Biology subjects

Meyer, L.

Publications and source records attributed to Meyer, L..

At least 19 recordsLinked to original sources

bioRxiv2026

Cerebral organoids recapitulate interneuron chain migration in the human cortex

The human brain is incomplete at birth, with streams of late-born interneurons migrating into the postnatal cortex. This process is absent in rodents, limiting mechanistic investigation to post-mortem tissue. Here, we show that human cerebral organoids cultured for over six months recapitulate postnatal interneuron migration, enabling its mechanistic and genetic dissection. Live imaging and mathematical modeling revealed that interneurons intrinsically migrate in chains, while astrocyte interactions promote stream organization. Spatial and single-cell transcriptomics identified a distinct molecular signature of human postnatal migratory streams enriched for neurodevelopmental disorder-associated genes. Perturbation of the autism-associated genes CNTN5 and FGF14 differentially disrupted chain organization and migration. Thus, long-term cerebral organoids enable mechanistic analysis of previously inaccessible aspects of postnatal human brain development and their contributions to neurodevelopmental disease.

developmental biology↗

bioRxiv2026

Temporal Dissociation of Syntactic Disambiguation and Memory Retrieval during Sentence Processing: Naturalistic MEG Evidence from Interpretable Models

Human sentence comprehension proceeds word-by-word, with prior research proposing two central sources of cognitive demand during incremental processing: forward-looking disambiguation of the incoming information stream, and backward-looking retrieval of information associated with previous words from working memory. Recent work has shown that Transformer-based language models successfully generate predictions about sentence processing load in human psycho- and neurolinguistic data by operationalizing disambiguation cost as next-token surprisal, and memory retrieval cost as normalized attention entropy (NAE). Such models, however, remain difficult to interpret as it is not well understood what factors play causally into the decision to assign a cost value to a given word in such artificial neural networks. Here, we present interpretable and cognitively grounded models of disambiguation and memory retrieval and evaluate their neural alignment and spatio-temporal correlates using human magnetoencephalography responses to naturalistic narrative speech. Multivariate temporal response function modeling demonstrates firstly that these human-bias-informed models fare equally well in accounting for observed human language processing data as their Transformer counterparts. This same modeling framework then suggests that surprisal and NAE temporally dissociate in the cortical language network -- surprisal being predictive of bilateral superior temporal gyrus and supramarginal gyrus activation [~]300-500 ms, and NAE being predictive of activity in the same regions, but later [~]750-850 ms. By demonstrating that interpretable neurocomputational models can achieve meaningful brain alignment while maintaining explanatory transparency, this work offers a methodological blueprint for bridging the gap between algorithmic theory and neural implementation.

neuroscience↗

bioRxiv2026

Bridging the neural synchronization to linguistic structures and natural speech comprehension

Speech comprehension involves the inference of abstract information from continuous acoustic signals. Prior work suggests that electrophysiological activity is synchronized with abstract linguistic structures (phrases and sentences) during the processing of isochronous syllable sequences. It is yet unclear whether this prior evidence generalizes to natural speech comprehension, which requires the flexible processing of continuous speech, where syllables and other types of linguistic units are anisochronous. Our magnetoencephalography experiment investigated neural synchronization to acoustic (syllables) and abstract units (phrases and sentences) using continuous speech ranging from artificial isochronous to more natural anisochronous. We find that neural synchronization to phrases and sentences, but not syllables, is resilient to naturalistic anisochrony. This suggests that linguistic structure processing reflects endogenous inferences that are fundamentally distinct from the exogenous processing of syllables driven by speech acoustics. Lateralization and linear regression results extend this functional dissociation as hemispheric asymmetry: stimulus-independent leftward lateralization for linguistic structure processing but stimulus-driven rightward lateralization (or bilaterality) for both syllable and acoustic processing. Our findings provide a more realistic characterization of the flexible neural mechanisms supporting the efficient comprehension of natural speech.

