{
  "schema_version": "1.0",
  "source": "biorxiv",
  "data_as_of": "2026-09-09T08:17:44.457Z",
  "selected_count": 30,
  "sampled": true,
  "records": [
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.09.03.749114:v1",
      "title": "Molecular architecture and assembly of the human RNA Degradosome",
      "summary": "The PNPase exoribonuclease interacts with the SUV3 helicase to form the human RNA Degradosome responsible for processive mitochondrial RNA turnover and quality control. Although structural data reveals the trimeric PNPase architecture along with the monomeric and dimeric states of SUV3, the molecular basis of their assembly for processive RNA degradation remains poorly understood. Here we present the molecular characterization of the human RNA Degradosome and define critical molecular features that regulate complex formation. We identify the protein regions required for RNA Degradosome formation and establish the minimum components necessary for the SUV3-PNPase interaction. Chemical crosslinking mass spectrometry analysis reveals distance restraints that position the SUV3 N-terminal domain alongside of the PNPase S1 domain, defining an important interface for complex formation. These findings provide mechanistic insight into how PNPase and SUV3 assemble to form the human RNA Degradosome.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.09.03.749114",
      "metadata": {
        "doi": "10.64898/2026.09.03.749114",
        "version": "1",
        "authors": "Gee, J. A.; Williams, J. G.; Pillon, M. C.",
        "category": "biochemistry",
        "type": "new results",
        "license": "cc_by_nc_nd",
        "institution": "University at Buffalo"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.09.03.749102:v1",
      "title": "A High-Throughput Assay to Identify Specific Nascent Chain Inhibitors",
      "summary": "\"Undruggable\" proteins without surface-accessible binding sites pose significant challenges to target-based drug discovery. Innovative approaches are needed to tackle these proteins. One promising strategy is targeting them in their nascent chain form at the ribosome, where they have a different conformation than in the folded form. A systematic approach to screen for such compounds has however been lacking. Here, we present a high-throughput assay to identify small molecules that specifically inhibit a protein of interest in its nascent-chain form. The assay employs a human in vitro transcription/translation system and monitors expression of the protein in real time via fluorescence detection. Specific inhibitors for the nascent chain of interest can then be identified by comparison with a counter screen. The assay was optimized to maximal sensitivity and reaction costs of ~$0.01 per well, enabling large-scale screens. We validated performance with the reference compound PF846 on the nascent chain of the protein PCSK9. Feasibility for high-throughput screening was demonstrated using a library of 1,760 compounds against the oncogenic KRAS variant A146T and the protein ApoC3, with mean Z' scores of 0.69 and 0.88, respectively. Sixteen global translation inhibitors were identified in each campaign, while no compounds met the criteria for POI-selective inhibition. The assay thus provides a robust platform for larger-scale screening campaigns.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.09.03.749102",
      "metadata": {
        "doi": "10.64898/2026.09.03.749102",
        "version": "1",
        "authors": "Fischer, P. D.; Hiller, S.",
        "category": "biochemistry",
        "type": "new results",
        "license": "cc_by",
        "institution": "University of Basel"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.09.03.749093:v1",
      "title": "Spatiotemporal pectin remodelling, glycoproteins, and LEA proteins maintain cell wall integrity during desiccation and rehydration in Ramonda serbica",
      "summary": "Vegetative desiccation tolerance requires specialised cell wall (CW) adaptations to withstand severe mechanical stress during dehydration and rehydration. While intracellular protective strategies in resurrection plants, including Ramonda serbica, are well documented, the CW response remains poorly understood. Here, we integrated immunocytochemical profiling, FTIR spectroscopy, quantification of CW-bound phenolics, transcriptomics, and ionically bound CW proteomics across hydrated (HL), desiccated (DL), and rehydrated states (R1-1h, R2-24h, R3-48h). Reversible CW folding was facilitated by condensed arabinogalactan-proteins (AGPs) and extensins, alongside a site-specific balance between pectin methylesterification and demethylesterification. Structural compaction was further reinforced by the accumulation of CW-bound hydroxycinnamates, which persisted through R1 phase. Moreover, basic 7S globulin, miraculin, -galactosidase, and two LEA4 protein family members were strongly accumulated during DL and R1, providing the first evidence of ionically CW-bound LEA proteins. Initial rewatering (R1) triggered a rapid transcriptomic reactivation of pectin-degrading/modifying enzymes, carbohydrate-active enzymes, and subtilases, accompanied by unesterified pectin enrichment. By 24-48 h (R2-R3), CW-bound hydroxycinnamic acids declined, and CW architecture, gene expression, and proteome profiles returned to baseline levels. Overall, our findings reveal a coordinated spatiotemporal apoplastic network - driven by glycoproteins, pectin modulation, CW-bound hydroxycinnamates, and LEA4 proteins - essential for rapid desiccation recovery.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.09.03.749093",
      "metadata": {
        "doi": "10.64898/2026.09.03.749093",
        "version": "1",
        "authors": "Pantelic, A.; Ilina, T.; Milic, D.; Kutyrieva-Nowak, N.; Lekic, S.; Popovic, L.; Balliau, T.; Vujisic, L.; Leszczuk, A.; Blein-Nicolas, M.; Vidovic, M.",
        "category": "plant biology",
        "type": "new results",
        "license": "cc_by_nd",
        "institution": "Group for Plant Molecular Biology  Institute of Molecular Genetics and Genetic Engineering  University of Belgrade"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.09.03.749081:v1",
      "title": "Divergent nitrogen transition pathways during global agricultural development",
      "summary": "Reactive nitrogen (N) inputs underpin global food production, but increasing protein provision while limiting agricultural N pressure remains a major sustainability challenge. Here, we analyzed changes in N use, cropland N surplus and protein supply across 130 countries from 1992 to 2022 to assess whether recurrent N-transition patterns emerge during agricultural and economic development. Countries followed divergent trajectories rather than converging toward a common N transition. Absolute decoupling, with increasing protein supply and declining cropland N surplus, occurred in 35.4% of countries, while others showed relative improvements or increasing N pressure. Cropland N surplus rose more steeply as agricultural N inputs intensified. Long-term trajectories revealed contrasting forms of N-system reorganization, from persistently lower-pressure systems to intensifying systems. Absolute decoupling occurred across diverse economic contexts and was not systematically associated with development level. Higher-development countries that decoupled generally reduced N surplus from higher starting levels but still ended with higher surpluses. Thus, increasing protein provision while reducing N surplus is achievable, but improvement does not necessarily imply convergence toward low N pressure.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.09.03.749081",
      "metadata": {
        "doi": "10.64898/2026.09.03.749081",
        "version": "1",
        "authors": "Bozal-Leorri, A.; Corrochano-Monsalve, M.",
        "category": "systems biology",
        "type": "new results",
        "license": "cc_by_nc_nd",
        "institution": "University of the Basque Country"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.09.03.749080:v1",
      "title": "Paralemmin-2 is a membrane-anchored cytoskeletal constituent of Axon Initial Segments and nodes of Ranvier",
