Proceedings of the National Academy of Sciences, Volume 121, Issue 45, November 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 45, November 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 45, November 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 45, November 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 45, November 2024.

Skeletal muscle actin (ACTA1) mutations are a prevalent cause of skeletal myopathies consistent with ACTA1’s high expression in skeletal muscle. Rare de novo mutations in ACTA1 associated with combined cardiac and skeletal myopathies have been reported, but ACTA1 represents only ~20% of the total actin pool in cardiomyocytes, making its role in cardiomyopathy controversial. Here we demonstrate how

Mitochondrial biogenesis relies on both the nuclear and mitochondrial genomes, and imbalance in their expression can lead to inborn errors of metabolism, inflammation, and aging. Here, we investigate N6AMT1, a nucleo-cytosolic methyltransferase that exhibits genetic codependency with mitochondria. We determine transcriptional and translational profiles of N6AMT1 and report that it is required for the

A faster cruising speed increases drag and thereby the thrust ( T ) needed to fly, while weight and lift ( L ) requirement remains constant. Birds can adjust their wingbeat in multiple ways to accommodate this change in aerodynamic force, but the relative costs of different strategies remain largely unknown. To evaluate the efficiency of several kinematic strategies, I used a robotic wing [E. Ajanic

The proton-motive force (PMF), consisting of a pH gradient and a membrane potential (ΔΨ) underpins many processes essential to bacterial growth and/or survival. Yet bacteria often enter a bioenergetically diminished state characterized by a low PMF. Consequently, they have increased tolerance for diverse stressors, including clinical antibiotics. Despite the ubiquity of low metabolic rates in the environment

Stroke causes pronounced and widespread slowing of neural activity. Despite decades of work exploring these abnormal neural dynamics and their associated functional impairments, their causes remain largely unclear. To close this gap in understanding, we applied a neurophysiological corticothalamic circuit model to simulate magnetoencephalography (MEG) power spectra recorded from chronic stroke patients

Collagens are the foundational component of diverse tissues, including skin, bone, cartilage, and basement membranes, and are the most abundant protein class in animals. The fibrillar collagens are large, complex, multidomain proteins, all containing the characteristic triple helix motif. The most prevalent collagens are heterotrimeric, meaning that cells express at least two distinctive procollagen

Over the course of evolution, land plant mitochondrial genomes have lost many transfer RNA (tRNA) genes and the import of nucleus-encoded tRNAs is essential for mitochondrial protein synthesis. By contrast, plastidial genomes of photosynthetic land plants generally possess a complete set of tRNA genes and the existence of plastidial tRNA import remains a long-standing question. The early vascular plants

A key function of the lexicon is to express novel concepts as they emerge over time through a process known as lexicalization. The most common lexicalization strategies are the reuse and combination of existing words, but they have typically been studied separately in the areas of word meaning extension and word formation. Here, we offer an information-theoretic account of how both strategies are constrained

The maturation and installation of the active site metal cluster (FeMo-co, Fe 7 S 9 CMo- R -homocitrate) in Mo-dependent nitrogenase requires the protein product of the nifB gene for production of the FeS cluster precursor (NifB-co, [Fe 8 S 9 C]) and the action of the maturase complex composed of the protein products from the nifE and nifN genes. However, some putative diazotrophic bacteria, like Roseiflexus

Active dendritic integrative mechanisms such as regenerative dendritic spikes enrich the information processing abilities of neurons and fundamentally contribute to behaviorally relevant computations. Dendritic Ca 2+ spikes are generally thought to produce plateau-like dendritic depolarization and somatic complex spike burst (CSB) firing, which can initiate rapid changes in spatial coding properties

To maintain CO 2 fixation in the Calvin–Benson–Bassham cycle, multistep regulation of the chloroplast ATP synthase (CF 1 F o ) is crucial to balance the ATP output of photosynthesis with protection of the apparatus. A well-studied mechanism is thiol modulation; a light/dark regulation through reversible cleavage of a disulfide in the CF 1 F o γ-subunit. The disulfide hampers ATP synthesis and hydrolysis

Transgenic crops producing crystalline (Cry) proteins from the bacterium Bacillus thuringiensis (Bt) have been used extensively to control some major crop pests. However, many populations of the noctuid moth Helicoverpa zea , one of the most important crop pests in the United States, have evolved practical resistance to several Cry proteins including Cry1Ac. Although mutations in single genes that

