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SPNS1 is an essential cellular factor for EV-A71 by acting as a transporter of viral pocket factor

Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceHuman enterovirus A71 (EV-A71) is a major cause of hand, foot and mouth diseases which poses a global threat to human health. Despite intensive investigations, the cellular factors that are critical for EV-A71 infection remain enigmatic, …

Building hierarchically nested structure by rapid neural sequences

Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceThe human mind excels at building complex, multilevel structures, which we use daily from constructing a sentence to planning a multistep project. Yet, how the brain actually builds these mental hierarchies has remained largely unknown. This …

Contrastive independent component analysis for salient patterns and dimensionality reduction

Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceVisualizing data and finding patterns in data are ubiquitous problems in the sciences. Increasingly, applications seek signal and structure in a contrastive setting: a foreground dataset relative to a background dataset. The goal is to learn …

Coexistence of trapped and flow-transported nuclei enables fast pigeon post communication across multinucleated cell

Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceSyncytia house up to hundreds of thousands of nuclei within a single cell, often gigantic in size. For coordination of gene expression over such long distances, nuclei need to communicate. In search of a fast mechanism of communication, we …

CDCA7 facilitates MET1-mediated CG DNA methylation maintenance in centromeric heterochromatin via linker histone H1

Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceA key question in epigenetic memory is how DNA methylation is maintained and inherited within tightly packed heterochromatin. This process is crucial for genome stability, and its disruption can cause ICF syndrome, a disorder associated with …

Globally aggregated biodiversity data impact predictive and descriptive research

Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceGiven the increasingly central importance of data aggregators and infrastructures as critical resources for the global research community it is important to understand how they are evolving. Specifically, it would be useful to know how much …

Heterogeneous template-dependent transcription dynamics of T7 RNAP revealed by single-molecule imaging

Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceBacteriophage T7 RNA polymerase is a key tool in RNA synthesis, but its efficiency can be hindered by premature stalls and low yields. This study sheds light on the causes of these limitations: the flexibility and electrostatic potential of …

Organization principles of dynamic three-dimensional genome architecture associated with centromere clustering states

Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceChromosomes occupy the nuclear space in many ways. Primary chromosomal arrangements are such that centromere regions of different chromosomes either form a cluster, as in yeasts, or are scattered around the nuclear periphery, more common in …

A metabolic cell death program downstream of SARM1 couples NAD+ depletion to BAX activation and APAF1 degradation

Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceLoss of the essential metabolic cofactor Nicotinamide adenine dinucleotide (NAD+) as a result of neuronal NADase SARM1 activation is a potent trigger of axonal degeneration and neuronal death, but how this signal executes cell death program …

IL-27 promotes Treg cell expression of CD122 and fitness at homeostasis

Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceTreg cells are a specialized population of T cells that dampen inflammation and maintain tolerance. Numerous studies highlight the ability of the cytokine IL-27 to promote Treg cell responses during inflammation, but the impact of IL-27 on …

Resolved tropical cyclones trigger CO2 uptake and phytoplankton bloom in an Earth system model simulation

Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceEarth system models typically work with spatial resolution of 100 to 200 km. This is too coarse for the representation of small-scale mechanisms and extreme events, such as intense tropical cyclones (e.g. hurricanes). We present a km-scale …

Upper mantle temperatures illuminate the Iceland hotspot track and understanding of ice–Earth interactions in Greenland

Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceThe Greenland continent is of interest due to its interaction with the Iceland hotspot and because it supports an ice sheet which is, and will be, a primary contributor to global sea level rise. Using multiple data sets, we estimate 3D …

Multiple weak brakes act in concert to control STIM1 and store-operated calcium entry

Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceStore-operated calcium entry (SOCE) is essential for many physiological processes, and inadequate regulation of this pathway leads to a variety of human diseases. The ER calcium-sensing protein STIM1 is known to control SOCE, but a structural …

Chatbot Voting Advice Applications inform but seldom sway young unaligned voters

Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceMany people struggle to identify where political parties stand on the issues that matter most to them. This study introduces a Voting Advice Application (VAA) Bot powered by generative AI, that provides information about party positions using …

Evolved birth physiology meets modern birth practice: Sustained effects of planned cesarean delivery on child hair cortisol in Brazil

Proceedings of the National Academy of Sciences, Volume 122, Issue 50, December 2025. SignificanceDuring labor, babies are exposed to mechanical forces and hormones that help prepare them for life outside the womb. Using data from a large sample of 4 to 7 y old children from Brazil, we found that those born by planned cesarean section had …