      "summary": "The axon initial segment (AIS) and nodes of Ranvier (NoR) are essential for action potential initiation and propagation. They share many features of their molecular architecture, and their assembly mechanisms converge on the membrane-associated periodic skeleton (MPS). Here, we identify Paralemmin-2 (Palm2) as a component of both the AIS and NoR. Palm2 depletion shortens the AIS and reduces neuronal excitability. Endogenous Palm2 in the AIS is non-periodic, but upon overexpression it associates with the MPS, localizing to actin rings and reducing {beta}IV-spectrin abundance and periodicity. In NoR of the central and peripheral nervous system, Palm2 localizes to different subdomains - nodal or paranodal, respectively. Palm2, and its homolog Palm1, bind the deubiquitinase USP7, implicating paralemmins in proteostasis at the MPS. The complementary localizations of Palm2 and Palm1 at the AIS/NoR or axon shafts, respectively, parallel the distributions of {beta}-spectrin and ankyrin isoforms between these axonal compartments. We propose that Palm2 modulates the submembrane cytoskeleton and its membrane attachment, and thus contributes to the assembly, functioning and remodeling of the AIS and NoR.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.09.03.749080",
      "metadata": {
        "doi": "10.64898/2026.09.03.749080",
        "version": "1",
        "authors": "Macarron-Palacios, V.; Metzendorf, N. G.; Hultqvist, G.; Acuna, C.; Kneilmann, S.; Hubrich, J.; Wüstefeld, L.; Martens, H.; Kilimann, M. W.; D'Este, E.",
        "category": "cell biology",
        "type": "new results",
        "license": "cc_by_nd",
        "institution": "Max Planck Institute for Medical Research"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.09.03.749066:v1",
      "title": "HSPD1 promotes neuroblastoma by augmenting MYCN expression",
      "summary": "MYCN amplification is associated with poor outcomes in neuroblastoma (NB). MYCN encodes a transcription factor that induces the expression of mitochondrial one-carbon enzymes and chaperones, promoting metabolic reprogramming and aggressiveness in NB tumor cells. While the contribution of MYCN to changes in the mitochondrial proteome is well established, how mitochondrial proteostasis contributes to MYCN activity remains poorly understood. Mitochondrial HSP60 (HSPD1) is a conserved mitochondrial chaperone promoting the mitochondrial one-carbon pathway and mitochondrial translation by folding the one-carbon enzyme MTHFD2 and preventing aggregation of mitochondrial ribosomal proteins. Here, we show that HSPD1 depletion in MYCN-amplified NB cells led to reduced mitochondrial translation, MYCN expression, and tumorigenesis in vitro and in vivo. In addition, HSPD1 mRNA and protein correlate with MYCN expression in NB tumors. These results establish HSPD1 as a promising target for the treatment of MYCN-amplified NB.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.09.03.749066",
      "metadata": {
        "doi": "10.64898/2026.09.03.749066",
        "version": "1",
        "authors": "Alassam, S. S.; Manikandan, D. B.; Ben-David, H.; Cohen, L.; Kaluski-Kopatch, S.; Hruby, L.; Dror, S.; Sorensen, P. H.; Delaidelli, A.; Leprivier, G.; Elkabets, M.; Rotblat, B.",
        "category": "cancer biology",
        "type": "new results",
        "license": "cc_by_nc",
        "institution": "Ben Gurion University of the Negev"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.09.03.749064:v1",
      "title": "Tube-in-tube oxygen saturator enabling precise and dynamic control of liquid-phase oxygen concentrations for human cell culture applications",
      "summary": "This study demonstrates the feasibility of using a Teflon-AF-based tube-in-tube saturator for fast and precise adjustment of oxygen concentrations in liquids, extending its relevance to human cell culture applications beyond organ-on-chip systems. The system achieves high, near-saturation oxygen concentrations of the liquid phase, with performance influenced by various parameters such as temperature, volume flow rate, and tube length. We demonstrate that the tube-in-tube saturator exhibits high sensitivity to variations in these parameters at low oxygen concentrations, whereas this sensitivity diminishes as saturation is approached. To elucidate the underlying mass transfer processes, kinetic experiments were combined with computational fluid dynamics simulations. The simulation results are in good agreement with the experimental data, and the developed model enables a reliable prediction of oxygen concentrations in the liquid phase under varying operating conditions. Owing to its design, performance, versatility, and portability, this system introduces a new approach for the precise and rapid control of oxygen concentrations in liquids for microscale and macroscale human cell culture applications, offering seamless integration with natural vascular or artificial perfusion networks.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.09.03.749064",
      "metadata": {
        "doi": "10.64898/2026.09.03.749064",
        "version": "1",
        "authors": "Biermann, M.; Nuber, U. A.; Etzold, B. J. M.",
        "category": "bioengineering",
        "type": "new results",
        "license": "cc_no",
        "institution": "Friedrich-Alexander-University Erlangen-Nuernberg, Department of Chemical and Biological Engineering, Institute for Power-to-X Technologies, Dr-Mack-Str. 81, 90"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.09.03.749062:v1",
      "title": "A 13-subunit c-ring in the Chlamydomonas chloroplast ATP synthase lowers the H⁺/ATP cost of carbon fixation",
      "summary": "The chloroplast F1Fo ATP synthase is a rotary motor that converts the light-driven proton-motive force into the chemical energy of ATP. The number of c-subunits in its rotor fixes the number of protons translocated per ATP formed, a fundamental parameter of bioenergetic systems. The reference spinach enzyme possesses fourteen c-subunits and a H+/ATP ratio of 4.67. Green algae additionally operate a carbon-concentrating mechanism that sustains CO2 fixation in water at a substantial cost in ATP, yet the structure of the algal motor, and whether its bioenergetic parameters differ from those of vascular plants, remains unresolved. Here, a 2.2 [A] structure of the ATP synthase of Chlamydomonas reinhardtii reveals that the enzyme carries a thirteen-membered c-ring, the first departure from c14 in a chloroplast, and with a lower predicted H+/ATP ratio of 4.33. Ordered waters trace a Grotthuss proton relay through the membrane, where an insulating triad separates the proton loading and unloading sites and couples flux to rotation. A single substitution in the redox switching {gamma}-subunit abolishes the contact with the catalytic {beta}-subunit that idles the enzyme in darkness in vascular plants. These unique features of the algal ATP synthase lower the H+/ATP cost of carbon fixation in the light and facilitate acetate metabolism in the dark.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.09.03.749062",
      "metadata": {
        "doi": "10.64898/2026.09.03.749062",
        "version": "1",
        "authors": "Lorencik, K.; Pintscher, S.; Richardson, K.; Takahashi, H.; Proctor, M.; Rawski, M.; Hunter, C. N.; Hitchcock, A.; Blaza, J. N.; Johnson, M. P.",
        "category": "biochemistry",
        "type": "new results",
        "license": "cc_by_nc_nd",
        "institution": "University of Sheffield"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.09.03.749044:v1",
      "title": "Mitochondrial protein import couples proteostasis failure to mitochondrial permeabilization",
      "summary": "Proteostasis failure is a hallmark of stress and disease, yet how it compromises mitochondrial integrity remains unclear. Here, we identify mitochondrial protein import as a critical pathway linking proteostasis failure to mitochondrial injury. We show that Raptinal, previously characterized as a rapid inducer of apoptosis, impairs the folding of newly synthesized proteins rather than directly disrupting mitochondrial membranes. The resulting proteotoxic stress drives mitochondrial outer membrane permeabilization and intrinsic apoptosis independently of BCL-2 family pore-forming proteins. VBIT4, a compound commonly used to maintain mitochondrial integrity, inhibited this pathway, and chemical proteomics with a photoaffinity analogue implicated the TIM23 import machinery. Genetic or pharmacological inhibition of the TIM23-PAM axis suppressed mitochondrial permeabilization without affecting canonical BAX-BAK-dependent apoptosis. These findings establish that mitochondrial protein import couples translation-associated proteotoxic stress to mitochondrial injury and identify regulation of import flux as a determinant of mitochondrial integrity during proteostasis failure.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.09.03.749044",
      "metadata": {
        "doi": "10.64898/2026.09.03.749044",