Neovascular age-related macular degeneration (nvAMD) is the leading cause of severe vision loss in the elderly in the developed world. While the introduction of therapies targeting vascular endothelial growth factor (VEGF) has provided the first opportunity to significantly improve vision in patients with nvAMD, many patients respond inadequately to current anti-VEGF therapies. It was recently demonstrated

Cells adapt to environments and tune gene expression by controlling the concentrations of proteins and their kinetics in regulatory networks. In both eukaryotes and prokaryotes, experiments and theory increasingly attest that these networks can and do consume biochemical energy. How does this dissipation enable cellular behaviors forbidden in equilibrium? This open question demands quantitative models

The proportions of carbon (C), nitrogen (N), and phosphorus (P) in surface ocean particulate matter deviate greatly from the canonical Redfield Ratio (C:N:P = 106:16:1) in space and time with significant implications for global carbon storage as this matter reaches the deep ocean. Recent work has revealed clear latitudinal patterns in C:N:P, yet the relative importance of ecological, physiological

Mammalian tail length is controlled by several genetic determinants, among which are Hox13 genes, whose function is to terminate the body axis. Accordingly, the precise timing in the transcriptional activation of these genes may impact upon body length. Unlike other Hox clusters, HoxB lacks posterior genes between Hoxb9 and Hoxb13 , two genes separated by a ca. 70 kb large DNA segment containing a

High-resolution full waveform seismic tomography of the Earth’s mantle beneath the south and central Atlantic Ocean brings into focus a series of asthenospheric low shear velocity channels, or “fingers” on both sides of the southern and central mid-Atlantic ridge (MAR), elongated in the direction of absolute plate motion with a spacing of ∼ 1,800 to 2,000 km, and associated with bands of shallower

The drastic shape deformation that accompanies the structural phase transition in thermosalient materials offers great potential for their applications as actuators and sensors. The microscopic origin of this fascinating effect has so far remained obscure, while for technological applications, it is important to learn how to drive transitions from one phase to another. Here, we present a combined computational

The snowball Earth hypothesis predicts that continental chemical weathering diminished substantially during, but rebounded strongly after, the Marinoan ice age some 635 Mya. Defrosting the planet would result in a plume of fresh glacial meltwater with a different chemical composition from underlying hypersaline seawater, generating both vertical and lateral salinity gradients. Here, we test the plumeworld

Quorum sensing (QS) is a cell-to-cell communication process that enables bacteria to coordinate group behaviors. In Vibrio cholerae colonies, a program of spatial-temporal cell death is among the QS-controlled traits. Cell death occurs in two phases, first along the colony rim, and subsequently, at the colony center. Both cell death phases are driven by the type 6 secretion system (T6SS). Here, we

Fluxes of energy generate active forces in living matter, yet also active fluctuations. As a canonical example, collections of molecular motors exhibit spontaneous oscillations with frequency jitter caused by nonequilibrium phase fluctuations. We investigate phase fluctuations in reactivated Chlamydomonas reinhardtii axonemes, which are accessible to direct manipulation. We quantify the precision of

Whole-genome sequencing of bacterial pathogens is used by public health agencies to link cases of food poisoning caused by the same source of contamination. The vast majority of these appear to be sporadic cases associated with small contamination episodes and do not trigger investigations. A “contamination episode” refers to one or more contamination events from a single source over a period of time

The role of nonneuronal cells in the resolution of cerebral ischemia remains to be fully understood. To decode key molecular and cellular processes that occur after ischemia, we performed spatial and single-cell transcriptomic profiling of the male mouse brain during the first week of injury. Cortical gene expression was severely disrupted, defined by inflammation and cell death in the lesion core

Within a cell, protein-bound methionines can be chemically or enzymatically oxidized, and subsequently reduced by methionine sulfoxide reductases (Msrs). Methionine oxidation can result in structural damage or be the basis of functional regulation of enzymes. In addition to participating in redox reactions, methionines play an important role as the initiator residue of translated proteins where they

