Biology subjects

Robinson, D.

Publications and source records attributed to Robinson, D..

At least 19 recordsLinked to original sources

bioRxiv2026

BirdCODE: Detecting bird communication at scale

Deep learning-based animal sound identification is regularly applied to large audio datasets for ecological monitoring and citizen science, but existing methods lack the fine temporal resolution required to extract insights into animal communication from these same datasets. Here we introduce Bird Communication Detector (BirdCODE), a deep learning model that detects and classifies the vocalizations of over 9000 bird species with precise temporal boundaries, a several hundredfold increase the number of species over previous bioacoustic sound event detection models. In extensive benchmarking, BirdCODE achieves state-of-the-art performance in detection and classification of bird sounds. Applying BirdCODE to 1.3M citizen-science recordings, we present four case studies of how BirdCODE-computed sound event boundaries can be used to carry out phylogenetic analyses, to describe geographic and temporal variation in acoustic communication, and to characterize cross-species interactions. Together, these demonstrate how BirdCODE can enable large-scale, data-driven studies of bird communication. Model code, weights, and predictions are publicly available.

bioinformatics↗

bioRxiv2026

Genomic Determinants of Lethality and Therapeutic Vulnerability in Castration-Resistant Prostate Cancer

Despite extensive characterization, the molecular determinants that shape disease progression and therapeutic outcomes in metastatic castration-resistant prostate cancer (mCRPC) remain incompletely defined. This large, multi-institutional analysis reveals that the genomic determinants of outcomes in primary prostate cancer are distinct from those in castration-resistant disease. We identify androgen-regulated MYC fusions as potent primary genetic drivers catalyzing early progression. Additionally, across independent mCRPC cohorts, we validate TP53, RB1, and CDKN1B alterations as the strongest genetic drivers of poor survival. Mechanistically, CDKN1B loss induces an AR-positive epithelial-mesenchymal transition rather than neuroendocrine differentiation, while TP53 loss triggers whole-genome duplication and subsequent adaptive copy-number gains. Within TP53-altered tumors, AR amplifications confer improved survival while AR mutations are protective regardless of TP53 status. Integrating these genomic events with transcriptomic phenotypes, we derive CAPrisk, a multi-omic prognostic classifier. CAPrisk stratifies patients with mCRPC into three risk groups with >33-month survival differences and predicts outcomes across androgen receptor pathway inhibitors, taxanes, PARP-inhibitors, and radium-223. Together, these findings expand the clinical utility of genomic profiling in advanced prostate cancer and establish a framework for risk stratification in lethal disease. IN BRIEF (eTOC BLURB)Rebernick et al. analyze a multi-institutional cohort of 1,331 prostate cancer samples and identify the genomic determinants of progression to lethal, castration-resistant disease. They define rare AR-regulated MYC fusions and haploinsufficient CDKN1B loss as drivers of poor outcome while highlighting AR alterations as predictors of improved prognosis. They develop CAPrisk, a multi-omic classifier that stratifies patient outcomes across androgen receptor pathway inhibitors, taxanes, PARP-inhibitors, and radium-223. HIGHLIGHTS- AR-regulated MYC fusions are rare ([~]2%) truncal events driving aggressive disease. - Distinct AR alterations drive favorable outcomes in TP53-altered and non-altered contexts. - Haploinsufficient CDKN1B loss predicts poor survival in AR-positive tumors. - A multi-omic model predicts outcomes across four standard-of-care therapies. MI-OncoSeq TeamChandan Kumar, Erica Rabban, Kayla Muschong, Lakshmi P. Kunju, Javed Siddiqui, Yu Ning, Rui Wang, Fengyun Su, Yelena Kleyman-Smith, Josh N. Vo, Jin Chen, Rahul Mannan Stand Up To Cancer TeamWassim Abida, Joanna Cyrta, Glenn Heller, Davide Prandi, Joshua Armenia, Ilsa Coleman, Matteo Benelli, Eliezer M. Van Allen, Andrea Sboner, Tarcisio Fedrizzi, Juan Miguel Mosquera, Brian D. Robinson, Navonil De Sarkar, Lakshmi P. Kunju, Scott Tomlins, Daniel Nava Rodrigues, Massimo Loda, Anuradha Gopalan, Victor E. Reuter, Colin C. Pritchard, Joaquin Mateo, Diletta Bianchini, Susana Miranda, Suzanne Carreira, Pasquale Rescigno, Julie Filipenko, Jacob Vinson, Robert B. Montgomery, Himisha Beltran, Elisabeth I. Heath, Howard I. Scher, Philip W. Kantoff, Mary-Ellen Taplin, Nikolaus Schultz, Johann S. deBono, Francesca Demichelis, Peter S. Nelson, Mark A. Rubin, Charles Sawyers

