arXiv · cs.HCBuildable★ flagship
One universal plug so any brain-signal AI can be personalized to a new user cheaply.
Brain-computer interfaces read EEG (electrical brain signals) and need to be tuned per person, because everyone's brain signals differ. Many pretrained EEG models exist, but each usually needs its own custom retraining setup to adapt to a user, which doesn't scale for manufacturers. Nimbus Personalizer offers one standard interface — take any frozen (unchanged) EEG model's output, attach a lightweight learnable "head," and produce a personalized brain-state readout — that works across many different model architectures without a new adaptation stack each time. The claim is systems-level, not a new algorithm: because it's model-agnostic, a company integrates once and can swap the underlying model freely, and this cheap head recovers much of the accuracy you'd get from expensive full retraining at a tiny fraction of the effort.
Technical view
Nimbus Personalizer defines a trunk-agnostic personalization contract: encode → Bayesian head → BrainState, with an optional affine mid-tier, sitting atop heterogeneous frozen EEG encoders. The contribution is framed as the API surface, not the ML method (LDA/Bayesian-on-embeddings). Evidence spans five classical trunks (EEGNet, Shallow, Deep, Conformer, ATCNet) across four motor-imagery datasets (18 cells) plus a foundation encoder (REVE) under the same personalizer; where embedding capacity exists, the cheap head recovers much of full fine-tune/PEFT accuracy at orders-of-magnitude lower adaptation wall time, with calibration-only-when-clean holding in 12/18 cells. OEMs could integrate this single contract once and swap frozen trunks without rebuilding a per-architecture personalization pipeline.
arXiv · q-bio.QMBuildable
A statistics toolkit pins down exactly how much a chemical compound slows cancer cell growth despite messy lab data.
When scientists test whether a chemical stops cells from multiplying, the raw measurements are often noisy and inconsistent between repeated experiments, making it hard to trust simple statistical tests. This paper builds a more careful mathematical approach to squeeze reliable answers out of that messy data, applying it to quinolinic acid, a compound tested against melanoma (skin cancer) cells, immune cells called macrophages, and skin cells called keratinocytes. Instead of relying on textbook statistics that assume clean, independent data, they combine simple confidence-interval estimates with a curve-fitting model, checked by leaving out one experimental repeat at a time to see if the model still holds up. This gives researchers a trustworthy way to quantify a drug's real effect even when their raw lab results are variable, which is common in biology.
Technical view
The paper develops a parametric cell-viability modeling framework for crystal violet assay data that violates classical i.i.d. assumptions due to substantial inter-replicate variability. It pairs model-free confidence intervals and pooled within-replicate variance estimation with deterministic least-squares fitting to experimental means, validated via leave-one-replicate-out cross-validation, and applies a shared mechanistic model across B16-F10 melanoma, RAW264.7 macrophage, and HaCaT keratinocyte cell lines to quantify quinolinic acid's antiproliferative dose-response. This offers a reusable statistical pipeline for extracting robust dose-response parameters from noisy, non-independent in vitro viability data, useful to anyone analyzing crystal violet or similar assays without inflating false confidence from classical parametric tests.
arXiv · q-bio.PEConceptual
Epidemics spread as waves that can suddenly jump speed — and now we know exactly when.
When a disease spreads through a population, it can be thought of as a wave of infection moving outward, similar to ripples in a pond. This wave can be 'pulled', meaning it's driven and limited by the sparse leading edge of infected people, or 'pushed', where the bulk of infected people behind the front actively drive it forward faster. The researchers used both computer simulations of the classic SIR epidemic model (Susceptible-Infected-Recovered) and mathematical theory to map out exactly which conditions produce each kind of wave, discovering that the switch between the two types can happen smoothly or suddenly, with the wave's speed jumping abruptly at a critical point. Understanding this matters because it changes how fast and how predictably an outbreak spreads, and even reveals a middle zone where either type of wave could occur.
Technical view
The authors study front propagation in spatial SIR-type PDEs where transmission rate depends on the infected fraction, mapping the parameter phase space separating pulled fronts (dynamics set by the linear leading-edge decay rate) from pushed fronts (nonlinear, bulk-driven). Combining numerical PDE solutions with analytical front-propagation theory, they identify both continuous and discontinuous pulled-to-pushed transitions, the latter exhibiting a discontinuous jump in front speed at the critical threshold, plus a bistable parameter region admitting either front type. This gives epidemiologists and mathematical biologists a concrete, numerically validated phase diagram and analytical criteria for predicting epidemic wave speed regimes and their transitions, directly applicable to spatial compartmental disease models.
arXiv · cs.LGBuildable
An AI now designs custom proteins that can grip multiple, shifting target shapes at once.
Protein binders are custom-designed molecules that latch onto a specific target, like a key fitting a lock, and they're crucial tools in drug design and biology research. Most AI protein-design tools assume there's just one fixed target shape to design against, but real biological targets often shift between multiple states or come in multiple related versions, and previous tools struggle with that complexity. Chamaileon is a new generative AI system trained to design one protein sequence that can work across many different target contexts simultaneously, using a training method that teaches it to co-design sequence and structure together with awareness of context, plus a sampling trick that blends multiple design paths to optimize one final sequence. This matters because it opens the door to more realistic, flexible protein binders for situations where biology isn't static, like targets that change shape or come in several variants.
Technical view
Chamaileon reframes binder design as cross-context binding landscape modeling, addressing the single-target/single-state limitation of prior hallucination and joint sequence-structure generative approaches. It introduces In-Context Complex Co-Design (I3CD), a training paradigm for context-aware joint sequence-structure modeling across multiple targets/states, and Mixture-of-Paths Sampling (MoPS), an inference-time strategy that optimizes a single sequence jointly across multiple contexts for scalability. This provides a template for multi-target/multi-state generative protein design that researchers could adapt to design binders robust to conformational heterogeneity or paralog cross-reactivity, rather than the conventional single-state binder pipelines.
arXiv · q-bio.BMConceptual
Cell blobs made of proteins buffer chemical noise by splitting into multiple internal phases.
Inside cells, certain proteins clump together into liquid-like droplets called biomolecular condensates, which act like membrane-free compartments that help organize cellular chemistry. This study explores how the specific pattern of electric charges along disordered proteins (proteins that don't fold into fixed shapes) determines whether two protein types mix into one droplet or separate into distinct sub-regions within it, and how that affects the droplet's ability to buffer against random fluctuations in concentration. Using both a mathematical polymer theory and molecular dynamics simulations (computer models that track how individual molecules move and interact), the researchers found that protein pairs with dissimilar charge patterns tend to demix into separate phases, while similar-pattern pairs stay mixed, and the theory's predictions matched what the detailed simulations showed once surface tension and droplet size effects were included. This matters because it reveals a mechanism cells might use to keep their internal chemistry stable despite random noise.
Technical view
The authors model liquid-liquid phase separation of polyampholytic intrinsically disordered protein sequence pairs using random phase approximation (RPA) polymer theory augmented with interfacial tension and finite-size corrections, cross-validated against molecular dynamics simulations. RPA predicts temperature-sensitive binary versus ternary LLPS behavior, with demixing into multiple coexisting phases occurring for sequence pairs with dissimilar charge patterning but not for similarly patterned pairs, and MD simulations corroborate these predictions once interfacial and droplet-size effects are incorporated into the RPA framework. This links condensate phase multiplicity (number of coexisting liquid phases) to sequence charge patterning and provides a quantitative theory-simulation pipeline researchers can use to predict or engineer noise-buffering subcompartmentalization in synthetic or biological condensates.
arXiv · q-bio.QMRunnable
A visual tool lets biologists scroll through tissue samples watching cells' life stories unfold in space.
Spatial transcriptomics is a technology that measures which genes are active in cells while keeping track of exactly where those cells sit within a slice of tissue, unlike older methods that scrambled that positional information. Loom is a visualization software system built to help scientists explore this data by tracing pseudo-temporal trajectories, essentially reconstructing the likely order in which cells changed over time, comparing different tissue samples or regions, and zooming into local neighborhoods of cells to see how they interact. The tricky part is combining this spatial gene data with reference cell-type databases and simulated cell behavior over time, since these different data types don't naturally line up. Loom solves this with a custom visual symbol (glyph) and computational backend that lets researchers explore all these layers together, making it easier to spot spatially organized biological processes, like how a tumor's edge evolves, directly from the data.
Technical view
Loom is a visual computing/analytics system for spatial transcriptomics (ST) data that supports pseudo-temporal trajectory analysis, cross-sample/cross-region comparison, and local microenvironment examination, addressing the multi-modal registration challenge of integrating ST data with single-cell reference atlases and temporal simulation outputs. It combines a novel glyph-based visual encoding with a computational backbone to jointly represent spatial enrichment, pseudo-temporal ordering, and gene expression dynamics within a unified interface. This targets computational biologists and bioinformatics tool builders needing to integrate trajectory inference (e.g., pseudotime methods) with spatial coordinate data and reference-based cell annotation in one interactive system, rather than stitching together separate single-purpose tools.
arXiv · q-bio.QMConceptual
Nearly 2 million patient records test how well current formulas predict kidney failure across ethnicities.
Chronic kidney disease progresses at different speeds in different people, and doctors rely on mathematical formulas (equations) that estimate kidney function from a blood test called creatinine to guide treatment decisions. This study used records from nearly two million adults across many clinics and hospitals, tracked for over a decade, to check how well current and older versions of these formulas actually predict kidney function and future kidney failure across a large, ethnically diverse population. It matters a lot because some older formulas adjusted their results based on a patient's race, which has been controversial since race isn't a reliable biological measure, and newer race-free formulas have replaced them; this study essentially puts those formulas to a massive real-world test to see which ones give the most accurate, fair predictions. The findings help determine which equation clinicians should trust to catch kidney disease early and predict who is headed toward kidney failure.
Technical view
This is a retrospective multicenter cohort study of 1,909,042 adults with serum creatinine measurements from 2012-2014, followed through January 2025 across primary care, acute care, and hospital settings, comparing current versus previously recommended GFR-estimating equations (including race-stratified versions) for predicting CKD stage prevalence and kidney failure risk. Primary outcomes include AUC-ROC for kidney failure prediction and CKD stage prevalence stratified by region of origin/ethnicity, enabling head-to-head comparison of equation performance (e.g., CKD-EPI variants) at population scale. Clinicians and epidemiologists can use these findings to select or validate GFR equations for multiethnic populations and to quantify the real-world impact of removing race coefficients from kidney function estimation.
arXiv · nlin.CDBuildable
Two chaotic 'brain cell' math models wired together spawn a wild, fractal, unpredictable pattern.
Rulkov maps are simplified mathematical models of how a single neuron (brain cell) fires electrical spikes over time, and researchers often connect multiple such maps to study how networks of neurons might behave together. This paper introduces a new way of linking two Rulkov neuron models, offering a rough biological story for what happens when the coupling's influence on the slower-changing parts of the neuron model grows large. The authors mathematically prove the linked system stays bounded (doesn't blow up to infinity) and retains a mathematical hallmark of chaos, then run computer simulations showing the connected pair produces a wildly complex, never-repeating attractor pattern with a fractal (infinitely detailed, non-whole-number-dimensional) structure. This matters for neuroscience-inspired math because it shows how even a very simple coupling rule between two chaotic 'neurons' can generate rich, chaotic collective behavior worth studying further.
Technical view
The paper defines a novel cross-coupling scheme for two Rulkov neuron maps and proves analytically that it preserves boundedness of trajectories and the existence of a snap-back repeller, which by the Marotto theorem guarantees Devaney chaos, provided these properties hold in the uncoupled system. For two standard chaotic Rulkov maps under this coupling, numerical simulations reveal a global strange attractor with a non-integer Kaplan-Yorke (Lyapunov) dimension, supported by time series, Lyapunov exponent spectra, bifurcation diagrams, and basin-of-attraction analysis, with a proposed generalization to arbitrary numbers of coupled maps. This gives dynamical-systems researchers both a rigorous chaos-preservation proof technique and a concrete numerically-characterized coupled-neuron-map model to extend toward larger chaotic neural network motifs.
arXiv · cs.DCRunnable
One Linux setting quietly wastes 30% of the energy used to simulate brain-like spiking networks.