neuroscience↗

bioRxiv2025

The microbial tryptophan metabolite indole acts on the gastrointestinal tract to improve glucose homeostasis by enhancing GLP-1 secretion and L-cell differentiation

Aims/hypothesisGrowing evidence implicates gut microbiota-derived metabolites in metabolic homeostasis. Indole, a microbial tryptophan metabolite, has been reported to enhance Glucagon-like peptide-1 (GLP-1) secretion in vitro, and its derivatives have been inversely associated with risk of type 2 diabetes (T2D). We hypothesised that indole acts via the gastrointestinal tract to modulate glucose homeostasis, and aimed to test this hypothesis using in vitro and in vivo models. MethodsThe acute effects of indole on GLP-1 secretion in vitro, and on glucose tolerance and hormone secretion in mice, were determined. Subsequently, the effects of indole on intestinal epithelial cell fate and L-cell differentiation in murine ileal organoids and in vivo were studied. Finally, the utility of chronic indole administration in a murine model of T2D was explored. ResultsIndole stimulated in vitro GLP-1 secretion in a concentration-dependent manner, and improved acute glucose control in vivo. Additionally, we demonstrate that indole drives enteroendocrine L-cell differentiation in murine ileal organoids, resulting in increased L-cell density and longer-term glucoregulatory benefits in vivo. Finally, sub-chronic indole administration improved glucose tolerance and insulin sensitivity in diabetic mice. Conclusions/interpretationOur findings identify indole as an anti-diabetic molecule that acts on the gut, and raise the possibility of incorporating indole into nutraceutical supplements to aid in the treatment or prevention of T2D. This highlights the importance of gut microbiota-derived metabolites in metabolic health and opens new avenues for developing novel strategies to combat T2D. Research in ContextO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIGut microbiota-derived metabolites play a role in metabolic homeostasis. C_LIO_LIIndole, a microbial tryptophan metabolite, enhances GLP-1 secretion in vitro. C_LIO_LIIndole derivatives are inversely associated with type 2 diabetes (T2D) risk. C_LI What is the key question?O_LIDoes indole act on the gut to modulate glucose homeostasis? C_LI What are the new findings?O_LIIndole stimulates GLP-1 secretion and improves acute glucose control in vivo. C_LIO_LIIndole drives enteroendocrine L-cell differentiation in murine ileal organoids, increasing L-cell density and long-term glucoregulatory benefits. C_LIO_LISub-chronic indole administration improves glucose tolerance and insulin sensitivity in mice with type 2 diabetes, showing the potential of gut microbiota-derived metabolites as therapeutic targets. C_LI How might this impact clinical practice in the foreseeable future?O_LIIndole could be incorporated into nutraceutical supplements for T2D prevention or treatment. C_LI

physiology↗

bioRxiv2025

Enteropancreatic neurons drive the glucoregulatory response to ingested lipid

Enteropancreatic neurons project from the small intestinal wall to the pancreas. Though well positioned to mediate the effects of ingested nutrients on pancreatic function, the metabolic role of these neurons is unclear. Diets rich in olive oil promote weight loss and improve remission rates in patients with T2DM. Here, we show that olive oil improves acute glucose tolerance by stimulating insulin release via neurotensin receptor type 1 (NTSR1)-expressing enteropancreatic neurons. These neurons are necessary for the effects of olive and neurotensin on glucose tolerance, and their activation is sufficient to improve glucose tolerance. These findings suggest a mechanism by which dietary olive oil regulates blood glucose levels and present a novel functional role for enteropancreatic neurons in regulating glucose homeostasis.

physiology↗

bioRxiv2024

Impacts of taxonomic change on the Amazonian palm flora

Although taxonomy is an evolving discipline, taxonomic change is rarely accounted for in macroecological studies. By tracking the history of species descriptions and synonymizations of more than 800 names of Amazonian palms, we reveal shifts in species counts across space and time, the factors associated with taxonomic lumping, and the time needed to detect synonyms. The 175 Amazonian palm species known to date are the result of a gradual accumulation of new descriptions and a few distinct revisions events that led to the recognition of approximately 800 heterotypic synonyms. Most of these synonyms were detected after the mid-1990s and caused an 80% decrease in species counts within just three decades. The time to detect synonyms ranged from 3 to 227 years. Species with a large population, widespread distribution, and those described early were more frequently lumped. This suggests undetected synonyms inflate species richness unevenly across taxa and regions. Our study highlights how much taxonomic revisions can affect our understanding of biodiversity. Without them, we risk building our ecological analyses and conservation assessments on shaky ground.

