arXiv · q-bio.QMBuildable★ flagship
Ranking AI-guessed biology facts so human experts review the likeliest-true ones first.
Biomedical databases rely on 'annotations' — statements linking, say, a gene to a function — and AI can now generate huge numbers of candidate annotations, but a human expert still has to verify each one, which is slow and expensive. This work builds a system to triage those candidates: score how plausible each one is, so curators tackle the most promising ones first instead of wading through them randomly. It works from a biomedical knowledge graph (a network of biological entities and their known relationships), turns entities into numerical 'embeddings' that capture their connections, and trains classifiers to judge each proposed link. A clever detail is how they generate believable fake examples ('negative sampling' using biological communities) so the classifier learns a reliable sense of what's true versus false. It matters because it directly attacks the curation bottleneck that slows down turning raw biomedical data into trustworthy knowledge.
Technical view
The framework estimates the plausibility of candidate biomedical annotations using biomedical knowledge graphs (bioKGs). Starting from knowledge-graph embeddings, it trains relation-specific binary classifiers with a community-based negative sampling strategy to produce reliable confidence scores that prioritize candidates for expert curation. The community-based negatives are the key methodological choice, aiming for harder, more realistic negatives than random sampling and thus better-calibrated plausibility estimates. Practitioners can plug in existing KGE methods and apply the relation-specific classifier plus community-negative-sampling recipe to rank their own candidate annotations before manual review.
arXiv · q-bio.NCConceptual
Tweaking how sensor noise depends on distance brings back an AI agent's drive to actively seek out information.
'Active inference' is a framework where an artificial agent picks actions partly to reduce its own uncertainty about the world, a incentive researchers call 'epistemic value' — like a curious explorer. Earlier work showed that in a common simplified setting (linear-Gaussian, meaning the world's dynamics and sensor noise follow nice bell-curve statistics) this curiosity mathematically vanishes: the agent behaves exactly like a passive filter that gets no benefit from choosing where to look. This paper finds a fix: if the sensor's accuracy gets worse depending on the agent's own state, like a camera that gets noisier the farther away it points, the curiosity-driven incentive to act reappears. That makes sense because the agent's actions can now indirectly control how noisy its future observations will be, giving it a real reason to move toward better vantage points — a subtle but important design consideration for AI and robotic agents balancing 'doing the task' against 'gathering better information.'
Technical view
In standard linear-Gaussian active inference, the Kalman-filter-like agent's Expected Free Energy epistemic term becomes a state/action-independent constant, collapsing the information-seeking drive; the only previously known fix required control entering the state dynamics multiplicatively. This paper shows a distinct, unexplored fix on the observation side: making the observation noise covariance R(x) state-dependent (e.g., accuracy degrading with distance) while running the standard first-order Gaussian filter (R evaluated at the predicted mean) restores a genuine epistemic drive, because the posterior covariance becomes coupled to the controllable latent mean. This gives active-inference/POMDP practitioners a concrete, minimal model modification — state-dependent R rather than multiplicative control-dynamics coupling — to recover exploration incentives in otherwise information-blind linear-Gaussian agents, relevant to sensor-planning and active-SLAM-style applications.
arXiv · q-bio.NCConceptual
Two nostrils beat one when animals sniff along surfaces chasing a scent trail, new physics estimates show.
Some animals, like sharks and even humans to a degree, smell in 'stereo' using two nostrils, similar to how two ears help you locate sound. This paper asks a simple physics question: when is having two nostrils actually useful compared to just one? Using rough back-of-the-envelope calculations, the researchers found that stereo smelling pays off specifically when odor concentrations jump around a lot in space and when the air near a surface carries smell in long, smooth streaks. In practice, this means two nostrils are most valuable when an animal is tracking a scent trail along the ground or a wall, hunting for the sharp 'edges' where the smell suddenly changes.
Technical view
The authors use scaling/order-of-magnitude analysis of odor plume statistics to compare bilateral (stereo) versus unilateral (mono) olfactory sensing. They show the advantage of stereo sampling scales with the magnitude of local concentration gradients and with the spatial correlation length of turbulent odor fields, both of which are elevated in near-surface boundary layers compared to open air. This predicts stereo olfaction should be selected for in surface-trail-following behaviors rather than open-air plume tracking, giving a testable, mechanism-level hypothesis for comparative olfactory neuroscience and robotic odor-sensor array design.
arXiv · cs.LORunnable
A logic program that reads a family tree and calculates the odds each relative carries a disease gene.
Many inherited diseases follow simple rules discovered by Gregor Mendel, like whether a gene is on a regular chromosome versus the X or Y sex chromosome. Genetic counselors use family history — who has symptoms, who doesn't — to estimate the probability that a particular family member carries the disease-causing gene, even without testing everyone's DNA. This paper builds a computer program called mendelprob.pl using 'probabilistic logic programming,' a style of coding that mixes formal logic rules with probability, to automate these calculations across multiple generations. Users can plug in what's known about a family's symptoms and genotypes, and the program calculates the likelihood of inheritance patterns automatically instead of a counselor doing it by hand.
Technical view
The authors present mendelprob.pl, a ProbLog (probabilistic logic programming) implementation that encodes Mendelian inheritance laws to compute posterior probabilities of genotypes and phenotypes across pedigrees for two-allele genes, covering autosomal, X-linked, and Y-linked modes of inheritance. The system takes user-specified genotype/phenotype observations at various pedigree nodes and propagates probabilistic inference through generations via ProbLog's logic-program semantics rather than bespoke Bayesian network code. This gives genetic counseling workflows a reusable, declarative tool for automated risk assessment that could be extended to more complex multi-allele or linked-gene disorder models.
arXiv · q-bio.QMBuildable
A math toolkit untangles how fat molecules move between cell compartments over time, from messy real data.
Cells contain many different tiny compartments (organelles), and lipids (fat molecules) constantly move between them, changing over time — this creates data with multiple intertwined dimensions: which lipid, which compartment, and when. That kind of data is naturally represented as a 'tensor,' basically a multi-dimensional table, and this paper builds a pipeline to analyze it even when measurements are noisy or missing, using mathematical techniques (HOSVD and CP decomposition) that essentially find the hidden patterns underlying the mess. Applying this to real mammalian lipid-transport data, they successfully identified specific lipid-organelle pairs that change quickly, and groups of lipids that rise and fall together across compartments and time. This gives biologists a way to spot meaningful patterns in complex multi-dimensional datasets that would otherwise be too tangled to interpret.
Technical view
The authors develop an end-to-end tensor decomposition pipeline (using HOSVD and CP/PARAFAC methods) augmented with a binary mask to handle missing entries and an explicit measurement-error framework, applied to a three-way tensor of lipid identity × organelle localization × time. The method recovers latent factors representing lipid-organelle pairs with fast temporal dynamics and co-varying lipid modules across organelles and time, effectively performing unsupervised multi-way factor analysis on sparse, noisy multi-omics data. This provides a template other researchers could adapt to any sparse multi-axis biological tensor (e.g., proteomics across cell types and conditions) by swapping in their own mask/error model.
arXiv · quant-phBuildable
Machine learning trims the huge quantum search space needed to simulate molecules on today's noisy quantum computers.
Simulating molecules accurately on a computer, to find things like their lowest-energy stable shape, requires exploring an enormous number of possible electron configurations — far too many to check exhaustively. A method called Quantum Selected Configuration Interaction uses a quantum computer to sample promising configurations, then a classical computer polishes the answer, avoiding some of the training difficulties ('barren plateaus') that plague other quantum algorithms. This paper adds a machine learning tool called a Restricted Boltzmann Machine, essentially a pattern-recognition network, to intelligently pick out the smaller set of configurations that actually matter, instead of relying only on generic symmetry rules. Combined with an existing chemistry technique called Density Matrix Embedding Theory, this should make molecular simulations cheaper and more accurate on near-term quantum hardware.
Technical view
The paper introduces QSCI-RBM, which trains a Restricted Boltzmann Machine to generate a compact, physically-relevant electron configuration subspace for Sample-based Quantum Diagonalization / Quantum Selected Configuration Interaction, replacing symmetry-only configuration recovery that tends to overinflate subspace size. This is integrated into a Density Matrix Embedding Theory (DMET) framework, so the RBM-selected subspace feeds fragment-level correlated wavefunction reconstruction, reducing classical diagonalization cost while retaining accuracy. Practitioners working on hybrid quantum-classical electronic structure methods could adopt this RBM-based selection step as a drop-in replacement wherever QSCI/SQD configuration recovery is currently symmetry-constrained only.
arXiv · q-bio.GNRunnable
An AI trained on genomes reads tumor mutations and predicts what they'll look like on a cancer scan.
Scientists still don't know what many genes do, and standard methods for finding cancer-driving genes only work well for genes that are frequently mutated, missing rarer but still important ones. This study pairs a genome-analyzing AI model (Evo 2) with ordinary hospital imaging scans of tumors, using the AI to score how severe each mutation likely is, without needing to train it specifically for this task. By statistically linking those severity scores to features extracted from tumor scans across hundreds of patients with kidney, liver, and breast cancers, the researchers discovered dozens of new candidate cancer genes that standard mutation-frequency methods had missed. This shows that combining genome AI with existing medical images, which hospitals already collect, can be a cheap new way to find important genes.
Technical view
The method uses Evo 2, a genomic foundation model, to assign zero-shot severity scores to every somatic mutation across three TCGA cohorts (cRCC, HCC, BC; n=340), then correlates per-gene aggregated severity with radiomic features extracted from paired tumor imaging segmentations, controlling for total mutation burden as a confounder. In TCGA-cRCC (n=162) this recovers known renal cancer drivers and identifies 46 additional FDR-significant genes absent from curated cancer gene panels, demonstrating that imaging phenotypes can serve as a genome-wide association readout for rare mutations that frequency-based driver discovery misses. This establishes a generalizable radiogenomic screening framework combining any genome LLM's variant-effect scores with routine radiomics, replicable on other TCGA cohorts with paired imaging and sequencing data.
arXiv · q-bio.BMBuildable
An AI model designs antibodies by learning how they fold around a specific target's exact binding site.
Antibodies are the immune system's molecular weapons, and each one is shaped to grab onto a specific target (antigen) at a precise spot called an epitope. Existing AI models that generate protein sequences are good at handling single proteins in isolation but struggle to design antibodies tailored to a specific target's shape, because that requires understanding both molecules together, especially at the exact contact point. This paper introduces AAMFM, a model that jointly learns antibody sequence, antibody structure, and detailed antigen information (its 3D shape and known binding sites) all at once, using a special 'adapter' component to fuse these different data types into one shared representation. The goal is AI-designed antibodies that are more likely to actually bind their intended target effectively, useful for developing new antibody-based drugs.
Technical view
AAMFM is a multimodal foundation model that jointly represents antibody sequence and structure conditioned on antigen context, incorporating antigen geometric interface data and epitope annotations through a cross-modal adapter to enable joint antibody-antigen interaction modeling in a shared latent space, going beyond prior single-chain protein language models that lack explicit epitope-level pairing. The model is further fine-tuned toward functional relevance (details of the objective are cut off in the abstract), suggesting a downstream task such as binding affinity or developability optimization. This architecture is directly relevant to practitioners building epitope-targeted antibody generation pipelines, offering a template for fusing structural antigen context into sequence-generative antibody design rather than relying on antigen-agnostic generation followed by separate screening.
arXiv · q-bio.QMRunnable
New software tells scientists how much to trust a body-chemistry simulation when half its variables are invisible.
Biologists build math models (ODEs, equations that track how quantities change over time) to simulate things like cell signaling or disease spread, but usually only some of the variables can actually be measured in the lab while others stay hidden. This paper tackles the question of how confident we should be in such a model's predictions when so much is unseen. Their trick is to mix two techniques: a resampling method (leave-one-out jackknife+) that calibrates uncertainty using the data you do have, plus a sensitivity-based math shortcut that estimates uncertainty for the hidden parts without needing expensive simulations. The result, packaged as software called CUQDyn1 Plus, gives researchers a faster, more practical way to know how much to trust their models compared to slow traditional statistical (Bayesian) approaches.
Technical view
The framework pairs leave-one-out jackknife+ empirical calibration for observed state variables with sensitivity-matrix-based Gaussian uncertainty propagation for unobserved (hidden) states in nonlinear, potentially weakly identifiable ODE systems. CUQDyn1 Plus implements global parameter estimation, covariance propagation, bootstrap trajectory uncertainty bands, and simulation-based calibration diagnostics, with built-in comparison against full Bayesian workflows and automated reproducibility reporting. This offers a computationally cheaper alternative to MCMC-based UQ for high-dimensional systems biology models, and practitioners can plug in their own ODE model and observation set directly into the software.
arXiv · q-bio.PEConceptual
A biologist argues the famous population-growth equation is built on a mathematical lie about smooth, gap-free time.
The logistic equation is one of biology's most famous formulas, used to predict how a population grows and levels off as resources run out. This author pushes back on it philosophically: the equation assumes population change happens smoothly and continuously, but real births, deaths, and interactions happen in discrete, lumpy events with gaps in between that the equation glosses over. They argue that if you instead build a model from the ground up — tracking individual organisms and their interactions (a 'micro-scale' view) — the honest large-scale description isn't the logistic equation at all, but something closer to tracking matter or energy flowing through the system. The bigger claim is that biology currently lacks its own proper mathematical language and has been borrowing ill-fitting tools from physics.
Technical view
The piece is a conceptual critique arguing that the differential (continuous-time) formulation of the logistic equation implicitly assumes continuity of underlying demographic processes that real populations violate, since birth/death/interaction events are discrete and undefined between time steps. The author contends that deriving a macro-scale population equation from an explicit micro-scale (individual-based, interaction-level) model yields dynamics resembling mass/energy-flow accounting rather than the classical logistic form. This is a theoretical/foundational argument rather than a new model or dataset, aimed at motivating alternative mathematical frameworks purpose-built for biological (as opposed to physical) dynamics.
arXiv · q-bio.PEConceptual
Math shows microbial communities can collapse outright if there aren't enough food sources to go around.
Microbial communities — like the trillions of bacteria in soil or your gut — compete for shared resources, and scientists want to know what makes such a crowded community stable rather than collapsing. This paper studies an improved mathematical model (MiCRM) that accounts for 'cross-feeding,' where one microbe's waste product becomes another's food, something earlier simpler models ignored and which caused them to underestimate how much total life a community can support. Using a mathematical simplification that separates fast and slow processes, the authors work out exactly when such a community can even exist (feasibility) and remain stable over time. One striking finding: if there are fewer distinct food resources than there are competing species, the community simply cannot persist.
Technical view
The paper analyzes persistence, feasibility, and stability of the microbial consumer-resource model (MiCRM), which extends the classical MacArthur consumer-resource framework by incorporating cross-feeding (metabolic byproduct exchange) among species. Using a slow-fast timescale separation/approximation under simplifying assumptions, the authors derive conditions under which communities are feasible and stable, proving non-persistence when the number of resources M is less than the number of consumer species S. This gives ecologists and theorists analytical (rather than purely simulation-based) criteria for community viability that could inform experimental design or extend to more general cross-feeding network structures.
arXiv · cs.AIConceptual
Your brain isn't one repeated circuit scaled up — so maybe AI shouldn't be either, this paper argues.
Today's most powerful AI models (like large language models) are built from one repeating building block, the Transformer, used identically whether it's processing text, images, or sound. This paper points out that the brain doesn't work that way at all — different brain regions have physically different wiring suited to different jobs, like dense layers for spatial vision versus thick layers for tracking motion over time. The authors argue this isn't just an interesting biological fact but a real design flaw in AI: relying on one repeated structure for everything, rather than specialized structures for specialized tasks, may be limiting how efficiently AI systems learn. They point to convolutional neural networks (an older AI design tailored specifically for images) as proof that baking in the right structural assumptions can beat brute-force scaling, needing far less data to succeed.