Big supercomputers simulate "spiking" neural networks — software models of brain cells firing — to help design brain-inspired (neuromorphic) chips that use less power. These simulations spread work across many processors, and modern operating systems automatically shuffle data between processor "neighborhoods" (a feature called NUMA balancing) to try to speed things up. The researchers found that for this kind of program, that automatic shuffling backfires: switching it off cut energy use by 30%, without changing the simulation's results at all. That's a bigger energy saving than most other tricks computing centers use, and it's free — just flip a switch.
Technical view
The paper analyzes energy consumption of large-scale spiking neural network simulation codes on conventional CPU-based HPC systems, isolating the effect of Linux's automatic NUMA (Non-Uniform Memory Access) balancing feature. Because spiking-network memory access patterns interact dynamically with NUMA page-migration heuristics, the OS's balancing decisions add overhead without functional benefit; disabling automatic NUMA balancing yields a ~30% reduction in energy consumption with no change to simulation correctness. The effect is invisible in standard neuroscience workflows since output is unaffected, but shows up clearly in performance/energy profiling. Practitioners running spiking-network simulations on multi-socket NUMA nodes can replicate the gain via `/proc/sys/kernel/numa_balancing` or explicit process/memory pinning, ahead of costlier hardware or algorithmic efficiency efforts.
arXiv · q-bio.NCConceptual
A brain-inspired math model simulates why speech breaks down into stutters or dysfluency.
Speaking is a surprisingly complicated dance — you have to string sounds into words, take turns with a listener, and adjust on the fly. This paper builds a computer model of how the brain might plan and monitor speech, using a framework called active inference, where the brain constantly predicts what it will hear and say and corrects itself from feedback. The model breaks speech into phonemes (basic sound units) so researchers can simulate, purely in software, what happens when this prediction-and-correction loop misfires. The goal is to test theories about why fluency breaks down — stuttering, or the progressive speech problems seen in diseases like Parkinson's — by seeing what kinds of internal glitches produce dysfluent-sounding output, without needing to experiment on real patients.
Technical view
The authors formalize speech production and auditory segmentation as a POMDP-based active inference model over sequences of discrete phonemes, treating the brain as a generative model that plans motor actions and infers auditory outcomes under a shared internal model of turn-taking discourse. This provides a computational testbed for hypotheses about speech dysfluency mechanisms — transient (stuttering) or progressive (neurodegenerative) — by perturbing model parameters (e.g., precision weighting, policy depth) and observing emergent breakdowns in fluent phoneme sequencing. The framework's genericity means it's extensible to other hierarchical sequential-action domains beyond speech. Researchers could build on this by fitting parameters to clinical dysfluency data or comparing simulated deficits against behavioral/EEG markers of stuttering.
arXiv · q-bio.NCBuildable
A massive test of 200k+ brain-computer-interface pipelines finds no single winner works for everyone.
Brain-computer interfaces that read "motor imagery" — imagining moving your hand, say — to control a device struggle because everyone's brain signals look different. This study ran a huge, standardized comparison of decoding pipelines (combinations of signal processing and machine learning) across three public EEG datasets covering over 160 people, testing hundreds of thousands of pipeline-subject combinations. Two approaches — one based on "covariance" math describing signal patterns, another called Common Spatial Patterns — tended to be strongest, but which one wins still depends on the dataset and person. The practical payoff: instead of testing every possible pipeline for a new user, this work narrows down a small "portfolio" of good candidates to try first, saving huge amounts of trial-and-error.
Technical view
The authors ran a large-scale within-session benchmark using the MOABB LeftRightImagery paradigm across three public motor-imagery EEG datasets (Cho2017, PhysionetMI, Zhou2016; n=52/109/4), evaluating combinations of frequency bands, preprocessing, feature extraction, and classifiers — 216,714 raw evaluation rows aggregated to per-subject observations. Covariance tangent-space projection and CSP-based feature families consistently outperformed alternatives, but their relative ranking was dataset- and subject-dependent, quantifying the inter-individual heterogeneity problem that plagues MI-BCI generalization. The core contribution is a portfolio-based search-space reduction: a small candidate pipeline set (identified from this benchmark) can be tried to approximate optimal performance, which practitioners can adopt directly via MOABB to cut calibration time for new users or datasets.
arXiv · q-bio.PEConceptual
New math counts exactly how many trait-groupings on a family tree match evolutionary branches perfectly.
When biologists classify species, they can group them either by their family tree (who evolved from whom) or by shared physical traits — and these two groupings often don't match. A "monophyletic" group is the clean case where a shared trait actually corresponds to one single branch of the evolutionary tree. This paper works out formulas for exactly how many different ways a trait can be assigned to species on a given tree so it forms one of these tree-matching groups — essentially counting problems applied to evolutionary biology. It also connects this to "maximum parsimony," a classic method for reconstructing trees by assuming the simplest explanation (fewest trait changes) is most likely correct.
Technical view
The paper derives closed-form and general combinatorial formulas for counting monophyletic characters (leaf-trait assignments corresponding to a single clade) on an arbitrary phylogenetic tree, with simplified formulas for binary characters and specific tree shapes. It further establishes a linear-time algorithmic connection between monophyly and maximum parsimony, a standard tree-reconstruction optimality criterion, characterizing when parsimony-optimal characters are also monophyletic. This gives phylogenetics researchers exact enumerative baselines useful for null-model comparisons, character-simulation studies, or evaluating how "tree-like" real trait data are relative to random expectation.
arXiv · q-bio.QMRunnable
Bone-density scans need scanner-specific yardsticks before doctors can trust small changes over time.
DXA scans are the standard X-ray test for bone density (used to diagnose osteoporosis), and a newer software add-on called 3D-DXA can extract extra 3D detail — like how much bone is dense outer shell versus spongy interior — from the same scan. But different scanner machines can give slightly different numbers on the same patient, so before doctors can trust that a change in a follow-up scan is real and not just machine noise, they need to know how repeatable each measurement is on each specific machine. This study scanned patients twice, with full repositioning between scans, on five different scanner units across several clinics, to establish those precision baselines and calculate the smallest change that actually counts as meaningful — calibrating the ruler before using it to track disease or treatment.
Technical view
The study evaluates short-term precision (RMS-SD, RMS-CV) and least significant change (LSC at 95% CI) for 3D-DXA-derived volumetric/compartment BMD parameters (integral vBMD, trabecular vBMD, cortical sBMD via 3D-Shaper software) alongside conventional areal BMD (APEX software), using duplicate hip scans with full repositioning across five Hologic scanner units (Horizon Wi x2, Horizon A x2, Discovery W x1) at five clinical centers. This establishes scanner-model-specific precision benchmarks needed to interpret longitudinal 3D-DXA measurements clinically or in trials, since precision error propagates directly into the threshold for detecting real biological change. Clinicians adopting 3D-Shaper for longitudinal monitoring can use these LSC values as scanner-appropriate thresholds rather than assuming uniform precision across Hologic hardware generations.
arXiv · q-bio.PEConceptual
Math models reveal when bacteria should stay put versus swim away to maximize colony size.
Bacteria can swim toward food, but swimming costs energy — a trade-off that matters when nutrients are limited or the environment is closed with no fresh supply arriving. This study builds a mathematical model that explicitly includes this energy cost, then asks: what swimming strategy actually produces the most bacteria in the end, not just the fastest short-term growth? The surprising finding is that in environments where food shows up unpredictably, the best strategy isn't a simple "swim more when hungry" rule — instead, motility should rise and fall in a more complex pattern, essentially hedging bets against uncertainty.
Technical view
The authors formulate a PDE-based reaction-diffusion model of bacterial populations coupled to nutrient fields, explicitly incorporating the metabolic cost of motility as an energetic trade-off, then pose an optimal control problem maximizing total population yield (final cell count) rather than instantaneous growth rate. Solving this across different resource-distribution regimes, they find the optimal motility-response function is context-dependent: predictable landscapes favor simple monotonic chemotactic responses, while unpredictable environments favor a non-monotonic motility strategy as a robust bet-hedging solution. This provides a normative framework for interpreting observed diversity in real motility phenotypes and could be extended with stochastic PDEs or agent-based validation against chemotaxis data.
arXiv · cond-mat.softBuildable
Young red blood cells jam differently in tiny vessels, offering clues to altitude sickness.
Reticulocytes are young, not-yet-mature red blood cells that, unlike familiar disc-shaped mature ones, come in different shapes and stiffnesses. This matters because blood must squeeze through extremely narrow passages in the body, and how easily cells deform affects flow and clogging. The researchers combined lab experiments (flowing real blood through microscopic channels) with computer simulations of individual cells squeezing through fluid, cataloging different reticulocyte shapes and measuring how much slower stiffer ones move through tiny channels compared to how the spleen's narrow slits filter them. They then connect these mechanical differences to mountain sickness, the illness some people get at high altitude, since low oxygen changes how many young red cells are circulating.
Technical view
The study combines microfluidic microchannel flow experiments with dissipative particle dynamics (DPD) simulations to characterize reticulocyte biomechanics across subtypes (multilobular, cup-shaped, near-discocytic), parameterized (R1-R3) from transit-time and shape-under-flow data in 5-micron channels. Single-cell simulations show up to 30-50% slower transit for stiffer subtypes (R1) in narrow channels, while splenic-slit-like bending-dominated geometries discriminate subtypes far less (10-20%), and pairwise simulations reveal hydrodynamic coupling effects (leading cells altering follower dynamics) relevant to clogging. The work links reticulocyte mechanical heterogeneity to acute/chronic mountain sickness pathophysiology, and the DPD parameterization provides a reusable computational framework for modeling immature RBC populations in other microvascular contexts.
arXiv · q-bio.QMConceptual
New algebra lets scientists cleanly break complex gene-regulation networks into building blocks.
Boolean networks are simplified models where each part of a system (like a gene) is either "on" or "off," with its state depending on others — widely used to model gene regulation or cell signaling. As these models get bigger, it becomes hard to understand the whole system at once, so scientists want to break them into smaller modules the way you'd disassemble a machine into parts, but in a way that respects how the parts' behaviors actually recombine into the whole system's behavior over time. This paper introduces a formal mathematical structure, a type of algebra called a semiring, that lets you rigorously decompose a Boolean network's dynamics into its component modules, giving a solid theoretical foundation for a task researchers previously did more informally.
Technical view
The paper introduces a semiring algebraic structure on the space of Boolean network dynamics, enabling systematic decomposition of any Boolean network's global dynamics into the dynamics of its constituent modules/subnetworks in a compositionally compatible way. This gives a formal foundation for network modularity supporting reduction, design, control, and reverse-engineering tasks on large Boolean models (e.g., gene regulatory or signaling networks), replacing ad hoc decomposition heuristics with an algebraic framework carrying provable composition properties. The semiring formalism opens the door to applying established algebraic methods (e.g., tropical algebra, automata theory) to Boolean network analysis, letting practitioners formally verify modular reduction strategies rather than relying solely on simulation-based checks.
arXiv · q-bio.QMBuildable
A map that shows exactly which tropical forests to save, replant, or manage first.
Tropical forests are bursting with species but shrinking fast, and countries struggle to decide where to focus limited conservation money and effort. This research builds a combined map that overlays where trees could ecologically thrive against where human activity (farming, logging, development) is putting the most pressure. By predicting the ranges of 254 major tree species and cross-referencing that with land-use pressure data, the team flags 'refuge' zones worth protecting and 'conflict' zones where nature and human use collide. Tested on Costa Rica, the idea is to give governments a single, data-driven tool to prioritize what to protect, restore, or manage instead of guessing.
Technical view
The authors construct a synthetic spatial indicator by combining multi-species distribution models (254 dominant canopy tree species, used as a proxy for forest biodiversity) with open-access land-use/anthropogenic pressure layers, classifying pixels into refuge versus conflict zones based on the divergence between ecological potential and human pressure. Costa Rica serves as a national-scale case study to validate the indicator against the existing protected-area network, revealing gaps in current coverage. Practitioners could replicate the pipeline with their own species distribution models and land-use rasters to generate country-specific prioritization maps for CBD-aligned conservation planning.
arXiv · cs.CVBuildable
Scientists decoded what a person was looking at, from live brain scans, in real time.
