Proceedings of the National Academy of Sciences
Articles in this Issue
Force-dependent structural dynamics of the giant nesprin-2
The nesprin protein family serves as a critical physical bridge between the cytoskeleton–a fundamental structural scaffold and mechanotransduction hub of the cell, and the nucleus–an intriguing and em...
Protein language models trained on biophysical dynamics inform mutation effects
Structural dynamics are fundamental to protein functions and mutation effects. Current protein deep learning models are predominantly trained on sequence and/or static structure data, which often fail...
Generalizations of the quadratic bound optimization principle
The quadratic bound (QB) principle proposed by Böhning and Lindsay in 1988 is an important special case of the majorization–minimization or minorization-maximization optimization principle. The quadra...
MTFR1L is a cardiac antiaging factor for maintenance of mitochondrial homeostasis
Mitochondrial dysfunction is a hallmark of aging and a key contributor to age-related diseases including cardiovascular disease. However, molecular pathways that safeguard mitochondrial homeostasis in...
Gpr171 regulates embryonic hematopoietic stem cell emergence via ERK1/2 and Notch signaling
Hematopoietic stem cells (HSCs), which sustain lifelong blood cell production, emerge from hemogenic endothelium during embryonic development through the regulation of multiple signaling pathways. How...
Cortical O <sub>2</sub> supply and metabolism are suppressed in the aged mice
Current evidence suggests that the rejuvenating effects of parabiosis on brain function arise from the exchange of blood factors that enhance synaptic plasticity, promote neurogenesis, and reduce neur...
Discovery and mechanism of negative allosteric modulation of the α7 nicotinic acetylcholine receptor by nanobodies
α7 nicotinic receptors are neurotransmitter-gated ion channels involved in neurological and inflammatory diseases. Ligands acting on its neurotransmitter binding site and on the channel domain of α7 h...
Impact of boiling liquid droplets: Vapor entrapment suppression
There hardly is a fluid mechanics phenomenon attracting more attention than the impact of a droplet, due to its undeniable beauty, many applications, and the numerous challenges it poses. One of the c...
Mating regulates growth, metabolism, and digestive efficiency in the female <i>Drosophila</i> midgut
Adaptive changes in organ size and function occur in most animals, but how these changes are regulated is not well understood. Previous research found that mating in Drosophila...
Dynamics of working memory drift and information flow across the cortical hierarchy
Working memory is supported by widespread and distributed brain regions spanning across the cortical hierarchy. However, how working memory content evolves and is transmitted across cortical regions r...
Mechanistic basis for relaxation of DNA supercoils by human topoisomerase IIIα–RMI1–RMI2
Topoisomerase enzymes are essential for the regulation of DNA topology. Human topoisomerase IIIα is a Type 1A topoisomerase that exists as a complex with RMI1 and RMI2, known as TRR. The TRR complex c...
mGluR1 signaling is necessary for strengthening winner climbing fiber inputs in the developing mouse cerebellum
Functional neural circuits are sculpted by strengthening frequently used synapses and removing unnecessary connections. At birth, cerebellar Purkinje cells receive inputs with similar synaptic strengt...
Clever algorithms for glasses work by time reparameterization
The ultraslow dynamics of glass-formers has been explained by two views often considered as mutually exclusive: One invokes locally hindered mobility, and the other rests on the complexity of the conf...
Coral species from another ocean may be the only way to save Caribbean reefs
Perceiving AI as labor-replacing reduces democratic legitimacy and political engagement
AI is expected to reshape society and labor markets, yet experts remain divided on whether AI will primarily displace human labor or generate new employment opportunities. Despite the importance of th...
Nuclear MBL-1 modulates mitochondrial morphology through carnitine palmitoyltransferase in <i>Caenorhabditis elegans</i> with toxic trinucleotide repeats
Expansion of nucleotide repeat sequences is linked to a growing number of neuromuscular degenerative disorders. Metabolic changes, including disruptions in mitochondrial function and dynamics, charact...
Metabolic rewiring and biomass redistribution enable optimized mixotrophic growth in Chlamydomonas
Aquatic photosynthetic systems account for approximately one-half of all global carbon assimilation and could be a significant source of renewable fuels and feedstocks. However, rapid growth and bioma...
A sexually dimorphic neuronal cluster in the mouse medial amygdala responds to male sexual status
Increasing scientific interest has been directed toward understanding sexual dimorphism in the brain. Although several brain structures exhibit masculine or feminine characteristics, strictly binary a...
The EPS-I exopolysaccharide transforms <i>Ralstonia</i> wilt pathogen biofilms into viscoelastic fluids for rapid dissemination in planta
Ralstonia solanacearum species complex (RSSC) pathogens cause destructive plant wilt diseases of a wide variety of crops, leading to significant agricultural losses worldwide. Thes...
A surface-exposed cardiolipin synthase provides an unexpected paradigm for maintaining the Gram-negative outer membrane
Gram-negative bacteria have long been thought to confine primary glycerophospholipid synthesis to the inner membrane (IM). Here, we challenge this paradigm by identifying ClsO, an outer membrane (OM)...
Disorder-induced stress–flow misalignment in soft glassy materials revealed using multidirectional shear
Controlling the mechanical response of soft glassy materials—such as emulsions, foams, and colloidal suspensions—is key for many industrial processes. While their steady-state flow behavior is reasona...
Slippage reconfiguration of trinucleotide repeat hairpins impedes resolution by human replication protein A
Abnormal expansions of trinucleotide repeats (TNRs) are a major cause of neurodegenerative diseases, often driven by the formation of stable hairpin structures that interfere with protein machineries...
Symmetry-protected topological polarons
Emergent quasiparticles in solids often exhibit unique topological properties as a result of the complex interplay between charge, orbital, spin, and lattice degrees of freedom. Among these quasiparti...
Optimization via the strategic law of large numbers
This paper proposes a framework for the global optimization of a possibly multimodal continuous function in a bounded rectangular domain. We first show that global optimization is equivalent to an opt...
Type I IFN autoantibodies underlie chikungunya live-attenuated vaccine encephalitis
Human autoantibodies neutralizing type I interferons (IFNs) have emerged as strong, common, and global determinants of a growing number of severe viral diseases, including hypoxemic viral pneumonia, a...