventing Ahly binding to human A549 epithelial cells. Peptide 88 protects A549 cells from recombinant toxin and attenuates cytotoxicity in S. aureus co-culture experiments, whilst showing no toxicity to A549 cells. Bicyclic peptides thus represent a new and promising anti-virulence modality: small, synthetically accessible molecules that mimic antibody recognition, with therapeutic potential against S. aureus infections.

molecular biology↗

bioRxiv2026

Targeting autoimmunity in Rheumatoid Arthritis with nanoparticles displaying Liprin-1 peptide

Nanoparticle-based strategies offer a promising tool for inducing antigen-specific immune tolerance across various autoimmune conditions, by acting as master switch to turn-off the autoimmune response. Building on our previous work demonstrating the therapeutic potential of plant-made nanoparticles in rheumatoid arthritis, we present a systematic evaluation of key parameters--including dosing regimen, route of administration, and immunization schedule--to optimize both efficacy and safety. We developed virus-based nanomaterials expressing Tomato Bushy Stunt Virus (TBSV) nanoparticles engineered to display the immunodominant Liprin-1 peptide in the Nicotiana benthamiana plant platform. The mechanisms responsible for the observed protective effects against rheumatoid arthritis were also investigated. Our findings highlight the critical role of repeated intravenous administration and precise dosing in promoting regulatory T cell (Treg) induction and cytokine modulation. Furthermore, we dissected the individual contributions of the Liprin-1 peptide and the viral capsid scaffold in driving immune tolerance. These results support the potential of plant-derived nanoparticles as a versatile and effective platform for antigen-specific immunotherapy, with rheumatoid arthritis serving as a proof-of-concept model for broader applications in the field of autoimmunity. One Sentence SummaryPlant-made nanomaterials induce tolerance in arthritis models via repeated IV dosing, triggering an antigen-specific regulatory immune response.

pharmacology and toxicology↗

bioRxiv2025

Regulation of N-glycosylation efficiency by eukaryotic oligosaccharyltransferase

Oligosaccharyltransferase (OST) catalyses the key step of N-glycosylation, transferring immature N-glycans to select Asn residues in nascent proteins in the endoplasmic reticulum (ER). Asn are more likely to be glycosylated in the context of a "glycosylation sequon", N-x-S/T (x=P), but not every sequon is glycosylated. Tight positive and negative regulation of site-specific N-glycosylation across the glycoproteome is essential because some Asn require glycosylation for productive protein folding or function, while others must remain unglycosylated. Despite its importance, the underlying bases for this regulation are illdefined. Here we characterise the molecular determinants regulating OST catalytic efficiency. We identify preferred substrates of OST, and show that the local sequence determines glycosylation efficiency by fine-tuning binding to an extended groove in OST along an eight residue stretch centered at the Asn acceptor. Tight control of OST activity is achieved through a switch, set ON when a peptide binds with high complementarity to the groove, triggering release of the assisting base Glu350 for catalysis. Based on analysis of buried sequons, we identify sequence characteristics associated with inherently non-preferred acceptor substrates for OST, and show these have a high propensity for local secondary structure incompatible with the optimal conformation of a peptide bound to OST. Finally, we validate these mechanisms by examining the determinants of efficient glycosylation at a variably glycosylated Asn in a set of human Fabs. These mechanistic and functional insights show how local protein sequence controls glycosylation occupancy with immediate implications in secretory protein function and evolution, pathogen immunity and epistasis, and in engineering protein sequences for the desired degree of site-specific glycosylation.

biochemistry↗

bioRxiv2025

Human neurons undergo protracted functional maturation into adulthood

Summary ParagraphHuman cognitive development is uniquely prolonged1-3, reflecting the extended postnatal maturation of the cerebral cortex where cell-type differentiation4,5, synaptogenesis6,7, myelination8 and transcriptional regulation5,9,10 all follow protracted developmental timelines. However, when human cortical neurons reach functional electrophysiological maturity and how their developmental trajectory compares to other species remains unknown. Here we show through patch-clamp recordings of human temporal cortex from infancy to adulthood that supragranular pyramidal neurons exhibit pronounced neoteny of their functional properties, with physiological maturation continuing well into adulthood. Comparing human and mouse developmental trajectories reveals human neurons are on a much slower developmental timeline, maturing physiologically hundreds of times slower than mouse and 2-6 times slower than would be predicted from anatomical brain growth differences between species. This reflects a fundamentally different allometric relationship between physiological and anatomical maturation; while mouse neuronal physiology closely tracks brain growth, human physiological development follows its own extended timeline. This slow maturation results in different stages of cognitive development being supported by functionally distinct neuronal populations, with the progression from infancy to middle age characterized by specific electrophysiological profiles. Notably, a neuronal subtype thought to be human-specific, with electrophysiological traits that enhance computational capacity, appears only in late adolescence or early adulthood. This extreme protraction of neurophysiological development provides a cellular basis for prolonged human cognitive maturation, demonstrating that neuronal physiological neoteny represents a fundamental evolutionary adaptation in human brain development.