Cancer Biology↗

bioRxiv2026

A pooled screening approach reveals bacterial chemoreceptors for short-chain carboxylic acids

Bacterial chemotaxis is a key process in host colonization and virulence, mediated by large repertoires of chemoreceptors. Despite their physiological and ecological importance, mapping these chemoreceptors to their cognate metabolic ligands remains a major challenge due to the vast number of potential interactions. To address this, we developed a pooled screening assay that enriches functional chemoreceptors from a gene library. Using this approach, we identified a previously uncharacterized group of chemoreceptors in Pseudomonas species with Cache_3-Cache_2 domains that sense short-chain C3 carboxylic acids. Sequence and computational structural analyses revealed that these chemoreceptors exhibit domain features similar to a recently reported C1 formate chemoreceptor despite substantial sequence divergence. Functional assays of representative chemoreceptors confirmed robust chemotactic responses to C3 carboxylic acids, with limited responses to formate. Integrating structural and molecular dynamics analyses suggests that increased binding pocket size and altered flexibility, relative to the formate chemoreceptor, facilitate recognition of larger C3 carboxylic acid ligands. Together, our approach provides a simple and scalable framework for mapping ligand-chemoreceptor interactions and enables systematic characterization across diverse metabolites.

microbiology↗

bioRxiv2026

Repertoire-wide contextual mapping reveals signal functions in cooperatively breeding crows

Communication structures society, and is likewise shaped by relationships and shared tasks; yet, for most socially complex species, we know little of their full vocal repertoire and its functions. We investigated how communication structures the who, what, and when of social interactions in cooperative carrion crows - group-living birds who rely on coordinated behaviors, as in chick care. Leveraging machine learning to integrate large-scale data from crow-borne audio-loggers and nest cameras, we charted the vocal repertoire across 24 cooperative groups and mapped all discovered call types to behaviors and social context. We found that crows used a rich repertoire across three domains of joint behavior - flocking, chick care, and territorial display. Relatively quiet call types were abundant and included close-range calls that may coordinate chick care by announcing nest visits. Our study demonstrates how combining continuous-capture data and machine learning can reveal a holistic understanding of how vocalizations function across contexts.

animal behavior and cognition↗

bioRxiv2025

FOXO1 inhibition and FADD knockdown have opposing effects on anticancer drug-induced cytotoxicity and p21 expression in osteosarcoma

Forkhead box class O1 (FOXO1) and fas-associated death domain (FADD) regulate cell death pathways and homeostatic processes such as cell cycle progression and apoptosis. FADD phosphorylation promotes nuclear localization of FOXO1 and FOXO1 regulates FADD expression. Therefore, it is plausible that FOXO1 and FADD have synergistic or antagonistic effects on cell cycle regulation and the response to anticancer drug treatment in cancer cells. In the present study we report that AS1842856-mediated inhibition of FOXO1 reverses anticancer drug-induced cytotoxicity while FADD knockdown increases anticancer drug-induced cytotoxicity in osteosarcoma (OS). Reversed anticancer drug-induced cytotoxicity was accompanied with G2/M cell cycle arrest and increased expression of p21. The anti-cancer function of FOXO1 was further supported by the observation that OS cells that express higher basal levels of FOXO1 had increased sensitivity to camptothecin-induced cytotoxicity. FADD knockdown reversed FOXO1 inhibition-induced increase in p21 expression. The results presented in this study indicate that FOXO1 has a tumor suppressor function while FADD has a tumor promoting function in OS following anticancer drug treatment. The experimental approach used in this investigation also indicates that FADD antagonists the effect of FOXO1 on p21 expression in OS.

cancer biology↗

bioRxiv2025

MITF-Independent Melanocyte Progenitors are Highly Susceptible to GNAQ-induced Uveal Melanoma in Adult Zebrafish

