{"source":"biorxiv","name":"bioRxiv preprints","kind":"widget","via":"native","records":[{"id":"10.1101/2023.07.25.550219","title":"Energy allocation explains how protozoan phenotypic traits change in response to temperature and resource supply","subtitle":"Andrea Perna · IMT School for Advanced Studies, Lucca · 2026-07-18","value":"ecology","href":"https://doi.org/10.1101/2023.07.25.550219","props":{"doi":"10.1101/2023.07.25.550219","authors":"Perna, A.; Rivoli, E. S.; Reiss, J.; Perkins, D. M.","institution":"IMT School for Advanced Studies, Lucca","category":"ecology","date":"2026-07-18","abstract":"To survive and reproduce, living organisms need to maintain an efficient balance between energy intake and energy expenditure. Changes in environmental conditions can disrupt previously efficient energy allocation strategies, and organisms are required to change their behaviour, physiology, or morphology to cope with the new environment. However, how multiple phenotypic traits interact with one another and with environmental conditions to shape energy allocation remains poorly understood. To better understand this type of phenotype-environment interactions, we develop a predictive framework, grounded in energetic and biophysical principles that allows us to make predictions on how metabolic rate and movement speed should change in response to environmental temperature and resource supply, differentiating between short-term, acute exposure to novel conditions and longer-term exposure that allows acclimation or adaptation. We tested these predictions by exposing axenic populations of the ciliate Tetrahymena pyriformis to different combinations of temperature and resource availability. We measured population growth, cell size, respiration, and movement. Acute increases in temperature led to higher movement speeds and respiration rates, consistent with expectations from physical scaling relationships such as the Boltzmann-Arrhenius equation and the viscous drag acting on movement. However, by around 3.5 days after the introduction of Tetrahymena into a novel environment, all measured traits shifted toward values closer to those of the original environment. These changes likely reflect phenotypic acclimation responses that restored a more efficient energy allocation under the new conditions. Changes in cell size played a key role in this process, by simultaneously affecting multiple phenotypic traits, including metabolic rate and the energetic costs of movement. In small microbial consumers like Tetrahymena, body size can change rapidly, relative to ecological and seasonal timescales. Changes in body size can therefore be effectively leveraged - alongside physiological and biochemical regulations - to cope with environmental changes.\n\nOpen researchThe raw data and all the analysis code used for this work are publicly available on github (https://github.com/pernafrost/Tetrahymena), and they are also deposited in Dryad (https://doi.org/10.5061/dryad.2v6wwpzvv). By downloading and running the code, it is possible to reproduce all the figures presented in the manuscript and in the Appendix. Please refer to the linked repositories for additional information, and feel free to contact the authors in case you need additional guidance."}},{"id":"10.64898/2026.06.17.732918","title":"Human vault RNAs exhibit diverse expression patterns and inter-locus compensation","subtitle":"Thomas R Cech · University of Colorado Boulder · 2026-07-18","value":"molecular biology","href":"https://doi.org/10.64898/2026.06.17.732918","props":{"doi":"10.64898/2026.06.17.732918","authors":"Hemphill, W. O.; Zaug, A. J.; Hecht, C. J. S.; Cech, T. R.","institution":"University of Colorado Boulder","category":"molecular biology","date":"2026-07-18","abstract":"In 1986, a class of small, noncoding RNAs was discovered in association with an enormous, enigmatic ribonucleoprotein complex - the \"vault\" particle - and thus dubbed vault RNAs (vtRNAs). However, its since been recognized that the vast majority ([&ge;]95%) of these noncoding vtRNA molecules are not associated with the mysterious vaults, raising questions about their potential independent function(s). Moreover, humans express four vtRNAs from two different loci, and debate has arisen about whether the vtRNA paralogs share any functional connection, and whether they should remain classified together. Herein, we report the expression patterns of the four VTRNA paralogs in a variety of human cell lines, including various single- and multi-gene VTRNA-knockout cell lines. Knockout of one or more of the three VTRNA1 genes leads to increased expression of vtRNA2-1, suggesting that their biological functions are related. Additionally, we interrogated the effects of vtRNA knockout on HEK293T cell growth, viability, and viral infection, and were unable to replicate previously reported associations. Collectively, our findings point to a potential functional connection between even the most distantly related human vtRNA paralogs, while reaffirming that their biological roles and mechanisms still require critical study."}},{"id":"10.64898/2026.05.28.728065","title":"Alveolar Epithelial Cell Loss of the Mitochondrial Regulator TFAM Drives Progressive Lung Fibrosis","subtitle":"Melanie Königshoff · Center of Lung Aging and Regeneration, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh School of Medicine, Pittsburg · 2026-07-18","value":"pathology","href":"https://doi.org/10.64898/2026.05.28.728065","props":{"doi":"10.64898/2026.05.28.728065","authors":"Hu, Q.; Onwuka, U.; Cardenes, N.; Packwood, M.; Huang, E. L.; Shi, J.; Melo-Narvaez, M. C.; Dutta, P.; Zhou, Z.; Beaulieu, D.; Chuan, B.; Suresh, P.; Redding, K. M.; Twardowski, L.-M.; Varley, S.; Pineda, R. H.; Sembrat, J.; Sullivan, M. L. G.; Franks, J.; Watkins, S. C.; Croix, C. S.; Kliment, C. R.; Eickelberg, O.; Lehmann, M.; Bueno, M.; Kaufman, B. A.; Königshoff, M.","institution":"Center of Lung Aging and Regeneration, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh School of Medicine, Pittsburg","category":"pathology","date":"2026-07-18","abstract":"Idiopathic pulmonary fibrosis (IPF) is characterized by failed alveolar epithelial repair and progressive fibrotic remodeling. Although aberrant reprogramming of alveolar type 2 (AT2) cells and accumulation of transitional AT2 states are increasing recognized as central features of IPF, the epithelial-intrinsic mechanisms that initiate these pathogenic states remain incompletely understood. Here, we identify mitochondrial transcription factor A (TFAM), a regulator of mitochondrial DNA maintenance, as a critical regulator of AT2 cell homeostasis. TFAM expression was reduced in AT2 cells from human IPF lungs. Inducible AT2 cell-specific Tfam deletion in mice caused spontaneous fibrotic remodeling and increased susceptibility to bleomycin-induced lung injury. TFAM-deficient AT2 cells acquired KRT8+ transitional and p21+ senescence-associated features before the onset of fibrotic transformation, accompanied by impaired oxidative phosphorylation, redox imbalance, mitochondrial superoxide accumulation, repression of mtDNA-encoded respiratory genes, and disrupted mitochondrial ultrastructure. TFAM-deficient AT2 cells developed a profibrotic secretory program that promoted extracellular matrix deposition and fibroblast activation. We further identified insulin-like growth factor-binding protein 2 (IGFBP2) as a secreted mediator induced in TFAM-deficient AT2 cells. IGFBP2 was elevated in AT2 cells in human IPF lung tissue and bronchoalveolar lavage fluid (BALF) from patients with IPF. IGFBP2 was detected in supernatants from fibrotic human precision-cut lung slices (hPCLS). IGFBP2 neutralization attenuated profibrotic remodeling in fibrotic hPCLS. Collectively, our findings identify TFAM-dependent mitochondrial homeostasis as an epithelial checkpoint linking AT2 cell-state stability to impaired epithelial-mesenchymal crosstalk driving pulmonary fibrosis."