Browse Articles

A Type VII-secreted toxin enables inter-mycobacterial competition

Abstract Most bacteria have evolved mechanisms to compete with other bacteria, often through the specialised secretion of proteinaceous toxins. However, mycobacteria have not previously been reported to engage in this form of competition. The thick and unusual mycobacterial cell wall, comprised of peptidoglycan, arabinogalactan and mycolic acids, is generally thought to be highly protective to these bacteria. Here, we show that some mycobacteria can use endo-D-arabinanases of the GH183 family for inter-bacterial competition. These microorganisms secrete an endo-D-arabinanase effector via the type VII secretion system (T7SS) that cleaves the arabinogalactan layer of the mycobacterial cell envelope. We describe the molecular basis for this activity using structural biology and biochemistry, and identify a protein family that protects the bacterium from the activity of this toxin. The widespread presence of genes potentially encoding similar T7SS-secreted toxins in the Mycobacteriales suggests extensive inter-mycobacterial competition.

Reclassification and weighting of multiple causes of death: US death certificates 2003–2023

Death certificates record causes of death as reported by certifiers (Entity Axis) and as standardized by mortality coding rules (Record Axis). Conventional statistics reduce these to a single underlying cause, ignoring other contributing conditions; weighting schemes can instead distribute the burden across all listed causes. We evaluated reclassification from Entity to Record axis and weighting across all 56,986,831 US death certificates from 2003 to 2023, mapping International Classification of Diseases (ICD)-10 codes to 14 broad disease categories and testing three weighting schemes: W1 (50% to the underlying cause, 50% shared equally among contributing causes), W2 (equal weighting across all causes), and W2A (equal weighting at the ICD-10 code level). Entity and Record Axes agreed on underlying cause in 48,313,403 deaths (84.8%) by broad category and 39,260,709 deaths (68.9%) by ICD-10 code ( SI Appendix , Table S5 A and B ); concordance reached 70.4% using 3-character. Reclassification markedly increased COVID-19 (+92%) and Transport deaths (+43%) while decreasing Other External Causes (−54%). Weighting substantially altered burden attribution: COVID-19 (−44 to –63%) and Falls (−46 to –66%) decreased, Other External causes more than tripled (+204 to 254%), and deviations from unweighted counts were more pronounced with W2 and W2A than W1. Weighting also brought disease-category counts closer to Entity Axis values and restored Respiratory seasonality suppressed during the pandemic. Systematic differences between reported and reclassified causes of death, and the choice of weighting scheme, profoundly alter disease burden estimates for several causes, with major implications for resource allocation and public health priorities.

Advanced paternal age is associated with reduced reproductive success and offspring racing performance in Australian Thoroughbred racehorses

Electrochemical selective oxygen transfer enables energy-efficient environmental deoxygenation

Selectively targeting inosine monophosphate dehydrogenase-2 impairs brain metastatic potential while preserving immune cell function

Brain metastases (BM) occur in 26% of cancer patients and have a 90% mortality rate within 1 y of diagnosis, yet the current standard of care remains palliative. We have previously shown that de novo GTP synthesis is a druggable metabolic vulnerability in BM cells, through its rate-limiting enzyme, inosine monophosphate dehydrogenase (IMPDH). IMPDH inhibitors have progressed to phase-II oncology trials in the past, failing largely due to dose-limiting toxicities associated with off-target inhibition of IMPDH1, the constitutively expressed isoenzyme in normal human lymphocytes. Here, we determined that a single subtype (isoenzyme) of IMPDH, IMPDH2, is specifically upregulated in brain metastasis-initiating cells (BMICs), absent in normal brain tissue, and is sufficient to drive the formation of BM. Moreover, we show that genetic knockout of IMPDH2 stops the proliferation of BM cells in vitro and the onset of BM in vivo. We synthesized IMPDH2-selective compounds and showed that they maintain a potent antiproliferation effect on BMICs, but spare immune cell function compared to previously developed pan-IMPDH inhibitors. Furthermore, we introduce a positive correlation between compound selectivity for IMPDH2 and the ability to synergize with Osimertinib: the standard of care for EGFR-mutant non–small cell lung cancer. Overall, our results suggest that specifically blocking IMPDH2 is an effective therapeutic strategy for BM by overcoming the immune suppressive effects that have hindered the clinical development of pan-IMPDH inhibitors in the past. An IMPDH2 specific therapy could be coadministered with primary tumor standard of care treatments to provide a safe and interceptional approach for BM.

