Proceedings of the National Academy of Sciences
Articles in this Issue
Molecular basis of Spns1-mediated lysophospholipid transport from the lysosome
Spns1 mediates the rate-limiting efflux of lysophospholipids from the lysosome to the cytosol. Deficiency of Spns1 is associated with embryonic senescence, as well as liver and skeletal muscle atrophy...
Carbon gain in upper but loss in deeper cropland soils across China over the last four decades
Increasing soil organic carbon (SOC) in agricultural systems is a primary nature-based option for mitigating climate change, improving soil fertility, and ensuring food security. However, the conseque...
Memory control deficits in the sleep-deprived human brain
Sleep disturbances are associated with intrusive memories, but the neurocognitive mechanisms underpinning this relationship are poorly understood. Here, we show that sleep deprivation disrupts prefron...
The unexplored potential of exosomes in the muscle–brain axis
Molecular mechanism governing the plasticity of use-dependent spike broadening in dorsal root ganglion neurons
Use-dependent spike broadening (UDSB) results from inactivation of the voltage-gated K + (Kv) channels that regulate the repolarization of the action potential....
A mechanosensitive circuit of FAK, ROCK, and ERK controls biomineral growth and morphology in the sea urchin embryo
Biomineralization is the utilization of different minerals by a vast array of organisms to form hard tissues and shape them in various forms. Within this diversity, a common feature of all mineralized...
In situ architecture of a nucleoid-associated biomolecular co-condensate that regulates bacterial cell division
In most bacteria, cell division depends on the tubulin-homolog FtsZ that polymerizes in a GTP-dependent manner to form the cytokinetic Z-ring at the future division site. Subsequently, the Z-ring recr...
X*Y females exhibit steeper reproductive senescence in the African pygmy mouse
A wave of studies has recently emphasized the influence of sex chromosomes on both lifespan and actuarial senescence patterns across vertebrates and invertebrates. Basically, the heterogametic sex (XY...
Higher-order transient structures and the principle of dynamic connectivity in membrane signaling
We examine the role of higher-order transient structures (HOTS) in M2R regulation of GIRK channels. Electron microscopic membrane protein location maps show that both proteins form HOTS that exhibit a...
Conservation of symbiotic signaling since the most recent common ancestor of land plants
Plants have colonized lands 450 million years ago. This terrestrialization was facilitated by developmental and functional innovations. Recent evo-devo approaches have demonstrated that one of these i...
The carnivorous plant <i>Genlisea</i> harnesses active particle dynamics to prey on microfauna
Carnivory in plants is an unusual trait that has arisen multiple times, independently, throughout evolutionary history. Plants in the genus Genlisea are carnivo...
Evolution takes multiple paths to evolvability when facing environmental change
Life at all scales is surprisingly effective at exploiting new opportunities, as demonstrated by the rapid emergence of antimicrobial resistance and novel pathogens. How populations acquire this level...
Dual-action kinase inhibitors influence p38α MAP kinase dephosphorylation
Reversible protein phosphorylation directs essential cellular processes including cell division, cell growth, cell death, inflammation, and differentiation. Because protein phosphorylation drives dive...
Structural and functional dynamics of human cone cGMP-phosphodiesterase important for photopic vision
Cone cGMP-phosphodiesterase (PDE6) is the key effector enzyme for daylight vision, and its properties are critical for shaping distinct physiology of cone photoreceptors. We determined the structures...
Reply to Caruso Bavisotto et al.: Toward exploring the potential of muscle-secreting exosomes in the muscle–brain axis
Structure-guided design and synthesis of C22- and C32-modified FK520 analogs with enhanced activity against human pathogenic fungi
Invasive fungal infections are a leading cause of death worldwide. Translating molecular insights into clinical benefits is challenging because fungal pathogens and their hosts share similar eukaryoti...
An animal model recapitulates human hepatic diseases associated with <i>GATA6</i> mutations
Heterozygotic GATA6 mutations are responsible for various congenital diseases in the heart, pancreas, liver, and other organs in humans. However, there is lack...
Reconciling heterogeneous dengue virus infection risk estimates from different study designs
Uncovering rates at which susceptible individuals become infected with a pathogen, i.e., the force of infection (FOI), is essential for assessing transmission risk and reconstructing distribution of i...
Tamsulosin ameliorates bone loss by inhibiting the release of Cl <sup>−</sup> through wedging into an allosteric site of TMEM16A
TMEM16A, a key calcium-activated chloride channel, is crucial for many physiological and pathological processes such as cancer, hypertension, and osteoporosis, etc. However, the regulatory mechanism o...
Nucleation mechanism of multiple-order parameter ferroelectric domain wall motion in hafnia
Ferroelectric hafnia exhibits promising robust polarization and silicon compatibility for ferroelectric devices. Unfortunately, it suffers from difficult polarization switching. Methods to enable easi...
Structures of methane and ammonia monooxygenases in native membranes
Methane- and ammonia-oxidizing bacteria play key roles in the global carbon and nitrogen cycles, respectively. These bacteria use homologous copper membrane monooxygenases to accomplish the defining c...
The CYLD–PARP1 feedback loop regulates DNA damage repair and chemosensitivity in breast cancer cells
Poly(ADP-ribose) polymerase 1 (PARP1) plays a crucial role in DNA repair and genomic stability maintenance. However, the regulatory mechanisms governing PARP1 activity, particularly through deubiquiti...
RAP-2 and CNH-MAP4 Kinase MIG-15 confer resistance in bystander epithelium to cell-fate transformation by excess Ras or Notch activity
Induction of cell fates by growth factors impacts many facets of developmental biology and disease. LIN-3/EGF induces the equipotent vulval precursor cells (VPCs) in Caenorhabditis...
Elucidation of a distinct photoreduction pathway in class II <i>Arabidopsis thaliana</i> photolyase
Class II photolyases (PLs) are a distant subclade in the photolyase/cryptochrome superfamily, displaying a unique Trp–Tyr tetrad for photoreduction and exhibiting a lower quantum yield (QY) of DNA rep...
Higher-order transient membrane protein structures
This study shows that five membrane proteins—three GPCRs, an ion channel, and an enzyme—form self-clusters under natural expression levels in a cardiac-derived cell line. The cluster size distribution...