{"source":"biorxiv","name":"bioRxiv preprints","kind":"widget","via":"native","records":[{"id":"10.64898/2026.07.02.735529","title":"A pipeline for identifying small noncoding RNA (sRNA) candidates in bacteria","subtitle":"Jonathan Perreault · INRS · 2026-07-10","value":"molecular biology","href":"https://doi.org/10.64898/2026.07.02.735529","props":{"doi":"10.64898/2026.07.02.735529","authors":"Elhedi, S.; NDiaye, K. D. S.; Perreault, J.","institution":"INRS","category":"molecular biology","date":"2026-07-10","abstract":"Bacterial small non-coding RNAs (sRNAs) are central post-transcriptional regulators, yet their computational identification suffers from high false-positive rates due to transcriptional noise and the absence of canonical coding features.\n\nWe developed a three-stage pipeline integrating sRNA prediction (sRNA-Detect), transcription start site mapping (TSSAR, dRNA-seq), and Rho-independent terminator detection (RNIE), applied across nine phylogenetically diverse bacterial species spanning six phyla.\n\nSequential filtering achieved 1.4 to 33 fold precision improvements across nine species, reducing candidate sets by up to 99.6% while recovering known sRNAs at rates reflecting reference database depth (6% recall in S. aureus, 33-34% in E. coli and S. enterica)\n\nTSS and RIT constraints constitute universal, genome-size-independent biological filters that substantially enrich sRNA predictions across bacterial diversity. Precision variation across species reflects database incompleteness rather than pipeline failure, with unmatched predictions in poorly annotated organisms representing candidate novel sRNAs rather than false positives. RNA-seq coverage depth provides a reliable secondary indicator of biological relevance, though its interpretation requires accounting for sequencing depth variation across datasets."}},{"id":"10.64898/2026.07.02.731374","title":"The nucleolus is a mechanosensitive condensate that adapts ribosome biogenesis to mechanical forces","subtitle":"Monika Elzbieta DOLEGA · Institute for Advanced Biosciences, University of Grenoble-Alpes, CNRS UMR5309, INSERM U1209; La Tronche, 38700, France · 2026-07-10","value":"cell biology","href":"https://doi.org/10.64898/2026.07.02.731374","props":{"doi":"10.64898/2026.07.02.731374","authors":"Shetty, Y.; Elias, K. O.; Badawi, S.; Pernet, L.; Ribba, A.-S.; Oddou, C.; Wacheul, L.; Belmudes, L.; Moutaux, E.; Zorbas, C.; Fraboulet, S.; Coute, Y.; Erdel, F.; Lafontaine, D. L. J.; Dolega, M. E.","institution":"Institute for Advanced Biosciences, University of Grenoble-Alpes, CNRS UMR5309, INSERM U1209; La Tronche, 38700, France","category":"cell biology","date":"2026-07-10","abstract":"Intracellular compartmentalization is fundamental to cellular organization, yet mechanobiology has been largely understood through membrane-delimited structures and associated signaling pathways. Whether mechanical forces directly regulate biomolecular condensates, which organize many core cellular functions, remains largely unknown. This question is particularly relevant for the nucleolus, a prominent nuclear condensate that coordinates ribosome biogenesis and is known to remodel in response to diverse biochemical perturbations, placing it at the interface between cellular state and biosynthetic control. Here, we show that mechanical compression remodels nucleolar organization and reduces (ribosomal DNA) rDNA transcription, and identify nucleolin as a key mediator of this adaptive response. Compression induces rapid and reversible redistribution of nucleolin from the nucleolus to the nucleoplasm, accompanied by reduced occupancy at rDNA promoter regions and changes in rDNA transcription and precursor rRNA processing. The nucleolar response occurs independently of classical post-translational regulation of nucleolin and instead depends on the rate of nuclear deformation, with nucleolar organization and function scaling with nuclear volume loss, supporting a mechanism of biophysical regulation. Together, our findings establish the nucleolus as a mechanosensitive condensate and reveal dual regulation of ribosome biogenesis by mechanical compression, through rapid nucleolin-based biophysical adaptation followed by slower epigenetic remodeling."}},{"id":"10.64898/2026.07.02.736211","title":"Dynein-microtubule forces drive nucleokinesis and transmigration in T cells","subtitle":"Erdem D Tabdanov · Penn State College of Medicine · 2026-07-10","value":"cell biology","href":"https://doi.org/10.64898/2026.07.02.736211","props":{"doi":"10.64898/2026.07.02.736211","authors":"Tagay, Y.; Zhovmer, A. S.; Sarkar, N.; Stoop, J.; Su, L.; Fleszar, L.; Peterman, E.; Rasmussen, J. P.; Cartagena-Rivera, A. X.; Tsygankov, D.; Tabdanov, E. D.","institution":"Penn State College of Medicine","category":"cell biology","date":"2026-07-10","abstract":"Beyond the mechanical capacity of canonical actomyosin-driven amoeboid motility in permissive extracellular environments, the nucleus becomes the principal barrier to T cell migration in confining tissues. We establish the dynein-microtubule (MT) force-transmission axis as an essential mechanism for nuclear translocation during confined T cell migration and transmigration. We argue that dynein acts both as a motor and as an F-actin-anchored force-transmission element (fulcrum), sliding MTs and the MT-coupled nucleus along the cell cortex to drive nucleokinesis and productive cell displacement. Dynein is the primary driver of nucleokinesis: its inhibition arrests nucleus movement independently of myosin II activity, while F-actin dynamics remain spatiotemporally decoupled from nuclear oscillations. During transmigration, dynein and actomyosin act cooperatively and non-redundantly, and only combined inhibition abolishes nuclear passage. Computational modeling demonstrates that dynein-mediated pulling, together with volume exclusion imposed by the nucleus, is sufficient to generate self-organized nuclear oscillations. Dynein inhibition in zebrafish Langerhans cells impairs protrusion dynamics in situ, identifying the dynein-MT axis as an evolutionarily conserved mechanobiological program. Collectively, these findings identify the dynein-MT mechanical unit as a potential target for engineering T cells with enhanced solid-tumor infiltration."}},{"id":"10.1101/2025.11.05.684726","title":"Western Ghat birds exhibit a unique pattern of seasonal elevational shifts and a combination of thermal regime dependent shift strategies.","subtitle":"Ali Khan Faizee · Indian Institute of Science Education and Research, Tirupati · 2026-07-10","value":"ecology","href":"https://doi.org/10.1101/2025.11.05.684726","props":{"doi":"10.1101/2025.11.05.684726","authors":"Faizee, A. K.; Ramesh, V.; Robin, V. V.","institution":"Indian Institute of Science Education and Research, Tirupati","category":"ecology","date":"2026-07-10","abstract":"Elevational migration is globally exhibited by montane bird species through elevational range shifts to track seasonal changes in weather patterns and resources. Studies investigating the patterns and mechanisms of such elevational shifts have been limited in spatial scale owing to the difficulty of sampling data across montane gradients. Here, we integrated data from the worlds largest participatory science project (eBird) with systematic surveys to examine patterns and mechanisms that may explain bird elevational range shifts in the Nilgiri Hills of the Western Ghats Biodiversity Hotspot. We calculate the extent of shifts in elevational ranges for birds present year-round in the Nilgiris between the hottest and coldest months and quantify the associations between these shifts and species traits using phylogenetic generalized least squares regressions. We found that 77% (54/70) of the species investigated showed seasonal shifts in their elevational ranges. Birds in the Nilgiris showed nearly equal proportions of downslope (37%) and upslope (33%) winter shifts. All species had significant range overlap between seasons but employed different shifting strategies. Species with narrow thermal regimes predominantly shifted downslope in winter (niche tracking), while those with the widest thermal regimes shifted upslope (niche switching), revealing that species adapt to climatic variability through contrasting thermal strategies. Our results suggest that climatic constraints, specifically thermal regime, could be a major driver of seasonal shifts in elevational ranges of birds in the Nilgiris. Understanding these elevational shift strategies is critical for conservation planning in tropical montane systems facing accelerating climate change."