Technical view
This is an architectural-critique paper contrasting the AI field's convergence on a single repeated Transformer block across modalities with neuroscience's cytoarchitectural evidence (Brodmann areas, Patch-seq single-cell data) that different cortical regions use structurally distinct circuits — e.g., dense Layer 4 for spatial encoding vs. thick Layers 5/6 for temporal integration — matched to distinct computational functions. The authors use CNNs' local receptive fields and hierarchical depth as historical evidence that hard-coding the right structural prior yields strong sample efficiency, and argue the field abandoned this lesson in favor of a homogeneous scaling paradigm. It's a position/synthesis paper rather than a new model, aimed at motivating heterogeneous, function-specific architectures ('system of systems') as a research direction rather than one dominant repeated module.
arXiv · q-bio.NCConceptual
One simple equation explains why tilted lines around you make 'up' feel like it's leaning too.
If you stare at tilted lines in your peripheral vision, your sense of which way is 'up' subtly shifts — a well-documented illusion. Earlier researchers (Li and Matin) found three separate rules describing exactly how this shift behaves depending on the tilt of one or more lines. This paper shows all three rules are really just one underlying principle in disguise: your brain seems to average the orientations of everything you see using a specific mathematical trick (treating each line's angle as doubled, then finding its average direction), similar to how you'd find the overall direction a group of arrows points. That single elegant formula predicts all the previously separate observations, suggesting the brain has one unified mechanism for judging 'vertical' and eye level from visual context, rather than several ad hoc rules.
Technical view
The authors derive a closed-form model showing Li & Matin's three empirical regularities of the visually induced perceived vertical (linear shift from a single tilted line, linear summation of two lines, cancellation under symmetric tilts) all follow from one equation: the induced vertical equals half the argument of the first circular moment of stimulus orientations in doubled-angle space, φ = ½arg(c₁), c₁ = Σ A_j e^{i2γ_j}. This is mathematically equivalent to the principal axis of the orientation structure tensor or an orientation population vector, and the angle-doubling is required because orientation is axial (θ ≡ θ+π), forcing a circular-mean readout. This 'orientation order-parameter' (PLUMB) model gives vision scientists a single testable computational primitive to fit/predict induced-vertical data instead of three separate empirical rules, and is straightforward to implement and validate against existing psychophysics datasets.
arXiv · q-bio.GNBuildable
Scientists crack open an AI trained on DNA to check if it really 'knows' what genes turn other genes on.
AI models trained on raw DNA sequences (genomic language models) can predict useful things about gene regulation, but nobody really knows what's going on inside them — whether they've learned genuine biological concepts or just superficial patterns in the data. This paper uses a technique borrowed from AI interpretability research: training a second, simpler model to decompose the big model's internal activity into distinct, human-understandable 'features,' then testing whether those features are real by actively intervening on them and checking the effect. Applied to two different DNA-processing AI models, they find thousands of features that correspond to known DNA patterns where proteins called transcription factors bind and control genes — but they also show a naive way of checking these features is misleading because it gets confused by simple DNA composition quirks (like GC content).
Technical view
The authors apply sparse dictionary learning (top-k sparse autoencoders) to hidden activations of two genomic foundation models with different tokenization schemes — Nucleotide Transformer (6-mer) and DNABERT-2 (byte-pair encoding) — recovering thousands of monosemantic features that align with transcription-factor binding motifs. They then use causal intervention (activation patching/ablation) rather than passive correlation to validate that these features causally drive model behavior, and demonstrate that naive validation against position weight matrices is confounded by GC-content composition, requiring composition-controlled baselines. This gives a reusable pipeline — SAE training plus causal intervention plus confound-controlled validation — for auditing whether 'concepts' inside any genomic (or other biological sequence) foundation model are genuine versus artifactual.
arXiv · q-bio.GNRunnable
AI models trained on public cell data might be 'cheating' on the very tests used to grade them.
AI models for analyzing single cells (like Geneformer and scGPT) are trained on huge public databases of cell measurements — but the standard tests used to grade how good these models are also draw from those same public databases. That's a problem: a model might look like it's cleverly generalizing to new data when it's actually just recognizing data it already memorized during training, the same way a student might ace a test because they saw the answer key beforehand. The authors built an auditing tool, scContam, that checks each cell in a benchmark for two signs of this 'contamination': a fingerprinting technique that flags overlap with the training data, and an attack-style method that detects if the model is suspiciously overconfident on cells it's seen before. They find two of the most popular benchmarks are massively contaminated — over three-quarters of their cells show clear overlap with training data — casting doubt on many published performance claims.
Technical view
scContam is a per-cell contamination-auditing framework combining a MinHash-based gene-set fingerprinting signal (checked against the explicit pretraining corpus, e.g. Genecorpus-30M) with a loss-based membership inference attack (MIA-scFM) to detect training-set leakage into evaluation benchmarks. Applied across four scIB integration benchmarks and three single-cell foundation models (Geneformer, scGPT, UCE), the audit finds 80.4% and 77.0% of cells in the widely-cited PBMC 3k and CELLxGENE pancreatic islet atlas benchmarks respectively show significant fingerprint overlap (p<0.05) with pretraining data, while post-cutoff datasets show much less overlap — implying reported zero-shot benchmark gains may substantially reflect memorization rather than generalization. Practitioners evaluating or publishing scFM benchmarks can apply scContam directly to flag or filter contaminated cells before drawing generalization conclusions.
arXiv · stat.MEBuildable
A neural network learns to predict the shape of a curve — like a brain scan outline — from mixed data types like images and numbers.
In fields like neuroimaging, researchers often care about the pure 'shape' of an outline or contour — imagine tracing the boundary of a brain structure — after stripping away its size, position, rotation, and starting point, since only the shape itself carries meaningful information. This paper builds a deep-learning model that predicts such shapes from a mix of different data types at once, like combining a patient's scan images with simple numeric measurements. The clever trick is representing each curve as a complex number function (a compact math representation of 2D shapes) and showing that the 'average' shape you want to predict is mathematically the top pattern extracted from how the shape's variation relates to the input data. To make this work with messy real inputs, they build custom neural network pieces — like using splines for simple numbers and convolutional networks for images — that automatically respect the fact that shape shouldn't change if you rotate, resize, or shift a curve, and it also works even when the curve's data points are unevenly or sparsely sampled.
Technical view
The method models open planar curves as complex-valued functions and shows the conditional full Procrustes mean shape is the leading eigenfunction of the conditional covariance operator given multimodal covariates. To estimate this covariance surface, the authors introduce a deep conditional covariance smoother with modality-specific encoders (e.g. splines for scalar covariates, CNNs for image covariates) — a flexibility classical spline-based smoothers lack — while the architecture is constructed to be invariant to translation, rotation, and scale by design, and to handle sparse/irregularly sampled curves. This gives practitioners in shape analysis (e.g., neuroimaging contour prediction) a differentiable, mixed-covariate regression framework that could be extended to closed curves, higher-dimensional shapes, or alternative encoder architectures for other covariate types.
arXiv · q-bio.NCBuildable
Feeding AI eye-tracking video shows why your center vision reads faces, edges see the world.
Our eyes see sharply in the very center (where you're looking) and blurrily at the edges, and different brain regions specialize in each: central vision zones overlap with face- and word-recognition areas, while peripheral zones overlap with scene-recognition areas. This study asks whether that split could just emerge naturally from the kind of visual input we get in daily life, rather than being hardwired. Researchers took real head-mounted video and eye-tracking data of people going about their day, then trained an AI vision model separately on center-only crops, edge-only crops, and blurred edge crops (mimicking how peripheral vision actually resolves detail), using a self-teaching method that learns from raw video without labels. They then tested what each version of the AI got good at. The point is to show that specialized brain regions might arise simply from what kind of visual information is available at each location, not some innate blueprint.
Technical view
The authors use egocentric video and gaze data from the Visual Experience Dataset to train ResNet-18 encoders via SimCLR contrastive learning under three eccentricity-constrained input conditions: gaze-contingent foveal crops, raw peripheral crops, and peripheral crops passed through a NeuroFovea perceptual transform that approximates peripheral pooling/loss of acuity. Downstream evaluations (implied to include tasks like face/word vs. scene recognition) test whether fovea-trained and periphery-trained networks spontaneously specialize in ways that mirror primate cortical eccentricity biases. This is a self-supervised, naturalistic-statistics test of whether task-relevant coding differences can emerge purely from the differing information content available at each retinal eccentricity, without built-in inductive biases. Replication would involve reproducing the eccentricity-conditioned cropping/NeuroFovea pipeline on VEDB and comparing learned representations against known face/word/scene-selectivity benchmarks.
arXiv · q-bio.PEConceptual
Math explains how a shark can wait 156 years just to have babies.
The Greenland shark is astonishingly long-lived — females don't even mature until around age 156, and some individuals may live nearly 400 years. This paper uses a mathematical theory called 'evolutionary entropy,' which describes how variable or spread-out a population's births and deaths are across age, to figure out what kinds of reproductive timelines are even possible for an animal with such an extreme lifespan. Instead of observing sharks directly (hard to do over centuries), the researchers use population math with named threshold rules to back out plausible scenarios: how long a generation lasts, when reproduction is concentrated, and where the 'sweet spot' for reproductive timing would be to keep entropy maximized. They find the numbers push generation times toward two centuries or more. This matters because it gives biologists a rigorous way to reason about the life histories of species we can barely study directly.
Technical view
The authors apply age-structured evolutionary entropy theory — using the homogeneity and critical-threshold theorems for open-group (non-equilibrium) populations — to constrain plausible reproductive schedules for Somniosus microcephalus given estimated female maturity (~156 years) and lifespans approaching 400 years. They compute a critical threshold q_c ≈ 0.9763, indicating the population sits in a near-unity persistence regime, and derive longevity-calibrated scenarios for generation time and reproductive quantiles that straddle the boundary between finite-maximum and asymptotic entropy regimes, implying generation times near or above two centuries. This is a demographic-theoretic (not empirical/genetic) analysis, useful as a template for applying entropy-based life-history theory to other extreme-longevity species where direct longitudinal data is infeasible. Replication would require the same open-group entropy formalism applied with updated empirical maturity/mortality estimates as they become available.
arXiv · cond-mat.stat-mechBuildable
A fix for the math trick scientists use to fast-forward molecular simulations without lying to themselves.
Simulating how molecules move and fold is so computationally expensive that scientists often only get short bursts of simulation, then use a mathematical shortcut called a Markov state model to stitch those bursts into a picture of the molecule's long-term behavior. The catch is that this shortcut is normally only accurate if you pick a coarse time-step that's long enough to smooth over the model's built-in bias, which unfortunately erases the fast, often most interesting, events. This paper shows a way to get unbiased answers at any timescale, even short ones, without needing to lengthen the time-step, by reformulating how the transition data is combined and weighted. That means researchers can now catch both the fast, fleeting molecular events and the slow overall behavior accurately from the same underlying data. It matters because it removes a long-standing tradeoff in one of the most widely used tools in molecular simulation science.
Technical view
Standard Markov state models (MSMs) build a single transition matrix from MD trajectory data at a chosen lag time, which must be long enough for the coarse-grained dynamics to appear Markovian — but this induces systematic bias and obscures faster sub-lag-time processes. The paper introduces a reformulation that yields provably unbiased coarse-grained observables at any fixed lag time and for any fixed coarse-graining, in the limit of infinite properly-weighted data, by restructuring how transition probabilities are estimated/combined rather than relying on a single global transition matrix. This effectively decouples the bias-variance tradeoff from lag-time selection, letting practitioners recover short-timescale kinetics that were previously washed out by the Markovian-lag requirement. Researchers building MSM pipelines (e.g., in PyEMMA/MSMBuilder-style workflows) could adopt this estimator to get lag-time-robust rate and mechanism estimates from existing trajectory data.
arXiv · cs.LGRunnable
Sorting breast cancer patient records by AI reveals hidden groups doctors might miss.
Hospitals generate huge amounts of electronic health record data on breast cancer patients, but that data is often too complex and high-dimensional for a human to spot patterns in directly. This study uses 'unsupervised clustering' — an AI technique that groups similar patients together without being told in advance what the groups should be — to find hidden subpopulations in three separate real-world datasets. To make the clustering work better, they first compressed the data using UMAP, a technique that squashes many messy variables down into a simpler map while preserving the relationships between patients. They then checked how good the resulting patient groups were using several statistical quality scores. The goal is to surface medically meaningful patient subgroups that could inform more personalized diagnosis or treatment, patterns that might otherwise stay buried in the raw records.
Technical view
The authors apply DBSCAN density-based clustering to three independent EHR-derived breast cancer datasets, both directly and after UMAP dimensionality reduction as a preprocessing step, to test whether nonlinear embedding improves cluster structure recovery. Clustering quality is assessed quantitatively via DBCV, DCSI, and DISCO indices rather than relying on visual inspection alone. The results reportedly confirm that UMAP preprocessing enhances DBSCAN's ability to recover well-separated, medically relevant clusters across datasets. Practitioners working with heterogeneous EHR tabular data could replicate this UMAP+DBSCAN+multi-index-validation pipeline as a template for unsupervised subtype discovery in other disease datasets.
arXiv · cs.LGBuildable
One software framework, swap a config file, retarget the same neural net to three different science problems.
Modern AI models that understand 3D molecular or material structures ('equivariant graph neural networks') are powerful, but usually each one is custom-built for a single task, so scientists can't easily reuse them elsewhere. This paper introduces GEqTrain, a framework that separates three things that are normally tangled together: how the input data is described, how the model is built, and what task it's being trained to do. Instead of rewriting code for a new project, a scientist edits a configuration file that declares what data fields to use, what model pieces to stack, and what loss function to optimize. The same core AI backbone can then be pointed at wildly different problems, like converting a coarse molecular simulation back into atomic-level detail, predicting how atoms will behave in an NMR scan, or generating new molecular structures. This matters because it turns a one-off research model into a reusable scientific tool.
Technical view
GEqTrain is a Hydra-configuration-driven framework that decouples dataset semantics (typed node/edge/graph-level fields), model composition (a shared equivariant GNN backbone with declaratively assembled stacks), and training objectives (losses, schedules) so a single backbone can be retargeted across tasks via config changes rather than code changes. The authors demonstrate this on three distinct 3D scientific tasks within one software stack: coarse-grained-to-atomistic backmapping of biomolecular systems, NMR chemical shift prediction in molecular solids, and equivariant generative modeling. This addresses a real engineering pain point in the equivariant-GNN ecosystem (e.g., NequIP/Allegro-style models) where task-specific forks proliferate; practitioners could adopt GEqTrain's config schema to add new 3D scientific tasks without reimplementing equivariance-preserving infrastructure.
arXiv · cs.LGBuildable
Hospital AI forgets stale treatment habits but keeps its memory of your actual biology intact.
AI systems that help doctors in the ICU can quietly get worse over time because hospital treatment protocols change, even though patients' underlying biology doesn't. The problem with most fixes is that they update the whole AI model at once, which risks corrupting what it correctly learned about stable human physiology just to catch up with shifting institutional habits. This paper's approach splits the AI into two separate streams, one that models the patient's biology and one that models treatment decisions, and only updates the treatment part when it detects both a change in the data patterns and a drop in accuracy. It also keeps an automatic log explaining which treatment factors triggered each update, and, when making a prediction, pulls in relevant, date-matched medical research to justify itself, similar to how a doctor might reference recent literature. The result is a system meant to stay accurate and explainable even as clinical practices evolve underneath it.
