Browse Articles

Epstein–Barr virus (EBV) infection causes human germinal center B cell–derived lymphomas in the absence of EBNA2 expression

EBV is associated with human B cell lymphomas, including Burkitt lymphomas (BLs), diffuse large B cell lymphomas (DLBCLs), Hodgkin lymphomas (HLs), and Plasmablastic lymphomas (PLs). EBV+ lymphomas in immunocompetent humans are usually derived from germinal center (GC)-experienced B cells and have stringent latency forms that do not express the viral transforming protein, EBNA2. Human EBV+ lymphomas that lack EBNA2 expression are largely driven by the viral LMP1 and LMP2A proteins, which activate NF-κB and B cell receptor-like signaling, respectively, or by Myc translocations. However, EBNA2 is required for EBV-mediated transformation of B cells in vitro and there is currently no model system for studying how EBV transforms human GC-derived B cells into lymphomas in vivo in the absence of EBNA2 expression or Myc translocation. Here, we show that human tonsil GC B cells (GCBs) infected with an EBNA2-deleted EBV mutant proliferate on a CD40L/IL21-expressing feeder layer and form lymphomas in NSG mice that resemble human DLBCLs (both ABC and GCB subtypes) and PLs. These EBV-induced lymphomas occur in the absence of Myc overexpression, often have normal karyotypes, and do not contain mutations in cellular genes (including p53) commonly mutated in uninfected human DLBCLs. Using this model system, we show that LMP2A induces plasmablast differentiation, increases expression of genes involved in lymphocyte mobility and trafficking and enhances tumor invasiveness in vivo. This new model system can thus be used to define roles of viral and cellular proteins in EBV-induced human GCB-derived lymphomas that lack EBNA2 expression.

Epithelial cell fusion is required for tissue repair following UV-A irradiation

Cell cycle–dependent and independent mechanisms lead to the generation of mononucleated and multinucleated polyploid cells. The more than doubling of a cell’s nuclear genome by endoreplication has been found to be an adaptation to genotoxic stress, enabling cell survival despite DNA damage. However, it remains unknown whether cells that increase ploidy via multinucleation also arise in response to genotoxic stress. Here, we use ultraviolet light A (UV-A) to induce permanent DNA damage in cells within the adult fruit fly epithelium. UV-A irradiation causes an injury-like response where giant multinucleated, polyploid cells arise following cell death. The epithelial cells undergo endoreplication, which is required to compensate for cell loss, but is surprisingly dispensable for tissue repair. UV-A irradiation also induces cell fusion, which generates multinucleated cells that encompass almost the entire epithelial area post injury. Cell fusion can be inhibited by expression of a dominant negative Rac or Cdc42 GTPase, which then blocks epithelial tissue repair postirradiation. Apoptotic nuclei were detected at the site of cell junction breakdown, suggesting that apoptosis itself or an apoptotic signal is required for polyploidization in this model. Expression of the effector caspase inhibitor, p35, led to inhibition of apoptosis, the endocycle, and cell fusion post UV-A. Therefore, we have found that caspase activation is necessary for polyploidization post injury and enhancing cell ploidy via multinucleation is another strategy to enable cell survival and tissue repair following genotoxic stress.

Perturbation of RNA homeostasis impairs mitochondrial respiration during poxvirus infection through excess RNA accumulation

Induction of RNA degradation in infected cells is a strategy used by many viruses to promote efficient replication. Vaccinia virus, the prototype poxvirus and the vaccine platform for smallpox and mpox, encodes two decapping enzymes to accelerate mRNA and double-stranded RNA (dsRNA) degradation during infection, through functional coordination with host cell RNA exonuclease. Previous studies have largely focused on RNA degradation as a mechanism for regulating viral gene expression and evading innate immune sensing. Here, we show that impaired RNA degradation in vaccinia virus–infected cells, due to either depletion of viral decapping enzymes or cellular exonuclease, severely compromises mitochondrial respiration and integrity. We further demonstrated that accumulation of excess dsRNA and mRNA, including pseudouridine-modified RNAs, is sufficient to induce profound defects in mitochondrial respiration and integrity. Notably, this impairment occurs independently of interferon induction and dsRNA innate immune sensor Protein Kinase R. Moreover, excess RNA suppresses respiration in purified cell-free mitochondria and physically associates with mitochondria in cell-free and cellular contexts, supporting an immune-independent mechanism. Excess mRNA and dsRNA reduce mitochondrial membrane potential in both cells and purified mitochondria, indicating disruption of the proton gradient as the mechanism underlying impaired mitochondrial respiration and integrity. Together, these findings identify excess mRNA and dsRNA as perturbants of mitochondrial homeostasis in cells with dysfunctional RNA degradation during vaccinia virus infection, revealing a paradigm-shift concept linking RNA metabolism to mitochondrial function. The finding carries broad implications for understanding RNA and mitochondrial biology and RNA-based therapeutics and vaccines.