neuroscience↗

bioRxiv2025

Life at the extremes: Maximally divergent microbes with similar genomic signatures linked to extreme environments

Extreme environments impose strong mutation and selection pressures that drive distinctive, yet understudied, genomic adaptations in extremophiles. In this study, we identify 15 bacterium-archaeon pairs that exhibit highly similar k-mer-based genomic signatures despite maximal taxonomic divergence, suggesting that shared environmental conditions can produce convergent, genome-wide patterns that transcend evolutionary distance. To uncover these patterns, we developed a computational pipeline to select a composite genome proxy assembled from non-contiguous subsequences of the genome. Using supervised machine learning on a curated dataset of 693 extremophile microbial genomes, we found that 6-mers and 100 kbp genome proxy lengths provide the best balance between classification accuracy and computational efficiency. Our results provide conclusive evidence of the pervasive nature of k-mer-based patterns across the genome, and uncover the presence of taxonomic and environmental components that persist across all regions of the genome. The 15 bacterium-archaeon pairs identified by our method as having similar genomic signatures were validated through multiple independent analyses, including 3-mer frequency profile comparisons, phenotypic trait similarity, and geographic co-occurrence data. These complementary validations confirmed that extreme environmental pressures can override traditionally recognized taxonomic components at the whole-genome level. Together, these findings reveal that adaptation to extreme conditions can carry robust, taxonomic domain-spanning imprints on microbial genomes, offering new insight into the relationship between environmental mutagenesis and selection and genome-wide evolutionary convergence.

bioinformatics↗

bioRxiv2025

CO2 sensitive connexin channel synapses in the VTA release 5HT to regulate dopaminergic neurons

Hypercapnic arousal is a life-preserving reflex that promotes awakening in response to elevated PCO2, yet the cellular mechanisms by which CO2 is detected remain incompletely understood. Serotonergic neurons of the dorsal raphe (DR) have been implicated in hypercapnic responses, but the molecular sensor that directly detects CO2 within this circuit is unknown. Here, we show that the CO2-gated connexin 26 (Cx26) hemichannel is expressed on serotonergic terminals projecting from the DR to the ventral tegmental area (VTA). Brief elevations in PCO2 modulated the excitability of VTA dopamine neurons through serotonergic signaling without altering glutamatergic transmission, and these effects were abolished by pharmacological inhibition of hemichannels. By expressing Cx26 and genetically encoded GRAB5HT sensors in cultured cells, we further demonstrate that Cx26 hemichannels opened by elevated PCO2 are directly permeable to serotonin. Selective removal of CO2 sensitivity from Cx26 in DR serotonergic neurons delayed arousal from sleep during transient hypercapnia and reduced activation of VTA dopamine neurons in vivo. Together, these findings identify Cx26 hemichannels as a direct CO2 sensor that enables serotonin release through a channel co-synapse and contributes to hypercapnic arousal.

neuroscience↗

bioRxiv2025

Cell-to-cell signalling mediated via CO2: activity dependent CO2 production in the axonal node opens Cx32 in the Schwann cell paranode.

