Search bioRxiv⌕ Search

Biology subjects

Yang, Y.

Publications and source records attributed to Yang, Y..

At least 307 records · Page 17Linked to original sources

Modeling the effect of temperature on species coexistence

O_LITemperature reshapes organismal performance and species interactions, yet competition models rarely treat the declining warm side of thermal performance curves explicitly, even though that regime is likely to become increasingly important under climate warming. C_LIO_LIWe develop a density-dependent generalized Lotka-Volterra framework for pairwise exploitative competition in which effective competition coefficients depend on relative temperature-dependent consumption, and we analyse coexistence using the structural feasibility domain. C_LIO_LIWithin this model class, one result is robust: pairwise structural coexistence is maximized when competitors have equal effective consumption, so with symmetric overlap the temperature of maximal coexistence is the temperature at which their consumption thermal performance curves intersect. C_LIO_LIStronger ecological predictions are parameter dependent. In particular, whether coexistence declines more steeply under warming than under cooling, and whether the coexistence maximum for species with different thermal optima is shifted toward the lower optimum, depend on thermal-curve shape, relative peak heights, baseline competition, resource overlap, and any temperature dependence in carrying capacities. C_LIO_LIFor the illustrative asymmetric unimodal curves analysed here, shared optima produce maximal coexistence near the optimum and a steeper decline under warming than under cooling, whereas different optima produce an intermediate coexistence peak biased toward the lower optimum. A qualitative comparison with classic Drosophila pairwise competition experiments at 19{degrees}C and 25{degrees}C is consistent with these expectations. C_LIO_LIBecause the empirical comparison relies on broad thermal categories, unequal species groups, and binary pairwise outcomes, it should be interpreted as a proof of concept rather than a definitive quantitative test. More generally, our results clarify which aspects of temperature-dependent pairwise coexistence are robust consequences of thermal asymmetry and which are contingent on parameterization. C_LI

ecology↗

Adapting CRISPR-associated transposons for rapid and high-throughput reverse genetics

CRISPR-associated transposons (CAST) use guide RNAs to direct their transposition and are being harnessed as tools for programmable genome engineering across diverse bacterial species. However, CAST systems have not been adapted for high-throughput genetic screening. Here, we present MultiCAST, a streamlined platform for rapid and scalable guide RNA-directed transposon insertion in bacteria. MultiCAST generates targeted insertions in a single step through conjugative delivery of conditionally replicative plasmids encoding the CAST enzymatic machinery and a selectable mini-transposon expressing the guide RNA. By leveraging the inserted guide sequence as a molecular barcode, MultiCAST enables pooled, high-throughput genetic screens using only amplicon sequencing. We identified factors that influence transposition efficiency and the accuracy of insertion frequency measurements derived from guide sequencing. Adjusting the ratio of donor and recipient strain during conjugation mitigates guide-transposon "crosstalk", in which a single recipient cell acquires multiple donor plasmids containing distinct guides. Furthermore, we developed a machine learning-based predictive model for selecting highly active guides based on target sequence features that strongly correlate with activity. The nucleoid-associated protein H-NS was also found to inhibit CAST activity, providing a mechanistic explanation for variable insertion frequencies among non-essential genes. To demonstrate the scalability of MultiCAST, we screened a pooled mutant population created from >5,200 guides targeting 88 genes in E. coli across twelve nutrient conditions, accurately identifying genes with condition-specific fitness effects. The simplicity, speed, and throughput of MultiCAST make genome-scale functional screens more accessible across a wide range of bacterial species. SignificanceEfficient gene disruption is essential for understanding bacterial gene function, but traditional genetic approaches are labor-intensive and generally not well-suited for high-throughput studies. We developed MultiCAST, a simple and scalable method that harnesses guide RNA-directed CRISPR-associated transposons for targeted bacterial gene disruption. MultiCAST enables single and pooled transposon mutagenesis in a single step and eliminates the need for complex sequencing library preparation protocols by using the guide sequence as a quantifiable surrogate for mutant abundance. This approach allows thousands of mutants to be generated and screened simultaneously across multiple conditions using only amplicon sequencing. By dramatically reducing the time, cost, and complexity of reverse genetics, MultiCAST opens new possibilities for genome-scale functional studies, accelerating the discovery of bacterial gene functions.

