Browse Articles

Dynamics of memory B cells and plasmablasts in healthy individuals

Our adaptive immune system relies on the persistence over long times of a diverse set of antigen-experienced B cells to encode our memories of past infections and to protect us against future ones. While longitudinal repertoire sequencing promises to track the long-term dynamics of many B cell clones simultaneously, sampling and experimental noise make it hard to draw reliable quantitative conclusions. Leveraging statistical inference, we infer the dynamics of memory B cell clonal dynamics and conversion to plasmablasts, which includes clone creation, degradation, abundance fluctuations, and differentiation. We find that memory B cell clones degrade slowly, with a half-life of 10 y. Based on the inferred parameters, we predict that it takes about 50 y to renew 50% of the repertoire, with most observed clones surviving for a lifetime. We infer that, on average, 1 out of 100 memory B cells differentiates into a plasmablast each year, more than expected from purely antigen-stimulated differentiation, and that plasmablast clones degrade with a half-life of about one year in the absence of memory imports. Our method is general and could be applied to other longitudinal repertoire sequencing B cell subsets.

Integrated multi-dataset screening to predict prognosis and identify immunotherapy gene targets in hepatocellular carcinoma patients

Orbital longitudinal magnetoelectric coupling in rhombohedral multilayer graphene

Magnetoelectric coupling enables the manipulation of magnetization by electric fields and polarization by magnetic fields. While typically found in heavy element materials with large spin–orbit coupling, recent experiments on rhombohedral-stacked pentalayer graphene have demonstrated a longitudinal magnetoelectric coupling (LMC) without spin–orbit coupling. Here, we develop a microscopic theory of LMC in layered quantum materials and identify how it is controlled by a “layer-space” quantum geometry. Focusing on rhombohedral multilayer graphene systems, we find that the interplay between LMC and valley-polarized order produces a butterfly shaped magnetic hysteresis controlled by out-of-plane electric field: a signature of LMC and a multiferroic valley order. Furthermore, we identify a nonlinear LMC in rhombohedral multilayer graphene under time-reversal symmetry, while the absence of centrosymmetry enables the generation of a second-order nonlinear electric dipole moment in response to an out-of-plane magnetic field. Our theoretical framework provides a quantitative understanding of LMC, as well as the emergent magnetoelectric properties of rhombohedral multilayer graphene.

Polishing dental ceramics using shear-thickening slurry

Ten-year ¹⁵ N labeling reveals the nitrogen retention threshold for maximizing carbon sequestration in a temperate forest

Anthropogenic nitrogen (N) deposition comprising reduced (NH x ) and oxidized (NO y ) forms, differentially influences ecosystem processes. However, their long-term fates and collective impacts on ecosystem nitrogen use efficiency (NUE) and carbon (C) sequestration remain unresolved. Here, using a decade-long paired labeling ( 15 NH 4 + and 15 NO 3 − ) experiment in a temperate forest, we demonstrate that initially distinct fates of different N forms converged within 2 y due to low initial loss rates prior to organic incorporation. After 10 y, overall ecosystem retention was remarkably similar (55.3 to 65.6%) for both N forms. A process -based N-cycling model was built and parameterized by our 15 N recovery data and the model predicted declining ecosystem NUE with increasing N deposition level. We further identified a deposition-induced C sequestration potential of 41.41 kg C kg −1 N under an incremental deposition of 10 kg N ha −1 y −1 , exceeding prior estimates at comparable loads. This study provides mechanistic, high-resolution temporal data critical for refining N-cycle models and reveals an optimal N deposition range (20 to 30 kg N ha −1 y −1 ) that maximizes C sequestration while minimizing environmental risks (e.g., nutrient imbalance, eutrophication) in temperate forests.