Microtubule-dependent endosomal transport is crucial for polar growth, ensuring the precise distribution of cellular cargos such as proteins and mRNAs. However, the molecular mechanism linking mRNAs to the endosomal surface remains poorly understood. Here, we present a structural analysis of the key RNA-binding protein Rrm4 from Ustilago maydis . Our findings reveal a different type of MademoiseLLE

RNA oxidation, predominantly through the accumulation of 8-oxo-7,8-dihydroguanosine (8-oxo-rG), represents an important biomarker for cellular oxidative stress. Polynucleotide phosphorylase (PNPase) is a 3′-5′ exoribonuclease that has been shown to preferentially recognize 8-oxo-rG-containing RNA and protect E scherichia coli cells from oxidative stress. However, the impact of 8-oxo-rG on PNPase-mediated

The role of ventral hippocampus (vHipp) astroglial gliotransmission in depression was studied using chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS) rodent models. CRS increased Cx43 hemichannel activity and extracellular glutamate levels in the vHipp and blocking astroglial Cx43 hemichannel-dependent gliotransmission during CRS prevented the development of depression and

The visual system needs to identify perceptually relevant borders to segment complex natural scenes. The primary visual cortex (V1) is thought to extract local borders, and higher visual areas are thought to identify the perceptually relevant borders between objects and the background. To test this conjecture, we used natural images that had been annotated by human observers who marked the perceptually

Researchers looking for sustainable materials with optimal mechanical properties may draw inspiration from a baseball tradition. For nearly 100 y, a mysterious mud harvested from an undisclosed river site in New Jersey (USA) has been the agent of choice in the USA’s Major League Baseball for “de-glossing” new baseballs. It is unclear, however, what makes this “Rubbing Mud” work. Here, we perform a

Northeast China’s Early Cretaceous Yixian Formation preserves spectacular fossils that have proved extraordinarily important in testing evolutionary hypotheses involving the origin of birds and the distribution of feathers among nonavian dinosaurs. These fossils occur either flattened with soft tissue preservation (including feathers and color) in laminated lacustrine strata or as three-dimensional

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), the anion channel mutated in cystic fibrosis (CF) patients, is activated by the catalytic subunit of protein kinase A (PKA-C). PKA-C activates CFTR both noncatalytically, through binding, and catalytically, through phosphorylation of multiple serines in CFTR’s regulatory (R) domain. Here, we identify key molecular determinants of the CFTR/PKA-C

The “27 Club” refers to the widespread legend that notable people, particularly musicians, are unusually likely to die at age 27. A 2011 inquiry in The BMJ showed this is not the case, dismissing the 27 Club as a myth. We expand on this discourse by demonstrating that although the existence of the phenomenon cannot be empirically validated, it is real in its consequences. Using Wikipedia data, we show

Urban heat mitigation is a pressing concern for cities. Intense urban heat poses a threat to human health and urban sustainability. Tree planting is one of the most widely employed nature-based heat mitigation methods worldwide. Therefore, city policy makers require knowledge of how much temperature will be reduced by increasing urban tree canopy (UTC). Cooling efficiency (CE), which was been proposed

Members of the Bacteroidota compose a large portion of the human gut microbiota, contributing to overall gut health via the degradation of various polysaccharides. This process is facilitated by lipoproteins, globular proteins anchored to the cell surface by a lipidated N-terminal cysteine. Despite their importance, lipoprotein synthesis by these bacteria is understudied. In Escherichia coli , the

In the last decade, several novel functions of the mammalian Apurinic/Apyrimidinic Endodeoxyribonuclease 1 (APE1) have been discovered, going far beyond its canonical function as DNA repair enzyme and unveiling its potential roles in cancer development. Indeed, it was shown to be involved in DNA G-quadruplex biology and RNA metabolism, most importantly in the miRNA maturation pathway and the decay

Over two decades ago, increased levels of RNA oxidation were reported in postmortem patients with ALS, Alzheimer’s, Parkinson’s, and other neurodegenerative diseases. Interestingly, not all cell types and transcripts were equally oxidized. Furthermore, it was shown that RNA oxidation is an early phenomenon, altogether indicating that oxidative RNA damage could be a driver, and not a consequence, of