ecology↗

bioRxiv2024

Mapping the druggable targets displayed by human colonic enteroendocrine cells

Enteroendocrine cells (EECs) are specialized intestinal hormone-secreting cells that play critical roles in metabolic homeostasis, digestion, and gut-brain communication. They detect diverse stimuli including endocrine, immune, neuronal, microbial, and dietary signals, through a complex array of receptors, ion channels, and transporters, to modulate the release of over 20 hormones. These molecular sensors serve as potential drug targets to modulate hormone secretion, but until recently, catalogues of such targets in human colonic EECs have not been produced. To address this gap, we performed bulk and single-cell RNA sequencing on fluorescently labelled EECs isolated from human colonic organoids, identifying and cataloguing potential druggable targets. This catalogue includes receptors, orphan GPCRs, transporters, and hormones not previously reported in human colonic EECs. Comparison with murine EECs highlighted interspecies similarities and differences, key data to facilitate the design and optimise the predictive accuracy of pre-clinical models. We also functionally validated two receptors not previously identified in human EECs: IL-13R1, was expressed in both peptide-producing EECs and serotonin producing Enterochromaffin cells (ECs), and its ligand IL-13 stimulated the secretion of glucagon-like peptide-1 (GLP-1) and serotonin measured in real-time, and GPR173, which was selectively expressed in ECs and, when activated by its agonist Phoenixin-20, also promoted serotonin release. These analyses provide a valuable resource for therapeutic interventions aimed at modulating gut hormone secretion, with potential applications in treating gastrointestinal, metabolic, and other related disorders.

cell biology↗

bioRxiv2024

Cultivation protocols the rhodophytes, Devaleraea mollis and Palmaria hecatensis from Alaska

Species diversification is crucial for the long-term viability, competitiveness, and sustainability of the seaweed farming industry in the United States. This study investigated the effects that temperature (4, 8 and 12{degrees}C), photoperiod (8L:16D, 12L:12D and 16L:8D), and irradiance (20, 40, 100 {+/-} 10 {micro}mol photons m-2 s-1) had on the specific growth rate (SGR) of Devaleraea mollis and Palmaria hecatensis from Alaska. Outputs were used to adjust indoor cultivation protocols for D. mollis and develop the first protocols for P. hecatensis. This study also explored the use of two low-cost commercial nutrient products (F/2 and Jacks Special 25-5-15) as alternatives to the recommended nutrient medium, von Stosch Enrichment. Assessments determined whether their use resulted in similar SGRs without compromising biomass quality or raising production costs. Results showed that both species responded differently to each factor, indicating distinct ecological and physiological adaptations. D. mollis exhibited higher growth rates in warmer temperatures and responded to higher irradiance levels with spore release but showed no clear preference between neutral and long-day photoperiods. In contrast, P. hecatensis demonstrated higher growth rates in cooler environments with a long-day photoperiod promoting the most growth without spore release. Nutrient supplementation revealed that growth in D. mollis was affected by nutrient formulation, while P. hecatensis showed no significant growth variation. These findings underscore the importance of species and geographic-specific protocols for seaweed farming. Further research is needed to optimize the potential cultivation protocols provided here. Cultivation protocols would also benefit from exploring the ecological and physiological nuances of both species.

ecology↗

bioRxiv2024

Identification and characterization of tertiary lymphoid structures in brain metastases