Sensitive and quantitative biosensing technique based on NV centres-doped nanodiamonds applied to lateral flow assays

The assembly rules guiding hetero-oligomeric bacterioferritin organization and their evolutionary signature

Homomeric and heteromeric protein complexes are ubiquitous across all domains of life. The evolutionary transition from homo- to hetero-oligomers by gene duplication and chain specialization is widespread, yet it entails challenging requirements for maintaining oligomerization and functionality. Chain specialization in ferritins, which occurs in bacteria, vertebrates, and plants, is a salient example of this phenomenon. In heteroferritins, the two essential functions, ferroxidase activity and electron transfer, are split between two specialized chain types. Many heteroferritins assemble into complexes with variable subunit ratios, implying the existence of assembly rules that balance compositional flexibility with structural constraints. Here, we identify the assembly rules governing the organization of the heterobacterioferritin from Magnetospirillum gryphiswaldense (MSR-1 Bfr) by analyzing its cryo-EM reconstructions. These rules consist of structural constraints that limit the number of possible arrangements and promote juxtaposition of the two, now separated functions. These constraints support compositional flexibility while preserving function, thereby providing resilience to stochastic variation in oligomer stoichiometry. Bioinformatic analysis revealed that the assembly rules identified in MSR-1 Bfr are widespread across the Bfr family and coevolved with chain specialization. Together, these findings support leading models of hetero-oligomer evolution and reveal the emergence of order-exerting mutations that shape the organization of multimeric protein complexes while conserving function.

Monitoring public reaction to an unnecessary earthquake early warning alert

Phage Mu enlists the β-sliding clamp for late gene transcription

The phage Mu C protein (MuC), along with core RNA polymerase (RNAP) and σ 70 , is required for transcription of phage late genes. We found that overexpression of MuC was lethal in Escherichia coli and observed that host replication was overinitiating under these conditions. Suppressors of MuC lethality mapped to dnaA , diaA , and dnaX . DnaA initiates replication at oriC , assisted by DiaA. Reinitiation is prevented by hydrolysis of ATP-DnaA to ADP-DnaA by Hda and DnaN (β-sliding clamp or Clamp). DnaX, the tau/gamma subunit of Pol III, is part of the Clamp loader complex. Coexpression of hda and dnaN rescued MuC lethality. This result suggested that MuC was interfering with either Hda or DnaN. We noticed that MuC contains two near-consensus Clamp-binding motifs (CBM), one at the N terminus and one at the C-terminus. Changing the consensus residues of either CBM abolished MuC lethality, abrogated MuC-dependent transcription, and reduced plaque-forming units. Inactivation of a ts Clamp through temperature shift specifically inhibited MuC-dependent transcription but not σ 70 -dependent transcription. We show that MuC interacts with the Clamp to activate late gene transcription both in vivo and in vitro. This study demonstrates the involvement of the E. coli Clamp, a processivity factor essential for DNA replication, for transcription by E. coli RNAP. We observed that members of the Mor/MuC family of transcription factors all possess at least one CBM, suggesting that engaging the Clamp for transcription is likely to be more prevalent than hitherto recognized.

Multiscale insights into biofilm development on hydrophobic fouling-release coatings

Genomics and genetic rescue

Melanophore and fluoroleucophore photo-protect the Arabian killifish, Aphanius dispar, embryo from ultraviolet light

Abstract Pigment cells in fish species play crucial roles in forming colour patterns of each species and other physiological characteristics, including photoprotection. Research on animal pigment cells’ photoprotection has primarily concentrated on black pigment cells, known as melanophores. However, the roles of other pigment cells on UV protection remain poorly understood. In addition, UV sensitivity/resistance mechanisms have been studied in a small number of selected model organisms, and difference of UV sensitivity has not been fully investigated in different species. In this study, we use the Arabian killifish embryos as a novel model for studying the mechanisms of UV protection by different pigment cells. This species features highly fluorescent pigment cells called fluoroleucophores and black pigment cells melanophores. The fluorescent pteridine pigments and black melanin pigments are generated by genes gch (GTP cyclohydrolase) and tyr (tyrosinase), respectively. We generated gch-/- and gch-/-tyr-/- double mutant lines using CRISPR/Cas9 genome editing and examined the UV sensitivity of WT and these mutant embryos. Firstly, we have observed that Arabian killifish embryos showed higher UV resistance to the one in zebrafish from which majority of UV toxicity studies was conducted in fish species so far. Secondly, both morphology and gene expression data revealed that the gch-/-tyr-/- double mutant line exhibited the highest UV sensitivity, and the gch-/- line also demonstrated a greater stress response compared to wild type (WT). The study revealed a diversity of UV resistance between fish species and also identified the roles of black and fluorescent pigment cells in providing effective UV protection from the early stages of embryonic development.