Technical view
The architecture structurally decouples physiological from treatment representations into two streams, restricting parameter updates to the treatment stream, gated by a dual trigger combining distributional drift detection and accuracy degradation, with automated audit logs attributing each adaptation event to specific treatment features and their importance shifts. At inference, an attribution-driven Temporal RAG module retrieves patient-specific, era-matched PubMed evidence anchored to the patient's dominant physiological features to ground predictions. Experiments use 84,792 MIMIC-IV ICU stays spanning 2008-2022 evaluated under strict chronological (not random) splitting, directly testing robustness to real temporal protocol drift rather than i.i.d. generalization. This offers a template for building drift-resilient clinical decision support: separate the covariate-shift-prone components from the stable ones, gate updates accordingly, and log/ground predictions for auditability — replicable on other multi-year EHR cohorts with documented protocol changes.
arXiv · cs.LGBuildable
An AI that predicts your blood sugar learns your body's own quirks, not just averages.
For people with Type 1 Diabetes, predicting how blood glucose will change soon is crucial for catching dangerous highs or lows before they happen. Most existing prediction tools are trained on population averages or only weakly adjust for the individual, so they miss the fact that everyone's body responds differently. This paper proposes a system called SCGP that explicitly learns a compact 'fingerprint' of each person from their contextual data, separate from the glucose trend itself, and then uses that fingerprint to condition its predictions. By keeping 'who this person is' and 'how glucose is currently moving' as separate pieces instead of mashing all the data together early on, the model can tailor its forecasts more precisely to each individual. The aim is more accurate, personalized glucose forecasts that could give patients and doctors more useful early warnings.
Technical view
SCGP (Subject-Conditioned Glucose Prediction) is a multimodal deep learning architecture that learns a compact subject-specific embedding from contextual (non-glucose) inputs and uses it to condition a separate glucose-dynamics model, explicitly avoiding early fusion of heterogeneous modalities in favor of late conditioning. This design targets a known weakness in population-level or implicitly-personalized T1D forecasting models: failure to capture individual variation in glucose response dynamics. The separation of subject characterization from temporal dynamics modeling is the core architectural claim, positioned as improving subject-specific forecast accuracy over baseline approaches. Practitioners building CGM (continuous glucose monitor) forecasting pipelines could adopt this two-branch conditioning pattern as a modular addition to existing time-series forecasters.
arXiv · q-bio.NCConceptual
A fly keeps one steering goal in mind not by picking a winner, but by muting all options equally.
When a fly walks toward a target, its brain holds that direction as a localized 'bump' of neural activity among a ring of goal-direction cells called FC2 neurons. Scientists wondered whether the fly's brain keeps this bump singular and clean through a competitive 'winner takes all' process, where the strongest direction actively suppresses rivals, similar to how a compass-like circuit elsewhere in the fly brain works. Using a complete wiring diagram of a fly brain (a connectome), the researchers traced the actual connections and found that inhibition between these neurons is delivered almost equally to all of them by a small set of relay cells, rather than being concentrated between nearby competing directions. This global, blanket-style inhibition lacks the local reinforcing connections a true winner-take-all competition would need. The finding suggests the fly's brain doesn't actively choose among competing goals in this circuit, it just cleanly maintains whatever single goal was already set by another part of the brain.
Technical view
Using dense connectomic reconstruction from a single FlyWire brain, the authors trace the inhibitory circuitry acting on FC2 neurons (fan-shaped body cells encoding goal heading as a bump of activity) and find inhibition is delivered almost uniformly across all FC2 neurons by four FB5A cells, with only a minor distance-dependent contribution from hDelta interneurons and negligible direct FC2-FC2 connections. This connectivity pattern lacks the local recurrent excitation required for a ring-attractor-style winner-take-all competition (unlike the fly's compass circuit), implying the global inhibition functions as normalization/gain control that maintains a single clean activity bump rather than actively arbitrating between competing goal candidates. The result reframes goal maintenance in FC2 as a passive stabilization mechanism, with goal selection presumably occurring upstream; researchers modeling central-complex navigation circuits can use this connectome-derived inhibition topology (global vs. local) as a concrete constraint when building or testing ring-attractor versus normalization models.
arXiv · cs.LGBuildable
Reading brain waves to guess what video someone just watched.
This study asks whether you can peek at electrical signals recorded directly from the surface of the brain (called ECoG, from electrodes placed in epilepsy patients for medical reasons) and figure out what category of thing a person was watching in a video, like a face or an animal. The researchers fed these messy, noisy brain recordings into deep learning models — the same kind of AI used for image and speech recognition — training them on fewer than 50 examples per category, which is a tiny amount of data. They tried different network designs and filtered the brain signals into different frequency bands to see which parts of the recording actually carried useful information. The payoff is a step toward brain-computer interfaces that could someday interpret what a person is perceiving just from their neural activity.
Technical view
Using a 17-subject clinical ECoG dataset with video stimuli, the authors benchmark end-to-end deep learning architectures for decoding visual semantic category from raw time-series intracranial signals under a low-sample regime (<50 examples/class). They compare frequency-band-filtered inputs and network architectures, using mixup augmentation to combat data scarcity, then analyze the best model to identify which spectral bands, time windows, and cortical regions drive classification. This provides a template for feasibility studies of ECoG-based semantic decoding and a reference architecture/preprocessing pipeline (band filtering + mixup) for low-data neural decoding tasks.
arXiv · q-bio.PEConceptual
In food webs, being popular can help species survive — or doom them.
Ecosystems are networks where species interact — eating each other, competing, or helping one another — and this paper studies a mathematical model of these networks to understand which species end up thriving versus dying out. A key factor is a species' 'degree,' meaning how many other species it interacts with, like how many friends someone has in a social network. Past models assumed the strength of each interaction was random and unrelated to how connected a species was, but real ecosystems often show that well-connected species interact differently than isolated ones. By building this connection-strength relationship into the model, the researchers found two opposite outcomes are possible: sometimes highly-connected 'hub' species are favored and survive preferentially, and other times those same hubs are actually suppressed and more likely to vanish. This helps explain why some real ecosystems seem to reward being a generalist while others punish it.
Technical view
The authors extend the generalized Lotka-Volterra model (analyzed via dynamical mean-field theory) by introducing degree-dependent interaction strengths on a structured random interaction topology, rather than the usual i.i.d. interaction-strength assumption. Solving the resulting self-consistent mean-field equations, they identify two qualitatively distinct regimes — a hub-favored phase where high-degree species are preferentially viable (positive stationary abundance), and a hub-suppressed phase with the opposite trend. This gives ecologists a tunable analytic framework for testing how degree-correlated interaction strengths reshape stability and species survival in large random ecological networks, extendable to other structured-interaction generalizations of GLV.
arXiv · cs.LGConceptual
Can AI read your thoughts from a scalp cap? Turns out, not really — yet.
Some AI systems claim they can translate brain signals recorded from a cap on your scalp (EEG) directly into text, which would be huge for people who can't speak due to paralysis. But there's a catch: these systems only work when they're secretly given hints about the correct answer during testing, a trick called 'teacher-forcing' — without that crutch, they produce gibberish. This has led researchers to argue whether EEG actually contains enough real information to reconstruct language at all, or whether the models are essentially cheating. This paper designs a smarter test, borrowed from how neuropsychologists study brain function, and discovers that a major reason previous benchmarks failed is that EEG signals themselves are unstable over time, which had been muddying the results and fueling the debate. The findings help clarify what's realistically possible for future brain-to-text technology.
Technical view
The authors critique the widely-used EEG-to-text (EEG2Text) evaluation protocol, showing that models trained with teacher-forcing collapse to meaningless output under free-running (non-teacher-forced) decoding, which is the only realistic real-world deployment condition. Applying a neuropsychology-inspired benchmark design, they identify EEG signal instability (non-stationarity across trials/sessions) as a confound that has been misattributed to fundamental limits of linguistic decodability from EEG. This reframes the EEG2Text debate: rather than concluding EEG lacks decodable language information, the results suggest benchmark design and signal-stability handling are the primary bottlenecks, pointing future work toward stability-aware training/evaluation protocols rather than abandoning EEG as a modality.
arXiv · q-bio.PEConceptual
Feeding predators extra food can make their population dynamics wildly more complex.
When two predator species compete for the same prey, their population sizes over time can behave in surprisingly complicated ways — sometimes settling down, sometimes oscillating forever, sometimes crashing. Mathematicians already had a well-studied model (the Bazykin model) describing this competition, which includes realistic details like predators taking time to handle and digest prey. Separately, ecologists know that giving predators an 'additional food' source (used in real pest-control strategies to help keep harmful insect populations low) changes the dynamics too. This paper combines both ingredients into one unified model and rigorously maps out all the different long-term behaviors the system can produce depending on the parameters, finding that the system can have up to three different stable balance points. The practical payoff is a better mathematical foundation for designing biological pest control strategies that use supplemental feeding.
Technical view
The paper unifies the Bazykin predator-competition model (Holling type-II functional response, exhibiting a degenerate Bogdanov-Takens bifurcation of codimension 3 and a degenerate Hopf bifurcation of codimension ≤2) with an additional-food term, and performs a global bifurcation analysis of the combined system. They show the system admits up to three interior equilibria and characterize how additional food reshapes the bifurcation structure relative to the base competition model. This provides bifurcation-theoretic groundwork (equilibrium counts, degenerate bifurcation loci) that biological-control researchers could use to predict how supplemental feeding shifts a predator-competition system between stable coexistence, oscillatory, and extinction regimes.
arXiv · cs.LGBuildable
A biology-inspired shortcut for training neural nets works better if you tidy up its inputs.
Normally, training a neural network requires 'backpropagation,' a process that sends error signals backward through the exact same connections used going forward — which is powerful but considered biologically implausible for how real brains might learn. An alternative called Direct Feedback Alignment (DFA) instead sends error signals through fixed random connections, which is simpler and more brain-like, but it doesn't work as well as standard training. This paper investigates why DFA sometimes fails, finding the culprit is 'anisotropy' — essentially, imbalance or skew — that can creep in either from the pattern of neuron activity or from the pattern of errors being fed back. By specifically correcting for skew in the activity patterns, they achieve a large accuracy improvement (about 40 percentage points in certain controlled cases), and correcting error skew helps too. This kind of insight could make brain-inspired, backprop-free learning methods more practical and competitive.
Technical view
The authors decompose DFA's weight-update failure modes by noting the update is an outer product of a presynaptic-activity factor and a random-projected-error factor, either of which can introduce damaging anisotropy when high-variance directions carry task-irrelevant nuisance. Using controlled synthetic regimes, they isolate activity-conditioning (yielding ~40-percentage-point accuracy gains) from error-conditioning (1.77–7.53 point gains over vanilla DFA), and show the two corrections combine additively (0.40–0.90 extra points). Effects replicate across tanh and one-vs-rest output settings, giving a concrete recipe — separately whitening/conditioning activity and error statistics — for closing the gap between DFA and backpropagation without abandoning DFA's biologically-plausible fixed random feedback.
arXiv · q-bio.BMConceptual
Redesigning a workhorse enzyme so lab-made RNA comes out cleaner.
Most RNA vaccines and therapies (like mRNA COVID vaccines) are manufactured using a viral enzyme called T7 RNA polymerase, which is great at churning out RNA quickly and accurately targeting the right starting point. The problem is it also makes unwanted byproducts — extra bits of double-stranded RNA, oddly extended or cut-short RNA — which lower the yield and, worse, can trigger the immune system to attack the RNA product as if it were foreign, which is a safety concern for RNA drugs. Cleaning up these byproducts afterward is possible but always involves trading off purity against how much usable product you keep. Rather than cleaning up after the fact, this paper reviews the strategy of engineering the enzyme itself — tweaking its structure — so it makes fewer mistakes in the first place. This upstream fix could make RNA-based medicines cheaper, safer, and easier to manufacture at scale.
Technical view
This is a review synthesizing structural and mechanistic knowledge of T7 RNA polymerase byproduct formation — double-stranded RNA from self-priming/RNA-dependent RNA synthesis, 3'-extended transcripts, abortive initiation products, and premature termination — during in vitro transcription (IVT). It surveys enzyme-engineering approaches (structure-guided mutagenesis) aimed at suppressing these side reactions at the source, as an alternative/complement to reaction-condition optimization and downstream purification (e.g., chromatography, RNase III treatment), which inherently trade off yield against purity. For practitioners in RNA therapeutics manufacturing, this consolidates candidate T7 RNAP variants and structural rationale relevant to reducing innate-immune-activating dsRNA contaminants in mRNA vaccine/therapeutic production.
arXiv · q-bio.NCConceptual
The more you lean on a tool like AI, the harder it becomes to stop leaning.
This paper builds a mathematical model of what happens when people rely on tools — from an abacus to a map to, now, AI like large language models — to help them think. It treats the person's own skill and their reliance on the tool as two forces that constantly influence each other over time. The surprising finding is that this system has a tipping point: once a tool becomes available and easy enough to use, people's own competence can suddenly collapse toward near-total dependence, and simply making the tool less available afterward doesn't bring their skill back — you'd need to remove it far more drastically than the original threshold that caused the collapse. That means two people with identical access to the same tool today can end up in totally different, lasting states — one still skilled, one dependent — purely because of which path they took first, like whether they practiced the skill before or after they started using the tool heavily. It's a cautionary, quantitative take on the classic worry that convenient tools like AI could erode human ability.
Technical view
The paper formalizes user, tool, and task as a single coupled dynamical system where competence (retained skill) and reliance (outsourced effort) co-evolve, revealing bistability: above a critical tool-availability threshold the competent fixed point is destroyed and the system collapses to a low-competence attractor, while reducing availability afterward exhibits hysteresis, requiring a much lower threshold to reverse. The collapse threshold is shown to depend jointly on prior user competence and the tool's transparency, meaning identical present-day access can yield divergent long-run states purely from path-dependence (order of exposure). This offers a dynamical-systems framework — with concrete bifurcation/hysteresis structure — for reasoning quantitatively about AI-tool-driven skill erosion, useful for modeling policy interventions like phased tool introduction or transparency requirements.
arXiv · q-bio.PEConceptual
Disease outbreaks ripple differently through a food chain depending on where 'gravity' pulls species together.
In nature, predators and prey don't just interact based on population size — physical distance matters too, similar to how gravity's pull depends on both mass and distance; the closer two things are, the stronger their interaction. This paper builds a model of a three-level food chain (like plants, herbivores, and top predators) where the strength of interaction between levels depends on this distance-based 'gravity' effect, and then adds disease into the mix. Without disease, the three species settle into a stable, coexisting balance. But when the researchers introduce infection at the middle level of the food chain, the whole system starts oscillating in cycles rather than staying stable; when they instead infect the top predator, the outcome is different and more drastic — the population can collapse toward extinction rather than just cycling. By adjusting how strongly this spatial 'gravity' effect operates, they show it changes which of these outcomes occurs, offering insight into how disease location and spatial ecology together shape whether an ecosystem stays balanced or breaks down.
Technical view
The authors couple a gravity-model-style distance/abundance-dependent interaction term into a tri-trophic eco-epidemiological ODE system, establishing that the disease-free chain has a stable coexistence equilibrium as baseline. They show infection at the intermediate trophic level destabilizes this equilibrium via a Hopf bifurcation (producing sustained limit-cycle oscillations), whereas infection at the top predator drives a distinct transition from persistence to extinction rather than oscillation, and they characterize how varying gravity-coupling strength modulates these transitions. This gives a tractable bifurcation-analysis framework for linking spatially-mediated (distance/abundance-weighted) trophic coupling to disease-driven regime shifts, extendable to parameterize with real spatial-ecology and epidemiological data.
arXiv · q-bio.NCConceptual
Why some neurons fire like clockwork and others in noisy bursts, explained by one knob.