microbiology↗

Genetic Ablation and Multi-Omics Profiling Reveal CEP55 as a Key Driver of Tumorigenesis in Diverse Cancer Models

BackgroundCEP55 is a centrosomal protein with emerging oncogenic roles. It is overexpressed in many cancers, where it drives genomic instability, phenocopies PTEN loss and hyperactivates the PI3K/AKT pathway, thereby promoting aggressive and therapy-resistant tumors. MethodsWe developed an inducible Cep55 knockout (KO) mouse model as well as generated primary, immortalized (SV40), and transformed (E1A/Ras) mouse embryonic fibroblasts (MEFs) for functional and proteomic assays. Tumorigenesis was studied using E1A/Ras MEF transplantation and a Pten-deficient genetically engineered mouse model (GEMM). Multi-omics apparatus including proteomics, and spatial transcriptomics, histopathology, immunobloting and functional assays were employed to elucidate underlying mechanisms. Findings were cross-validated using human cancer datasets. ResultsCep55 ablation remodeled the extracellular matrix (ECM), disrupted integrin and oncogenic signaling, reduced AKT/ERK activation, and induced stress pathways. Cep55 knockouts (KO) cells showed impaired proliferation, migration, invasion, and adhesion. In vivo, unlike the embryonic lethality observed in constitutive KOs, the inducible Cep55 deletion was well-tolerated in adult mice. Strikingly, tumors derived from Cep55-null EIA/RAS-transformed MEFs exhibited delayed onset and progression. In the genetically engineered cancer-prone mouse model, Cep55 deletion on a Pten-deficient background led to a greater than seven-fold increase in median survival. Spatial transcriptomics on cancerous tissues revealed that CEP55 regulates ECM remodeling, integrin expression, trafficking, and cell adhesion, supporting its critical role in tumor progression to metastasis. ConclusionCEP55 is dispensable for adult homeostasis but essential for tumorigenesis, especially with PTEN loss. Its deletion suppresses transformation, delays tumor growth, and prolongs survival, supporting CEP55 as a therapeutic target in PTEN-deficient cancers. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC="FIGDIR/small/685219v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@3d81e8org.highwire.dtl.DTLVardef@1bd5a7org.highwire.dtl.DTLVardef@167ecf3org.highwire.dtl.DTLVardef@1f57b95_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

DNA Framework Nanoreactor for Programmable Membrane Fusion

Membrane fusion is a fundamental yet transient process that has long resisted direct structural and kinetic dissection. Here we introduce a DNA framework vesicle (DFV) nanoreactor that transforms this elusive biological phenomenon into a programmable, visualizable, and quantifiable process-a nanoreaction confined in space yet extended in time. By embedding lipid membranes and SNARE proteins within precisely defined DNA apertures, DFVs convert stochastic vesicle collisions into geometry-controlled fusion events with tunable kinetics. Cryo-electron microscopy resolves a complete sequence of six intermediates, revealing how nanoscale confinement reshapes the energetic landscape of bilayer merger. Quantitative fluorescence and nano-flow cytometry further establish a direct link between spatial design and fusion probability. Extending this concept to living cells, DFVs enable controllable membrane fusion and augmentation on VAMP2-expressing membranes, achieving direct cytosolic delivery of functional siRNA via fusion-driven transfer rather than endocytosis. This framework bridges structural precision and functional mimicry, offering a unified platform to reconstruct, quantify, and harness membrane fusion as a programmable process for synthetic biology and nanomedicine.

