- BioRxiv Biochemistry
- BioRxiv Bioinformatics
- BioRxiv Biophysics
- BioRxiv Cancer Biology
- BioRxiv Pharmacology and Toxicology
- BioRxiv Systems Biology
- BioRxiv Zoology
- by Xu, A. Q., Hung, M. S., Chen, B., Sopena, M. L., Chakravarty, P., Camara, A., Calado, D. P.Booster vaccination can restore antibody titres and protection, but whether it improves long-term durability by expanding plasma cell (PC) numbers or also by shifting PC fate toward intrinsically longer-lived states remains unclear. Here we established longitudinal in vivo ground truth for PC persistence by combining PC-specific genetic timestamping, clonal tracking, and multi-timepoint single-cell profiling across spleen and bone marrow. We resolved PC longevity as a layered, non-binary architecture comprising short-, intermediate-, and long-lived programs, and showed that program identity is […]
- by Mojiri, S., Dobbs, J. M., Sachweh, J., Castillo, N., Ries, J., Mahamid, J.Super-resolution cryogenic correlative light and electron microscopy (SR-cryo-CLEM) integrates molecular specificity and structure on the single-molecule level, but contemporary approaches require low laser powers to preserve specimen vitrification. Here, we perform SR-cryo-CLEM via single molecule localization microscopy (SMLM) on thin biological lamellae and demonstrate that their geometry and minimally-absorbent composition permit excitation laser powers three orders of magnitude higher than standard cryo-EM grids, allowing improved localization precision and imaging speeds.
- by Wang, J., li, F., Zheng, X., Zhang, Y., Chen, J., Lv, G.Abstract Abscisic acid (ABA) is involved in Cd tolerance in Arabidopsis, but the underlying mechanisms are unclear. In this study, we revealed that the ABI5-WRKY45-LSU1 axis confers the tolerance of Arabidopsis to Cd stress. Under Cd stress, the biosynthesis of ABA is increased, and the expression of transcription factor ABI5 is upregulated. Accordingly, the abi5-8 mutants show increased Cd sensitivity. ABI5 directly binds the ABRE element in the WRKY45 promoter to activate its transcription. Overexpression of WRKY45 rescues the Cd-hypersensitive […]
- by Wold, E., Merrill, N. M., Serhan, H., Udager, A., Liu, C. J., Gu, N., Bao, L., Qin, Z., Heth, J., Soellner, M., Merajver, S. D., Morikawa, A.Patient-derived organoids from breast cancer brain metastases enable real-time drug sensitivity testing integrated with genomic profiling. Drug response varied by subtype and molecular alterations. PI3K inhibitors showed activity regardless of PIK3CA mutation status. Pronounced tumor heterogeneity highlighted the urgent need for effective therapies personalized for each patient. Functional assays and molecular matching can help tailor therapy for patients who need the most effective next treatment quickly and warrant further translational evaluation to address this unmet need.
- by Bate, J., Hardinge, P., Jathoul, A. P., Wilson, M. R., Murray, J. A. H.Museum collections of Coleoptera contain genetic material of potential interest to biotechnology, and non-destructive DNA extraction enables the preservation of important specimens with concomitant release of mitochondrial and genomic DNA. Mini-barcoding of regions of the mitochondrial cytochrome oxidase subunit I (MT-COI) gene helps identify and eliminate known species from further investigation. Here we identify a novel luciferase gene, using Consensus Degenerate Hybrid Oligonucleotide (CODEHOP) primers targeting the region of the luciferase gene spanning the fourth exon, intron, and fifth exon […]
- by Nazir, A., Wang, H., Lu, Z., Lau, J., Peale, F., Jesudason, R., Connolly, K. A., Andrusivova, Z., Lau, J., Gierke, S., Peng, L., Chan, S., Jiang, J., Rost, S., Lubeck, E., Simone, M. D., Daniel, B., McGinnis, L. M., Maddalo, D., Joshi, N. S., Garraway, L. A., Regev, A.Prostate cancer (PCa) is a lethal malignancy that displays profound resistance to immune checkpoint blockade (ICB), via mechanisms that are poorly understood. Here, we investigate the causes of CD8 T cell exhaustion and mechanisms of tumor progression in a PCa animal model, by single cell and spatial profiling, along a time course, following orthotopic transplantation of RB1/TP53/PTEN-deficient mouse organoids, competent to express neoantigens. The resulting tumors were castration resistant, consisting of largely basal and L2 malignant cells with upregulated inflammatory […]
- by Kroos, G. C., Fernandes, K., Seddon, P., Ashcroft, T., Gemmell, N. J.Airborne environmental DNA (eDNA) is a promising tool for detecting a wide range of taxa including threatened and invasive species, yet its application in management is constrained by a limited understanding of its temporal persistence, particularly in nature. We investigated the temporal persistence of airborne eDNA in a natural outdoor setting, using Bennetts wallaby Notamacropus rufogriseus as a case study. We captured airborne eDNA from a single Bennetts wallaby carcass, deployed in an area where wallabies are otherwise not present. […]