Imagine reading someone's mind well enough to reconstruct the picture they're currently looking at — that's the goal of 'perceptual decoding' from brain scans. Normally the best image-reconstruction algorithms are too slow and computationally heavy to run during a live scan; they need the full dataset collected afterward. This team adapted a state-of-the-art model called MindEye2 so it can run fast enough to decode brain activity within seconds, while the person is still in the scanner, using a cloud computing platform called RT-Cloud. They showed it can still reliably reconstruct fine details of what someone saw in this compressed, real-time setting, which matters because real-time feedback opens doors to new brain-training therapies and interactive brain-computer interfaces.
Technical view
The paper presents a real-time-compatible adaptation of MindEye2, a computationally intensive fMRI-to-image reconstruction pipeline, re-engineered to fit within a seconds-scale processing budget without access to later session data. Implementation runs on RT-Cloud, an open-source scalable cloud platform for closed-loop fMRI, and the authors demonstrate single-trial decoding of perceived natural images during an actual real-time scan session. This closes much of the gap between offline state-of-the-art decoding accuracy and the constraints of real-time neurofeedback, providing a template for researchers wanting to build closed-loop perceptual or clinical neurofeedback paradigms.
arXiv · q-bio.PERunnable
A hidden math trick separates 'how contagious' a virus is from 'how many were already immune.'
When scientists watch an outbreak unfold, they usually can only measure a blended number — how fast the disease spreads given both its true contagiousness and however much immunity already existed in the population — not the two factors separately. This is a problem because you might wrongly think a virus is mild just because lots of people were already immune, or vice versa. The researchers discovered a conserved quantity in epidemic math — something like a physics conservation law but for outbreaks — that lets them mathematically tease apart the virus's raw transmissibility from the population's pre-existing immunity, using only the case-count curve from a single outbreak. They tested this on simulated epidemics and then applied it to the 1918 flu pandemic, for the first time estimating rather than assuming how much immunity people already had.
Technical view
The paper identifies a conservation law for 'epidemic momentum' (prevalence weighted by remaining infection potential) in standard compartmental epidemic models, which provides an additional constraint beyond the usual growth-rate fitting and thus allows separate identification of R0 and the pre-epidemic susceptible fraction x⁻ from R_eff = R0·x⁻. Validation is performed on stochastic epidemic simulations before reanalyzing 1918 influenza time series, yielding independent estimates of transmissibility and prior immunity rather than assuming one. This offers epidemiologists a new inference method applicable to any single time series of case counts, potentially resolving longstanding ambiguity in retrospective R0 estimates for historical or emerging pathogens.
arXiv · q-bio.NCBuildable
An AI watches brainwave squiggles and automatically tosses out the noisy junk.
EEG caps read electrical brain activity through the scalp, which is great for studying things like child brain development, but the raw signal is a tangled mess mixing real brain signals with noise from things like eye blinks or muscle twitches. A technique called ICA (independent component analysis) can mathematically separate that tangle into distinct components, but a human expert then has to manually inspect each one and decide which are real brain signals versus junk — a slow, expertise-heavy bottleneck. This work builds a computer-vision-based system that automates that classification step, essentially teaching software to recognize what a 'good' versus 'noisy' brain signal component looks like. The payoff is faster, more scalable EEG research and the possibility of using EEG in near real-time applications.
Technical view
The authors present an automated independent component (IC) classification architecture for EEG artifact rejection, framing IC recognition as a computer-vision problem (likely operating on scalp topography maps and/or time-frequency representations of each component) rather than relying on manual expert review after ICA decomposition. The system aims to match manual classification accuracy while removing the human bottleneck, enabling large-scale EEG studies and near-real-time processing pipelines. Practitioners doing EEG-based cognitive or clinical research could integrate this as a drop-in automated artifact-rejection stage in their existing ICA preprocessing pipeline.
bioRxiv · pharmacology and toxicologyConceptual
Liver cells in the danger zone pause dividing to survive a toxic hit, not to heal faster.
After liver damage from something like an overdose of acetaminophen (Tylenol), the liver normally repairs itself by having its cells rapidly divide. But this study found that right after injury, liver cells briefly stop dividing altogether — and this pause is strongest in cells located in the 'mid-zone,' a specific region of liver tissue that happens to process the most acetaminophen. Using a technique that maps gene activity across different liver zones, plus other lab tests, the researchers traced this pause to a stress-response pathway (called Atf4-Chop) that puts the brakes on cell division via a specific brake-pedal gene. The takeaway is that liver cells seem to prioritize surviving the initial chemical stress over immediately multiplying, which is a previously underappreciated early step in how the liver bounces back from injury.
Technical view
Using spatial transcriptomics combined with immunohistochemistry and functional assays, the authors show that mid-zone hepatocytes — the zone with peak acetaminophen (APAP) metabolism — exhibit the most pronounced transient proliferation arrest during early APAP-induced liver injury, driven by an Atf4-Chop stress-response axis that upregulates the cell-cycle inhibitor Btg2. Pericentral zone evidence for the same arrest was comparatively weak, indicating zonation-specific stress signaling rather than a uniform liver-wide response. This establishes a testable model where hepatocytes transiently trade proliferation for stress adaptation post-injury, giving hepatotoxicity researchers a specific pathway (Atf4-Chop-Btg2) to target or knock out in mouse models to test whether blocking this arrest accelerates or worsens recovery.
bioRxiv · plant biologyRunnable
A citrus-peel chemical attacks the fungus that rots potatoes from the inside out.
Potato dry rot, caused by a fungus called Fusarium, damages potatoes both in the field and in storage, and D-limonene — the compound that gives citrus fruit its smell — has been known to fight fungi in general terms, but exactly how it works at the cellular level was unclear. This study measured precisely how much D-limonene it takes to stop the fungus (finding a fairly low effective dose), and showed it distorts the fungus's thread-like growth structures, weakens its ability to infect, and reduces its ability to reproduce via spores. The researchers also read out which genes turn on or off in the fungus when exposed to D-limonene, identifying nearly 1,900 affected genes tied to particular biological pathways. This helps turn a natural, citrus-derived compound into a more scientifically grounded potential treatment for protecting stored potatoes.
Technical view
The study quantifies D-limonene's antifungal potency against Fusarium oxysporum (causal agent of potato dry rot) with an IC50 of 8.32 µL/mL, and shows dose-dependent effects on hyphal morphology, pathogenicity, spore germination/viability, and chitin staining patterns (via calcofluor white/fluorescent brightener 28), indicating cell-wall disruption. RNA-seq identified 1,884 differentially expressed genes (1,027 down, 857 up) with KEGG pathway enrichment mapping the transcriptional stress response to D-limonene exposure. This gives postharvest pathology researchers a quantified dose-response benchmark and a candidate gene/pathway list to pursue mechanistic follow-up (e.g., cell-wall or membrane-integrity pathway knockouts) or to formulate D-limonene-based biofungicide treatments for stored potatoes.
bioRxiv · neuroscienceConceptual
Damage a brain relay station in baby monkeys, and adult memory circuits misfire like in schizophrenia.
Scientists study a small hub deep in the brain called the medial pulvinar, which relays signals to the prefrontal cortex — the part of your brain responsible for planning and working memory. They damaged this hub in newborn marmoset monkeys and found that, as the animals grew up, their prefrontal cortex developed abnormally and they struggled with memory tasks as adults — but the same damage done to adult monkeys caused no such problems. The early damage specifically stunted a class of brain cells called parvalbumin interneurons, which normally act like brakes that keep neural activity organized. This matters because schizophrenia is believed to stem from exactly this kind of miswired inhibition in the prefrontal cortex, so the study pinpoints a critical early developmental window where things can go wrong.
Technical view
Bilateral neonatal lesions of the marmoset medial pulvinar altered adolescent prefrontal diffusion MRI trajectories and produced adult working memory deficits absent after equivalent adult-onset lesions, establishing developmental-timing specificity. Early lesions reduced thalamocortical input onto layer 3 parvalbumin (PV) interneurons, lowered prefrontal gamma oscillatory power, decreased PV expression, and left fast-spiking interneurons in an immature electrophysiological state. The findings implicate thalamocortical input as a driver of PV interneuron maturation and gamma-band inhibitory circuit function, offering a primate developmental model for testing interventions that target this critical window in schizophrenia-relevant circuitry.
bioRxiv · neuroscienceConceptual
Brain synapses use a clever calcium trick to avoid getting scrambled by conflicting learning signals.
Brain cells strengthen or weaken their connections based on how much calcium flows in during activity — more calcium above one threshold triggers strengthening, while a different calcium source above a lower threshold triggers weakening. In certain neurons deep in a brain region called the striatum, both signals can show up at the same synapse during learning, which risks garbling the message. This study uses computer models to show that these neurons have a built-in tuning system, called metaplasticity, that lets a synapse cleanly pick just one outcome — strengthen or weaken — even when both competing signals are present. The researchers tested this using tricky learning scenarios where different inputs share overlapping features, which is exactly when this kind of confusion would normally occur. It matters because it explains how the brain keeps learning reliable even when signals overlap and compete.
Technical view
The authors model striatal projection neurons, which use two distinct calcium sources with separate thresholds to gate LTP versus LTD, and show via metaplasticity (activity-dependent threshold modification) that synapses exposed to co-occurring LTP- and LTD-inducing calcium signals during learning resolve to expressing only one plasticity form. Using linear and nonlinear feature binding problem (FBP/NFBP) tasks — chosen because overlapping input features force competing calcium signals onto shared synapses — they identify complementary, opposing roles for the two thresholds in disambiguating plasticity outcomes. The work provides a mechanistic, simulation-based account of how dual-threshold calcium systems avoid destructive interference during associative learning, offering testable predictions for threshold dynamics in striatal circuits.
bioRxiv · neuroscienceConceptual
Feeling less warmth with age might really be feeling warmth less reliably.
When your skin senses hot or cold, two things matter: how sensitive you are (the lowest temperature you can notice) and how consistent or precise that sense is from one moment to the next. Most research only measures sensitivity and ignores precision, but this study looked at both in healthy adults aged 21 to 80 and in patients with diabetic nerve damage (a common complication that dulls sensation). Using statistical models, the researchers found that aging raises the threshold for feeling cold, warmth, and pain, and separately affects how precisely people can judge these sensations. This distinction matters because it could give doctors a sharper, two-part tool to tell normal aging apart from actual nerve disease, potentially catching problems earlier.
Technical view
Using Bayesian hierarchical psychometric modeling, the study jointly estimated threshold (sensitivity) and slope (precision) parameters for cold detection, warm detection, cold pain, and heat pain in 75 healthy adults (21-80 years) and 33 patients with diabetic polyneuropathy (DPN), with per-participant estimates feeding into classification analyses. Aging alone shifted thresholds upward for cold detection, warm detection, and cold pain, while precision measures provided additional discriminative information beyond thresholds. The approach demonstrates that psychometric slope, not just threshold, adds classification value for distinguishing DPN from normal aging, suggesting sensitivity-only assessments in clinical thermosensory testing may be systematically underpowered.
bioRxiv · neuroscienceConceptual
A weird brain 'blackout wave' — not the seizure — may be what makes shock therapy actually work.
Electroconvulsive therapy (ECT) is a powerful treatment for severe depression and other psychiatric conditions, but nobody fully understands why it works — it's long been assumed the induced seizure itself is the key ingredient. This study points to a different culprit: a phenomenon called cortical spreading depression, essentially a slow-moving wave of brain cells briefly shutting down that sweeps across the brain's surface. The researchers found the same distinctive brain wave patterns in mice given electric shock treatment and in real ECT patients, and showed this wave switches on a gene called Fos that marks the brain rewiring itself — plus other changes linked to good treatment outcomes. This reframes ECT's mechanism, suggesting the 'reset' wave, not just the seizure, may drive its therapeutic benefits, which could help refine treatment and reduce side effects.