        "version": "1",
        "authors": "Sun, Z.; Holthusen, H.; Berndl, S.; Behnsen, A.; Schwojer, S. J.; Gobbato, G.; Sorensen, G.; Warscheid, B.; Sieber, S. A.; Hartl, F. U.; Hornung, V.",
        "category": "cell biology",
        "type": "new results",
        "license": "cc_by",
        "institution": "Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.09.03.748889:v1",
      "title": "Cell cycle control of chromatin creates a therapeutic window for epigenetic therapy in tumors",
      "summary": "The relationship between cell cycle length and differentiation competence is well established in developmental biology, particularly in embryonic stem cells, where a short G1 phase maintains pluripotency and G1 lengthening permits lineage commitment. Whether this principle operates in cancer cells, where the cell cycle is deregulated and G1 is frequently shortened, and whether it can be pharmacologically exploited for therapy, has not been tested. Here we show that the duration of G1 is a causal determinant of chromatin state in cancer cells and that extending G1 creates a therapeutic window for epigenetic drugs. Using acute myeloid leukemia (AML) as a model, we demonstrate that low-dose palbociclib, at concentrations well below those required for cytostatic arrest, extends G1 without halting proliferation. This modest prolongation reshapes the histone modification landscape: repressive marks (H3K9me2/3, H4K20me2/3) increase while acetylation decreases, and chromatin accessibility rises broadly in the euchromatic compartment. Naturally slow-cycling AML lines share this epigenetic signature regardless of their oncogenic driver mutations, and pharmacologically extending G1 in fast-cycling cells recapitulates it, establishing G1 length as a causal regulator of the cancer epigenome rather than a passive correlate. To identify epigenetic vulnerabilities created by G1 extension, we performed complementary drug and CRISPR-Cas9 screens in G1-extended AML cells. Both approaches converged on LSD1 (KDM1A): slow-cycling AML cells are intrinsically sensitive to LSD1 inhibition, while fast-cycling cells become sensitive when G1 is prolonged. The combination of low-dose palbociclib and LSD1 inhibition triggers differentiation and significantly prolongs survival in AML xenograft models. p21 (CDKN1A) emerges as the central molecular determinant of this response. In slow-cycling AML cells, p21 is highly expressed and its knockdown abolishes LSD1 inhibitor sensitivity. Structure-function analysis using p21 mutants separates the two known activities of p21: the CDK-inhibitory function (which extends G1) is required for sensitization, whereas the PCNA-binding function is dispensable. Three pharmacological routes converge on the same endpoint, CDK inhibition, G1 extension, and a differentiation-competent chromatin state: direct CDK4/6 inhibition by palbociclib, p21 overexpression, and p21 induction through HDAC or EZH1/2 inhibitors. Palbociclib bypasses the requirement for p21 entirely, confirming that G1 length itself, not p21 as a protein, is the critical variable. Mechanistically, the combination of G1 extension and LSD1 inhibition produces a qualitatively distinct chromatin state rather than an additive one. ATAC-seq reveals thousands of combination-exclusive accessible regions, enriched for footprints of myeloid differentiation transcription factors including SPI1/PU.1, IRF1, and STAT1/2. A double-lock principle governs this remodeling: palbociclib drives the removal of repressive marks (H3K9me3 and H3K27me3), while LSD1 inhibition installs active marks at the newly accessible regions. The ncBAF chromatin remodeling complex, identified in our CRISPR screen and validated by knockout of its essential subunits BRD9 and SMARCD1, is specifically required for this response. Loss of ncBAF abolishes the combination-induced chromatin remodeling and differentiation program but does not affect the initial G1 extension or retinoic acid-induced differentiation, indicating that ncBAF specifically couples cell-cycle modulation to chromatin remodeling rather than acting as a general differentiation factor. The principle generalizes beyond AML. In melanoma, breast cancer, and small-cell lung cancer (SCLC), sensitivity to LSD1 inhibition tracks with p21 expression and cycling speed. Primary melanoma samples stratified by p21 recapitulate the same pattern: p21-high, slow-cycling cells are sensitive; p21-low, fast-cycling cells are resistant but can be sensitized by palbociclib cotreatment. Cisplatin-induced drug-tolerant persister (DTP) cells, which emerge as a slow-cycling, chemo-resistant population and upregulate both p21 and LSD1, become vulnerable to LSD1 inhibition and are eradicated by the combination. In melanoma patient-derived xenograft (PDX) models, p21-high tumors respond to LSD1 inhibitor monotherapy, while p21-low tumors are sensitized by palbociclib cotreatment, with p21 knockdown abolishing the response. Together, these findings establish cell-cycle duration as a tunable regulator of the cancer epigenome and demonstrate that pharmacological G1 extension converts cytostatic CDK4/6 inhibition into an epigenetic sensitization strategy. Both fast-proliferating and slow-cycling tumor compartments (including drug-resistant persisters) can be targeted by matching the epigenomic state to the appropriate combination of cell-cycle modulators and epigenetic drugs. p21 emerges as a candidate biomarker for patient stratification. More broadly, our work repositions the cell cycle from a passive conduit for proliferation signals to an active, druggable regulator of chromatin fate, with implications that extend from cancer therapy to stem cell biology and regenerative medicine.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.09.03.748889",
      "metadata": {
        "doi": "10.64898/2026.09.03.748889",
        "version": "1",
        "authors": "Hayatigolkhatmi, K.; Valzelli, R.; Ceccacci, E.; Hosseini, A.; El Menna, O.; Romanenghi, M.; Pallavicini, I.; Soda, E.; Ejlli, O.; Villa, E.; Falvo, P.; Blanco, E.; Aranda, S.; Barkhordar, R.; Soriani, C.; Ronzoni, S.; Giardina, G.; Rodighiero, S.; Bertolini, F.; Mai, A.; Polletti, S.; Lanfrancone, L.; Noberini, R.; Leuzzi, G.; Pelicci, P. G.; Bonaldi, T.; Di Croce, L.; Minucci, S.",
        "category": "cancer biology",
        "type": "new results",
        "license": "cc_by_nd",
        "institution": "Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.09.02.748910:v1",
      "title": "Intravital single-cell behavior profiling reveals disrupted germinal center B cell motility and interactions by EZH2 gain-of-function mutation",
      "summary": "Germinal center (GC) B-cells give rise to the majority of non-Hodgkin lymphomas, underscoring the need to pinpoint critical processes that initiate and drive lymphomagenesis. Lymphoma driver mutations can alter GC B cell functions and B cell fate decisions. Here, we studied how EZH2 oncogenic mutation in GC B cells alters cellular motility and interactions with T follicular helper (Tfh) cells and follicular dendritic cells (FDCs) to determine B cell fate. By combining intravital imaging, single-cell behavior analyses, and RNA sequencing, we uncover how lymphoma-associated EZH2 mutations reprogram the behaviors of GC B cells in vivo. We found that EZH2 mutations increased single-cell motility speeds and morphological plasticity of GC B cells, redirecting migration toward the FDC-rich light zone subregions rather than to the dark zone. Although mutant EZH2 GC B cells exhibited normal engagement quality with FDCs, they showed shorter interaction times and reduced surface engagement with Tfh cells. Notably, EZH2 mutant B cells required prior contact with FDC before engaging with Tfh cells, thus impairing DZ recycling. This motility phenotype scaled with local mutant clone abundance, suggesting a behavioral strategy underlying how mutant cells outcompete WT cells. Lastly, we developed scMOTIPh, a computational framework that integrates single-cell behavioral features with transcriptomic profiles. Applying scMOTIPh to mutant GC B cells within the FDC-rich zone revealed enhanced ATP production, metabolic and antigen-presentation programs, and suppression of cell-death pathways, which is consistent with a tendency for malignant transformation and survival fitness. These findings provide an in vivo, single-cell view of how an epigenetic lesion rewires the local microenvironment by modulating single-cell behaviors within native GCs, revealing a dynamic mechanism for early lymphomagenesis.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.09.02.748910",
