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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2025

Population Trends of the Adder (Vipera berus) in Sweden:A Rapid Review and Meta-Analysis

BackgroundThe conservation status of the common European adder (Vipera berus) in Sweden is ambiguous. While the species is officially classified as "Least Concern" (LC) on the national Red List, localised reports and long-term studies suggest significant population declines, creating a need for a consolidated evidence summary. ObjectiveTo systematically review and synthesise available scientific and official evidence to determine the overall population trend for the adder in Sweden and to identify the principal drivers behind this trend, with a specific focus on habitat, urbanisation, and procreation. MethodA rapid review of the literature was conducted using a defined Boolean search strategy across academic databases (Web of Science, Scopus, PubMed), preprint servers (bioRxiv), government archives, and citizen science portals. The research question was structured using the PECO framework. The search yielded 255 initial hits, which, after screening, resulted in 12 core sources for inclusion. Evidence was weighted using a four-level hierarchy to assess its robustness. The rapid nature of this review carries an inherent risk of time bias, as studies published after the search date are not included. ResultThe analysis reveals a significant discrepancy between the species official national status and the findings from high-quality longitudinal studies. While the national Red List assesses the species as "Least Concern," the most robust evidence indicates severe and rapid local population declines. The primary identified threats are habitat fragmentation from infrastructure and urban development, and acute effects of climate change, particularly extreme drought. A critical gap in national environmental monitoring was also identified, with no dedicated, systematic programme for reptiles. ConclusionThe probable national trend for the adder in Sweden is a slow, cryptic decline driven by local extirpations. The official "Least Concern" status risks being a lagging indicator that masks underlying threats. DiscussionThe findings highlight a paradox where the most reliable, high-resolution scientific data conflicts with broad-scale national assessments. This suggests that the current conservation status may engender a false sense of security, potentially delaying necessary conservation interventions. The lack of a national monitoring programme is a major limitation to evidence-based management. Recommendations include establishing such a programme and integrating habitat connectivity into landscape planning to mitigate the impacts of fragmentation.

ecology↗
bioRxiv2025

Trehalose promotes wound healing in vitro by enhancing the migration of human keratinocytes via the VEGF/JNK/PI3K pathway

BackgroundTrehalose is a naturally occurring disaccharide found in invertebrates but cannot be synthesized by vertebrates. We previously reported that high-concentration trehalose induces a transient senescent-like state in fibroblasts, leading to cell cycle arrest and growth factor secretion via CDKN1A/p21, and this process promoted keratinocyte proliferation, enhancing capillary formation and wound closure in vivo. ObjectiveThis study aimed to investigate the effect of trehalose on human keratinocytes. MethodsPreviously published RNA-seq data of cytokine-untreated samples from our group of trehalose-treated human keratinocytes were re-analyzed, and an in vitro scratch assay was performed using cells treated with mitomycin C. ResultsThe trehalose-treated group exhibited increased wound closure. A significantly increased secretion of vascular endothelial growth factor (VEGF) was observed in keratinocytes treated with high-concentration trehalose, which is one of the most crucial molecules inducing angiogenesis in the skin. Significant upregulation of mRNA level and protein secretion of VEGF was confirmed using qPCR and ELISA, respectively. Furthermore, treatment with axitinib, a VEGF receptor inhibitor, significantly suppressed trehalose-induced activation of keratinocyte migration. Additionally, the increase in trehalose-induced migration activity was significantly inhibited by the Jun N-terminal kinase (JNK) inhibitor SP600125 and the PI3K inhibitor LY294002. ConclusionTrehalose promotes wound healing via VEGF secretion from keratinocytes and the PI3K and JNK pathways. The findings of this study may lead to the development of novel therapeutic agents that can alter the wound healing process. IMPORTANTO_LIManuscripts submitted to Review Commons are peer reviewed in a journal-agnostic way. C_LIO_LIUpon transfer of the peer reviewed preprint to a journal, the referee reports will be available in full to the handling editor. C_LIO_LIThe identity of the referees will NOT be communicated to the authors unless the reviewers choose to sign their report. C_LIO_LIThe identity of the referee will be confidentially disclosed to any affiliate journals to which the manuscript is transferred. C_LI GUIDELINESO_LIFor reviewers: https://www.reviewcommons.org/reviewers C_LIO_LIFor authors: https://www.reviewcommons.org/authors C_LI CONTACTThe Review Commons office can be contacted directly at: office@reviewcommons.org

cell biology↗
bioRxiv2025

Cleavage of MEP-1 by DPF-3 Reveals Novel Substrate Specificity and Its Impact on Reproductive Fitness