bioengineering↗

LRP8 is a Receptor for Yellow Fever Virus

Yellow fever virus (YFV), an arbovirus causing substantial human morbidity and mortality, was the first human virus discovered over a century ago. The live-attenuated 17D vaccine is among the most successful vaccines in medicine. Despite the importance of YFV, its receptor has remained unknown. Here, we performed a barcoded, genome-wide human ORF library screen and identified LRP8 (also named APOER2) as a receptor for YFV. We show that LRP8 expression specifically boosts YFV infection in cell lines by promoting entry. AAV-mediated expression of human LRP8 in mouse liver aggravates infection and pathology. LRP8 knockdown abolishes YFV infection in brain cells, primary human hepatocytes, and notably in mosquitoes. Biochemically, LRP8 directly interacts with YFV particles via the viral envelope protein. This function of LRP8 is conserved across species, particularly in mosquitoes and primates. A soluble LRP8 decoy protein can block YFV infection in vitro and in mice, providing a potential therapeutic or prophylactic strategy. Our findings provide groundwork for understanding YFV entry, tropism, and pathogenesis, and may enable development of novel therapeutics to treat YFV infection.

microbiology↗

Episodic memories enable powerful algorithms for goal-directed decision making that are context-aware and explainable

Most current methods for goal-directed action selection in the face of changing goals and contingencies require DNNs or LLMs. Therefore they are less suited for implementation in edge devices, where low energy-consumption is imperative. The brain shows that similar functionality can be produced with just 20W, even with low precision of synaptic weights. In addition, it endows our action selection with explanations in terms of prior experience, a capability that is missing in those learning approaches where prior experiences are compressed into parameter values. We show that experimental data from neuroscience and cognitive science suggest a concrete alternative where experiences are organized into cognitive maps. It only requires local online learning in shallow networks with binary synaptic weights, and provides explanations for selected actions in terms of related prior experiences. This brain-inspired approach also requires substantially fewer computation steps for navigation in abstract state spaces with deterministic or stochastic actions.

neuroscience↗

Engineering Linear Cap-independent mRNA Vaccines with Intrinsic Adjuvanticity for Potent Cancer Immunotherapy

mRNA cancer vaccines have shown promising efficacy in early-phase clinical trials, but existing platforms struggle to boost antitumor efficacy without added cost or complexity. Here, we present a streamlined linear cap-independent RNA (LciRNA) cancer vaccine platform that achieves stable expression in vivo without 5 capping or ribonucleotide modification, and innately stimulates immune responses to enhance antitumor immunity. By fusing a UPA protective sequence, composed of a viral exoribonuclease-resistant RNA (xrRNA) and a poly(A) binding protein (PABP) motif, with an optimized Enterovirus A internal ribosome entry site, LciRNA resists 5 exonuclease decay and drives superior in vivo expression. Mechanistically, UPA sequence not only impedes exonuclease-mediated decay but also recruits RNA-binding proteins to stabilize LciRNA. Moreover, LciRNA robustly activates dendritic cell pattern-recognition receptor pathways, promotes dendritic cell maturation, and upregulates proinflammatory signals. In murine melanoma and HPV-associated tumor models, it elicits strong systemic and intra-tumoral T cell responses and superior tumor control, demonstrating how immune stimulation-translation synergy underpins its efficacy. This work establishes a next-generation cost-effective mRNA cancer vaccine platform with simplified production and enhanced efficacy, highlighting immuno-translation coupling as a paradigm for future mRNA cancer vaccines.

bioengineering↗

Variable and conserved features of copy-back viral genome populations generated de novo during Sendai virus infection

Copy-back viral genomes (cbVGs) are generated during the replication of negative-sense RNA viruses when the polymerase drops off from the genome and reattaches to the nascent strand. cbVGs have strong immunostimulatory properties and impact infection outcomes. Despite their importance, the composition and mechanisms of de novo cbVG generation and accumulation remain unclear due to challenges in obtaining cbVG-free virus stocks (clean stocks). Here, we obtained several clean stocks by independently rescuing recombinant Sendai virus (SeV) six times and verified their cleanliness through PCR, RNA sequencing, and absence of immunostimulatory activity. High multiplicity-of-infection passaging of clean stocks produced six high-MOI passaged stocks, each with distinct cbVG populations. Among them, polymerase drop-off (break) positions occurred throughout the genome, while polymerase reattachment (rejoin) positions preferentially occurred near the trailer end. Few common breaks were observed between stocks, while there was a hot rejoin region near the trailer end. In each stock, a few cbVG species dominated and remained stable across passages, all conforming to the rule of six, regardless of length. Low-abundance cbVGs were variable across passages, indicating the continuous generation of new cbVGs, despite the stabilization of a subset of species. Intriguingly, cbVG species which originated from polymerase drop-off at or close to nucleotide 1 were present in all stocks, suggesting that cbVG species originating at the 3 end of the genome are conserved products of SeV replication.