}},{"id":"10.64898/2026.07.06.736898","title":"Selective convergence and graded divergence of hippocampal and amygdala subregions using functional connectivity","subtitle":"Doruk Yiğit Erigüç · Max Planck Institute for Human Cognitive and Brain Sciences · 2026-07-18","value":"neuroscience","href":"https://doi.org/10.64898/2026.07.06.736898","props":{"doi":"10.64898/2026.07.06.736898","authors":"Erigüc, D. Y.; Marsiglia, M.; John, A.; Bayrak, S.; Wan, B.; Jakovcic, A.; DeKraker, J.; Royer, J.; Bernhardt, B.; Valk, S. L.","institution":"Max Planck Institute for Human Cognitive and Brain Sciences","category":"neuroscience","date":"2026-07-18","abstract":"The hippocampus and amygdala are neighboring medial temporal lobe structures linked to memory and affect, yet how their subregions are jointly embedded within distributed isocortical systems remains unclear. Using resting-state fMRI from 722 Human Connectome Project Young Adult participants, we mapped hippocampal and amygdalar subregions within a unified cortex-wide framework, quantifying subregion-to-cortex connectivity via Pearson correlation (broad co-fluctuation) and GLASSO partial correlation (relatively more direct functional association). We introduced two count-based metrics: dominance (relative hippocampal vs. amygdalar representation) and sharedness (balanced co-representation). Direct associations showed both structures sharing coupling with paralimbic areas and, more modestly, default mode regions, while broader co-fluctuations extended into somatomotor and paralimbic networks. Divergence patterns depended on the estimator: hippocampal subregions preferentially coupled with default-mode and visual networks under direct association, while amygdalar nuclei favored ventral attention and limbic networks; broader co-fluctuations additionally implicated somatomotor cortex for amygdala and visual cortex for hippocampus. These principles held at the subfield/nucleus level, varying along the hippocampal long axis and identifying the paralaminar nucleus as the most hippocampus-like amygdalar subregion. Data-driven connectivity gradients confirmed both systems separation and fine-scale interdigitation. Hippocampal and amygdalar subregions are thus embedded in cortex not as discrete systems, but through structured, spatially organized co-representation."}},{"id":"10.64898/2026.07.07.736939","title":"InsectDCT: A generalized pipeline for detection, taxonomic classification, and tracking of insects in camera-trap recordings","subtitle":"Kim Bjerge · Aarhus Universitet (ECE) · 2026-07-18","value":"ecology","href":"https://doi.org/10.64898/2026.07.07.736939","props":{"doi":"10.64898/2026.07.07.736939","authors":"Bjerge, K.; Wogram, S. F. A.; Serra-Marin, P. E.; Sakhiashvili, O.; Hoye, T. T.","institution":"Aarhus Universitet (ECE)","category":"ecology","date":"2026-07-18","abstract":"Automated monitoring of insect pollinators in natural environments with insect camera traps and trained deep learning algorithms provides novel data for insect ecological studies. However, efficient and accurate image recognition analysis of the recorded images or videos is challenging, particularly for images containing small insects against complex backgrounds with diverse vegetation communities. Even when insects can be detected in images, identifying their taxonomy remains difficult, particularly in footage with low image resolution, light conditions, and distances from the plants, and in cases where insects appear blurry or only partially visible.\n\nIn this work, we present InsectDCT, an AI-based pipeline for automated detection, hierarchical classification, and tracking of insects in footage of natural vegetation tested in different environments. The InsectDCT pipeline consists of three levels: insect Detection and localization, hierarchical taxonomic Classification, and spatio-temporal Tracking. In the first stage, insects are detected in time-lapse images or video recordings using the You Only Look Once (YOLO11) object detection architecture. Detection performance is improved using motion-enhanced images, which improve robustness in cluttered and 3 dimensional environments. The detector is trained on an extensive dataset that contains more than 60,000 images collected using camera traps deployed across a wide range of plant families and floral habitats. In the second stage, detected insects are classified using a hierarchical taxonomy-aware classification framework that covers 80 taxonomic groups. Classification is performed at multiple taxonomic levels, including order, family, and genus/species, allowing coarse and fine-grained ecological analyzes while accounting for varying levels of visual ambiguity. In the third stage, a multi-object tracking module is applied to high temporal-resolution image sequences and video data to associate detections of the same individual across time. InsectDCT code and all datasets are made publicly available."}},{"id":"10.64898/2026.06.15.732472","title":"Germline hypomethylation shapes dynamic CpG reservoirs in ape genomes","subtitle":"Soojin V. Yi · University of California, Santa Barbara · 2026-07-18","value":"genomics","href":"https://doi.org/10.64898/2026.06.15.732472","props":{"doi":"10.64898/2026.06.15.732472","authors":"Son, D. R.; Loh, E. Y.- H.; Jeong, H.; Ma, J.; Eichler, E. E.; Yi, S. V.","institution":"University of California, Santa Barbara","category":"genomics","date":"2026-07-18","abstract":"Telomere-to-telomere (T2T) genome assemblies resolve DNA methylation of complete ape genomes, including repetitive and satellite-rich compartments that were largely inaccessible in previous primate reference genomes. Here, integrating complete ape genome assemblies with long- and short-read germline and somatic DNA methylomes, we demonstrate dual roles of germline DNA methylation. While solidifying germline DNA methylation as a major driver of genome-wide long-term CpG erosion, we report an unexpected reservoir of hypomethylated CpGs that exist in previously inaccessible regions. Specifically, peri/centromeric satellites are markedly hypomethylated in sperm across great apes, despite their heterochromatic context and rapid sequence turnover. Moreover, we found their hypomethylation extends into adjacent non-satellite DNA at the boundaries of satellite-rich heterochromatic sequences and adjacent euchromatic sequences, forming centromeric hypomethylated extension domains, or CHEDs. CHEDs are enriched in recently duplicated genes, and CHED-associated genes show reproducible, enriched expression in the brain and testis. Extending our analyses to other structurally dynamic regions, including lineage-specific insertions, recent segmental duplications and structurally divergent regions, we show that these regions are also CpG-rich and relatively hypomethylated in sperm. Together, our results reveal a unique germline hypomethylation landscape in ape genomes in which structurally dynamic regions act not only as substrates of rapid genome evolution, but also as transient reservoirs of CpG-rich sequence contexts, promoting evolutionary innovations involving new genes and tissue-biased expression."}},{"id":"10.64898/2026.05.19.726053","title":"Lifestyles of Gypsy-family transposons shape their regulatory mechanisms","subtitle":"Susanne Bornelöv · University of Cambridge · 2026-07-18","value":"genomics","href":"https://doi.org/10.64898/2026.05.19.726053","props":{"doi":"10.64898/2026.05.19.726053","authors":"Papameletiou, A.-M.; Czech Nicholson, B.; Bornelöv, S.; Hannon, G. J.","institution":"University of Cambridge","category":"genomics","date":"2026-07-18","abstract":"Transposable elements are a highly diverse group of selfish genomic elements, prevalent across the tree of life, whose uncontrolled propagation poses a threat to genome stability. Recent studies have explored the evolution of Drosophila melanogaster transposable elements, their co-evolution with the host genome, and mechanisms that regulate their activity. However, little is known about their cross-species evolutionary patterns. Long terminal repeat (LTR) retrotransposons are the most active group of transposable elements in Drosophila. They are broadly separated into retroelements, which are active in the germline, and insect endogenous retroviruses that express in the gonadal soma. Somatic elements are hypothesised to infect the germline through their acquisition of virus-derived proteins such as Envelope and sORF2, thus multiplying through successive generations. In this study, we curated the sequences of LTR retrotransposons in 249 drosophilid genomes, allowing us to study their evolution across these species and highlight their varying degrees of conservation. Furthermore, we reveal multiple instances of Envelope protein loss or inactivation that suggest shifts in the expression pattern of these transposons, likely accompanied by adopting different transcriptional control mechanisms. We contrast this with the evolutionary history of sORF2, which we found to be much more stable. Lastly, we examined variations in transposon LTR regions responsible for transcriptional regulation and use predictive modelling to suggest six transcription factors likely involved in their tissue-specific expression. Altogether, we reveal complex, interspecies evolutionary patterns of Gypsy-family LTR retrotransposons and highlight examples of their coevolution with their host genome."