Burkholderia thailandensis has emerged as a nonpathogenic surrogate for Burkholderia pseudomallei , the causative agent of melioidosis, and an important Gram-negative model bacterium for studying the biosynthesis and regulation of secondary metabolism. We recently reported that subinhibitory concentrations of trimethoprim induce vast changes in both the primary and secondary metabolome of B. thailandensis

From tumorigenesis to advanced metastatic stages, tumor cells encounter stress, ranging from limited nutrient and oxygen supply within the tumor microenvironment to extrinsic and intrinsic oxidative stress. Thus, tumor cells seize regulatory pathways to rapidly adapt to distinct physiologic conditions to promote cellular survival, including manipulation of mRNA translation. While it is now well established

As the world’s climate continues to change, human populations are exposed to increasingly severe and extreme weather conditions that can promote migration. Here, we examine how extreme weather influences the likelihood of undocumented migration and return between Mexico and the United States. We used data from 48,313 individuals observed between 1992 and 2018 in 84 Mexican agricultural communities

Protein kinase A (PKA) is a key regulator of cellular functions by selectively phosphorylating numerous substrates, including ion channels, enzymes, and transcription factors. It has long served as a model system for understanding the eukaryotic kinases. Using cryoelectron microscopy, we present complex structures of the PKA catalytic subunit (PKA-C) bound to a full-length protein substrate, the cystic

To be clinically efficient, beta cell replacement therapies such as pig islet xenotransplantation must ensure sufficient insulin secretion from grafted islets. While protection from host immune reaction is essential for islet engraftment and their subsequent functioning, intrinsic physiological properties of used cells are also a key factor. We have previously shown that islets with adenoviral-mediated

There has been recent interest in trying to understand the connection between transfer RNA (tRNA) posttranscriptional modifications and changes in-cellular environmental conditions. Here, we report on the identification of the modified nucleoside 5-methylcytidine (m 5 C) in Escherichia coli tRNAs. This modification was determined to be present at position 49 of tRNA Tyr-QUA-II. Moreover, m 5 C levels

Caste differentiation involves many functional traits that diverge during larval growth and metamorphosis to produce adults irreversibly adapted to reproductive division of labor. Investigating developmental differentiation is important for general biological understanding and has increasingly been explored for social phenotypes that diverge in parallel from similar genotypes. Here, we use Monomorium

From infancy, children show heightened interest in events that are impossible or improbable, relative to likely events. Do young children represent impossible and improbable events as points on a continuum of possibility, or do they instead treat them as categorically distinct? Here, we compared 2- and 3-y-old children’s learning (N = 335) following nearly identical events that were equi-probable,

Similar to DNA and histone, RNA can also be methylated. In its most common form, a N6-methyladenosine (m 6 A) chemical modification is introduced into nascent messenger ribonucleic acid (mRNA) by a specialized methyltransferase complex and removed by the RNA demethylases, Fat mass and obesity-associated (FTO), and ALKBH5. The fate of m 6 A-marked mRNA is uniquely diverse, ranging from degradation to

To address rising global food demand, the development of sustainable technologies to increase productivity is urgently needed. This study revealed that foliar application of zinc oxide nanoparticles (ZnO NPs; 30 to 80 nm, 0.67 mg/d per plant, 6 d) to rice leaves under heatwave (HW) stress increased the grain yield and nutritional quality. Compared with the HW control, the HWs+ZnO group presented increases

Establishment of root nodule symbiosis is initiated by the perception of bacterial Nod factor ligands by the plant LysM receptor kinases NFR1 and NFR5. Receptor signaling initiating the symbiotic pathway depends on the kinase activity of NFR1, while the signaling mechanism of the catalytically inactive NFR5 pseudokinase is unknown. Here, we present the crystal structure of the signaling-competent Lotus

Pastures, on which ruminant livestock graze, occupy one third of the earth’s surface. Removing livestock from pastures can support climate change mitigation through carbon sequestration in regrowing vegetation and recovering soils, particularly in potentially forested areas. However, this would also decrease food and fiber production, generating a tradeoff with pasture productivity and the ruminant

Fe–S clusters are essential cofactors involved in many reactions across all domains of life. Their biogenesis in Escherichia coli and other enterobacteria involves two machineries: Isc and Suf. Under conditions where cells operate with the Suf system, such as during oxidative stress or iron limitation, the entry of aminoglycosides is reduced, leading to resistance to these antibiotics. The transition