Neurons talk by firing electrical spikes, and the gaps between spikes (the inter-spike interval) carry information — but those gaps are also noisy and irregular. This paper studies a simple model neuron that gets pushed toward firing by 'excitatory' inputs and pulled back by 'inhibitory' ones, like a tug-of-war. Normally a neuron fires once its voltage crosses a fixed line, but here the researchers let that firing line itself shift depending on recent activity ('adaptive threshold'), since real neurons often behave this way. They find that when the threshold rises along with the neuron's voltage (a 'depolarizing' adaptive threshold), the spike timing becomes noisier than with a fixed threshold, which matters for understanding how reliably brain circuits can pass along signals.
Technical view
The authors analyze ISI statistics of a leaky integrate-and-fire neuron driven by independent excitatory and inhibitory Poisson-like presynaptic spike trains (an E-I circuit), comparing fixed-threshold dynamics against an adaptive threshold that co-varies with membrane potential (depolarizing case) versus one that moves oppositely (hyperpolarizing case, implied by the title). Using the coefficient of variation of the ISI as the noise metric, they derive that depolarizing adaptation increases ISI variability relative to the fixed-threshold baseline at matched mean firing rate, likely via analytical first-passage-time or Fokker-Planck techniques standard in integrate-and-fire theory. This gives a tractable framework for predicting how threshold adaptation mechanisms (seen in cortical neurons) reshape spike-timing reliability, useful for modelers calibrating single-neuron noise sources in network simulations.
arXiv · math.DSConceptual
A dengue model that only sprays mosquitoes and opens hospital beds when things get bad.
Dengue fever keeps coming back in tropical countries despite control efforts, and part of the problem is that real-world resources — hospital beds, insecticide spraying — are limited and not always running at full blast. Most disease models unrealistically assume infinite hospital space and constant fogging (mosquito spraying), which doesn't match reality. This paper builds a more realistic math model where fogging only kicks in once reported infections cross a certain trigger level, and hospitals can only treat so many patients at once. By tracking how the disease behaves under these on/off, capacity-limited rules, the model reveals distinct 'modes' the epidemic can settle into depending on how policies respond as case numbers climb, helping planners see when their intervention thresholds are actually protective versus too little too late.
Technical view
The authors formulate a non-smooth (piecewise/switched) ODE model of dengue transmission with two realistic constraints: a finite hospital capacity limiting effective treatment rate, and a threshold-triggered fogging intervention activated only once reported infections exceed a set fraction of capacity. This creates three distinct dynamical regimes corresponding to different combinations of active constraints as the outbreak progresses. They prove existence and local stability of disease-free and endemic equilibria within each regime and use numerical continuation to trace how these equilibria and their stability change across parameter space (e.g., the fogging trigger fraction or capacity level). This is directly usable by public-health modelers wanting to set data-driven thresholds for vector control and hospital-surge policy rather than relying on continuous, resource-unconstrained interventions.
arXiv · q-bio.PEConceptual
Exact math for how disease outbreaks end when lockdown rules switch on and off with case counts.
When governments respond to an epidemic, they don't just apply one policy forever — they escalate restrictions when cases rise and relax them when things improve, creating a system that switches between different 'modes.' This paper builds an exact mathematical model of an SIR-style epidemic (Susceptible-Infected-Recovered) where the disease's own current severity can trigger a policy switch, and the switching itself follows a random (Markovian) process. Rather than relying on rough approximations, the authors work out precise formulas for how many people ultimately get infected and how long the outbreak lasts, given this feedback loop between disease size and policy response. This kind of exact accounting matters because it lets policymakers evaluate, in a mathematically rigorous way, how sensitive an epidemic's total damage and duration are to when and how aggressively interventions kick in.
Technical view
The paper develops an exact finite-population stochastic SIR framework augmented with a finite-state Markovian 'phase' process representing intervention regimes, where transmission, recovery, and direct-immunity rates depend on the active phase, and phase-transition rates can themselves be state-dependent (i.e., policy escalates as a function of current infection counts). Exploiting the monotone, non-increasing nature of the susceptible compartment, the authors derive level-wise recursions for the joint Laplace-Stieltjes transform and probability generating function of the extinction time and total infections generated, yielding exact distributions and mixed moments linking epidemic duration to infection burden — replacing costly global stochastic simulation with recursive exact computation. This gives epidemic modelers a tractable, exact alternative to Monte Carlo methods for evaluating state-dependent, feedback-driven intervention policies at the level of full distributions rather than just means.
arXiv · q-bio.GNBuildable
Shrinking huge cell datasets down to real, traceable cells instead of fake made-up ones.
Scientists studying individual cells generate enormous datasets that are expensive to store and hard to double-check, so researchers try to compress them down to a smaller representative set for training AI models. The catch is that standard compression techniques often invent synthetic, fictional 'average' cells that don't correspond to any real measurement, making it impossible to trace a weird AI prediction back to its source. This paper instead selects only real, actually-measured cells — keeping their original ID tags and gene names — under a strict budget on how many cells and genes you're allowed to keep, using two selection strategies that mathematically try to preserve the statistical shape of the full dataset. The payoff is a much smaller dataset that's just as auditable as the original, so if a model does something surprising, you can go back and check the actual real cell that caused it.
Technical view
The authors formalize traceable single-cell dataset distillation as selecting a coreset of real cells and genes (not synthetic profiles) under fixed budgets, preserving original barcodes/identifiers and gene symbols for full data provenance. They propose Fixed-CF, which matches empirical characteristic functions statically, and Minmax-CF, which solves an entropy-regularized discrete min-max optimization that upweights directions in feature space poorly captured by the current selection while only adding observed (real) cells. Evaluated across donor-, technology-, and perturbation-level distribution shifts on three datasets, the method aims to match or approach synthetic-distillation performance while retaining full auditability — practically useful for anyone building single-cell foundation models who needs regulatory-grade traceability from prediction back to raw assay data.
arXiv · cs.CLConceptual
Researchers built an AI 'jailbreaker' to test if chatbots can be tricked into designing dangerous biology.
As AI language models get folded into scientific research, there's a worry they could be manipulated into giving out dangerous biological know-how — like instructions for harmful pathogens — faster than safety measures can keep up. To actually test this risk instead of just guessing, the researchers built a specialized 'attacker' AI called Intern-BioBreaker whose job is to craft clever prompts designed to trick other AI models into revealing unsafe biological guidance or generating harmful genetic sequences. Crucially, they didn't stop at the computer: some of the AI-generated genetic designs were actually synthesized in a real lab, inserted into host cells, and tested to see if they produced the intended (and potentially concerning) biological products. This end-to-end computer-to-wet-lab pipeline is meant to give an early, concrete warning of where AI safety guardrails are currently failing, rather than a theoretical worry.
Technical view
The authors introduce Intern-BioBreaker, a purpose-built bio-red-teaming model that automatically generates adversarial jailbreak prompts targeting frontier LLMs, probing whether alignment safeguards can be bypassed to extract operational guidance for safety-sensitive biological procedures or to elicit sequence-level outputs (e.g., protein or genetic designs) with potentially hazardous function. Distinctively, the evaluation extends beyond computational red-teaming: selected model-generated sequences are carried through actual DNA synthesis, host expression, and orthogonal protein verification to empirically confirm whether the designs yield the intended biological product. This computational-to-physical validation loop is a methodological template for biosecurity evaluation of LLMs that grounds jailbreak success in wet-lab ground truth rather than model self-report, relevant to AI safety teams and biosecurity policymakers assessing dual-use risk in scientific-copilot deployments.
arXiv · q-bio.BMBuildable
An AI 'GPS' maps exactly where a protein likes to grip and slide along your DNA.
Proteins that regulate genes don't just sit on one spot of DNA — many actually slide along the genome searching for the right target, like a bead sliding on a string, and how tightly they stick at each point (their 'binding energy') determines where they end up and how fast they find their target. Measuring this energy everywhere along a genome experimentally is impractical, so the researchers instead trained a machine-learning model on real measured protein-DNA structures and their known binding strengths, teaching it to recognize deep patterns in both the protein's shape and the DNA sequence that predict binding energy anywhere. They applied this trained model to a real gene-regulating protein (PU.1) as it slides along mammalian chromosomes, producing a full map of where it binds strongly, how stable those spots are, and how easily the protein can reach them — turning an experimentally near-impossible measurement into a computed genome-wide landscape.
Technical view
The authors curated a dataset of protein-DNA co-structures paired with measured binding free energies and trained a machine-learning model that learns latent, invariant representations of both the protein interface and the DNA sequence, fusing them to predict binding free energy for arbitrary sequence-protein pairs. After validating predictive accuracy against known binding data, they applied the model to compute the genome-wide energy landscape of the single-domain transcription factor PU.1 as it diffuses along mammalian chromosomes, extracting predicted binding-site locations along with statistical measures of thermodynamic stability and kinetic accessibility (how easily the site is reached via 1D sliding/3D diffusion search). This provides a generalizable computational tool for predicting transcription-factor binding landscapes genome-wide from structure and sequence alone, useful to researchers modeling gene regulation or facilitated-diffusion search dynamics without exhaustive experimental binding assays.
bioRxiv · biophysicsBuildable
How a cell decides to move isn't just how fast — it's the order of its wiggles, and that order carries a hidden signal.
When scientists track cells crawling around under a microscope, they usually just measure how fast the cell moves or how far it wanders, but this study argues that the exact sequence of movement steps also matters. The researchers reanalyzed tens of thousands of cell movement tracks where a protein called MYO10 was knocked down and/or cells were exposed to collagen (a common tissue protein), both known to affect how directionally cells move. They built a clever statistical test that scrambles the order of a cell's movement steps while keeping everything else the same, to isolate whether the order itself — not just the overall stats — carries meaningful information. They found that combining the two treatments produced a surprising 'buffering' effect on directional persistence, and that this effect specifically depends on the sequence of movements, not just aggregate speed or distance, revealing a layer of cell behavior that standard metrics miss.
Technical view
The authors reanalyze 48,134 migration trajectories from 117 fields of view in a public 2x2 factorial dataset (MYO10 knockdown x collagen exposure), applying equal-field and equal-repeat inference alongside a novel order-preserving null model that shuffles increment sequence while holding trajectory length, net displacement, and static polarity fixed. Both perturbations reduced motility individually, but their combination produced a positive buffering interaction specifically in directional persistence, and the analytical order-null showed most of this interaction depends on the serial ordering of increments rather than aggregate statistics. Exact decomposition localized the effect to directional organization arising from both shared-field and cell-relative motion, with leave-one-cell-out analysis ruling out trivial self-inclusion artifacts. This provides a reusable statistical framework (the order-null) for detecting sequence-dependent signals in any trajectory dataset where conventional MSD/persistence-time summaries might discard biologically relevant temporal structure.
bioRxiv · cancer biologyConceptual
Block one cancer-driving pathway in melanoma, and the tumor just reroutes power through a backup pathway — via a single switch protein.
Melanoma, an aggressive skin cancer, is often driven by an overactive chain of signals called the MAPK pathway, and drugs that block part of this chain (MEK1/2-ERK1/2) are used as treatment, but tumors often become resistant. Scientists already knew that a related backup pathway (ERK5) can kick in when the main one is blocked, but this study asks the reverse question: what happens if you block the backup pathway instead? They discovered that blocking ERK5 actually makes the main MAPK pathway even more active, creating a two-way feedback loop between the pathways. They traced this to a specific switch protein called R-Ras, whose levels rise when ERK5 is blocked, and showed that removing R-Ras breaks this compensatory activation — suggesting that any single-pathway cancer drug might backfire by triggering hidden reinforcement circuits, and that targeting R-Ras alongside these drugs could prevent resistance.
Technical view
In BRAFV600E melanoma cells, the authors show that genetic or pharmacological ERK5 inhibition paradoxically further activates the canonical MEK1/2-ERK1/2 pathway, revealing bidirectional crosstalk between the two MAPK branches implicated in resistance to RAF/MEK/ERK-targeted therapy. Building on prior transcriptomic data showing R-Ras upregulation upon ERK5 silencing, they demonstrate that R-Ras mRNA and protein increase following both genetic and pharmacological ERK5 inhibition, and that R-Ras knockdown abolishes the reciprocal ERK1/2 hyperactivation. This identifies R-Ras as a molecular node mediating compensatory crosstalk between ERK5 and ERK1/2 signaling under single-pathway blockade. The finding suggests combination strategies co-targeting R-Ras (or its downstream effectors) alongside MAPK-pathway inhibitors could suppress this adaptive resistance mechanism in BRAF-mutant melanoma.
bioRxiv · scientific communication and educationBuildable
Scientists checked a million research papers to see who actually shares their data — and money matters a lot.
Funders and journals increasingly require scientists to share the data behind their papers, but nobody really knows how often this actually happens across science as a whole. This study scanned nearly a million open-access biomedical papers published in an 18-month window, using automated tools to read the full text and detect whether each paper actually contained a genuine data-sharing statement, then cross-referenced who funded each paper. They found that overall only about 9% of papers shared their data openly, but this jumped to 20-24% for papers funded by certain major funders — showing that funder policy and enforcement make a real, measurable difference. This kind of large-scale audit gives funders and institutions hard evidence about which policies actually translate into better science practices, rather than relying on assumptions or small surveys.
Technical view
The authors built a dual-source text-extraction pipeline (MinerU for PDFs, PMC XML otherwise) combined with the oddpub v7.2.3 algorithm to detect data-sharing statements across 951,949 open-access biomedical articles (Jan 2024-Jun 2025), enriching results with funder, journal, and institutional metadata from OpenAlex. Overall open-data prevalence was 8.7%, rising to 11.7% for funder-linked articles, with more than tenfold variation across funders — leading major funders reaching 20-24% observed open-data rates. This establishes a scalable, automated methodology (full-text NLP + metadata linkage) for continuous, large-scale compliance monitoring that could be replicated by funders or meta-research groups to track policy effectiveness over time rather than relying on manual audits or self-report surveys.
bioRxiv · neuroscienceConceptual
Cannabis use during pregnancy leaves a molecular fingerprint in fetal brains — but mainly in boys, later in pregnancy.
As cannabis use during pregnancy becomes more common, scientists want to know if it actually harms fetal brain development, not just whether babies born to cannabis-using mothers happen to have worse outcomes (which could be explained by other factors). This study looked directly at donated human fetal brain tissue from pregnancies with documented cannabis exposure, measuring which genes were turned on or off (transcriptomics) and which proteins were present (proteomics) at two different stages of pregnancy. They found that cannabis exposure barely affected female fetal brains early in pregnancy, but caused major, wide-ranging disruption in male fetal brains later in the second trimester. The disrupted biological pathways overlapped with those already linked to autism, schizophrenia, and other neurodevelopmental conditions, providing direct molecular evidence — not just statistical correlation — that prenatal cannabis exposure can measurably alter a developing brain, especially in male fetuses at a specific developmental window.