microbiology↗

Cell cycle-driven epigenetic resetting maintains stem cell fate for shoot branching

Adult mammalian stem cells typically maintain stem cell identity through proliferative quiescence. In contrast, we demonstrate that stem cell maintenance in Arabidopsis bud precursor cells requires active cell-cycle progression. Inhibiting division silences the shoot meristem marker gene SHOOT MERISTEMLESS (STM) and promotes differentiation. Whereas proliferation dilutes H3K27me3 levels to counteract silencing. Meanwhile, we identified two classes of transcription factors recruiting polycomb repressive complex 2 (PRC2) to epigenetically silence STM. The balance between these forces establishes a cell cycle-coupled epigenetic "Sisyphus" mechanism that maintains pluripotency. This cell fate switch is bistable; modeling and experimental data confirm that prolonged quiescence triggers irreversible differentiation. We propose that sequence-dependent PRC2 recruitment in plants enables precise silencing of fate-determining genes, while cell proliferation sustains pluripotency by resetting epigenetic marks.

plant biology↗

Three transcription factors coordinate the archaeal cell cycle progression through a regulatory braking point mechanism

Archaea of the order Sulfolobales execute a well-structured cell cycle program similar to that of eukaryotic cells. However, unlike eukaryotes, archaea lack cyclins and cyclin-dependent kinases and thus the mechanism of cell cycle regulation remained enigmatic. Here, we show that three essential ribbon-helix-helix domain transcription factors, namely, aCcr1, aCcr2, and aCcr3, play pivotal roles in controlling the cell cycle progression in the thermoacidophilic archaeon Saccharolobus islandicus. Coordinated expression of aCcr1 during M-G1 phase, aCcr3 during G1-S phase, and aCcr2 throughout the cell cycle ensures the timely transcription of the key genes that define the cell cycle phases. These include genes involved in chromosome dimer resolution, chromosome segregation, cell division, chromatin organization, DNA replication and repair, protein phosphorylation and degradation and metabolisms of amino acids, tRNA and carbohydrates. The synergy between aCcr1, aCcr2, and aCcr3 is achieved through their differencial affinities for the promoters and the levels of protein expression. We propose that the global regulation of the Sulfolobales cell cycle may be achieved not through transcriptional activation, but rather by repression of the key genes during strategic moments of the cell cycle. We propose a braking point model for the cell cycle control in Sulfolobales, which may represent a simple evolutionary intermediate on the way to the more complex cell cycle regulation in eukaryotes.

microbiology↗

Elevated Temperatures Representing Heatwave Conditions Shift Active Nitrifying Communities and Their Viruses in Tidal Flats and Agricultural Soils

Global heatwave intensification associated with climate change will impact the nitrogen cycle, yet its effect on specific nitrifier groups or their interactions with viruses remains unclear. Using 13CO2-DNA-based stable isotope probing (SIP) coupled with metagenomics, we show that elevated temperatures associated with heatwave conditions restructure active nitrifying communities and their viruses in Yangtze River estuary tidal flats and adjacent agricultural soils. In tidal flats, high temperatures shifted active ammonia-oxidizing archaea and bacteria (AOA and AOB), and nitrite-oxidizing bacteria (NOB) from marine to terrestrial ecotypes. In contrast, heatwave conditions stimulated terrestrial ecotypes of AOA but suppressed AOB in agricultural soils. 13C-labeled nitrifier-infecting viruses also showed temperature-driven shifts in activity, lifestyle, and auxiliary metabolic genes in concert with hosts. Notably, AOA viruses carried the plastocyanin gene, potentially augmenting host metabolism. These findings demonstrate heatwaves drive complex shifts in nitrifier communities and their interactions with viruses, impacting global nutrient cycling under climate extremes.

microbiology↗

A systematic comparison of cooperation and coordination across behavioural, psychological, and neural scales