Brain metastases (BrM) are the most common cancers in the brain. We performed transcriptome-wide gene expression profiling combined with spatial immune cell profiling to characterize the tumor immune microenvironment in BrM from different primary tumors. We found that BrM from lung carcinoma and malignant melanoma showed overall higher immune cell infiltration as compared to BrM from breast carcinoma. RNA sequencing-based immune cell deconvolution revealed gene expression signatures indicative of tertiary lymphoid structures (TLS) in subsets of BrM, mostly from lung cancer and melanoma. This finding was corroborated by multiplex immunofluorescence staining of immune cells in BrM tissue sections. Detection of TLS signatures was more common in treatment-naive BrM and associated with prolonged survival after BrM diagnosis in lung cancer patients. Our findings highlight the cellular diversity of the tumor immune microenvironment in BrM of different cancer types and suggest a role of TLS formation for BrM patient outcome.

cancer biology↗

bioRxiv2024

Ecotype formation in the European anchovy fuelled by structural variants of different origins and genetic interactions with a southern lineage

The formation of ecotypes is shaped by mechanisms that reduce gene flow through complex interactions between ecological, historical, and genomic factors. In the European anchovy (Engraulis encrasicolus), marine and coastal ecotypes have been identified in the North-East Atlantic and Mediterranean Sea, yet the genomic basis of their divergence remains unclear. Here, we present the first genome-scale analysis of this species complex, integrating whole-genome sequencing (WGS) and RAD-seq data from populations across its distribution range. In addition to the marine and coastal ecotypes, we identify a previously undetected lineage which is present in southern Morocco, the Canary Islands and even in South Africa. This southern Atlantic lineage exhibits a gradient of admixture with northern populations near the Atlantic-Mediterranean transition zone. Genomic differentiation landscapes reveal large regions of high linkage disequilibrium, likely corresponding to thirteen structural variants (SVs) segregating within or between the lineages. Notably, three of the six SVs contributing to the gene flow barrier between northern ecotypes originated in the southern lineage, supporting a partially shared evolutionary history between the coastal ecotype and the southern lineage. Our findings suggest that anchovy ecotype divergence has been shaped by a combination of ancient structural variation, admixture, and local adaptation. This study highlights how SVs that arose between geographically isolated lineages can act as key genetic elements in ecotype formation, reinforcing reproductive isolation through distinct evolutionary pathways.

evolutionary biology↗

bioRxiv2024

A Supervised Machine Learning Approach with Feature Selection for Sex-Specific Biomarker Prediction

Biomarkers play a crucial role in various aspects of healthcare, offering valuable insights into disease diagnosis, prognosis, and treatment selection. Recently, machine learning (ML) techniques have emerged as effective tools for uncovering novel biomarkers and improving predictive modelling capabilities. However, bias within ML algorithms, particularly regarding sex-based disparities, remains a concern. In this study, a supervised ML model was developed in order to predict 9 common biomarkers widely used in clinical settings. These biomarkers included triglycerides, body mass index, waist circumference, systolic blood pressure, blood glucose, uric acid, urinary albumin-to-creatinine ratio, high-density lipoproteins and albuminuria. During the validation test, it was observed that the ML models successfully predicted values within 5 and 10% error of the actual values. Out of the 121 female individuals tested, the following percentages of predicted values fell within this 10% range: 93% for albuminuria, 86% for waist circumference, 76% for BMI, and the lowest being 64% for systolic blood pressure and blood glucose. For the 119 male individuals tested, the percentages were as follows: 92% for albuminuria, 96% for waist circumference, 91% for BMI, 74% for blood glucose, and 68% for systolic blood pressure. Triglycerides, uric acid, urinary albumin-to-creatinine ratio and high-density lipoproteins all predicted lower than 50% for both male and female subgroups. Overall, the male subgroup had higher prediction scores than the female group. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=118 SRC="FIGDIR/small/597741v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@182bfbcorg.highwire.dtl.DTLVardef@fa00a1org.highwire.dtl.DTLVardef@13f4a87org.highwire.dtl.DTLVardef@35f411_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2024