      "metadata": {
        "doi": "10.64898/2026.09.02.748910",
        "version": "1",
        "authors": "Min, C.; Choe, K.; Chen, X.; Karagiannidis, I.; Sivakumar, N.; Xu, C.; Melnick, A.; Phillip, J. M.; Beguelin, W.",
        "category": "immunology",
        "type": "new results",
        "license": "cc_by_nc_nd",
        "institution": "Johns Hopkins University"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.09.02.746746:v1",
      "title": "A Multi-Omics Study of Cognitive Resilience to Alzheimer's Disease",
      "summary": "Alzheimers disease (AD) is the most severe form of dementia. While significant efforts have been made to identify AD risk factors and develop therapeutics, much less attention has been given to neurobiological factors and molecular signatures associated with cognitive resilience. Substantial evidence suggests that modifiable factors, such as physical and mental activity, may contribute to cognitive reserve and resilience. To this end, we developed a resilient cohort of paired genetics, transcriptomics and proteomics data from the prefrontal cortex of 282 cognitively normal older adults. We conducted extensive preprocessing and rigorous quality control (QC), including QC on sequence metrics and sample matching across multiomics. This cohort can be leveraged for identification of molecular signatures of cognitive resilience to AD and is freely shared with the research community.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.09.02.746746",
      "metadata": {
        "doi": "10.64898/2026.09.02.746746",
        "version": "1",
        "authors": "Wang, E.; Xie, B.; Wang, M.; Fu, Y.; Wang, X.; Li, Y.; Xu, P.; Liu, H.; Ho, L.; Tu, Z.; Mobbs, C.; Gaiteri, C.; Ehrlich, M. E.; Bennett, D. A.; Haroutunian, V.; Peng, J.; Zhang, B.",
        "category": "genomics",
        "type": "new results",
        "license": "cc_by_nc_nd",
        "institution": "Icahn School of Medicine at Mount Sinai"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.09.01.748658:v1",
      "title": "Differential LncRNA expression profile in the plasma of preeclampsia and normal pregnancies",
      "summary": "Background: Early detection of preeclampsia with noninvasive and reliable biomarkers is the foremost step for minimizing adverse effects during pregnancy. However, none maternal serum analyte evaluated so far is sufficiently accurate to allow recommending their routine use. Methods: Microarray was used to first identify differentially expressed LncRNA and mRNA. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to determine bio-functions and signaling pathways. Quantitative real-time polymerase chain reaction was used to validate the results of microarray. Finally, the lncRNA-mRNA co-expression network was constructed to find the interaction of genes. Result: A total of 1476 differentially expressed lncRNAs and 594 mRNAs were identified. Both RNA-seq and RT-qPCR showed the expression of T241171,T338586, uc002ywy.3 was up-regulated, and the expression of ENST00000524858, T131416, T357032, uc.335+ was down regulated in the plasma of patients with preeclampsia. Pathway analysis showed the targeted mRNAs were enriched in apoptosis, sulfur metabolism, starch and sucrose metabolism. ceRNA network found that LncRNA-uc002ywy.3 might be the upstream regulator of miRNA-4498. LncRNA-uc002ywy.3/miRNA-4498 was predicted to interplay with genes involved in programmed cell death-1and its ligand (PD-1/PD-L1) pathway by KEGG analysis. Conclusion s PD-1/PD-L1 signaling pathway may be involved in the development of preeclampsia. The dysregulated LncRNA-uc002ywy.3/miRNA-4498 shed light on a new layer involved in the regulatory network of preeclampsia.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.09.01.748658",
      "metadata": {
        "doi": "10.64898/2026.09.01.748658",
        "version": "1",
        "authors": "Peng, L.; Lai, W.; Huang, J.; Zhong, Y.",
        "category": "physiology",
        "type": "new results",
        "license": "cc_by",
        "institution": "The Second Xiangya Hospital of Central South University"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.09.01.748657:v1",
      "title": "Metagenomic and metabolomic analysis of a bryozoan-associated microbial complex from the Hanjiang River, China",
      "summary": "Background Bryozoans are ancient colonial animals that have existed for over 470 million years and are widely distributed across aquatic environments. Recently, many spherical colloids (average diameter{approx}1 meter in diameter), containing bryozoans and diverse microorganisms, were found in the Hanjiang river in China. In this study, we investigated these bryozoan-dominated microbial complexes using metagenomic sequencing, metabolomic profiling, and complementary approaches. Results The results revealed that the microbial structure dominated by bryophytes included eukaryotes such as fungi, microalgae, and small parasites etc., as well as prokaryotes such as bacteria and viruses. All members form a highly integrated consortium that collaboratively maintains community function and stability, which displayed the shape and structure of a regular microbial complex and increased in size. Additionally, the results suggested the predominately presence of Proteobacteria were particularly abundant and are known to produce bryostatins in response to bryozoan signals. Interesting, it was implied that a decrease or even a loss in virulence occurs when pathogenic microorganisms become members of the complex. This is the first study focusing on the composition and metabolites of the unusual microorganism complex. The results discovered the close and intriguing connections within the microbial communities dominated by the ancient organism bryozoan through multi-omics technologies. It showed that both eukaryotes and prokaryotes can coordinate or compete, thereby forming a stable composite structure.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.09.01.748657",
      "metadata": {
        "doi": "10.64898/2026.09.01.748657",
        "version": "1",
        "authors": "Zhu, H.; Lin, X.; Wang, R.; Zhang, T.; Xu, W.; Gao, W.; Fang, F.; Huang, J.; Sun, Y.",
        "category": "zoology",
        "type": "new results",
        "license": "cc_by",
        "institution": "Hanshan Normal University"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.09.01.748526:v1",
      "title": "The Adhesion GPCR Flamingo-Like 1 (FMIL-1) Directs Synapse Formation in a Nociceptive Circuit",
      "summary": "The species-specific anatomy of nervous systems suggests that circuit architecture is largely encoded by genetic blueprints. In C. elegans, PVD nociceptive neurons synapse with PVC and AVA interneurons to drive escape responses to noxious stimuli. We used fluorescent markers for PVD synapses with PVC and AVA in a candidate screen to detect connectivity genes. This approach revealed that the LIM homeodomain transcription factor MEC-3 and its target, FMIL-1 (Flamingo-like), function in PVD to direct connectivity with PVC and AVA. FMIL-1 is an adhesion class G Protein-coupled receptor (aGPCR), a protein family with members also implicated in mammalian synapse formation. We show that FMIL-1 acts early in PVD and is also sufficient to induce ectopic synapses in another circuit, thus suggesting that FMIL-1 promotes synaptogenesis. Our work establishes a new experimental circuit in C. elegans for investigating neuronal connectivity and provides evidence that FMIL-1/aGPCRs regulate synapse formation.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.09.01.748526",
      "metadata": {
        "doi": "10.64898/2026.09.01.748526",
        "version": "1",
        "authors": "Kennedy, T.; Oje, D.; Howerter, K.; Reese, S.; McWhirter, R.; O'Brien, B. M. J.; Stern, J.; Ottley, M.; Arac, D.; Ozkan, E.; Sando, R.; Dillin, A.; Miller, D. M.",
        "category": "neuroscience",
        "type": "new results",
        "license": "cc_by",
        "institution": "University of California, Berkeley"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.08.27.747591:v2",
      "title": "Coarse composition suffices: tabular in-context learning for multi-activity antimicrobial peptide profiling",
