Biology subjects

Meyer, B.

Publications and source records attributed to Meyer, B..

At least 19 recordsLinked to original sources

bioRxiv2026

Human cerebral assembloids as a model to study the interaction of glioblastoma with resident glial cells

Glioblastoma (GB) is a highly invasive brain cancer characterized by extensive peritumoral glial reactivity. Although GB infiltration and recurrence remain major therapeutic challenges, the contribution of GB-induced gliosis to tumor progression is poorly understood. To investigate glia-GB interactions, we developed human iPSC-derived cerebral forebrain assembloids containing innate microglia and macroglia and transplanted them with GB cells. The model recapitulates key tumor features observed in patients, including distinct tumor regions, reactive gliosis, and altered tissue stiffness. Single-cell RNA sequencing revealed an unexpected enrichment of extracellular vesicles (EVs) in peritumoral reactive glia, which we validated in patient samples. EV inhibition impaired formation of the peritumoral niche, whereas EVs from GB-containing assembloids induced glial reactivity in GB-free assembloids. Furthermore, the modularity of our system enables incorporation of additional niche components, such as monocytes, allowing investigation of the monocyte-glia-tumor axis and providing a powerful platform to dissect mechanisms regulating the GB microenvironment.

neuroscience↗

bioRxiv2026

Long-term stability of cellular-resolution brain-computer interface recordings after stroke

Implantable brain-computer interfaces (iBCIs) with single-neuron resolution are showing great promise for restoring mobility and communication in individuals with spinal cord injury or motor neuron disease. Stroke is the most common cause of acquired brain injury and a major contributor to long-term disability, making chronic stroke a highly relevant indication for iBCIs. However, whether stable intracortical recordings can be obtained from the structurally lesioned human brain is unknown. We report recordings from four 64-channel microelectrode arrays implanted in a participant with chronic aphasia after a large left-hemispheric stroke. The arrays targeted right-hemispheric frontoparietal regions homotopic to the damaged left-hemispheric language network. Across 111 sessions spanning 1,240 days, unit yield and signal quality remained stable. Waveform-based tracking reliably identified individual units across sessions, including across extended recording gaps. Short- and long-term unit stability was comparable to previous reports from iBCI participants without structural brain lesions, and tracked units showed consistent spiking properties across sessions. Our findings provide the first evidence that single-neuron recordings can remain stable over the long term in the stroke-lesioned human brain. They establish the feasibility of chronic, cellular-resolution iBCIs after stroke and support the development of neurorestorative applications for deficits caused by structural brain injury.

neuroscience↗

bioRxiv2026

Pulsed priming with the FAK inhibitor narmafotinib enhances both gemcitabine/Abraxane and FOLFIRINOX chemotherapy response in pancreatic cancer