}},{"id":"10.64898/2026.06.02.729618","title":"Argininosuccinate Synthase 1 links hepatic urea cycle to whole body lipid metabolism","subtitle":"M. Celeste Simon · University of Pennsylvania · 2026-07-10","value":"cancer biology","href":"https://doi.org/10.64898/2026.06.02.729618","props":{"doi":"10.64898/2026.06.02.729618","authors":"Kim, L. C.; Lesner, N. P.; Cai, X.; Han, X.; Jung, J. W.; Xu, J. P.; Coffey, N. J.; Zheng, D.; Brown, M. L.; Mesaros, C.; Arany, Z.; Simon, M. C.","institution":"University of Pennsylvania","category":"cancer biology","date":"2026-07-10","abstract":"The hepatic urea cycle is consistently suppressed in liver disease and hepatocellular carcinoma (HCC), but whether loss of individual enzymes contributes to disease initiation and progression remains unknown. Using mice with hepatocyte-specific deletion of argininosuccinate synthase 1 (ASS1), the urea cycle enzyme that condenses citrulline and aspartate into argininosuccinate, we investigated the role of ASS1 in diet and carcinogen-induced liver disease progression. We found that complete loss of hepatic Ass1 is lethal, but high fat diet extends lifespan. Unexpectedly, animals with approximately 85% loss of hepatic Ass1 are completed protected from diet-induced obesity, liver steatosis, fibrosis, and HCC. We determined that hepatic Ass1 loss activates fatty acid oxidation in peripheral oxidative tissues leading to increased energy expenditure and protection from disease phenotypes. Moreover, targeting Ass1 after obesity onset promotes weight loss and reverses liver steatosis. These findings implicate hepatic ASS1 as a novel regulator of whole-body lipid metabolism that can be targeted to prevent obesity, liver disease, and HCC."}},{"id":"10.64898/2026.07.03.736328","title":"Cytogenomic signatures of hybridisation in the genus Carpobrotus reveal biased parental dominance","subtitle":"Sonia Garcia · Institut Botanic de Barcelona (IBB, CSIC-CMCNB) · 2026-07-10","value":"plant biology","href":"https://doi.org/10.64898/2026.07.03.736328","props":{"doi":"10.64898/2026.07.03.736328","authors":"Pascual-Diaz, J. P.; Torres, M.; Bacovsky, V.; Horakova, L.; Kruzlicova, J.; Novotna, P.; Novoa, A.; Vitales, D.; Garcia, S.","institution":"Institut Botanic de Barcelona (IBB, CSIC-CMCNB)","category":"plant biology","date":"2026-07-10","abstract":"O_LIHybridisation is frequently associated with plant invasions; however, its consequences for genome organisation and chromosome evolution remain poorly understood in invasive species. We investigated the extent of hybridisation in the invasive Carpobrotus edulis--acinaciformis hybrid complex and determined the cytogenomic contribution of parental species in hybrid accessions.\nC_LIO_LIWe combined whole-genome sequencing, population genomic analyses, genome size estimation, repeatome characterisation, chromosome counting and fluorescence in situ hybridisation to compare parental species and hybrid accessions from South Africa and the Mediterranean Basin.\nC_LIO_LIPopulation genomic analyses revealed widespread hybridisation and introgression, with most invasive accessions showing admixed ancestries. Pattersons D-statistic supported asymmetric allele sharing towards C. edulis. Hybrid accessions displayed genome sizes indistinguishable from C. edulis, whereas C. acinaciformis possessed significantly larger genomes. Repeatome analyses identified marked differences in repetitive DNA composition, particularly in satellite DNA abundance and chromosomal distribution. A newly identified satellite repeat (CarpoSat) showed contrasting chromosomal patterns between parental species, whereas hybrids resembled C. edulis satellite pattern.\nC_LIO_LIOur results demonstrate that Carpobrotus hybrid accessions are a swarm of later-generation hybrids and backcrosses showing a strong bias towards C. edulis, indicating asymmetric introgression. These findings highlight the value of integrating cytogenetic and genomic approaches to understand genome evolution in invasive hybrid complexes.\nC_LI"}},{"id":"10.64898/2026.07.03.736350","title":"Domain Insertion Improves the Precision of a CRISPR Adenine Base Editor","subtitle":"Dominik Niopek · Institute of Pharmacy and Molecular Biotechnology, Faculty of Engineering Sciences, Heidelberg University, Heidelberg, Germany · 2026-07-10","value":"synthetic biology","href":"https://doi.org/10.64898/2026.07.03.736350","props":{"doi":"10.64898/2026.07.03.736350","authors":"Müller, M. M.; Southern, N. T.; Niopek, D.","institution":"Institute of Pharmacy and Molecular Biotechnology, Faculty of Engineering Sciences, Heidelberg University, Heidelberg, Germany","category":"synthetic biology","date":"2026-07-10","abstract":"Adenine base editors (ABEs) enable efficient A*T to G*C conversion, but their broad activity windows frequently cause unintended bystander edits. We hypothesized that insertion of a bulky, inert protein domain into the base editor would limit the effective reach of the deaminase, thereby preferentially directing editing to the intended target adenine.\n\nHere, we systematically map domain insertion sites within the high-activity TadA8e adenine base editor using structure-guided design and computational inference. We find that TadA8e accepts domain insertions at multiple surface sites, with overall activity and editing window width dependent on insert position rather than domain identity. Excitingly, inserting domains at residue L68 preserved robust editing across multiple genomic loci while tightly focusing the editing window around position 5. Insertion of superfolder GFP at this site produced a base editor variant with a narrower editing window, the ability to track edited cells by fluorescence, and markedly reduced Cas-independent off-target editing. Our work highlights domain insertion engineering as a powerful strategy to create more focused and precise CRISPR base editors."}},{"id":"10.1101/2025.05.20.655067","title":"Second-cleavage-driven non-canonical priming expands prime editing in 5 direction","subtitle":"Peng-Fei Xia · Shandong University · 2026-07-10","value":"synthetic biology","href":"https://doi.org/10.1101/2025.05.20.655067","props":{"doi":"10.1101/2025.05.20.655067","authors":"Chen, P.-R.; Yuan, X.-Z.; Wang, S.-G.; Xia, P.