Technical view
Using integrated transcriptomic and global proteomic profiling of first- and second-trimester (T1/T2) human fetal brain tissue from cannabis-exposed versus unexposed pregnancies (with confounding drug use excluded), the authors report a sex- and timepoint-specific effect: minimal molecular perturbation in female T1 brains but pronounced, system-level pathway disruption in male T2 brains. The disrupted pathways show molecular signatures overlapping known gene sets implicated in autism spectrum disorder and schizophrenia. This multi-omic design moves beyond correlational epidemiology by directly demonstrating molecular-level neurodevelopmental disruption, and the identified pathway/gene sets provide candidate targets for follow-up mechanistic studies or biomarker development in prenatal cannabis exposure research.
bioRxiv · zoologyRunnable
Meet the roundworm living in a pet cockroach's gut — now with its full genome sequenced for the first time.
Deep inside the digestive tract of cockroaches and similar insects live tiny worms called nematodes that feed on the host's gut microbes rather than the host itself. This paper studies one such worm, Cranifera cranifera, found in a captive cockroach species commonly bred as pet food, describing new details of the male worm's body structure and, more importantly, sequencing its complete genome using long-read technology (which reads longer stretches of DNA at once for a more complete picture). This makes it only the third such genome ever assembled for this entire group of gut-dwelling worms, filling in a major gap in the genetic map of a poorly studied but ecologically common category of parasites. Having this genome available lets scientists compare how these gut worms are related to free-living and parasitic worm relatives, and gives future researchers a genetic reference to study this overlooked corner of animal life.
Technical view
The authors present new male morphological data and the first nuclear genome assembly for Cranifera cranifera (Thelastomatoidea), a gut-dwelling nematode of the cockroach Blaptica dubia, generated via long-read sequencing — only the third nuclear genome available for this superfamily. The assembly spans 246 Mb across 7,563 contigs with an N50 of 43 kb and 94% BUSCO completeness (nematoda_odb12), accompanied by a complete 24,646 bp mitochondrial genome with full protein-coding, rRNA, and tRNA gene complements. This genomic resource enables phylogenomic placement of Thelastomatoidea relative to free-living rhabditids and parasitic Spirurina, and provides a reference for comparative genomics of commensal gut nematodes across arthropod hosts.
bioRxiv · molecular biologyConceptual
Bungee jumping rewires your blood chemistry more than a stressful thought ever does.
This study asks what actually happens inside your bloodstream when you're stressed, and whether it matters if the stress is mental, physical, or both at once. Researchers measured hundreds of proteins and metabolites in blood before and after three kinds of stress: a psychological stress test, a physical workout, and bungee jumping (which combines fear and physical exertion). Even though the classic stress hormone system ramped up equally in all cases, only physical exertion and especially the combined bungee-jump stress caused big, coordinated shifts in blood proteins and metabolism — pure mental stress barely moved the needle. The takeaway is that 'stress' isn't one thing biologically; different flavors of stress leave very different molecular fingerprints, which matters for how we study stress-related disease.
Technical view
Using longitudinal deep plasma proteomics plus targeted metabolomics across psychological, controlled physical, and combined (bungee jump) stress paradigms, the authors decoupled HPA-axis activation from downstream molecular remodeling. Psychological stress alone produced minimal proteomic/metabolomic change despite robust cortisol-axis engagement, while physical stress drove rapid, coordinated proteome shifts with stressor-specific metabolic signatures, and combined stress produced the strongest, most persistent response — establishing a graded, modality-dependent molecular dose-response. Cross-paradigm integration identified a shared stress-responsive protein core enriched for immune granule effectors and RNA-related factors, suggesting a convergent circulating signature usable as a biomarker panel. This dataset is a candidate reference for dissociating cortisol-axis output from actual tissue/immune remodeling in future acute-stress biomarker or resilience studies.
bioRxiv · molecular biologyBuildable
Scientists found the molecular hinge silencing fetal hemoglobin — and a way to break it.
Sickle cell disease and beta-thalassemia are blood disorders where adult hemoglobin doesn't work right, but everyone made a healthy backup version called fetal hemoglobin before birth that gets switched off after infancy. This research pinpoints the exact molecular 'clasp' between two proteins, GATAD2A and CHD4, that a larger silencing machine uses to keep fetal hemoglobin turned off in adults. Using AI structure prediction (AlphaFold 3) plus a real crystal structure, the team mapped precisely which small regions of each protein grip onto each other, then confirmed it in the lab. Breaking that clasp is a promising strategy to flip fetal hemoglobin back on in adults, potentially offering a new therapy path for these common inherited blood diseases.
Technical view
The MBD2a-NuRD complex silences gamma-globin (HBG) in adult erythroid cells, and this work used AlphaFold 3 modeling combined with a recent crystal structure to identify the specific interface between GATAD2A's CR2 helical domain and CHD4's C-terminal C1b/C2ab domains within the HDAC core subcomplex. The predicted interaction was validated biophysically in vitro, and targeted mutations at the interface were shown to disrupt binding. This structural map defines a druggable protein-protein interaction distinct from prior NuRD-targeting approaches, giving medicinal chemists a concrete interface to design small molecules or peptides that reactivate fetal hemoglobin (HbF) as a strategy for sickle cell disease and beta-thalassemia.
bioRxiv · cell biologyConceptual
Heart cells loosen their molecular grip exactly where the mechanical strain is highest.
Cells in your heart muscle stay connected to their neighbors using junction proteins called cadherins, which act like molecular Velcro anchored to the cell's internal skeleton. Using a specialized light-polarization microscope, researchers could see whether these cadherin molecules line up neatly in an orderly pattern or sit more chaotically at real junctions inside heart muscle cells. They found that at junctions under heavy mechanical load — where the cell's muscle fibers pull hardest — the cadherins were actually less orderly, while calmer, low-load junctions showed tighter alignment. This is surprising because it suggests that strong, reliable cell-to-cell adhesion in a beating heart doesn't require the proteins to be neatly arranged — messier can still mean sturdier.
Technical view
Using fluorescence polarization microscopy, the authors quantified orientational order of N-cadherin ectodomains at cardiomyocyte adherens junctions and compared it to desmoglein 2 at desmosomes. N-cadherin order was spatially heterogeneous and inversely correlated with mechanical load, being lowest at vinculin-enriched axial junctions (myofibril termination sites, high tension) and highest at vinculin-poor lateral junctions (low tension), whereas desmoglein 2 order was uniform across junction types. This decouples ectodomain crystalline-like packing from adhesive robustness under load, challenging assumptions from in vitro cadherin array studies. The polarization-microscopy approach itself is a reusable tool for probing how mechanical force reorganizes membrane protein architecture in situ in other load-bearing junctions.
bioRxiv · cell biologyBuildable
Flip one chemical bond in a fat molecule and cells become far easier to kill.
Ferroptosis is a form of cell death where fats in a cell's membrane get damaged by oxidation until the cell falls apart, and scientists want to understand what makes cells more or less vulnerable to it. This study tested many different fatty acids and found a surprising twist: the shape of the fat molecule matters, not just its length or how unsaturated it is. Trans-fats (the same kind flagged as unhealthy in food) made cells much more prone to this oxidative death than their nearly identical cis-fat cousins, even though the two only differ in the geometry of a single chemical bond. This finding hints that trans-fat structure itself, not just diet quantity, could be a lever for triggering or preventing ferroptosis-related disease and possibly cancer therapy.
Technical view
The authors screened structurally diverse fatty acids for effects on ferroptosis sensitivity and found that trans-unsaturated fatty acids act as potent sensitizers relative to cis isomers with identical chain length and saturation. Linoelaidic acid (trans-PUFA) enhanced lipid peroxidation and increased accumulation of ferroptosis-susceptible phospholipid species more than its cis counterpart linoleic acid, and even the trans monounsaturated petroselaidic acid sensitized cells, indicating the effect isn't restricted to polyunsaturated species. This establishes double-bond geometry (cis/trans stereochemistry) as an independent axis of ferroptosis regulation beyond chain length and unsaturation degree, suggesting lipidomic profiling of dietary/endogenous trans-fatty acid incorporation into membrane phospholipids as a route to modulate ferroptosis sensitivity in disease or therapeutic contexts.
bioRxiv · developmental biologyConceptual
A tiny patch of cells marks where your sharpest-vision eye spot will form, weeks after conception.
The macula is the small central part of your retina responsible for your sharpest vision, and scientists have long wondered how the eye 'decides' early on where this special region will be. This study found a distinct cluster of cells — identifiable by two marker genes, CYP26A1 and CRYAA — that appears in the human retina as early as seven weeks after conception, in the area that will become the macula. Using single-cell gene sequencing, tissue staining, and spatial mapping, the researchers showed this patch develops into a specialized support-cell (glial) population unique to the macula, rather than the region just developing on the same schedule as the rest of the retina. Remarkably, part of this molecular signature persists into adulthood, suggesting this early cellular decision leaves a lasting mark on eye anatomy relevant to conditions like macular degeneration.
Technical view
Building on prior work implicating CYP26A1-driven retinoic acid suppression in macular specification, this study defines a CRYAA-positive progenitor-glial compartment in temporal human retina from post-conception week 7, characterized via single-cell RNA-seq, immunohistochemistry, and spatial morphometry. The compartment tracks regional gliogenic maturation and gives rise to a macula-specific Müller glial subpopulation, and spatial mapping shows the CYP26A1+ domain stays sharply delimited even as surrounding retinal tissue expands — arguing against a simple uniform pan-retinal maturation gradient. CYP26A1 expression persists into adult macular tissue, providing a candidate developmental origin and marker set for macula-specific cell states relevant to modeling macular degeneration or engineering macula-like tissue in retinal organoids.
bioRxiv · ecologyBuildable
Night-shift hawkmoths are secretly propping up Kenya's papaya harvests alongside daytime bees.
Most research on crop pollination focuses on bees working during the day, but this study looked at what happens after dark on small papaya farms in Kenya's Taita Hills, a biodiversity hotspot. By covering flowers at different times and comparing wind-only, hand-pollinated, day-only, and night-only conditions, researchers could isolate exactly who was doing the pollinating work. They discovered that daytime bees and nighttime hawkmoths visit completely different time windows and neither one substitutes for the other — both are needed, and together they boost fruit set and fruit weight roughly equally. This matters because conservation and farming policy usually only protects daytime pollinators, potentially leaving farmers vulnerable if nocturnal moth populations decline unnoticed.
Technical view
The study used flower-visitor observations plus five experimental pollination treatments (open, wind-only/closed, hand-pollination, day-only exclusion, night-only exclusion) on subsistence papaya farms in the Taita Hills, Kenya, to partition diurnal versus nocturnal pollinator contributions. Results show complete temporal niche partitioning between diurnal bees and nocturnal Sphingidae (hawkmoths), with additive rather than redundant contributions to fruit set and fruit weight — i.e., losing either guild is not compensated by the other. Supplementary hand-pollination trials indicate that even combined natural pollination may fall short of maximum yield potential, implying a persistent pollination deficit. The exclusion-treatment framework here is directly replicable for other dioecious/self-incompatible tropical crops to quantify hidden nocturnal pollinator dependencies before recommending pollinator management interventions.
bioRxiv · ecologyBuildable
Gull poop, decoded with DNA, reveals just how messy a generalist predator's diet really is.
Figuring out exactly what a wild animal eats is hard, especially for a species like the lesser black-backed gull that will eat almost anything from fish to garbage. This study tests DNA metabarcoding — a method that reads tiny fragments of DNA left in droppings or stomach contents to identify prey species — as a tool for cataloguing gull diets. The researchers collected samples from gull chicks at two English coastal colonies, comparing different body-source samples (like feces versus digestive-tract contents) to see if the method gives consistent, reliable results for such a broad, opportunistic eater. Because gull numbers have shifted unpredictably over decades as human food waste and natural prey availability change, having a trustworthy way to track their real diet helps explain and predict those population trends.
Technical view
The study benchmarks DNA metabarcoding against known methodological biases (primer bias, differential DNA degradation, prey detectability) for characterizing diet in Larus fuscus, a highly generalist mesopredator, using paired faecal/regurgitate samples from pre-fledging chicks alongside pharyngeal, stomach, and intestinal tract samples from two coastal and inland UK colonies. By cross-validating sample types and colony contexts, the work assesses how much metabarcoding output depends on sample source versus true dietary diversity, which is a key methodological question for any generalist-species diet study. The resulting validated pipeline and sample-type comparison give ecologists a replicable protocol for scaling DNA-based diet analysis to other opportunistic mesopredators where traditional prey-identification (e.g., pellet dissection) underperforms.
bioRxiv · ecologyBuildable
Rotting hollows in dying ash trees turn out to be tiny biodiversity arks.
Old, decaying trees aren't just dying wood — their trunk hollows, called rot holes, form little pockets of habitat packed with insects and other invertebrates, some of them rare or threatened. This study looked specifically at European ash trees, which are being wiped out across Europe by a disease called ash dieback, and asked what determines which invertebrates live in each rot hole and how many species show up. Researchers sampled invertebrates from rot holes at 14 sites across Wales, then compared how local conditions (like hole size or moisture) and broader geography influenced the community living inside. Because ash has been overlooked compared to other habitat trees like oak, and because dieback disease threatens to wipe these habitats out entirely, this research helps reveal what biodiversity could be lost if ash rot holes disappear.
Technical view
The study samples and family-level identifies invertebrate assemblages from rot holes (dendrotelmata) in Fraxinus excelsior across 14 sites in Wales, addressing a gap since prior rot-hole invertebrate research has concentrated on other host tree species (notably oak/beech) and narrower taxonomic groups. It disentangles local microhabitat characteristics (biotic/abiotic conditions within individual rot holes) from biogeographical/site-level factors in structuring community diversity and composition, treating each rot hole as a distinct microcosm. Given the ongoing loss of ash across Europe to ash dieback (Hymenoscyphus fraxineus), the dataset establishes a pre-decline baseline of saproxylic invertebrate diversity that conservation planners can use to prioritize veteran ash retention or design artificial habitat replacements. The sampling/identification protocol is directly transferable to other veteran tree species for comparative rot-hole biodiversity surveys.
bioRxiv · bioengineeringConceptual
Plant-based breaded shrimp is tougher and chewier than the real thing, taste tests confirm.
Companies are making fake shrimp from plants to take pressure off overfished oceans, but people often reject these products because they feel wrong in the mouth. Researchers used a machine that bites down on food like a robotic jaw (Texture Profile Analysis) to measure hardness, stiffness, and chewiness of plant-based versus real breaded shrimp, then had 107 people actually taste and rate them. The plant-based version turned out notably harder, stiffer, and much chewier than conventional shrimp. This matters because it helps food scientists pinpoint exactly which texture traits to fix if they want plant-based seafood to win over skeptical eaters.
Technical view
The study benchmarks four breaded shrimp products using instrumental Texture Profile Analysis (14-15 replicates each) against a 107-participant within-subjects sensory panel measuring hedonic liking, Just-About-Right ratings, CATA descriptors, and purchase intent. Plant-based shrimp showed significantly elevated hardness (14.9 vs 9.6 N), stiffness (592 vs 382 kPa), and chewiness (10.5 vs 2.5 N) relative to conventional shrimp. The design lets researchers test whether instrumental TPA metrics actually predict human sensory perception and purchase behavior, offering food developers a roadmap for reformulating texture (e.g., protein matrix or hydration adjustments) to close the gap with target consumer JAR ranges.
bioRxiv · bioengineeringBuildable
Scientists synced a microscope's focus to a bone-squeezing machine so images stop blurring.
When researchers watch living bone tissue under a powerful microscope while mechanically pressing on it, the bone shifts slightly and throws the image out of focus, ruining the data. Instead of fixing blurry footage after the fact, this team built a real-time fix: they mechanically linked the microscope lens's up-and-down motion directly to the same motor that presses the bone, so the lens automatically follows the bone's movement as it happens, adjusted by a dial. This kept a test fluorescent marker looking steady and correctly lit instead of flickering as if it were changing. It matters because clean, reliable images let scientists actually trust what they see when studying how bones respond to physical stress, like exercise or injury.