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a particularly lethal malignancy with few treatment options available. Extensive remodelling of extracellular matrix (ECM) generates a highly fibrotic tumour landscape, which impairs therapeutic response. ObjectiveWe investigated whether stromal priming via the highly specific Focal Adhesion Kinase (FAK) inhibitor narmafotinib (AMP945) in combination with the two major standard-of-care chemotherapies in PDAC, gemcitabine/Abraxane and FOLFIRINOX, reduces fibrosis and enhances treatment efficacy. Design3D organotypic matrices, intravital imaging, and in vivo subcutaneous and orthotopic PDAC models were used to provide a rationale for a first-line priming regimen of narmafotinib prior to chemotherapy. ResultsNeoadjuvant chemotherapy induces fibrosis in PDAC indicating a need for upfront first-line priming of the ECM to normalise the stroma for optimal treatment response. Narmafotinib is a new potent small molecule FAK inhibitor. Phase I safety data shows excellent safety, tolerability, and pharmacokinetics following oral administration in humans. We reveal that narmafotinib treatment during early ECM remodelling ( priming) reduces fibrosis, while limiting subsequent PDAC invasion. Moreover, intravital imaging demonstrates real-time FAK inactivation and cell cycle stalling, leading to improved chemotherapeutic efficacy upon narmafotinib priming in vivo. Long-term assessment in patient-derived models shows that narmafotinib priming prior to gemcitabine/Abraxane or FOLFIRINOX reduces PDAC progression and extends survival in both chemotherapy settings. ConclusionsOur results using these Phase II-ready drug combinations strongly support the clinical assessment of narmafotinib in PDAC. Narmafotinib is currently in Phase Ib/IIa trials, assessing a pulsed dosing regimen prior to gemcitabine/Abraxane, and warrants further clinical assessment in combination with FOLFIRINOX. SIGNIFICANCE OF THIS STUDYO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIPancreatic cancer (PC) is one of the most lethal malignancies and is characterised by a dense, fibrotic stroma, which impairs chemotherapy efficacy. C_LIO_LIThe non-receptor tyrosine kinase FAK is known to promote cancer fibrosis and therefore represents a therapeutic target to normalise the PC stroma and to improve chemotherapy performance. C_LI What this study addsO_LINeoadjuvant chemotherapy induces early fibrosis indicating a need for upfront first-line priming of the ECM to blunt or normalise stromal fibrosis for optimal response to therapy. C_LIO_LIThe small molecule inhibitor narmafotinib (which is currently under Phase Ib/IIa clinical trial assessment) shows high specificity towards FAK as well as desirable pharmacokinetics and pharmacodynamics in healthy human volunteers. C_LIO_LIEarly short-term narmafotinib priming reduces fibrosis and improves the efficacy of subsequent standard-of-care gemcitabine/Abraxane chemotherapy. C_LIO_LIFOLFIRINOX (oxaliplatin, irinotecan, leucovorin and 5-fluorouracil) is a multi-agent chemotherapy preferentially used in PDAC patients with good performance status. Our results demonstrate that narmafotinib priming also improves FOLFIRINOX efficacy, leading to extended survival in patient-derived PDAC models. C_LI How this study might affect research, practice, or policyO_LIThis study supports the clinical development of narmafotinib in combination with both gemcitabine/Abraxane (ACCENT trial) and further FOLFIRINOX standard-of-care chemotherapies for PDAC patient treatment. C_LIO_LIThe first-line priming strategy and early ECM normalisation used in this study may also be applicable to other combination therapy settings and warrants further investigation in ongoing clinical studies. C_LI

cancer biology↗

bioRxiv2026

Targeting DNA Methylation Reactivates Type I Interferon Signalling in Bone-Metastatic Breast Cancer

Bone metastasis remains a major clinical challenge in advanced breast cancer. Downregulation of type I interferon signalling, a critical immunomodulatory pathway in anti-cancer immunity and disease progression, is a defining feature of this process. Here, we utilised an IFN-reporter system to perform unbiased epigenetic compound screens to identify agents that could restore type I IFN signalling. This screen identified Decitabine, a DNA hypomethylating agent, that enhanced tumor immunogenicity across a broad range of mouse and human breast cancer cell lines, including bone-derived lines. Mechanistically, suppression of interferon-stimulated genes is highly correlated with elevated DNMT1 expression in bone metastasis compared with primary tumor, in both mouse models and matched human samples. Decitabine treatment was sufficient to reactivate interferon stimulated genes in bone-derived 4T1.2 cell lines via hypomethylation of type I interferon pathway gene promoter regions. Correspondingly, in the syngeneic 4T1.2 metastasis mouse model, Decitabine treatment conferred a survival benefit and reduced metastatic potential, particularly in bone. Our findings reveal DNA methylation as a key regulator of the transcriptional programs underlying bone metastasis, providing mechanistic insight into how Decitabine reactivates type I interferon signalling and reduces metastatic potential, highlighting epigenetic reprogramming as a promising approach for targeting metastatic breast cancer. STATEMENT OF SIGNIFICANCEBone metastasis remains a major clinical challenge and a key mechanism of progression to bone is the suppression of tumor-inherent type I interferon signalling. We identified Decitabine, a DNA hypomethylating agent, as a promising therapeutic agent to enhance tumor immunogenicity across a broad range of breast cancer cell lines, including bone metastasis-derived lines. Our findings support DNA methylation as a key regulator of transcriptional programs associated with bone metastatic progression, and provide mechanistic insight into how Decitabine reactivates type I interferon signalling and reduces metastatic potential in vivo. These results highlight epigenetic reprogramming as a promising approach for targeting metastatic breast cancer.