}},{"id":"10.64898/2026.07.14.738476","title":"The Spontaneous Evolution of Biology","subtitle":"Sara ten Have · Origin Peptides · 2026-07-18","value":"biochemistry","href":"https://doi.org/10.64898/2026.07.14.738476","props":{"doi":"10.64898/2026.07.14.738476","authors":"ten Have, S.; McMillan, E.; Medway, T.; Kent, R.; Prescott, A. R.","institution":"Origin Peptides","category":"biochemistry","date":"2026-07-18","abstract":"We have demonstrated the potential of amino acids to polymerise into peptides, proteins, and form cell-like structures in the absence of cellular machinery, including nucleic acids, lipids or sugars. Not only has cell-free protein replication been observed, but evidence of protein templating strongly suggests protein mediated replication. We believe this is the first experimental demonstration of the link between the Miller-Urey experiment which produced amino acids from elemental starting material, and cell-like structures.\n\nLife, by definition, is the condition that distinguishes animals and plants from inorganic matter, including the capacity for growth, reproduction, functional activity, and continual change preceding death. Here we have characterised peptides which form reproducibly, into structures with longevity and which subsequently catalyse the polymerisation of free amino acids into copies of themselves. The proteomic analysis of these samples over time also enables evolution of peptide sequences to be seen and quantified. This evolution of both complex structure and functionally active proteins may potentially demonstrate a credible path to the beginnings of life, which we call the Spontaneous Evolution of Biology (SEB) Theory.\n\nOne Sentence SummaryWe have shown how peptides and proteins can be made from amino acids in an aqueous media without cells, lipids or nucleic acids, duplicating themselves and forming complex structures which resemble cells."}},{"id":"10.64898/2026.02.22.707331","title":"Dynamic, single-cell monitoring of CAR T cell identity and activation with Raman spectroscopy","subtitle":"Ariel Stiber · Stanford University · 2026-07-18","value":"bioengineering","href":"https://doi.org/10.64898/2026.02.22.707331","props":{"doi":"10.64898/2026.02.22.707331","authors":"Stiber, A.; Quach, B.; Ogunlade, B.; Georgiadis, A.; Chang, K.; Li, Y.; Quinn, P.; Wang, H.; Tsui, K. C. Y.; Ang, C.; Sotillo, E.; Miklos, D. B.; Mackall, C.; Good, Z.; Dionne, J. A.","institution":"Stanford University","category":"bioengineering","date":"2026-07-18","abstract":"Chimeric antigen receptor (CAR) T cell therapies have reshaped treatment for cancers and immune-mediated diseases, yet their safety and efficacy depend on both the proliferation of engineered cells and their dynamic functional state -- features that remain challenging to monitor in real-time clinical settings. Current methods require targeted labels, extensive processing, and provide only static snapshots of cell identity and activation. Here, we introduce a surface-enhanced Raman spectroscopy (SERS) and machine learning (ML) approach that enables single-cell identification of engineered CAR T cells without molecularly-targeted labels and time-resolved, semi-continuous monitoring of their functional activation state through a single physical readout spanning donor-derived cells and patient blood. From intrinsic vibrational signatures of live cells, we detect spectral differences resulting from engineered receptor expression in donor-derived CD19- and GD2-targeted CAR T cells (nine and five donors, respectively) with 81-85% donor-level accuracy, and resolve dynamic antigen-specific activation trajectories with temporal precision. Applying this same SERS-ML method to longitudinal samples from a four-patient CD19-CAR T therapy cohort, we classify patient peripheral blood mononuclear cells across pre-and post-infusion timepoints with a mean patient-level accuracy of 84%, and show that isolated CAR-positive T cells are distinguishable from both CAR-negative T cells and background populations with average 86-88% accuracies. These capabilities stem from biochemical signatures consistent with processes such as receptor expression, tonic signalling, and immune synapse formation, demonstrating a single method that reports both cellular identity and activation state with biochemical specificity across cell engineering and clinical monitoring contexts. Our results extend CAR T cell monitoring beyond static phenotyping and support the potential of SERS-ML analysis for rapid, point-of-care assessment of engineered immune cells across the therapeutic lifecycle."}},{"id":"10.64898/2026.05.07.721507","title":"A Beta-Binomial Model for Estimating Zero- or One-inflated Pain Trajectories","subtitle":"Yanxi Liu · Johns Hopkins Bloomberg School of Public Health: Johns Hopkins University Bloomberg School of Public Health · 2026-07-18","value":"bioinformatics","href":"https://doi.org/10.64898/2026.05.07.721507","props":{"doi":"10.64898/2026.05.07.721507","authors":"Liu, Y.; Harris, R. E.; Clauw, D.; Bayman, E.; Leroux, A.; Lindquist, M. A.","institution":"Johns Hopkins Bloomberg School of Public Health: Johns Hopkins University Bloomberg School of Public Health","category":"bioinformatics","date":"2026-07-18","abstract":"Chronic pain is a widespread public health issue that imposes substantial health, emotional, and economic burdens on individuals and communities. Because pain is subjective and lacks objective biomarkers, it is typically measured using patient-reported scores, often on a numerical scale from zero to ten. Increasingly, pain studies use ecological momentary assessment, with multiple daily assessments over days and across study phases (e.g., a series of baseline and post-intervention assessments). These data frequently show many ratings at the extremes (i.e., at minimum or maximum pain scores), commonly referred to as zero-and one-inflation in the statistical literature, along with considerable within-person variability both within and across days. These phenomena present challenges for statistical analyses, as they violate assumptions of most commonly used statistical techniques (e.g., the normality assumption of linear mixed models). We propose a Bayesian beta-binomial mixed-effects model for modeling potential zero- or one-inflated pain scores while accounting for variability using random effects on the mean and variance parameters across subjects. A simulation study demonstrates that the method accurately estimates model parameters across realistic sample sizes, time points, and zero- and one-inflation levels. An application to data from two longitudinal pain studies demonstrates that the model fits the data better and, when correctly specified, yields accurate uncertainty intervals for longitudinal changes in pain compared to existing models, especially for zero- and one-inflated outcomes. Additionally, the model directly estimates the probability of clinically meaningful pain events. The proposed method provides a powerful statistical framework for studying the patient-reported pain trajectories."}},{"id":"10.1101/2025.10.29.685379","title":"DNA branch migration across intact membranes powers an inside-out GPCR analog for lysis-free detection of intracellular RNA with on-membrane amplification","subtitle":"Rizal F. Hariadi · Arizona State University · 2026-07-18","value":"biophysics","href":"https://doi.org/10.1101/2025.10.29.685379","props":{"doi":"10.1101/2025.10.29.685379","authors":"Sasmal, R.; Yadav, S.; Wisna, G. B. M.; Acharya, N.; Swanson, C.; Yan, H.; Joshi, H.; Hariadi, R. F.","institution":"Arizona State University","category":"biophysics","date":"2026-07-18","abstract":"Interrogating the sequence-specific DNA/RNA content of a living cell without destroying it, is an elusive goal in biology and diagnostics with transformative potential. A DNA/RNA-based approach, however, must relay the recognition event across the intact lipid bilayer, a step that has long been considered impossible because hydrophilic, massively charged DNA/RNA is incompatible with the hydrophobic membrane interior. Here, we show that DNA branch migration can be driven across a lipid bilayer, converting an intracellular nucleic-acid sequence into an amplified, extracellular optical signal while preserving cell viability and compartmentalization, a synthetic transmembrane signal transduction analogous to natural receptors, such as G-protein-coupled receptors (GPCRs), but operating in reverse. We demonstrate this principle with Hybridization Across Lipid for Oligonucleotide Sensing (HALOS), an amphiphilic DNA hairpin comprising a toehold for recognition, a stem for stability, a loop, and cholesterols for transmembrane anchoring. Upon binding to a sequence-specific nucleic acid target, toehold-mediated strand invasion drives DNA branch migration across the bilayer, switching HALOS from a closed to an open conformation that relays the signal to the opposite face. Molecular dynamics simulations revealed that a cholesterol belt stabilizes the DNA stem within the membrane, preserving the hairpin structure necessary for transmembrane signaling. Notably, this branch migration proceeds despite the kinetic barrier of hybridization through the hydrophobic bilayer interior. By combining HALOS with an isothermal hybridization chain reaction (HCR), we established a platform that enables intracellular nucleic acid target detection and amplified fluorescent reporting from outside synthetic vesicles and live mammalian cells, achieving nanomolar-range sensitivity. These results establish DNA branch migration across lipid membranes as a design principle for programmable lysis-free molecular sensing in intact cells."