Technical view
The study shows that electroconvulsive stimulation (ECS) in mice reliably triggers cortical spreading depression (CSD), evidenced by neuronal oscillation signatures matching those observed in ECT patients, challenging the conventional model that generalized seizure alone drives ECT efficacy. CSD induction was associated with upregulation of the immediate early gene Fos, a canonical marker of activity-dependent plasticity, alongside molecular factors correlated with positive clinical ECT outcomes. This links a specific, mechanistically tractable cortical phenomenon (CSD) to ECT's plasticity-inducing effects, opening a path to dissect CSD's causal contribution separately from seizure activity and potentially optimize stimulation protocols around CSD induction.
bioRxiv · neuroscienceBuildable
Two neighboring thalamus zones split the job of pain 'where' versus pain 'how bad it feels.'
Pain has two sides: the physical sensation of where and how intense it is, and the emotional distress it causes. This study looks at a brain structure called the mediodorsal thalamus, which relays pain information to the prefrontal cortex, and asks whether two of its subregions handle these two sides of pain separately. Using precise lesions and light-based manipulation of specific neural pathways in rats, the researchers found that one subregion (MDmc) is needed for both the physical sensitivity to pain and the desire to avoid painful situations, pointing to distinct wiring for the sensory versus emotional aspects of pain. This matters because chronic pain often involves emotional suffering that current treatments don't address well, and understanding these separate circuits could lead to more targeted therapies.
Technical view
Using subdivision-selective excitotoxic lesions, anterograde tracing, laminar activity mapping, and projection-specific optogenetics targeting medial-central (MDmc) versus lateral (MDl) mediodorsal thalamus terminals in the anterior cingulate cortex (ACC) and prelimbic cortex (PrL), the authors dissociate sensory-discriminative from affective-motivational pain processing. Both MDmc and MDl lesions produced mechanical and thermal hypersensitivity, but only MDmc lesions increased pain-related avoidance behavior, implicating MDmc-ACC/PrL circuitry specifically in the affective-motivational dimension of pain. This provides a circuit-level dissociation within a thalamic nucleus previously treated as functionally uniform, giving a template for pathway-specific optogenetic dissection of sensory versus affective pain components that could inform selective analgesic targeting.
bioRxiv · neuroscienceConceptual
Brain immune cells bite chunks off neurons to haul away trash the neuron can't dispose of itself.
Neurons are long, thin cells, and their internal 'garbage disposal' units — organelles that break down old proteins — normally travel back to the cell body to be recycled. But some of these garbage units are too big to fit through the neuron's narrow branches, creating a problem: how do they get cleared out? This study shows that microglia, the brain's resident immune and cleanup cells, solve this by briefly touching a neuron's branch, pinching off just the piece containing the stuck garbage unit, and carrying it away — leaving the rest of the neuron undamaged. The researchers name this new process 'skoupocytosis,' after the Greek word for garbage, and identify a molecule, ABHD16a, that gathers at these pinch sites. This reveals an entirely new way brain cells cooperate to keep neurons clean, which is important since failed cleanup is linked to neurodegenerative disease.
Technical view
Using in vitro and in vivo imaging, the authors demonstrate that microglia make transient membrane contact with neuronal processes at sites where proteolytic (lysosome-related) organelles too large for retrograde axonal transport are stationed, and excise a small membrane-bound fragment containing the organelle without damaging the remaining process — a mechanism they term skoupocytosis. The phosphatidylserine lipase ABHD16a accumulates at these microglia-neuron contact sites, implicating phosphatidylserine externalization as an eat-me signal analogous to other phagocytic pruning processes. This identifies a previously uncharacterized trans-cellular proteostasis mechanism, suggesting microglial dysfunction could contribute to neuronal proteolytic organelle accumulation in aging or neurodegenerative disease, and nominates ABHD16a as a candidate molecular handle for further mechanistic and disease-model studies.
bioRxiv · molecular biologyBuildable
Tiny mutations in one autism-linked protein rewire its molecular handshake atom by atom.
Shank1 is a scaffolding protein that helps hold together the machinery at brain synapses, and mutations in the Shank protein family are linked to autism and some cancers. This study focuses on a small, flexible loop within a binding pocket of Shank1 (called a PDZ domain) that grabs onto partner proteins, and tests five disease-linked mutations to see how they change that grip. Using lab experiments plus computer simulations that model atoms jiggling over time, the researchers mapped exactly which molecular contacts get rearranged by each mutation. Most mutations weakened binding overall, but one, called R736Q, was unusual: it became more heat-stable and actually gripped one particular partner protein (GKAP) even tighter than normal. This fine-grained, partner-specific picture helps explain why the same protein family can cause different diseases depending on the exact mutation and binding partner involved.
Technical view
Using molecular dynamics simulations combined with experimental binding assays, the authors characterize how five disease-associated missense mutations in the Shank1 PDZ domain — including its unique flexible β2-β3 loop — redistribute sidechain-sidechain contact networks to alter peptide-specific binding affinities. While most mutants broadly weaken interactions with partner peptides, the R736Q variant uniquely increases thermal stability and paradoxically enhances binding affinity for the GKAP peptide relative to wild type, demonstrating that binding effects are not uniformly destabilizing but partner-dependent. This structural-dynamics framework — resolving which specific sidechain contacts shift per mutation — offers a template for predicting how other PDZ domain disease mutations will differentially affect distinct postsynaptic protein interaction networks, relevant to autism and cancer-associated Shank dysregulation.
bioRxiv · cell biologyBuildable
Cells have a built-in janitor that can be switched on to clear out the protein behind rapid aging.
Hutchinson-Gilford Progeria Syndrome is a rare, devastating disease where children age prematurely, caused by a toxic protein called progerin building up in cells' nuclei due to a single gene mutation. Scientists already knew that if cells are given the right trigger, they can break down and clear out progerin, which reverses some of the disease's cellular damage — but exactly which cellular machinery does this clearing was unclear. This study points to a protein-tagging complex called the Anaphase Promoting Complex (APC), which normally marks unwanted proteins for destruction, as a key player: by analyzing gene activity data from progeria patients' skin cells, the researchers found APC-related genes were disrupted, and boosting APC activity helped degrade progerin. This matters because it identifies a specific molecular lever — ramping up APC activity — that could potentially be targeted to treat this fatal childhood aging disease.
Technical view
Through meta-analysis of RNA-seq data from HGPS patient skin biopsies, the authors identified dysregulated expression of genes encoding Anaphase Promoting Complex (APC) subunits and substrates, an E3 ubiquitin ligase previously linked to cellular aging when its activity declines. Pharmacological stimulation of APC activity decreased progerin levels via ubiquitin-dependent autophagic degradation, directly implicating APC as a mediator of progerin clearance rather than merely a correlated aging marker. This establishes APC activation as a candidate therapeutic strategy for HGPS and provides a mechanistic link between a core cell-cycle ubiquitin ligase and clearance of a lamin-derived proteotoxic species, a route researchers could pursue with APC activators or by mapping which specific APC substrates/subunits are rate-limiting for progerin turnover.
bioRxiv · cell biologyBuildable
A 'dead' backup gene may quietly sabotage brain cell power plants in schizophrenia.
Our cells carry pseudogenes — broken, non-functional copies of real genes — that were long dismissed as junk DNA. This study looks at one such pseudogene copy of NDUFV2, a gene essential for mitochondria (the energy factories inside cells) to make power for neurons. The researchers found that in people with schizophrenia, this pseudogene becomes overactive, and when it's more active, the real NDUFV2 gene and the cell's energy production both drop. By artificially dialing the pseudogene up or down in lab-grown cells, they could test whether it's actually causing the energy dysfunction, rather than just being a bystander. This matters because it suggests a new, previously overlooked mechanism — a 'junk' gene messing with mitochondria — that could help explain the biological roots of schizophrenia.
Technical view
NDUFV2P1 is a processed pseudogene of NDUFV2, a core subunit of mitochondrial Complex I, and its expression is elevated in SZ patient brain and peripheral tissue, inversely correlating with NDUFV2 levels and respiratory function in EBV-transformed lymphoblastoid cell lines. In-silico analysis ruled out siRNA-like sequence complementarity as the interference mechanism, pointing instead to another post-transcriptional mode of action (e.g., competitive RNA-binding or ceRNA-like sequestration). The authors directly manipulated PG abundance (overexpression/knockdown) in LCLs to establish causality on NDUFV2 expression, Complex I-dependent respiration, and downstream neuronal activity readouts. This positions PG as a testable post-transcriptional regulator and a candidate node for modeling SZ-associated mitochondrial dysfunction, replicable via CRISPR-based PG modulation in iPSC-derived neurons.
bioRxiv · developmental biologyConceptual
Turning on one gene in the wrong place makes mouse testes build a broken one-way valve.
Deep inside the testis, sperm-forming tubules connect to a drainage network called the rete testis, and a special valve-like structure (the Sertoli valve) normally lets fluid flow one way to prevent backflow. Earlier work showed that a gene called SOX17, when missing from the rete testis lining, causes this valve to fail, fluid to flow backward, and fertility to drop. Here the researchers did the opposite experiment: they engineered mice to switch SOX17 on in an extra location — the Sertoli cells that don't normally have it — using a hormone-gene promoter as an 'on switch.' They then examined whether misplaced SOX17 caused an overgrown, malformed valve and studied how that affected sperm production. This kind of gain-of-function test helps confirm that SOX17 isn't just necessary but actively instructs valve formation, refining our understanding of a subtle but critical piece of the male reproductive plumbing.
Technical view
Building on RT-specific Sox17 conditional knockouts that show Sertoli valve (SV) disruption and RT-fluid backflow causing defective spermiogenesis, the authors generated an AMH promoter-driven Sox17 transgenic mouse to ectopically express SOX17 in Sertoli cells rather than its native rete testis epithelium. This gain-of-function model produced hyperplastic SV formation, directly implicating SOX17 dosage/localization as instructive (not merely permissive) for SV morphogenesis. Phenotyping of spermatogenesis and valve architecture in AMH-Sox17 Tg testes complements the cKO loss-of-function data, together framing SOX17 as a key transcriptional determinant of a fluid-flow-control structure at the RT-tubule interface. This dual loss/gain approach offers a template for dissecting non-cell-autonomous SOX17 signaling targets in future mechanistic studies.
bioRxiv · evolutionary biologyBuildable
Sperm-packing proteins evolve fast because X and Y chromosomes are secretly at war.
In many animals, sperm cells replace the normal DNA-packing proteins (histones) with tighter, specialized ones called protamines, and oddly these protamines evolve very quickly across species — nobody knew why. This study used gene-editing to swap the protamine gene Mst77F between fruit fly species and watched what happened to sperm carrying the X versus the Y chromosome. They found that mismatched or ancestral versions of the protein caused X-carrying sperm specifically to pack their DNA poorly, making them lose out to Y-carrying sperm and skewing offspring toward males — a phenomenon called meiotic drive, essentially a genetic conflict between sex chromosomes. The findings suggest protamines evolve rapidly not for some obvious fertility reason but because they're a battleground gene, constantly being tweaked to stop one chromosome from cheating in the race to fertilize eggs, revealing a hidden evolutionary arms race inside male reproduction.
Technical view
Using in vivo allelic replacement of the protamine-like gene Mst77F in Drosophila melanogaster, the authors show that substituting orthologous protamine sequences disrupts DNA compaction specifically in X-bearing (versus Y-bearing) spermatids, reducing X-sperm viability and skewing progeny sex ratio toward males — a signature of meiotic drive. Comparative analysis with D. yakuba shows Mst77F is dispensable for baseline male fertility there but remains required to suppress sex-ratio distortion, decoupling its fertility function from its drive-suppression function. This supports a model where recurrent intragenomic conflict over chromosome-specific chromatin compaction, rather than canonical sperm-competition or fertility pressures, drives protamine's unusually fast molecular evolution. The allelic-swap paradigm is directly extendable to other rapidly evolving protamines/spermatid chromatin proteins to test drive-suppression hypotheses genus-wide.
bioRxiv · evolutionary biologyConceptual
From oak trees to humans, life hits peak baby-making at almost exactly 37% of its lifespan.