Cooperation and coordination are the two fundamental mechanisms for enhancing social welfare. However, the intrinsic differences between the dynamics of cooperation and coordination remain elusive, particularly from an interpretable perspective that bridges behavioural, psychological, and neural scales. Here, we compare and analyze cooperation and coordination within a unified framework by assigning participants to an adjustable public goods game for iterated real-time interactions. By integrating model-free behavioural patterns and psychological intentions, we show that individuals are driven by increased flexibility and are more susceptible to peer influence in decision-making under cooperation. While under coordination, it is easier to reach the group consensus, inspiring individuals to stick more closely to their existing behavioural patterns and the default social norms. Furthermore, although peer punishment can enhance reciprocal contributions in all scenarios, the detailed impact and the resultant adverse phenomena (anti-social punishment) in cooperation and coordination are different. Notably, behavioural motive differences are also reflected in the neural responses recorded via fNIRS, in which coordination is associated with activation of the rTPJ and more consistent inter-brain synchronization in the dmPFC, while there is a negative correlation between dmPFC-rTPJ connectivity and contributions under cooperation. In addition, rTPJ during the punishment phase is significantly activated compared with the investment phase. Our study systematically reveals the fundamental differences between cooperation and coordination at the multi-scale levels, which not only deepens the understanding of reciprocal behaviour in social groups, but also provides a foundation for designing targeted incentive mechanisms.

animal behavior and cognition↗

Calcium transient was triggered by Na+ influx in phase 0 and regulated by Ca2+ influx in phase 2 of the action potential in adult rat left ventricular cardiomyocyte

BackgroundCa2+-induced Ca2+ release (CICR) has been the prevailing model in cardiomyocytes for over 50 years. However, whether Na+ influx plays a direct role in triggering Ca2+ release has remained unclear. We previously discovered that action potential (AP) phase 0 triggered Ca2+ release while phase 2 regulated the decay phase during the Ca2+ transient (CT). We hypothesized that CICR might only exist under experimental conditions, not during physiological AP cycles. MethodsSimultaneous recordings of ion currents and CT from the same rat left ventricular cardiomyocyte were employed to investigate the temporal relationship between cation influxes and CT. ResultsThe reactivation time for CT was approximately 250 ms. AP phase 0 triggered the CT, while phase 2 only regulated CT width. Pulses from -40 to +80 mV with 6 ms duration were applied to validate whether the reverse Na+/Ca2+ exchanger (NCX) could trigger CT. Pulses of -40 and -30 mV with 6 ms duration induced giant Na+ influx and tail current, but only Na+ influx triggered CT, not tail current. Pulses from -20 mV to +80 mV with 6 ms duration triggered CT via tail current, not via reduced Na+ influx. In Ca2+ free solution, Na+ influx was still able to trigger CT until sarcoplasmic reticulum (SR) Ca2+ content was remarkably reduced. Moreover, increased reverse NCX current induced by ramp-like depolarizing pulses did not trigger CT but widened its shape. Additionally, when SR function was destroyed by caffeine (20 mM/L), field stimulations caused progressively elevated cytosolic Ca2+ levels, indicating that SR has a buffering function for maintaining cytosolic Ca2 concentration. ConclusionsOnce Na+ influx triggers CT, Ca2+ influx cannot trigger a second CT during an AP cycle due to the limitation imposed by the reactivation time. Na+ influx might enter SR via an unknown channel or transporter at the terminal cisternae during the AP and induce Ca2+ release by acting on the SR luminal-facing site of the ryanodine receptor 2 (RyR2) channel and/or by increasing the positive potential gradient across the SR membrane.

biophysics↗

REST elevation-dependent chromatin remodeling and alternative Grk6 transcript synthesis hyperactivates Cxcr4-Sdf1 signaling in cerebellar granule cell progenitors

