Browse Articles

Distinct neural dynamics in the ventral hippocampus and medial prefrontal cortex during social information processing

Social information processing involves coordinated neural activity across distributed brain circuits, with the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC) playing pivotal roles. However, whether these regions employ distinct coding strategies for different social stimuli remains unclear. Using in vivo electrophysiological recordings in freely interacting mice, we show that although both regions respond to social cues, they engage divergent neural coding mechanisms. During social interaction, the mPFC predominately recruits high gamma oscillations with amplitudes modulated by the phase of theta oscillations, whereas the vHPC primarily depends on low gamma activity phase-locked to theta rhythms. Information-theoretic and machine learning analyses demonstrate that neural populations in the mPFC encode social information more robustly than those in the vHPC. Moreover, integrating spiking activity with local field potential oscillations enhances decoding accuracy compared to spike-only models. Neural manifold analysis showed greater signal-noise angle in the mPFC compared to the vHPC, indicating more discriminative and stable social representations in the mPFC. Our findings demonstrate distinct engagement of neuronal populations and gamma oscillations in the vHPC and mPFC during social information processing.

General phase segregation and phase pinning effects in lanthanide-doped lead halide perovskite with dual-wavelength lasing

Potentiation of ryanodine receptor–mediated calcium release by MAPK is responsible for epidermal transformation and carcinogenesis

Epidermal growth factor (EGF) induces anchorage-independent growth in promotion-sensitive (P + ) mouse epidermal cell model JB6 primarily through activation of the MAPK/ERK signaling pathway. The β-blocker carvedilol inhibits EGF-promoted JB6 transformation, but the underlying mechanism is unknown. Since carvedilol suppresses overactivated ryanodine receptors (RyRs) independently of its adrenergic blocking effects, we hypothesized that EGF-promoted transformation requires RyR-mediated calcium (Ca 2+ ) release and that carvedilol inhibits transformation via targeting RyRs. All RyR subtypes were present in epidermis and strongly upregulated by ultraviolet (UV) radiation, as demonstrated in an RyR2-tdTomato reporter mouse model. In vitro, EGF induced ERK phosphorylation and RyR2 upregulation and increased RyR agonist 4-chloro-m-cresol (4-CMC)-evoked Ca 2+ release, which is inhibitable by structurally divergent RyR stabilizers and inhibitors of MAPK and PLC, but not by most β-blockers. Expression of constitutively active K-RAS and MEK-1 or UV also potentiated 4-CMC-evoked Ca 2+ release. RyR agonists and the Ca 2+ ionophore ionomycin promoted JB6 transformation while RyR stabilizers, the intracellular Ca 2+ chelator BAPTA/AM, and inhibitors of MAPK and PLC blocked transformation. The RyR shRNAs abolished the transformation-inhibitory effect of carvedilol. The IC 50 values of five carvedilol derivatives for suppressing RyR-mediated Ca 2+ release positively correlated with the IC 50 values for transformation inhibition. In vivo, UV-induced DNA damage and skin inflammation were enhanced by topical 4-CMC treatment but attenuated in the RyR2-E4872Q knock-in mice in which RyR2 activity is reduced. Human skin tissue microarray analysis confirmed spatial colocalization of phospho-ERK and RyR2 in the same tumor areas. Thus, potentiation of RyR-mediated Ca 2+ release by MAPK is an important pathway leading to carcinogenesis.

Direct evidence for the absence of coupling between shear strain and superconductivity in Sr2RuO4

Coexistence of trapped and flow-transported nuclei enables fast pigeon post communication across multinucleated cell

Multi-nucleated cells exist in all domains of life, ranging from animals, plants, and fungi to single-celled organisms such as the slime mold Physarum polycephalum . The large cell size, in the case of Physarum reaching centimeters and more, challenges the coordination of nuclei activity as signals need to cross large distances. In search of a mechanism for fast long-ranged communication among nuclei, we quantify nuclei dynamics and cytoplasmic flows in Physarum ’s tubular network. We observe nuclei in two interchangeable, dynamic states: mobile, flowing within the cytoplasmic shuttle flow, or trapped in the tube’s porous cell cortex. As we find nuclei to accumulate at the tube’s inner fluid–porous interface we theoretically explore and confirm, with physiological parameters, that slowing down of mobile nuclei during flow is sufficient for diffusible signal exchange between mobile and trapped nuclei. We analytically derive that communication akin to pigeon post with mobile nuclei serving as pigeons shuttling between trapped nuclei acting as waypoints, gives rise to signaling velocities that account for the rapid intracellular reorganization observed in Physarum . Since signal transfer by flow-transported nuclei outcompetes the mere diffusion of signals encoded in cytosolic proteins, pigeon post communication surpasses alternative signaling mechanisms, even diffusive relay signaling up to 20-fold in velocity. The key ingredients of pigeon post communication, namely alternating flows and waypoints, exist in other multi-nucleated cells and may also be generalized beyond intracellular signaling.