- by Wilhite, D. R., Miller, D., Schilz, A., Brown, M. B., Fennessy, J., Fennessy, S., Newman, K.Giraffe in human care are known to experience significant clinical issues related to their feet. To characterize normal foot anatomy, we analyzed six sets of front and hind feet from wild Angolan giraffe and one calf in human care. We used computed tomography, three-dimensional reconstruction, sagittal sections, and gross dissection to acquire as much gross anatomical detail as possible. Significant anatomical findings include the deep digital flexor tendon that is very gracile as it crosses the fetlock and proximal phalanges […]
- by Bhattiprolu, S.Three-dimensional organoid cultures have emerged as powerful models for studying human tissue biology, disease mechanisms, and drug responses. Fluorescence confocal microscopy of organoids generates complex volumetric image data that is increasingly analyzed using deep learning pipelines for cell segmentation, morphometry, and phenotyping. However, training and benchmarking such pipelines requires large annotated datasets, the manual curation of which is prohibitively expensive and time-consuming. Here we present a parametric, physics-based computational framework for generating synthetic 3D fluorescence organoid images with exact ground-truth […]
- by Shivashanmugam, T., Mehta, A.Neural correlates of consciousness are often evaluated along single dimensions, such as large-scale integration or metabolic activity, yet it remains unclear whether either is sufficient, or whether conscious states require the joint satisfaction of multiple biological constraints. Here, we evaluate the prediction that conscious states occupy a regime defined by the co-occurrence of sufficient metabolic support and preserved perturbational complexity. We performed a targeted cross-study synthesis of published benchmarks from [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) and transcranial magnetic stimulation combined […]
- by Kafetzopoulos, V.Large-scale brain activity can be described as walks on a connectome, and its dressed resolvent gives a compact walk-sum account of how signal flows among regions. A non-abelian extension of the resolvent introduces spectral-mode operators whose generators predict, empirically, that specific brain regions should display amplified cross-frequency phase-amplitude coupling with the rest of the brain. We refer to such regions as empirical cross-frequency generators. Methodologically, we introduce a joint cortical-subcortical source-imaging approach that combines a high-resolution cortical parcellation with a […]
- by Gordon, E. M., Rajesh, A., Chauvin, R. J., Labonte, A., Adeyemo, B., Dworetsky, A., Lynch, C. J., Krimmel, S. R., Cho, P., Wang, A., Baden, N. J., Scheidter, K. M., Monk, J., Metoki, A., Ren, J., Nishino, T., Park, Y., Rafka, E., Pruett, J. R., Kepecs, A., Liu, H., Fair, D. A., Liston, C., Woo, C.-W., Kay, B. P., Marek, S., Petersen, S. E., Sylvester, C. M., Schwarzlose, R. F., Raichle, M. E., Laumann, T. O., Dosenbach, N. U. F.Task fMRI and electrophysiology have revealed distributed, linked cortical patches with shared category preferences (e.g., faces, objects, places) smaller than cytoarchitectonic areas. Resting-state functional connectivity (RSFC) similarly showed that somato-cognitive action network (SCAN) nodes interleave with effectors (foot, hand, mouth), subdividing the precentral gyrus. Here, using multiple precision functional mapping (PFM) modalities (RSFC, task, lags), we discovered that most of association cortex is organized like face processing and SCAN, with small, discrete patches interconnected into chains. Such patch-chains densely tile […]
- by Soler-Saez, I., Galiana-Rosello, C., Grillo-Risco, R., Falony, G., Tepav?evi?, V., Vieira Silva, S., Garcia-Garcia, F.Biological sex is a key determinant in the onset and progression of multiple diseases. In multiple sclerosis (MS), females exhibit higher disease prevalence, earlier onset, and more pronounced inflammatory activity, whereas males tend to experience a more severe neurodegenerative course, characterized by accelerated central nervous system damage and increased brain atrophy. The gut microbiome has emerged as a critical factor in MS, as its composition can either ameliorate or exacerbate disease progression. In this study, we aimed to identify reproducible […]
- by Pallais, J. P., Razzoli, M., Rodriguez, P., McGonigle, S., Daugherty, A., Hillman, H., Verteramo, L., Schrank, P., Parthiban, P., Chang, X., Wang, H., Veglia, G., Koehl, J., Bose, M., Ehrlich, M. E., Salton, S., Araque, A., Lettieri Barbato, D., Revelo, X., Ruan, H.-B., Williams, J. W., Bartolomucci, A.Microglia, the resident macrophages of the central nervous system, are recognized for their heterogeneity and integral role in brain function and diseases. In the context of high fat diet (HFD) feeding and obesity, microglia become overactive, acquiring a prevailing lipid associated microglial phenotype (also known as LAM). Yet, how microgliosis is induced and regulated remains unclear. Here we report a key role for the Complement 3a Receptor (C3aR), on HFD-induced hypothalamic gliosis and weight gain in mice. HFD consumption leads […]