Cancer Biology↗

bioRxiv2026

Characterisation of vaginal Lactobacillus isolates from South African women towards the development of a biotherapeutic to optimise the vaginal microbiome

HIV remains among the worlds most serious healthcare challenges, with adolescent girls and young women in sub-Saharan Africa at particularly high risk of infection. Bacterial vaginosis (BV) is a key risk factor for HIV acquisition, however current treatment strategies are limited. Optimal vaginal Lactobacillus spp. protect against BV and HIV, largely through immunoregulatory and antimicrobial activities mediated in part by lactic acid. Towards the development of a Lactobacillus-containing live biotherapeutic for African women, we sampled 181 vaginal Lactobacillus isolates from 25 BV-negative South African women. Fifty isolates were selected for evaluation of inflammatory responses using vaginal epithelial cells, D- and L-lactate and lactic acid production and culture acidification. Aside from a single Lactobacillus salivarius strain, L. crispatus isolates acidified the culture media the most and produced the most D- and L-lactic acid. Inflammatory cytokine responses to Lactobacillus strains were variable, with L. crispatus eliciting the lowest levels of cytokine production. When all properties were evaluated collectively, L. crispatus strains exhibited the most desirable biotherapeutic characteristics. Whole genome sequence analysis of ten L. crispatus isolates showed that the majority were more closely related to one another than to isolates from other geographical regions. This supports the need for live biotherapeutics to be tailored for the population of intended use. No antimicrobial resistance elements were detected, while putative bacteriocins and intact prophage sequences were identified in all isolates. L. crispatus isolates displayed characteristics essential for optimal live biotherapeutic performance, however additional analysis is required to determine the functionality of identified putative prophages. ImportanceHIV is a leading cause of morbidity and mortality in sub-Saharan Africa, where adolescent girls and young women are three times more likely to acquire HIV than their male counterparts. A key risk factor for HIV is bacterial vaginosis (BV), a condition characterised by the loss of beneficial Lactobacillus species and increased abundance of non-optimal, inflammatory bacteria. Although BV affects approximately 25% of women in sub-Saharan Africa, effective therapeutics are lacking. Live biotherapeutics containing optimal Lactobacillus spp. represent a promising strategy to improve BV treatment outcomes and reduce HIV infection risk. We isolated 181 vaginal Lactobacillus spp. from 25 BV-negative South African women and characterized 50 selected isolates. This led to the identification of live biotherapeutic candidates for African women with distinct genomes compared to isolates from other geographical regions. This study contributes to current knowledge of the characteristics that should be considered when screening novel isolates for this purpose.

microbiology↗

bioRxiv2026

A right-hemispheric language network at single-neuron resolution

Human language depends on highly specialized left-hemispheric brain networks. Damage to these networks causes severe language impairments (aphasia), one of the most common, debilitating and costly consequences of left-hemispheric brain injury, especially stroke. The limited recovery of aphasia despite intensive rehabilitation efforts emphasizes the need to understand the basis of residual language abilities at the single-neuron level, which has remained unexplored so far. Here, we report large-scale microelectrode recordings with single-unit resolution over a period of ten months from the right-hemispheric prefrontal and parietal association cortex of an individual with stroke-induced chronic non-fluent aphasia. Single neurons exhibited regionally specific responses during comprehension, retrieval and articulation of words, the core operations of language. Distinct subpopulations encoded linguistic information in a task-specific manner, despite correlated firing patterns across tasks. Both single-neuron activity and temporally coordinated population dynamics were predicted by semantic and phonological embeddings derived from large language models (LLMs), revealing a regional dissociation in which semantic features preferentially accounted for prefrontal activity and phonological features for parietal activity. Our findings suggest that right-hemispheric circuits, homotopic to the left language network, can support language processing through structured, functionally organised activity at the level of single neurons. This study opens an avenue for developing mechanistically specific neurorehabilitation and neurorestorative strategies for aphasia, such as brain-computer interfaces (BCIs), that leverage right-hemispheric language resources.