}},{"id":"10.64898/2026.01.15.699627","title":"Self-organized Recovery of Coordinated Locomotion in Crickets via Prosthetic Limb Integration","subtitle":"Dai Owaki · Tohoku University · 2026-07-18","value":"neuroscience","href":"https://doi.org/10.64898/2026.01.15.699627","props":{"doi":"10.64898/2026.01.15.699627","authors":"Owaki, D.; Aonuma, H.","institution":"Tohoku University","category":"neuroscience","date":"2026-07-18","abstract":"Distributed sensorimotor interactions facilitate the coordination of multi-legged locomotion in insects without centralized control, yet the mechanisms that allow coordinated locomotion to re-emerge following limb loss remain poorly understood. Here, we systematically evaluate the effects of leg amputation and the integration of prosthetic legs on walking coordination in crickets Gryllus bimaculatus. Spherical treadmill experiments revealed that leg amputation disrupts inter-leg phase coupling, decreases locomotor speed, and alters spatial foot placement in a state-dependent manner, indicating impaired load-mediated coordination. Prosthetic legs did not merely restore intact kinematics; instead, they selectively reinstated coherent temporal coordination and axis-specific spatial organization. This structured recovery illustrates that re-introducing mechanically relevant sensory constraints is sufficient to re-engage distributed coordination networks, even in the absence of anatomical integrity. The selective recovery of temporal over spatial coordination, demonstrated here quantitatively for the first time, reveals the hierarchical architecture of distributed locomotion control and elucidates an embodied principle by which sensory-mechanical feedback facilitates the self-organization of resilient multi-legged locomotion following morphological intervention. Load-mediated sensory signals thus emerge as a key driver of distributed coordination in biohybrid systems, providing design principles for adaptive prosthetic engineering and sensorimotor rehabilitation."}},{"id":"10.64898/2026.01.09.698545","title":"Stepwise DNA unwinding gates TnpB genome-editing activity","subtitle":"Jennifer A. Doudna · University of California, Berkeley · 2026-07-18","value":"biochemistry","href":"https://doi.org/10.64898/2026.01.09.698545","props":{"doi":"10.64898/2026.01.09.698545","authors":"Zhou, Z.; Saffarian-Deemyad, I.; Shi, H.; Weiss, T.; ur-Rehman, M. M.; Vohra, K.; Skopintsev, P.; Yoon, P. H.; Trinidad, M. I.; Langeberg, C. J.; Kamalu, M.; Amerasekera, J.; Zhou, Y.; Doherty, E. E.; Aris, K. D. P.; Al-Sayyad, N.; Thornton, B. W.; Weissman, R. F.; Wasko, K. M.; Esain-Garcia, I.; DeTurk, E. C.; Savage, D. F.; Jacobsen, S. E.; Bryant, Z.; Doudna, J. A.","institution":"University of California, Berkeley","category":"biochemistry","date":"2026-07-18","abstract":"TnpB is a compact RNA-guided endonuclease and evolutionary ancestor of CRISPR-Cas12 that offers a promising platform for genome engineering. However, the genome-editing activity of TnpBs remains limited and its underlying determinants are poorly understood. Here, we used biochemical and single-molecule assays to examine the DNA-unwinding mechanism of Youngiibacter multivorans TnpB (Ymu1 TnpB). DNA unwinding proceeds through a discrete, long-lived partially unwound intermediate state before reaching a fully unwound open state. The open state forms inefficiently and collapses readily in the absence of negative supercoiling. An optimized variant, Ymu1-WFR, stabilizes formation of both the intermediate and open states, resulting in enhanced DNA cleavage in vitro and increased genome editing in plants. These findings identify the physical basis for the observed minimal activities of natural TnpBs, revealing how stabilizing specific unwinding states enables efficient DNA targeting."}},{"id":"10.64898/2026.07.06.736651","title":"LeafRank: A phylodynamic framework for inferring relative fitness from single-cell phylogenies in chromosomally unstable tumors","subtitle":"Ruping Sun · Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA · 2026-07-18","value":"bioinformatics","href":"https://doi.org/10.64898/2026.07.06.736651","props":{"doi":"10.64898/2026.07.06.736651","authors":"Wu, C.; Leder, K.; Wang, Z.; Sun, R.","institution":"Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA","category":"bioinformatics","date":"2026-07-18","abstract":"Tumors contain cancer cells with diverse growth potentials that shape evolutionary trajectories, yet this fitness diversity remains difficult to quantify in cases of whole-genome duplication (WGD) and chromosomal instability. We present LeafRank, a mathematical framework that leverages single-cell DNA-seq phylogenies to infer the relative fitness of individual cells. Using a multi-type branching process model, LeafRank integrates full tree topology, including branch lengths and bifurcation patterns, to estimate marginal fitness probabilities under punctuated evolutionary regimes driven by rare driver events. To account for elevated aberration rates following WGD, we introduce a tree-rescaling strategy that adjusts for lineage-specific genomic instability. Unlike methods focused on predefined subclones, LeafRank ranks all sampled cells, enabling flexible assessment of growth heterogeneity. Simulations demonstrate high accuracy across spatial and non-spatial virtual tumors. Applied to ovarian cancer, LeafRank reveals directional and parallel selection in WGD tumors and identifies recurrent copy number events enriched in high-fitness lineages. WGD lineages do not show immediate growth advantages but acquire fitness through subsequent alterations."}},{"id":"10.64898/2026.07.04.736459","title":"Thematic Shifts in Early-High-Impact Cancer Genomics and Diagnostics Research: A Bibliometric and Semantic Analysis","subtitle":"Zheng Su · AnyHelix Ltd., The Cloud, Tai Kok Tsui, Hong Kong, China · 2026-07-18","value":"bioinformatics","href":"https://doi.org/10.64898/2026.07.04.736459","props":{"doi":"10.64898/2026.07.04.736459","authors":"Su, Z.; Li, T.","institution":"AnyHelix Ltd., The Cloud, Tai Kok Tsui, Hong Kong, China","category":"bioinformatics","date":"2026-07-18","abstract":"Cancer genomics and diagnostics is a rapidly evolving field in which identifying which topics attract early citation prominence can inform laboratory investment, clinical translation, and research strategy. We developed a bibliometric framework to identify and characterize the most influential recent publications in this domain across two consecutive annual cohorts. Using a mathematically exact threshold-expansion algorithm, we ranked over 10,000 OpenAlex-indexed research articles per cohort by 18-month post-publication citation count. Large language model (LLM)-based topical relevance filtering yielded 50 substantively on-topic papers per cohort (100 total). LLM-based concept extraction and a two-stage, embedding-guided normalization pipeline produced 1,090 canonical concepts organized into 77 parent themes, enabling structured cross-cohort comparison of paper-level concept prevalence. The most cited papers in both cohorts were large-scale genomic infrastructure resources rather than single-disease mechanistic studies. Between consecutive cohorts, normalized frequencies increased most for clonal evolution and intratumoral heterogeneity, single-cell and spatial omics technologies, spatial transcriptomics, immune cell infiltration, and copy number variation, while liquid biopsy and ctDNA-related themes showed the largest declines. These findings indicate that early citation impact in cancer genomics is shifting toward integrative, spatially resolved, and heterogeneity-aware research, and demonstrate that LLM-augmented citation ranking provides a replicable, semantically enriched lens for monitoring thematic evolution in precision oncology. A web interface for exploring the results is available at https://pri.pepkio.com/."