Melanocytes reside in diverse microenvironments that influence their susceptibility to oncogenic transformation; however, investigation of rare melanoma subsets has been limited by the lack of suitable pre-clinical animal models. Here, we developed a primary, immune-competent zebrafish model to study uveal melanoma (UM) using choroidal melanocyte-targeted injection and electroporation of plasmids encoding human GNAQQ209L together with CRISPR/Cas9 cassettes for somatic tumor suppressor gene deletion. Single-cell transcriptional profiling of primary melanocytes and melanoma derived from the eye and skin revealed distinct transcriptional programs, with epithelial-to-mesenchymal transition pathways enriched in ocular tumors. In addition, choroidal fibroblasts from tumor-bearing eyes exhibited marked transcriptional changes, including increased fibronectin and collagen expression, consistent with stromal remodeling. Given prior associations between mitfa loss and accelerated GNAQQ209L tumor onset, the model was applied to determine whether melanocyte differentiation state contributes to the emergence of GNAQ-driven tumors. The increased susceptibility resulted from expansion of Mitfa-independent melanocyte progenitor populations in germline mitfa mutant zebrafish, rather than somatic mitfa loss in differentiated melanocytes, as conditional, melanocyte-specific mitfa deletion in adult zebrafish did not accelerate tumor growth. Furthermore, pax3a-positive melanocyte progenitor cells in mitfa-deficient zebrafish embryos and adult eyes and skin were highly susceptible to transformation induced by GNAQQ209L but not BRAFV600E. Analogous PAX3 positive populations were also identified in mouse and human single-cell transcriptomic datasets. Collectively, these findings establish a critical role for Mitfa-independent melanocyte progenitors in UM pathogenesis. Statement of SignificanceChoroid-targeted GNAQQ209L expression induces anatomically correct uveal melanoma in adult zebrafish, with germline mitfa deletion expanding mitfa-independent melanocyte progenitors with enhanced susceptibility that are transcriptionally distinct from the subpopulation transformed by BRAFV600E.

cancer biology↗

bioRxiv2025

EHE cell cultures: a platform for mechanistic and therapeutic investigation

Epithelioid hemangioendothelioma (EHE) is a difficult to treat vascular sarcoma defined by TAZ- CAMTA1 or YAP-TFE3 fusion proteins. Human cell lines needed to further understand the pathogenesis of EHE have been lacking. Herein, we describe a method to generate EHE extended primary cell cultures. An integrated multi -omic and functional approach was used to characterize these cultures. The cell cultures, relatively homogenous by single cell RNA-Seq, demonstrated established characteristics of EHE including increased proliferation, anchorage independent growth, as well as the overall gene expression profile and secondary genetic alterations seen in EHE. Whole genome sequencing (WGS) identified links to epigenetic modifying complexes, metabolic processes, and pointed to the importance of the extracellular matrix (ECM) in these tumors. Bulk RNA-Seq demonstrated upregulation of pathways including PI3K-Akt signaling, ECM/ECM receptor interaction, and the Hippo signaling pathway. Development of these extended primary cell cultures allowed for single-cell profiling which demonstrated different cell compartments within the cultures. Furthermore, the cultures served as a therapeutic platform to test the efficacy of TEAD inhibitors in vitro. Overall, the development of EHE primary cell cultures will aid in the mechanistic understanding of this sarcoma and serve as a model system to test new therapeutic approaches.

cancer biology↗

bioRxiv2025

A typology of Australian terrestrial bird communities

AimIncreasing interest in holistic measurement of the response of fauna communities to interventions requires suitable community condition metrics. However, the development of such metrics is hindered by the absence of broad-scale typologies at suitable spatial and ecological resolutions. We aimed to derive a preliminary typology of terrestrial bird communities for Australia, based on bird co-occurrence data, and describe and map the likely distribution of each community type across the continent. LocationMainland Australia, continental islands Time period1973-2022 Major taxa studiedAves MethodsWe used fine-scale co-occurrence data from standard 2-ha surveys in BirdLife Australias citizen-science database. After filtering to reduce bias, we used hierarchical clustering followed by iterative consultation with experts to identify reliably distinct and recognisable terrestrial bird communities across Australia. We used Maxent to model the likely distributions of each community, and developed community descriptions based on each communitys composition and distribution. ResultsThe resultant typology included 29 reliably distinct and recognisable bird communities with major clusters corresponding with seven broad geographical regions. The distributions of bird communities did not correspond tightly to the boundaries of major vegetation groups, with most communities occurring across multiple vegetation types. Main ConclusionsOur preliminary typology of bird communities provides a standard classification at a continental scale. It newly defines distinct bird communities as entities for which condition benchmarks can be established to allow assessment of their conservation status and monitoring of change over time. Refinement will enable cryptic communities in areas with sparse data to be identified. The method could be translated to other regions where adequate coverage of data in the form of standardised surveys of fauna are available. Vast biodiversity datasets delivered through citizen science programs provide the opportunity to develop such typologies for fauna communities, as a precursor to developing targeted and informative community condition metrics.