-F.","institution":"Shandong University","category":"synthetic biology","date":"2026-07-10","abstract":"Cleavage-dependent CRISPR-Cas gene editing relies on RNA-guided DNA cleavages that push cellular machinery to incorporate intended edits. Yet, a second cleavage on the already cut DNA strand can also be executed by CRISPR nucleases. This feature, however, has never been repurposed for gene editing. Here, we report the first integration of the second cleavage activity of Cas9 for precision gene editing, allowing previously impossible prime editing in the 5 direction of a nick. We elucidate the second-cleavage-driven pathway that primes non-canonical reverse transcription events upstream of the nick. We identify the competition between the non-canonical and canonical routes, which can be modulated by rationally designing RNA templates with intended edits. We demonstrate that cellular physiologies elevate editing efficiency from individual reverse-transcripts yet exert limited influence on the pathway competitions. Our findings reshape the design principle of prime editing and open an entirely new dimension for engineering CRISPR-Cas systems with the intrinsic, non-host-specific second cleavage activity."}},{"id":"10.64898/2026.07.02.736195","title":"Differentiable Design for Morphogenesis I: Simulation and Simulacra","subtitle":"Bianca Dumitrascu · Columbia University · 2026-07-10","value":"systems biology","href":"https://doi.org/10.64898/2026.07.02.736195","props":{"doi":"10.64898/2026.07.02.736195","authors":"Beker, O.; Dumitrascu, B.","institution":"Columbia University","category":"systems biology","date":"2026-07-10","abstract":"Cells build tissues through local exchanges of force and information, yet the rules governing these interactions are difficult to infer from sparse observations. Here, we introduce waxMorph, a differentiable cell-based framework for generating and reconstructing three-dimensional morphogenesis. In synthetic and biological data, waxMorph reproduced established mechanochemical shape programs, inferred continuous trajectories from static tissue volumes, and recovered spatially organized latent signals. In a developing mouse myocardium dataset, it reconstructed unobserved intermediate geometries more accurately than optimal-transport interpolation, while in forelimbs it distinguished related developmental trajectories. By varying the capacity and spatial organization of the latent cues available to cells, waxMorph also provides a model-based way to quantify the complexity of shape assembly. waxMorph is built within the spatial-computing ecosystem of NVIDIA Warp. It provides an open-source, Python-native, GPU-accelerated, hybrid physics-AI framework for learning how local cellular interactions give rise to biological form."}},{"id":"10.1101/2025.10.21.683709","title":"mAIcrobe: an open-source framework for high-throughput bacterial image analysis","subtitle":"Ricardo Henriques · Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa · 2026-07-10","value":"microbiology","href":"https://doi.org/10.1101/2025.10.21.683709","props":{"doi":"10.1101/2025.10.21.683709","authors":"Brito, A. D.; Alwardt, D.; Mariz, B. d. P.; Filipe, S. R.; Pinho, M. G.; Saraiva, B. M.; Henriques, R.","institution":"Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa","category":"microbiology","date":"2026-07-10","abstract":"Quantitative analysis in bacterial microscopy is often hindered by diverse cell morphologies, population heterogeneity, and the requirement for specialised computational expertise. To address these challenges, mAIcrobe is introduced as an open-source framework that broadens access to advanced bacterial image analysis by integrating a suite of deep learning models. mAIcrobe incorporates multiple segmentation algorithms, including StarDist, CellPose, and U-Net, alongside comprehensive morphological profiling and an adaptable neural network classifier, all within the napari ecosystem. This unified platform enables the analysis of a wide range of bacterial species, from spherical Staphylococcus aureus to rod-shaped Escherichia coli, across various microscopy modalities within a single environment. The biological utility of mAIcrobe is demonstrated through its application to antibiotic phenotyping in E. coli and the identification of cell cycle defects in S. aureus DnaA mutants. The modular design, supported by Jupyter notebooks, facilitates custom model development and extends AI-driven image analysis capabilities to the broader microbiology community. Building upon the foundation established by eHooke, mAIcrobe represents a substantial advancement in automated and reproducible bacterial microscopy."}},{"id":"10.64898/2026.07.02.736025","title":"Gene Supplementation of MYO7A or activation of Myo7b for treatment of Usher syndrome 1B","subtitle":"Elvir Becirovic · Laboratory for Retinal Gene Therapy, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Switzerland · 2026-07-10","value":"molecular biology","href":"https://doi.org/10.64898/2026.07.02.736025","props":{"doi":"10.64898/2026.07.02.736025","authors":"Mittas, D. M.; Otify, D. Y.; Gavrilov, Z.; Heigl, T.; Suchomski, J.; Deltuvaite, P.; Hinrichsmeyer, K.; Mercey, O.; Kynast, F.; Motlik, J.; Ellederova, Z.; Ardan, T.; Klingl, A.; Grünert, J.; Mehlfeld, V.; Kolesnikova, A.; Nyshchuk, R.; Juhasova, J.; Juhas, S.; Drutovic, S.; Fischer, M. D.; Veith, M.; Stranak, Z.; Boon, N.; Wijnholds, J.; Wiest, A.; Kielkowski, P.; Gökce, G.; Guichard, P.; Hamel, V.; Ammer, H.; Michalakis, S.; Koch, S.; Biel, M.; Becirovic, E.","institution":"Laboratory for Retinal Gene Therapy, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Switzerland","category":"molecular biology","date":"2026-07-10","abstract":"Mutations in MYO7A result in the most severe subtype of Usher syndrome, the leading genetic cause of deafblindness. The large size of MYO7A requires dual adeno-associated virus (AAV) vectors for gene transfer or alternative methods to treat retinal defects. Here, we evaluated two treatment approaches: i) Supplementation of the human MYO7A gene via dual mRNA trans-splicing AAVs, and ii) CRISPR/Cas-mediated activation of the related murine Myo7b gene. Upon MYO7A supplementation, the transgenic MYO7A transcript and protein were expressed and correctly localized in retinal pigment epithelial (RPE) and photoreceptors of mice, pigs, and human retinal organoids. In RPE-and photoreceptor-specific Myo7a knockout mice, we could restore MYO7A expression and localization of melanosomes in RPE cells to wild-type levels. Myo7b activation led to partial restoration of melanosome localization, and the localization of MYO7B protein was largely comparable to MYO7A. These findings indicate that both approaches are in principle suitable for the therapy of Usher syndrome."}},{"id":"10.64898/2026.07.01.735788","title":"Volatile diacetyl triggers rapid fmo-2 expression through DHAP-glycerol shunt induction","subtitle":"Marco Giorda · Altos Labs · 2026-07-10","value":"molecular biology","href":"https://doi.org/10.64898/2026.07.01.735788","props":{"doi":"10.64898/2026.07.01.735788","authors":"Giorda, M.; Sen, A.; Denzel, M. S.","institution":"Altos Labs","category":"molecular biology","date":"2026-07-10","abstract":"C. elegans can locate ephemeral food sources by sensing bacterially-derived volatiles. However, whether these olfactory cues can also trigger anticipatory nutrient-responsive programs remains unknown. Using unbiased transcriptomics and metabolomics, we discover that fasting worms exposed to the volatile food cue diacetyl rapidly induce expression of enzymes in the DHAP-Glycerol shunt, a metabolic pathway at the intersection of glycolysis and glycerolipid biosynthesis. We demonstrate that this pathway, known to be activated by glucotoxicity and hyperosmotic stress, is also modulated by food availability. Shunt induction requires the MDT-15 transcription factor and drives rapid metabolic remodeling, characterised by the accumulation of glycerol and phosphatidylglycerols. When food deprivation persists, the shunts activity triggers expression of the dietary restriction marker fmo-2, promoting thermotolerance and food-seeking behaviours. Our findings reveal that volatile diacetyl can rapidly modulate gene expression in C. elegans, providing new insights into the DHAP-Glycerol shunt function in metabolic homeostasis."