Every living thing faces a tradeoff: reproduce early and risk dying before you're at your best, or wait and grow stronger/wiser but risk running out of time. This study compared reproductive timing across plants, animals, and humans and found a striking pattern — peak reproductive effort tends to happen at roughly 37% (mathematically, 1/e) of a species' maximum lifespan, regardless of whether that lifespan is two years or eighty. That number isn't arbitrary: it's the same fraction that shows up in a classic math puzzle called the 'optimal stopping' or secretary problem, where the best strategy for picking the best option from a sequence (like job candidates) is to skip the first 37% just to gather information, then commit to the next best thing you see. The authors argue that evolution may have converged on this same mathematical solution for the different but structurally similar problem of when to prioritize reproduction, suggesting deep, shared mathematical logic underlying how life allocates effort across time.
Technical view
The authors performed a cross-taxonomic comparative analysis of age-specific reproductive effort across plants, animals, and humans, normalizing reproductive timing to species-specific maximum lifespan, and found peak effort consistently clustering near t/T_max ≈ 1/e (~37%), independent of absolute lifespan or phylogenetic group. They connect this empirical convergence to Bruss's 1984 optimal stopping theory (the 1/e-law of best choice), which proves that observing 1/e of a sequential option pool before committing maximizes the probability of selecting the best option under uncertainty. The paper integrates this stopping-rule framework with population dynamics models (balancing mortality risk against fecundity/size-dependent benefit) to argue the reproductive timing pattern is a life-history analog of optimal sequential decision-making. This offers a testable quantitative null model — 1/e scaling — against which species-specific deviations in reproductive scheduling (e.g., due to extrinsic mortality or resource variance) can be benchmarked in future life-history datasets.
bioRxiv · genomicsRunnable
Scientists finally fully sequenced 8,000 of the genome's most notoriously repetitive, unreadable regions.
Centromeres are the crucial pinch-points on chromosomes that ensure DNA gets split correctly when cells divide, but they're made of long, highly repetitive DNA sequences that were essentially unreadable with older sequencing technology — like trying to read a book that's the same page repeated thousands of times with tiny variations. Using newer long-read genome assembly methods, this team fully sequenced centromeres from 320 people of Asian ancestry, then combined that with existing global genome datasets to build a catalog of over 8,000 complete centromeres. This lets them see, for the first time at scale, how much these repetitive regions vary between individuals and populations, and how they've evolved — details that were previously invisible. Understanding centromere diversity matters because errors in centromere function cause chromosome mis-segregation, linked to birth defects, infertility, and cancer, so a detailed map is a foundational resource for studying those diseases and human genome evolution.
Technical view
Leveraging phased long-read genome assemblies from the Asian Pan-Genome Project (320 individuals, 6,312 centromeres) integrated with HPRC and HGSVC assemblies, the authors assembled a gapless, multidimensional variation map spanning 8,000+ complete human centromeres — a region historically intractable for reference-based short-read approaches. They quantify that centromeric alpha-satellite arrays constitute 4.19–6.01% of the genome with substantial size/architecture variation across chromosomes, and apply a refined alpha-satellite clustering method to resolve higher-order repeat structure and population stratification patterns. This dataset enables downstream analyses of centromere evolutionary trajectories, satellite array expansion/contraction dynamics, and genotype-phenotype studies of centromere-associated chromosomal instability. The assemblies and variation catalog are positioned as a reusable reference resource for pangenome-scale centromere research, analogous to what HPRC provided for euchromatic regions.
bioRxiv · bioengineeringBuildable
AI plus droplet robots redesign an enzyme by testing 30,000 variants and learning its 'fingerprint.'
Enzymes are proteins that speed up chemical reactions, and engineers often want to tweak them to work on new target molecules, but there are far too many possible DNA sequence variants to test by hand. This study combines two powerful tools: microfluidic droplet sorting, which can rapidly test millions of tiny enzyme variants trapped in droplets, and generative machine learning, which learns patterns from that messy, high-volume data even when individual measurements are rough or indirect. They built a huge library of over 5 million variants of a peroxygenase enzyme (a type used in green chemistry), screened tens of thousands of them for activity, and used that data to train a model capturing what sequence changes shift the enzyme's target specificity. This 'fingerprint' approach shows how AI and high-throughput lab robotics can work together to redesign enzymes faster than trial-and-error alone, which matters for industries wanting cheaper, greener catalysts for chemical manufacturing.
Technical view
The authors combine microfluidic ultrahigh-throughput screening (uHTS) with generative ML to engineer substrate specificity into an unspecific peroxygenase (AbrUPO) from Aspergillus brasiliensis, expressed in a Komagataella phaffii (Pichia pastoris) library of >5 million variants. Droplet-based sorting generated a training set of >30,000 unique sequence-function pairs from indirect, lower-fidelity assay readouts, which were used to build a generative model 'fingerprint' capturing sequence-specificity relationships for the target enzyme class. The approach demonstrates that noisy, high-throughput functional data — rather than requiring precise biochemical characterization per variant — can sufficiently constrain generative sequence design for enzyme engineering. This uHTS+generative-ML pipeline is a template replicable for other enzyme classes where uHTS assays exist but produce only low-fidelity or indirect functional signals.
bioRxiv · bioinformaticsRunnable
A free, AI-built single-file tool aims to replace expensive proprietary genomics software.
When scientists sequence single cells' RNA to study gene activity, they typically rely on a tool called Cell Ranger — but it's proprietary, meaning its license blocks people from freely modifying, sharing, or repurposing it, which is a growing problem now that AI 'agents' are being used to automatically run scientific analyses and need open, inspectable tools. This project builds an open-source alternative called STAR Suite by massively expanding an existing open aligner (STAR) into an all-in-one executable that handles the whole pipeline — from trimming raw sequencing reads to sorting cells by their barcodes to quality control — without needing a patchwork of other software. Notably, most of the huge amount of new code (over 130,000 lines) was written with AI assistance under human direction, itself a case study in AI-assisted scientific software engineering. This matters because it gives researchers and their AI lab assistants a transparent, freely modifiable, and shareable foundation for processing genomic data, instead of being locked into a closed commercial tool.
Technical view
STAR Suite extends the STAR aligner codebase (28,228 lines) with 132,226 additional lines of C/C++, built largely through human-directed AI-assisted software engineering, into a dependency-free single executable covering adapter trimming, feature-barcode assignment, 10x Flex probe processing, SLAM-seq analysis, sorting, and QC — filling the gap left by Cell Ranger's restrictive license (no redistribution, modification, or non-10x use) and the lack of a production-ready open-source Flex pipeline. By consolidating the full transcriptomics processing chain into one integrated binary, it removes the tool-chaining fragility that impedes both bench biologists and AI agents automating sequencing analysis, improving reproducibility and AI-discoverability of the pipeline. Practitioners can adopt it as a drop-in open alternative for 10x-style single-cell/Flex data processing, and its single-executable, no-external-dependency design makes it straightforward to containerize or wrap for agent-driven automated analysis workflows.
bioRxiv · biophysicsConceptual
A membrane-cutting protein doesn't know which way to cut — the membrane itself tells it.
Inside cells, a molecular machine called ESCRT-III pinches off small membrane bubbles from the *inside* of a tube, a neat trick called 'reverse-topology' fission — but strangely, in test-tube experiments with simplified membranes, the same machine does the opposite, pinching from the outside instead. This paper asks why, and finds the answer isn't in the ESCRT machine itself but in the membrane it's working on: real cell membranes have an asymmetric mix of fat molecules (lipids) between their inner and outer layers, and disrupting that asymmetry in yeast doesn't stop the machine from working, but makes it much more sensitive to the membrane's physical state, causing sorting errors and stalled traffic. Using both engineered yeast and reconstituted artificial membranes, they show that simply making the two membrane faces asymmetric is enough to set the direction of bending, even without other help. This flips the usual assumption that direction is hardwired into the protein, and shows instead that the membrane's own composition is doing critical directional work — relevant to any process, from cell division to viral budding, that depends on ESCRT-driven membrane shaping.
Technical view
ESCRT-III normally drives reverse-topology membrane fission (budding away from the cytoplasm) in vivo, yet in minimal in vitro reconstitutions it assembles on the outside of membrane necks and produces normal-topology fission — a longstanding discrepancy. Using genetic perturbation of phospholipid asymmetry and sphingolipid homeostasis in budding yeast, the authors show ILV (intraluminal vesicle) formation becomes highly sensitive to membrane physical state without ESCRT-dependent trafficking being abolished outright, manifesting as inefficient cargo sorting and stalled endosomal intermediates. In vitro reconstitution and synthetic in vivo cargo systems demonstrate that asymmetric protein/lipid distribution across the bilayer alone is sufficient to dictate deformation direction, independent of any intrinsic topological bias in the ESCRT-III machinery. This reframes ESCRT directionality as an emergent property of bilayer asymmetry rather than protein-encoded, suggesting future mechanistic work should manipulate lipid scramblase/flippase activity and leaflet composition as primary variables in ESCRT fission assays.
bioRxiv · plant biologyConceptual
In seeds, mom's and dad's genes don't just each do their thing — they argue through a chain of command.
When a plant seed forms, genes inherited from the mother and father aren't always equally active — some genes are switched on only if they came from the dad, others only from the mom, a phenomenon called genomic imprinting. This study looks at how those 'parent-specific' genes are wired into larger control networks in a wild mustard relative, rather than studying them one by one. The researchers found imprinting mostly affects a small number of biological pathways, and a few imprinted genes act like network hubs that boss around many other genes — one especially important hub, called NRPE1, controls epigenetic marks (chemical tags on DNA that switch genes on/off). Interestingly, the father's genes were picky, mainly influencing other paternal genes, while the mother's genes freely influenced both — suggesting the sexes use different strategies in this ongoing tug-of-war over seed resources.
Technical view
The authors generated a species-level imprintome for Arabidopsis arenosa endosperm and integrated it with gene regulatory network (GRN) inference to characterize regulatory relationships among paternally expressed genes (PEGs) and maternally expressed genes (MEGs). Imprinting was concentrated in a limited set of pathways enriched for dosage-sensitive processes, consistent with parental conflict theory, and several imprinted genes — notably the RNA Pol V subunit NRPE1 — emerged as regulatory hubs, implicating RNA-directed DNA methylation in imprinting maintenance. Network directionality was asymmetric: PEG-encoded regulators preferentially targeted other PEGs, whereas MEG-encoded regulators targeted both PEG and MEG targets without bias. This asymmetry provides a testable network-level signature of parental conflict and a candidate gene list (centered on NRPE1) for follow-up perturbation studies of endosperm dosage control.
bioRxiv · plant biologyBuildable
Scientists moved one plant enzyme to a new cellular compartment to try to make photosynthesis less wasteful — it wasn't enough alone.
Plants lose a lot of energy to a wasteful process called photorespiration, a side reaction that happens when the enzyme plants use to capture CO2 accidentally grabs oxygen instead. Researchers have been trying to build shortcut 'bypass' pathways that intercept the wasteful byproduct before it costs the plant too much energy, usually by installing new enzymes in the cell's mitochondria or other compartments. Here, the team took an enzyme from algae (glycolate dehydrogenase) that normally works in one compartment and instead installed it directly in the chloroplast — the solar-panel part of the cell where photosynthesis happens — in both algae and tobacco plants. The enzyme worked and stayed active there, but on its own it didn't make the plants grow faster or photosynthesize better, showing that a single relocated enzyme isn't enough; a full multi-enzyme pathway is needed to actually deliver a payoff.