Laser-generated focused ultrasound for thrombus characterization and fragmentation: ex vivo feasibility study

Direct imaging-based gradient metasurface sensor enabling spectrometer-free ultrasensitive biomolecule detection

Supersaturation-controlled assembly pathway directs hierarchical chirality expression in ionic luminophores

The controlled expression of molecular chirality across multiple length scales is a central feature of many natural assemblies, yet remains a significant challenge to achieve in synthetic materials. Here, we show that supersaturation—particularly its temporal evolution—acts as a powerful kinetic parameter for directing chiral expression during antisolvent diffusion. By tuning diffusion conditions, two distinct assembly pathways can emerge from the same ion-paired luminophores. In all cases, nucleation is initiated upon reaching a critical supersaturation threshold, consistent with a common nucleation process. The subsequent growth pathways diverge depending on how supersaturation is sustained over time. When antisolvent diffusion is rapidly completed and the system transitions to an evaporation-dominated regime, gradual reorganization of intermediate assemblies produces macroscopic vortex-like films with pronounced chiral organization, whose large circularly polarized light emission dissymmetry factors (|g CPLE |) originate primarily from structure-induced scattering. In contrast, when supersaturation is continuously maintained through ongoing antisolvent diffusion, higher nucleation density combined with restricted growth leads to square microcrystals that exhibit only weak supramolecular chirality. The two pathways yield distinct chiroptical signatures with opposite CPLE signs and an order-of-magnitude difference in chiroptical response, with vortex films reaching |g CPLE | values up to 0.09. This study establishes a mechanistic link between supersaturation evolution and hierarchical chiral assembly and offers insights for designing macroscopic chiral photonic architectures with relevance to biomimetic and chiroptical applications.

An F1-score-weighted ensemble of deep learning models for enhanced cloud detection in remote sensing imagery

Spatial transcriptomics reveals coordinated ventricular patterning and maturation in the developing human heart

ENO1 couples HDAC1 to regulate histone lactylation and gene transcription

Histone deacetylases (HDACs) regulate transcription and catalyze deacetylation predominantly within canonical transcriptional complexes. Nevertheless, the mechanistic role of other HDAC-associated proteins in orchestrating this process remains incompletely understood. To systematically decode endogenous HDAC interactomes in living cells, we developed BimPL, a heterobifunctional molecule-enabled proximity labeling strategy. Leveraging BimPL and quantitative proteomics, we robustly captured established HDAC complexes and identified putative interactors, including glycolytic enzyme enolase-1 (ENO1). Importantly, we uncover that ENO1 translocates into the nucleus and interacts with HDAC1 at chromatin, which in turn blunts the activity of HDAC1 through locally generated phosphoenolpyruvate (PEP). Consequently, the ENO1–HDAC1 coupling promotes histone lysine lactylation (Kla), which drives transcriptional reprogramming of oncogenes in hepatic malignancies. Our study establishes BimPL as a versatile tool for mapping endogenous protein interactomes and reveals a metabolic enzyme-orchestrated HDAC regulatory mechanism for histone lactylation, highlighting ENO1’s moonlighting function in epigenetic reprogramming.

Associations between habitual light exposure-related behaviors and sleep timing and sleep complaints in an international community sample

Abstract Sleep is essential for health and light is an important environmental signal influencing its timing, quality, and regulation. Retinal light exposure reflects the interplay between environmental illumination and behavioral choices, yet it remains unclear which habitual light exposure-related behaviors meaningfully impact sleep outcomes. In this preregistered secondary data analysis, we examined associations between these behaviors, sleep timing, and sleep complaints in a large, international community sample ( N  = 775, M age = 32.6 ± 14.6 years). Participants completed the Light Exposure Behavior Assessment (LEBA), with four behavioral domains included in the analyses. Sleep timing, sleep disturbances and sleep-related daytime impairment were measured using established questionnaires. Bayesian analyses indicated that time spent outdoors and device use in bed were most strongly associated with sleep outcomes. Greater time outdoors was linked to earlier sleep timing and fewer sleep complaints, whereas more frequent device use in bed was associated with greater sleep disturbance and daytime impairment. Morning and daytime lighting practices and evening light control showed no conclusive evidence. Together, these findings highlight the relevance of everyday light exposure-related behaviors for sleep and support behavioral approaches to promoting healthy sleep in real-world contexts.

Investigating ancient human DNA preservation on cave walls and in rock art

Abstract Previous efforts to link Palaeolithic cultural records to specific populations through DNA analysis have focused on materials from archaeological floor deposits such as bones, sediments, and artefacts. In this study, we explore whether rock art, a spatially distinct expression of human activity, can also preserve DNA traces from its creators. We analyse DNA preservation in pigment samples collected in and around 24 rock art panels from 11 caves across Spain and Portugal, including simple marks (from nine sites), hand stencils (Maltravieso Cave, Extremadura, Spain), and figurative paintings (Cave of Altamira, Cantabria, Spain). We recover traces of ancient human mitochondrial and nuclear DNA, unaccompanied by faunal DNA, from a pigmented calcite crust at Escoural Cave (Portugal), as well as from an unpigmented cave wall sample from the same site. The absence of faunal DNA in both samples suggests direct DNA deposition through human contact. In contrast, three additional unpigmented samples, from Escoural and Covarón Cave (Asturias, Spain), yielded mixtures of human and faunal DNA, suggesting indirect deposition. Although our results do not conclusively link ancient human DNA preservation to the generation of cave art, we show that traces of human DNA can persist on cave walls for thousands of years.

