Proceedings of the National Academy of Sciences, Volume 120, Issue 49, December 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 49, December 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 49, December 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 49, December 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 49, December 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 49, December 2023.

The ability of cells to move in a mechanically coupled, coordinated manner, referred to as collective cell migration, is central to many developmental, physiological, and pathophysiological processes. Limited understanding of how mechanical forces and biochemical regulation interact to affect coupling has been a major obstacle to unravelling the underlying mechanisms. Focusing on the linker protein

Lipid nanoparticles (LNPs) are advanced core-shell particles for messenger RNA (mRNA) based therapies that are made of polyethylene glycol (PEG) lipid, distearoylphosphatidylcholine (DSPC), cationic ionizable lipid (CIL), cholesterol (chol), and mRNA. Yet the mechanism of pH-dependent response that is believed to cause endosomal release of LNPs is not well understood. Here, we show that eGFP (enhanced

We detected ENU-induced alleles of Mfsd1 (encoding the major facilitator superfamily domain containing 1 protein) that caused lymphopenia, splenomegaly, progressive liver pathology, and extramedullary hematopoiesis (EMH). MFSD1 is a lysosomal membrane-bound solute carrier protein with no previously described function in immunity. By proteomic analysis, we identified association between MFSD1 and both

Successful chromosome segregation into gametes depends on tightly regulated interactions between the parental chromosomes. During meiosis, chromosomes are aligned end-to-end by an interface called the synaptonemal complex, which also regulates exchanges between them. However, despite the functional and ultrastructural conservation of this essential interface, how protein–protein interactions within

Interferon-induced ubiquitin (Ub)-like modifier ISG15 covalently modifies host and viral proteins to restrict viral infections. Its function is counteracted by the canonical deISGylase USP18 or Ub-specific protease 18. Notwithstanding indications for the existence of other ISG15 cross-reactive proteases, these remain to be identified. Here, we identify deubiquitinase USP16 as an ISG15 cross-reactive

It has previously been reported that antioxidant vitamins can help reduce the risk of vision loss associated with progression to advanced age-related macular degeneration (AMD), a leading cause of visual impairment among the elderly. Nonetheless, how oxidative stress contributes to the development of choroidal neovascularization (CNV) in some AMD patients and geographic atrophy (GA) in others is poorly

Older adults show declines in spatial memory, although the extent of these alterations is not uniform across the healthy older population. Here, we investigate the stability of neural representations for the same and different spatial environments in a sample of younger and older adults using high-resolution functional MRI of the medial temporal lobes. Older adults showed, on average, lower neural

The evolution of cooperation is a major question in the biological and behavioral sciences. While most theoretical studies model cooperation in the context of an isolated interaction (e.g., a Prisoner’s Dilemma), humans live in heterogeneous social environments, characterized by large variations in fitness interdependence—the extent to which one’s fitness is affected by others. Theoretical and experimental

Immunoglobulin M (IgM) is an evolutionary conserved key component of humoral immunity, and the first antibody isotype to emerge during an immune response. IgM is a large (1 MDa), multimeric protein, for which both hexameric and pentameric structures have been described, the latter additionally containing a joining (J) chain. Using a combination of single-particle mass spectrometry and mass photometry

Algorithms of social media platforms are often criticized for recommending ideologically congenial and radical content to their users. Despite these concerns, evidence on such filter bubbles and rabbit holes of radicalization is inconclusive. We conduct an audit of the platform using 100,000 sock puppets that allow us to systematically and at scale isolate the influence of the algorithm in recommendations

Severity of neurobehavioral deficits in children born from adverse pregnancies, such as maternal alcohol consumption and diabetes, does not always correlate with the adversity’s duration and intensity. Therefore, biological signatures for accurate prediction of the severity of neurobehavioral deficits, and robust tools for reliable identification of such biomarkers, have an urgent clinical need. Here

The Ganges–Brahmaputra–Meghna river basin, running through Tibet, Nepal, Bhutan, Bangladesh, and northern India, is home to more than 618 million people. Annual monsoons bring extensive flooding to the basin, with floods predicted to be more frequent and extreme due to climate change. Yet, evidence regarding the long-term impacts of floods on children’s health is lacking. In this analysis, we used

Pseudomonas aeruginosa can cause a wide array of chronic and acute infections associated with its ability to rapidly switch between planktonic, biofilm, and dispersed lifestyles, each with a specific arsenal for bacterial survival and virulence. At the cellular level, many of the physiological transitions are orchestrated by the intracellular second messenger c-di-GMP and its receptor-effector FleQ

Thrombocytopenia, hemorrhage, anemia, and infection are life-threatening issues following accidental or intentional radiation exposure. Since few therapeutics are available, safe and efficacious small molecules to mitigate radiation-induced injury need to be developed. Our previous study showed the synthetic TLR2/TLR6 ligand fibroblast stimulating lipopeptide (FSL-1) prolonged survival and provided