}},{"id":"10.64898/2026.06.01.729380","title":"Sequence charge decoration organizes salt response regimes in intrinsically disordered proteins: an interpretable machine-learning","subtitle":"Mahesh Aryal · North Dakota State University · 2026-07-18","value":"biophysics","href":"https://doi.org/10.64898/2026.06.01.729380","props":{"doi":"10.64898/2026.06.01.729380","authors":"Aryal, M.","institution":"North Dakota State University","category":"biophysics","date":"2026-07-18","abstract":"The conformational ensembles of intrinsically disordered proteins (IDPs) respond sensitively to ionic strength, with the direction and magnitude of response varying widely across sequence classes from polyelectrolyte contraction to polyampholyte swelling. Recent sequence-conditioned models provide rapid access to full ensembles or ensemble-averaged properties at specified solution conditions, but do not directly identify which low-dimensional polymer physics descriptors organize salt response behavior. Here, we construct a 511-sequence library spanning controlled{kappa} -variants, NCPR series, IDRome-stratified natural IDRs, and low-FCR IDRome sequences, and perform 2,555 CALVADOS-2 simulations across five monovalent salt concentrations (50 mM to 500 mM). For each sequence, we extract the salt-response slope, dRg/d[salt], and assign one of four regimes: polyelectrolyte contraction, polyampholyte swelling, non-monotonic response, or salt-insensitive behavior. Using eight theory-motivated sequence descriptors, we find that sequence charge decoration weighted by chain length, SCD x N, is the dominant coordinate organizing salt response, accounting for ~40% of total SHAP attribution and exceeding the next feature by more than twice. Ridge regression explains substantial in-distribution variance (R2 = 0.83 under random cross-validation), whereas gradient-boosted trees improve in-distribution performance (R2 = 0.97) and retain predictive power under the more stringent leave-one-subset-out validation test (R2 = 0.60), indicating that salt response contains transferable but nonlinear sequence-encoded structure. Regime classification robustly recovers the direction of salt response, with no polyelectrolyte-polyampholyte confusion, whereas non-monotonic and salt-insensitive sequences remain harder to distinguish from static sequence features alone. Together, these results establish SCD x N as a compact, interpretable organizing coordinate for CALVADOS-2-derived IDP salt response and provide a polymer-physics, feature-level complement to ensemble-level generative models."}},{"id":"10.64898/2026.07.16.738905","title":"Similar Synaptic and Current Input Properties of Aromatase and Nonaromatase Neurons in the Zebra Finch Auditory Telencephalon","subtitle":"Basilio Furest Cataldo · University of Massachusetts, Amherst · 2026-07-19","value":"neuroscience","href":"https://doi.org/10.64898/2026.07.16.738905","props":{"doi":"10.64898/2026.07.16.738905","authors":"Furest Cataldo, B.; Anderson, P. N.; Remage-Healey, L.","institution":"University of Massachusetts, Amherst","category":"neuroscience","date":"2026-07-19","abstract":"Abstract/SummaryEstrogens, commonly known for their role in sexual development and maturation, support a wide variety of brain functions, including cognition, neuroprotection, and sensory processing. For example, in a songbird auditory forebrain region, caudomedial nidopallium (NCM), neuroestrogens are elevated in response to conspecific vocal and social stimuli; in turn, elevated neuroestrogens in NCM are known to rapidly enhance auditory processing independent of sex. Despite the pivotal role of neuroestrogens for brain function, it remains largely unknown whether aromatase (neuroestrogen-synthesizing) neurons differ in their cellular and physiological properties from non-aromatase-expressing neurons, as might be expected from specializations seen in other steroidogenic cell types (e.g., adrenal cells). Therefore, we systematically profiled aromatase and nonaromatase expressing NCM neurons to determine how they might differ in synaptic and current input properties, using ex vivo whole-cell electrophysiology followed by immunohistochemistry to reveal aromatase expression. Current-clamp recordings revealed no differences between aromatase and nonaromatase neurons, aside from a modest divergence in the time to reach peak membrane afterhyperpolarization. Similarly, voltage-clamp recordings of post-synaptic currents revealed no significant differences between the two cell types, suggesting that they share similar synaptic input density. Therefore, aromatase and nonaromatase NCM neurons share similar intrinsic membrane properties (e.g. excitability) and synaptic input dynamics in the higher songbird pallium. Our findings leave open the possibility that diverging computational and/or modulatory roles for aromatase vs. non-aromatase neurons could be due to projection- or neurochemical-specificity in their afferents and efferents.\n\nSignificance StatementNeuroestrogens, locally synthesized in the brain by aromatase-expressing neurons, modulate neural circuit function across diverse brain regions, yet it remains unclear whether these cells represent a specialized neuronal population. We used whole-cell electrophysiology and post hoc identification of recorded neurons in the zebra finch auditory forebrain to compare the intrinsic and synaptic properties of aromatase and nonaromatase neurons. Confirming and extending previous findings, we show that aromatase-expressing neurons are not defined by unique electrophysiological properties. Instead, they appear to be functionally integrated within auditory circuits, supporting an alternative idea that neuroestrogen signaling acts through flexible neuromodulatory mechanisms rather than specialized neuronal properties. These findings do not exclude the possibility that aromatase neurons receive selective modulatory input from other brain regions."}},{"id":"10.64898/2026.07.14.738599","title":"Developmental enrichment enhances a topographically structured proprioceptive cortical code","subtitle":"Mario Prsa · University of Fribourg · 2026-07-19","value":"neuroscience","href":"https://doi.org/10.64898/2026.07.14.738599","props":{"doi":"10.64898/2026.07.14.738599","authors":"Palacio Manzano, M.; Ma, F.; Hoffmann Schreiner, C.; Ravussin, Y.; Prsa, M.","institution":"University of Fribourg","category":"neuroscience","date":"2026-07-19","abstract":"The organization of proprioceptive cortex emerges from experience-dependent patterns of limb use during development, rather than merely reflecting peripheral innervation. However, the degree and specifics of these developmental changes remain poorly understood. To address this question, we investigated how early environmental enrichment (EE) reshapes the topography and functional properties of the mouse forelimb proprioceptive cortex. Using wide-field calcium imaging, we found that EE did not induce major reorganization of the mesoscale activation map. To resolve cellular level topology, we developed a large-field fluorescence macroscope enabling unbiased single neuron imaging across the entire activation area. We identified a topographically organized preference in directional tuning in which somatosensory and motor regions of the map encode distinct movement axes within the peripersonal space. Developmental enrichment reshaped this anisotropic representation at the cellular level. Rather than reducing the directional bias by homogenizing tuning across movement directions, EE strengthened the anisotropy by sharpening its topographic segregation and concentrating neuronal tuning around a common peripersonal axis. Our findings therefore reveal that enriched limb use and sensorimotor exploration reinforce an ecologically relevant specialization of the mouse proprioceptive cortex for movements directed toward the body."}},{"id":"10.64898/2026.07.13.738282","title":"Phosphoproteomic Insights into TRPV4 - AMPK Signaling Axis in the Choroid Plexus Epithelium: Implications for Therapeutic Targeting in Hydrocephalus","subtitle":"Bonnie Blazer-Yost · Indiana University, Indianapolis · 2026-07-18","value":"neuroscience","href":"https://doi.org/10.64898/2026.07.13.738282","props":{"doi":"10.64898/2026.07.13.738282","authors":"Mahendran, G.; Torabi, M.; Blazer-Yost, B.","institution":"Indiana University, Indianapolis","category":"neuroscience","date":"2026-07-18","abstract":"BackgroundHydrocephalus is characterized by abnormal accumulation of cerebrospinal fluid (CSF) due to disrupted secretion, circulation, or reabsorption. CSF homeostasis is regulated by ion and water channels on choroid plexus epithelial (CPe) cells, including the mechanosensitive cation channel, transient receptor potential vanilloid 4 (TRPV4). Although TRPV4 antagonism prevents hydrocephalus progression in rats, how TRPV4 activity modulates CSF production remains unclear.