Loss of function mutations of Cx32, which is expressed in Schwann cells, cause X-linked Charcot Marie Tooth disease, a slowly progressive peripheral neuropathy. Cx32 is thus essential for the maintenance of myelin. During action potential propagation, Cx32 hemichannels in the Schwann cell paranode are thought to open and release ATP. As Cx32 hemichannels are directly sensitive to CO2, we have tested whether CO2 produced in the axon, as a consequence of the energetic demands of action potential propagation, might gate Cx32 hemichannels. Using isolated sciatic nerve from the mouse, we have shown that the critical components required for intercellular CO2 signalling are present (nodal mitochondria, the source of CO2; a CO2-permeable aquaporin, AQP1; paranodal Cx32; and carbonic anhydrase). We have used a membrane impermeant fluorescent dye FITC, which can permeate Cx32 hemichannels, to demonstrate the opening of Cx32 in Schwann cells in response to an external CO2 stimulus or during action potential propagation in the isolated nerve. Pharmacological blockade of AQP1 or allosteric enhancement of carbonic anhydrase activity greatly reduced Cx32 gating during action potential firing. By contrast, inhibition of carbonic anhydrase with acetazolamide greatly increased Cx32 gating. Cx32 gating was unabected by the G-protein blocker GDP{beta}S, indicating that it was not mediated by G protein coupled receptors. By expressing a modified Cx32 subunit, Cx32DN, that coassembles with Cx32WT, we have shown that the activity dependent dye loading of Schwann cells depends upon CO2 binding to Cx32. This CO2-dependent opening of Cx32 also mediates an activity dependent Ca2+ influx into the paranode and, by increasing the leak current across the myelin sheath, slows the conduction velocity. Our data demonstrate that CO2 can act via connexins to mediate neuron-to-glia signalling and that CO2 permeable aquaporins and carbonic anhydrase are key components of this signalling mechanism.

neuroscience↗

bioRxiv2025

The Origin, Diagnosis, and Prognosis of Oligomannose-Type Diffuse Large B Cell Lymphoma

The acquisition of N-glycosylation sites occupied by oligomannose-type glycans in the immunoglobulin complementarity-determining region (CDR) is an early clonal tumor-specific identifier of follicular lymphoma (FL). CDR-located N-glycosylation sites are also acquired in germinal-center-B-cell-like diffuse large B-cell lymphomas (GCB-DLBCL), but their significance is less defined. We used RNA-seq immunoglobulin assembly to determine the frequency and CDR location of the acquired N-glycosylation sites (AGS) in two large independent DLBCL cohorts. Composition of the glycans occupying the AGS was determined using liquid chromatography-mass spectrometry and correlated with cell-of-origin, FL signature (defined by EZB phenotype or BCL2 translocation), transcript profile, and clinical outcome. CDR-located AGS were observed in 41-46% of GCB-DLBCL but were rare in other DLBCL. Only CDR-located AGS of DLBCL with an FL signature were occupied by oligomannose-type glycans. These DLBCL were termed Mann-type DLBCL. Conversely, the AGS of the other DLBCL were either non-glycosylated or occupied by complex-type glycans. Mann-type status was an independent marker of short progression-free survival and overall survival. In contrast, the other GCB-DLBCL cases, including those with an FL signature but without AGS, had the best outcomes. Mann-type DLBCL overexpressed gene-sets of cell growth, survival, and cycling, and underexpressed proinflammatory and apoptotic pathways, irrespective of concomitant MYC translocations. Acquisition of Mann-type glycans is a highly selective environmental pressure, identifying the most aggressive GCB-DLBCL with an origin related to FL. The detection of AGS in the CDR of GCB-DLBCLs with a BCL2 translocation defines Mann-type DLBCLs, refines prognosis and marks a precise tumor interaction to block early therapeutically. Key pointsO_LIAcquisition of Mann-type glycans is a tumor-specific environmental pressure identifying the most aggressive GCB-DLBCL with an origin related to FL. C_LIO_LIMann-type DLBCL can be diagnosed by the concomitant detection of AGS in the CDR and a BCL2 translocation. C_LI

cancer biology↗

bioRxiv2025

On the mechanisms of permselectivity of connexin hemichannels to small molecules

Connexins can either that act as hemichannels, to facilitate ion and small molecule movement from the cytosol to the extracellular space or as gap junction channels to provide a pathway for solute exchange between cells. Connexins are ubiquitously expressed throughout the body and are implicated in a wide range of processes. The permselectivity of connexin hemichannels for small neurochemicals remains poorly understood. By coexpressing genetically encoded fluorescent sensors for ATP, glutamate and lactate with a range of connexins, we examined the ability of different hemichannels to permit release of these compounds under physiological conditions and in response to physiological stimuli (small changes in PCO2 and transmembrane depolarisation). We found that some connexin hemichannels were relatively non-selective (Cx26, Cx32, Cx43, Cx31.1) allowing passage of ATP, glutamate and lactate. By contrast other connexin hemichannels (Cx36, Cx46 and Cx50) were highly selective. Cx36 and Cx46 hemichannels allowed release of ATP, but not glutamate or lactate. The size of the permeating molecule cannot be the sole determinant of permselectivity. By contrast, Cx50 hemichannels permitted the release of lactate and glutamate but not ATP. We also found that the nature of the opening stimulus could alter the permselectivity of the hemichannel-for some of the relatively non-selective connexins, hemichannel opening via depolarisation was ineffective at allowing release of lactate. By performing a mutational analysis, informed by the differential selectivity of the closely related Cx46 and Cx50 hemichannels, we found that the charge on the N-terminus and N-terminus-TM2 interactions are key contributors to permselectivity for ATP.