Technical view
The study tests chloroplast-targeted expression of Chlamydomonas reinhardtii glycolate dehydrogenase (CrGDH), normally mitochondrial, as the entry enzyme of a photorespiratory bypass, avoiding the multi-organelle trafficking required by prior bypass designs. Proof-of-concept was established in Chlamydomonas, then extended to stable transgenic tobacco lines confirmed by immunodetection to accumulate active CrGDH in chloroplasts. Photosynthetic rate and biomass measurements showed no improvement (and in some cases slight decrements) relative to wild type under tested conditions, indicating CrGDH expression alone is not rate-limiting for bypass efficacy. The result argues that a complete chloroplast-localized bypass (downstream enzymes converting glycolate to CO2-conserving intermediates in situ) is necessary, providing a design constraint for future single-compartment photorespiratory engineering efforts.
bioRxiv · plant biologyBuildable
A crop-killing virus hijacks its host's own DNA-copying machinery — and scientists just mapped which parts it grabs.
Geminiviruses are tiny viruses that devastate crops like tomatoes and cotton worldwide, and they're so stripped-down that they carry only one key protein of their own, called Rep, to copy their DNA — everything else they borrow from the plant cell's own genome-copying toolkit. Because the virus has so few of its own genes, understanding it means understanding which host proteins it recruits and how. The researchers used a technique called proximity labeling (essentially attaching a chemical tag to anything that gets close to the Rep protein inside infected cells) to catch the plant proteins the virus pulls in during infection with two different geminiviruses. This gives a parts list of the hijacked cellular machine, which is valuable because blocking one of these host connection points could be a new way to protect crops without needing to constantly chase mutating viral genes.
Technical view
Using TurboID proximity labeling in planta during infection with tomato yellow leaf curl virus (TYLCV) and abutilon mosaic virus (AbMV), the authors mapped the host protein interactome surrounding the viral Rep initiator protein, which alone catalyzes strand-specific nicking/ligation for rolling-circle replication of the circular ssDNA genome. This approach captures transient and weak interactions missed by traditional co-IP, generating a candidate list of host DNA replication/repair factors recruited to the geminiviral replisome across two virus species for comparison. Overlap and divergence between TYLCV and AbMV interactomes can indicate core versus virus-specific host dependencies. The resulting host-factor map is directly actionable for reverse-genetics validation (e.g., CRISPR knockout/knockdown) to identify susceptibility genes as targets for engineering geminivirus-resistant crops.
bioRxiv · systems biologyConceptual
Lab-grown mini-brains with Alzheimer's mutations point to two master switches driving the disease's gene chaos.
Alzheimer's disease is usually described by two hallmarks — sticky amyloid plaques and tangled tau protein — but it also massively scrambles which genes are turned on and off in brain cells, and this study hunts for the 'master switches' behind that scrambling. The researchers grew brain organoids (small 3D clusters of human brain-like tissue grown in a dish) carrying the same genetic mutations found in inherited Alzheimer's, then tracked how gene activity changed over time and across different regions of the tissue. By reconstructing the web of which genes control which other genes, they identified 110 transcription factors — proteins that act like master control switches — that seem specific to the disease process, and found that two of them, KLF5 and KLF8, appear to sit upstream of most of the others. The fact that many of these same switches are also overactive in real Alzheimer's patient brain samples makes them promising new drug targets beyond the usual plaque-and-tangle story.
Technical view
Using APP-Swedish/PSEN1-M146V mutant brain organoids (BORGs) profiled longitudinally with bulk and spatial transcriptomics, the authors reconstructed developmental gene regulatory networks (GRNs) and identified 110 AD-specific candidate master transcription factors. Motif analysis found KLF5 and/or KLF8 binding sites enriched in the promoters of 75 of these TFs, nominating KLF5/KLF8 as upstream master regulators of the AD-associated transcriptional program. Cross-validation against human AD patient transcriptomic data confirmed significant overexpression of 64 of the 110 candidate TFs, supporting disease relevance beyond the organoid model. This GRN-based prioritization offers concrete, testable hub-TF candidates (starting with KLF5/KLF8) for perturbation studies aimed at modulating AD-associated transcriptional dysregulation independent of amyloid/tau-targeted approaches.
bioRxiv · neuroscienceRunnable
A specific brain wiring pathway makes lonely mice too anxious and scared to want friends.
When young mice are kept isolated from other mice for a long time, they don't just become indifferent to company — they become actively anxious and fearful around other mice, avoiding social contact even when given the chance. The researchers built a detailed behavioral test to tease apart 'not wanting to socialize' from 'being too vigilant and scared to,' and found the isolated mice's avoidance is driven by heightened social wariness, like being on edge around others. Using tools that let them switch specific brain wiring on and off, plus real-time brain imaging, they traced this effect to a single communication pathway running from a region called the bed nucleus of the stria terminalis (part of what's known as the extended amygdala, involved in fear and anxiety) to the brain's reward center, the nucleus accumbens. Pinpointing this circuit matters because it offers a specific target for understanding — and potentially treating — social withdrawal linked to loneliness, isolation, or anxiety disorders.
Technical view
Using a novel integrative behavioral assay to dissociate social motivation from social fear/vigilance, the authors show that chronic juvenile social isolation in mice produces an anxiety-like, hypervigilant state that suppresses social motivation and increases social fear/hesitancy, rather than simple social indifference. Intersectional, projection-specific circuit manipulations combined with in vivo calcium imaging identified the adBNST (anterodorsal bed nucleus of the stria terminalis, an extended amygdala structure) to nucleus accumbens (NAc) projection as necessary and sufficient for isolation-induced deficits in social motivation. This dissociates a specific anxiety-related circuit node from broader reward circuitry in mediating isolation's behavioral effects, giving researchers a defined projection-level target for optogenetic/chemogenetic follow-up and potential translational relevance to isolation- and anxiety-linked social withdrawal in humans.
bioRxiv · neuroscienceConceptual
Your brain re-plays cause-and-effect chains, not just time order, when you remember a TV show.
When you watch a story with multiple interwoven plotlines, like a TV drama cutting between storylines, what determines how you later remember and connect the events — is it just what happened right before what, or is it about which events actually caused which? This study had people watch and later recall a TV show with five interleaved storylines while their brains were scanned, and separately asked other participants to judge which events caused which. It turned out that cause-and-effect relationships, more than simple time order, best predicted which events people's minds jumped to during recall. Brain scans showed that a network involved in stitching together meaning (the default mode network) actually reactivated earlier, causally-linked events at moments when a new event began, suggesting causality is one of the brain's key tools for weaving separate events into one coherent memory.
Technical view
Combining a naturalistic fMRI paradigm (viewing/recall of a multi-storyline TV show) with independently collected behavioral cause-effect judgments, the authors show that causal relationships outperform other predictors (e.g., temporal proximity) in explaining recall transition patterns between events. Multivariate pattern analysis of default mode network (DMN) activity revealed that across-event neural patterns encode causal structure, and critically, DMN activity at event boundaries shows reinstatement of patterns from prior causally-related (but not merely temporally adjacent) events. Causal network distance between successive events further predicted neural pattern similarity, linking graph-theoretic causal structure directly to neural representational geometry. This provides a mechanistic account — causally-triggered pattern reinstatement at boundaries — for how narrative causal structure gets encoded into episodic memory, and a paradigm replicable with other multi-thread narrative stimuli and causal-annotation protocols.
bioRxiv · neuroscienceBuildable
Mice learning new rules keep the same brain cells firing at the same times — but reassign what those cells mean.
Your prefrontal cortex, the brain's planning and decision-making hub, needs to both learn new things and hold onto old skills — a balancing act researchers call plasticity versus stability. This study tracked the same individual neurons in mice's prefrontal cortex for months while the mice learned a task and then had to adapt as the rules kept changing. They found that over time, learning made it more predictable WHEN a given neuron would be active during a trial, but not WHAT that neuron was actually representing — the same neuron might respond to a completely different task feature after a rule switch. Using a new mathematical technique, the researchers showed this isn't random noise; instead, the brain reuses a fixed toolkit of task representations and flexibly reassigns them to neurons depending on the current rule, like keeping the same seats in a theater but swapping which actors sit in them each night.
Technical view
Longitudinal single-neuron tracking of mouse medial prefrontal cortex across months of rule-switching in an association task showed that learning stabilizes the temporal activity profile (when neurons fire within a trial) of individual neurons, while their functional selectivity (what task variable they encode) continues to change even after temporal stabilization. The authors developed Sparse Tensor Component Analysis (STCA) to decompose population activity and demonstrate that this apparent instability is not random drift but structured, rule-dependent recombination of a small, fixed set of latent task representations across neurons. This decouples 'when' from 'what' at the single-neuron level and offers a reusable computational framework (STCA) for distinguishing genuine representational drift from systematic recombination in other longitudinally-tracked neural datasets. The findings support a model where PFC provides a stable temporal scaffold that supports flexible, combinatorial task representation rather than fixed neuron-to-variable mappings.
bioRxiv · neuroscienceRunnable
Electrodes in 36 human brains map exactly which regions talk to each other during working memory tasks.
Working memory — holding information in mind briefly, like remembering a card's location in a matching game — relies on many brain regions talking to each other, but exactly how that conversation is organized has been unclear. This study used electrodes implanted in the brains of epilepsy patients (already there for medical monitoring) to record activity from over 1,600 locations while people played a card-matching game, capturing real neural signals with far more precision than typical scalp scans. The researchers looked at how different brain wave rhythms lined up across regions and found that frontal (front of the brain) and temporal (side of the brain) areas consistently acted as communication hotspots. They even found direction of information flow — frontal regions tended to send signals in one rhythm and receive them in another — and identified distinct brain-wide 'states' the brain moves through during memory tasks, offering a detailed wiring diagram of how the brain coordinates memory formation and retrieval.
Technical view
The authors analyzed intracranial local field potentials from 1,652 electrode sites across 36 epilepsy patients performing a naturalistic card-matching working memory task, examining phase-amplitude coupling (PAC) and phase-phase coupling (PPC) across recognition, encoding, and retrieval conditions. Frontal and temporal regions emerged as recurrent, condition-dependent connectivity hubs, with event-related coupling dynamics reproducible across participants. Directed phase transfer entropy identified frequency-specific directional information flow, notably frontal cortex acting as a theta-band source and alpha-band sink, indicating frequency-multiplexed feedforward/feedback signaling. A time-delay-embedded hidden Markov model further extracted task-locked latent network states with condition-dependent occupancy dynamics, giving practitioners a validated multi-method (PAC/PPC + transfer entropy + HMM) pipeline for characterizing distributed oscillatory coordination from large-scale iEEG datasets.
bioRxiv · neuroscienceConceptual
A gene pair keeps the brain's protective 'nets' in shape so social circuits don't unravel.
Deep in the brain's outer layer sit special brake-like neurons (Parvalbumin interneurons) that keep other brain cells from firing too much. These neurons are wrapped in a mesh called a perineuronal net, which acts like scaffolding to stabilize them. This study shows two genes, Dlx5 and Dlx6, control the genetic instructions for building and maintaining that mesh in adult brains. When the genes are switched off, the mesh gets remodeled abnormally, throwing off the balance of excitation and inhibition and disrupting social behavior in mice — suggesting these genes are a hidden maintenance crew for stable brain wiring.
Technical view
Using conditional Dlx5/6 inactivation in GABAergic neurons, the authors combined transcriptomics, histology, ex vivo electrophysiology, and in vivo EEG to show Dlx5/6 govern a PNN-homeostasis gene program in adult cortex. Loss of Dlx5/6 dysregulated multiple PNN-associated transcripts and caused region-specific PNN mesh remodeling in prefrontal and somatosensory cortex, paralleled by altered excitatory/inhibitory synaptic organization around PV interneurons. This links a known GABAergic transcription factor pair to adult PNN maintenance and network stability, offering candidate targets/genes for studying PV-circuit dysfunction in psychiatric models.
bioRxiv · neuroscienceConceptual
Brain's 'fastest' receptor secretly runs in slow motion in some synapses, and now we know why.
AMPA receptors are the brain's speed demons — proteins that let neurons respond to the chemical glutamate almost instantly, in milliseconds. But researchers found that some synapses, especially in a brain region called ventral CA1 (part of the memory-related hippocampus), produce surprisingly sluggish AMPA responses instead. They traced this oddity to a helper protein, CNIH3, that seems to act like a molecular tag marking which receptors run slow. This matters because it reveals a whole hidden layer of diversity in how neurons process signals — not all 'fast' wiring is actually fast.