\n\nMethodsBecause TRPV4 function is phosphorylation-dependent, we examined its activation (GSK1016790A) and inhibition (RN1734) and the downstream signaling alterations in human choroid plexus papilloma cells (HIBCPP) using phosphoproteomic mass spectrometry.\n\nResultsOur phosphoproteomic analysis revealed significant changes in kinases and tight junction (TJ) proteins regulating epithelial barrier integrity. TRPV4 activation altered TJ proteins such as Zonula Occludens-1 (ZO-1), and Claudin-7 (CLDN7) and AMP-activated protein kinase (AMPK), phosphorylation, with a notable foldchange increase of AMPK inhibitory phospho form (Ser496). Further our electrophysiological and biochemical analyses demonstrated that AMPK activation followed by TRPV4 stimulation increased AMPK Ser496 phosphorylation, and epithelial permeability was subsequently elevated, although it was statistically not significant. In contrast, AMPK inhibition prior to TRPV4 activation resulted in the opposite effect with substantial epithelial barrier tightness which was evident from the ZO-1 expression. Moreover, a pharmacologically available anti-diabetic drug, metformin exhibited a similar trend like Compound C in reducing the barrier epithelial permeability after TRPV4 agonist treatment, highlighting that metformin promotes barrier tightness via an AMPK-dependent pathway coupled to TRPV4 signaling.\n\nConclusionsOverall, these findings identify an AMPK-TRPV4 signaling axis that modulates epithelial permeability and may influence CSF regulation, highlighting a potential therapeutic target for hydrocephalus."}},{"id":"10.64898/2026.07.13.738236","title":"Modulation of retroviral capsid assembly halts ARC-mediated TDP-43 intercellular spreading","subtitle":"Gorka Gerenu Lopetegi · Biogipuzkoa HRI · 2026-07-18","value":"neuroscience","href":"https://doi.org/10.64898/2026.07.13.738236","props":{"doi":"10.64898/2026.07.13.738236","authors":"Jimenez-Zuniga, A.; Sanchez-Molleda, A.; Martinez-Ascension, A.; Jimenez-Salvador, I.; Fuentetaja, M.; Garcia ibarlucea, M.; Ramis Cortes, R.; Rodriguez-Gomez, L.; Hernandez-Eguiazu, H.; Alcain Dominguez, M.; Zuniga-Elizari, J. L.; Moragon Rodriguez, S.; Saez-Mas, A.; Blazquez, L.; Lafarga, V.; Fernandez Capetillo, O.; Leonardo, A.; Bergara, A.; Lopez de Munain Arregui, A.; Gil-Bea, F.; Gerenu Lopetegi, G.","institution":"Biogipuzkoa HRI","category":"neuroscience","date":"2026-07-18","abstract":"Intercellular propagation of pathological TDP-43 drives the progression of ALS and FTD, yet the mechanisms enabling transmission remain elusive. Here, we demonstrate that Activity-regulated cytoskeleton associated protein (ARC/Arg3.1) is pathologically subverted to act as a retroviral-like capsid vehicle for TDP-43 spreading. In a Drosophila model, we reveal that massive Arc1 upregulation drives glia-to-neuron TDP-43 seeding, while its genetic ablation halts pathological transfer, improves motor function, and extends survival. In parallel human cellular models, stress-induced ARC colocalizes with TDP-43 to orchestrate its intercellular transmission. Guided by ARCs capsid architecture, we reproposed Lenacapavir, an FDA-approved HIV-1 capsid modulator, as a stable binder of ARC/Arg3.1 capsid interfaces. Lenacapavir treatment effectively blocks TDP-43 propagation in vitro and rescues disease phenotypes in vivo. Our findings establish ARC as a conserved vehicle for pathological protein transmission and deliver an immediately translatable pharmacological strategy to arrest disease progression in ALS and FTD."}},{"id":"10.64898/2026.07.13.738146","title":"A structured-illumination miniscope for optically sectioned imaging and real-time neural decoding","subtitle":"Jingfeng Zhou · Beijing Normal University · 2026-07-18","value":"neuroscience","href":"https://doi.org/10.64898/2026.07.13.738146","props":{"doi":"10.64898/2026.07.13.738146","authors":"Lin, H.; Wang, S.; Zhu, Y.; Yin, Z.; Guo, Q.; Zhou, J.","institution":"Beijing Normal University","category":"neuroscience","date":"2026-07-18","abstract":"Single-photon miniscopes enable large-scale calcium imaging in freely behaving animals but are limited by out-of-focus background fluorescence that degrades image contrast and single-cell signal fidelity. Multiphoton approaches address this limitation but remain costly and complex. Here we introduce a lightweight (<3 g), low-cost structured illumination miniscope that achieves optical sectioning in freely behaving mice. Using HiLo imaging implemented with a simple Ronchi grating and time-multiplexed excitation, the system strongly suppresses background fluorescence while preserving the speed, field of view, and accessibility of widefield miniscopes, and supports optical-sectioned multi-plane imaging to increase neuronal yield. Using hippocampal recordings, we show enhanced region-of-interest (ROI)-based signal quality and spatial information readout, allowing simple ROI-averaged signals to approach the performance of offline algorithm-extracted signals. We further demonstrate a proof-of-principle closed-loop brain-machine interface enabled by rapid online signal extraction and real-time neural decoding. Together, these results establish structured illumination as a practical and accessible strategy for achieving high-contrast calcium imaging with miniaturized microscopes."}},{"id":"10.64898/2026.07.13.738341","title":"Molecular architecture of excitatory and inhibitory neurons in the first gustatory relay","subtitle":"Nilay Yapici · Cornell University · 2026-07-18","value":"neuroscience","href":"https://doi.org/10.64898/2026.07.13.738341","props":{"doi":"10.64898/2026.07.13.738341","authors":"Mahishi, D.; Yapici, N.; Papadimitriou, E. M.","institution":"Cornell University","category":"neuroscience","date":"2026-07-18","abstract":"Taste perception is a major determinant of food intake and is dynamically modulated by hunger and satiety signals across species. While the peripheral and cortical representations of taste sensory stimuli are well characterized, far less is known about how metabolic state shapes taste processing in subcortical structures such as the brainstem. The rostral nucleus of the solitary tract (rNTS) is the first central relay for gustatory input, yet how fasting remodels transcriptional programs in rNTS neurons remains poorly defined. To address this gap, we performed cell-type-specific bulk nuclear RNA sequencing of molecularly defined excitatory (Vglut2+) and inhibitory (Vgat+) rNTS neurons. We combined Cre-dependent Sun1-sfGFP nuclear tagging with fluorescence-activated nuclear sorting to profile each population in ad libitum-fed and 24-hour-fasted mice. The two populations were transcriptionally distinct and differed in their baseline complement of hunger- and metabolic-sensing genes. Fasting elicited a transcriptional response that was largely restricted to excitatory, Vglut2+, rNTS neurons, while the inhibitory population was minimally affected. In excitatory neurons, fasting reduced the expression of Gabrd, the {delta} subunit of the GABAA receptor that mediates extrasynaptic tonic inhibition, while leaving synaptic GABAA subunits and the glutamatergic or GABAergic neurotransmission machinery unchanged. RNAscope in situ hybridization confirmed Gabrd expression in Vglut2+ rNTS neurons and showed that Gabrd is also expressed in the non-Vglut2+ population; the cell-type specificity of the fasting response therefore reflects differential regulation of a shared gene rather than its restricted expression. Our results identify a cell-type-specific, state-dependent transcriptional signature in which fasting downregulates a mediator of tonic GABAergic inhibition in excitatory rNTS neurons, providing a candidate substrate for the metabolic modulation of taste processing within the brainstem.