      "summary": "Antimicrobial peptides (AMPs) often act against multiple pathogen classes, making multi-label activity prediction a more realistic screening target than binary antimicrobial classification. The ESCAPE benchmark formalizes this setting, but leading approaches typically rely on multimodal, structure-conditioned deep models that are costly to train and tune. We show that a simple, sequence-only pipeline can match and surpass these methods by combining 330 interpretable sequence descriptors with TabPFN, a tabular foundation model that performs in-context prediction in a single forward pass without gradient-based training or hyperparameter search. On ESCAPE (82,359 peptides; five labels), a label-powerset TabPFN model achieves mAP-5=77.8%, improving on the previously best reported 72.1%. A probabilistic classifier chain is the first method to match or exceed the best published average precision on each of the five labels simultaneously. The gains persist under the prior state-of-the-art single-fold training protocol, indicating they are not a training-set-size artefact, and are largest for remote homologues (+11.2 points below 30% sequence identity). Ablations further show that predicted structure is unnecessary at inference and that performance is not driven by any single descriptor family: ten global physicochemical scalars recover 91% of full-feature performance. Finally, explicitly modelling label dependence yields targeted benefits for scarce activities and supports ranking which activity to assay next from partial positive evidence.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.08.27.747591",
      "metadata": {
        "doi": "10.64898/2026.08.27.747591",
        "version": "2",
        "authors": "Pal, A.; Kumar, R.; Solanki, D.; Pareek, P.; Singh, J.; Singla, J.",
        "category": "bioinformatics",
        "type": "new results",
        "license": "cc_by",
        "institution": "IIT Roorkee"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.08.25.747098:v2",
      "title": "A two-signal, two-receiver signalling system: Snake mobbing in the Arabian babbler",
      "summary": "Mobbing is a collective antipredator behaviour in which animals approach and harass a threat while coordinating signals to alert conspecifics, recruit allies, or deter predators. In group-living Arabian babblers (Argya squamiceps), snake mobbing relies on two signals that differ in receivers: acoustic \"zwick\" calls inaudible to the snake and visual wing-lift displays perceived by both conspecifics and the snake, raising the question of whether each signal has one receiver or involves a more complex structure. We elicited snake-mobbing events with dummy vipers and recorded babbler groups using a synchronized acoustic camera enabling individual caller identification and postural analysis. We examined mob formation, the effect of group size on signalling, and the interplay between the two signal types. First signalling (recruitment) order was independent of sex, age and rank. Individual call rate decreased as group size increased, supporting the hypotheses of social buffering and predation risk dilution. Mobbing individuals responded faster (with signalling) to a joint visual-acoustic conspecific display and the onset of a visual display than to an acoustic-only signal. When coupled, wing-lifts significantly altered vocal characteristics, decreasing peak frequency and increasing call rate, thus strengthening the acoustic signal. Moreover, calls emitted toward the end of the wing-lift display exhibited a stronger drop in peak frequency. Together, these findings demonstrate the multi-functional role of multimodal mobbing signals during a risky cooperative task balancing social communication and predator deterrence.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.08.25.747098",
      "metadata": {
        "doi": "10.64898/2026.08.25.747098",
        "version": "2",
        "authors": "Guggenberger, M.; Keynan, O.; Yovel, Y.",
        "category": "animal behavior and cognition",
        "type": "new results",
        "license": "cc_by_nc_nd",
        "institution": "Tel Aviv university"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.08.19.745674:v2",
      "title": "RevPert: predicting candidate drivers of transcriptomic state transitions via gallery-native reverse perturbation",
      "summary": "Cellular state transitions underlie adaptation, ageing and disease, yet prioritizing catalogued genetic perturbations whose expression signatures match an observed transcriptomic shift remains difficult. Most models predict phenotype from a nominated intervention, whereas genetic inverse benchmarks are largely restricted to within-screen identity recovery. Here we introduce RevPert, a gallery-native reverse perturbation model that ranks a fixed genetic catalog for a query contrast {Delta}Y* = YB - YA by combining signed Pearson connectivity with a learned residual. Across Replogle Essential Perturb-seq (four lines) and LINCS-KO screens (ten lines), RevPert recovered held-out interventions at leading performance relative to matched baselines. Applied to public drug-resistance contrasts in HCC and CML, dual-arm ranking placed pre-specified disease anchors far higher on the expected arms than ranking the same signatures by differential-expression magnitude alone (Essential residual model for HCC; a transductive GWPS residual for CML). RevPert therefore couples within-screen reverse ranking to a screen-external signed-geometry check; the latter calibrates literature anchors and is not claimed as held-out recovery.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.08.19.745674",
      "metadata": {
        "doi": "10.64898/2026.08.19.745674",
        "version": "2",
        "authors": "Liang, S.; Yang, C.; Wang, J.; Li, y.",
        "category": "bioinformatics",
        "type": "new results",
        "license": "cc_by",
        "institution": "The No. 944 Hospital of Joint Logistic Support Force of PLA"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.06.03.730005:v2",
      "title": "Glucocorticoid rhythm disruption drives hyperinsulinaemia in mice through beta cell glucocorticoid receptor signalling",
      "summary": "Aims/hypothesis: Hyperinsulinaemia is typically viewed as a secondary, compensatory response to insulin resistance or elevated glycaemia. However, we previously found that disrupting the daily glucocorticoid rhythm in mice rapidly increases circulating insulin several-fold while fasting glucose remains normal. This raised the question of what generates and sustains the hyperinsulinaemia. Because glucocorticoids act directly on beta cells through the glucocorticoid receptor (GR), we tested whether beta cell GR is required for this rise in insulin and whether elevated insulin is necessary to maintain glucose homeostasis. Methods: Glucocorticoid rhythms were disrupted in male C57BL/6J mice by subcutaneously implanting corticosterone pellets that raise the trough and lower the peak while maintaining near-physiological mean glucocorticoid exposure, a manipulation we refer to as GC-flattening. Placebo-treated mice served as controls, and high-fat-diet-fed mice provided a metabolic comparison. Beta cell function was assessed by dynamic glucose stimulated insulin secretion and beta cell specific Ca2+ imaging. The requirement for beta cell GR was tested using adult-inducible beta cell specific GR knockout mice, thereby limiting developmental effects of constitutive GR deletion. Combined beta cell and hepatocyte GR knockout mice were used to test the consequences of further reducing systemic insulin availability. Insulin sensitivity and glucose tolerance were assessed in vivo. Insulin clearance was assessed from plasma C-peptide:insulin ratios, direct measurement of the disappearance of intravenously administered human insulin, and hepatic insulin-degrading enzyme abundance and activity. Results: GC-flattening produced rapid, sustained hyperinsulinaemia while blood glucose remained normal, distinct from the more gradual hyperinsulinaemia and hyperglycaemia observed in high-fat-diet-fed mice. Islets from GC-flattened mice retained enhanced insulin secretion and Ca2+ responses to glucose after isolation, indicating a persistent increase in beta cell glucose responsiveness. During GC-flattening, beta cell GR deletion reduced cumulative circulating insulin exposure by approximately 40% (p < 0.001) and worsened glycaemic control despite similar or greater insulin sensitivity, demonstrating that the GR-dependent rise in insulin helps maintain glucose homeostasis. Direct measurement on Day 3 confirmed reduced insulin clearance in GC-flattened mice. This was accompanied by a reduced plasma C-peptide-to-insulin ratio and decreased hepatic insulin-degrading enzyme abundance and activity. Further lowering circulating insulin by combined beta cell and hepatocyte GR deletion worsened glycaemic control further. Conclusions/interpretation: Disruption of glucocorticoid rhythmicity directly initiates hyperinsulinaemia by enhancing glucose-stimulated insulin secretion through beta cell GR signalling and by reducing insulin clearance. The resulting increase in insulin is required to maintain glucose homeostasis, demonstrating that hyperinsulinaemia can be an early adaptive response to altered endocrine timing rather than simply a consequence of insulin resistance or hyperglycaemia.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.06.03.730005",