neuroscience↗

bioRxiv2026

Reprogramming mRNA localization by targeted RNA-protein interference

RNA binding proteins (RBPs) associate with RNAs in intricate ribonucleoprotein complexes and regulate various aspects of RNA life cycle and, by extension, cell functions. Despite their significance, elucidating the functional contributions of specific RNA-RBP binding events, particularly in long-term phenotypic assays, remains challenging. Here, we harness the specificity of CRISPR/dCas13 to interfere with specific RNA-RBP interactions. We apply this methodology to GA-rich mRNA localization elements which recruit the RNA-binding protein CNBP and serve as platforms for the assembly of mRNA trabicking complexes. We show that dCas13/gRNA binds to target transcripts in a highly specific manner and interferes with CNBP recruitment leading to altered target mRNA localization and cell motility, consistent with the function of the targeted mRNAs. We describe optimizations and considerations for the stable implementation of this system. We further use it to show that interfering with the localization of the GA-containing NET1 mRNA reduces cancer cell invasiveness and metastatic lung colonization. These data reveal a potential role for mRNA localization in oncogenic progression and illustrate how this CRISPR-based system can be used for longterm functional investigations of RNA-RBP interactions in vivo.

cell biology↗

bioRxiv2025

Non-polio enteroviruses compromise the electrophysiology of a human iPSC-derived neural network

The non-polio enteroviruses enterovirus-D68 (EV-D68) and enterovirus-A71 (EV-A71) are highly prevalent and considered pathogens of increasing health concern. While most enterovirus infections are mild and self-limiting, severe complications ranging from meningitis, encephalitis, to acute flaccid paralysis can occur, especially in children and immunocompromised patients. Despite the global burden of neurological complications caused by EV-D68 and EV-A71, the underlying neuropathogenesis remains poorly understood. In particular, the impact of the infection on neural function has not been clearly elucidated. Here, we compare the replication kinetics, cellular tropism, and electrophysiological effects of EV-D68 and EV-A71 infection in a physiologically relevant human pluripotent stem cell-derived neural co-culture model, consisting of excitatory neurons and astrocytes. Inoculation with contemporary circulating EV-D68 strains and an EV-A71 strain resulted in decreased neural activity in the co-cultures, with EV-D68 A2/2018 inducing the most rapid and robust negative effect on neural co-cultures, followed by EV-D68 B3/2019. EV-D68 strains preferentially infected neurons, whereas EV-A71 infection was detected in both cell types to the same extent. Despite the lack of viral release of infectious virus particles of EV-D68 B3/2019 in the supernatant, the infection could spread in the cultures and reduce neurotransmission. Higher viral load and broader tropism of EV-A71 did not result in enhanced impairment of neural function. Our results demonstrate that neurotropic non-polio enteroviruses lead to disruption of spontaneous neural activity in a virus-specific manner, which does not correlate with their replication efficiency.

microbiology↗

bioRxiv2025

Evolution of objectives can enable prosocial behaviour without social awareness

AO_SCPLOWBSTRACTC_SCPLOWDivision of labour is fundamental to the functioning of societies and socially living organisms. While it has been central to their study for decades, no complete picture has emerged yet. Some of the most fascinating questions arise in the context of self-organised societies, like those of social insects, that coordinate their behaviour with completely decentralised simple decision-making performed by individuals that only have local information at their disposal. Based on empirical evidence, these collectives appear to balance task engagement globally across their whole task network for the benefit of the colony overall. How can this pro-social coordination be achieved by independently acting individuals? How is a global workforce balancing possible based on only local perception with no knowledge of the global colony status or needs? Central to solving these problems is the question how can the relevant information flow through the task network so that a changed task demand in one part of the colony can lead to adjustments in distant other parts? We detail a model that presents a potential answer to this conundrum. Our model is informed by evolutionary game theory and rests on the assumption that the perception of an individuals sensory input can evolve. We present simulation studies and a mathematical proof to show that pro-social behaviour will evolve in a collective of agents that adjust their behaviour using primitive and biologically plausible learning mechanisms if we assume an evolving perception function.