\n\nHighlightsO_LIExcitatory and inhibitory rNTS neurons are intermingled, not spatially segregated, in rNTS\nC_LIO_LIVglut2+ and Vgat+ rNTS nuclear transcriptomes are distinct at baseline\nC_LIO_LIFasting reshapes the Vglut2+ transcriptome but leaves Vgat+ neurons largely unchanged\nC_LIO_LIFasting downregulates Gabrd, a mediator of tonic inhibition, in Vglut2+ neurons\nC_LI"}},{"id":"10.64898/2026.07.13.738150","title":"Tracking Inflammation and Fibroblast Activation in Hypertensive Heart Failure Across the Cardio-Renal Axis","subtitle":"James T Thackeray · Hannover Medical School · 2026-07-18","value":"physiology","href":"https://doi.org/10.64898/2026.07.13.738150","props":{"doi":"10.64898/2026.07.13.738150","authors":"Strunk, M.; Hess, A.; Gutberlet, M.; Willmann, M.; Ross, T. L.; Bengel, F. M.; Thackeray, J. T.","institution":"Hannover Medical School","category":"physiology","date":"2026-07-18","abstract":"Hypertension and heart failure are associated with increased risk of chronic kidney disease. Cardiorenal syndrome is characterized by excessive systemic inflammation and progressive fibrosis. We hypothesized that transient hypertension in mice due to infusion of angiotensin II and phenylephrine (Ang/Phe) would induce parallel immune cell and fibroblast activation in both the heart and kidney, where the intensity of inflammation and fibroblast activity would predict decline in function of both organs. Adult male C57Bl/6N mice were randomized to receive 7d infusion of either Ang/Phe (n=41) or vehicle (n=27) by subcutaneous osmotic minipump. Despite removal of minipumps at 7d, Ang/Phe mice displayed persistent myocyte hypertrophy, interstitial fibrosis, and modestly reduced systolic function to 6 weeks. Molecular imaging of chemokine receptor CXCR4 using 68Ga-pentixafor at 3d of Ang/Phe infusion revealed transient inflammation in the left ventricle. Imaging of fibroblast activation protein (FAP) revealed diffuse fibroblast activity in the left ventricle. Both imaging signals predicted subsequent functional decline. Magnetic resonance imaging of the kidney revealed transient prolongation of T1 relaxation in at 2 weeks after Ang/Phe infusion that returned to normal by 6wk, despite a progressive reduction in renal perfusion. CXCR4 and FAP PET displayed no change in kidney inflammation or fibroblast activation. Comparison of imaging data described a direct correlation between cardiac and renal CXCR4 PET signal at 3d and FAP PET signal at 7d. The intensity of cardiac inflammation correlated with subchronic fibrosis in the kidney cortex. Total body molecular imaging enables simultaneous evaluation of the immune-fibrosis network in heart-kidney crosstalk after short term hypertension and may provide valuable guidance of novel therapies."}},{"id":"10.64898/2026.07.17.738806","title":"Hexadecimal data encryption in paranemic crossover (PX) DNA","subtitle":"Arun Richard Chandrasekaran · SUNY Albany · 2026-07-18","value":"synthetic biology","href":"https://doi.org/10.64898/2026.07.17.738806","props":{"doi":"10.64898/2026.07.17.738806","authors":"Karpen, A.; Chandrasekaran, A. R.","institution":"SUNY Albany","category":"synthetic biology","date":"2026-07-18","abstract":"DNA is highly programmable and efficient for encoding information. In this work, we use the paranemic crossover (PX) DNA structures for a binary-encoded system. As substrates for data storage, we designed a combination of PX and anti-PX structures where the four strands of the PX motif are complementary to those in the anti-PX motif. To write data, we programmed encoding elements in each of the four strands of the PX and anti-PX motifs. The encoded data remains encrypted until the samples are processed at a specific temperature, when the PX and anti-PX motifs reassociate to four distinct duplexes, defined by the encoding elements and retrieved using an electrophoretic readout. We show that the encoded information is stable for several days when stored at 20 {degrees}C, 37 {degrees}C or outdoors, with the encrypted structures showing higher nuclease resistance compared to the decrypted structures. Using this strategy, we demonstrate hexadecimal encoding using a combination of 4 bits, encrypting specific words and color codes. We envision such systems could find use barcoding, secure messaging and authentication."}},{"id":"10.64898/2026.07.17.739196","title":"Host skin lipids trigger MAT-dependent mating, pathogenic hyphal growth, and parasexual reproduction of Malassezia furfur","subtitle":"Giuseppe Ianiri · University of Molise · 2026-07-18","value":"microbiology","href":"https://doi.org/10.64898/2026.07.17.739196","props":{"doi":"10.64898/2026.07.17.739196","authors":"Patriarca, E.; Tirtiaux, B.; David-Palma, M.; Averette, A.; Gushiken Ibanez, E.; Poumay, Y.; LeibundGut-Landmann, S.; Heitman, J.; Coelho, M. A.; Ianiri, G.","institution":"University of Molise","category":"microbiology","date":"2026-07-18","abstract":"The lipophilic yeast genus Malassezia dominates the human skin mycobiome and, while typically commensal, is associated with skin disorders in which hyphal cells are frequently observed. However, the mechanisms underlying hyphal differentiation and its contribution to pathogenesis remain poorly understood. Here, we show that hyphal growth in Malassezia furfur requires a complete mating-type system and is promoted by noncanonical reproductive interactions. Interspecific mating generates stable diploid hybrids with evidence of recombination, whereas intraspecific mating produces cell-fusion products that undergo recombination and haploidization, consistent with a parasexual cycle. Functional analyses reveal that the pheromone/receptor (P/R) locus governs cell recognition and fusion, while the homeodomain (HD) locus is required for hyphal development despite having lost canonical mating-type determination. Leveraging in vitro and in vivo skin models, we show that hyphal cells invade the epidermis more efficiently and elicit stronger inflammatory responses than yeast cells. Together, these findings link parasexual-like reproduction, mating-type loci function, and morphogenesis in Malassezia to pathogenic interactions with the host."}},{"id":"10.64898/2026.07.17.739246","title":"Powassan virus infects mouse testes with phagocytic cells playing a protective role","subtitle":"Shannan  L. Rossi · University of Texas Medical Branch Office of University Advancement: The University of Texas Medical Branch at Galveston Development Office · 2026-07-18","value":"microbiology","href":"https://doi.org/10.64898/2026.07.17.739246","props":{"doi":"10.64898/2026.07.17.739246","authors":"Hager-Soto, E.; Arroyave, E.; Saldarriaga, O.; Eyzaguirre, E.; Freiberg, A. N.; Rossi, S. L.","institution":"University of Texas Medical Branch Office of University Advancement: The University of Texas Medical Branch at Galveston Development Office","category":"microbiology","date":"2026-07-18","abstract":"Powassan virus (POWV) is an emerging tick-borne orthoflavivirus with consistently increasing annual prevalence. Though understood as a vector-transmitted virus associated with neurological disease, a 2016 fatal case of an immune-compromised 63-year-old man reported testicular pain with postmortem detection of viral antigen in the testes suggested an altered tropism. The extent to which POWV can infect testes remains unclear. We used a BALB/c mouse model of POWV to elucidate the potential of POWV to establish infection in testes and model a potential mechanism of testicular tropism. Here, we report that POWV productively infects the male reproductive tract of mice. We find that POWV consistently infects mouse testes and epididymides at 3-and 5-days post-infection (dpi) with peak titers measuring 6.1 log10 PFU/gram tissue in testes. Furthermore, we find that at 5dpi POWV-infected mice testes are significantly higher in mass than uninfected controls. Due to macrophages being implicated in driving testicular pathogenesis in Zika virus, a related orthoflavivirus, we depleted phagocytic cells using clodronate liposomes prior to POWV infection and compared to control liposome treated mice. Depletion of phagocytic cells was associated with higher and sustained viremia, and significantly higher viral organ burden in the male reproductive tract of mice. Gene expression analysis revealed a robust antiviral, inflammatory, and chemokine response in the testes that was further amplified following phagocytic-cell depletion. These findings implicate the male reproductive tract as a previously underrecognized target of POWV disease and identify phagocytic cells as key in limiting viral infection of testes in mice."