Technical view
The authors address z-axis motion artifacts in intravital two-photon imaging of mechanically loaded bone by mechanically coupling the objective's piezo motor to the loading actuator's piezo motor via a potentiometer-tuned reduction, enabling hardware-level real-time axial compensation instead of post-hoc image correction. This synchronization eliminated spurious fluorescence intensity fluctuations in a static fluorescent reference marker that would otherwise arise from out-of-plane drift during loading cycles. The approach avoids the computational overhead and calibration complexity of software-based motion correction and could be replicated by any lab pairing piezo-driven loading rigs with two-photon or confocal objectives for other mechanobiology imaging setups.
bioRxiv · biophysicsConceptual
A sticky bacterial protein flickers between folded and floppy shapes, one molecule at a time.
Bacteria build tough biofilm structures called curli using a protein called CsgA, which is notoriously hard to study because it clumps together almost instantly in bulk experiments, giving scientists conflicting pictures of its shape. Here researchers used optical tweezers, a technique that grabs and stretches a single molecule with focused laser beams like microscopic tongs, to watch one CsgA molecule at a time fold and unfold. They found the protein doesn't settle into one fixed shape but flickers between fully folded, partially folded, and loosely tangled states. This matters because curli is a target for new antibiotics, and understanding this shape-shifting behavior could reveal why the protein is so prone to clumping into disease-relevant amyloid fibers.
Technical view
Using single-molecule force spectroscopy with optical tweezers, the authors directly measured unfolding/refolding trajectories of individual CsgA monomers, resolving distinct conformational states — fully folded, partially folded, and collapsed-but-disordered — that coexist in dynamic equilibrium, reconciling the discrepancy between ensemble studies (which show intrinsic disorder) and structural predictions (a folded beta-solenoid). The metastable folded states appear to be the aggregation-prone species that ensemble techniques miss due to rapid amyloid conversion. This mechanistic insight into CsgA's conformational landscape provides a framework for targeting specific folding intermediates with anti-biofilm or anti-amyloid compounds, and the optical-tweezers approach is a template for studying other aggregation-prone functional amyloid precursors.
bioRxiv · cancer biologyConceptual
Removing one cytoskeleton protein makes breast cancer cells far worse at invading tissue.
Septins are structural proteins inside cells that help control how cells move and divide, and higher levels of them are linked to more aggressive breast cancer, though scientists weren't sure exactly how they contribute to cancer spreading. This team genetically deleted one septin gene, SEPT7, from aggressive breast cancer cells and then grew tumor-like clusters in a gel made of collagen, the protein that makes up much of our connective tissue, to mimic real tissue invasion. Without SEPT7, the cancer cells were much worse at pushing into the collagen gel and forming the finger-like protrusions cells normally use to muscle through tissue. This matters because it points to septins as a possible drug target for stopping cancer from spreading through the body.
Technical view
The authors used conditional CRISPR knockout of SEPT7 in metastatic triple-negative breast cancer cells (Hs578T) and assessed invasion using 3D spheroid assays in collagen gels plus single-cell migration studies in collagen matrices and microfluidic pillar devices mimicking matrix pore geometry. SEPT7 deletion strongly impaired 3D collagen invasion, implicating septins in actin-based protrusion formation needed to navigate confined extracellular matrix pores. The pillar-device approach isolates protrusion-driven migration from bulk invasion, giving researchers a tractable assay to dissect which septin-actin interactions specifically drive matrix penetration, a potential entry point for anti-metastatic therapeutics targeting septin filament assembly.
bioRxiv · plant biologyConceptual
A desert tree literally reshapes its DNA packaging each summer to survive brutal heat.
Prosopis cineraria is a tough desert tree native to Arabia that survives repeated scorching summers, and researchers wanted to know how it manages this year after year. They tracked the tree across six points in the year using multiple advanced genetic tools, including one that maps how DNA is folded and organized in 3D inside the cell nucleus, plus tools that read gene activity and chemical tags on DNA. During peak heat, the boundaries that normally keep sections of folded DNA separate loosen up and merge, which switches on clusters of heat-protection genes; in cooler months, the tree instead prioritizes genes for immunity and flowering. This matters because it reveals a reversible, season-by-season survival strategy at the genetic level, information that could help breed heat-resilient crops as climate change intensifies.
Technical view
Using seasonal multi-omic profiling (Hi-C for 3D chromatin architecture, transcriptomics, histone ChIP for H3K4me3/H3K27ac, and DNA methylation) across six time points, the authors show that Prosopis cineraria dynamically remodels topologically associating domain (TAD) boundaries in response to heat: boundaries weaken and domains merge during peak heat, correlating with gain of active promoter/enhancer marks at heat-protective gene clusters. In cool seasons, chromatin state instead favors immune and developmental/flowering gene programs, suggesting a temporal risk-avoidance strategy that decouples reproduction from lethal heat exposure. Promoter CHH methylation changes accompany these shifts, implicating a coordinated epigenetic switch; this establishes a reference epigenomic model for reversible (non-mutational) heat adaptation that could inform engineering heat tolerance in crop chromatin regulators.
bioRxiv · plant biologyConceptual
A stress-alarm molecule from bacteria-like plant parts decides which immune defense a plant picks.
Plants have leftover bacterial-style machinery inside their chloroplasts (the solar-power factories in plant cells), including enzymes that make an alarm molecule called ppGpp, originally known for helping bacteria respond to stress. This study asks whether that alarm signal just turns plant immunity up or down like a volume knob, or whether it actually chooses which type of defense strategy the plant uses. By comparing genetically modified Arabidopsis plants with either too much or none of this alarm molecule, the researchers found it shifts the balance between two different plant hormone defense systems, and that plants with too much of the signal became much easier for a harmful bacterium to infect. This matters because it uncovers an unexpected link between an ancient stress-response chemical and modern plant disease resistance, which could inform crop protection strategies.
Technical view
The authors manipulated ppGpp levels in Arabidopsis via RSH3 overexpression (RSH3OX, high ppGpp) versus rsh-quadruple knockout (rshq, null ppGpp) lines and profiled nuclear-encoded defense gene expression tied to salicylic acid (SA) and jasmonic acid (JA) pathways. RSH3OX plants upregulate hormone-inactivating enzymes while rshq plants show altered MeSA-to-SA conversion gene expression, and pathogen challenge induces RSH2/RSH3 synthase expression prior to defense gene activation, dependent on SA biosynthesis and a functional bacterial Type III secretion system. RSH3OX plants exhibit hypersusceptibility to Pseudomonas syringae pv. tomato DC3000 and impaired pattern-triggered immunity, positioning plastid-derived ppGpp as a retrograde signal that qualitatively reallocates defense output between SA and JA branches rather than simply scaling immunity — a mechanism researchers could target via RSH enzyme modulation for engineered disease resistance.
bioRxiv · scientific communication and educationConceptual
Researchers checked how many scientific papers actually run every plausible version of their analysis.
When scientists analyze data, they make dozens of small decisions — how to clean the data, which statistical model to use, and so on — and different reasonable choices can lead to different conclusions. A technique called multiverse analysis addresses this by running the analysis many different valid ways at once and reporting the whole range of results instead of just one cherry-picked answer. This paper is a survey of science itself: the authors combed through 1,545 papers that cited the founding papers on this technique and checked how many actually used it versus just talked about it, finding that about 40% (613 studies) truly implemented it. This matters because it shows how much this transparency tool has actually caught on in practice, versus remaining a nice idea researchers cite but don't use.
Technical view
The authors conducted a systematic bibliometric review, searching Web of Science (as of May 2026) for articles citing six foundational multiverse-analysis papers, then classified 1,545 classifiable citing articles as either implementing or merely discussing multiverse-style methods. 613 articles (39.7%) implemented an actual multiverse analysis; for each, the authors coded the specific framework used, number of specifications run, which of four decision nodes were varied (measurement, data processing, modeling, estimation), and how results were visualized/interpreted. This gives methodologists an empirical adoption baseline and a taxonomy of implementation practices, useful for identifying underused decision nodes (e.g., measurement vs. modeling) and for benchmarking future meta-research on robustness and specification-curve reporting standards.
bioRxiv · neuroscienceRunnable
One browser tool now maps mouse brain slices onto a reference atlas, no software install needed.
Neuroscientists studying mouse brains often need to line up thin slices of brain tissue against a standard reference map so they can pinpoint exactly which brain region a signal came from, but doing this normally requires juggling several different software programs, some finicky to install. NeuroFlow packages the whole pipeline, aligning images, detecting signals, counting them, and visualizing results, into one tool that runs directly in a web browser on any computer, with no extra installation. It can stretch and warp images to match the brain's natural curves (nonlinear alignment) and even re-slice the reference brain at an angle in real time to match how the tissue was actually cut. This matters because it removes a major technical barrier, letting more labs do rigorous, reproducible brain-mapping analysis without needing a programmer on the team.
Technical view
NeuroFlow is a browser-based, cross-platform workflow that unifies image registration, signal detection, quantification, and visualization for mouse brain histology against a reference atlas, running entirely client-side with no server backend or local Python environment required. It supports both affine and nonlinear (deformable) registration plus real-time oblique reslicing of the reference atlas to match arbitrary sectioning angles, addressing a common mismatch between standard coronal atlases and non-standard cutting planes. By consolidating a typically multi-tool pipeline (e.g., separate registration, cell-counting, and plotting software) into a single local-processing browser app, it lowers the installation and platform-compatibility barrier for labs doing region-based quantitative histology, and its modular stages could be adapted or extended for other atlas-based quantification workflows.
bioRxiv · molecular biologyRunnable
A robot-run DNA test can tell if your sausage is really beef—or secretly pork.
This study checks whether a machine-automated method for pulling DNA out of meat samples works reliably enough to catch food fraud, like mislabeled or mixed meat products. Meat is a tricky material to extract clean DNA from because fat, proteins, and processing can degrade or contaminate the sample, throwing off later tests. The researchers ran meat through an automated extraction robot and kit, then measured how much DNA came out, how pure and intact it was, and whether it could still be read accurately by a genetic test targeting a pig-specific gene. The DNA came out abundant, clean, and worked essentially perfectly in the follow-up test, meaning food-safety labs can trust this faster, hands-off method instead of laborious manual extraction. That matters because reliable species testing underpins food labeling laws, allergen safety, and religious/dietary compliance (like verifying no pork in halal products).
Technical view
The authors analytically validated an automated DNA extraction workflow (Qiagen QIAcube Connect + DNeasy Mericon Food Kit) for meat matrices, assessing concentration, yield, purity, fragment integrity via gel electrophoresis, and PCR inhibition using real-time PCR against the porcine cytochrome b gene. Mean yield was 219.5 ng/uL concentration (21,519.7 ng total), exceeding acceptance thresholds, with fragment sizes larger than the target amplicon and qPCR linearity of R2=0.99-1.00. This supports adopting the automated pipeline as a validated, high-throughput alternative to manual kits in regulatory or forensic food-authentication labs, with cytochrome b qPCR as the downstream species-ID assay. Labs could replicate this by running the same validation panel (yield, A260/280 purity, gel integrity, inhibition-spiked qPCR) on their own matrices before switching extraction protocols.
bioRxiv · molecular biologyConceptual
Two proteins grab each other with floppy 'molecular Velcro' to keep genomes properly packed away.
Cells need to keep certain stretches of DNA tightly shut, like sealed archive boxes—this is called heterochromatin, and a protein called HP1 is one of the main things that seals it. This study found that ORC, a protein complex previously known mainly for kicking off DNA copying, also helps HP1 do its sealing job. They discovered that ORC and HP1 grip each other using short, flexible, 'unstructured' segments—floppy protein regions rather than rigid lock-and-key shapes—with four separate contact points pairing up like matching hooks. When the researchers mutated these contact points in fruit flies, the sealed DNA boxes leaked open, genes that should stay silent got switched on, and even the cell's ribosome-making factory (the nucleolus) got disorganized. This reveals a previously hidden role for a DNA-replication machine in maintaining genome organization, which matters because sealed-DNA failures are linked to aging and disease.
Technical view
The paper maps a multivalent interaction between Drosophila Orc1 and HP1a mediated by intrinsically disordered regions: two short linear motifs (R1, R2) in Orc1's IDR pair with the HGM and CTE motifs flanking HP1a's chromoshadow/chromo domains, with the interaction further requiring HP1 dimerization for avidity. Mutating R1/R2 disrupts ORC-HP1a binding and causes loss of Position-Effect Variegation suppression, rDNA decondensation, and other heterochromatin/nucleolar defects, implicating ORC as a structural scaffold beyond its canonical replication-licensing role. This establishes a motif-based mechanism (akin to other HP1-binding PxVxL/CSD-adjacent interactions) that researchers could probe further via structural studies of the ORC1-HP1a IDR complex or by testing whether other IDR-containing chromatin factors use similar paired-motif logic.
bioRxiv · cell biologyBuildable
Scientists find which cellular 'motor proteins' a neuron-disorder gene controls to build nerve branches.
Neurons need to sprout long, branching extensions called neurites to wire up the nervous system, and this construction relies on tiny molecular motors called kinesins that haul cargo along microtubule tracks. A protein called KIFBP acts like a brake, switching off certain kinesins, and when KIFBP is broken in people it causes a serious developmental disorder called Goldberg-Shprintzen Syndrome, involving intellectual disability and nerve damage. The researchers deleted the KIFBP gene from cultured neuron-like cells using CRISPR gene-editing, confirmed these cells couldn't grow neurites properly, and then used a fluorescently tagged version of KIFBP to fish out exactly which proteins it physically grabs onto as neurons mature. By identifying KIFBP's specific kinesin partners, they pinpoint which motors are misbehaving without their brake, a step toward understanding—and maybe someday treating—the disorder.
Technical view
Using CRISPR-Cas9 knockout of KIFBP in Neuro-2a cells, the authors confirm a neurite-extension defect and then use doxycycline-inducible GFP-KIFBP with immunoprecipitation coupled to mass spectrometry to systematically map the KIFBP interactome across neuronal differentiation timepoints. This proteomic approach identifies specific kinesin targets (beyond prior candidates) bound by KIFBP during differentiation, providing a resource for linking individual kinesins to the cytoskeletal disorganization phenotype seen in KIFBP loss and Goldberg-Shprintzen Syndrome. Practitioners could use the reported interactome hits to design targeted kinesin knockdown/rescue experiments to causally test which motor(s) drive the neurite phenotype, or compare against patient-derived neuron proteomics.
bioRxiv · cell biologyBuildable
One signaling protein decides whether a ball of cells builds a clean hollow tube or a tangled mess.
Many organs, like kidneys or glands, are built from sheets of cells that fold into hollow tubes with a central cavity called a lumen—getting this shape right is essential, and going wrong is a hallmark of cancer. The researchers study a protein called SGEF that acts as a molecular switch, helping cells stick together properly and organize their internal scaffolding. Using kidney cells grown in 3D as hollow balls (cysts), they filmed the whole building process on camera and removed SGEF to see what happened: instead of one clean cavity, the cysts formed multiple collapsed, disorganized cavities, and key 'glue' proteins that hold cells together weakened. Putting SGEF back fixed the problem, showing it's genuinely necessary, not just correlated—a finding relevant to understanding how organs form and how that process breaks down in diseases like cancer.