      "metadata": {
        "doi": "10.64898/2026.06.03.730005",
        "version": "2",
        "authors": "Wilson, J.; Arzeno, A. S.; Sharma, S.; Agas, A.; Lungstrum, J.; Teruel, M. N.",
        "category": "physiology",
        "type": "new results",
        "license": "cc_by",
        "institution": "Weill Cornell Medicine"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.05.27.728155:v2",
      "title": "Trustworthy ML/AI for Aging Clocks: Preventing Systematic Prediction Bias in Biological Age Estimation",
      "summary": "Machine learning (ML)- and artificial intelligence (AI)-based aging clocks are increasingly used to quantify physiological and molecular aging from omics and medical imaging data as distinct from chronological age. Here, we characterize a fundamental but underappreciated statistical limitation of commonly used ML/AI regression models for continuous outcomes: systematic prediction bias and its propagation to downstream association estimates. This issue becomes more challenging when the true outcome, biological age, is latent and therefore unobserved during ML/AI model training. We demonstrate that systematic prediction bias can distort and, in some cases, even reverse downstream association analyses that use aging clocks as ML/AI-predicted outcomes to assess their associations with exposures or clinical factors. For example, it can produce spurious associations suggesting that older predicted brain age is linked to better cognitive performance, or that older epigenetic age is associated with better kidney function. To address this problem, we introduce a principled and broadly applicable ML/AI regression framework based on constrained optimization, yielding better calibrated aging-clock estimates and valid downstream inference.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.05.27.728155",
      "metadata": {
        "doi": "10.64898/2026.05.27.728155",
        "version": "2",
        "authors": "Lee, H.; Ye, Z.; Yang, Y.; Pan, Y.; Maron, B.; Wang, Z.; Kochunov, P.; Thompson, P.; Hong, L. E.; MA, T.; Chen, C.; Chen, S.",
        "category": "bioinformatics",
        "type": "new results",
        "license": "cc_by",
        "institution": "University of Maryland, School of Medicine"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.05.18.725733:v2",
      "title": "Immune Aging is an Independent Risk Factor for Cardiovascular Disease",
      "summary": "Cardiovascular disease remains the leading cause of mortality, yet current clinical predictors miss substantial disease-risk. While the immune system contributes to this residual risk, its complexity has hindered broadly applicable, clinically scalable metrics of immune-state. Here, we establish the prognostic relevance of IMM-AGE, a system-level metric of immune-aging, to cardiovascular disease. We learn reference-free, low-dimensional representations of IMM-AGE across cell, protein, and mRNA measurements, enabling high-fidelity quantification across modalities, blood fractions, and platforms, including standard hospital flow cytometers. Among UK-Biobank participants, 56.9% of IMM-AGE variation remained unexplained by routine clinical measures, and across diverse cohorts totaling ~48,000 individuals, elevated IMM-AGE was independently associated with future cardiovascular risk, intervention outcomes, and mortality. Moreover, incorporation of IMM-AGE into the PREVENT 10-year risk equation significantly improved risk stratification. These findings establish immune-aging as an independent biological dimension of cardiovascular disease-risk and support IMM-AGE as a practical tool for precision risk assessment.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.05.18.725733",
      "metadata": {
        "doi": "10.64898/2026.05.18.725733",
        "version": "2",
        "authors": "Feldman, E.; Santana, E. J.; Celestin, B.; Golden, N.; Bagherzadeh, S.; Maysel, S.; Mathi, K.; Short, S.; Caroll, M.; Sullivan, S. S.; Lukacisin, M.; Ji, X.; Klein, Y.; Caspi, O.; Nguyen, P.; Fearon, W. F.; Kim, B.; Shah, S.; Mahaffey, K. W.; Maecker, H. T.; Davis, M. M.; Milman, N.; Few-Cooper, T. J.; Haddad, F.; Shen-Orr, S. S.",
        "category": "immunology",
        "type": "new results",
        "license": "cc_by_nc_nd",
        "institution": "Technion - Israel Institute of Technology"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.03.25.714151:v3",
      "title": "Comparison of the Distribution of Fitness Effects Across Primates",
      "summary": "The distribution of fitness effects (DFE) of mutations is a key determinant of both the efficacy of natural selection and the genetic load of populations. It also provides an indirect summary of the underlying fitness landscape, so the extent to which the DFE is conserved across species is informative about the invariance of those landscapes. Here, we infer the DFE of amino-acid-changing mutations in 38 catarrhine subspecies using site-frequency spectrum (SFS)-based methods. We find that effective population size (Ne) is the dominant axis of cross-species variation in the population-scaled DFE for deleterious mutations, with the apparent clade-level clustering of estimates explained mainly by shared Ne rather than by clade-specific effects. A quantile-based test further shows that the underlying unscaled DFE does not vary significantly across species, so differences are consistent with Ne-rescaling of a single conserved DFE. Consistent with this, the deleterious (non-adaptive) substitution rate {omega}na declines significantly with Ne, reflecting more efficient purging of slightly deleterious mutations in larger populations. Turning to adaptive substitution, we find weaker, suggestive evidence that the adaptive rate {omega}a increases with Ne. These conclusions are robust to the choice of DFE parametrization, phylogenetic regression framework, the effect of GC-biased gene conversion, and ancestral misidentification. We also extend the DFE estimation procedure to relax the assumption of additive fitness effects, finding that dominance is only weakly identifiable from the SFS but has minimal impact on comparative DFE inference.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.03.25.714151",
      "metadata": {
        "doi": "10.64898/2026.03.25.714151",
        "version": "3",
        "authors": "Sendrowski, J.; Pedersen, B. M.; Bergman, J.; Pankratov, V.; Bataillon, T.",
        "category": "evolutionary biology",
        "type": "confirmatory results",
        "license": "cc_by",
        "institution": "Aarhus University"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2026.01.05.697602:v2",
      "title": "Elements of Olfactory Intelligence in Drosophila",
      "summary": "The ability to make the world of odorants intelligible is a key capability of the Drosophila olfactory system that we shall call olfactory intelligence. Characterizing the functional logic of the Drosophila early olfactory system that makes the natural world of odorants intelligible is a major challenge in neuroscience. Starting by modeling the space of odorants using constructs of both semantic and syntactic information, we establish that the Antenna Lobe and Mushroom Body Calyx first decompose the confounding representation of the Antenna into a concentration independent odorant semantics information and the ON-OFF timing of the syntactic information. Subsequently the two streams of information are integrated and produce a novel time and rank-based representation of Kenyon Cell outputs, called the marked first spike sequence code. In conjunction with a novel distance measure for the spike sequence code, we demonstrate that the rank-based representation supports accurate classification of ON-OFF odorant semantics. Computationally, these elements of olfactory intelligence are realized by a class of differential divisive normalization processors modeling the feedback circuits in a causal chain of stages including the Antenna, Antennal Lobe and the Mushroom Body Calyx. Consequently, the early olfactory system makes the natural world of odorants intelligible.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2026.01.05.697602",