Weak In‐Plane Ferromagnetism and Electronic Nematicity in the Distorted Triple‐Q Magnetic Phase of Co _1/3 TaS ₂

ABSTRACT An intercalated transition‐metal dichalcogenide hosts a triple‐ Q (3 Q ) noncoplanar antiferromagnetic state that co‐exists with electronic nematicity, indicating broken threefold rotational symmetry. This nematicity exhibits versatile field‐ and strain‐tunability, making it promising for spintronics applications. However, its microscopic connection to magnetism has remained unclear. Here, we report rotational hysteresis observed in both magnetoresistance and magnetic torque, revealing strongly pinned in‐plane weak ferromagnetic moments in the triple‐ Q phase and the magnetism‐driven nature of the co‐existing nematicity. In particular, when fields are rotated within a narrow angular range to restrict magnetization reversal, we observe additional hysteresis loops. This hysteresis can be well explained by domain repopulation, further supported by our theoretical simulations based on the spin Hamiltonian of . These results demonstrate that the weak in‐plane ferromagnetic moment offers an additional handle on the spin‐driven electronic nematicity, providing a microscopic picture of the field‐tunable electronic responses in the 3 Q state of .

Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells

Engineering CRISPR-Cas systems for improved or altered function is critical to both research and therapeutic applications. Unfortunately, most optimization, especially directed evolution in bacterial hosts, fails to capture the functional requirements of the complex mammalian cellular milieu, where activity is usually required. Robust strategies to enable continuous directed evolution of genome-targeting agents directly in human cells remain lacking. Here, we introduce CRISPR-MACE (Mammalian cell-enabled Adenovirus-assisted Continuous Evolution) as a foundational technology to address this need. CRISPR-MACE integrates virus-based continuous evolution with anti-CRISPR-based tunable selection to generate Streptococcus pyogenes Cas9 variants with both increased and decreased DNA binding capacity and nearly 1,000-fold-enhanced resistance to AcrIIA4, the strongest known inhibitor of SpCas9. Notably, across independent evolution campaigns, the same Cas9 gatekeeper mutation reproducibly emerged first, enabling subsequent adaptive steps along two interdependent axes of Cas9 function. In addition to advancing CRISPR technologies, this work establishes key principles and synthetic circuits for continuously evolving CRISPR-Cas systems directly in human cells.

Rational sycophants and catastrophic risks

Sycophants praise and support leaders’ proposals to gain personal and professional advantage. A rational sycophant is an advisor who supports actions they expect to be harmful even when rewards and punishments for good and bad advice are equal in magnitude. Rational sycophancy arises when the outcome distribution of a proposed action has a negative expected value but a positive median (outcome asymmetry). The risk is greatest when a small yet meaningful fraction of outcomes are catastrophic, which occurs in long-tailed distributions. Given that single realizations from long-tailed distributions reveal little about the underlying distribution, even after outcomes are observed, a leader may be unable to distinguish rational sycophancy from wise counsel. As a result, rational sycophants may gain influence and increase the likelihood of catastrophic policy outcomes.

China’s one-child policy amplifies intergenerational inequality via enlarged differential fertility

Using the staggered rollout of China’s one-child policy (OCP) across provinces and birth cohorts as a quasi-natural experiment, we demonstrate that differential fertility between richer and poorer households exacerbates intergenerational income inequality. Rural/poorer families, who are less constrained by the OCP than their urban/richer counterparts, tend to have more children but invest less in each child’s human capital. This reduction in mobility is primarily driven by the rising economic status of children born to urban/wealthier families. Our estimates suggest that the OCP accounts for approximately 25% of the observed decline in intergenerational income mobility in China and thus highlight a demographic channel through which economic inequality persists across generations.