}},{"id":"10.64898/2026.07.09.737452","title":"Acidosis-triggered fatty acid overload induces endothelial cell dysfunction.","subtitle":"Olivier FERON · UCLouvain · 2026-07-10","value":"cell biology","href":"https://doi.org/10.64898/2026.07.09.737452","props":{"doi":"10.64898/2026.07.09.737452","authors":"Al-Siyabi, S.; Ibanez, S.; Serafimov, K.; Lallement, J.; Marchand, D.; Laloux, F.; Guilbaud, C.; Demulder, D.; Vlieghe, H.; Moghassemi, S.; Bouzin, C.; Amorim, C.; FERON, O.; Dessy, C.","institution":"UCLouvain","category":"cell biology","date":"2026-07-10","abstract":"Vascular ischemia is characterized not only by hypoxia but also by acidosis, which affects endothelial cells (ECs) due to increased H+ production from glycolysis and a deficit in H+ washout. We recently documented that an acidic environment facilitates the flip-flop transport of the non-ionized form of fatty acids (FAs) across the plasma membrane of cancer cells. In this study, we investigated how acidosis influences the capacity of highly glycolytic ECs to manage FAs and participates to endothelial dysfunction. We first tracked lipid droplet (LD) formation using Oil Red O staining and holotomographic microscopy. Purified monounsaturated oleate but also a mixture of FAs that reflect in vivo serum composition, resulted in dose- and time-dependent LD accumulation through FA transporter-independent mechanisms. Acid-exposed ECs exhibited enhanced mitochondrial respiration fueled by FAs, and endoplasmic reticulum (ER) stress, as indicated by the expression of ATF4 and CHOP. This phenotype was further associated with elevated reactive oxygen species production, which correlated with reduced nitric oxide (NO) availability. FA removal from EC culture media promoted lipolysis from LDs, supported by ATGL lipase induction which however slowed under acidic conditions. While ER stress persisted upon FA washout, NO availability was restored to levels comparable to those in FA-unexposed ECs. This observation coincided with dynamic mobilization of antioxidant defenses in acid-exposed ECs, as evidenced by low levels of reduced glutathione and enhanced cystine uptake, alongside a decrease in carnitine and FA-fueled mitochondrial respiration. Collectively, these data underscore the vulnerability of ECs to passive FA capture promoted by local acidosis, thereby contributing to a silent source of endothelial dysfunction in the postprandial state or during chronic exposure to elevated lipid levels."}},{"id":"10.1101/2025.01.24.634785","title":"A novel RNA-binding activity of ECD contributes to U5 snRNP stability and pre-mRNA splicing","subtitle":"Vimla Band · University of Nebraska Medical Center · 2026-07-10","value":"cell biology","href":"https://doi.org/10.1101/2025.01.24.634785","props":{"doi":"10.1101/2025.01.24.634785","authors":"Raza, M.; Rajan, A. R.; Kalluchi, A.; Mohapatra, B.; Saleem, I.; Kennedy, B. B.; Bhakat, K. K.; Band, H.; Rowley, M. J.; Band, V.","institution":"University of Nebraska Medical Center","category":"cell biology","date":"2026-07-10","abstract":"Human ecdysoneless protein (ECD) plays an essential role in regulating cell cycle progression and cell survival. ECD has previously been implicated in RNA splicing through its association with spliceosomal proteins. Here, using EMSA, fluorescence polarization assays, and mutational analysis, we demonstrate that ECD directly binds to RNA. Enhanced CLIP-seq analysis identified a broad repertoire of mRNAs bound to ECD in cells. RNA-seq analyses revealed that ECD depletion leads to widespread splicing aberrations and altered gene expression. ECD binding to RNAs was enriched near splice sites, and a substantial fraction of ECD-bound transcripts exhibited splicing defects upon ECD depletion. ECD associates with and stabilizes the U5 snRNP complex specific proteins. While depletion of ECD reduced the levels of key U5-specifc proteins, these proteins exhibited an increased association with the R2TP complex in knockout cells. Notably, we found ECD to directly bind to U5 snRNA, and an RNA binding defective mutant of ECD ({Delta}135-148) failed to rescue the reduced levels of U5-specific proteins or the proliferation defect induced by ECD depletion. Collectively, these findings demonstrate that ECD binds to RNAs, including the U5 snRNA, and that RNA-binding is required for ECD to stabilize the U5 snRNP and for cellular functions.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC=\"FIGDIR/small/634785v4_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (22K):\norg.highwire.dtl.DTLVardef@f5aa4forg.highwire.dtl.DTLVardef@80606borg.highwire.dtl.DTLVardef@3a4c8eorg.highwire.dtl.DTLVardef@1780b0f_HPS_FORMAT_FIGEXP  M_FIG C_FIG"}},{"id":"10.64898/2026.07.09.737329","title":"Cell-type-specific ATF6α programs regulate epithelial mitochondrial homeostasis and pericyte remodeling during physiological and exposure-accelerated lung aging","subtitle":"Anna Blumental-Perry · University at Buffalo · 2026-07-10","value":"cell biology","href":"https://doi.org/10.64898/2026.07.09.737329","props":{"doi":"10.64898/2026.07.09.737329","authors":"Huang, X.; Bard, J. E.; Tumenbayar, B.-I.; Vedagiri, K.; Nelson, C. E.; Kenche, H.; Reynolds, C. E.; Leme, A. S.; Moore, S. J.; Perry, N. A.; Shapiro, S. D.; Perry, Y.; Bae, Y.; Blumental-Perry, A.","institution":"University at Buffalo","category":"cell biology","date":"2026-07-10","abstract":"Proteostasis declines with lung aging, while the role of the Unfolded Protein Response (UPR) in lung aging and age-associated pulmonary diseases remains understudied. We investigated how deficiency in the UPR sensor ATF6 affects physiological and smoke exposure-accelerated lung aging. ATF6 -deficient mice exhibited accelerated alveolar simplification, a sign of lung parenchymal aging, which was exacerbated by smoking. Nevertheless, small airway vascular fibrotic remodeling, a prominent smoking-induced pathology, was not evident in smoke-exposed ATF6 -deficient mice. Mechanistically, these divergent phenotypes arose from cell-type-specific ATF6 programs. In alveolar epithelial type 2 cells (AEC2s), the facultative progenitors of the lung parenchyma, ATF6 maintained mitochondrial bioenergetics and sustained efficient re-differentiation into alveolar epithelial type 1 cells (AEC1s). In lung pericytes, ATF6 promoted extravasation, re-differentiation into myofibroblast-like cells, and production of collagens 1 and 3. These findings identify ATF6 as a cell-type-specific regulator of differentiation programs during lung aging and highlight the need to study ATF6 under defined physiological and pathological contexts before therapeutically targeting this pathway."