Browse Articles

SLEEPY: a comprehensive Python module for simulating relaxation and dynamics in nuclear magnetic resonance

Abstract Nuclear magnetic resonance is a powerful method for characterizing dynamics of biological systems in a native-like environment. Accurate dynamics characterization, however, often requires simulations of complex NMR experiments. While a number of simulation programs exist for NMR simulation (SIMPSON, Spinach, SpinEvolution), none of these are focused on easy simulation of motional effects on NMR experiments. The SLEEPY Python module makes it straightforward to simulate arbitrary pulse sequences while including both relaxation and exchange processes. SLEEPY furthermore allows simulation of solid-state (static and spinning) and solution NMR experiments, using both truncated and full Hamiltonians (rotating frame/lab frame). We demonstrate its application to a wide variety of experiments, including transverse (T 1 ρ ), and longitudinal relaxation (T 1 ), nuclear Overhauser effect magnetization transfers, recoupling, and paramagnetic effects. We also provide an extensive online tutorial that explains how to use the various capabilities of SLEEPY. This tool can then be used for both better understanding of the impact of dynamics on NMR and in reproduction of experimental results.

Resetting the clock by integrating urban nature and its biodiversity into the 15-minute city concept

Oomycetes manipulate plant innate immunity through galacturonide oxidases

Abstract Phytophthora infestans is a damaging crop pathogen and a model oomycete for studying plant-pathogen interactions. We report the functional characterisation of a group of P. infestans berberine bridge enzyme-like proteins (BBEs) and their role in plant infection. We demonstrate that BBE-encoding genes are upregulated early during infection and that the secreted enzymes specifically oxidise fragments of pectin, the most abundant charged polysaccharide in the plant cell wall. We further show that these enzymes preferentially oxidise longer pectin fragments, which evade detection by the plant and fail to trigger reactive oxygen species (ROS) signalling. Microscopy revealed that the most abundant P. infestans BBE localises at germ tube tips prior to leaf penetration, and at haustoria during early infection. Combined with the reduced infection observed upon silencing of the encoding genes, these findings point to a key role for this enzyme class in host penetration and colonisation by microbial pathogens. The identification of BBEs as oomycete pathogenicity factors opens new opportunities for crop protection and food security.

CrystalFlow: a flow-based generative model for crystalline materials

Enhanced hybridization-proximity labeling discovers protein interactomes of single RNA molecules

Abstract RNAs engage diverse protein partners and localize to specific subcellular compartments, yet dissecting proteomes associated with low-abundance or dispersed RNA molecules remains a challenge. We present an enhanced hybridization-proximity labeling (HyPro) technology for in situ proteome profiling of endogenously expressed RNA microcompartments. We re-engineer the HyPro enzyme and optimize proximity biotinylation conditions to identify proteins associated with compact RNA-containing nuclear bodies, small pre-mRNA clusters, and individual transcripts. Applying this approach to pathogenic G4C2 repeat–containing C9orf72 RNAs, retained as single-molecule foci in the nuclei of amyotrophic lateral sclerosis (ALS) patient-derived pluripotent stem cells, we reveal extensive interactions with disease-linked paraspeckle markers and a specific set of pre-mRNA splicing factors. These findings highlight early RNA processing and localization defects in ALS that may contribute to this late-onset neurodegenerative disorder. Overall, HyPro provides a broadly applicable platform for mapping RNA-protein interactions, enabling insights into RNA biology and its dysregulation in disease.

Vegetation cover change as a growing driver of global leaf area index dynamics

Artificial intelligence coupled to pharmacometrics modelling to tailor malaria and tuberculosis treatment in Africa

A dirigent protein redirects extracellular terpenoid metabolism for defense against biotic challenges

Optineurin is an adaptor protein for ubiquitinated substrates in Golgi membrane-associated degradation

Abstract Golgi membrane-associated degradation (GOMED) is a process that leading to the degradation of proteins that have passed through the trans-Golgi membranes upon Golgi stress. GOMED is morphologically similar to autophagy, but the substrates degraded are different, and they thus have different biological roles. Although the substrate recognition mechanism of autophagy has been clarified in detail, that of GOMED is completely unknown. Here we report that GOMED degrades its substrate proteins selectively via optineurin (OPTN), as we found that the degradation of GOMED substrates is s`uppressed by the loss of OPTN. OPTN binds to K33 polyubiquitin-tagged proteins that have passed through the Golgi, which are then incorporated into GOMED structures for eventual degradation. In vivo, GOMED is known to be involved in the removal of mitochondria from erythrocytes, and in Optn-deficient mice, mitochondria are not degraded by GOMED, resulting in the appearance of erythrocytes containing mitochondria. These findings provide insight into the substrate recognition mechanism of GOMED.

