Proceedings of the National Academy of Sciences
Articles in this Issue
HLA-B*15:01-positive severe COVID-19 patients lack CD8 <sup>+</sup> T cell pools with highly expanded public clonotypes
Understanding host factors driving asymptomatic versus severe disease outcomes is of key importance if we are to control emerging and re-emerging viral infections. HLA-B*15:01 has been associated with...
8,000 years of wild and domestic animal body size data reveal long-term synchrony and recent divergence due to intensified human impact
The long-term evolution of domestic mammal body size in Western Europe since the Early Neolithic is mainly attributed to human selection. However, the relative influence of environmental and anthropog...
Vacuum tunneling of vortices in two-dimensional <sup>4</sup> He superfluid films
At low temperature T we expect vacuum tunneling processes to occur in superfluid 4 He films. We distinguish between extr...
The RNA-binding protein TRIM71 is essential for hearing in humans and mice and times auditory sensory organ development
The RNA-binding protein TRIM71 is essential for brain development, and recent genetic studies in humans have identified TRIM71 as a risk gene for congenital hyd...
Identification of AMOTL2 as an antiviral factor that enhances the human type I interferon response against Zika virus
Zika virus (ZIKV) has caused multiple human outbreaks, with more recent epidemics associated with severe outcomes in infants. Today, ZIKV is endemic to many countries and presents a persistent threat...
Unprecedented suppression of Panama’s Pacific upwelling in 2025
The Gulf of Panama’s (GOP) seasonal upwelling system has consistently delivered cool, nutrient-rich waters via northerly trade winds every January–April for at least 40 y. Here, we document the failur...
Metabolic rewiring of isoniazid sensitivity in <i>Mycobacterium tuberculosis</i>
Isoniazid (INH) inhibits mycolic acid synthesis in Mycobacterium tuberculosis ( Mtb ) and is a cornerstone of treatment...
Structural insights into the substrate uptake and inhibition of the human creatine transporter (hCRT)
Creatine plays a vital role in cellular energy production and adenosine triphosphate (ATP) homeostasis and has also been identified as a neurotransmitter in the mammalian brain. Creatine is transporte...
Oyster farming acts as a marine carbon dioxide removal (mCDR) hotspot for climate change mitigation
Bivalve farming, a vital component of global aquaculture, has been proposed as a potential marine carbon dioxide removal (mCDR) strategy, yet its role remains contentious. Using field mesocosms, we de...
Subaerial oxidative uranium mobilization at the culmination of the Great Oxidation Event
Redox-sensitive elements figure prominently in studies of the evolution of Earth’s surface redox state, including the first major rise in atmospheric O 2 , the...
Pulsed biogenic methane emissions coupled with episodic warming during the Toarcian Oceanic Anoxic Event
Reconstructing carbon release fluxes during ancient climatic warming events is important for improving predictions of carbon cycle and climate dynamics under future anthropogenic warming scenarios. We...
Therapeutic restoration of mitochondria–endoplasmic reticulum cross talk for osteoarthritis
Osteoarthritis is a prevalent joint disease in the aging population. The hallmark of osteoarthritis is the degeneration of the joint cartilage, characterized by changes in chondrocytes including mitoc...
<i>Pdgf</i> mediates a transient regeneration-activated cell state in planarian tissue regeneration
The role of induced gene expression is crucial for tissue regeneration. The transient regenerative cellular state that discriminates between missing-tissue and non-missing-tissue injuries remains to b...
Using bioinformatics for identifying and plugging metabolic pathway holes
Mechanisms underlying allosteric modulation of antiseizure medication binding to synaptic vesicle protein 2A (SV2A)
Brivaracetam (BRV) and levetiracetam (LEV) are antiseizure medications (ASMs); UCB-J is a PET tracer targeting synaptic vesicle protein 2A (SV2A); UCB7361 is closely related to padsevonil, an experime...
Rethinking early-life pathogen exposure: Lessons from a natural experiment controlling hookworms
Tumor-expressed GPNMB orchestrates Siglec-9 <sup>+</sup> TAM polarization and EMT to promote metastasis in triple-negative breast cancer
Metastasis remains the leading cause of cancer-related mortality, driven by complex interactions within the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) play a pivotal role in met...
Lysosomal reduced thiols are essential for mouse embryonic development
While it has been appreciated for decades that lysosomes can import cysteine, its significance for whole-organism physiology has remained uncertain. Recent work identified MFSD12 as a transmembrane pr...
Direct measurement of plume velocity to characterize point source emissions
An explosion of recent research uses remote imaging spectroscopy from aircraft and spacecraft to detect and quantify methane point source emissions. These instruments first map the methane enhancement...
Digital SERS bioanalysis of single-enzyme biomarkers
Digital bioanalysis enables highly sensitive detection of biomolecules at the single-molecule level, making it a widely used technique in biomedical research. However, conventional approaches typicall...
AhR signaling in skin-resident CD207 <sup>+</sup> cells is involved in UV-B-induced amelioration of neuroinflammation
Environmental stimuli, including the exposure to ultraviolet (UV)-B light, are known to play a role in the modulation of immune-mediated mechanisms in multiple sclerosis (MS). In experimental autoimmu...
Surrogate optimization of variational quantum circuits
Variational quantum eigensolvers are touted as a near-term algorithm capable of impacting many applications. However, the potential has not yet been realized, with few claims of quantum advantage and...
The molecular structure of the master growth regulator in plants emerges into the spotlight
Evolving choice hysteresis in reinforcement learning: Comparing the adaptive value of positivity bias and gradual perseveration
The tendency to repeat past choices more often than expected from the history of outcomes has been repeatedly empirically observed in reinforcement learning experiments. It can be explained by at leas...
Daily liver rhythms: Coupling morphological and molecular oscillations
In mammals, a hierarchically organized circadian timing system orchestrates daily rhythms of nearly all physiology. A master pacemaker in the brain’s suprachiasmatic nucleus (SCN) synchronizes subsidi...