}},{"id":"10.64898/2026.07.08.737008","title":"Dichloroacetate improves animal survival, growth, neuromuscular activity, mitochondrial stress and physiology, and elevated lactate in C. elegans pdha-1 and dld-1 RNAi models of pyruvate dehydrogenase complex deficiency (PDCD)","subtitle":"Marni J Falk · CHOP and UPENN · 2026-07-10","value":"cell biology","href":"https://doi.org/10.64898/2026.07.08.737008","props":{"doi":"10.64898/2026.07.08.737008","authors":"Remes, C.; Mathew, N. D.; Miranda, V.; Haroon, S.; O'Hara, T.; Anderson, V. E.; Lavorato, M.; Keith, K.; Xiao, R.; Nakamaru-Ogiso, E.; Falk, M. J.","institution":"CHOP and UPENN","category":"cell biology","date":"2026-07-10","abstract":"Pyruvate dehydrogenase complex (PDHc) deficiency (PDCD) is a primary mitochondrial disorder characterized by neurodevelopmental disability, altered intermediary metabolism and early mortality. Dichloroacetate (DCA), a pyruvate analogue, is a well-described PDHc activator that remains under clinical investigation for treatment of PDCD. Here, we studied the in vivo efficacy of a 5-point log concentration range of DCA on animal health and metabolism in C. elegans with feeding RNA interference (RNAi) expression knockdown of either PDHA-1 or DLD-1 homologues at graded degrees to model variable disease severity. These worm models recapitulate phenotypic features of PDCD observed in human patients, including reduced survival, delayed growth, locomotor impairment, and elevated lactate and/or pyruvate tissue levels. DCA treatment appeared well-tolerated, with no gross morphologic toxicity seen at doses up to 25 mM. Significantly improved health, survival, tissue lactate levels, and mitochondrial physiology were observed at 25 mM in pdha-1(RNAi) knockdown animals. DCA treatment in dld-1(RNAi) C. elegans models (undiluted, 1:20 dilution, and 1:100 dilution) showed significant therapeutic benefits on survival, neuromuscular function and metabolic phenotypes primarily in the moderate (1:20) and/or mild (1:100) dld-1(RNAi) deficiency strains, but not in full-dose dld-1(RNAi). Importantly, linear growth, neuromuscular activity, and mitochondrial physiology were significantly improved with DCA treatment even in the most severe dld-1(RNAi) undiluted model. Overall, preclinical modeling provides objective evidence of DCA therapeutic efficacy in C. elegans expression knockdown strains for two well-conserved homologues of PDHA1 and DLD that represent distinct genetic etiologies of PDHc deficiency, with demonstrated beneficial effects on survival, healthspan, tissue lactate, and mitochondrial physiology. These data further confirm that DCAs therapeutic effect correlates with PDHc disease phenotype severity in dld-1(RNAi) animals.\n\nSYNOPSIS: Dichloroacetate (DCA) treatment demonstrated significant preclinical beneficial effect on survival, neuromuscular function, linear growth, tissue lactate, and mitochondrial metabolism in two C. elegans models with variable degrees of pyruvate dehydrogenase complex (PDHc) deficiency (PDCD), providing confirmatory evidence to support its therapeutic potential in human PDCD patients."}},{"id":"10.64898/2026.07.02.735969","title":"Functions of TIAM1 at the interface of centriole assembly and autolysosome cycling","subtitle":"Paula Almeida Coelho · California Instittue of Technology · 2026-07-10","value":"cell biology","href":"https://doi.org/10.64898/2026.07.02.735969","props":{"doi":"10.64898/2026.07.02.735969","authors":"Coelho, P. A.; Yu, C.; Glover, D. M.","institution":"California Instittue of Technology","category":"cell biology","date":"2026-07-10","abstract":"Centrosome amplification is frequently associated with chromosomal instability and tumor progression, but how cells coordinate centriole assembly with the control of centrosome numbers and quality remains poorly understood. TIAM1 is a RAC1 guanine nucleotide exchange factor previously implicated in centrosome-associated signaling and {beta}TrCP-dependent control of PLK4 abundance. Here, we examined how Tiam1 regulates autophagy-lysosome homeostasis in mouse embryonic fibroblasts induced to overexpress PLK4. In contrast to a previous model in which Tiam1 loss promotes productive centriole overduplication, we found, by super-resolution imaging and expansion microscopy, an abnormal distribution of PLK4 on the centrioles centriole-associated structures following TIAM1 depletion, suggesting that TIAM1 may support the organization or maturation of centrioles. TIAM1 depletion also resulted in increased LC3B-positive puncta and enlarged LAMP1-positive compartments, but this was not accompanied by increased LC3B-II accumulation after bafilomycin A1 treatment.\n\nThese findings suggest that TIAM1 may act at the interface between centriole assembly and endolysosomal/autolysosomal organization, linking TIAM1 to lysosome-associated centrosome quality-control pathways."}},{"id":"10.64898/2026.06.23.733964","title":"Acetylation-dependent remodeling of the secretory pathway shapes the senescence-associated secretome","subtitle":"Christoph Kaether · Leibniz Institute on Aging -  Fritz Lipmann Institute · 2026-07-10","value":"cell biology","href":"https://doi.org/10.64898/2026.06.23.733964","props":{"doi":"10.64898/2026.06.23.733964","authors":"Nasrashvili, T.; Emini, B.; Cirri, E.; Rahnis, N.; Poempner, N.; Gerner, C.; Grillari, J.; Heller, R.; Kaether, C.","institution":"Leibniz Institute on Aging -  Fritz Lipmann Institute","category":"cell biology","date":"2026-07-10","abstract":"Cellular senescence is characterized by stable cell cycle arrest and the senescence-associated secretory phenotype (SASP), which drives tissue remodeling and inflammation. Underlying SASP with its increased secretion of cytokines and other secreted proteins is a massive reorganization of the secretory pathway. While transcriptional regulation of senescence has been extensively studied, the contribution of post-translational modifications (PTM) to secretory pathway regulation remains poorly understood.\n\nHere, we combined quantitative proteomics with multi-layered PTM profiling of phosphorylation, ubiquitination and acetylation to investigate how intracellular trafficking and secretion are regulated in senescence. Using doxorubicin-induced senescence as the primary model, we identified extensive proteome remodeling, with pronounced changes in ER-Golgi-associated pathways and secretory machinery. Acetylation emerged as the most prominently regulated PTM, particularly affecting proteins involved in vesicle trafficking and ER proteostasis. Comparable proteome and PTM remodeling were also observed in replicative senescence, indicating that these changes are not restricted to a single senescence model.\n\nFunctional analyses revealed activation signatures of the acetyltransferases p300/CBP, linking global acetylation changes to enzymatic activity. Pharmacological inhibition of p300/CBP using A485 selectively modulated senescence-associated features without reversing growth arrest, consistent with a senomorphic-like effect during senescence establishment. Secretome profiling further demonstrated changes in the composition of secreted factors, consistent with modulation of the senescence-associated secretory phenotype.\n\nTogether, these findings indicate that acetylation-dependent regulation of the secretory pathway shapes the senescence-associated secretome, revealing a mechanistic link between post-translational regulation, intracellular trafficking, and extracellular signaling in senescence."