Multi-messenger dynamic imaging of laser-driven shocks in water using a plasma wakefield accelerator

Contrastive independent component analysis for salient patterns and dimensionality reduction

In recent years, there has been growing interest in jointly analyzing a foreground dataset, representing an experimental group, and a background dataset, representing a control group. The goal of such contrastive investigations is to identify salient features in the experimental group relative to the control. Independent component analysis (ICA) is a powerful tool for learning independent patterns in a dataset. We generalize it to contrastive ICA (cICA). For this purpose, we devise a linear algebra–based tensor decomposition algorithm, which is more expressive but just as efficient and identifiable as other linear algebra–based algorithms. We establish the identifiability of cICA and demonstrate its performance in finding patterns and visualizing data, using synthetic, semisynthetic, and real-world datasets, comparing the approach to existing methods.

Metabolic syndrome promotes endometrial cancer by Oleic acid-mediated polyamine accumulation

Abstract Metabolic syndrome increases the risk of endometrial cancer development and progression, but the mechanism remains unclear. We find that polyamine metabolites are notably elevated in the sera and tumor tissues of endometrial cancer patients with metabolic syndrome. Oleic acid, one of the many components in hyperlipidemia, is the key factor for upregulating Ornithine Decarboxylase 1 (ODC1) (the rate-limiting enzyme in polyamine metabolism) and downstream polyamines. Mechanistically, Oleic acid binds to and stabilizes Homeobox B9 (HOXB9) by inhibiting the binding of HOXB9 to E3 ligase Praja2. Stable HOXB9 then competes with OAZ1 and combines with ODC1 to block ODC1 degradation. Targeting HOXB9 or ODC1 reduces polyamine levels and suppresses tumor growth/spread. Oleic acid-HOXB9-ODC1 stable cascading axis then is confirmed in patient tissues, and ODC1 inhibitors boost patient-derived tumor cells’ chemosensitivity. This study links fatty acids to polyamine buildup, reveals a mechanism for metabolic syndrome-driven endometrial cancer, and points to HOXB9 and ODC1 as potential therapeutic targets.

Localized nutrient colimitation of phytoplankton growth rates across the subtropical South Pacific Ocean

The simultaneous depletion of multiple nutrients in seawater potentially leads to colimitation of phytoplankton growth across large oceanic extents. Single limitation versus colimitation carries implications for mathematically predicting growth, its response to environmental forcing, and evaluating biogeochemical feedbacks. However, identifying colimited growth has proved challenging due to a lack of appropriate methods. Here, we present the results of 12 experiments conducted across the South Pacific that used a matrix of nutrient additions to strongly diluted surface seawater. Dilution restricted both grazing rates and nutrient drawdown due to phytoplankton accumulation. We find that despite simultaneous depletion of nitrate, phosphate, and iron concentrations throughout the oligotrophic gyre, community-level phytoplankton growth rates were only constrained by nitrogen. In contrast, zones of colimitation and serial limitation by nitrogen and iron were found along the eastern gyre margin. At the nitrogen-iron co-/serially limited sites, growth response surfaces to nutrient additions varied, suggesting the need for dynamic models to accurately represent colimited phytoplankton growth in the ocean.

Structure of ATTRv-F64S fibrils isolated from skin tissue of a living patient

Abstract Amyloid transthyretin-derived (ATTR) amyloidosis is a degenerative, systemic disease characterized by transthyretin fibril deposition in organs like the heart, kidneys, liver, and skin. In this study, we report the cryo-EM structure of transthyretin fibrils isolated from skin tissue of a living patient carrying a rare genetic mutation (ATTRv F64S). The structure adopts a highly conserved fold previously observed in other ATTR fibrils from various tissues or different genetic variants. Mass spectrometry was used to evaluate fibril content and to identify common post-translational modifications. The structural consistency between ATTR filaments from different tissues or patients validates non-invasive skin biopsy as a diagnostic tool.