Technical view
Building on prior work showing SGEF (a RhoG-specific GEF) partners with the Scribble polarity complex to regulate 2D junction assembly, this study uses quantitative morphometrics and long-term live imaging of MDCK cyst cultures to show SGEF knockdown causes multi-lumen, collapsed-cyst phenotypes with reduced E-cadherin, beta-catenin, and ZO-1, plus disrupted actomyosin distribution. Re-expression of wild-type SGEF rescues normal single-lumen cyst morphology, while partial rescue with E-cadherin/ZO-1 constructs helps dissect which downstream junctional components are necessary versus SGEF-dependent. This positions SGEF as a node linking RhoG-GTPase signaling to junctional integrity, collective migration, and lumenogenesis, offering a tractable 3D system for further mechanistic dissection (e.g., testing specific Rho-effector pathways downstream of SGEF).
bioRxiv · cell biologyConceptual
Scientists grew a working kidney inside a genetically edited sheep embryo missing its own kidney genes.
There's a huge shortage of organs for transplant, and one radical idea is to grow human or human-compatible organs inside animals by deleting the animal's own organ-building genes and letting donor cells fill the gap—a technique called blastocyst or morula complementation. Pigs have been the usual test animal, but this study tries sheep instead, editing out a gene called SALL1 that's required for kidneys to form, while also removing sheep molecules that would trigger immune rejection in other species. The scientists used gene-editing tools to knock out SALL1 in sheep skin cells, then cloned those cells to make embryos, implanted them, and let donor cells step in to build the missing kidney. The result was developing fetal kidneys built largely from the donor cells rather than the host's own tissue, a proof-of-concept step toward one day growing transplantable human organs in livestock.
Technical view
The authors targeted SALL1 (required for kidney organogenesis) via CRISPR in male sheep fibroblasts already lacking the xenoantigens CMAH and GGTA1, using either a single gRNA within zinc-finger cluster 2 or a dual-gRNA strategy removing all ZF domains, then generated triple-knockout embryos via somatic cell nuclear transfer/cloning and embryo transfer. The resulting SALL1-null host embryos support donor-cell-derived fetal kidney formation via morula complementation, demonstrating sheep as a viable xenogeneic host species alongside pigs for organ-niche complementation strategies. This extends the blastocyst-complementation toolkit (organ-disabling knockout + immunocompatible donor line + interspecies chimera) to a new host species, providing a template others could adapt with different organ-null genes or donor genotypes.
bioRxiv · ecologyConceptual
Hunters, not wolves, are what's actually killing most wild red foxes in Scandinavia.
To understand how a wildlife population survives year to year, ecologists need to know not just how many animals die, but why and when—information that's hard to get without tracking individual animals closely. This study fitted 126 red foxes with GPS collars across Sweden and Norway over eight years, letting researchers pinpoint each animal's location up until death and then investigate the actual cause. They used a statistical survival-analysis method (borrowed from medical research on patient survival) to calculate the odds of a fox surviving a given year and what factors raised or lowered the risk. Hunting turned out to be by far the biggest killer (nearly two-thirds of deaths), far ahead of car strikes, disease, or starvation, and young foxes were roughly twice as likely to die as adults, especially in autumn and early winter. This kind of precise, cause-specific data helps wildlife managers set hunting regulations and predict population trends more accurately than guesswork.
Technical view
Using 126 GPS-collared red foxes tracked 2011-2019 across a latitudinal gradient in Scandinavia, the authors applied the Andersen-Gill extension of the Cox proportional hazards model to estimate cause-specific mortality hazards and annual survival probabilities. Hunting accounted for 63% of deaths, followed by vehicle collisions (14%), stress/malnutrition (11%), sarcoptic mange (9%), and predation (3%); annual survival was 0.58 for adults versus 0.32 for subadults, with subadults facing roughly double the hazard, males elevated relative to females, and peak risk in autumn/early winter. The Andersen-Gill framework allows time-varying covariates and staggered entry, making this a reusable analytical template for other GPS-telemetry mortality studies; the close match to prior non-collar estimates also cross-validates historical harvest-based survival figures for the species.
bioRxiv · biochemistryConceptual
An enzyme with two active sites secretly only fires one at a time—and mass spec caught it in the act.
Many enzymes work as paired units (like a molecular duo), and scientists have long suspected the two halves talk to each other to coordinate their chemistry, but this 'cross-talk' is notoriously hard to observe directly with normal lab techniques, which only give snapshots or averages. Here, researchers studied a bacterial enzyme called FraB, a potential drug target in Salmonella, using a specialized technique called native mass spectrometry that can weigh intact protein complexes and see exactly which molecules are attached to each half in real time. They found something surprising: both halves of the paired enzyme grab onto the starting material, but only one half actually finishes the chemical reaction at a time—a 'half-site' reactivity pattern where the partner sits and waits. This kind of fine-grained view of enzyme teamwork could help drug designers figure out how to jam the enzyme by blocking the communication between its two halves rather than just its active site.
Technical view
The authors combine native mass spectrometry (nMS) with surface-induced dissociation (SID) and kinetic assays to characterize substrate-, product-, and mixed-occupancy states of homodimeric Salmonella enterica FraB deglycase in real time, resolving inter-subunit cooperativity that ensemble kinetics or static crystal structures cannot capture. They show both active sites in the dimer bind substrate, but catalysis proceeds asymmetrically with only one site generating product at a time—evidence of half-site reactivity and allosteric cross-subunit communication. This nMS/SID + kinetics pipeline is a generalizable approach for probing intermediate-resolved allostery in other oligomeric enzymes, and the half-site mechanism in FraB (a validated antivirulence drug target) suggests inhibitor strategies that exploit or lock the asymmetric state rather than targeting a single active site.
bioRxiv · biochemistryBuildable
Chemists chemically tag every 'molecular scissors' enzyme active in the Chagas disease parasite at once.
Serine hydrolases are a huge family of enzymes that snip other molecules apart, and they're common drug targets, but almost nothing is known about which ones exist and function in the parasite that causes Chagas disease, a serious illness spread by insects in Latin America. The researchers used special chemical probes that only stick to serine hydrolase enzymes while they're actively working, then pulled all the tagged enzymes out of whole parasite cells and identified each one using a technique that weighs and sequences proteins (mass spectrometry). This let them build essentially a working parts-list of the enzyme family in this parasite—finding 37 active enzymes including many previously totally uncharacterized ones. Having this map matters because any of these enzymes could be a starting point for new Chagas disease drugs, since you first need to know what tools the parasite actually uses before you can figure out how to disable it.
Technical view
The study performs activity-based protein profiling (ABPP) on live Trypanosoma cruzi epimastigotes using cell-permeable fluorophosphonate (FP)-alkyne probes that covalently label catalytically active serine hydrolases, combined with label-free quantitative MS (LFQ-MS) and genome-wide in silico curation of predicted serine hydrolases. This identified 37 enriched, catalytically active serine-hydrolase-like proteins (63% of 56 curated candidates), spanning lipases, peptidases, esterases, and uncharacterized hydrolases with conserved or partial catalytic triads/dyads. The resulting activity-based serinome map provides a prioritized target list and validated probe-labeling workflow that others can extend with competitive ABPP (using candidate inhibitors) to identify selective chemical starting points for anti-Chagas drug discovery.
bioRxiv · biochemistryBuildable
One AI model both dreams up protein shapes and simulates the physics that moves them.
Proteins constantly wiggle into many different shapes, and predicting this full range of shapes (the 'conformational ensemble') normally requires slow, expensive physics simulations called molecular dynamics. Scientists have built two separate kinds of AI shortcuts for this: one that directly generates plausible protein shapes, and one that learns a faster, simplified physics engine to speed up simulations. UniFlow merges both into a single model using a 'normalizing flow,' a neural network that can rapidly generate new shapes while also calculating exact energy and force values for them, working in a coordinate system based on bond angles rather than raw 3D positions for efficiency. The payoff is a single faster tool that could let researchers study bigger proteins over longer timescales than brute-force simulation allows.
Technical view
UniFlow uses an internal-coordinate normalizing flow that supports i.i.d. sampling with exact likelihood evaluation, while the same learned density also yields differentiable energy and force computation, letting it double as a coarse-grained ML force field. This unifies generative ensemble modeling and ML force-field learning, normally trained as separate objectives, in one scalable framework. Practitioners could use it either to sample equilibrium ensembles directly without running MD, or to drive accelerated MD using its learned forces, with a shared representation improving consistency between the two. The key claim to test when replicating is scalability to larger protein systems versus prior coarse-grained force fields.
bioRxiv · biochemistryConceptual
A disease-causing bacterium builds its toxin using a rare two-iron chemical tool inside one enzyme.
Some bacteria make specialized molecules that help them attack their host, built by enzymes that perform unusual chemistry. This study examines an enzyme called HvfB, from a bacterium that causes ear and respiratory infections, which builds a toxin called oxazolin by attaching six sulfur-containing ring structures onto it. The researchers discovered that HvfB needs a 'mixed-valent diiron cofactor' — two iron atoms sitting together in different charge states — to perform this chemistry, and had to genetically fuse HvfB to its weakly-interacting partner protein just to study it properly. Understanding this iron machinery matters because it reveals a new chemical trick bacteria use to build toxins, potentially pointing to new antibiotic targets.
Technical view
MNIO-family enzymes catalyze diverse post-translational modifications in RiPP natural product biosynthesis using multi-iron cofactors, but cofactor identity had been characterized in only one prior case; here the authors characterize HvfB, which installs six copper-binding 5-thiooxazole groups on the H. influenzae virulence factor oxazolin. Due to weak HvfB-HvfC interaction, they engineered a genetic fusion of the partner proteins to enable biochemical/spectroscopic study, identifying a mixed-valent diiron cofactor as catalytically required. This expands known cofactor diversity within the MNIO family and offers a mechanistic template for related PTM chemistries and potential antivirulence drug targeting.
bioRxiv · bioengineeringBuildable
Software scans an entire protein surface to find hidden spots where a drug could permanently attach.
Covalent drugs work by forming a permanent chemical bond to a target protein, which can make them very potent, but designing them usually requires already knowing exactly where to aim. CovSite instead scans a protein's whole surface to find promising 'reactive sites' using only its 3D shape and the drug candidate's chemical formula. It runs four filters in sequence — finding reactive atoms, checking they're exposed on the surface, predicting their charge state, and ranking reactivity with quantum-chemistry-style calculations. Tested on over 2,000 known drug-protein pairs, it found the correct binding site 98.5% of the time, which could speed up early drug discovery by removing the need for prior knowledge of the target.
Technical view
CovSite is a blind covalent-screening pipeline requiring only protein structure and electrophile SMILES, applying four sequential physicochemical filters — nucleophile identification, solvent accessibility, environment-dependent pKa/deprotonation prediction, and semi-quantum-mechanical reactivity ranking — to prioritize candidate reactive residues across an entire protein surface. Benchmarked on 2,062 diverse covalent protein-ligand complexes spanning six nucleophilic residue types, it achieves a 98.5% blind hit rate for the true reactive site on a held-out set. This enables target-agnostic covalent inhibitor screening at scale, useful for early hit identification or proteome-wide ligandability mapping without prior mechanistic knowledge of the binding site.
bioRxiv · bioengineeringBuildable
Scientists used smart trial-and-error to teach a physics model how proteins grip onto RNA.
When proteins bind RNA — central to how cells read genes — scientists need a way to score how energetically favorable that binding is, but existing tools weren't well-calibrated for the task. This paper tunes a scoring function inside Rosetta, a widely used protein modeling program, so its predicted binding strengths actually match real lab measurements. Since testing every parameter combination by brute force would be too slow, they used Bayesian Optimization, a smart search method that picks the most informative next experiment, to efficiently find the best-fitting parameters. The tuned function revealed meaningful differences across RNA subtypes, confirming it captures real physics rather than just fitting noise, and opens the door to further predictive uses beyond binding-strength estimation.
Technical view
The authors recalibrate Rosetta's protein-RNA energy function against experimental binding data, using Bayesian Optimization to navigate the high-dimensional parameter space efficiently instead of exhaustive grid search. The tuned score function shows statistically significant, RNA-subclass-specific interaction terms, supporting its physical validity beyond curve-fitting. This gives structural biologists a validated, drop-in energy function for Rosetta-based protein-RNA docking, design, and mutagenesis prediction, and the Bayesian Optimization workflow itself is reusable for tuning other Rosetta score terms against experimental benchmarks.
bioRxiv · bioengineeringRunnable
A new microscope films cell metabolism 588 times faster by ditching slow, step-by-step scanning.
To watch chemical activity inside living cells without adding dyes, scientists shine infrared light that makes molecules vibrate and heat up slightly, an approach called optothermal imaging — but the classic version needs slow, repeated scanning that misses fast activity across many cells. IPSOM captures the same information in a single camera snapshot instead of many sequential ones, by shifting the light's phase instantaneously rather than mechanically step by step. This makes single-frame imaging 588 times faster and multi-wavelength imaging 8 times faster, while still covering a wide field of view. The team demonstrated it by watching fat cells break down lipids in real time, showing it can track fast metabolic changes across large populations of living cells as they actually happen.
Technical view
IPSOM replaces conventional mechanical phase-shifting in mid-infrared optothermal microscopy with an instantaneous, single-frame phase-shifting scheme, achieving a 588-fold speedup for single-wavelength imaging and 8-fold for multi-wavelength hyperspectral acquisition over a 300x350 μm field of view. It is a label-free, wide-field vibrational imaging modality exploiting endogenous IR absorption/thermal contrast, avoiding the raster-scanning bottleneck of prior optothermal/photothermal methods. Demonstrated application to lipolysis-driven lipid remodeling in live adipocytes shows the system resolves rapid, population-scale metabolic dynamics, positioning it for high-throughput live-cell metabolic phenotyping or drug-response screening.
bioRxiv · bioinformaticsBuildable
A checklist that tests whether a 'newly discovered' cell type is real or just a clustering fluke.
When scientists analyze single-cell RNA data to find new cell subtypes, they typically run one clustering algorithm once and trust it, even though clustering results can shift with tiny changes in method. This pipeline stress-tests clustering without needing pre-existing labels, checking two distinct kinds of consistency: does the same grouping reappear if you resample which cells you look at, and does it reappear if you rebuild the underlying data representation from scratch? It runs seven clustering setups and five quality metrics to turn the process into an audit rather than a one-shot guess. Tested on a mouse retina dataset, it correctly recovered known cell types with 96.3% accuracy, showing it can distinguish real biological subpopulations from statistical noise — important since false 'discoveries' waste huge amounts of downstream research effort.
Technical view
The pipeline treats single-cell clustering as an auditable, methods-agnostic decision process, separately quantifying two often-conflated stability notions — reproducibility under cell resampling (bootstrap) versus reproducibility under re-embedding (retraining the dimensionality-reduction representation) — across seven clustering configurations, multiple cluster-count settings, and five non-redundant quality metrics, all without ground-truth labels. On a mouse retinal atlas used as a whole-dataset control, it recovers an eight-cell-type annotation with 96.3% accuracy (ARI = 0.91) unsupervised, with further validation on two cell populations of known opposite ground-truth stability. This gives practitioners a standardized diagnostic to distinguish robust cell-type discoveries from clustering artifacts before making downstream biological claims, applicable as a pre-publication QC step for any scRNA-seq dataset.
bioRxiv · bioinformaticsConceptual
'Interpretable' disease-prediction AI gives different, contradictory explanations depending on tiny training choices.