}},{"id":"10.64898/2026.07.02.736014","title":"Tissue lamination state switches neuronal translocation from active to passive in the vertebrate retina","subtitle":"Caren Norden · Gulbenkian Institute for Molecular Medicine · 2026-07-10","value":"developmental biology","href":"https://doi.org/10.64898/2026.07.02.736014","props":{"doi":"10.64898/2026.07.02.736014","authors":"Cruz, M. R.; Paixao, T.; Coelho, J.; Norden, C.","institution":"Gulbenkian Institute for Molecular Medicine","category":"developmental biology","date":"2026-07-10","abstract":"Neuronal migration is essential for establishing functional tissue architecture in the developing central nervous system. While cell-intrinsic mechanisms driving neuronal movement have been identified, how migratory strategies adapt to dynamic developmental tissue changes remains less understood. Here, we address this question using retinal bipolar cells generated across unlaminated and laminated stages. This enables direct comparison of neuronal translocation across tissue states. Combining quantitative live imaging with targeted perturbations, we show that the migration mode of bipolar cells switches depending on tissue lamination state. Bipolar cells born before photoreceptor layer formation undergo directed, microtubule-dependent somal translocation. In contrast, later-born cells exhibit passive, non-directed displacement driven by collective tissue movements. Interference with tissue-wide movements impairs this displacement, while disrupting photoreceptor layer formation restores directed translocation. Independent of strategy, cells achieve accurate laminar positioning, indicating that tissue context determines neuronal migration mode, a principle likely relevant across the developing neural and other tissues."}},{"id":"10.64898/2026.07.08.737378","title":"Restoration of tropical dry evergreen forest in southern India: balancing carbon sequestration with biodiversity conservation","subtitle":"Mani Shanmugam · Pitchandikulam Forest · 2026-07-10","value":"ecology","href":"https://doi.org/10.64898/2026.07.08.737378","props":{"doi":"10.64898/2026.07.08.737378","authors":"Shanmugam, M.; Pulla, S.; Epinal, L. N.","institution":"Pitchandikulam Forest","category":"ecology","date":"2026-07-10","abstract":"Tropical dry evergreen forests (TDEFs) are a unique and highly threatened forest type of the dry tropics. Their restoration could be strengthened if native species demonstrate carbon sequestration comparable to widely used non-native trees. We assessed biodiversity and carbon sequestration in a restored TDEF in India, developed over 50 years from a largely barren landscape. The site now supports high woody-plant diversity, with 91 native species across 34 families. Aboveground biomass (AGB) averaged 66.91 {+/-} 41.2 Mg ha-{superscript 1}, comparable to seasonally dry tropical forests globally. Although native species were planted more recently and are shorter than non-natives, they contributed 23.86 {+/-} 23.4 Mg ha-{superscript 1} to AGB and show potential for future increases in basal area. Given their comparable wood densities and capacity to attain similar heights, native species are predicted to sequester carbon at levels similar to non-natives in the long term. AGB was unrelated to species diversity. Overall, native TDEF species can achieve carbon storage while maintaining ecological integrity."}},{"id":"10.1101/2023.10.26.564294","title":"Pre-Cambrian origin of envelope-carrying retrotransposons in metazoans","subtitle":"Rippei Hayashi · The John Curtin School of Medical Research, Department of Genome Sciences, College of Health & Medicine, Australian National University · 2026-07-10","value":"evolutionary biology","href":"https://doi.org/10.1101/2023.10.26.564294","props":{"doi":"10.1101/2023.10.26.564294","authors":"Chary, S.; Hayashi, R.","institution":"The John Curtin School of Medical Research, Department of Genome Sciences, College of Health & Medicine, Australian National University","category":"evolutionary biology","date":"2026-07-10","abstract":"Retrotransposons or endogenous retroviruses (ERVs) essentially carry open reading frames of gag and pol, which are utilized to selfishly replicate themselves in the host germline genome. One rare example of ERVs that additionally carry envelope genes is Ty3/gypsy errantiviruses in Drosophila. Though they are structurally analogous to retroviruses, it remained unclear whether envelope-containing Ty3/gypsy elements represent recent, lineage-specific acquisitions of viral fusogens or an ancient association between retrotransposons and envelope-like genes. We systematically searched for intact envelope-containing ERVs that are homologous to Ty3/gypsy in invertebrate metazoan genomes and found that they are widespread across taxa including ancient animals such as cnidarians, ctenophores and tunicates. Many elements occur as multiple highly similar copies in their respective genomes, consistent with recent genomic expansion in some host lineages. Envelope genes are classified into those that resemble glycoprotein F from paramyxoviruses and glycoprotein B from herpesviruses, and both types are equally abundant and widespread. Phylogenetic and structural analyses revealed that envelope genes have largely diverged with pol genes as well as with the host organisms throughout their evolutionary history and recombined infrequently, suggesting that the envelope acquisition to ERVs is ancient and likely dates to before the split of bilaterian and non-bilaterian animals in Pre-Cambrian era."}},{"id":"10.64898/2026.07.09.737478","title":"Cell-type-resolved spatial proteogenomics from matched genome and proteome of the same cells","subtitle":"Matthias Mann · Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany · 2026-07-10","value":"biochemistry","href":"https://doi.org/10.64898/2026.07.09.737478","props":{"doi":"10.64898/2026.07.09.737478","authors":"Zwiebel, M.; Wahle, M.; Stadler, R.; Levesque, M. P.; Dummer, R.; Nordmann, T. M.; Mann, M.","institution":"Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany","category":"biochemistry","date":"2026-07-10","abstract":"The genome and proteome of the same cells are rarely measured together, which is especially consequential in cancer, where somatic mutations vary across clones and drive disease. We show that a single standard proteomics extraction tip can retain peptides on-tip after digestion while genomic DNA passes into the normally discarded flowthrough. Combined with Deep Visual Proteomics, flowthrough co-isolation enables cell-type-resolved spatial proteogenomics from archival FFPE tissue, demonstrated in melanoma."}},{"id":"10.64898/2026.07.09.736951","title":"Hybrid quantum-classical de novo design of MHC-binding peptides","subtitle":"Timothy Jenkins · Department of Biotechnology and Biomedicine, Technical University of Denmark · 2026-07-10","value":"biochemistry","href":"https://doi.org/10.64898/2026.07.09.736951","props":{"doi":"10.64898/2026.07.09.736951","authors":"Engdal, E. S.; Funk, J.; Bacarreza, O.; Machado, L.; Johansen, K. H.; Kemming, J.; Farnsworth, T.; Brasas, V.; Lefevre-Morand, R. Y. L.; Slysz, M.; Noerregaard, O. L.; Sandberg, O. A. D. A.; Makarovskiy, A.; Lodahl, P.; Acevedo-Rocha, C. G.; Kurowski, K.; Hadrup, S. R.; Clements, W. R.; Jenkins, T.","institution":"Department of Biotechnology and Biomedicine, Technical University of Denmark","category":"biochemistry","date":"2026-07-10","abstract":"Deep generative models have become a leading approach for designing therapeutic molecules, yet efficiently exploring vast biomolecular sequence spaces remains difficult, particularly for targets with limited training data. The prior distribution that seeds a generative model shapes which regions of sequence space it explores, and recent work suggests that non-classical distributions sampled from quantum processors can serve as a structured alternative to the factorised Gaussian priors used by default. Whether such priors help on complex biological design tasks has been largely untested. Here we present what is, to our knowledge, the first end-to-end hybrid quantum-classical pipeline for de novo design of MHC class I-binding peptides, coupling a generative adversarial network (GAN) to latent vectors sampled from a real photonic quantum processor. Tested in silico across 131 HLA alleles, quantum-derived priors increased the yield of predicted strong binders, with the largest relative gains for understudied alleles where classical baselines perform worst. We selected three understudied alleles for further evaluation, finding that large gains coincided with broader sequence exploration at non-anchor positions while anchor specificity was preserved. On these three alleles, we validated the designs in vitro using peptide-MHC stability ELISAs, confirming that quantum-designed peptides are potent stabilisers of peptide-MHC class I complexes. These results establish structured, hardware-realisable non-classical priors as a useful inductive bias for generative peptide design, with direct relevance to personalised immunotherapies and vaccines."