综合性期刊最新文献

Mucociliary clearance is a vital defense mechanism of the human airways, protecting against harmful particles and infections. When this process fails, it contributes to respiratory diseases like chronic obstructive pulmonary disease (COPD) and asthma. While advances in single-cell transcriptomics have revealed the complexity of airway composition, much of what we know about how airway structure impacts clearance relies on animal studies. This limits our ability to create accurate human-based models of airway diseases. Here we show that the airways in female rats and in humans exhibit species-specific differences in the distribution of ciliated and secretory cells as well as in ciliary beat, resulting in significantly higher clearance effectiveness in humans. We further reveal that standard lab-grown cultures exhibit lower clearance effectiveness compared to human airways, and we identify the underlying structural differences. By combining diverse experiments and physics-based modeling, we establish universal benchmarks to assess human airway function, interpret preclinical models, and better understand disease-specific impairments in mucociliary clearance.

Proteins with chemically regulatable phase separation are of great interest in the fields of biomolecular condensates and synthetic biology. Intrinsically disordered proteins (IDPs) are the dominating building blocks of biomolecular condensates which often lack orthogonality and small-molecule regulation desired to create synthetic biomolecular condensates or membraneless organelles (MLOs). Here, we discover a well-folded globular protein, lipoate-protein ligase A (LplA) from E. coli involved in lipoylation of enzymes essential for one-carbon and energy metabolisms, that exhibits structural homomeric oligomerization and a rare LCST-type reversible phase separation in vitro. In both E. coli and human U2OS cells, LplA can form orthogonal condensates, which can be specifically dissolved by its natural substrate, the small molecule lipoic acid and its analogue lipoamide. The study of LplA phase behavior and its regulatability expands our understanding and toolkit of small-molecule regulatable protein phase behavior with impacts on biomedicine and synthetic biology.

Global ocean surface temperatures were at record levels for more than a year from April 2023 onwards, exceeding the previous record in 2015–2016 by 0.25 °C on average between April 2023 and March 2024¹. The nearly global extent and unprecedented intensity of this event prompted questions about how exceptional it was and whether climate models can represent such record-shattering jumps in surface ocean temperatures². Here we construct observation-based synthetic time series to show that a jump in global sea surface temperatures that breaks the previous record by at least 0.25 °C is a 1-in-512-year event under the current long-term warming trend (1-in-205-year to 1-in-1,185-year event; 95% confidence interval). Without a global warming trend, such an event would have been practically impossible. Using 270 simulations from a wide range of fully coupled climate models, we show that these models successfully simulate such record-shattering jumps in global ocean surface temperatures, underpinning the models’ usefulness in understanding the characteristics, drivers and consequences of such events. These model simulations suggest that the record-shattering jump in surface ocean temperatures in 2023–2024 was an extreme event after which surface ocean temperatures are expected to revert to the expected long-term warming trend.

Habitat fragmentation generally reduces biodiversity at the patch scale (α diversity)¹. However, there is ongoing debate about whether such negative effects can be alleviated at the landscape scale (γ diversity) if among-patch diversity (β diversity) increases as a result of fragmentation^2,3,4,5,6. This controversial view has not been rigorously tested. Here we use a dataset of 4,006 taxa across 37 studies from 6 continents to test the effects of fragmentation on biodiversity across scales by explicitly comparing continuous and fragmented landscapes. We find that fragmented landscapes consistently have both lower α diversity and lower γ diversity. Although fragmented landscapes did tend to have higher β diversity, this did not translate into higher γ diversity. Our findings refute claims that habitat fragmentation can increase biodiversity at landscape scales, and emphasize the need to restore habitat and increase connectivity to minimize biodiversity loss at ever-increasing scales.

Frictional interfaces are found in systems ranging from biological joints to earthquake faults. When and how these interfaces slide is a fundamental problem in geosciences and engineering^{1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20}. It is believed that there exists a threshold shear force, called static friction, below which the interface is stationary^4,10, despite many studies suggesting that this concept is outdated^{1,21,22,23,24,25,26,27,28}. By contrast, rate-and-state friction formulations^1,26,27 predict that interfaces are always sliding²⁹, but this feature is often considered an artefact that calls for modifications³⁰. Here we show that nominally stationary interfaces subjected to constant shear and normal loads, with a driving force that is notably below the classically defined static friction for which creep is known to occur^9,27,28,29, are sliding, but with diminishingly small rates down to 10⁻¹² m s⁻¹. Our precise measurements directly at the interface are enabled by digital image correlation^18,31,32. This behaviour contradicts classical models of friction but confirms the prediction of rate-and-state friction^1,26,27. The diminishing slip rates of nominally stationary interfaces reflect interface healing, which would manifest itself in higher peak friction in subsequent slip events^15,27,33, such as earthquakes and landslides, substantially modifying their nucleation and propagation and hence their hazard^3,12,13,34.

Endomesoderm specification by a maternal β-catenin signal and body axis patterning by interpreting a gradient of zygotic Wnt/β-catenin signalling was suggested to predate the split between Bilateria and their sister clade Cnidaria. However, in Cnidaria, the roles of β-catenin signalling in these processes have not been demonstrated directly. Here, by tagging the endogenous β-catenin in the cnidarian Nematostella vectensis, we confirm that its oral-aboral axis is indeed patterned by a gradient of β-catenin signalling. Strikingly, we show that, in contrast to bilaterians, Nematostella endomesoderm specification is repressed by β-catenin and takes place in the maternal nuclear β-catenin-negative part of the embryo. This completely changes the accepted paradigm and suggests that β-catenin-dependent endomesoderm specification was a bilaterian innovation linking endomesoderm specification to the subsequent posterior-anterior patterning.