Proteases are enzymes that catalyse the hydrolysis of peptide bonds in proteins for their functional, modification or degradation. Members of the Dipeptidyl Peptidase IV (DPPIV) family are exopeptidases that cleave dipeptides off the N-termini of their substrate peptides, typically after proline or alanine. Recently, we showed that human DPP4 and Caenorhabditis elegans DPF-3 have a larger target repertoire in vitro, permitting cleavage after additional amino acids. Here, we use TAILS (Terminal Amine Isotopic Labelling of Substrates) to identify DPF-3 targets in vivo and observe cleavage of MEP-1 after threonine, confirming a broader substrate specificity of DPF-3 also in vivo. Demonstrating physiological relevance, we show that rendering MEP-1 resistant to cleavage disrupts its stability, leading to developmental abnormalities such as defective gonadal migration and reproductive issues. Collectively, our findings highlight a previously unappreciated complexity in the substrate specificity of DPPIV family proteases and suggest that their physiological roles may extend beyond what is currently known. IMPORTANTO_LIManuscripts submitted to Review Commons are peer reviewed in a journal-agnostic way. C_LIO_LIUpon transfer of the peer reviewed preprint to a journal, the referee reports will be available in full to the handling editor. C_LIO_LIThe identity of the referees will NOT be communicated to the authors unless the reviewers choose to sign their report. C_LIO_LIThe identity of the referee will be confidentially disclosed to any affiliate journals to which the manuscript is transferred. C_LI GUIDELINESO_LIFor reviewers: https://www.reviewcommons.org/reviewers C_LIO_LIFor authors: https://www.reviewcommons.org/authors C_LI CONTACTThe Review Commons office can be contacted directly at: office@reviewcommons.org

molecular biology↗
bioRxiv2025

Rapidly and reproducibly building a comprehensive catalogueof resistance-associated variants for M. tuberculosis

BackgroundCatalogues of genetic variants associated with resistance underpin whole-genome sequencing (WGS)-based predictions of drug susceptibility in Mycobacterium tuberculosis, and are essential for molecular diagnostics and surveillance. The current gold standard catalogues are those released by the WHO but the underlying data are not fully released and they are difficult to interpret. Open and reproducible methods would help address these problems, extending the important work already done. MethodsWe have developed an automated method, catomatic, that uses a binomial test to associate informative isolates with resistance or susceptibility, and built a catalogue (catomatic-1) from the same 39,358 samples used to construct the first edition of the WHO catalogue (WHOv1). We performed a sensitivity analysis to optimise statistical and bioinformatic parameters for each drug, and benchmarked catomatic-1 against WHOv1 using an independent Validation Dataset of 14,380 isolates. FindingsBy using simpler statistics, catomatic-1 algorithmically classified 1,329 genetic variants, ranging from five for linezolid to 440 for pyrazinamide. WHOv1 included generalisable rules added by a panel of experts, increasing its predictive coverage, but at the cost of reproducibility. Despite not including such expert rules, catomatic-1 achieves comparable performance for all drugs, with sensitivities for first-line agents above 88% on the independent Validation Dataset. The automated process allowed us to efficiently explore parameter space; for instance, detecting resistant variants with low read support improved the sensitivity for all drugs. InterpretationPerformant resistance catalogues for M. tuberculosis can be built automatically using transparent and reproducible statistical methods. As more data are collected, catalogue content and performance will evolve, highlighting the need for proper versioning, machine/human readability, and open access. This approach demonstrates resistance catalogues used in surveillance and diagnostics can be rapidly and reproducibily updated. FundingThe National Institute for Health and Care Research (NIHR), Engineering and Physics Sciences Research Council (EPSRC) and ORACLE Corporation. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed and preprint servers (bioRxiv, medRxiv), and publicly available mutation catalogues for studies linking Mycobacterium tuberculosis genomic variants with drug resistance using whole-genome or targeted sequencing and phenotypic drug-susceptibility testing (pDST). Search terms combined "Mycobacterium tuberculosis", "genome sequencing", "mutation catalogue", "mutation effects", "drug resistance", and individual drug names, with no language or date restriction. We included studies providing paired, clinical genomic and pDST or MIC data, excluding purely in-silico or case-only reports. This work directly builds on methodologies and data published by five prior studies, and makes primary comparisons with the First (WHOv1) and Second (WHOv2) Editions of the WHO Catalogue of mutations in Mycobacterium tuberculosis. Added value of this studyWe developed catomatic, a transparent, reproducible tool for building catalogues of resistance- and susceptibility-associated genetic variants. Trained on the same samples used to build WHOv1 and benchmarked on an independent Validation Dataset, catomatic achieves comparable sensitivity, specificity, and definitive prediction rates to WHOv1 without expert-rule augmentation and despite using simpler statistics. It optimises parameters per drug, produces machine-readable outputs (CSV/JSON), and demonstrates that adjusting read-support thresholds can improve detection of minor resistance subpopulations. Implications of all the available evidenceCatalogues of resistance-associated variants for M. tuberculosis can be rapidly and transparently constructed. Making catalogues available in human/machine-readable formats with uncertainty estimates will improve uptake of WGS for M. tuberculosis surveillance and diagnostics; using a reproducible process permits diagnostic test manufacturers, researchers, clinical and public health laboratories to select the level of statistical support necessitated by their specific use-case, Policymakers should balance the benefits of expert rules against loss of reproducibility. Future work will expand the size of the datasets used, integrate minimum inhibitory concentration data, and establish consensus workflows for routine, transparent catalogue updates.