animal behavior and cognition↗

bioRxiv2025

Inhibition of adenylyl cyclase 1 (AC1) and exchange protein directly activated by cAMP (EPAC) restores ATP-sensitive potassium (KATP) channel activity after chronic opioid exposure

Prolonged exposure to Gi/o receptor agonists such as opioids can lead to a sensitization of adenylyl cyclases (ACs), resulting in heterologous sensitization or cyclic AMP (cAMP) overshoot. The molecular consequences of cAMP overshoot are not well understood, but this adaptive response is suggested to play a critical role in the development of opioid tolerance and withdrawal. We found that genetic reduction of AC1 and simultaneous upregulation of ATP-sensitive potassium (KATP) channel subunits, SUR1 or Kir6.2, significantly attenuated morphine tolerance and reduced naloxone-precipitated withdrawal. In vitro models utilized an EPAC2-GFP-cAMP biosensor to investigate sensitization of adenylyl cyclase in SH-SY5Y neuroblastoma cells and HEK{Delta}AC3/6 knockout cells. Acute application of DAMGO significantly decreased the cAMP signal from the EPAC2-GFP-cAMP biosensor, while chronic DAMGO administration resulted in enhanced cAMP production following AC stimulation. Inhibition of cAMP overshoot was observed with naloxone (NAL), pertussis toxin (PTX), and the neddylation inhibitor, MLN4924 (Pevonedistat), as well as co-expression of {beta}-adrenergic receptor kinase C-terminus ({beta}ARK-CT). After establishment of the AC1-EPAC sensitization in the in vitro models, we found that inhibition of AC1 or EPAC enhanced potassium channel activity after chronic morphine treatment, using a thallium-based assay in SH-SY5Y cells. Similar data were obtained in mouse dorsal root ganglia (DRG) after chronic morphine treatment. This study presents evidence for investigating further AC1 signaling as a target for opioid tolerance and withdrawal, by increasing EPAC activity and affecting potassium channels downstream of opioid receptors. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/636278v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@185bb82org.highwire.dtl.DTLVardef@d97ea4org.highwire.dtl.DTLVardef@1097addorg.highwire.dtl.DTLVardef@1616fcf_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG

neuroscience↗

bioRxiv2024

Acoustic Recognition of Individual Animals in thePresence of Unknown Individuals

Passive acoustic monitoring is firmly established as an effective non-invasive technique for wildlife monitoring. The analysis of animal vocalizations recorded in their natural habitats is commonly used to monitor species occupancy, distribution mapping and community composition. However, the ability to distinguish between individual animals by their vocalisations remains under-explored and presents an exciting opportunity to study individual animal behavior and population demographics in more detail. In this work, we investigate bioacoustic individual-level recognition. In contrast to existing work, we focus on settings where only a subset of the existing population is known and labeled. This is crucial because wildlife populations are constantly changing so that solutions operating only within a known set of individuals are not realistically applicable in the wild. Using two novel datasets, we show that models initially trained to classify only known individuals can also be extended to detect new and previously unknown individuals not included in the training set. We demonstrate that feature extractors pretrained on species classification can be successfully adapted for this task. Extending individual-level recognition to unknown individuals, so-called out-of-distribution classification, is a crucial step towards making individual recognition a realistic possibility in the wild. HighlightsO_LIWe show that features learned by models pretrained on bird species data can be transferred to individual classification tasks with minimal effort. C_LIO_LIWe define and explore the out-of-distribution classification problem on individual animal vocalisations and address various subtleties and eco-logical use cases. C_LIO_LIWe compile and contribute two additional datasets to facilitate further research on individual acoustic recognition. C_LI

bioinformatics↗

bioRxiv2024

A circadian clock drives behavioral activity in Antarctic krill (Euphausia superba) and provides a potential mechanism for seasonal timing