      "metadata": {
        "doi": "10.64898/2026.01.05.697602",
        "version": "2",
        "authors": "Lazar, A. A.; Zhou, Y.",
        "category": "neuroscience",
        "type": "new results",
        "license": "cc_no",
        "institution": "Columbia University"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.64898/2025.12.24.696231:v2",
      "title": "SynTEF1 restores the functional disease phenotype of SCA27B in an hiPSC-derived neuronal model",
      "summary": "Spinocerebellar Ataxia 27B (SCA27B), caused by a deep-intronic GAA repeat expansion in the first intron of the FGF14 gene, is one of the most frequent genetic ataxias. Its underlying disease mechanisms remain largely unknown, and disease-modifying therapies targeting upstream processes are lacking. Here we hypothesized that (i) SCA27B is driven by transcriptional repression of FGF14, which encodes a protein regulating ion channels at the axon initial segment (AIS), resulting in reduced Na+ channel availability and neuronal excitability, and that (ii) these defects can be restored by a synthetic elongation transcription factor (Syn-TEF1). We assessed FGF14 mRNA levels by qPCR and neuronal function by whole-cell patch-clamp recordings in iPSC-derived neurons from two SCA27B patients and two healthy controls. Patients carried GAA repeat expansions that were either monoallelic (391/16 repeats) or biallelic (315/290 repeats), exceeding the common pathogenicity threshold of >250 repeats. FGF14 mRNA levels were reduced approximately to 60% and 70% of control levels in monoallelic and biallelic SCA27B neurons, respectively. This was accompanied by impaired excitability, with cumulative action potential (AP) firing reduced to 38% and 45% of control levels in monoallelic and biallelic lines, respectively, and peak Na current density reduced to 46% and 41%, while voltage-dependent gating of Na channels remained unchanged. Treatment with Syn-TEF1 significantly increased FGF14 mRNA expression and restored cumulative AP firing to 83% and 135% of control levels in monoallelic and biallelic neurons, respectively, and Na peak current density to 95% and 138%. These findings strongly suggest that the pathophysiological cascade in SCA27B - from FGF14 repression to impaired Na+ currents and decreased neuronal excitability - can be reversed by an elongation transcription factor. Our results thus provide a rationale for further exploring Syn-TEF1 as a first gene-targeted, disease-modifying therapeutic approach for SCA27B.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.64898/2025.12.24.696231",
      "metadata": {
        "doi": "10.64898/2025.12.24.696231",
        "version": "2",
        "authors": "Gsell, F. G.; Pellerin, D.; Vinogradov, O.; Zuchner, S.; Haag, C.; Hedrich, U.; Napierala, M.; Saporta, M.; Yanick, C.; Brais, B.; Baumgartner, M. E.; Lerche, H.; Schwarz, N.; Synofzik, M.",
        "category": "neuroscience",
        "type": "new results",
        "license": "cc_by_nc",
        "institution": "Division Translational Genomics of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research and Center of Neurology, University of Tuebingen"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.1101/2025.10.30.685705:v4",
      "title": "Mathematical Modeling of Late-Stage LC Aggregation and Cardiac Injury Following Establishment of a Pathogenic Plasma-Cell Clone",
      "summary": "AL amyloidosis is a rapidly progressive disorder characterized by clonal plasma cell expansion, excessive production of light chains (LCs), and their misfolding into aggregation-prone monomers. These monomers assemble into oligomers and ultimately deposit as amyloid fibrils, particularly within cardiac tissue, where they contribute to myocardial stiffening and direct cardiotoxicity. A reduced-order mechanistic model is developed to describe LC secretion by a pathogenic plasma-cell clone, LC unfolding and aggregation, cardiac deposition, and the resulting myocardial injury during advanced cardiac AL amyloidosis. Simulations reveal pronounced nonlinear LC aggregation kinetics: oligomer concentrations remain low during the early part of the modeled terminal cardiac-progression interval and subsequently increase rapidly as autocatalytic conversion becomes dominant. When aggregation is assumed to occur within cardiac tissue, fibril deposition is approximately 30 times greater, and oligomer-induced cardiotoxicity is about five times higher, compared with aggregation occurring in the blood plasma. These differences stem from the smaller cardiac volume, which accelerates autocatalytic oligomer formation. A combined cardiac damage criterion, integrating both oligomer-induced cardiotoxicity and fibril-associated myocardial stiffening, was introduced and found to reach values approximately tenfold higher when LC aggregation occurs within cardiac tissue compared with aggregation in the blood plasma. This parameter may provide a candidate model-based measure of cardiac aging or disease severity. The model also predicts that therapeutic intervention markedly reduces, but does not eliminate cardiac injury, highlighting the importance of early treatment initiation in AL amyloidosis.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.1101/2025.10.30.685705",
      "metadata": {
        "doi": "10.1101/2025.10.30.685705",
        "version": "4",
        "authors": "Kuznetsov, A. V.",
        "category": "biophysics",
        "type": "new results",
        "license": "cc_by_nc_nd",
        "institution": "North Carolina State University"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.1101/2025.02.04.636500:v2",
      "title": "Modulation of oscillatory activity in response to very weak intensity transcranial magnetic stimulation in the human primary motor cortex",
      "summary": "Transcranial Magnetic Stimulation is widely used to probe and modulate human brain function, yet the neural effects of stimulation delivered at very low intensities remain unclear. Here, we show that very low intensity magnetic pulses can alter ongoing oscillatory activity in the human primary motor cortex. In healthy participants, we combined transcranial magnetic stimulation with electroencephalography to assess neural responses to single pulses and rhythmic stimulation in the motor cortex. Conventional high intensity stimulation produced robust evoked responses and synchronized beta-frequency oscillations. Low-intensity rhythmic stimulation, despite generating much weaker direct responses, modified local oscillatory activity in a manner consistent with phase-dependent enhancement of ongoing rhythms. These findings suggest that cortical oscillations can be influenced by magnetic fields substantially weaker than those typically used in human studies. Low-intensity stimulation may therefore offer a route towards portable, energy-efficient technologies for investigating and modulating brain networks.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.1101/2025.02.04.636500",
      "metadata": {
        "doi": "10.1101/2025.02.04.636500",
        "version": "2",
        "authors": "Corominas-Teruel, X.; Bracco, M.; Lohof, A.; Sherrard, R.; Colomina, M. T.; Mahon, S.; Charpier, S.; Valero-Cabre, A.",
        "category": "neuroscience",
        "type": "new results",
        "license": "cc_by_nc_nd",
        "institution": "Paris Brain Institute"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.1101/2025.01.04.631301:v3",
      "title": "DeepPROTECTNeo: A Context-aware Personalized and Reverse Vaccinology-guided Deep Learning Framework for Immunogenicity Prediction",