microbiology↗
bioRxiv2025

Towards decoding inner speech from EEG and MEG

Despite the prevalence of inner speech in everyday life, research on this has been limited, particularly when it comes to non-invasive methods. This preprint aims to fill this gap by using EEG and MEG to collect data from three different inner speech paradigms, and by conducting an initial decoding analysis. Specifically, we tested silent reading, repetitive inner speech, and generative inner speech tasks. We collect a high number of inner speech trials from a few participants. Besides comparing across recording modalities we also compare across inner speech types. Our aim is to analyse the decodability of inner speech within each task and between tasks by the use of transfer learning. We find that in both EEG and MEG, silent reading can be decoded relatively well with 30-40% accuracy across 5 words. However, the decoding performance of both types of inner speech is mostly at chance level. This prohibited further transfer learning investigations between tasks. While the inner speech results are primarily negative, we believe our exploration of data size and various decoding methods is valuable. The dataset itself is useful for the research community as it contains a much larger number of trials within one participant than any other inner speech dataset. Having multiple sessions also allows for testing across-session performance. Finally, we systematically compare silent reading decoding performance within 3 participants across four non-invasive modalities. These are EEG, 2 types of MEG machines, Elekta and CTF, and optically-pumped magnetometers (OPMs). We also compare the spatiotemporal dynamics of silent reading between these modalities. This is especially aimed at validating OPMs as a new kind of non-invasive brain recording technology. We find comparable performance to EEG, but OPM performance did not reach traditional MEG.

neuroscience↗
bioRxiv2025

A Druggable Tumor Suppressor and Leukemic Stem Cell Marker

Withdrawal StatementThe authors have withdrawn this preprint because the co-authors were not in agreement about posting the work in its current form. The authors request that this work not be cited. Please contact the corresponding author (Dr. Xunlei Kang, kangxu@health.missouri.edu) with questions.

cancer biology↗
bioRxiv2025

A Critical Re-evaluation of the Somatic Mutation Theory (SMT)Conceptual and Quantitative Limits of the Cell-Centric Paradigm

The Somatic Mutation Theory (SMT) frames cancer as a stochastic process driven by the accumulation of random mutations in somatic cells. Using a Poisson-Erlang waiting-time model, we test whether empirical mutation rates and cell-division frequencies permit such multi-hit carcinogenesis within biologically realistic timescales. Even under optimistic assumptions, expected waiting times exceed progenitor-cell lifespans by several orders of magnitude, rendering sequential multi-hit carcinogenesis statistically and biologically implausible. The analysis exposes SMTs internal inconsistencies and supports a paradigm shift from mutation accumulation to communication breakdown as the root cause of cancer. Companion Paper NoticeThis preprint constitutes Part I of a coordinated two-part series on the origins of cancer. Part I critically re-examines the Somatic Mutation Theory (SMT), demonstrating its conceptual and quantitative limits as a cell-centric paradigm. Part II - From Cell-Centric to System-Centric Carcinogenesis: The Repair and Capacity Adaptation (RCA) Conceptual Framework (Olsen & Liisberg, 2025b; Zenodo 10.5281/zenodo.17495975) - presents the complementary systems-biology framework that explains carcinogenesis as failure of progenitor-cell maturation within a degraded connective-tissue microenvironment. Together, the two papers mark a paradigm shift from mutation accumulation to communication-system failure as the root cause of cancer. A laymans summary of Part I is available as supplementary material for non-specialist readers.