Technical view
Building on prior findings of slow AMPA receptor kinetics in CA1 pyramidal cells with mosaic, region-specific distribution (Pampaloni et al., 2021, 2022), the authors identify the auxiliary subunit CNIH3 as a molecular signature enriched where slow AMPA responses predominate, notably ventral over dorsal CA1. This provides a genetic/molecular handle for isolating and manipulating slow AMPA receptor populations experimentally (e.g., via CNIH3 knockout or overexpression) to test their functional role in synaptic integration and dendritic computation.
bioRxiv · neuroscienceBuildable
A cellular delivery motor turns out to be essential for neurons' internal trash-recycling system.
Neurons rely on a protein called KIF1A to act like a delivery truck, hauling cargo along their long branches. Mutations in KIF1A cause a range of brain disorders, but scientists didn't know it was also needed for autophagy — the process cells use to package up and break down worn-out parts, like an internal recycling service. Using human neurons grown from stem cells, the researchers found that without KIF1A, a key recycling-bin protein can't reach the far ends of the neuron, and cleanup stations (lysosomes) also go missing there. This means some KIF1A-related brain diseases may partly stem from neurons drowning in un-recycled cellular junk.
Technical view
In gene-edited human iPSC-derived neurons, KIF1A loss impaired axonal trafficking of ATG9, the transmembrane lipid scramblase required for autophagosome nucleation, reducing autophagosome biogenesis and axonal autophagosome density. KIF1A loss also depleted axonal lysosomes, blocking autophagosome maturation, and a heterozygous pathogenic KAND variant linked to Rett-like phenotypes reproduced aspects of this deficit. This establishes autophagic cargo trafficking as a distinct KIF1A-dependent pathway beyond synaptic vesicle transport, giving KAND researchers a new mechanistic axis (ATG9/lysosome delivery) to test therapeutically.
bioRxiv · neuroscienceConceptual
Two distant brain regions pass a lightning-fast baton to make you move exactly when you decide to.
When you decide to move on your own, without any outside cue telling you 'go now,' your brain has to coordinate that decision internally. Researchers trained mice to press at a precisely self-chosen moment, then used a technique called optogenetics — using light to briefly switch off specific neurons — to interrupt brain activity at exact instants. They found that two regions far apart, the prefrontal cortex (planning) and the cerebellum (fine motor timing), hand off the job to each other in rapid sequence right before the movement starts. This shows self-initiated action isn't one region's job — it's a relay race between brain areas.
Technical view
Using a novel self-timed movement task requiring high temporal precision without external go-cues, the authors applied brief, precisely timed optogenetic photoinhibition pulses to dissect the causal chain of movement initiation. Results show rapid, sequential recruitment of neurons in prefrontal cortex followed by lateral cerebellum is causally necessary for triggering the movement, implicating a cortico-cerebellar relay rather than a single locus. This provides a template (timed optogenetic silencing plus self-paced behavioral tasks) for mapping causal sequences in other endogenously-driven behaviors.
bioRxiv · molecular biologyBuildable
Scientists found a hidden DNA-repair trick cells use only when they've stopped dividing.
CRISPR gene editing cuts DNA, and cells then patch the cut back together — but how they patch it varies, and predicting the outcome has been tricky, especially in plants. By comparing thousands of CRISPR cut sites across plants, animals, and algae, researchers found the real deciding factor isn't the species but whether the cell is actively dividing. Dividing cells use one known repair route, while resting (non-dividing) cells use a mostly overlooked route the authors name 5'CMEJ, which cleverly reuses leftover DNA overhangs from the original cut instead of trimming them away. This gives a much better rule of thumb for predicting what CRISPR edits will actually look like in real tissues.
Technical view
Meta-analysis of 2,098 SpCas9 target sites across plants, animals, and an alga showed deletion signatures track cell-division state rather than taxonomy: dividing cells favor Polymerase Theta-mediated end joining (TMEJ), while non-dividing cells predominantly use a previously underappreciated pathway, 5' Complementarity-Mediated End Joining (5'CMEJ). Unlike classical resection-dependent pathways that rely on 3' overhangs, 5'CMEJ exploits 5' overhangs from SpCas9's staggered cleavage geometry. This reframes CRISPR outcome prediction models to incorporate cell-cycle/division status as a primary variable, particularly relevant for editing quiescent plant tissues or post-mitotic cells.
bioRxiv · cell biologyConceptual
A lipid pileup in a cell's shipping hub creates swirls that trap and confuse traffic-control proteins.
Cells have an internal shipping and sorting hub called the Golgi, and its job depends on small proteins (GTPases) that mark different compartments so cargo goes to the right place. Researchers discovered that too much of a particular lipid modification (palmitoylation, basically a fatty tag added to proteins) causes the Golgi to twist into layered 'whorls,' like tangled sheets. These whorls act like magnets, pulling in GTPases that normally belong to entirely different parts of the cell, while excluding the proteins that should normally be there. It's a surprising case of a membrane's physical state — not a biological signal — dictating where cellular traffic-control proteins end up.
Technical view
Excess S-palmitoylation at the Golgi was shown to generate multilamellar, filipin-poor membrane whorls that aberrantly recruit ARF, Rab, and Rho family GTPases normally restricted to distinct organelles, while excluding native Golgi transmembrane proteins, coat proteins, ER proteins, and a GPI-anchored protein — indicating selective recognition rather than nonspecific aggregation. Blocking ARF6 myristoylation or Rab11a geranylgeranylation strongly reduced recruitment, while prenylation alone was insufficient, pointing to a composite lipid-modification code required for whorl targeting. This identifies membrane lipid state itself as an organizing input for GTPase localization, useful for dissecting lipidation-dependent trafficking signals experimentally.
bioRxiv · cell biologyConceptual
Bringing back a 'lost' heart gene helps at first, then triggers faster heart failure.
When the heart is under strain (like high blood pressure), it grows thicker to cope, and a gene called Klf9 naturally drops in activity during this process. Scientists wondered what would happen if they forced Klf9 to stay on instead, so they engineered mice where it could be switched back on and then subjected them to pressure overload on the heart. At first, keeping Klf9 active blocked the thickening response, which sounds good — but within one to two weeks it disrupted the heart's metabolism and pushed the mice into heart failure earlier than normal. The takeaway is that Klf9's natural decline isn't a malfunction; it's a necessary adaptation that lets the heart's metabolism cope with extra strain.
Technical view
Genome-wide ChIP profiling showed Klf9 occupancy is enriched at metabolic gene promoters during cardiac hypertrophy, and Klf9 levels normally fall as hypertrophy progresses. Using conditional Klf9 knock-in mice, forced restoration of Klf9 during 1-2 weeks of pressure overload initially suppressed hypertrophic growth but produced metabolic maladaptation and accelerated onset of heart failure. This establishes Klf9 downregulation as a required adaptive step for compensatory hypertrophy, positioning Klf9 as a potential node for studying the switch between compensated hypertrophy and metabolic decompensation.
bioRxiv · cell biologyConceptual
A brain-infecting virus hijacks the cell's internal 'GPS hub' to build its own factory.
Japanese Encephalitis Virus, a mosquito-borne brain infection, needs a home base inside infected cells to replicate — and this study shows it commandeers the centrosome, a structure that normally organizes the cell's internal skeleton and helps cells divide. A specific piece of one viral protein (an NS3 helicase, an enzyme that unwinds genetic material) latches onto this hub, and when researchers expressed just that piece alone, it clustered around the centrosome just like the virus's replication factories do during real infections. Removing the centrosome altogether hampered the virus, showing this isn't accidental — the virus actively exploits the cell's organizational center to help itself multiply.
Technical view
The study maps a centrosome-targeting region within the C-terminal helicase domain of JEV NS3 that drives association of viral replication structures with host microtubule-organizing centers (MTOCs). Ectopic expression of this NS3 fragment alone produced pericentriolar aggresomes mimicking the distribution of helicase-containing viroplasm seen in actual infection, and centriole depletion assays confirmed a proviral, functional role for the centrosome. This defines a druggable viral-host interaction interface (the helicase's centrosome-targeting motif) as a candidate target for antiviral strategies against JEV and potentially related flaviviruses.
bioRxiv · developmental biologyBuildable
Scientists mapped which enzymes keep the placenta's foundation cells on track early in pregnancy.
The placenta isn't one tissue but three cell types working together: stem-like cells that keep dividing, cells that fuse into a barrier for nutrient exchange and hormone production, and cells that burrow into the mother's uterus to anchor the pregnancy. Using lab-grown versions of the stem cells, researchers measured which proteins and 'on/off' chemical tags (phosphate marks) are present as these cells decide their fate. They focused especially on kinases, a class of enzyme that acts like molecular switches, flipping other proteins on or off. Finding which kinases are essential could eventually help explain pregnancy complications like preeclampsia or implantation failure.
Technical view
The team applied label-free quantitative LC-MS/MS proteomics and phosphoproteomics to human trophoblast stem cells (hTSCs) to catalog protein and phosphosite abundance across the CTB stem state and its EVT/STB differentiated derivatives. By integrating these proteomic datasets with genomic/transcriptomic data, they nominate protein kinases whose expression or phosphorylation state tracks lineage decisions. This generates a candidate kinase list for functional follow-up (e.g., inhibitor or knockdown studies) to test necessity in CTB self-renewal versus EVT/STB differentiation. The dataset itself is a resource for mining kinase-substrate signaling networks active during early placental development.
bioRxiv · developmental biologyBuildable
Watching a single protein move between a cell's nucleus and its sticky edges as kidneys form.
Beta-catenin is a protein with a double life: inside the nucleus it helps turn genes on, while at the cell's edges it helps glue neighboring cells together. Both jobs matter for building a kidney's filtering units (nephrons), but scientists didn't know how a cell switches this protein between its two roles as development unfolds. The researchers built a glowing sensor, called a chromobody, that lights up wherever beta-catenin is located, and used it to film living frog embryos as their primitive kidneys formed. They saw beta-catenin's location shift systematically between nucleus, cell interior, and cell-cell junctions at different developmental stages. This live view helps explain how the same molecule can both instruct cell identity and hold tissue architecture together at the right times.
Technical view
The authors engineered an accelerated-turnover beta-catenin chromobody for high-temporal-resolution live imaging, avoiding the lag artifacts of stable fluorescent fusions, and applied it to Xenopus pronephric (kidney) development. Time-lapse imaging across nephrogenesis stages resolved beta-catenin partitioning among nuclear, cytoplasmic, and adherens-junction pools, revealing a developmental shift in localization that correlates with progenitor renewal versus differentiation and patterning events downstream of Wnt signaling. This provides a quantitative, in vivo readout distinguishing beta-catenin's transcriptional co-activator function from its structural cadherin-linked role, a tool that could be adapted to other Wnt-dependent organogenesis systems to test causal links between subcellular localization and cell fate decisions.
bioRxiv · developmental biologyConceptual
A single gene decides whether fly brain stem cells retire on schedule or keep making neurons.
In brains, most neuron-making stem cells (called neuroblasts) shut down once development finishes, which is why adults make far fewer new neurons than embryos. The fruit fly's mushroom body, a brain region for learning and memory similar in role to our hippocampus, is a good model for studying why this shutdown happens. This study found that a gene called Kruppel acts like a retirement notice for the fly's mushroom body stem cells: when scientists silenced it, the stem cells kept dividing well into adulthood instead of disappearing. Even though Kruppel is normally present only at low levels at this later stage, removing it during a brief pupal window was enough to prevent the stem cells from being properly eliminated. Understanding what keeps neurogenesis stem cells on a schedule could inform strategies to safely reawaken neuron production in adult brains, such as after injury.