ecology↗

bioRxiv2025

Determination of the mechanisms of MCPA resistance in Amaranthus powellii

Resistance to 2-methyl-4-chloro-phenoxyacetic acid (MCPA) was recently confirmed in a population of green pigweed (Amaranthus powellii) from Dresden, Ontario, Canada, with a resistance factor of 4.4. Resistance to synthetic auxin herbicides in Amaranthus species has previously been linked to non-target site resistance mechanisms with low-level resistance factors (<10). Based on this information an investigation into the mechanism of resistance to MCPA was conducted in this population of green pigweed. No significant differences in absorption, translocation, and metabolism of 14C-MCPA existed between the resistant and a susceptible population of green pigweed. An RNA-Sequencing experiment to identify differentially expressed genes also confirmed this result. Genes that were differentially expressed in the resistant population were linked to target site modifications. A single nucleotide polymorphism (SNP) conferring a leucine to phenylalanine substitution was identified in auxin response factor (ARF) 9. This mutation may be in the Phox and Bem1p (PB1) domain in ARF9 which facilitates the interaction between ARFs and Aux/IAA repressor proteins. The results demonstrate that the mechanism of resistance to MCPA is not a non-target site mechanism and may be linked to a target site modification. Specifically, a SNP in ARF9 could disrupt the interaction between ARF9 and other Aux/IAAs which could prevent ubiquitination of Aux/IAAs and subsequent lethal action of MCPA.

plant biology↗

bioRxiv2024

Spatial evidence of cryptic methane cycling and methylotrophic metabolisms along a land-ocean transect in a California coastal wetland

Methylotrophic methanogenesis in the sulfate reduction zone of coastal and marine sediments couples with anaerobic methane oxidation (AOM), forming the cryptic methane cycle. This study provides evidence of cryptic methane cycling in the sulfate-reducing zone across a land-ocean transect of four stations--two brackish, one marine, and one hypersaline--within the Carpinteria Salt Marsh Reserve (CSMR), Southern California, USA. The top 20 cm of sediment from the transect underwent geochemical and molecular (16S rRNA) analyses, in-vitro methanogenesis incubations, and radiotracer incubations using 35S-SO4, 14C-mono-methylamine, and 14C-CH4. Sediment methane concentrations were consistently low (3 to 28 {micro}M) except at the marine station, where they increased with depth (max 665 {micro}M). Methanogenesis from mono-methylamine was detected throughout the sediment at all stations with estimated rates ranging between 0.14 and 3.8 nmol cm-3 d-1. 16S rRNA analysis identified methanogenic archaea capable of producing methane from methylamines in sediment where methanogenesis was found to be active. Metabolomic analysis of porewater showed mono-methylamine was mostly undetectable (<3 {micro}M) or present in trace amounts (<10 {micro}M) suggesting rapid metabolic turnover. In-vitro methanogenesis incubations showed no linear methane buildup, suggesting a process limiting methane emissions. AOM activity, measured with 14C-CH4, overlapped with methanogenesis from mono-methylamine activity at all stations, with rates ranging from 0.03 to 19.4 nmol cm-3 d-1. Porewater geochemical analysis showed the CSMR sediments are rich in sulfate and iron. Porewater sulfate concentrations (9-91 mM) were non-limiting across the transect, which support members of sulfate-reducing bacteria and likely responsible for sulfate reduction activity (1.5-2,506 nmol cm-3 d-1) at all stations in the CSMR. Porewater sulfide and iron (II) profiles indicated that the sediment transitioned from a predominantly iron-reducing environment at the two brackish stations to a predominantly sulfate-reducing environment at the marine and hypersaline station. AOM activity was likely coupled to sulfate and possibly iron reduction, coinciding with the presence of anaerobic methanotrophs and bacteria involved in these reductions. 16S rRNA analysis identified anaerobic methanotrophs at the marine and hypersaline stations, where they coexisted with putative methanogens, suggesting both groups, or methanogens alone, may be involved in cryptic methane cycling, preventing significant methane buildup in the sulfate-reducing zone. Differences in rate constants from 14C radiotracer incubations suggest a non-methanogenic process oxidizing mono-methylamine to inorganic carbon, likely mediated by sulfate-reducing bacteria. Understanding the potential competition of sulfate reducers with methanogens for mono-methylamine needs further investigation as it might be another important process responsible for low methane emissions in salt marshes.