      "summary": "Background: The development of personalized cancer vaccines relies on accurately identifying neoepitopes capable of eliciting strong immune responses. T cell receptor (TCR)-epitope interactions are fundamental to cancer immunotherapy. Traditional computational approaches focus primarily on epitope-major histocompatibility complex (MHC) binding, often overlooking the critical contribution of TCR binding. Furthermore, the clinical applicability of existing methods is constrained by fragmented pipelines that require separate workflows for variant calling, HLA typing, and independent peptide-MHC (pMHC) or peptide-TCR (pTCR) evaluation stages. Results: We present DeepPROTECTNeo, a unified deep learning framework that integrates genomic variant detection, HLA typing, high-affinity pMHC binding prediction, variant-driven TCR repertoire mining, followed by a hybrid transformer-Convolutional Neural Network dual-branch feature extractor with an explicit cross-attention-based deep learning model for TCR-epitope binding prediction. Our reverse vaccinology-inspired biologically informed architecture integrates Bidirectional Long short-term memory (Bi-LSTM) sequence features, convolutional-attention physicochemical/evolutionary descriptors via gated fusion, and TCR numbered contextual embeddings to enable residue-level interpretable modelling. Under a strict TCR-split strategy, it achieved a mean AUROC of 0.7856 and AUPRC of 0.7932 outperforming six state-of-the-art predictors by 4-5% with tight inter-fold stability. The architecture maintains high robustness against structural hard negatives and imbalanced datasets, successfully recovering 18 of 34 validated high-affinity neoepitopes from a patient-specific cancer cohort. Conclusions: Experiments results demonstrate that DeepPROTECTNeo is a powerful, reliable end-to-end neoantigen prioritization framework that effectively models complex TCR-epitope interfaces directly from clinical sequencing data, providing a robust interpretable foundation to accelerate personalized cancer immunotherapy.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.1101/2025.01.04.631301",
      "metadata": {
        "doi": "10.1101/2025.01.04.631301",
        "version": "3",
        "authors": "Das, D.; Bhaduri, S.; Mitra, P.",
        "category": "bioinformatics",
        "type": "new results",
        "license": "cc_by_nc_nd",
        "institution": "IIT Kharagpur: Indian Institute of Technology Kharagpur"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.1101/2024.12.20.629771:v3",
      "title": "Encoding of natural variability in a dexterous motor skill over multiple days in the cortex of freely behaving mice",
      "summary": "Skilled, goal-directed movements exhibit trial-to-trial variability even in experts, particularly in response to dynamic environmental conditions or when perfect repetition is not required for success. Identifying where, to what extent, and how stably this variability is encoded in the nervous system is essential for understanding how learned movements are robustly maintained over time yet flexibly executed on each trial. We record calcium fluorescence activity in forelimb motor cortex (M1), a key node in the multi-areal network responsible for movement control, in freely-moving mice of both sexes as they performed a self-paced, precision reach-to-grasp task. High trial counts and rich single-trial variability enable rigorous statistical analysis of moment-to-moment movement encoding across matched behavioral sets over five days. Approximately 80% of recorded neurons significantly encoded paw, digit, and head movements during reaching, as quantified using linear models. Across days, encoding similarity shows a small but measurable decline that increases with the interval between recording sessions. This drift is heterogeneously distributed across the population, with many neurons retaining high encoding similarity even in sessions four days apart, as assessed using shuffle controls and comparison to encoding for trial-averaged movements. Thus, over the timescale examined, M1 is capable of maintaining stable encoding of movement details at the level of single cells, even for complex, sensory-guided tasks like reach-to-grasp. Together, these results raise the question of whether downstream circuits support consistent behavior by preferentially relying on neurons with greater stability or instead through population-level readout that is robust to a modest level of representational change.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.1101/2024.12.20.629771",
      "metadata": {
        "doi": "10.1101/2024.12.20.629771",
        "version": "3",
        "authors": "de Laittre, E. A.; MacLean, J. N.",
        "category": "neuroscience",
        "type": "new results",
        "license": "cc_by_nc_nd",
        "institution": "University of Chicago"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.1101/2024.09.08.611898:v2",
      "title": "MorphoNavigator-3D: Generalizable single-cell phenotyping of cancer spheroids using Bayesian-optimized deep-learning workflows",
      "summary": "Accurate quantification of drug responses in 3D tumor-immune co-cultures remains challenging because complex spatial architecture and cellular heterogeneity limit the interpretability of bulk viability assays. Here, we present MorphoNavigator-3D ('Morphological Navigator in 3D';MoNa-3D), an automated framework for high-resolution, annotation-free single-cell analysis in complex 3D co-cultures. The approach integrates optimized live-cell staining, deep learning-based segmentation, and Bayesian optimization (BO) to adapt end-to-end image-analysis workflows across diverse experimental conditions. MoNa-3D was applied to clear cell renal cell carcinoma (ccRCC)-immune cell 3D-spheroid co-cultures, exposed to PI3K/mTOR pathway inhibitors and immunomodulatory compounds in a high-content imaging-based drug screen. The pipeline was used to extract multiscale phenotypic features encompassing ATP-based cell viability, morphology, nuclear remodeling, spatial dispersion, and immune infiltration. This analysis resolved distinct drug-induced phenotypes: PI3K/mTOR inhibitors promoted spheroid disintegration, nuclear enlargement, and immune exclusion, whereas immunomodulators preserved spheroid architecture and T-cell engagement. Multivariate phenotypic integration distinguished drug classes and revealed intra-class variation, including divergent spatial responses to dual PI3K/mTOR versus mTORC1 inhibition. These phenotypes were consistent with known drug mechanisms, supporting the biological interpretability of the framework. Together, these findings establish MoNa-3D as a generalizable platform for multidimensional phenotypic profiling across complex 3D multicellular systems, supporting applications in drug discovery, tumor-immune interaction studies, and precision oncology.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.1101/2024.09.08.611898",
      "metadata": {
        "doi": "10.1101/2024.09.08.611898",
        "version": "2",
        "authors": "Mogollon, I.; Feodoroff, M.; Nylund, A.; Montedeoca, A.; Atarsaikhan, G.; Neto, P.; Horvath, P.; Rannikko, A.; Cerullo, V.; Pietiainen, V.; Paavolainen, L.",
        "category": "cancer biology",
        "type": "new results",
        "license": "cc_by_nc_nd",
        "institution": "Institute for Molecular Medicine Finland -FIMM, Helsinki Institute for Life Sciences -HiLIFE, University of Helsinki, Helsinki, Finland"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    },
    {
      "source": "biorxiv",
      "source_id": "10.1101/2023.11.16.567496:v2",
      "title": "PanScreen: A Comprehensive Approach to Off-Target Liability Assessment",
      "summary": "Drug development projects are getting increasingly more expensive while their success rate is stagnating. Safety issues attributed to off-target binding represent a major reason for the failure of new drugs. Besides desired on-target binding, small molecules may interact with off-targets, triggering adverse effects. Therefore, the development of novel methods for early recognition of such issues that are resource-efficient and cost-effective becomes vital. Here, we introduce PanScreen, an online platform for the automated assessment of off-target liabilities. PanScreen combines structure-based modeling techniques with state-of-the-art deep learning methods to not only predict accurate binding affinities but also give insight into potential modes of action. We show that the predictions are approaching experimental accuracy found in public datasets and that the same technology can also be used for other research areas, such as drug repurposing. Such fast and inexpensive methods allow researchers to test not only drug candidates, but all small molecules that might come into contact with a human organism for potential safety concerns very early in the development process. PanScreen is publicly available at www.panscreen.ch.",
      "published_date": "2026-09-06",
      "url": "https://doi.org/10.1101/2023.11.16.567496",
      "metadata": {
        "doi": "10.1101/2023.11.16.567496",
        "version": "2",
        "authors": "Sellner, M. S.; Joos, F. L.; Odermatt, A.; Lill, M. A.; Smiesko, M.",
        "category": "bioinformatics",
        "type": "new results",
        "license": "cc_by_nc",
        "institution": "University of Basel"
      },
      "fetched_at": "2026-09-09T08:17:44.457Z"
    }
  ],
  "next_cursor": null
}