Linear-time prediction of proteome-scale microbial protein interactions

Protein–protein interactions (PPIs) underpin biological function, yet proteome-scale interaction prediction remains bottlenecked by the quadratic computational complexity of all-vs.-all pairwise comparisons. Here, we present FlashPPI, a contrastive learning framework, grounded in residue-level interactions, that enables linear-time prediction of physical protein interfaces across a microbial proteome. By leveraging a genomic language model that captures cross-protein coevolutionary signals from metagenomic sequences, FlashPPI aligns interacting partners in a shared latent space. We demonstrate a four-fold performance increase over existing sequence-based methods, while reducing proteome-wide screening time from days to minutes. Crucially, FlashPPI achieves comparable screening performance to state-of-the-art structure-folding models at a fraction of the computational cost. Finally, we integrate FlashPPI into an interactive web platform that combines predicted networks with functional annotations and genomic context, making proteome-wide network analysis rapid and accessible for microbial discovery.

Plasma-based flow control for performance enhancement of vertical-axis wind turbines

Amphibian-inspired neuromorphic dynamic vision systems based on ferroelectric field-effect transistor

Shared spatial and temporal principles govern connectome dynamics across timescales

While the brain processes information at various speeds, little is known about how the functional connectome can concurrently support multiple speeds in parallel. FMRI and electrophysiological modalities have been used to study connectome dynamics at slow and fast speeds, respectively. But it is often implicitly assumed that these modalities capture the same underlying neural processes, with fMRI doing so through a low-pass temporal filter. However, recent work suggests the alternative possibility that connectome dynamics comprise distinct processes operating at multiple timescales. If such multiscale connectivity processes indeed coexist, a key question is whether their patterns and sequences are organized on the basis of shared regularities, i.e., common spatial and temporal principles. In simultaneous human fMRI and source-localized EEG, we investigated the connectome’s foundational constituents—the instantaneous coactivation patterns—across six timescales of neural activity, from infraslow through γ-band. We found streams of recurrent coactivation patterns, or states, that operate in parallel and asynchronously across timescales, thereby forming a timescale-overarching spatial principle. These states also occurred in highly similar sequences at all timescales, revealing a timescale-overarching temporal principle. Together, these findings indicate that the connectome comprises multiple dynamic streams operating in parallel at distinct speeds, from tens of milliseconds to seconds, rather than a single stream filtered by each modality’s temporal resolution. Spatial and temporal principles that span these streams enable their integration into a unified system. Consequently, research on human behavior and mental disorders should account for the full range of the connectome’s timescales.

Research on dynamic cost prediction method for power technology upgrading projects based on improved transformer neural network

Cluster replicability in single-cell and single-nucleus atlases of the mouse brain

Opposing range-dependent interactions create complex spatial patterns of antibiotic tolerance in multispecies biofilms

Many microbial communities form multispecies biofilms where cells interact through diffusible molecules. In these biofilms, multiple interactions, often with opposing effects, occur simultaneously, yet we lack quantitative frameworks to predict how they combine to shape community functions. Here, we hypothesized that complex spatial patterns can emerge when opposing interactions have distinct spatial ranges. To test this, we studied how two Pseudomonas aeruginosa exoproducts, HQNO and rhamnolipids, jointly modulate Staphylococcus aureus antibiotic tolerance by respectively increasing and decreasing it. Using microfluidics-based imaging, we quantified spatial-tolerance patterns at single-cell resolution and found that tolerance indeed shows a complex spatial pattern: S. aureus cells survived treatment only at intermediate distances from P. aeruginosa , while cells closer or farther away did not. Combining experiments and modeling, we showed that this remarkable pattern emerges because rhamnolipids have a stronger but short-ranged effect, while HQNO has a weaker but longer-ranged effect. We found that spatial arrangement affects overall tolerance by shifting the balance between the two opposing interactions. Finally, using bioprinting, we confirmed that HQNO and rhamnolipids modulate tolerance in highly mixed biofilms. In more segregated biofilms, spatial arrangement still strongly modulated tolerance, but independently of these compounds, suggesting additional interactions. Together, our results show that spatial-tolerance patterns emerge from the combined effect of opposing range-dependent interactions and cannot be predicted from either alone. By predicting how opposing interactions jointly determine community properties, our framework provides a foundation for understanding and ultimately engineering microbiome functions.