microbiology↗

bioRxiv2023

Whale shark residency and small-scale movements around oil and gas platforms in Qatar

Artificial structures in the ocean can influence the movements and residency of migratory fishes. Whale sharks seasonally aggregate near oil and gas platforms in Qatar to feed on fish spawn, creating one of the largest aggregations for the species. We used passive acoustic telemetry to examine their fine-scale movements, residency, and seasonality and investigate whether the platforms influence their habitat use in the area. Tags had a mean retention of 161 {+/-}186 SD days and 32 of the 117 tags were recorded in multiple seasons in the acoustic array (21 stations). Most detections were recorded during the season that was established with other methods from May to September, confirming that this whale shark aggregation is seasonal. Whale sharks stayed up to 77 consecutive days in the array (mean = 16 {+/-} 12.51 days) and had a mean residency index Rmax of 0.31, highlighting the importance of this site to their ecology. While most detections were made at a receiver near a platform, other platforms had few detections and the distance from the centre of the aggregation was the main explanatory variable in a GLM, indicating that the platforms do not influence the whale sharks habitat use. Instead, they moved with the current during the morning, when they feed on fish eggs at the surface which also float with the current, and swam against the current in the late afternoon and at night to be at the presumed fish spawning site again in the early morning. Our results highlight the importance of this small feeding area for whale sharks which face a high threat level in the region.

animal behavior and cognition↗

bioRxiv2023

Gene-by-environment interactions influence the fitness cost of gene copy-number variation in yeast

Variation in gene copy number can alter gene expression and influence downstream phenotypes; thus copy-number variation (CNV) provides a route for rapid evolution if the benefits outweigh the cost. We recently showed that genetic background significantly influences how yeast cells respond to gene over-expression (OE), revealing that the fitness costs of CNV can vary substantially with genetic background in a common-garden environment. But the interplay between CNV tolerance and environment remains unexplored on a genomic scale. Here we measured the tolerance to gene OE in four genetically distinct Saccharomyces cerevisiae strains grown under sodium chloride (NaCl) stress. OE genes that are commonly deleterious during NaCl stress recapitulated those commonly deleterious under standard conditions. However, NaCl stress uncovered novel differences in strain responses to gene OE. West African strain NCYC3290 and North American oak isolate YPS128 are more sensitive to NaCl stress than vineyard BC187 and laboratory strain BY4743. Consistently, NCYC3290 and YPS128 showed the greatest sensitivities to gene OE. Although most genes were deleterious, hundreds were beneficial when overexpressed - remarkably, most of these effects were strain specific. Few beneficial genes were shared between the NaCl-sensitive isolates, implicating mechanistic differences behind their NaCl sensitivity. Transcriptomic analysis suggested underlying vulnerabilities and tolerances across strains, and pointed to natural CNV of a sodium export pump that likely contributes to strain-specific responses to OE of other genes. Our results reveal extensive strain-by-environment interaction in the response to gene CNV, raising important implications for the accessibility of CNV-dependent evolutionary routes under times of stress.

evolutionary biology↗

bioRxiv2023

Rme-6 integrates EGFR trafficking and signalling to regulate ERK1/2 signalosome dynamics