Rates of speciation and past extinctions affect food webs on continental scales

Zwitterionic Polymers: Synthesis, Architectures, Properties, and Biomedical Applications

ABSTRACT Zwitterionic polymers are a class of polymeric materials characterized by repeating units bearing equal numbers of positively and negatively charged groups. Their unique chemical structure confers a strong hydration effect via ionic solvation, leading to distinctive properties such as resistance to protein adsorption and cell adhesion, effective interfacial lubrication, enhanced drug stability, and antifreezing capability. Consequently, zwitterionic polymers have garnered significant attention in biomedical applications in recent years. This review summarizes zwitterionic polymers through an application‐oriented “synthesis–architecture–application” framework. We emphasize that their biomedical performance is not determined solely by types of zwitterionic polymers, but by the hierarchical relationship among synthetic strategy, chain‐level topology, material architecture, and application‐specific biological interactions. Conversely, application requirements guide the selection of material architecture, polymer topology, synthetic strategy, and zwitterionic polymers. From this perspective, synthetic routes are discussed as tools for controlling polymer topology and architecture, while biomedical applications are analyzed in terms of the material forms and interfacial properties they require. We further discuss the current translational status of zwitterionic polymers, their major clinical challenges, and potential solutions. This review provides an application‐oriented design roadmap for linking zwitterionic chemistry, polymer synthesis, material architecture, and biomedical translation.

Semantic knowledge guides innovation and drives cultural evolution

Cultural evolution allows ideas and technologies to accumulate across generations, reaching their most complex and open-ended form in humans. While social learning enables the transmission of such innovations, the cognitive processes that generate them remain poorly understood. Classical theories typically treat innovation as random variation, a simplification insufficient for explaining the complexity of human cultural evolution. We propose that semantic knowledge—the associations linking concepts to their properties and functions—guides human innovation and drives cumulative culture. To test this, we combined an agent-based model, which examines how semantic knowledge shapes cultural evolutionary dynamics, with a large-scale behavioral experiment (N = 1,243) testing its role in human innovation. Across both approaches, we found that semantic knowledge directed exploration toward meaningful solutions, enhanced innovation success, and enabled generalization from prior discoveries. Moreover, semantic knowledge interacted synergistically with social learning to amplify innovation and accelerate cumulative cultural change. In contrast, experimental participants lacking access to semantic knowledge performed no better than chance, even when social learning was possible, and relied on shallow exploration strategies for innovation. Together, these findings suggest that semantic knowledge is a key cognitive process underpinning human cumulative culture.

Reading ability in both deaf and hearing adults is linked to neural representations of abstract phonology derived from visual speech

Reading is central to academic and vocational success. Some deaf children face reading challenges due to limited access to spoken or signed language. Robust phonological representations are key to reading development in hearing children. Spoken language phonology may be one of many contributors to reading development in deaf children. Indeed, speechreading ability correlates with reading skill in both deaf and hearing individuals, suggesting it is linked to reading development regardless of hearing status. Further support for this hypothesis would be provided by evidence that similar neural representations of speech phonology are evoked by visual speech and other language forms (auditory speech and text) and that these neural representations are related to reading proficiency. We used fMRI and representational similarity analysis (RSA) to identify shared neural representations of spoken language phonological structure. A group of deaf adult participants (N = 22), with a mixture of sign language and spoken language backgrounds and reading abilities, were presented with single lexical items as visual speech and dynamic text (cursive text, revealed letter-by-letter to promote a phonological reading strategy). Adult hearing participants (N = 25) were presented with the same words, but as visual speech and auditory speech. Shared neural representations of phonological structure of English words were found in each group in the superior and middle temporal cortex (STC/MTC) and these abstract representations were more similar across different language forms in better readers. Our data provide neurobiological evidence of the contribution of visual speech to abstract phonological representations of spoken language, that relate to reading proficiency, in both deaf and hearing adults.

Phosphoethanolamine cytidylyltransferase 2 integrates DAG metabolism and TBK1 activation to regulate antiviral innate immunity

Phosphatidylethanolamine (PE) biosynthesis is critical for membrane biology and cellular homeostasis. However, its specific role in antiviral innate immunity remains poorly understood. Here, we demonstrate that inhibition of phosphoethanolamine cytidylyltransferase 2 (PCYT2), a key enzyme in PE biosynthesis, promotes TBK1 activation to enhance the antiviral innate immune response. Mechanistically, PCYT2 deficiency leads to the accumulation of diacylglycerol, which activates protein kinase C-δ (PKCδ). We identify PKCδ as a direct kinase for TBK1 and demonstrate that it binds to and phosphorylates TBK1 at Ser716. This Ser716 phosphorylation facilitates the subsequent canonical phosphorylation of TBK1 at Ser172, resulting in hyperactivation of the TBK1–IRF3 axis. Our findings uncover a link between PE metabolism and antiviral innate immunity, suggesting that targeting the PE biosynthesis pathway could be a potential therapeutic strategy against viral infections.