cell biology↗

bioRxiv2025

Connexin50 hemichannels are opened by CO2: implications for lens physiology

Connexin50 (Cx50) is expressed in lens fibre cells. As mutations of Cx50 cause cataracts its physiological role in the lens must be important. We have used recent cryoEM structures of Cx50 and the predictive power of Alphafold3 to identify the presence of a carbamylation motif, originally described in Cx26, that suggests that Cx50 might be CO2 sensitive. By expressing the naturally truncated version of Cx50 in HeLa cells and utilising coexpression of genetically encoded sensors iGluSnFr or eLACCO1.1, we have demonstrated the CO2-dependent opening of Cx50 hemichannels, and their permeability to lactate and glutamate. By mutating the two key residues of the carbamylation motif, K105 and K140, we have shown that the motif is required for CO2 sensitivity. Mutations of the residue V44 cause cataracts and these mutations abolish the CO2 sensitivity of Cx50. Using Fluo-4 Ca2+ imaging with lens slices we have demonstrated CO2-dependent Ca2+ influxes into fibre cells that are blocked by La3+ and exhibit the same CO2 dose dependence as Cx50 hemichannels. Lens fibre cells respond to glutamate via NMDA receptors and our data shows that the Ca2+ influx to raised PCO2 partially depends on NMDA receptor activation. We hypothesize that CO2-dependent gating of Cx50, subsequent release of glutamate resulting in the downstream activation of glutamate receptors, and the consequent alterations in transmembrane Na+ fluxes, provide homeostatic control of the microcirculation system that is critical for lens health.

cell biology↗

bioRxiv2025

CO2-dependent opening of Connexin 43 hemichannels

Sequence and structure comparisons between alpha and beta connexins, Cx43 and Cx26, revealed that Cx43 has a motif, the carbamylation motif, that confers CO2-sensitivity on a subset of beta connexins. By using a fluorescent dye loading assay, whole cell patch clamp recordings and real time measurement of ATP release via GRABATP we have demonstrated that Cx43 hemichannels open in a highly CO2 sensitive manner over the range 20 to 70 mmHg. Mutational analysis confirms that the equivalent residues to those in Cx26 that have been shown to be involved in mediating the effects of CO2 on gating of hemichannels and gap junction channels, also mediate Cx43 hemichannel gating. Our data predicts that Cx43 will be partially open and able to release ATP at resting physiological levels of PCO2. We have tested this prediction in acute hippocampal slices, by showing that CO2-dependent enhancement of synaptic transmission can be blocked by the Cx43-selective mimetic peptide Gap26. Our data resolves an inconsistency in the literature between in vivo studies suggesting that Cx43 hemichannels are at least partially open at rest, and in vitro studies, performed in the absence of HCO3-/CO2 buffering that show Cx43 hemichannels are shut. Our evidence suggests that the ancestral gene that duplicated to give the alpha and beta connexin clades must have possessed the carbamylation motif. CO2 sensitivity is thus a fundamental ancient characteristic of several connexins that has been lost in more recently derived members of this gene family.

neuroscience↗

bioRxiv2024

Comprehensive Analysis of Human Dendritic Spine Morphology and Density: Exploring Diversity of Human Dendritic Spines