Technical view
Using lineage-specific RNAi against Kruppel (Kr) and an existing Kr mutant allele (KrIf-1), the authors show that Kr is required cell-autonomously in mushroom body neuroblasts (MBNBs) to drive their pupal-stage cell cycle exit and elimination, since its knockdown or loss-of-function prolongs MBNB survival and permits neurogenesis into adulthood. Critically, Kr acts at low expression levels specifically during the pupal window, and temporally restricted depletion or misexpression at that stage is sufficient to alter MBNB retention, indicating a discrete, stage-specific checkpoint function distinct from its known embryonic patterning roles. This establishes Kr as a lineage-restricted terminator of a defined stem cell pool, offering a tractable genetic entry point for dissecting the transcriptional programs that limit adult neurogenesis in a well-characterized learning/memory circuit.
bioRxiv · ecologyConceptual
Even carefully fed farm partridges still carry high pesticide loads, hinting exposure isn't just from food.
Pesticides used to boost crop yields don't stay confined to the fields; they spread through the wider ecosystem and can build up in animals that were never the intended target. Grey partridges raised in semi-natural enclosures were given different diets, including some meant to reduce pesticide exposure, to see if changing what they eat would lower the chemical residues found in their bodies. Surprisingly, the birds still showed high pesticide contamination regardless of which diet they were fed, suggesting that simply controlling food intake isn't enough to protect wildlife. This points to other exposure routes, beyond eating contaminated food, such as contact with treated soil, dust, or water, that researchers hadn't fully accounted for. The finding matters because it complicates simple fixes like 'feed wildlife cleaner food' and pushes for a fuller picture of how pesticides move through farmland ecosystems.
Technical view
The study used semi-captive grey partridges under contrasted feeding treatments to isolate the contribution of diet to phyto-pharmaceutical product (PPP) body burden, measuring residual pesticide contamination profiles despite manipulated food intake. Contrary to the ingestion-centric exposure model, contamination remained high across feeding treatments, indicating that dietary control alone does not explain observed residue levels and that non-dietary exposure pathways (e.g., dermal, inhalation, or environmental matrix contact) likely contribute substantially. This challenges risk assessment frameworks that model non-target wildlife PPP exposure primarily through food-chain ingestion, suggesting multi-route exposure models are needed for accurate agroecosystem contamination assessments in farmland bird species.
bioRxiv · ecologyBuildable
When Chinese farmland is abandoned, some places sprout way more invasive weeds than others.
When farmers stop working a piece of land, nature starts to reclaim it, but that recovery can go two ways: native plants bounce back, or aggressive invasive species move in and take over. This study looked at abandoned farmland across China and asked what makes some abandoned plots more prone to invasive plant takeover than others. The researchers combined records from many published studies covering 57 invasive plant species and used statistical models to test which social and environmental factors, like regional wealth, climate, or even the number of local universities (used as a stand-in for scientific attention to the problem), best predict how many invasive species show up. This kind of big-picture synthesis helps identify which regions most need monitoring or intervention as farmland abandonment continues to spread. It reframes invasion risk as tied not just to ecology but to human and economic patterns across a landscape.
Technical view
The authors performed a literature-based synthesis, compiling occurrence records for 57 invasive alien plant (IAP) species reported in abandoned croplands across China, and modeled study-level recorded species richness with generalized linear mixed models (GLMMs) using province as a random effect to account for spatial non-independence. Fourteen candidate socio-economic and environmental predictors were screened for multicollinearity, standardized, and entered into the models, including an unconventional proxy (count of Higher Education Institutions) for regional research/survey intensity, addressing a known confound in meta-analyses of invasion records. The approach is explicitly exploratory given heterogeneity in underlying study designs, but it offers a reusable framework and predictor set for researchers building national-scale invasion risk maps or prioritizing abandoned-cropland monitoring in other regions.
bioRxiv · ecologyConceptual
Two bumble bee species living side by side follow completely different life schedules.
Bumble bee colonies follow a yearly life cycle: a queen starts a nest, workers build up the colony, then new queens are produced before the colony dies off in fall. This study tracked two common bumble bee species living in the same areas over three years to see whether they follow the same schedule or different ones, and why. By watching activity at wild nests, like when foraging traffic picked up, when new queens appeared, and when colonies died off, researchers found the two species have distinctly different timing strategies. They also tested whether a colony's growth rate depended on how crowded the area was, since classic theory predicts that growth patterns should shape the best time to switch from building up the colony to producing new queens. The work helps explain how species with different life-history strategies can coexist while responding differently to a changing climate and season length.
Technical view
Using three years of field observations of wild Bombus griseocollis and B. impatiens nests, the authors quantified colony phenology milestones, nest-searching onset, peak worker activity, first gyne production, and colony senescence, via nest traffic monitoring, and tested for density-dependent colony growth as predicted by classic life-history/optimal-reproductive-timing models. The two co-occurring species show contrasting phenological schedules, which the authors interpret as reflecting divergent underlying life-history strategies (e.g., differing growth trajectories or resource-allocation timing) rather than simply differing responses to identical environmental cues. This provides an empirical, multi-year dataset linking colony-level demographic trajectories to phenological output, useful for parameterizing bumble bee phenology models under climate change scenarios or for comparative life-history analyses across social insect taxa.
bioRxiv · geneticsBuildable
A wild wheat relative deliberately trashes an extra chromosome from its own root cells.
Most cells in an organism carry the same set of chromosomes, but some species have extra 'B chromosomes' that are optional and get selectively thrown away in certain tissues during development, a strange and poorly understood process called programmed chromosome elimination. In the wild grass Aegilops speltoides, this elimination happens specifically in the roots, giving scientists a natural, controllable system to study how and why it occurs. The researchers built a detailed genetic map of this extra B chromosome and compared gene activity across tissues where the chromosome is being eliminated versus tissues where it's kept. They found that genes involved in cohesin, a protein complex that normally holds chromosome copies together during cell division, along with other B-chromosome-specific genes, are turned up specifically in the tissues where elimination is happening. This suggests the plant repurposes its own cell-division machinery to selectively discard chromosomes, a mechanism with parallels to disputed chromosome behaviors in other organisms, including insects and some vertebrates.
Technical view
The authors generated a chromosome-scale genome assembly of Aegilops speltoides, resolving 398 Mb of B-chromosome sequence, and performed comparative transcriptome profiling across seven tissue types spanning elimination-active, elimination-negative, and B-chromosome-nondisjunction states. Differential expression analysis identified 3,262 genes consistently upregulated specifically in elimination-associated tissues, notably including cohesin pathway components and additional B-chromosome-encoded genes, implicating altered sister-chromatid cohesion regulation as a candidate mechanism for the tissue-restricted, root-specific loss of the B chromosome. This dataset and assembly provide a genomic resource for functional validation (e.g., candidate gene knockdown or cohesin perturbation) to test causality in programmed chromosome elimination, and offer a comparative reference point for elimination mechanisms studied in other plant and animal systems.
bioRxiv · biochemistryBuildable
A drug screen found eight compounds that turn up your body clock's volume without shifting its timing.
Your body's internal clock, which governs sleep, metabolism, and many other daily rhythms, can weaken with age or disease, and a flatter rhythm has been linked to problems like obesity, cancer, and neurodegenerative disease. Rather than trying to reset the clock's timing, researchers looked for drugs that could make its daily swings stronger, or higher amplitude, without shifting when the rhythm peaks. They used cells engineered to glow in a pattern that tracks a core clock gene, then tested thousands of existing drugs (already approved or studied for other purposes) to see which ones boosted that glow's daily rise and fall. Eight compounds stood out, reliably strengthening the rhythm across multiple cycles in a dose-dependent way without messing up timing, and the team began checking whether these effects hold up in more complex, whole-body-like settings. This kind of amplitude-boosting drug could become a new class of therapy for clock-related health problems.
Technical view
The authors performed a high-throughput screen of a 5,631-compound drug-repurposing library using a Bmal1-luciferase transcriptional reporter in NIH3T3 fibroblasts to identify small molecules that increase circadian oscillation amplitude without altering period or phase. Eight hit compounds were validated as dose-dependent amplitude enhancers sustained across multiple circadian cycles, distinguishing them mechanistically from classical period-modulating clock drugs (e.g., CK1 or CRY modulators). The team further assessed physiological relevance of these hits, presumably extending beyond the peripheral fibroblast reporter system toward central clock or in vivo contexts, positioning these compounds as chemical starting points for target deconvolution and for therapeutic development in conditions linked to circadian dampening, such as metabolic syndrome or neurodegeneration.
bioRxiv · biochemistryConceptual
Scientists finally decoded the hidden chemical tug-of-war when amino acids grab CO2 from the air.
Amino acids and short protein chains (peptides) are being explored as sponges that soak up CO2 from water or air, which could help fight climate change, but nobody could cleanly measure everything happening inside the reaction at once. This team used a technique called isothermal titration calorimetry, which tracks the tiny bursts of heat released as molecules react, and combined it with acidity measurements and a scanning technique (NMR) that shows which molecules are present. By testing lysine, arginine, and peptides built from them, they figured out how CO2-grabbing, proton swapping, and water interactions are all tangled together in one process. Untangling this matters because it lets engineers design better, cheaper amino-acid-based materials for capturing carbon from power plants or the atmosphere.
Technical view
The authors validate ITC as a quantitative tool for resolving coupled carbamate formation, protonation, carbonate speciation, and hydration equilibria in aqueous amino-acid/peptide CO2 capture systems. Global fitting of ITC thermograms for L-lysine, L-arginine, and Lys/Arg-containing peptides yields thermodynamic parameters that independently reproduce pH titration curves and NMR-derived speciation, cross-validating the mechanistic model. Key finding: the characteristic biphasic calorimetric signal arises from a coupled carbonate-amine equilibrium rather than sequential independent steps, a mechanistic detail future capture-solvent design work can build on directly.
bioRxiv · biochemistryConceptual
Tiny bubbles shed in urine reveal sepsis is quietly wrecking kidneys days before doctors would notice.
Sepsis, a life-threatening overreaction to infection, often damages the kidneys (called S-AKI), but current tests only catch the damage after it's already happened rather than showing how it unfolds. Cells constantly release microscopic packages called extracellular vesicles into urine, and these packages carry protein and metabolic fingerprints of what's happening inside kidney cells. Researchers tracked these urine packages from 81 sepsis patients over eight days, comparing those who developed kidney injury to those who didn't, then confirmed their findings in a second independent group of patients. This kind of tracking could let doctors spot kidney damage forming in real time and intervene before permanent harm is done.
Technical view
This is a longitudinal multi-omics (proteomic + metabolomic) study of urinary extracellular vesicles (uEVs) from 81 sepsis patients (48 S-AKI, 33 sepsis-only), split into discovery (n=52) and validation (n=29) cohorts, sampled at Days 1, 4, and 8. High-resolution profiling of uEV cargo is used to map temporal molecular trajectories distinguishing S-AKI pathogenesis from general sepsis, aiming to identify mechanism-linked biomarkers rather than markers of dysfunction alone. Replication in an independent cohort strengthens the case for specific early proteo-metabolomic signatures as candidate diagnostics, a foundation others could test against additional cohorts or turn into a targeted panel assay.
bioRxiv · bioengineeringConceptual
Different patches of your eye's drainage system work at different speeds — and the genes explain why.
Fluid constantly drains out of your eye through a tissue called the trabecular meshwork, and oddly this drainage isn't uniform — some regions flow fast, others slow, and that pattern affects eye pressure and glaucoma risk. Researchers took eye tissue from mice and human donors, used a glowing tracer to map which regions had high versus low flow, then read out which genes were active in each region using a whole-tissue gene-activity scanning technique. They found specific genes and biological pathways that differ meaningfully between the fast- and slow-draining zones, and confirmed some of these with a separate staining method. Understanding why some regions clog while others don't could point to new glaucoma treatments that target the sluggish areas specifically.
Technical view
Using fluorescent tracer perfusion to demarcate high-flow (HF) versus low-flow (LF) regions in trabecular meshwork tissue from human donors and C57Bl/6J mice, the authors performed spatial whole-transcriptome profiling on sagittal sections, followed by differential expression and gene set variation analysis (GSVA) to compare HF vs LF pathway activity, with immunolabeling validation of select targets. The approach identifies segmental transcriptomic signatures linked to aqueous humor outflow regulation and intraocular pressure control across species. This cross-species spatial dataset offers a resource for identifying region-specific drug targets or biomarkers relevant to glaucoma therapeutics.