Remote sensing enables expansion of our understanding of controls on river width and active floodplain

Polyploidy: A macromutational force pushing bioeconomic developments

Polyploidization, the consequence of genome doubling, is a macromutation that reshapes genomes, phenotypes, and ecological interactions. Polyploidization often results in novel phenotypes, including alterations in size, physiology, biochemistry, and enhanced stress tolerance. Here, we discuss how strategically leveraging polyploidy can provide significant advancements within the modern bioeconomy committed to reducing our ecological footprint through the sustainable production and use of biological resources. The bioeconomy spans diverse sectors, including agriculture, health sciences, and biotechnology. By elucidating and leveraging the immediate, or short-term, effects of polyploidization, such as harnessing genetic diversity, extensive biomass production, diversification of metabolites, and improved stress resilience, we highlight how this process unlocks vast, underexplored bioeconomic opportunities. This includes accelerating the exploration of new breeding techniques, speeding up the domestication of new local varieties or medicinal plants, and offering possibilities for improved biofuel production, bioremediation strategies, therapies, and production and discovery of bioactive compounds. The multilayered effects of polyploidization shared across sectors can foster interdisciplinary exchange and are essential for advancing toward a more sustainable bioeconomy.

Volatile signaling in plant– <i>Metarhizium</i> –insect interactions: Implications for nitrogen cycling

Nitrogen exchange between plants and insects is a major component of ecosystem nitrogen cycling. Endophytic insect pathogenic fungi transfer insect-derived nitrogen to plants through symbiotic associations mediated by fungal mycelia, enabling plants to thrive even after losing nitrogen to insects. However, the mechanisms underlying this process remain unexplored. Here, we show that the widespread endophytic entomopathogen Metarhizium robertsii degrades the common root-derived antifungal compound caulilexin C to produce the volatile 1-methoxyindole. This compound is recognized by the Or74a olfactory receptor in Drosophila melanogaster larvae and attracts multiple Dipteran species to the plant– Metarhizium consortium. The recruited insects are subsequently infected and consumed, resulting in enhanced insect-derived nitrogen transfer to the plants. This self-reinforcing mechanism strengthens the plant–fungus symbiosis and reveals a pathway contributing to ecosystem nitrogen flux.

Meiosis-specific genes play roles in ploidy reduction in <i>Cryptococcus neoformans</i> titan cells

Cryptococcus neoformans is a fungal pathogen of humans that causes life-threatening meningoencephalitis. During infection, enlarged, polyploid titan cells are produced that promote persistence in the host, in part by resisting phagocytosis; under stress conditions, such as exposure to the antifungal drug fluconazole, titan cells can produce aneuploid or diploid, drug-resistant daughter cells. However, the mechanism underlying this ploidy reduction remains poorly understood. Interestingly, meiosis-related genes have been shown to be activated during Cryptococcus infection, leading us to hypothesize that the depolyploidization of C. neoformans titan cells may occur through a process resembling the ploidy reduction during meiosis. In this study, we show that titan cells developed from diploid strains predominantly produce diploid daughter cells with haploid daughters observed infrequently. We further demonstrate that meiosis-specific genes, including DMC1 and SPO11 , are critical for stable inheritance of a diploid genome in the daughter cells. Specifically, deletion of these genes in a heterozygous diploid background resulted in 1) titan cells with a significantly reduced capacity to produce daughter cells; 2) increased phenotypic variation among daughter cells produced by the titan cells, including traits that could be relevant to cell growth and viability; and 3) daughter cells produced by the titan cells exhibiting high levels of loss of heterozygosity (LOH) and aneuploidy, suggesting elevated genome instability. Taken together, these findings demonstrate the importance of meiosis-specific genes in the ploidy reduction process of titan cells derived from a heterozygous diploid background in an important human fungal pathogen.

