Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceExtremity musculoskeletal trauma is the most common injury pattern seen in humans. While in some instances, these musculoskeletal tissues heal, oftentimes tissue repair fails due to an aberrant cell fate program of the cells at the injury ...
Science Journals
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceThe prevailing assumption of millennial-scale stability has led to the widespread neglect of soil inorganic carbon (SIC) dynamics, especially in deep soil layers. Using a large-scale, depth-resolved resampling of China’s upland croplands, we ...
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceEarly-life adversity (ELA) can have lifelong consequences, yet identifying how early experiences shape individual variation in growth and reproduction has remained difficult in primates. Leveraging 64 y of behavioral, physiological, and ...
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceUnderstanding how species cope with rapid climate and land use change requires studying evolutionary responses across scales. UsingAmaranthus tuberculatus, a native species turned major agricultural weed, we bridge timescales by pairing a ...
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceOrphan G protein–coupled receptors (GPCRs) constitute a vast reservoir of potential drug targets but remain structurally elusive due to the absence of ligands, unclear G-protein coupling, and inherent instability. To address these challenges, ...
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceRegulating digital platforms is difficult when platforms control the data needed to assess design changes. This study demonstrates an alternative: an open, market-wide field experiment that allows independent measurement of market outcomes. ...
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificancePlants experience multiple environmental signals, such as light and temperature, that must be interpreted together to regulate growth and development. How this integrative capacity evolved across plant lineages remained unclear. By comparing ...
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceThe pineal gland is a central regulator of circadian rhythms and neuroendocrine homeostasis in primates, yet its cellular diversity and spatial regulatory logic remain poorly defined. By integrating single-nucleus and spatial multiomics in...
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceThis work uncovers a glial pathway by which chronic psychosocial stress drives maladaptive myelin and immune changes. We show that Pde4b upregulation in stress-specific immune-like oligodendrocytes (ImOL) orchestrates cyclic adenosine ...
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceGenome evolution in prokaryotes has been explained by either selection for streamlining or selection for functional diversification enabled by horizontal gene transfer. However, the extent to which these forces coexist or dominate in different ...
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceMCM8 and MCM9 form a hexameric helicase that is critical for preserving ovarian reserve and preventing premature ovarian insufficiency (POI), a major cause of female infertility. In this study, we demonstrate that MCM8-9 helicase activity is ...
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceRecognizing the Loess Plateau as the world’s largest afforestation area, we explored vegetation states across a large-scale survey to reassess precipitation thresholds of afforestation. We identified a forest maintenance threshold of 350 mm ...
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceMolecular recognition processes are ubiquitous to enact function. The current materials design efforts focused on energetics as primary factor to tune binding are suboptimal because they overlook the role of entropic forces, which is often ...
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceThe interaction between sphingomyelin (SM) and cholesterol, two of the most abundant lipids in plasma membranes of animal cells, provides many functional benefits. These include protection from microbial infection, prevention of unrestrained ...
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceBetter understanding plant photosynthetic responses to elevated temperature and leaf-to-air vapor pressure difference (Δe) is critical under climate change. By separating temperature and Δeeffects across multiple CO2levels, we demonstrate ...
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceCortical traveling waves (TWs) have been observed across species and cognitive states, yet their causal role in brain function has remained unclear. A major challenge has been the lack of tools to selectively impose TW-like spatiotemporal ...
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceChildren rapidly acquire an ability for language during early development. One theory, called iterated learning, posits that language evolves over generations to become more structured. This structure can then be exploited by learners through ...
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceSeeds evolved when plants retained the female spores inside the parent tissue. The growth of the spores was accommodated by removing part of the nucellus, the maternal tissue responsible for female meiosis. Here, we demonstrate that ...
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceLong-term hematopoietic stem cells (LT-HSC) maintain lifelong hematopoiesis while preserving the stem cell compartment through self-renewal. ATP2B1 identifies a rare population of LT-HSC across ontogeny which relies on the Transcription Factor ...
