Proceedings of the National Academy of Sciences
Articles in this Issue
Correction for Zhu et al., SETD2-mediated H3K14 trimethylation promotes ATR activation and stalled replication fork restart in response to DNA replication stress
Uncovering mitochondrial defects in photoreceptors opens therapeutic opportunities for Stargardt disease
Stargardt disease type 1 (STGD1) is the most common hereditary macular degeneration. It is caused by mutations in ABCA4 , which result in the progressive degene...
Constrained evolutionary funnels shape viral immune escape
Understanding how viral proteins adapt under immune pressure while preserving viability is crucial for anticipating antibody-resistant variants. We present a probabilistic framework that predicts vira...
Comparative analysis of naked mole-rat thermogenesis and its potential to maintain euthermia in response to cold
The naked mole-rat (NMR) is a subterranean rodent known for its unique thermal biology, exceptional longevity, and resistance to cancer and hypoxia. However, its thermal biology remains controversial,...
FABP7 controls radial glial scaffold stability during human cortical development
Radial glial (RG) cells serve as both neural progenitors and structural scaffolds for neuronal migration during cortical development. Although FABP7 has long been recognized as a marker of RG cells, i...
Compositional memory matters for early molecular systems
The error catastrophe refers to the proliferation of nonfunctional molecules in conditions where molecular replication has low accuracy, which is likely to correspond to conditions present at the Orig...
Evolutionary-based remodeling of ABA receptors reveals the structural basis of hormone perception and regulation
Drought limits crop productivity, and effective mitigation requires a mechanistic understanding of how abscisic acid (ABA) perception translates hormone levels into physiological responses. In seed pl...
WWOX maintains epidermal identity and suppresses EMT to prevent aggressive cutaneous squamous cell carcinoma
Cutaneous squamous cell carcinoma (cSCC), the second most common skin cancer, remains a major health burden worldwide. The WW domain–containing oxidoreductase (WWOX) is frequently altered in cancer; h...
Phase separation induced by active polymerization makes protocells robust against environmental changes
The origin of life remains a scientific mystery, particularly the emergence of protocells. One hypothesis proposes that protocells arose as droplets formed via liquid–liquid phase separation of polyme...
Rubisco kinetic acclimation at the holoenzyme level
In plants, the CO 2 -fixing enzyme Rubisco is hexadecameric, with each mature holoenzyme containing eight small subunits (SSus). Many plants express multiple SS...
Correction for Brodsky and Farge, How earthquakes organize stress
Evidence for strong purifying selection of human <i>47S</i> ribosomal RNA genes
The multicopy 47S ribosomal RNA (rRNA) genes are among the most highly expressed genes in the human genome, yet to-date essentially no disease-causing sequence...
Selective octopaminergic tuning of mushroom body circuits during memory formation
The catecholamines octopamine and tyramine undoubtedly have a major impact on the life of an insect. A wide range of physiological processes and behaviors are regulated by these neurotransmitters/horm...
Quantifying and combating zoonotic viruses poised for emergence: Using multiplex receptor screening and decoy engineering technologies
Viral discovery efforts have uncovered millions of zoonotic viruses across multiple continents, listed on the World Health Organization’s pandemic risk register. Over two-thirds of these zoonotic viru...
A plasma-based DNA test for quantification of disease burden in acute myeloid leukemia patients undergoing bone marrow transplantation
Allogeneic hematopoietic cell transplantation is the only curative option for many patients with acute myeloid leukemia (AML). In the current study, we designed and implemented a personalized assay, c...
Distinct evolutionary patterns of endemic and emerging parvoviruses and the origin of a new pandemic virus
Emergence of epidemic viruses in new hosts threatens both human and other animal populations, and often involves virus evolution to overcome barriers that normally prevent efficient infection and spre...
Podocin oligomers regulate the ordering of nephrin chains, providing the molecular basis of <i>NPHS2</i> interallelic interactions
The most frequent causative genes in podocytopathies are NPHS1 and NPHS2 that encode the main slit diaphragm components...
Structural basis of transcription-coupled RNA damage by incorporation of oxidized ribonucleotides
Oxidative stress induces damage to DNA, RNA, and nucleotide pools. Unlike well-studied DNA damage, the formation of RNA damage and the impact of an oxidized ribonucleotide pool on transcription fideli...
CHK2-USP37 axis stabilizes FOXO4 to sustain senescence and evade apoptosis
Cellular senescence, a state of permanent cell cycle arrest, contributes to tissue dysfunction and aging through the accumulation of apoptosis-resistant senescent cells. Although the transcription fac...
Medial temporal lobe encodes cognitive maps of real-world social networks
Humans routinely solve social problems by navigating densely interconnected networks—gossiping strategically, brokering across cliques, and coordinating with allies. Yet, the neural representations su...
Southern Ocean seabird population shifts over the Holocene revealed by peat sequestration of mercury from guano
Monitored seabird populations have declined by up to 70% worldwide since the 1950s. Yet, data on long-term seabird population dynamics prior to the anthropogenic era are largely unknown. This limits o...
Epigenetic constraints and enhancer innovation link neuronal plasticity to evolutionary adaptation
How nervous systems balance the generation of robust neuron types with gene expression plasticity mechanisms and how these processes impact cell-type evolution are unknown. Here, we use...
Trem2 exacerbates ischemic brain injury through Gpnmb in a photothrombotic stroke model
Ischemic stroke is a major public health challenge, with microglia-mediated neuroinflammation exerting both protective and detrimental effects on neuronal survival. The Triggering receptor expressed o...
Immune modulation promotes heart regeneration through macrophage and Granulin functions in medaka
Myocardial infarction results in irreversible cardiomyocyte loss and fibrotic remodeling in adult mammals, whereas some vertebrates retain the ability to regenerate cardiac tissue. Comparative studies...
YTHDC1 recognizes METTL16-dependent m <sup>6</sup> A on caRNAs and coordinates cotranscriptional splicing
N 6 -methyladenosine (m 6 A) RNA modification regulates diverse biological process. The m...