}},{"id":"10.64898/2026.07.09.737429","title":"Transposon end recognition and pairing by I-F3 CRISPR-associated transposase","subtitle":"Elizabeth H Kellogg · St Jude Children's Research Hospital · 2026-07-10","value":"biochemistry","href":"https://doi.org/10.64898/2026.07.09.737429","props":{"doi":"10.64898/2026.07.09.737429","authors":"Truong, V.; Miller, D.; Fatma, S.; Sheng, Y.; Pindi, C.; Ahsan, M.; Palermo, G.; Kellogg, E. H.","institution":"St Jude Children's Research Hospital","category":"biochemistry","date":"2026-07-10","abstract":"To develop gene therapy tools based on CRISPR-associated transposons (CASTs), it is essential to define how transposon ends are recognized and paired during transposition. Tn7-like transposons typically contain asymmetric left- and right-end sequences that flank and define DNA cargo. However, how the transposase recognizes these different sequences and assembles them into a paired end complex for cut-and-paste transposition remains unknown. Here we present the cryo-EM structure of type I-F3 (VchCAST) CAST transposase TnsB in complex with transposon DNA ends and host factor IHF, along with biochemistry, molecular dynamics, and in vivo analyses. Our structure reveals the stoichiometry and architecture of the assembly, as well as the DNA distortions required to accommodate transposon end asymmetry. Molecular dynamics suggests that these distortions are required for the coordinated assembly of the complex. Physical pairing of asymmetric left and right ends results in a novel protein-protein interface that is required for transposition efficiency. Our findings explain how transposases regulate the pairing of transposon end sequences for high-fidelity recognition, reveal a model of transposon end synapsis, and suggest future avenues to engineer DNA cargo for genome-editing applications."}},{"id":"10.64898/2026.07.08.737383","title":"Expanding genetic code to generate human brain organoids with both vasculature and microglia","subtitle":"Haishuang Lin · Suzhou Institute for Advanced Research, University of Science and Technology of China · 2026-07-10","value":"bioengineering","href":"https://doi.org/10.64898/2026.07.08.737383","props":{"doi":"10.64898/2026.07.08.737383","authors":"Lin, H.; Wang, Y.; Du, H.; Qin, Y.; Zhang, H.; Wang, P.; Wei, L.; Qin, j.","institution":"Suzhou Institute for Advanced Research, University of Science and Technology of China","category":"bioengineering","date":"2026-07-10","abstract":"Brain organoids offer an invaluable model system for studying human brain development and disease. However, the establishment of high-fidelity brain organoids with multiple cell lineages including vasculature and immune cells remains a huge challenge. Here, we present a new strategy to generate human cerebral organoids with vasculature and microglia-like cells using genetic code expansion technology (GCE-T) via site-specific protein engineering. The strategy integrates orthogonal genetic translation machinery in hPSCs via PiggyBac transposon system, enabling temporally control of ETV2 expression and endothelial differentiation in hPSC-derived cerebral organoids. The vascularized human cerebral organoids (vhCOs) exhibit coordinated development of multiple cell lineages and blood-brain barrier (BBB) features. Moreover, vhCOs form perfusable vascular network after transplanted in the immune-deficient mice. Single-nucleus RNA sequencing reveals enhanced neurovascular interactions, multi-brain-regional identities, diverse neuronal subtypes and specialized endothelial subclusters in vhCOs, closely resembling human fetal brain. Strikingly, we identify enriched microglia-like cells comprising three distinct subtypes in vhCOs, which contribute to microglia-vascular interactions and synergistically modulate vascular development. Upon Zika virus (ZIKV) infection, vhCOs show neurovascular dysfunction and impaired microglia development, offering new insights into viral-induced neurodevelopmental disorders. This study offers a unique platform for producing more valuable brain organoids with vasculature and immune components, opening a new avenue to advance organoid research and applications."}},{"id":"10.64898/2026.07.09.737190","title":"Regio-selective sulfation of heparin mimicking polymers defines in vivo activity","subtitle":"Mark Grinstaff · Boston University · 2026-07-10","value":"bioengineering","href":"https://doi.org/10.64898/2026.07.09.737190","props":{"doi":"10.64898/2026.07.09.737190","authors":"Grinstaff, M.; Loffredo, M.; Ham, H. O.; Varghese, M.; Haller, C.; Chaikof, E.","institution":"Boston University","category":"bioengineering","date":"2026-07-10","abstract":"Heparin, a naturally derived glycosaminoglycan, is the most commonly used anti-thromboembolic in the world. However, the biological origin of heparin inherently results in batch-to-batch variability, large dispersity indexes, and potential contamination, leading to inconsistent activity and patient-dependent dose-response. As such, new synthetic anticoagulants are of keen interest, particularly those that mimic heparin while being amenable to alterations in polymer structure and composition for performance optimization. Herein, we report the strategy, synthesis, and evaluation of well-defined, regioselectively functionalized di-sulfated polyamidosaccharides (disulPASs) including exploration of the structure-function relationship of molecular weight and sulfation density on anticoagulant activity. Polymerization of an orthogonally protected y-lactam monomer via anionic ring-opening, followed by selective deprotection and sulfation reactions affords disulPAS. Similar to heparin, disulPASs elongate clotting time through the intrinsic and extrinsic pathways, showing molecular weight and dose-dependent responses in clotting time; are non-cytotoxic and non-hemolytic, partially neutralized by protamine sulfate, and unlike heparin, are not degraded by heparinases. As compared to less sulfated and randomly sulfated iterations of PAS, disulPAS performs superiorly, with in vitro and in vivo clotting activity most similar to native heparin."