cancer biology↗
bioRxiv2025

A quantitative approach to discover nonlinear signaling linking combinatorial environments with cellular responses

Cells constantly integrate diverse inputs from the extracellular environment, yet our understanding of how cells effectively process information from multiple cues at the same time remains limited. We utilized an integrated imaging platform and RNAseq analysis to investigate the combined effects of growth factors on cellular signaling and gene expression. Paired stimuli by receptor ligands revealed diverse signaling signatures-- ranging from antagonism to synergy--driving global signaling programs and gene expression. Notably, correlation networks based on signaling signatures identified vulnerabilities in cancer cells when compared to synergistic drug combinations. Profiling kinase and phosphatase activities uncovered a crucial interplay, where cellular sensitivity and phospho-turnover dynamics are modulated by input history through coordinated basal kinase and phosphatase activities. Our novel methodology sheds light on cellular processing of multiple cues, elucidating intricate mechanisms underlying cellular adaptation to extracellular environmental variations. Based on previous preprint: doi: https://doi.org/10.1101/346957

cell biology↗
bioRxiv2025

CYFIP1 overexpression amplifies IL-6/STAT3 and IFN-γ/STAT1 signaling: potential implications for neuroinflammation and autism spectrum disorder

Autism spectrum disorder (ASD) encompasses a group of neurodevelopmental disorders characterised by impaired social interaction, delayed language development, and repetitive or restrictive behaviours. While both genetic and environmental factors contribute to ASD, the specific molecular mechanisms underlying these interactions remain unclear. In a recent preprint, we showed that cytokine signaling may be dysregulated in chromosome 15q-duplication syndrome (Dup(15q)), one of the most common syndromic forms of ASD. Specifically, Dup(15q) induced pluripotent stem cells (iPSC)-derived neurons exhibit an amplified Signal Transducer and Activator of Transcription-3 (STAT3) response to Interleukin-6 (IL-6), a proinflammatory cytokine often upregulated in ASD. To identify which gene in the 15q region may be responsible for modifying cytokine signalling responses in Dup(15q), we focus on the Cytoplasmic FMRP-Interacting Protein 1 (CYFIP1) gene, as increased CYFIP1 dosage in Dup(15q) is associated with increased severity of neurobehavioral symptoms in individuals with Dup(15q) and CYFIP1 dysregulation has been linked to altered expression of various genes involved in immunoregulatory signalling pathways. Here, we explore the eeects of CYFIP1 overexpression (CYFIP1-OE) on cytokine signaling, demonstrating that CYFIP1-OE in HEK293 cells modifies the expression and activity of several cytokine signaling-related transcription factors, including STAT3 and STAT1. Additionally, we use SH-SY5Y neuroblastoma cells to assess neuron-related phenotypes, showing that CYFIP1-OE alters IL-6-induced neurite outgrowth. These findings provide novel insights into how CYFIP1 may contribute to dysregulated cytokine responses in ASD, advancing our understanding of the molecular mechanisms that underlie neuroinflammatory processes in this disorder.

molecular biology↗
bioRxiv2025

MatClassRSA v2 release: A MATLAB toolbox for M/EEG classification, proximity matrix construction, and visualization

MatClassRSA is a MATLAB toolbox that performs magnetoen-cephalography and electroencephalography (M/EEG) classification and other analyses related to Representational Similarity Analysis (RSA). The toolbox is designed for cognitive neuroscience researchers who wish to perform classification-based decoding analyses of their data--often repeated trials of evoked responses--or derive Representational Dissimilarity Matrices (RDMs) as input to RSA. Organized as a collection of usercalled functions, MatClassRSA v2 comprises five main modules: Preprocessing, Reliability, Classification, RDM Computation, and Visualization. The Classification module supports multiple classifiers (LDA, RF, SVM) and classification schemes (e.g., multiclass, pairwise, cross-validated, train-test, hyperparameter optimization) and offers basic statistical analyses via permutation testing. Functions in other modules include, for example, trial-averaging and noise normalization; reliability estimation; non-classification RDM construction; and hierarchical and non-hierarchical clustering visualizations. The toolbox is freely available on GitHub under an MIT license and includes the main codebase, a User Manual, example function calls, and illustrative analyses. This preprint provides a general background of M/EEG classification for RSA as well as a narrative overview of the v2 MatClassRSA release, its updated functionalities, and illustrative analyses performed using the toolbox.

neuroscience↗
bioRxiv2017

The dynamics of preferential host switching: host phylogeny as a key predictor of parasite prevalence and distribution