The ARC Toolbox: Artificial Languages with Rhythmicity Control

Infants and adults show the remarkable ability to learn from statistical regularities in the environment. Seminal studies on statistical learning in language acquisition suggested that transitional probabilities between syllables are decisive for word learning. Yet, recent work cautioned that acoustic and phonological regularities confound transitional probabilities, compromising interpretability. Furthermore, prior linguistic background can impact the learning of a new (artificial) language. To control for such confounds, we developed an open-source Python toolbox that generates Artificial Languages with Phonological and Acoustic Rhythmicity Controls (ALPARC). First, we explain all functionalities of ALPARC and provide a step-by-step guide. Then, we demonstrate how ALPARC generates syllable streams encompassing pseudowords that are tailored to critical statistics of real languages. Our results show that ALPARC streams attain stationary transitional probability distributions and reduce acoustic and phonological confounds relative to stimuli used in prior studies. We conclude that ALPARC is a useful tool to overcome current uncertainties in future SL studies.

neuroscience↗

bioRxiv2024

Le Petit Prince Hong Kong (LPPHK): Naturalistic fMRI and EEG data from older Cantonese speakers

Currently, the field of neurobiology of language is based on data from only a few Indo-European languages. The majority of this data comes from younger adults neglecting other age groups. Here we present a multimodal database which consists of task-based and resting state fMRI, structural MRI, and EEG data while participants over 65 years old listened to sections of the story The Little Prince in Cantonese. We also provide data on participants language history, lifetime experiences, linguistic and cognitive skills. Audio and text annotations, including time- aligned speech segmentation and prosodic information, as well as word-by-word predictors such as frequency and part-of-speech tagging derived from natural language processing (NLP) tools are included in this database. Both MRI and EEG data diagnostics revealed that the data has good quality. This multimodal database could advance our understanding of spatiotemporal dynamics of language comprehension in the older population and help us study the effects of healthy aging on the relationship between brain and behaviour.

neuroscience↗

bioRxiv2024

Dissociating endogenous and exogenous delta activity during natural speech comprehension

Decoding human speech requires the brain to segment the incoming acoustic signal into meaningful linguistic units, ranging from syllables and words to phrases. Integrating these linguistic constituents into a coherent percept sets the root of compositional meaning and hence understanding. One important cue for segmentation in natural speech are prosodic cues, such as pauses, but their interplay with higher-level linguistic processing is still unknown. Here we dissociate the neural tracking of prosodic pauses from the segmentation of multi-word chunks using magnetoencephalography (MEG). We find that manipulating the regularity of pauses disrupts slow speech-brain tracking bilaterally in auditory areas (below 2 Hz) and in turn increases left-lateralized coherence of higher frequency auditory activity at speech onsets (around 25 - 45 Hz). Critically, we also find that multi-word chunks--defined as short, coherent bundles of inter-word dependencies--are processed through the rhythmic fluctuations of low frequency activity (below 2 Hz) bilaterally and independently of prosodic cues. Importantly, low-frequency alignment at chunk onsets increases the accuracy of an encoding model in bilateral auditory and frontal areas, while controlling for the effect of acoustics. Our findings provide novel insights into the neural basis of speech perception, demonstrating that both acoustic features (prosodic cues) and abstract processing at the multi-word timescale are underpinned independently by low-frequency electrophysiological brain activity.

neuroscience↗

bioRxiv2024

Direct excitatory synapses between neurons and tumor cells drive brain metastatic seeding of breast cancer and melanoma