To master the activation law and mechanism of surface lattice oxygen for the oxygen evolution reaction (OER) is critical for the development of efficient water electrolysis. Herein, we propose a strategy for triggering lattice-oxygen oxidation and enabling non-concerted proton–electron transfers during OER conditions by substituting Al in La 0.3 Sr 0.7 CoO 3− δ . According to our experimental data

Addressing the ongoing biodiversity crisis requires identifying the winners and losers of global change. Species are often categorized based on how they respond to habitat loss; for example, species restricted to natural environments, those that most often occur in anthropogenic habitats, and generalists that do well in both. However, species might switch habitat affiliations across time and space:

Building conditions, outdoor climate, and human behavior influence residential concentrations of fine particulate matter (PM 2.5 ). To study PM 2.5 spatiotemporal variability in residences, we acquired paired indoor and outdoor PM 2.5 measurements at 3,977 residences across the United States totaling >10,000 monitor-years of time-resolved data (10-min resolution) from the PurpleAir network. Time-series

Sediments in southern Laos and eastern Thailand confirm that the Australasian tektite strewn field came from an extraterrestrial impact crater on the Bolaven Plateau of southern Laos. The principal evidence is the Bolaven diamicton, a pebbly to bouldery breccia that is thickest and coarsest on the plateau. Tektites, the melted target material strewn widely by the forces of the impact 789.0 ± 1.8 ka

Neanderthals hunted and butchered straight-tusked elephants, the largest terrestrial mammals of the Pleistocene, in a lake landscape on the North European plain, 125,000 years ago, as recently shown by a study of the Last Interglacial elephant assemblage from Neumark-Nord (Germany). With evidence for a remarkable focus on adult males and on their extended utilization, the data from this location are

Two separate but related literatures have examined familial correlates of male androphilia (i.e., sexual attraction and arousal to masculine adult males). The fraternal birth order effect (FBOE) is a widely established finding that each biological older brother a male has increased the probability of androphilia 20–35% above baseline rates. Other family demographic variables, such as reproduction by

Remote patient monitoring is a critical component of digital medicine, and the COVID-19 pandemic has further highlighted its importance. Wearable sensors aimed at noninvasive extraction and transmission of high-fidelity physiological data provide an avenue toward at-home diagnostics and therapeutics; however, the infrastructure requirements for such devices limit their use to areas with well-established

Mammals play important ecological roles in terrestrial ecosystems, with their particular niches and their impacts on energy flow and nutrient cycling being strongly influenced by one of their most fundamental traits—their body size. Body size influences nearly all of the physiological, behavioral, and ecological traits of mammals, and thus, shifts in body size often serve as key mechanisms of adaptation

Tandem DNA repeats are often organized into heterochromatin that is crucial for genome organization and stability. Recent studies revealed that individual repeats within tandem DNA repeats can behave very differently. How DNA repeats are assembled into distinct heterochromatin structures remains poorly understood. Here, we developed a genome-wide genetic screen using a reporter gene at different units

Autoantibodies directed against complement component C1q are commonly associated with autoimmune diseases, especially systemic lupus erythematosus. Importantly, these anti-C1q autoantibodies are specific for ligand-bound, solid-phase C1q and do not bind to fluid-phase C1q. In patients with anti-C1q, C1q levels are in the normal range, and the autoantibodies are thus not depleting. To study these human

Soils are common sources of metal(loid) contaminant exposure globally. Lead (Pb) and arsenic (As) are of paramount concern due to detrimental neurological and carcinogenic health effects, respectively. Pb and/or As contaminated soils require remediation, typically leading to excavation, a costly and environmentally damaging practice of removing soil to a central location (e.g., hazardous landfill)

Optical three-dimensional (3D) molecular imaging is highly desirable for providing precise distribution of the target-of-interest in disease models. However, such 3D imaging is still far from wide applications in biomedical research; 3D brain optical molecular imaging, in particular, has rarely been reported. In this report, we designed chemiluminescence probes with high quantum yields, relatively

We present a comprehensive description of the aspect ratio impact on interfacial instability in porous media where a wetting liquid displaces a nonwetting fluid. Building on microfluidic experiments, we evidence imbibition scenarios yielding interfacial instabilities and macroscopic morphologies under different depth confinements, which were controlled by aspect ratio and capillary number. We report

The field of one-dimensional semiconducting materials holds a wide variety of captivating applications, such as photovoltaic cells, electronic devices, catalysis cells, lasers, and more. The tunability of electrical, mechanical, or optical attributes of a semiconductor crystal relies on the ability to control and pattern the crystal’s growth direction, orientation, and dimensions. In this study, we

The statistics of a passive tracer immersed in a suspension of active particles (swimmers) is derived from first principles by considering a perturbative expansion of the tracer interaction with the microscopic swimmer field. To first order in the swimmer density, the tracer statistics is shown to be exactly represented by a spatial Poisson process combined with independent tracer—swimmer scattering