Epidermal growth factor receptor (EGFR) signalling results in a variety of cell behaviours, including cell proliferation, migration and apoptosis, which depend on cell context. Here we have explored how the Rab5GEF, Rme-6, regulates EGFR signalling by modulating endocytic flux. We demonstrate that Rme-6, which acts early in the endocytic pathway, regulates EGFR trafficking through an endocytic compartment that is competent for ERK1/2 signalling. While overexpression of Rme-6 results in enhanced ERK1/2 nuclear localisation and c-Fos activation, loss of Rme-6 results in aberrant ERK1/2 signalling with increased cytoplasmic ERK1/2 phosphorylation (Thr202/Tyr204) but decreased ERK1/2 nuclear translocation and c-Fos activation, the latter leading to decreased cell proliferation. Phosphorylation of ERK1/2 by protein kinase 2 (CK2) is required for its nuclear translocation and our data support a model whereby Rme-6 provides a scaffold for a population of CK2 which is required for efficient nuclear translocation of ERK1/2. Rme-6 is itself a substrate for CK2 on Thr642 and Ser996 and phosphorylation on these sites can activate its Rab5GEF activity and endocytic trafficking of EGFR. Together our results indicate that Rme-6 co-ordinates EGFR trafficking and signalling to regulate the assembly and disassembly of an ERK1/2 signalosome. Summary statementHere we demonstrate how Rme-6, a Rab5GEF, co-ordinates trafficking and signalling of EGFR on the early endocytic pathway to ensure appropriate regulation of downstream ERK1/2 signalling.

cell biology↗

bioRxiv2022

Impact of adolescent intermittent ethanol exposure on interneurons and their surrounding perineuronal nets in adulthood.

BackgroundBinge alcohol exposure during adolescence results in long-lasting alterations in brain and behavior. For example, adolescent intermittent ethanol (AIE) exposure in rodents results in long-term loss of functional connectivity among prefrontal cortex (PFC) and striatal regions as well as a variety of neurochemical, molecular, and epigenetic alterations. Interneurons in the PFC and striatum play critical roles in behavioral flexibility and functional connectivity. For example, parvalbumin (PV) interneurons are known to contribute to neural synchrony, and cholinergic interneurons contribute to strategy selection. Furthermore, extracellular perineuronal nets (PNNs) surround some interneurons, particularly PV+ interneurons, to further regulate cellular plasticity. The effect of AIE exposure on expression of these markers within the PFC is not well understood. MethodsThe present study tested the hypothesis that AIE exposure reduces expression of PV+ and ChAT+ interneurons in the adult PFC and striatum and increases related expression of PNNs (marked by binding of Wisteria Floribunda agglutinin lectin; WFA) in adulthood. Male rats were exposed to AIE (5 g/kg/day, 2-days-on/2-days-off, i.g., P25-P54) or water (CON), and brain tissue was harvested in adulthood (> P80). Immunohistochemistry and co-immunofluorescence were used to assess expression of ChAT, PV, and WFA labeling within the adult PFC and striatum following AIE exposure. ResultsChAT and PV interneuron numbers in the striatum and PFC were unchanged after AIE exposure. However, WFA labeling in the PFC of AIE-exposed rats was increased compared to CON rats. Moreover, significantly more PV neurons were surrounded by WFA labeling in AIE-exposed subjects relative to controls in both PFC subregions assessed: the orbitofrontal cortex (CON = 34%; AIE = 40%) and the medial PFC (CON = 10%; AIE = 14%). ConclusionsThese findings indicate that while PV interneuron expression in the adult PFC and striatum is unaltered following AIE exposure, PNNs surrounding these neurons (indicated by extracellular WFA binding) are increased. This increase in PNNs may restrict plasticity of the ensheathed neurons, thus contributing to impaired microcircuitry in frontostriatal connectivity and related behavioral impairments.

neuroscience↗

bioRxiv2021

C9orf72-derived poly-GA DPRs undergo endocytic uptake in iNPC-derived astrocytes and spread to motor neurons

Dipeptide repeat proteins (DPRs) are aggregation-prone polypeptides encoded by the pathogenic G4C2 repeat expansion in the C9orf72 gene, the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). In this study, we focus on the role of poly-GA DPRs in disease spread. We demonstrate that recombinant poly-GA oligomers can directly convert into solid-like aggregates and form characteristic &[beta]-sheet fibrils in vitro. To dissect the process of cell-to-cell DPR transmission, we closely follow the fate of poly-GA DPRs in either their oligomeric or fibrillized form after administration in the cell culture medium. We observe that poly-GA DPRs are taken up via dynamin-dependent and - independent endocytosis, eventually converging at the lysosomal compartment and leading to axonal swellings in neurons. We then use a co-culture system to demonstrate astrocyte-to- motor neuron DPR propagation, showing that astrocytes may internalise and release aberrant peptides in disease pathogenesis. Overall, our results shed light on the mechanisms of poly- GA cellular uptake and cell-to-cell propagation, suggesting lysosomal impairment as a possible feature underlying the cellular pathogenicity of these DPR species.