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceB lymphocytes generate different antibody isotypes to combat antigens through a DNA breakage and joining process termed antibody class switch recombination (CSR). During CSR, the dynamic regulation of chromatin configuration juxtaposes the two ...
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceInducing programmed cell death represents one of the most promising therapeutic strategies for colorectal cancer (CRC). Our analysis revealed significantly elevated copper levels and increased expression of DLAT in CRC tissues compared to ...
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026. SignificanceBifunctional catalysts play vital roles and are widely used in catalysis. It is well established that the proximity of dual active sites determines catalytic performance. Yetspatial arrangement control over dual sites is restricted to two ...
Age-related hearing loss is a complex phenomenon. The earliest-onset degenerative event is the gradual loss of neural connections between the cochlea and auditory brainstem. To probe for perceptual deficits that might arise from this loss, cochlear synaptopathy was induced pharmacologically in young-adult gerbils, which were then tested in a challenging listening task for the perception of temporal fine structure. Treated gerbils behaved no differently than normal-hearing, young-adult animals. In contrast, old gerbils, which typically express many cochlear and central-neural pathologies, showed impaired perception. To probe for the underlying mechanisms, single-unit responses were obtained from the auditory nerve to the same test stimuli. Responses from old gerbils showed no impairment in temporal locking to the stimulus fine structure. However, responses were significantly more driven by slower temporal fluctuations of the stimulus envelope, suggesting that the central auditory system may be unable to extract the relevant information for discrimination from such altered inputs.
Nanopore technology offers real-time sequencing opportunities, providing rapid access to sequenced data and allowing researchers to manage the sequencing process efficiently, resulting in cost-effective strategies. Here, we present focused case studies demonstrating the versatility of real-time transcriptomics analysis in rapid quality control for long-read RNA-seq. We illustrate its utility through four experimental setups: (1) transcriptome profiling of distinct human cellular populations, (2) identification of experimentally enriched transcripts, (3) transcriptional analysis of cells under heat shock conditions, and (4) identification of experimentally manipulated genes (knockout and overexpression) in several yeast strains. We show how to perform multiple layers of quality control as soon as sequencing has started, addressing both the quality of the experimental and sequencing traits. Real-time quality control measures assess sample/condition variability and determine the number of identified genes per sample/condition. Furthermore, real-time differential gene/transcript expression analysis can be conducted at various time points post-sequencing initiation (PSI), revealing dynamic changes in gene/transcript expression between two conditions. Using real-time analysis, which occurs in parallel to the sequencing run, we identified differentially expressed genes/transcripts as early as 1 hr PSI. These changes were consistently observed throughout the entire sequencing process. We discuss the new possibilities offered by real-time data analysis, which have the potential to serve as a valuable tool for rapid and cost-effective quality checks in specific experimental settings and can be potentially integrated into clinical applications in the future.
In the growing diversity of human induced pluripotent stem cell (iPSC)-derived models of brain development, we present here a novel method that exhibits 3D cortical layer formation in a reproducible topography of minimal dimensions. The resulting adherent cortical organoids (ACOs) develop by self-organization after seeding frontal cortex-patterned iPSC-derived neural progenitor cells in 384-well plates during 8 weeks of differentiation. The organoids have stereotypical dimensions of 3 × 3 × 0.2 mm, contain multiple subtypes of neurons, astrocytes, and oligodendrocyte lineage cells, and are amenable to extended culture for at least 10 months. Longitudinal imaging revealed morphologically mature dendritic spines, axonal myelination, and robust neuronal activity. Moreover, ACOs compare favorably to existing free-floating brain organoid models on the basis of robust reproducibility in obtaining topographically standardized radial cortical structures and circumventing internal necrosis. Adherent human cortical organoids hold considerable potential for high-throughput drug discovery applications, neurotoxicological screening, and mechanistic pathophysiological studies of brain disorders.