RE1 Silencing Transcription Factor (REST) is a repressor of transcriptional initiation of genes involved in neurogenesis. Here, we show that conditional REST elevation in cerebellar granule cell progenitors (CGNPs) of RESTTG mice perturbed foliation, increased cell migration, and sustained C-X-C motif receptor 4 (Cxcr4) signaling, a pathway key to postnatal CGNP migration. Mechanistic studies uncovered a novel role for REST in controlling transcript diversity and exon skipping in CGNPs. Alternative transcript expression was detected in known Cxcr4 signaling regulator, G-protein-coupled receptor kinase-6 (Grk6). Further analysis of Grk6s isoform expression revealed an upregulation of a transcript lacking exon 10a (Grk6-207) in RESTTG CGNPs. Grk6-207 expression in wildtype CGNPs hyperactivated Cxcr4 signaling and increased chemotaxis. Structural modeling of Grk6-207 predicted changes in active site conformation and interactions with Cxcr4 and {beta}-Arrestin-1, supporting impairment of Cxcr4 signaling desensitization. Interestingly, REST elevation promoted increased chromatin accessibility at the exon10a-10b junction and exon 10a exclusion. Integrated multiomic analyses identified the enhancer of zeste (Ezh2) as a potential mediator of alternative transcript generation which demonstrated increased occupancy at the exon10a-10b locus in RESTTG CGNPs. Pharmacological inhibition of Ezh2 downregulated Grk6-207, confirming a role for Ezh2 in Grk6 exon10a exclusion and the increased migration in RESTTG CGNPs. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=67 SRC="FIGDIR/small/682654v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@166db32org.highwire.dtl.DTLVardef@1c0c5e0org.highwire.dtl.DTLVardef@ff2d6borg.highwire.dtl.DTLVardef@fed170_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Computer Vision Methods for Spatial Transcriptomics: A Survey

Spatial transcriptomics (ST) enables the simultaneous measurement of gene expression and spatial localization within tissue sections, providing unprecedented opportunities to dissect tissue architecture and functional organization. As a relatively new omics technology, bioinformatics has driven much of the innovation in ST. However, within these frameworks, "spatial" information is often reduced to locations and relationships between molecular profiles, without fully leveraging the wealth of submicron morphological detail and histological knowledge available. Advances in computer vision-based artificial intelligence (AI) are opening exciting new avenues beyond conventional bioinformatics approaches by modeling complex histological patterns and linking morphology to molecular states. More excitingly, they bring fresh perspectives to potentially address key limitations of ST, including its high cost, limited clinical applicability, and reliance on twodimensional (2D) analysis of inherently three-dimensional (3D) tissues. For instance, models that predict ST directly from histology images enable "virtual sequencing," drastically reducing costs while integrating morphological insights from pathology with molecular biomarkers, thus accelerating clinical translation. Moreover, computer vision techniques can reconstruct pixel-aligned 3D tissue models, overcoming the technical barriers of 2D acquisition and advancing 3D spatial omics analytics. In this paper, we present the first systematic survey of computer vision AI models for ST analytics, categorizing approaches across architectures, learning paradigms, tasks, and datasets, and tracing their technological evolution. We highlight key challenges and future directions, offering a panoramic perspective on vision-driven ST and its potential to transform both basic research and clinical practice. The curated collection of vision-driven spatial transcriptomics papers is available at https://github.com/hrlblab/computer_vision_spatial_omics.

bioinformatics↗

Simple, Fast and Highly Efficient One-or Two-step Proteomic Preparation Enables Deep Profiling of Microgram-level FF and FFPE Tissues

Large-scale tissue proteomics requires workflows that are efficient, rapid, and repeatable across diverse samples. Herein, we present Simple Workflow for Integrated and Fast Tissue-preparation (SWIFT), which enables complete processing of fresh- frozen (FF) and formalin-fixed, paraffin-embedded (FFPE) tissues in either one- or two-step formats, while maintaining deep proteome coverage with high repeatability from low to microgram-level tissues. For FF tissues, an incubation process integrating lysis, reduction, alkylation, and digestion generates peptide samples directly from tissues in [≤] 1.5 h. For FFPE tissues, concurrent deparaffinization, rehydration, and de- crosslinking is achieved within 0.5 h, followed by one-step peptide preparation. Furthermore, our workflows eliminate desalting and offline cleanup steps, thereby reducing variability and total processing time. Using our methods, we identified up to [~]10,000 protein groups and [~]150,000 peptides across multiple mouse organs on timsTOF Pro. Repeatability was high (pairwise Pearsons r > 0.96 across six experimental replicates), with dynamic ranges spanning 6-7 orders of magnitude. Organ-enriched protein analysis identified functionally distinct proteins unique to each tissue Paired FF and FFPE analyses revealed preservation-induced shifts, with FFPE tissues showing reduced detection of membrane-associated and respiratory proteins, including mitochondrial Complex I. Together, our fast and simplified workflows enable deep tissue proteomics for large-scale clinical and translational studies in a cost- effective and widely-accessible manner.