High-resolution lidar observations of sedimentation-induced size sorting of droplets near a laboratory cloud top

Cloud optical properties and precipitation, which are crucial to weather and climate, are strongly influenced by cloud microphysical properties that are still poorly understood. Here, we develop a high-resolution time-correlated single-photon-counting lidar and apply it to observe cloud microphysical properties at one-centimeter range resolution in a convection chamber under well-controlled conditions. Together with concurrent in-situ measurements and theoretical analysis, our lidar observations indicate that although turbulent mixing tends to homogenize the cloud in the bulk region, entrainment and sedimentation cause inhomogeneities in droplet concentrations near the cloud top. Specifically, the topmost region is directly affected by entrainment, and lidar profiles show clear evidence of entrained air and detrained cloud filament. The transition region below exhibits vertical size sorting of cloud droplets caused by sedimentation. Our results suggest that using a single sedimentation velocity for all cloud droplets, as is done in many atmospheric models, overlooks key physics relevant to the microphysical structure near the cloud top. Our conceptual model used to describe these measurements can serve as a step toward improving the current modeling of processes in the cloud top region.

Signatures of the sub-Rayleigh to supershear fracture transition in snow avalanche experiments

Abstract Snow slab avalanches occur when a crack propagates within a highly porous weak snow layer buried beneath a cohesive snow slab. Here, we report direct observations of a supershear event in snow fracture experiments following the spontaneous transition from sub-Rayleigh to intersonic crack propagation. The experiments involve artificially triggered avalanches on a small slope with a natural snowpack, captured with high-speed cameras and analyzed using digital image correlation. Deformation fields reveal distinct signatures: slope-normal collapse of the weak layer and slab flexure drive sub-Rayleigh propagation, while supershear fracture is related to slope-parallel deformation and slab tension. These results are further reinforced by numerical simulations that replicate the experiment and provide strong supporting evidence that the Burridge-Andrews mechanism governs the transition to supershear propagation. Analogous to supershear strike-slip earthquakes linked with substantial magnitudes, our findings suggest that supershear avalanches relate to widespread crack propagation and large avalanche dimensions, holding significant implications for risk mitigation strategies.

A metabolic cell death program downstream of SARM1 couples NAD ⁺ depletion to BAX activation and APAF1 degradation

SARM1 is a neuronal Nicotinamide adenine dinucleotide (NAD + ) hydrolase that drives axonal degeneration and neuronal death by depleting NAD + , yet how NAD + loss triggers axon loss and cell death has remained unclear. Here, we define a nonapoptotic death program downstream of endogenous SARM1 activation and NAD + loss using a genetically tractable nonneuronal eHAP cell model. Upon NAD + depletion, BAX is activated but caspase activation is suppressed due to APAF1 degradation via the E3 ligase HERC4, effectively uncoupling mitochondrial outer membrane permeabilization from apoptosome formation. Mechanistically, NAD + depletion inhibits mTOR/AKT signaling, destabilizing MCL1 and relieving BAX from repression. We further identified Neurofibromatosis type II, NF2, as a regulator that promotes SARM1 transcription through the Hippo–YAP/TAZ pathway. The SARM1-dependent BAX activation and the role of NF2 in axon degradation were validated in neuronal models of axon degeneration. Together, these findings reveal how SARM1-driven metabolic collapse rewires cell death execution, positioning BAX, MCL1, APAF1, NF2, and HERC4 as core effectors in a nonapoptotic degenerative pathway linking metabolic stress to neurodegeneration

A cis-regulatory element of the PHYTOCHROME A gene confers the submergence escape capacity for amphibious plants

Globally aggregated biodiversity data impact predictive and descriptive research

Here, we present an analysis of the growth and use of the Global Biodiversity Information Facility (GBIF) over the last 5 y. GBIF is the world’s largest data integrator for biodiversity information and plays a central role in research across the biodiversity and evolutionary science community. With the help of a comprehensive bibliographic dataset comprising 12,193 studies that used GBIF-mediated data, we demonstrate how the global scientific community utilizes the continuously fast-growing amount of open and Findable, Accessible, Interoperable, and Reusable biodiversity data in their research. Overall, more researchers engage with GBIF data, a potential consequence of the rising demands of more global environmental assessments, where GBIF-mediated data are being used as a key resource for biodiversity research. Studies utilizing species distribution modeling were most prevalent and data used for topics related to challenges of the Anthropocene (conservation, climate change, invasive, and pest species). More studies used observational data records, a category that also includes a substantial amount of citizen science data. Our data show that a thematic diversification of GBIF-using literature is accompanied by a rapid diversification of both the additional datasets that GBIF data are analyzed with, as well as the new analytical approaches taken by researchers. This emphasizes the growing importance of GBIF’s data infrastructure and services which support global sciences and reflect major shifts in applied science which dictate the need for GBIF and similar data infrastructures to evolve rapidly in order to maintain relevance for research.