Antarctic krill is a species with fundamental importance for the Southern Ocean ecosystem. Their large biomass and synchronized movements, like diel vertical migration (DVM), significantly impact ecosystem structure and the biological carbon pump. Despite decades of research, the mechanistic basis of DVM remains unclear. Circadian clocks help organisms anticipate daily environmental changes, optimizing adaptation. In this study, we used a recently developed activity monitor to record swimming activity of individual, wild-caught krill under various light conditions and across different seasons. Our data demonstrate how the krill circadian clock, in combination with light, drives a distinct bimodal pattern of swimming activity, which could facilitate ecologically important behavioral patterns, such as DVM. Rapid damping and flexible synchronization of krill activity indicate that the krill clock is adapted to a life at high latitudes and seasonal activity recordings suggest a clock-based mechanism for the timing of seasonal processes. Our findings advance our understanding of biological timing and high-latitude adaptation in this key species.

ecology↗

bioRxiv2024

Development of a protein synthesis network at the sarco/endoplasmic reticulum in adult cardiac myocytes

IntroductionThe endoplasmic reticulum (ER) is the site of synthesis and folding of membrane and secretory proteins, which constitute a large fraction of the total protein output of a mammalian cell. Striated muscle cells contain a specialized membrane system known as the sarcoplasmic reticulum (SR) that controls calcium homeoastasis and contraction, however the biochemical and physiological relationship between the ER and SR and how both compartments participate in protein synthesis remains incompletely understood. MethodsProtein quantification and imaging of selected marker proteins for ER and SR functions was performed to characterize the relationship of the ER and SR and its individual involvement in protein synthesis in neonatal and adult cardiac myocytes. Superresolution microscopy was used to examine the interaction of ribosomes and the SR in adult cardiac myocytes. ResultsQuantification of ER and SR-associated proteins of isolated ventricular cardiac myocytes showed that relative expression of ER/SR resident protein quality elements, as well as relative ribosome levels are decreased in adult cells, whereas SR-associated Ca2+ handling proteins increase. Immunocytoflourescence revealed that the membrane compartment that exists in early postpartum resembles mostly the ER and decreases in postnatal development. The SR is the main membrane network that exists in the adult cardiac myocytes, replacing the ER, in all but the perinuclear region. Immunocytoflourescence staining further indicated that both networks perform overlapping but distinct, specialized functions, such as localization of excitation-contraction coupling exclusively to the SR or initiation of secretion via the classical secretory pathway mainly from the ER. Ribosomes and mRNA were localized both in close proximity to the ER and the SR of adult ventricular cardiac myocytes. Superresolution microscopy confirmed that both the ER as well as the developed SR bind ribosomes and are direct sites of protein synthesis and protein homeostasis in adult cardiac myocytes. ConclusionOur findings suggest molecular differentiation and structural organization of the ER/SR in cardiac muscle development, resulting in the development of a protein synthesis network at the sarco/endoplasmic reticulum in adult cardiac myocytes.

cell biology↗

bioRxiv2024

Towards routine proteome profiling of FFPE tissue: Insights from a 1,200 case pan-cancer study

Proteome profiling of formalin-fixed paraffin-embedded (FFPE) specimens has gained traction for the analysis of cancer tissue for the discovery of molecular biomarkers. However, reports so far focused on single cancer entities, comprised relatively few cases and did not assess the long-term performance of experimental workflows. Here, we did so by analyzing 1,220 tumors from six cancer entities processed over the course of three years. Key findings include the need for a new normalization method ensuring equal and reproducible sample loading for LC-MS/MS analysis across cohorts, showing that tumors can, on average, be profiled to a depth of >4,000 proteins and discovering that current software fails to process such large data sets. We report the first comprehensive pan-cancer proteome expression resource for FFPE material comprising 11,000 proteins which is of immediate utility to the scientific community by way of a web resource. It enables a range of analysis including quantitative comparisons of proteins between patients or cohorts or the discovery of protein fingerprints representing the tissue of origin, or proteins enriched in certain cancer entities.