Biologically informed neural networks (BINNs) are AI models built so their internal parts map onto real biological pathways and genes, promising doctors an 'interpretable' way to predict disease risk from genetic and blood data. This study trained such models at huge scale — half a million people's genetic and protein data from the UK Biobank — to predict six common diseases, and while they predicted well, the researchers found two serious problems with trusting their explanations. First, which genes the model flags as important is skewed by how well-connected that gene is in the underlying network, not necessarily its true biological relevance. Second, training the same model multiple times with minor differences gives different, sometimes contradictory stories about what's driving each prediction — a warning against over-trusting these popular 'interpretable' AI models without extra checks.
Technical view
The authors implement a scalable BINN trained on UK Biobank genotype and plasma proteomic data (~500,000 individuals) across six common diseases, evaluating both predictive performance and attribution reliability. They find attribution scores are systematically confounded by graph topology (node degree, layer position), with normalization only partially correcting this at some cost to enrichment for known disease genes, and separately demonstrate substantial predictive multiplicity — independently trained models with similar accuracy assign meaningfully different importance to the same biological entities. This is a cautionary empirical result for anyone deploying pathway-structured neural networks for biomarker discovery: single-run attribution claims shouldn't be trusted without topology-bias correction and multi-run consistency checks.
bioRxiv · cancer biologyConceptual
A cancer drug already in clinics may also stop breast cancer from spreading, via a hidden gene switch.
PARP inhibitors are cancer drugs already approved for ovarian cancer in patients with certain gene mutations, and they're also linked to blocking metastasis (cancer spreading to other organs), but how that happens wasn't well understood, especially in triple-negative breast cancer, an aggressive subtype. This study shows PARP1, a protein best known for DNA repair, also controls which genes get switched on, specifically regulating two proteins, RhoGDIα and vimentin, that govern how cancer cells move and invade tissue. Researchers treated cancer cells with PARP inhibitors and measured migration and invasion in lab assays, then traced PARP1's direct binding to the relevant genes to confirm the mechanism. This matters because it suggests PARP inhibitors could help stop breast cancer spread even in patients without the BRCA mutations they're currently approved for.
Technical view
The study shows PARP1 drives triple-negative breast cancer (TNBC) metastatic progression through a gene-transcription-mediated mechanism independent of its canonical DNA-repair role, by regulating RhoGDIα and vimentin, cytoskeletal/invasion-related proteins. Using migration/invasion assays, proteomic profiling, immunoblotting, and chromatin immunoprecipitation, the authors show PARP inhibitors reduce metastatic phenotypes and link this to PARP1 occupancy at relevant gene loci, in both BRCA-proficient and BRCA-deficient TNBC. This positions PARP1 as a transcriptional regulator of a pro-metastatic RhoGDIα-vimentin axis, suggesting inhibitor utility beyond BRCA-mutant tumors and providing ChIP-validated target loci for follow-up mechanistic or combination-therapy studies.
bioRxiv · cancer biologyConceptual
A mercury-curcumin hybrid drug kills leukemia cells while letting healthy blood and immunity bounce back.
Acute lymphoblastic leukemia is normally treated with chemotherapy that kills cancer cells but also wrecks the bone marrow and immune system along the way. Researchers built a new molecule, called ‑Mercurin, by chemically fusing a mercury atom onto curcumin (the compound that gives turmeric its color), engineered so it can be injected into the bloodstream. In a rat model that develops leukemia naturally and still has a working immune system, the drug preferentially destroyed leukemic cells while allowing the bone marrow and immune cells to recover. It works by pushing cancer cells to build up damaging reactive oxygen molecules that break their mitochondria and trigger self-destruction. This matters because a treatment that spares the immune system could reduce the brutal side effects that make leukemia chemo so hard on patients.
Technical view
‑Mercurin is a first-in-class intravenous organomercury-curcumin conjugate, with mercury bonded to curcumin's α-carbon, previously shown in vitro/ex vivo to selectively kill leukemic cells via ROS-driven mitochondrial dysfunction and intrinsic apoptosis. This study extends that to an ENU-induced autochthonous ALL rat model with intact immune physiology, showing preferential blast clearance alongside restoration of hematopoietic output and immune cell composition — a dual efficacy/safety profile conventional cytotoxic chemotherapy lacks. The autochthonous, immunocompetent model is notable because it better mimics human disease biology than transplant models. Practitioners interested in redox-selective anticancer agents could use the α-carbon mercuration strategy as a template for tuning ROS-based tumor selectivity in other scaffolds.
bioRxiv · plant biologyConceptual
Two different plant viruses use their surface proteins to grab the same handful of mite host proteins.
Some plant viruses are unusual because they're wrapped in a protective envelope and are spread only by a tiny mite (a relative of spiders) rather than insects — and intriguingly, the viruses can also multiply inside the mite's own cells, not just the plant's. Scientists wanted to know how the virus's outer envelope proteins physically latch onto mite cell machinery to make that possible. They used a lab technique called yeast two-hybrid screening, essentially a matchmaking test that reveals which proteins from a library of mite genes physically bind to the viral surface proteins, and found 73 candidate mite proteins that interact with them. Two unrelated virus families turned out to grab many of the same mite proteins, suggesting a shared molecular strategy for invading and possibly manipulating the vector. Understanding this could reveal ways to block virus transmission by targeting the mite side of the relationship rather than the plant.
Technical view
The study screened putative envelope glycoproteins P61 (Cilevirus, CiLV-C) and G (Dichorhavirus, ClCSV) against a Brevipalpus yothersi cDNA library using membrane-based yeast two-hybrid assays, identifying 73 candidate vector interactors. The key finding is convergence: despite belonging to distinct viral families (Kitaviridae vs Rhabdoviridae) with independent evolutionary origins of arthropod association, both glycoproteins engage overlapping sets of host proteins, implying a conserved mechanism for vector cell entry or intracellular replication. This provides a candidate interactome for follow-up validation (e.g., co-immunoprecipitation, RNAi knockdown in mites) to pinpoint functional receptors or replication factors, and positions shared interactors as potential targets for vector-directed control strategies against Brevipalpus-transmitted viruses.
bioRxiv · neuroscienceConceptual
Your brain can speed up your reach and slow your decisions independently, not as one combined 'motivation' dial.
When you're hungry and reaching for a snack, does your brain crank up 'how eager I am' as a single setting that speeds both your reaching arm and your decision to grab it? Some theories say yes — one global sense of motivation drives everything together. This study tested that using a foraging-like game where people or animals reach toward a reward location and then decide how long to keep harvesting it, while researchers separately dialed up the time pressure and effort required for each part. They found the speed of reaching and the speed of deciding didn't move together — someone who reached fast wasn't necessarily quick to decide, and vice versa. That suggests the brain has more flexible, semi-independent control knobs for physical vigor and mental vigor rather than one shared throttle, which matters for understanding conditions like depression or Parkinson's where both movement and decision-making slow down, sometimes unevenly.
Technical view
Using a block-wise foraging task with independent manipulation of time cost and effort cost, the authors measured reach duration (movement vigor) and harvest duration (decision vigor) and found dissociable effects with no cross-subject correlation between the two vigor measures — evidence against a single global-utility model that jointly invigorates movement and decision from a shared reward/effort/time computation. They propose and fit a model allowing separate but interdependent optimization of movement and decision vigor based on distinct underlying variables. This is directly relevant to computational psychiatry and motor control researchers modeling vigor deficits (e.g., in Parkinson's, depression, apathy), suggesting dual-parameter models rather than single-utility vigor models should be tested against behavioral data.
bioRxiv · microbiologyConceptual
A single fungal protein keeps a dangerous mold's internal walls intact, and losing it makes drugs and immune cells work better.
Aspergillus fumigatus is a mold that can cause life-threatening lung infections in people with weakened immune systems, and it survives partly by carefully managing internal walls called septa that divide its thread-like cells into compartments, sealing them off when damaged to prevent the whole organism from falling apart. Researchers identified a protein, SppA, that sits at these internal walls and is switched on both by a master gene-control protein and in response to an antifungal drug that attacks the fungus's outer wall. When they deleted the gene for SppA, the fungus's internal walls became disorganized and the mold became much more vulnerable — both to antifungal drugs and to being killed by immune cells called neutrophils that are the body's first line of defense against this infection. This matters because it points to a weak spot that could be exploited to make existing antifungal treatments more effective.
Technical view
The authors characterize SppA, a septal pore-associated C2-domain protein in A. fumigatus whose expression is induced by the transcription factor ZfpA and by the echinocandin antifungal caspofungin. Deletion of sppA disrupts septal pore organization, increases hyphal susceptibility to damage, heightens echinocandin sensitivity, and impairs resistance to neutrophil-mediated killing during infection. This positions SppA within a cell-wall-stress-responsive pathway linking septal integrity to both drug susceptibility and innate immune evasion, making it a candidate target for combination therapy — e.g., a SppA inhibitor could potentiate echinocandins or enhance neutrophil clearance in invasive aspergillosis, and the ZfpA-SppA axis offers a starting point for mapping the broader septal stress-response network.
bioRxiv · neuroscienceConceptual
A stable, lab-made vitamin-A-like molecule helps injured spinal nerves regrow and restores movement in mice.
After a spinal cord injury, nerve fibers barely regrow on their own, partly because the body's natural repair signals — including one driven by retinoic acid, a vitamin-A-derived molecule — are too fragile and short-lived to sustain the process, and giving patients real retinoic acid doesn't work well because it breaks down quickly in the body. Scientists designed a synthetic stand-in, DM04, engineered to be chemically sturdier while still triggering many of the same growth-promoting genetic effects as natural retinoic acid, but through a different, less understood route than the classical one. In lab-grown neurons it encouraged new nerve branches to sprout, and in mice with spinal cord injuries it improved recovery of motor function like walking. This matters because a stable, drug-like molecule that reawakens the nervous system's own regrowth machinery could become a genuinely usable therapy where the natural signal falls short.
Technical view
DM04 is a chemically stabilized small-molecule mimic of retinoic acid (RA) designed to overcome the poor biochemical stability and transient receptor engagement that limit RA's therapeutic use. It reproduces RA-like transcriptional programs and phenotypes — promoting neurite outgrowth in primary neurons, upregulating canonical RA-responsive genes, and supporting neural induction from human iPSCs — while acting independently of canonical RARE-dependent transactivation, implying a distinct or complementary mechanism of receptor engagement. In a murine spinal cord injury model, DM04 treatment produced measurable improvements in motor recovery, and transcriptomic profiling showed both shared RA target gene activation and a unique gene signature. For researchers, DM04 offers a tractable pharmacological tool to dissect RARE-independent RA signaling and a lead compound for further preclinical development in CNS regeneration.
bioRxiv · bioinformaticsBuildable
An AI model reads millions of single cells per patient and explains, in plain terms, what's driving their immune state.
Modern lab tools can now read out the gene activity of hundreds of thousands of individual immune cells from a single patient sample, but turning that flood of data into a clear picture of what's happening biologically in that patient — and why — is genuinely hard. Most existing computer methods compress this data into a patient summary without being able to explain their reasoning in biological terms. The researchers built FloREN, an AI system that represents each patient's data as an interconnected network linking individual cells, genes, and the known biological relationships between them (like which genes regulate which, or how cells communicate), and trains it directly on the outcome of interest so its summaries are grounded in real biology. Because the model is built around this network structure, it can point to the specific genes and cell interactions that drove its conclusion about a patient, rather than acting as an unexplainable black box. This matters for making sense of huge immune datasets and for potentially predicting disease outcomes based on a patient's specific immune wiring.
Technical view
FloREN (Framework for Learning Over REgulatory-Embedding Networks) is a supervised, interpretable representation-learning method for patient-level scRNA-seq summarization. It models each sample as a heterogeneous graph integrating cells and genes alongside gene regulatory and cell-cell communication edges, then applies a graph transformer trained end-to-end on a supervised label, contrasting with prevailing unsupervised sample-embedding approaches (e.g., pseudobulk PCA, autoencoder latents) that lack biological interpretability. The graph-transformer architecture enables attention-based attribution back to specific genes, cells, and regulatory edges driving a prediction, giving practitioners a path to both accurate patient stratification and mechanistic hypothesis generation from large single-cell atlases. Groups with existing scRNA-seq cohorts and outcome labels (e.g., treatment response, disease severity) could apply FloREN as a drop-in alternative to unsupervised embeddings for building interpretable immune network biomarkers.
bioRxiv · biophysicsConceptual
A single letter change in a heart-disease gene makes a floppy protein segment quietly go stiff.
TSPO is a protein sitting in the outer membrane of mitochondria (the cell's energy factories) where it helps manage cholesterol movement and stress responses, and it's also a molecule doctors use as an imaging marker in diagnostic scans. Using a technique called NMR spectroscopy, which can capture how a protein's shape wiggles and shifts in solution rather than just a single frozen snapshot, researchers studied the human version of TSPO bound to a diagnostic imaging drug. They found that the very beginning of one of its five helical segments isn't a fixed, rigid spiral like the rest of the protein, but a floppy, flexible zone acting as a hinge between the cell's interior and the membrane. A common disease-linked genetic variant, A14V, which has been tied to heart problems, tightens up that floppy region by creating small new internal contacts, making it noticeably less flexible without changing the protein's overall shape. This matters because it shows exactly how a tiny genetic change can subtly retune a protein's behavior in a way that might affect the imaging drug's binding or the protein's normal function.
Technical view
Using solution NMR, the authors resolve the conformational dynamics of human TSPO bound to a third-generation PET ligand, identifying a dynamically disordered N-terminal segment of TM1 that forms a flexible cytosol-to-transmembrane boundary rather than a stably folded helix. The disease-associated A14V variant reduces this conformational heterogeneity, introducing short-range contacts that redistribute backbone dynamics while preserving the overall five-helix fold. This is a rare direct structural/dynamic characterization of a disease SNP's effect on membrane protein conformational ensembles rather than static structure, giving structural biologists a mechanistic hypothesis for how A14V could alter ligand engagement or cholesterol-handling function — relevant to interpreting TSPO PET imaging variability across genotypes and to future NMR or MD studies of TM1 dynamics in other TSPO variants.
bioRxiv · cancer biologyConceptual
Blocking one RNA-modifying enzyme slows down and confuses aggressive triple-negative breast cancer cells.
Triple-negative breast cancer is an aggressive form of breast cancer that lacks the usual hormone targets other treatments rely on, making it harder to treat, and an enzyme called METTL3 — which chemically tags RNA molecules with a mark called m6A that influences how genes get used — has been linked to helping it spread. Researchers used a gene-silencing tool to switch off METTL3 in three types of breast cells: normal, a less aggressive cancer type, and a highly aggressive, metastasis-prone cancer type. Turning off METTL3 lowered the overall RNA tagging and reduced how well all three cell types survived, but in the less aggressive cancer cells it also froze them at a specific checkpoint before cell division, essentially stalling their ability to multiply. This suggests METTL3 plays somewhat different roles depending on how aggressive the cancer already is, which matters for figuring out which patients might benefit most from drugs that target this enzyme.
Technical view
The authors performed siRNA-mediated METTL3 knockdown across MCF10A (normal), HCC1143 (low-metastatic TNBC), and MDA-MB-231 (high-metastatic TNBC) cell lines, assessing global m6A levels, viability, cell cycle, and migration, with transcriptomic profiling and RT-qPCR/m6A site prediction validation performed specifically in HCC1143. METTL3 depletion reduced global m6A marks and viability across all three lines, but produced a pronounced G2/M cell cycle arrest selectively in the low-metastatic HCC1143 line, pointing to subtype-dependent downstream mechanisms rather than a uniform oncogenic program. The HCC1143 transcriptomic dataset with m6A site predictions gives researchers a concrete starting point to nominate specific METTL3-regulated transcripts driving the G2/M arrest phenotype, useful for prioritizing candidate targets in METTL3 inhibitor development for less-metastatic TNBC subtypes.