Gene silencing is intimately connected to DNA condensation and the formation of transcriptionally inactive heterochromatin by Heterochromatin Protein 1α (HP1α). Because heterochromatin foci are dynamic and HP1α can promote liquid–liquid phase separation, HP1α-mediated phase separation has been proposed as a mechanism of chromatin compaction. The molecular basis of HP1α-driven phase separation and chromatin

Astrobiology studies are a top priority in answering one of the most fundamental questions in planetary science: Is there life beyond Earth? Saturn’s icy moon Enceladus is a prime target in the search for life in our solar system, identified by NASA as the second-highest priority site for a flagship mission in the next decade. The orbital sampling technique of impact ionization mass spectrometry indicated

The gut microbiota plays a role in many human diseases, but high-throughput sequence analysis does not provide a straightforward path for defining healthy microbial communities. Therefore, understanding mechanisms that drive compositional changes during disease (gut dysbiosis) continues to be a central goal in microbiome research. Insights from the microbial pathogenesis field show that an ecological

Proceedings of the National Academy of Sciences, Volume 120, Issue 49, December 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 49, December 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 49, December 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 49, December 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 49, December 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 49, December 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 49, December 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 49, December 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 49, December 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 49, December 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 49, December 2023.

Neural speech tracking has advanced our understanding of how our brains rapidly map an acoustic speech signal onto linguistic representations and ultimately meaning. It remains unclear, however, how speech intelligibility is related to the corresponding neural responses. Many studies addressing this question vary the level of intelligibility by manipulating the acoustic waveform, but this makes it

The ability of recent Large Language Models (LLMs) such as GPT-3.5 and GPT-4 to generate human-like texts suggests that social scientists could use these LLMs to construct measures of semantic similarity that match human judgment. In this article, we provide an empirical test of this intuition. We use GPT-4 to construct a measure of typicality—the similarity of a text document to a concept. We evaluate

The rate at which information scrambles in a quantum system can be quantified using out-of-time-ordered correlators. A remarkable prediction is that the associated Lyapunov exponent λ that quantifies the scrambling rate in chaotic systems obeys a universal bound λ < 2 π k B T / ħ . Previous numerical and analytical studies have indicated that this bound has a quantum-statistical origin. Here, we use

Peripheral neural interfaces, potent in modulating local and systemic immune responses for disease treatment, face significant challenges due to the peripheral nerves’ broad distribution in tissues like the fascia, periosteum, and skin. The incongruity between static electronic components and the dynamic, complex organization of the peripheral nervous system often leads to interface failure, stalling

There has been considerable progress in the development of computational methods for designing protein–protein interactions, but engineering high-affinity binders without extensive screening and maturation remains challenging. Here, we test a protein design pipeline that uses iterative rounds of deep learning (DL)-based structure prediction (AlphaFold2) and sequence optimization (ProteinMPNN) to design

Phagocytosis is a critical immune function for infection control and tissue homeostasis. During phagocytosis, pathogens are internalized and degraded in phagolysosomes. For pathogens that evade immune degradation, the prevailing view is that virulence factors are required to disrupt the biogenesis of phagolysosomes. In contrast, we present here that physical forces from motile pathogens during cell

In a family with inappropriate sinus tachycardia (IST), we identified a mutation (p.V240M) of the hyperpolarization-activated cyclic nucleotide–gated type 4 (HCN4) channel, which contributes to the pacemaker current (I f ) in human sinoatrial node cells. Here, we clinically study fifteen family members and functionally analyze the p.V240M variant. Macroscopic (I HCN4 ) and single-channel currents were

RNA-binding motif protein 10 (RBM10) is a frequently mutated tumor suppressor in lung adenocarcinoma (LUAD). Yet, it remains unknown whether cancer-derived mutant RBM10 compromises its tumor suppression function and, if so, the molecular insight of the underlying mechanisms. Here, we show that wild-type RBM10 suppresses lung cancer cell growth and proliferation by inactivating c-Myc that is essential

Inteins are self-splicing protein elements found in viruses and all three domains of life. How the DNA encoding these selfish elements spreads within and between genomes is poorly understood, particularly in eukaryotes where inteins are scarce. Here, we show that the nuclear genomes of three strains of Anaeramoeba encode between 45 and 103 inteins, in stark contrast to four found in the most intein-rich

The brain can efficiently learn a wide range of tasks, motivating the search for biologically inspired learning rules for improving current artificial intelligence technology. Most biological models are composed of point neurons and cannot achieve state-of-the-art performance in machine learning. Recent works have proposed that input segregation (neurons receive sensory information and higher-order

Singlet exciton fission (SEF) is initiated by ultrafast internal conversion of a singlet exciton into a correlated triplet pair ( T T ) 1 . The “reaction coordinates” for ultrafast SEF even in archetypal systems such as pentacene thin film remain unclear. Couplings between fast electrons and slow nuclei are ubiquitous across a range of phenomena in chemistry. Accordingly, spectroscopic detection of