Dendritic spines, small protrusions on neuronal dendrites, play a crucial role in brain function by changing shape and size in response to neural activity. So far, in depth analysis of dendritic spines in human brain tissue is lacking. This study presents a comprehensive analysis of human dendritic spine morphology and density using a unique dataset from human brain tissue from 27 patients (8 females, 19 males, aged 18-71) undergoing tumor or epilepsy surgery at three neurosurgery sites. We used acute slices and organotypic brain slice cultures to examine dendritic spines, classifying them into the three main morphological subtypes: Mushroom, Thin, and Stubby, via 3D reconstruction using ZEISS arivis Pro software. A deep learning model, trained on 39 diverse datasets, automated spine segmentation and 3D reconstruction, achieving a 74% F1-score and reducing processing time by over 50%. We show significant differences in spine density by sex, dendrite type, and tissue condition. Females had higher spine densities than males, and apical dendrites were denser in spines than basal ones. Acute tissue showed higher spine densities compared to cultured human brain tissue. With time in culture, Mushroom spines decreased, while Stubby and Thin spine percentages increased, particularly from 7-9 to 14 days in vitro, reflecting potential synaptic plasticity changes. Our study underscores the importance of using human brain tissue to understand unique synaptic properties and shows that integrating deep learning with traditional methods enables efficient large-scale analysis, revealing key insights into sex- and tissue-specific dendritic spine dynamics relevant to neurological diseases. New and NoteworthyThis study presents a dataset of nearly 4,000 morphologically reconstructed human dendritic spines across different ages, gender, and tissue conditions. The dataset was further used to evaluate a deep learning algorithm for three-dimensional spine reconstruction, offering a scalable method for semi-automated spine analysis across various tissues and microscopy setups. The findings enhance understanding of human neurology, indicating potential connections between spine morphology, brain function, and the mechanisms of neurological and psychiatric diseases.

neuroscience↗

bioRxiv2023

A cognitive map for value-guided choice in ventromedial prefrontal cortex

The prefrontal cortex is crucial for economic decision-making and representing the value of options. However, how such representations facilitate flexible decisions remains unknown. We reframe economic decision-making in prefrontal cortex in line with representations of structure within the medial temporal lobe because such cognitive map representations are known to facilitate flexible behaviour. Specifically, we framed choice between different options as a navigation process in value space. Here we show that choices in a 2D value space defined by reward magnitude and probability were represented with a grid-like code, analogous to that found in spatial navigation. The grid-like code was present in ventromedial prefrontal cortex (vmPFC) local field potential theta frequency and the result replicated in an independent dataset. Neurons in vmPFC similarly contained a grid-like code, in addition to encoding the linear value of the chosen option. Importantly, both signals were modulated by theta frequency - occurring at theta troughs but on separate theta cycles. Furthermore, we found sharp-wave ripples - a key neural signature of planning and flexible behaviour - in vmPFC, which were modulated by accuracy and reward. These results demonstrate that multiple cognitive map-like computations are deployed in vmPFC during economic decision-making, suggesting a new framework for the implementation of choice in prefrontal cortex.

neuroscience↗

bioRxiv2023

Latitudinal gradients in predation persist in urban environments

Urbanization can profoundly disrupt local ecology. But while urban areas now stretch across latitudes, little is known about urbanizations effects on macroecological patterns. We used standardized experiments to test whether urbanization disrupts latitudinal gradients in seed predation, a macroecological pattern that shapes community assembly and diversity. Using >56,000 seeds, we compared predation in urbanized and natural areas across 14,000 km of latitude, spanning the Americas. Predation increased 5-fold from high latitudes to the tropics, and latitudinal gradients in predation persisted in urban areas despite significant habitat modification. Urbanization reduced predation by vertebrates, but not invertebrates, and seemed to increase ant predation specifically. Our results show that macroecological patterns in predation intensity can persist in urbanized environments, even as urbanization alters the relative importance of predators. One-Sentence SummaryAcross 56,000 seeds and 112{degrees} of latitude, latitudinal gradients in seed predation are equally strong in natural vs. urban areas

ecology↗

bioRxiv2023

Cell type-specific gene expression dynamics during human brain maturation

The human brain undergoes protracted post-natal maturation, guided by dynamic changes in gene expression. Most studies exploring these processes have used bulk tissue analyses, which mask cell type-specific gene expression dynamics. Here, using single nucleus (sn)RNA-seq on temporal lobe tissue, including samples of African ancestry, we build a joint paediatric and adult atlas of 75 cell subtypes, which we verify with spatial transcriptomics. We explore the differences between paediatric and adult cell types, revealing the genes and pathways that change during brain maturation. Our results highlight excitatory neuron subtypes, including the LTK and FREM subtypes, that show elevated expression of genes associated with cognition and synaptic plasticity in paediatric tissue. The new resources we present here improve our understanding of the brain during its development and contribute to global efforts to build an inclusive brain cell map.

neuroscience↗