Interactions between neurons and cancer cells are found in many malignancies, but their relevance for metastatic organ colonization remain largely unknown. It is also unclear whether any direct synaptic communication between neurons and cancer cells of non-neural tumor types exists, and if so, whether this can support metastasis and thus cancer progression. Here we show that excitatory synapses are formed between neurons and brain-metastatic melanoma and breast cancer cells. This starts at an early microscopic stage after extravasation into the brain parenchyma, during residence of cancer cells in the perivascular niche, a critical step for their survival. These neuron-cancer synapses showed a bona fide synaptic ultrastructure, and generated excitatory postsynaptic currents mediated by glutamate receptors of the AMPA subtype in cancer cells. In accordance, AMPA receptor signatures were consistently detected in preclinical and patient samples of melanoma and breast cancer brain metastases. Genetic perturbation and pharmacological inhibition of AMPA receptors with the approved antiepileptic drug perampanel in models of breast and melanoma cancer reduced the number of brain metastases and overall brain metastatic burden. These findings demonstrate for the first time that neurons can form biologically relevant direct synapses with non-neural cancer cells. In brain metastasis, a particularly challenging complication of many common malignancies, this non-canonical stimulatory synaptic interaction offers novel therapeutic opportunities.

cancer biology↗

bioRxiv2023

Xrn1 biochemically associates to the eisosome after the post diauxic shift in yeast

mRNA degradation is one of the main steps of gene expression, and a key player is the 5-3 exonuclease Xrn1. In Saccharomyces cerevisiae, it was previously shown, by a microscopy approach, that Xrn1 is located to different cellular compartments, depending on physiological state. During exponential growth, Xrn1 is distributed in the cytoplasm, while it is present in the eisosomes after the post-diauxic shift (PDS). Here, we biochemically characterized the Xrn1-associated complexes in different cellular states. We demonstrate that, after PDS, Xrn1 but not the decapping (DCP), nor Lsm1-7/Pat1 complexes, was sequestered in the eisosomes, thus preserving mRNAs from degradation.

biochemistry↗

bioRxiv2023

cytoviewer: an R/Bioconductor package for interactive visualization and exploration of highly multiplexed imaging data

SummaryHighly multiplexed imaging enables single-cell-resolved detection of numerous biological molecules in their spatial tissue context. Interactive data visualization of multiplexed imaging data is necessary for quality control and hypothesis examination. Here, we describe cytoviewer, an R/Bioconductor package for interactive visualization and exploration of multi-channel images and segmentation masks. The cytoviewer package supports flexible generation of image composites, allows side-by-side visualization of single channels, and facilitates the spatial visualization of single-cell data in the form of segmentation masks. The package operates on SingleCellExperiment, SpatialExperiment and CytoImageList objects and therefore integrates with the Bioconductor framework for single-cell and image analysis. Users of cytoviewer need little coding expertise, and the graphical user interface allows user-friendly navigation. We showcase the functionality of cytoviewer by analysis of an imaging mass cytometry dataset of cancer patients. AvailabilityThe cytoviewer package can be installed from Bioconductor via https://www.bioconductor.org/packages/release/bioc/html/cytoviewer.html. The development version and further instructions can be found on GitHub at https://github.com/BodenmillerGroup/cytoviewer. We provide an R script to exemplify the usage of cytoviewer in the supplementary information. Supplementary informationsSupplementary data are available online.

bioinformatics↗

bioRxiv2023

Developmental biomechanics and age polyethism in leaf-cutter ants

Many social insects display age polyethism: young workers stay inside the nest, and only older workers forage. This behavioural transition is accompanied by genetic and physiological changes, but the mechanistic origin of it remains unclear. To investigate if the mechanical demands of foraging effectively prevent young workers from partaking, we studied the biomechanical development of the bite apparatus in Atta vollenweideri leaf-cutter ants. Fully-matured foragers generate peak in-vivo bite forces of around 100 mN, more than one order of magnitude in excess of those measured for freshly-eclosed callows of the same size. This change in bite force was accompanied by a sixfold increase in the volume of the mandible closer muscle, and by a substantial increase of the flexural rigidity of the head capsule, driven by a significant increase in both average thickness and indentation modulus of the head capsule cuticle. Consequently, callows lack the muscle force capacity required for leaf-cutting, and their head capsule is so compliant that large muscle forces may cause damaging deformations. On the basis of these results, we speculate that continued biomechanical development post eclosion may be a key factor underlying age polyethism, wherever foraging is associated with mechanical demands on the musculoskeletal system.

developmental biology↗