Accessibility–equality dynamics in urban blue and green spaces reshape human well-being

As urbanization accelerates, urban blue and green spaces are increasingly recognized as critical nature-based solutions for enhancing human well-being, delivering climate, environmental, and psychological benefits. Yet, the mechanisms by which access to these natural spaces and the equality of access by urbanites in diverse residential locations shape well-being remain poorly understood in the context of sustainable urban governance. Here, we systematically evaluated the spatiotemporal dynamics of urban blue and green space accessibility and equality across 279 Chinese cities from 2000–2100 and assessed their combined effects on well-being. We found that accessibility has a significant positive influence on well-being but follows an inverted-U-shaped pattern with distinct optimal thresholds. By contrast, equality shows a consistent, positive linear relationship with well-being. Although future accessibility is projected to improve, persistently high disparities among different segments of urban populations highlight the urgent need for equity-centered governance of blue and green spaces in cities. This perspective extends current approaches to environmental justice while revealing a structural mismatch between resource abundance and equitable distribution. To address this mismatch, we propose a prioritization framework that emphasizes context-specific, spatially targeted interventions, guided by four key drivers: the natural space to built-up area ratio, urban population size, the proportion of natural spaces with high accessibility, and urban landscape connectivity. By operationalizing these insights in an online toolkit for local governments, this work advances the fields of sustainable urban governance and equitable environmental planning.

Social interactions in isolated, confined, and extreme environments: A study of Antarctic winter teams using wearable sensors

Long-duration space missions expose crews to extreme psychological and social stressors due to prolonged isolation and confinement. To examine how such conditions impact individual and team functioning, we studied a 10-mo Antarctic overwintering mission at Concordia Station, an analog for spaceflight, using self-report measures and wearable proximity sensors. Twelve crew members were assessed at four time-points. Results revealed a progressive increase in feelings of loneliness and conflict, while cohesion and individual performance declined. Close-range interactions were positively associated with conflicts and paranoid thoughts and negatively related with individual performance, suggesting that more frequent contact did not equate to social support. Social interactions became increasingly clustered within national groups, highlighting the risk of social fragmentation and crew polarization. The use of wearable sensors proved feasible for long-term use in extreme environments. These findings underscore the importance of monitoring psychosocial functioning during extended missions and suggest that close confinement, rather than isolation alone, may trigger interpersonal strain.

Rice paper adsorbent for gold recovery

Growing global interest in gold (Au) has spurred the development of adsorption processes as sustainable technologies for effective Au recovery from industrial waste. However, the adsorbents used in such processes often require complex fabrication procedures and/or petroleum-based chemicals, aggravating economic and environmental burdens. To overcome these limitations, this study proposes the transformation of rice paper (RP), a biomass (starch)-based food material, into a high-performance Au adsorbent via facile aqueous-phase chemical modification (hydrazination). The resultant hydrazine-functionalized RP (Hz-RP) adsorbent features a stratified mesoporous structure and demonstrates high mechanical integrity in water. Hz-RP rapidly, effectively, and selectively recovers Au even in complex feed solutions (e.g., electronic waste leachate) via collaborative chemisorption and reduction, outperforming many Au adsorbents reported in the literature. Following Au adsorption, Hz-RP can be readily collected and calcined to obtain high-purity Au. System-level analyses indicate that a Hz-RP-based process to recover Au from discarded electronics is economically and environmentally beneficial. Thus, this study establishes a viable pathway toward a circular resource economy by demonstrating the sustainable recovery of Au from industrial waste and the valorization of biomass/food waste.

amyloid-predict and LLPS-predict: Predicting phase separation propensities in the intrinsically disordered proteome

Amyloid formation and liquid–liquid phase separation (LLPS) are two important phenomena in cellular biology, linked to both normal physiological functions and various pathologies. Here, we present a computational framework that scores amyloid propensities (amyloid-predict) or LLPS propensities (LLPS-predict) from protein language model embeddings, enabling rapid proteome-wide annotation of peptides and residues. amyloid-predict achieves classification performance that exceeds existing AI and physics-based tools on a hexapeptide benchmark while enabling substantially faster high-throughput screening; notably, amyloid-predict is sensitive to subtle mutational effects and is influenced by sequence patterning and context rather than amino acid composition alone. We apply these protein language model classifiers to all the IDRs in the human proteome and uncover several protein categories with significant enhancement in amyloid and/or LLPS propensity, suggesting insights into the biological roles of these protein categories. For example, signaling receptors, carbohydrate-binding proteins, and Ca 2+ binding proteins are enriched in aggregation propensity, while mRNA-binding proteins, ribonucleoprotein complex, and nuclear matrix proteins are enriched in LLPS propensity. Interestingly, we observe patterns of both high amyloid and LLPS propensity in several amyloid-forming and prionic proteins. Together, these results provide side-by-side landscapes of LLPS and amyloid potential across the disordered human proteome while offering a rapid screening tool for basic biology, disease-mechanism studies, and rational design of peptide therapeutics.