}},{"id":"10.64898/2026.07.08.737393","title":"Chemical Boosting of Foldase Condensates Accelerates Oxidative Protein Folding","subtitle":"Masaki Okumura · Tohoku University · 2026-07-10","value":"bioengineering","href":"https://doi.org/10.64898/2026.07.08.737393","props":{"doi":"10.64898/2026.07.08.737393","authors":"Watabe, M.; Kuramochi, T.; Fukushima, M.; Kinoshita, M.; Akiba, H.; Ban, K.; Hashimoto, M.; Uchida, N.; Kenta Arai, K. A.; Nakabayashi, T.; Buchner, J.; Muraoka, T.; Okumura, M.","institution":"Tohoku University","category":"bioengineering","date":"2026-07-10","abstract":"Dynamic biomolecular condensates play crucial roles in intracellular compartmentalization and physiological functions. While engineering tools for compartmentalization have expanded add-on functionalities, directly amplifying the inherent catalytic machinery within biological phase-separated droplets has remained elusive. Herein, we developed a phase-separated oxidative folding reaction chamber based on protein disulfide isomerase A6 (PDIA6) by chemically targeting its active site CxxC motif to enhance enzymatic activity within PDIA6 droplets. A para-substituted N-methylated pyridinylmethanethiol (pMePySH) enhanced the catalytic oxidative folding of bovine pancreatic trypsin inhibitor, proinsulin, and antibody up to 12-fold within in vitro PDIA6 droplets. Furthermore, pMePySH targeted PDIA6 foci within the endoplasmic reticulum, significantly promoting insulin secretion. These findings offer a powerful platform for the spatiotemporal manipulation of protein folding, with profound implications for the scalable manufacturing of therapeutic antibodies and other complex biopharmaceuticals."}},{"id":"10.64898/2026.07.08.737376","title":"Lower-limb mechanical power accounts for running energy expenditure and enables single-IMU estimation","subtitle":"Sukyung Park · Korea Advanced Institute of Science and Technology · 2026-07-10","value":"bioengineering","href":"https://doi.org/10.64898/2026.07.08.737376","props":{"doi":"10.64898/2026.07.08.737376","authors":"Jung, J.; Lim, H.; Park, S.","institution":"Korea Advanced Institute of Science and Technology","category":"bioengineering","date":"2026-07-10","abstract":"Energy expenditure (EE) during running depends on the interplay between active muscle work and elastic energy storage and return, yet the relative contribution of mechanical power to EE remains debated. Quantifying the relative contributions of segment-level mechanical power can provide a way to address this debate. In this study, we aimed to quantify how segment-level mechanical power contributes to EE during running and to demonstrate that these mechanistic insights support wearable-based EE estimation. Joint dynamics and respiratory gas-based EE were collected from healthy young adults running at multiple speeds. Scale factors were derived to quantitatively link efficiency-weighted segment power to measured EE. The stance leg consistently showed the strongest correlation with EE, and this dominance was preserved across speeds. Including swing-leg hip power further improved accuracy. Scale factors were approximately 0.45, suggesting that active muscle work and elastic energy return contribute comparably to the mechanical power associated with EE. Using a lightweight machine learning model, stance-leg and swing-leg hip joint power were reconstructed from a single sacral IMU, enabling accurate EE prediction. These findings demonstrate that lower-limb mechanical power is a robust predictor of running EE, supporting both the extensibility of biomechanically-informed frameworks and wearable-based EE monitoring."}},{"id":"10.64898/2026.07.08.736040","title":"Coordinate- and Sequence-Based Features for a new Combined Annotation-Dependent Depletion Framework of Structural Variants (CADD-SV v2.0)","subtitle":"Martin Kircher · University of Luebeck, Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Luebeck, Germany · 2026-07-10","value":"bioinformatics","href":"https://doi.org/10.64898/2026.07.08.736040","props":{"doi":"10.64898/2026.07.08.736040","authors":"Catona, O.; Kircher, M.","institution":"University of Luebeck, Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Luebeck, Germany","category":"bioinformatics","date":"2026-07-10","abstract":"Structural variants are a major source of genomic variation and contribute to human disease and evolution through diverse mechanisms, yet their functional interpretation remains challenging. We present CADD-SV v2.0, an improved machine learning framework for scoring SV deleteriousness that expands on the original CADD-SV implementation. This version introduces a unified Random Forest model trained on an expanded set of proxy-neutral and proxy-deleterious variants drawn from human and non-human primate genomes. The model integrates updated genomic annotations, including constraint metrics, regulatory elements, and chromatin architecture features. It scores Deletions, Insertions, Duplications and Inversions based on a single scoring framework that uses both the variant and its flanking regions. To complement this framework, we also explore sequence-based annotations derived from SegmentNT, a deep learning model that provides functional predictions from DNA sequence at nucleotide resolution. Our analysis evaluated whether sequence-derived functional signals can provide additional information for SV prioritization and whether additional models with these features alone or in combination with previous coordinate-based annotations can be used.\\ CADD-SV v2.0 outperforms its previous version and other tools in prioritizing deleterious variants across major SV types, including some previously unsupported, and substantially improves the computational workflow, increasing predictive power for genome-wide SV interpretation."}},{"id":"10.64898/2026.07.06.735233","title":"Fast Diffusion of Bound Ca: Analytical and Experimental Characterization of One- and Two-Dimensional Traveling Waves","subtitle":"Sergej Mironov · Georg-August-University · 2026-07-10","value":"biophysics","href":"https://doi.org/10.64898/2026.07.06.735233","props":{"doi":"10.64898/2026.07.06.735233","authors":"Mironov, S.","institution":"Georg-August-University","category":"biophysics","date":"2026-07-10","abstract":"Reaction-diffusion (RD) systems play a fundamental role in numerous biochemical and biophysical processes. Here, we present a novel analytical framework for solving RD equations by applying the Wentzel-Kramers-Brillouin-Jeffreys (WKBJ) formalism to Ca2+ nanodomains generated by individual membrane channels, a widely used paradigm for intracellular Ca2+ signaling. Previous models have primarily focused on stationary Ca2+ nanodomains while neglecting diffusion and saturation of intracellular Ca2+ buffers and sensors. In contrast, we derive analytical solutions without these simplifying assumptions.\n\nOur analysis demonstrates that sustained Ca2+ influx generates continuously expanding distributions of free Ca2+, whereas Ca2+-bound buffers and sensors propagate as traveling waves. These predictions are supported experimentally by measurements of one-dimensional fluorescence profiles produced by single-channel activity and two-dimensional profiles generated by whole-cell Ca2+ currents. The analytical framework developed here readily extends Michaelis-Menten-type kinetics to reaction-diffusion systems and may therefore be broadly applicable to biochemical and biophysical processes in which diffusion cannot be neglected.\n\nSignificance StatementWe present a novel analytical approach that combines Michaelis-Menten kinetics with diffusion through the Wentzel-Kramers-Brillouin-Jeffreys (WKBJ) formalism. The resulting closed-form solutions predict that free Ca2+ remains localized near active channels, whereas Ca2+-bound buffers and sensors propagate through the cytoplasm as traveling waves. Consequently, intracellular signaling may depend not only on local Ca2+ elevations but also on the propagation of mobile Ca2+-bound species. These theoretical predictions are validated experimentally in both one-dimensional and two-dimensional neuronal preparations."}}],"count":30,"generated_at":"2026-07-17T04:49:25.569Z","cached":true}