}},{"id":"10.64898/2026.07.17.739263","title":"Enrichment of polyphenol metabolism within the ubiquitous SAR116 Puniceispirillales bacterioplankton","subtitle":"Cameron Thrash · University of Southern California · 2026-07-18","value":"microbiology","href":"https://doi.org/10.64898/2026.07.17.739263","props":{"doi":"10.64898/2026.07.17.739263","authors":"Coelho, J. T.; Borton, M. A.; Thrash, C.","institution":"University of Southern California","category":"microbiology","date":"2026-07-18","abstract":"Marine dissolved organic matter (DOM) is a complex pool of substrates, and a central challenge in marine biogeochemistry is to determine which DOM compounds are produced, consumed, or exchanged by microorganisms. Aromatic compounds, including polyphenols, comprise an important chemical class of marine DOM generated both in situ and also supplied via atmospheric deposition, terrestrial runoff, or natural seeps. Here we demonstrate, through pangenomics and metabolic reconstruction, the enrichment of genes for degradation of a wide variety of polyphenols in the cosmopolitan SAR116 bacterioplankton (Puniceispirillales). Gene and pathway conservation, the evolutionary history of key ring-cleaving dioxygenases, and expression patterns from global ocean surveys support the conclusion that these transformations represent core elements of SAR116 ecophysiology. The degradation pathway for protocatechuate, an end member for many polyphenol transformations, occurred in all subclades, and we found evidence of different evolutionary histories for genes in this pathway, including gene loss, analogous substitution, and retention of horizontally transferred genes from the Gammaproteobacteria. Furthermore, variation in these and other pathway-specific gene losses suggest that some SAR116 polyphenol metabolism may occur through a division of labor in concert with other community members and/or require novel or promiscuous enzymes. The enrichment and expression of polyphenol degradation pathways define a previously underappreciated metabolic niche for SAR116 and provides new evidence emphasizing the importance of polyphenol metabolism in the marine carbon cycle."}},{"id":"10.64898/2026.07.18.739312","title":"Bovine-derived H5N1 influenza virus efficiently infects lactating swine via the mammary gland","subtitle":"Cody J Warren · The Ohio State University · 2026-07-18","value":"microbiology","href":"https://doi.org/10.64898/2026.07.18.739312","props":{"doi":"10.64898/2026.07.18.739312","authors":"Liu, M.; Chillson, N. N.; Martin, E. A.; Cochran, H. J.; Park, J. Y.; O'Boyle, B.; Huey, D.; Corps, K. N.; Bowman, A. S.; Warren, C. J.","institution":"The Ohio State University","category":"microbiology","date":"2026-07-18","abstract":"Since 2024, highly pathogenic influenza A(H5N1) viruses have spread extensively among U.S. dairy cattle, where they replicate efficiently in the mammary gland and are shed at high titers in milk. To directly assess susceptibility of commercial swine populations to bovine-derived H5N1 virus, lactating sows with prior influenza virus vaccination histories representative of U.S. commercial swine production systems were inoculated via the intramammary route and co-housed with their 1-week-old piglets to evaluate disease outcomes, viral replication, and potential for vertical transmission. Intramammary inoculation of lactating sows resulted in sustained viral RNA shedding in milk, while piglets exhibited sporadic oral viral RNA positivity that mirrored viral kinetics in milk. Lesions in mammary tissue and viral antigen staining, as well as development of neutralizing antibody responses and changes in milk color and consistency, further confirmed infection in the sows. Despite these molecular findings, none of the animals developed overt clinical disease, and respiratory involvement was not noted during the study period. Collectively, we demonstrate that intramammary exposure results in productive influenza A(H5N1) virus infection in lactating sows despite their vaccination histories, indicating the potential threat of viral spillover into commercial swine populations. The clinically inapparent nature of infection presents a risk of subclinical spread and underscores the importance of expanding viral surveillance to swine."}},{"id":"10.64898/2026.07.17.739236","title":"A Structurally Defined C12-Alkyl Quaternary Ammonium Compound reduces bacterial burden and biofilm in an infected wound model","subtitle":"CHAD J ROY · Tulane University School of Medicine · 2026-07-18","value":"microbiology","href":"https://doi.org/10.64898/2026.07.17.739236","props":{"doi":"10.64898/2026.07.17.739236","authors":"Kist, M.; Wulandari, I. G. A. I.; Buell, J. F.; Morici, L. A. J.; ROY, C. J.","institution":"Tulane University School of Medicine","category":"microbiology","date":"2026-07-18","abstract":"BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) remains a common cause of skin and soft tissue infections, and topical agents that combine antimicrobial activity with wound compatibility are needed. C12-alkyl(ethylbenzyl)dimethyl ammonium chloride is a novel C12 quaternary ammonium molecule (hereafter,  EQ12) related to benzalkonium chloride but designed to avoid the compositional heterogeneity and varied potency of conventional C8-C18 benzalkonium mixtures. We evaluated whether topical EQ12 is tolerated in healing wounds and whether it reduces MRSA burden in a splinted murine excisional wound infection model.\n\nMethodsFemale CD1 mice underwent 5-mm full-thickness dorsal excisional wounding, silicone splinting, and transparent dressing placement. For tolerability studies, uninfected wounds received EQ12 at 0.1 or 1 mg/mL or phosphate-buffered saline (PBS) and were followed for 14 days. For efficacy studies, wounds were inoculated with 1 x 104 CFU MRSA and treated topically every 8 hours for 3 days beginning 4 hours after infection with EQ12 (1 mg/mL), bacitracin (500 U/mL), or PBS. Wound tissues were harvested on days 2, 4, and 6 for quantitative culture. Dressing-associated biofilm was evaluated by scanning electron microscopy.\n\nResultsEQ12 did not alter body weight, wound inflammation scores, wound area, or percent wound closure compared with PBS in uninfected animals. In infected wounds, day 2 tissue burdens were not significantly different among treatment groups. By day 4, EQ12 significantly reduced MRSA burden compared with PBS, whereas bacitracin did not. By day 6, EQ12-treated animals had significantly lower MRSA burdens than both bacitracin- and PBS-treated controls. Mean tissue burden in the EQ12 group declined from 6.27 log10 CFU/g on day 4 to 5.53 log10 CFU/g on day 6, while bacitracin- and PBS-treated wounds remained persistently colonized. SEM revealed minimal adherent cocci or matrix-like bridging on dressings from EQ12-treated wounds, in contrast to dense microcolonies and biofilm-like structures on bacitracin and PBS dressings.\n\nConclusionsTopical EQ12 was compatible with gross wound healing and reduced MRSA burden in a dressed, splinted murine wound model. These data support continued development of EQ12 as a topical anti-staphylococcal wound-directed antimicrobial."}},{"id":"10.64898/2026.07.14.738416","title":"Nowhere to Hide: The Effect of Centromere Architecture on LTR Retrotransposon Dynamics","subtitle":"Frantisek Zedek · Department of Botany and Zoology, Faculty of Science, Masaryk University, Kotlarska 2, 611 37 Brno, Czech Republic · 2026-07-18","value":"evolutionary biology","href":"https://doi.org/10.64898/2026.07.14.738416","props":{"doi":"10.64898/2026.07.14.738416","authors":"Kratka, M.; Panda, K.; Jedlicka, P.; Bures, P.; Kubat, Z.; Smerda, J.; Marques, A.; Kejnovsky, E.; Zedek, F.","institution":"Department of Botany and Zoology, Faculty of Science, Masaryk University, Kotlarska 2, 611 37 Brno, Czech Republic","category":"evolutionary biology","date":"2026-07-18","abstract":"Centromere architecture can determine where transposable elements persist, yet its effects on retrotransposon turnover remain poorly understood. Here we test a chromosome-level \"nowhere-to-hide\" model, in which holocentric chromosomes, owing to distributed centromere activity and reduced chromatin compartmentalization, provide fewer stable repeat-rich refugia than monocentric chromosomes. We combined genome-wide LTR retrotransposon annotation, spatial modelling and FISH across 40 holocentric plant species and 31 closely related monocentric relatives from Poales, Cuscuta, and Melanthiaceae. Overall LTR retrotransposon abundance and Ty1-copia/Ty3-gypsy composition were explained mainly by lineage history and chromosome size, rather than by holocentricity itself. By contrast, element persistence and removal showed dependence on centromere architecture. Intact LTR retrotransposons were younger in holocentric genomes, and holocentric chromosomes lacked the chromosome-size-dependent spatial clustering of element age observed in monocentrics. Solo-LTR profiles further revealed weaker spatial clustering of removal signatures in holocentric chromosomes, consistent with a more homogeneous chromosome-wide landscape of ectopic recombination. Epigenomic analyses of a matched Luzula-Juncus pair indicated that young elements can occur in centromeric chromatin, whereas solo LTRs are associated with more euchromatic contexts. These results support the nowhere-to-hide model, showing that centromere architecture does not shape LTR retrotransposons accumulation, but their persistence and removal efficiency."}}],"count":30,"generated_at":"2026-07-25T12:28:33.948Z"}