Proceedings of the National Academy of Sciences
Articles in this Issue
CRISPR screens identify the ATPase VCP as a druggable therapeutic vulnerability in cholangiocarcinoma
Cholangiocarcinoma (CCA) remains a lethal malignancy with limited therapeutic options. Through genome-wide CRISPR-Cas9 screening, we identified the adenosine triphosphatase (ATPase) valosin-containing...
Could dark energy be changing over time?
Correction for Yeh et al., Three things we can do now to reduce the risk of avian influenza spillovers
Developing new technologies to protect ecosystems: Planning with adaptive management
Technology development is an essential investment for policymakers to address contemporary global crises, including climate change, biodiversity loss, the energy transition, and emergent infectious di...
Nanotechnology-driven coordination of shoot–root systems enhances rice nitrogen use efficiency
Enhancing nitrogen use efficiency (NUE) in agricultural production can reduce fertilizer input, mitigate greenhouse gas emissions and decrease water pollution incidence. However, improving NUE in farm...
<i>Bacillus subtilis</i> in defense mode: Switch-like adaptations to protistan predation
Single-cell eukaryotic predators in the soil are a primary cause of bacterial cell death. Yet, most functional genomic studies on soil bacteria have been performed without predation, thereby selecting...
A supporting-electrolyte-free four-compartment electrochemical reactor for aqueous and organic phase electrosynthesis
Electrosynthesis offers a promising method to make valuable chemicals under mild conditions; however, its application has been greatly hampered by issues including the requirement of a supporting elec...
Sperm meet the elevated energy demands to attain fertilization competence by increasing flux through aldolase
Prior to ejaculation, mammalian sperm are stored in the epididymis in a “resting” metabolic state. Upon ejaculation, sperm must alter their metabolism to generate the energy needed to support the moti...
Correction for Nehemy et al., Embolism resistance supports the contribution of dry-season precipitation to transpiration in eastern Amazon forests
A spatially differentiated water pollution policy leads to economic and health inequity
Disparities in air pollution exposure by socioeconomic status (SES) are well documented. However, there is much less evidence on the inequitable consequences of water pollution and policies affecting...
Transcriptional regulation of thorn tip sclerification in plants
A common characteristic of thorns, prickles, and spines is a hardened and sharp tip. This feature complicates cultivation and postharvest processing for many crops, yet the molecular mechanisms govern...
The multimodal transcriptional response of denervated skeletal muscle involves regulation of <i>Gramd1</i> genes impacting muscle size
The development and maintenance of the neuromuscular junction (NMJ) requires reciprocal signals between the nerve terminals and multinucleated skeletal muscle fibers (myofibers). This interaction driv...
Genetic dissection of nonconventional introns reveals codominant noncanonical splicing code in <i>Euglena</i>
Pre-mRNA splicing is essential for eukaryotic gene expression and is achieved through the accurate recognition of exon–intron boundaries. Although nonconventional introns, which do not follow the conv...
Structural and functional analysis of the <i>Mycobacterium tuberculosis</i> MmpS5L5 efflux pump presages increased bedaquiline resistance
Bedaquiline, an antitubercular drug that targets ATP-synthase, is a key component of a new oral drug regimen that has revolutionized the treatment of multidrug-resistant tuberculosis. Clinical bedaqui...
Muscle-specific increased expression of <i>JAG1</i> improves the skeletal muscle phenotype in dystrophin-deficient mice
Therapeutic strategies for Duchenne muscular dystrophy (DMD) will likely require complementary approaches. One possibility is to explore genetic modifiers that improve muscle regeneration and function...
ALKBH5 demethylates the m <sup>6</sup> A modification of SOCS3 in microglia/macrophages and alleviates neuroinflammation after brain injury
Microglia/macrophage-induced neuroinflammation plays a crucial role in the progression of traumatic brain injury (TBI). However, the involvement of N6-methyladenosine (m 6...
Within-country inequality and the shaping of a just global climate policy
Climate policy design must balance emissions mitigation with concerns for fairness, particularly as climate change disproportionately affects the poorest households within and across countries. Integr...
Preferential apical infection and spread of human metapneumovirus highlights the importance of inhaled delivery of neutralizing monoclonal antibody to treat established infections
Human metapneumovirus (hMPV) is a frequent cause of acute respiratory infections in infants, the elderly, and the immunocompromised. No vaccines or treatments are currently available beyond supportive...
Biomarkers of immune dysregulation and posttreatment inflammation in spinal muscular atrophy
Spinal Muscular Atrophy (SMA) is a neurodegenerative disorder primarily affecting motor neurons, but immune dysfunction may contribute to disease progression and treatment response. While AAV9-deliver...
Severe water crisis in southern Spain under expanding irrigated agriculture: A multidimensional drought analysis
The Axarquía region in southern Spain, a hotspot of avocado and mango production in Europe, underwent an extreme water crisis in 2019–2024. Reservoir levels dropped below the 8% outlet threshold and g...
Targeting endothelial ERG to mitigate vascular regression in retinopathies
Retinopathy of prematurity (ROP) and diabetic retinopathy (DR) are ocular disorders in which an initial loss of retinal capillaries leads to damaging tissue ischemia followed by a compensatory neovasc...
Antagonistic SnRK2 and PID kinases' action on auxin transport–mediated root gravitropism
Plants have evolved sophisticated mechanisms to adapt to environmental changes, with root gravitropism playing a pivotal role in nutrient and water acquisition. Our study reveals that SnRK2 kinases (S...
Why depolarization is hard: Evaluating attempts to decrease partisan animosity in America
Affective polarization is a corrosive force in American politics. While numerous studies have developed interventions to reduce it, their capacity for creating lasting, large-scale change is unclear....
A TGF-βR/IL-2R immunomodulatory fusion protein transforms immunosuppression into T cell activation to enhance adoptive T cell therapy
Adoptive T cell therapies have shown limited efficacy against solid tumors due in part to immunosuppressive cues such as from TGF-β and insufficient survival/proliferative signals within the tumor mic...
Dual Bmp-negative feedback loops modulate function of both AER and ZPA to buffer and constrain postaxial digit number
Several lines of evidence indicate that posterior (postaxial) digit number in tetrapod vertebrates is constrained to the pentadactyl state by interactions between the two major signaling centers that...