Molecular basis of XPF-ERCC1 targeting to SLX4-dependent DNA repair pathways

Abstract The preservation and faithful propagation of genetic information is essential for all life forms and depends on cellular pathways that enable replication, recombination, and repair of DNA. The multifunctional XPF-ERCC1 DNA endonuclease complex acts in several DNA repair pathways and interacts with numerous partner proteins and large DNA repair assemblies, including the nucleotide excision repair machinery and the SMX tri-endonuclease complex. Here, we report structures of XPF-ERCC1 in complex with the DNA repair factors SLX4 and SLX4IP, thereby identifying key residues responsible for direct interactions with XPF-ERCC1. When introduced into human cells, point mutations in these interfaces impair the interactions between XPF-ERCC1 and SLX4 or SLX4IP, and disruption of the XPF-SLX4IP interface leads to cis-platin sensitivity. Furthermore, our data reveal the structure of the human XPF-ERCC1-SLX4IP-SLX4 330-555 complex with DNA bound at its active site, and they complete the structural characterisation of molecular interactions required to assemble the SMX complex.

Droplet-on-demand mass spectrometry reveals curvature-dependent interfacial reactivity in aqueous microdroplets

Water microdroplets offer a chemical environment that can dramatically accelerate reaction rates compared to bulk-phase solutions and even drive chemical transformations not found in bulk solutions. While mass spectrometry has proven indispensable for studying microdroplet chemistry, current methods rely on ensemble-averaged data from polydisperse droplet populations, obscuring the molecular details and droplet-size dependencies of reactions in individual droplets. Here, we present a piezoelectric-driven droplet-on-demand platform that enables direct mass spectrometric analysis of single, size-controlled microdroplets. We demonstrate a broad range of reactions occurring within isolated droplets. These reactions yield products comparable to those generated in conventional spray-based microdroplet systems, confirming that enhanced reactivity is intrinsic to the microdroplet environment. Crucially, we reveal a pronounced droplet-size-dependent reactivity, with smaller droplets exhibiting markedly higher activity per unit surface area. This consistent trend across different reaction types underscores the pivotal role of curvature-modulated interfacial electric fields in governing microdroplet reaction dynamics. Higher electric field strengths cause more radicals to be formed, but these radicals recombine with one another, removing them for reactions with other substrates. Consequently, as our experimental data show, there is an optimum droplet size to yield the highest product reaction rate.

Structural basis for ACT1 oligomerization induced by IL-17 receptor hetero-tetramer

Climate sensitivity is widely but unevenly spread across zoonotic diseases

Climate change is expected to exacerbate infectious diseases, yet the climate sensitivity of zoonotic diseases (driven by spillover from animal reservoirs) is understudied compared to vector-borne and water-borne infections. To address this gap, we conducted a scoping review and quantitative synthesis to identify relationships between climatic indicators (temperature, precipitation, humidity) and zoonotic disease risk metrics worldwide. We identified 218 studies from 65 countries describing 852 measures across 53 diseases, with most studies testing linear (n = 193) rather than nonlinear (n = 28) relationships. We found evidence of climate sensitivity across diverse zoonotic diseases (significant nonzero relationships in 69.1% of temperature effects, 63.5% of precipitation effects, and 53.6% of humidity effects), but with variation in direction and strength. Positive effects of temperature and rainfall on disease risk were more common than negative effects (46.5% vs. 22.6% and 37.8% vs. 25.7% of all records, respectively). These studies were predominantly located in areas expected to have substantial increases in annual mean temperature (>1.5 °C in 97% of studies) and rainfall (>25 mm in 53% of studies) by 2041 to 2070. Notably, the most consistent relationship was between temperature and vector-borne zoonoses (56% of positive effects, mean Hedges’ g = 0.36). Our analyses provide evidence that climate sensitivity is common across zoonoses, likely leading to substantial yet complex effects of climate change on zoonotic burden. We emphasize the need for future studies to utilize biologically relevant models, apply rigorous space-time controls, consider causal perspectives, and address taxonomic and geographic biases to allow robust consensus of climate–risk relationships to emerge.

Calcium-sensitive synaptotagmin 11-lipid interaction modulates exo-endocytosis