pathology↗

bioRxiv2023

Benchmarking sample pooling for epigenomics of natural populations

Interest in the role of DNA methylation (DNAm) has grown in ecological and evolutionary research of natural populations. While researchers are typically interested in comparing population-level variation, individual sequencing is the current standard. Natural populations have low effect sizes and thus need large sample sizes to detect differences. The cost of sequencing the necessary samples can be prohibitive in DNAm work. Pooling DNA before library preparation is a powerful tool to reduce costs but no recommendations exist for DNAm pooling in ecology-epigenetics research. We test if pooled and individual libraries provide similar global and region-specific DNA methylation signals in a natural system of response to pollution. We generated whole-epigenome data for two freshwater invasive molluscs (Corbicula flumina and Dreissena polymorpha) collected from a polluted and unpolluted locality, Lake Maggiore, Italy. Our results support that pooling effectively captures the same genome-wide and global treatment-level signals as individual libraries but we note that pooled libraries yielded orders of magnitude more input data and differentially-methylated regions (DMRs) detected compared with individual libraries. We estimated greatly lower power for regions from individual libraries compared with pooled libraries. The post-hoc process of computationally pooling data from individual libraries produced results comparable to pooled libraries in volumes but had discrepancies between DMRs. We discuss the possible causes for the discrepancies and put our results in the context of the benefits and drawbacks of sample pooling for epigenomics of natural populations.

genomics↗

bioRxiv2023

Comparative Analysis of SARS-CoV-2 Antigenicity across Assays and in Human and Animal Model Sera

The antigenic evolution of SARS-CoV-2 requires ongoing monitoring to judge the immune escape of newly arising variants. A surveillance system necessitates an understanding of differences in neutralization titers measured in different assays and using human and animal sera. We compared 18 datasets generated using human, hamster, and mouse sera, and six different neutralization assays. Titer magnitude was lowest in human, intermediate in hamster, and highest in mouse sera. Fold change, immunodominance patterns and antigenic maps were similar among sera. Most assays yielded similar results, except for differences in fold change in cytopathic effect assays. Not enough data was available for conclusively judging mouse sera, but hamster sera were a consistent surrogate for human first-infection sera.

bioinformatics↗

bioRxiv2023

A temperature-controlled, circular maintenance system for studying growth and development of pelagic tunicates (Salps)

Salps are pelagic tunicates that are able to form large blooms under favorable conditions by alternating between sexual and asexual reproduction. While their role in the regional carbon cycle is receiving attention, our knowledge of their physiology is still limited. This knowledge gap is mainly due to their fragile gelatinous nature, which makes it difficult to capture intact specimens and maintain them in the laboratory. We present here a modified kreisel tank system, that was tested onboard using the Southern Ocean salp Salpa thompsoni and station-based using the Mediterranean species Salpa fusiformis. Successful maintenance over days to weeks allowed us to obtain comparable relative growth and developmental rates as in situ, and provided insight into their potential life cycle strategies. By providing a starting point for successful maintenance, we hope to stimulate future experimental research on this understudied taxonomic group.

physiology↗

bioRxiv2023

Intercomparison of growth models for Antarctic krill (Euphausia superba): towards a generalised understanding

Antarctic krill is a key species of the Southern Ocean, impacted by climate change and human exploitation. Understanding how these changes affect the distribution and abundance of krill is crucial for generating projections of change for Southern Ocean ecosystems. Krill growth is an important indicator of habitat suitability and a series of models have been developed and used to examine krill growth potential at different spatial and temporal scales. The available models have been developed using a range of empirical and mechanistic approaches, which provide alternative perspectives and cross-validation of analyses of the key processes influencing krill growth. Here we undertake an intercomparison of a suite of the available models to understand their sensitivities to major driving variables. This illustrates that the results are strongly determined by the model structure and technical characteristics, and the data on which they were developed and validated. Our results emphasize the importance of assessing the constraints and requirements of individual krill growth models to ensure their appropriate application. The study also demonstrates the value of the development of alternative modelling approaches to identify key processes affecting the dynamics of krill. Of critical importance for modelling the growth of krill is appropriately assessing and accounting for differences in estimates of food availability resulting from alternative methods of observation. We suggest that an intercomparison approach is particularly valuable in the development and application of models for the assessment of krill growth potential at circumpolar scales and for future projections. As another result of the intercomparison, the implementations of the models used in this study are now publicly available for future use and analyses.

ecology↗