Thalamocortical hodology to personalize electrical stimulation for focal epilepsy

Warm rings in mesoscale eddies in a cold straining ocean

Abstract The warm and saline Atlantic Water has long been recognized as being subjected to substantial heat loss during its transit towards the polar regions. In particular, the Lofoten Basin, a subpolar sea with energetic eddy activity and strong air-sea interactions, plays a crucial role in the transformation of Atlantic Water. Vertical heat transport at submesoscales (0.1-10 km) in the Lofoten Basin is potentially a key link in the heat transfer to the atmosphere. Here, based on multi-year Seaglider observations augmented by satellite altimeters, radiometers, and high-resolution numerical model results, we evaluate the oceanic vertical heat transport in the Lofoten Basin and demonstrate how geostrophic strain enhances heat transport. The enhancement is found to be associated with submesoscale ageostrophic motions along the mesoscale eddy edges, occurring on spatial scales smaller than 10 km and below the mixed layer depth. These strain-induced submesoscale vertical motions transport heat from the ocean interior to the surface, leading to a 0.4 °C increase in sea surface temperature and the formation of “warm ring” structures in both cyclones and anticyclones. The dominant role of submesoscale heat transport likely represents the primary mechanism for substantial heat loss from Atlantic Water in the Lofoten Basin.

Leveraging cation effect for low temperature aqueous Zn-based batteries

CCL28 contributes to angiogenesis and cardiac repair through CCR10+ endothelial cells after myocardial infarction in male mice

Retraction Note: ROCK1 mechano-signaling dependency of human malignancies driven by TEAD/YAP activation

Near-isotropic super-resolution microscopy with axial interference speckle illumination

Abstract Super-resolution microscopy has pushed the limits of biological imaging. However, achieving isotropic resolution across all spatial dimensions remains a challenge and often requires a complex and highly sensitive optical setup. Herein, we introduce axial interference speckle illumination-engineered structured illumination microscopy (AXIS-SIM), a minimal-modification approach that utilizes constructive interference from a simple back-reflecting mirror to enhance the axial resolution without additional phase control or complex beam shaping. AXIS-SIM provides superior optical sectioning and improves axial resolution beyond the typical axial resolution of conventional 3D-structured illumination microscopy (~300 nm), achieving lateral and axial resolutions of 108.5 and 140.1 nm, respectively. Furthermore, its robustness against alignment errors and sample-induced aberrations enables high-throughput 3D super-resolution imaging of diverse biological specimens. We demonstrate its potential by visualizing the 3D morphology of cell membranes, resolving the nanoscale distribution of lysosomes and microtubules and tracking lysosomal movements with enhanced axial clarity.

Maternal plasma cell-free RNA as a predictor of early and late-onset preeclampsia throughout pregnancy

Mitochondrial one-carbon metabolism is required for TGF-β-induced glycine synthesis and fibrotic responses

A pan-immunotherapy signature to predict intratumoral CD8+ T cell expansions

Abstract Effective cancer immunotherapy relies on the clonal proliferation and expansion of CD8+ T cells in the tumor. However, our insights into clonal expansions are limited, owing to an inability to track the same clones in tumors over time. Here, we develop a multi-site tumor mouse model system to track hundreds of expanding and contracting CD8+ T cell clones over multiple timepoints in tumors of the same individual. Through coupling of clonal expansion dynamics and single-cell RNA/TCR-seq data, we identify a transcriptomic signature in PD-1+Ly108+ precursor exhausted cells that strongly predicts rates of intratumoral clone expansion. The signature correlates with expansion in mice, both with and without immunotherapies, and in patients undergoing PD-1 blockade therapy. Expression of the signature during treatment corresponds with positive clinical outcomes. Downregulation of the signature precedes clone contraction—a phase in which clones contract but maintain revivable precursor exhausted cells in the tumor. LAG-3 blockade re-activates the expansion signature, re-expanding pre-existing clones, including previously contracted clones. These findings reveal how the study of clonal expansion dynamics provide a powerful ‘pan-immunotherapy’ signature for monitoring immunotherapies with implications for their future development.

Apolipoprotein A-IV fibrils: structural diagnosis of mixed cardiac amyloidosis

HSP90 as an evolutionary capacitor drives adaptive eye size reduction via atonal

Abstract Genetic variation fuels evolution, and the release of cryptic variation is key for adaptation. The heat shock protein 90 (HSP90) has been proposed to act as an evolutionary capacitor by revealing such hidden variation under stress. However, this idea remains debated, as the genetic basis of HSP90-regulated traits is often unknown, and many observed phenotypes are deleterious. Here, we show in Tribolium castaneum that HSP90 shapes evolution by unmasking a hidden trait providing enhanced fitness under specific conditions. Using RNA interference and chemical inhibition, we consistently reveal a reduced-eye phenotype that persists in descendant lines across generations without continued HSP90 disruption. Under constant light, reduced-eye beetles had higher reproductive success and greater trait penetrance than normal-eyed siblings, suggesting a selective advantage. Whole-genome sequencing and functional analysis identify the transcription factor atonal ( ato ) as the underlying gene. These results provide the first direct genetic link between an HSP90-buffered trait and context-dependent fitness benefits in animals, highlighting a potential mechanism by which cryptic variation contributes to adaptation.