This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (https://doi.org/10.24072/pci.evolbiol.100049).\n\nNew parasites commonly arise through host-shifts, where parasites from one host species jump to and become established in a new host species. There is much evidence that the probability of host-shifts decreases with increasing phylogenetic distance between donor and recipient hosts, but the consequences of such preferential host switching remain little explored. We develop a mathematical model to investigate the dynamics of parasite host-shifts in the presence of this phylogenetic distance effect. Host trees evolve under a stochastic birth-death process and parasites co-evolve concurrently on those trees, undergoing host-shifts, co-speciation and extinction. Our model indicates that host trees have a major influence on these dynamics. This applies both to individual trees that evolved under the same stochastic process and to sets of trees that evolved with different macroevolutionary parameters. We predict that trees consisting of a few large clades of host species and those with fast species turnover should harbour more parasites than trees with many small clades and those that diversify more slowly. Within trees, large clades should exhibit a higher infection frequency than small clades. We discuss our results in the light of recent cophylogenetic studies in a wide range of host-parasite systems, including the intracellular bacterium Wolbachia.

evolutionary biology↗
bioRxiv2017

Can net diversification rates account for spatial patterns of species richness?

The diversification rate hypothesis (DRH) proposes that spatial patterns of species richness result from spatial variation in net diversification rates. We developed an approach using a time-calibrated phylogeny and distributional data to estimate the maximum explanatory power of the DRH, over a given time period, to current species richness in an area. We used this approach to study species richness patterns of a large family of suboscine birds across South America. The maximum explanatory power of the DRH increased with the duration of the time period considered and grain size; it ranged from 13 - 37 fold local increases in species richness for T = 33 Ma to less than 2-fold increases for T [&le;] 10 Ma. For large grain sizes ([&le;] 8{degrees} x 8{degrees}) diversification rate over the last 10 Ma could account for all the spatial variance in species richness, but for smaller grain sizes commonly used in biogeographical studies (1{degrees} x 1{degrees}), it could only explain < 16% of this variance. Thus, diversification since the Late Miocene, often thought to be a major determinant of Neotropical diversity, had a limited imprint on spatial richness patterns at small grain sizes. Further application of our approach will help determine the role of the DRH in explaining current spatial patterns of species richness.\n\nNote to readersThis manuscript has been seen by a few researchers, some of whom suggested that before publishing our work in a peer-reviewed journal we should conduct simulations to demonstrate that our methods properly estimate the contribution of variance in diversification rates to spatial variation in species richness. Although we believe that our approach derives logically from theory and statistics and is therefore valid, we understand that it is rather unique and see why some readers would think that an independent validation is necessary. Unable to complete such validation in the near future, however, we decided to make this manuscript available as a preprint to share our ideas and hopefully stimulate discussion on what we believe is a most interesting topic. We also hope to receive feedback that may enable us to improve our work for publication in a journal at a later date.

evolutionary biology↗
bioRxiv2018

Cost of resistance: an unreasonably expensive concept

This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (https://doi.org/10.24072/pci.evolbiol.100052). The cost of resistance, or the fitness effect of resistance mutation in absence of the drug, is a very widepsread concept in evolutionary genetics and beyond. It has represented an important addition to the simplistic view that resistance mutations should solely be considered as beneficial mutations. Yet, this concept also entails a series of serious difficulties in its definition, interpretation and current usage. In many cases, it may be simpler, clearer, and more insightful to study, measure and analyze the fitness effects of mutations across environments and to better distinguish those effects from pleiotropic effects of those mutations.

evolutionary biology↗
bioRxiv2018

When higher carrying capacities lead to faster propagation

This preprint has been reviewed and recommended by Peer Community In Ecology (https://dx.doi.org/10.24072/pci.ecology.100004). Finding general patterns in the expansion of natural populations is a major challenge in ecology and invasion biology. Classical spatio-temporal models predict that the carrying capacity (K) of the environment should have no influence on the speed (v) of an expanding population. We tested the generality of this statement with reaction-diffusion equations, stochastic individual-based models, and microcosms experiments with Trichogramma chilonis wasps. We investigated the dependence between K and v under different assumptions: null model (Fisher-KPP-like assumptions), strong Allee effects, and positive density-dependent dispersal. These approaches led to similar and complementary results. Strong Allee effects, positive density-dependent dispersal and demographic stochasticity in small populations lead to a positive dependence between K and v. A positive correlation between carrying capacity and propagation speed might be more frequent than previously expected, and be the rule when individuals at the edge of a population range are not able to fully drive the expansion.

ecology↗