Proceedings of the National Academy of Sciences
Articles in this Issue
Freeze-induced crystallization: An overlooked pathway for mineral genesis in natural waters
Natural ice plays salient roles in making the Earth habitable and sustainable. Previously overlooked, its role in chemical processes is now of emerging interest, particularly due to the freeze concent...
ATP8B1 regulates PIP2 localization and cleavage of pyroptotic executioner Gasdermin D
Mutations in ATP8B1 cause progressive familial intrahepatic cholestasis, with symptoms including pruritus, pancreatitis, fat malabsorption, intestinal inflammat...
Cocrystal structure reveals the mechanism of FSP1 inhibition by FSEN1
FSP1 is an FAD-dependent oxidoreductase that uses NAD(P)H to regenerate the reduced forms of lipophilic quinone antioxidants, such as coenzyme Q10 and vitamin K. These quinone antioxidants function as...
Deciphering Ca <sup> <b>2+</b> </sup> permeation and valence selectivity in Ca <sub>V</sub> 1: Molecular dynamics simulations reveal the three-ion knock-on mechanism
Voltage-gated calcium (Ca V...
Surface melting–driven hydrogen absorption for high-pressure polyhydride synthesis
The synthesis of new polyhydrides with high superconducting T c is challenging owing to the high pressures and temperatures required. In thi...
Histone variant H2A.W7 represses meiotic crossover formation in <i>Arabidopsis</i> heterochromatin
In eukaryotic genomes, DNA is packaged into nucleosomes to form chromatin. The incorporation of canonical or variant histones into nucleosomes confers different properties and influences chromatin str...
Microtubule dynamics are defined by conformations and stability of clustered protofilaments
Microtubules are dynamic cytoskeletal polymers that add and lose tubulin dimers at their ends. Microtubule growth, shortening, and transitions between them are linked to GTP hydrolysis. Recent evidenc...
Molecular basis for ligand recognition and receptor activation of the prostaglandin D2 receptor DP1
The prostaglandin D2 receptor 1 (DP1), a rhodopsin-like Class A GPCR, orchestrates critical physiological and pathological processes, ranging from sleep regulation to inflammatory responses and cardio...
Ethanol induction of FGF21 in the liver is dependent on histone acetylation and ligand activation of ChREBP by glycerol-3-phosphate
Ethanol rapidly stimulates the liver to synthesize the hormone fibroblast growth factor 21 (FGF21), which then acts on the brain to elicit a multifaceted protective response. We show that in mice, thi...
Manifold fitting reveals metabolomic heterogeneity and disease associations in UK Biobank populations
NMR-based metabolic biomarkers provide comprehensive insights into human metabolism; however, extracting biologically meaningful patterns from such high-dimensional data remains a significant challeng...
An electrostatic network with strong connectivity is a phospho-sensor for regulating affinity of Syk–receptor association
Spleen tyrosine kinase (Syk) mediates early signaling events in immunity by coupling membrane receptors to immune responses. Syk comprises a tandem SH2 (tSH2) regulatory module—two SH2 domains connect...
Reversible molecular simulation for training classical and machine-learning force fields
The next generation of force fields for molecular dynamics will be developed using a wealth of data. Training systematically with experimental data remains a challenge, however, especially for machine...
<i>Arabidopsis</i> HOOKLESS1 acts as a histone acetyltransferase to promote cotyledon greening during seedling de-etiolation
Greening immediately after etiolated-seedling’s emergence from the soil is critical for plants to initiate their autotrophic life cycle through photosynthesis. The greening process relies on a complex...
Micropipette aspiration reveals differential RNA-dependent viscoelasticity of nucleolar subcompartments
The nucleolus is a multiphasic biomolecular condensate that facilitates ribosome biogenesis, a complex process involving hundreds of proteins and RNAs. The proper execution of ribosome biogenesis like...
Viral and host network analysis of the human cytomegalovirus transcriptome in latency
The human cytomegalovirus (HCMV) UL135 and UL138 genes play opposing roles regulating latency and reactivation in CD34...
Engineering a protease-stable, oral single-domain antibody to inhibit IL-23 signaling
Interleukin (IL)-23 is a validated therapeutic target in inflammatory bowel disease. While antibodies targeting IL23 demonstrate clinical efficacy, they face challenges such as high costs, safety risk...
Laser-induced graphene points to sustainable electronics
Allelic variations and gene cluster modularity act as nonlinear bottlenecks for cholera emergence
The underlying factors that lead to specific strains within a species to emerge as human pathogens remain mostly enigmatic. The diarrheal disease cholera is caused by strains from a phylogenetically c...
Specialized molecular pathways drive the formation of light-scattering assemblies in leucophores
Pigmentation plays a vital role in the survival of organisms, supporting functions such as camouflage, communication, and mate attraction. In vertebrates, these functions are mediated by specialized p...
Nanoimmunomodulation of the Aβ-STING feedback machinery in microglia for Alzheimer’s disease treatment
Imbalanced production and clearance of amyloid-β (Aβ) is a hallmark pathological feature of Alzheimer’s disease (AD). While several monoclonal antibodies targeting Aβ have shown reductions in amyloid...
Host complement C3 promotes malaria transmission by killing symbiotic bacteria in the mosquito midgut
Host-derived factors ingested during mosquito blood feeding are poorly understood modulators of malaria transmission. Here, we demonstrated that host complement C3, acquired by mosquitoes during...
Iñupiat marine mammal science a long time coming
Biochemical and structural basis of Dicer helicase function unveiled by resurrecting ancient proteins
A fully functional Dicer helicase, present in the modern arthropod, uses energy from ATP hydrolysis to power translocation on bound dsRNA, enabling the processive dsRNA cleavage required for efficient...
Lynn Landmesser (1943–2024): A pioneer in developmental neurobiology
Lynn Landmesser, whose studies transformed our view of how neurons find the proper partners on which to form synapses, died at the age of 80 in November 2024. Using elegant electrophysiological method...
Cardiolipin membranes drive Myosin VI activation, oligomerization, and processive cargo transport
Mitochondrial damage determines cell fate, leading to mitochondrial autophagy or cellular apoptosis in health and disease. The molecular mechanisms and role of the acto-myosin cytoskeleton regulating...