Payoff equivalence and complete strategy spaces of direct reciprocity

Repeated games and stochastic games are important frameworks to study direct reciprocity. Individuals react strategically to their coplayers’ previous behavior. While strategies in such games can be arbitrarily complex, explorations of evolutionary dynamics are often done in specific strategy spaces. Individuals may consider a fixed number of past rounds, or only some of the partner’s previous actions. Such restrictions can make the interpretation of the results difficult. Strategies found to be superior within a restricted set may lose stability when more complex strategies are permitted. We discuss two notions of completeness that rule out this possibility. If a strategy space, S, is best-reply-complete, then any strategy in S is guaranteed to have a best reply in S. If a space, S, is payoff-complete, then any strategy playing against an opponent in S can be replaced by an equivalent strategy within S without affecting either player’s payoff. Sufficient conditions for best-reply-completeness have been given in a seminal paper by Levínský et al. Here, we show that for strategies of bounded memory, the same conditions are sufficient for payoff-completeness. Furthermore, using those conditions, we illustrate how to construct many complete spaces for simple games. Taken together, our findings highlight the importance of complete strategy spaces, which are particularly useful when interpreting evolutionary simulations and determining best responses.

An improved YOLOv11 network for marine debris detection in underwater environment

Shaking and pushing skyrmions: Formation of a nonequilibrium phase with zero critical current

In three-dimensional chiral magnets, skyrmions are line-like objects oriented parallel to the applied magnetic field. The efficient coupling of magnetic skyrmion lattices to spin currents and magnetic fields permits their dynamical manipulation. Here, we explore the dynamics of skyrmion lattices when slowly oscillating the field direction by up to a few degrees on millisecond timescales while simultaneously pushing the skyrmion lattice by electric currents. The field oscillations induce a shaking of the orientation of the skyrmion lines, leading to a phase where the critical depinning current for translational motion vanishes. We measure the transverse susceptibility of MnSi to track various depinning phase transitions induced by currents, oscillating fields, or combinations thereof. An effective slip–stick model for the bending and motion of the skyrmion lines in the presence of disorder explains main features of the experiment and predicts the existence of several dynamical skyrmion lattice phases under shaking and pushing representing phases of matter far from thermal equilibrium.

Randomized trial of smartphone application and bed sensor for atrial fibrillation detection in high-risk patients

The dynamics of cooperation in asymmetric public goods games

When people collaborate in groups, they routinely face collective action problems: for the group effort to succeed, individuals need to cooperate despite any incentives to defect. These problems can be modeled with public goods games. To facilitate such an analysis, many studies assume the game is symmetric. Group members have the same means to cooperate (equal endowments), and contributions of different group members are equally effective (equal productivities). Studies that allow for some inequality tend to focus on one kind of inequality only. In practice, however, people can be unequal in many ways. The effect of these inequalities may in turn depend on the specific public goods game considered. To explore these issues, we combine a large-sample experiment with extensive theoretical work. We systematically vary four aspects: the group members’ endowments, their productivities, group size, and whether the public goods game exhibits linear returns or returns given by a threshold function. By exploring all four aspects, we obtain a unique dataset to explore the effect of asymmetry on cooperation. Based on this dataset, we study whether there is an advantage of “aligned inequality”: whether groups achieve a better surplus if more productive individuals have a larger endowment. For public goods games with linear returns, we find such an advantage, thereby corroborating previous research. If returns follow a threshold function, however, aligned inequality results in inferior payoffs. These results show that the effect of inequality on cooperation depends on the kind of public goods game considered.

Refractive outcomes and predictability after cataract surgery combined with GATT or Kahook Dual Blade goniotomy

Automated decision-making by chemical echolocation in active droplets

Motile microorganisms, like bacteria and algae, unify abilities like self-propulsion, autonomous navigation, and decision-making on the micron scale. While recent breakthroughs have led to the creation of synthetic microswimmers and nanoagents that can also self-propel, they still lack the functionality and sophistication of their biological counterparts. This study pioneers a mechanism enabling synthetic agents to autonomously navigate and make decisions, allowing them to solve mazes and transport cargo through complex environments without requiring external cues or guidance. The mechanism exploits chemo-hydrodynamic signals, produced by agents like active droplets or colloids, to remotely sense and respond to their environment—similar to echolocation. Our research paves the way for endowing autonomous, motile synthetic agents with functionalities that have been so far exclusive to biological organisms.

Integrative analysis of transcriptome and single-cell sequencing combined with experimental validation identifies biomarkers associated with T cell and senescence in sepsis