- by Huang, K., Marmor, G., van der Molen, T., Zhang, Z., Gicqueau, P., Reveles, J., Morrissey, K., Tang, J., Lu, L., Ilmi, K., Lue, J., Barba Zuniga, G., Miller, M. B., Kosik, K. S., Yang, H., Santander, T., Bullo, F., Hansma, P. K.Chronic pain presents a leading challenge in the world today for both clinicians and researchers. Because chronic pain is difficult to explain and treat, it is often managed with opioids despite providing limited relief and contributing to dependence and misuse. Persistent pain can be maintained by altered central nervous system processing even in the absence of distinct tissue damage or disease, which may limit the efficacy of conventional pharmacological therapies that target nociceptive signal transmission rather than maladaptive central nervous […]
- by Yang, Y., Zhao, L., Orouji, S., Zhu, Y., Johnson, R. L., Maxwell, D. S., Mica, I., Russell, K. P., Al-lazikani, B.Confirming target engagement in tumor experimental models remains a major challenge in oncology drug development. Pharmacodynamic biomarkers can help address this, but few systematic resources link drug targets to candidate biomarkers. We developed TargetTrace, a comprehensive resource to identify and prioritize pharmacodynamic biomarkers across nine key target classes, including transcription factors/cofactors, kinases, phosphatases, ubiquitin ligases, deubiquitinases, acetyltransferases, deacetylases, methyltransferases, and demethylases. Biomarker candidates were gathered from curated molecular interaction resources and refined using external annotations to improve accuracy. For enzyme […]
- by Dehghan Manshadi, M., Panchal, N. K., Sun, L.-Z., Setoodeh, P., Zare, H.Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide. Current treatments offer limited efficacy and no definitive cure, underscoring the urgent need for more selective and effective therapeutic strategies. This study investigated the synthetic lethality caused by co-targeting two metabolic genes, ATP citrate lyase (ACLY) and oxoglutarate dehydrogenase (OGDH), in HCC cells. Using valproic acid (VPA) and bempedoic acid (BA) as pharmacological inhibitors of OGDH and ACLY, respectively, we observed a strong synergistic effect in inhibiting the proliferation […]
- by Silva de Almeida, B. L., Bonidia, R., Bole, M., Avila-Santos, A., Stadler, P. F., Nunes da Rocha, U., de Carvalho, A. C. P. L. F.The prediction of biological sequence properties has traditionally relied on alignment-based methods that assume evolutionary homology and depend on curated reference databases. This, in turn, limits scalability and sensitivity for large or heterogeneous datasets, remote homologs, short sequences, and rapidly evolving genomic regions. Although Machine-Learning (ML) approaches offer alignment-free alternatives, their broader adoption is limited by: (i) the lack of standardized, externally validated benchmark models across diverse datasets, and (ii) the technical expertise required for feature engineering, model selection, and […]
- by Wang, Y., Reshetnikova, E., Katuwal, N. B., Bharti, V., Pereira, M. S., Oppong, B. A., Lee, D. A., Mittra, A., Freud, A. G., Vilgelm, A. E.CDK4/6 inhibitors are standard-of-care for metastatic estrogen receptor-positive (ER+) breast cancer, yet the development of resistance remains a significant clinical hurdle. While CDK4/6 inhibitors are primarily recognized for their ability to induce cytostasis, their role in modulating innate immune responses remains poorly defined. Here, we demonstrated that CDK4/6i treatment remodels the tumor cell surface to favor recognition and elimination by Natural Killer (NK) cells. Using a diverse biobank of patient-derived organoids (PDOs), we found that CDK4/6 inhibition robustly upregulated the […]
- by Wang, D., Jin, J., Qiao, J., Wei, L., Wu, S., Liu, Q.Experimental and predicted RNA three-dimensional structures are expanding rapidly, but RNA structure search still lacks a compact residue-level representation that supports database-scale comparison. Using family-held-out ablations across the currently available experimental RNA structure collection, we found that spatial-neighbour features are markedly more informative for family-level discrimination than conventional backbone and base descriptors. Building on this result, we developed RiboSeek, a search framework based on a 20-letter geometric alphabet (RS-20), an 80-letter structure-and-base composite alphabet (RS-80). Across family-level classification and retrieval […]