neuroscience↗

bioRxiv2021

Natural variation in the consequences of gene overexpression and its implications for evolutionary trajectories

Copy number variation (CNV) through gene or chromosome amplification provides a route for rapid phenotypic variation and supports long-term evolution of gene functions. Although the evolutionary importance of CNV is known, little is understood about how genetic background influences CNV tolerance. Here, we measured fitness costs of over 4,000 over-expressed genes in 15 Saccharomyces cerevisiae strains representing different lineages, to explore natural variation in tolerating gene overexpression (OE). Strain-specific effects dominated the fitness costs of gene OE. We report global differences in the consequences of gene OE, independent of the amplified gene, as well as gene-specific effects that were dependent on the genetic background. Natural variation in the response to gene OE could be explained by several models, including strain-specific physiological differences, resource limitations, and regulatory sensitivities. This work provides new insight on how genetic background influences tolerance to gene amplification and the evolutionary trajectories accessible to different backgrounds.

genomics↗

bioRxiv2020

Rethinking root-shoot growth dynamics

Using a simple plant growth model based on the logistic equation I re-evaluate how biomass allocation between roots and shoots articulates dynamically with the rate of whole-plant biomass production. Defined by parameters reflecting lumped physiological properties, the model constrains roots and shoots to grow sigmoidally over time. From those temporal patterns detailed trajectories of allocation and growth rate are reconstructed. Sigmoid growth trajectories of roots and shoots are incompatible with the dominant ‘functional equilibrium’ model of adaptive allocation and growth often used to explain plants’ responses to nutrient shortage and defoliation. Anything that changes the differential rates of growth between roots and shoots will automatically change allocation and, unavoidably, change whole-plant growth rate. Biomass allocation and whole-plant growth rate are not independent traits. Allocation and growth rate have no unique relationship to one another but can vary across a wide spectrum of possible relationships. When root-shoot allocation seems to respond to the environment it is likely to be a secondary illusory consequence of other primary responses such as localised root proliferation in soil or leaf expansion within canopy gaps. Changes in root-shoot allocation cannot themselves compensate directly for an impairment of growth rate caused by an external factor such as nutrient shortage or defoliation; therefore, such changes cannot be ‘adaptive’.‘The reasons are so simple they often escape notice.’ (James 2012, p. 6).Competing Interest StatementThe authors have declared no competing interest.View Full Text

plant biology↗

bioRxiv2020

Disease Risk Analysis in sea turtles: A baseline study to inform conservation efforts

The impact of a range of different threats has resulted in the listing of six out of seven sea turtle species on the IUCN Red List of endangered species. Disease risk analysis (DRA) tools are designed to provide objective, repeatable and documented assessment of the disease risks for a population and measures to reduce these risks through management options. To the best of our knowledge, DRAs have not previously been published for sea turtles, although disease is reported to contribute to sea turtle population decline. Here, a comprehensive list of health hazards is provided for all seven species of sea turtles. The possible risk these hazards pose to the health of sea turtles were assessed and "One Health" aspects of interacting with sea turtles were also investigated. The risk assessment was undertaken in collaboration with more than 30 experts in the field including veterinarians, microbiologists, social scientists, epidemiologists and stakeholders, in the form of two international workshops and one local workshop. The general finding of the DRA was the distinct lack of knowledge regarding a link between the presence of pathogens and diseases manifestation in sea turtles. A higher rate of disease in immunocompromised individuals was repeatedly reported and a possible link between immunosuppression and environmental contaminants as a result of anthropogenic influences was suggested. Society based conservation initiatives and as a result the cultural and social aspect of interacting with sea turtles appeared to need more attention and research. A risk management workshop was carried out to acquire the insights of local policy makers about management options for the risks relevant to Queensland and the options were evaluated considering their feasibility and effectiveness. The sea turtle DRA presented here, is a structured guide for future risk assessments to be used in specific scenarios such as translocation and head-starting programs.

ecology↗