biochemistry↗

The ecological dynamics and consequences of phytoplasma in a spring ephemeral

Ecologists have long sought to link within-population dynamics to patterns of species occurrence and persistence across the range. Theoretical models suggest pathogens have important implications for plant populations and perhaps even limit plant distributions, though more empirical evidence is needed, especially in wild plant populations. In the field, we characterized the infection dynamics of phytoplasma, a vectored and sterilizing bacterial pathogen, in wild populations of white trillium. We identified the highest molecular matches for the local bacterial strain and putative vectors. We then leveraged iNaturalist data to reveal patterns and potential drivers of phytoplasma occurrence across the range of white trillium. Within populations, we found that phytoplasma symptoms were more likely in low host density plots, where insects occupied a higher proportion of trillium, indicative of an encounter-dilution effect. Leafhoppers in the genus Empoasca were positive for phytoplasma, suggesting they are a candidate vector of disease between trilliums at our field site. The closest match to our local phytoplasma was related to Candidatus Phytoplasma pruni, ribosomal group 16SrIII-F. Phytoplasma symptoms were widely distributed across trilliums range, even at range edges, and probability of symptoms was significantly increased by proximity to cropland. We studied the impacts of a sterilizing, vector-transmitted pathogen on host plant populations and patterns of infection across host range. Our results suggest sap-feeding insects do not occupy all hosts at high host densities, thereby reducing transmission and leading to higher likelihood of finding infection at low host densities, and a higher proportion of host plants infected at low host densities. At a range-wide scale, we found evidence that the pathogen was able to persist across both the core and edge of host ranges. Thus, negative-density dependent sterilizing pathogens may challenge host populations across the range.

ecology↗

Voxel-accurate MRI-microscopy correlation enables AI-powered prediction of brain disease states

Magnetic resonance imaging (MRI) is essential for visualizing the healthy and diseased brain, yet the cellular basis of MRI signal and how it changes over time remain poorly understood. Here, we present BRIDGE (Brain Radiological Imaging with Deep-learning based Ground-Truth Exploration), a platform integrating in vivo MRI with in vivo two-photon (2P) and ex vivo super-resolution microscopy using a multi-step, iterative co-registration pipeline. It enables in vivo, longitudinal, and voxel-precise mapping of MRI signals to their cellular origins for the first time. The registered overlay reveals the cellular and anatomical origins of MRI signals and enables training of convolutional neural networks to enhance the effective resolution of MRI. Using BRIDGE, we identified a microenvironmental vessel biomarker for early metastatic colonization in patient-derived xenograft models of brain metastasis. In particular we found that distinct T2*-weighted hypointense lesions correspond to reduced blood flow and erythrostasis in perimetastatic capillaries. In glioma, longitudinal intravital studies further demonstrated direct correlations between non-vasogenic T2-weighted signal changes and patient-dependent tumor growth dynamics. Taken together, BRIDGE advances radiological interpretation by establishing a microscopic ground truth for MRI signatures over time, enabling deep learning-based predictive histology, and providing cellular-level insights into tumor microenvironment features with direct clinical imaging implications. Graphical abstractBRIDGE enables longitudinal voxel-to-voxel correlation and ground truth based automatic segmentation of MR images O_FIG O_LINKSMALLFIG WIDTH=177 HEIGHT=200 SRC="FIGDIR/small/680637v1_ufig1.gif" ALT="Figure 1"> View larger version (73K): org.highwire.dtl.DTLVardef@f1f64eorg.highwire.dtl.DTLVardef@1619e3eorg.highwire.dtl.DTLVardef@1dc2e7forg.highwire.dtl.DTLVardef@7097e1_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