Browse Articles

Mechanism of beta-arrestin 1 mediated Src activation via Src SH3 domain revealed by cryo-electron microscopy

Abstract Beta-arrestins (βarrs) are key regulators and transducers of G-protein coupled receptor signaling; however, little is known of how βarrs communicate with their downstream effectors. Here, we delineate structural mechanisms underlying βarr-mediated signal transduction. Using cryo-electron microscopy, we elucidate how βarr1 recruits and activates the non-receptor tyrosine kinase Src, a well-established signaling partner of βarrs. βarr1 engages Src SH3 through two distinct sites, each employing a different recognition mechanism: a polyproline motif in the N-domain and a non-proline-based interaction in the central crest region. At both sites βarr1 interacts with the aromatic surface of SH3, disrupting the autoinhibited conformation of Src and directly triggering its allosteric activation. This structural evidence establishes βarr1 as an active regulatory protein rather than a passive scaffold and suggests a potentially general mechanism for βarr-mediated signaling across diverse effectors.

Combining multimodal fatigue fracture surface images for analysis with a CNN

Abstract This work uses three different modalities, namely SEM, BSE and scanning white light interference (SWLI) to image fatigue fracture surfaces of Ti-6Al-4V. Convolutional neural networks (CNNs) that were pre-trained on images of the natural world were used to predict values such as distance from load line and crack growth rate. SEM images are routinely used to study the topography of fracture surfaces because the shallower interaction volume resolves surface features while BSE images and SWLI data add information about composition and surface height. Combining the three imaging modalities via the use of color channels facilitates overlaying them on the same grid for transferability of models pre-trained on colored images. This work shows that the imaging modalities under the guise of color channels have different levels of importance depending on the model being trained. It also documents how the combination of information from these modalities improves the classification and regression results by 20 and 60 %, respectively, relative to the secondary electron images alone. (162/200).

Coherent microwave comb generation via the Josephson effect

Abstract Frequency combs represent exceptionally precise measurement tools due to the coherence of their spectral lines. While optical frequency comb sources constitute a well-established technology, superconducting circuits provide a relatively unexplored on-chip platform for low-dissipation comb emitters able to span from gigahertz to terahertz frequencies. We demonstrate coherent microwave frequency comb generation by leveraging the ac Josephson effect in a superconducting quantum interference device. A time-dependent magnetic drive periodically generates voltage pulses, which in the frequency domain correspond to a comb with dozens of spectral modes here reported up to mode 46. The emitted power at the device level ranges from −170 dBm to −130 dBm per harmonic, corresponding to 40 dB dynamic range in the 4-8 GHz bandwidth. The micrometer-scale footprint and minimal dissipation inherent to superconducting systems foster the integration of our comb generator with advanced cryogenic electronics. Transferring optical techniques to the solid-state domain may enable new applications in quantum technologies.

Rapid test for detecting red–green color vision deficiencies using a neural network-assisted color-naming task

COMPASS subunit Bre2 regulates chromatin remodeler Arp9 to control Aspergillus flavus aflatoxin synthesis and virulence

Abstract Aspergillus flavus , along with its notorious secondary metabolite aflatoxin B1 ( AFB1), seriously endangers human health. Histone methyltransferase complex COMPASS (complex of proteins associated with Set1) plays a crucial role in regulating aflatoxin biosynthesis and virulence of A. flavus , but the underlying mechanism is unclear. Here, we find that Bre2, the key subunit of COMPASS, regulates AFB1 biosynthesis, fungal morphogenesis, and virulence through modulation of H3K4 methylation. ChIP-seq and biochemical analyses reveal that chromatin remodeling factor (CRF) Arp9 is directly targeted by Bre2, and Arp9 exerts bio-functions through interacting with the other CRFs such as RSC8, Arp7, and Sth1. ATAC-seq results indicate that Arp9 contributes to fungal pathogenicity by modulating chromatin conformation of genes that are involved in secondary metabolism, morphogenesis, and virulence. The study reveals an epigenetic signaling pathway mediated by chromatin remodeler Arp9 and provides a potential strategy for the control of pathogenic fungi and mycotoxins.

Lay beliefs about the badness, likelihood, and importance of human extinction

Abstract Human extinction would mean the end of humanity’s achievements, culture, and future potential. According to some ethical views, this would be a terrible outcome for humanity. But what are the public’s beliefs about human extinction? And how much do people prioritize preventing extinction over other societal issues? Across five empirical studies ( N  = 2,147; U.S. and China), we find that people consider extinction prevention a societal priority and deserving of greatly increased societal resources. However, despite estimating the likelihood of human extinction to be 5% this century, people believe that the chances would need to be around 30% for it to be the very highest priority (U.S. medians). In line with this, people consider extinction prevention to be only one among several important societal issues. We also find that people’s judgments about the relative importance of extinction prevention appear relatively fixed and hard to change by reason-based interventions.

Antibody waning and Bordetella pertussis resurgence after the COVID-19 pandemic in the Netherlands

An integrated multidimensional risk framework for volcanic hazard zones: insights from Mt. Vesuvius, Italy

Computing-in-memory architecture for Kolmogorov-Arnold networks based on tunable Gaussian-like memory cells

Abstract Inspired by the Kolmogorov-Arnold representation theorem, the Kolmogorov-Arnold networks serve as promising alternatives to multilayer perceptrons. Kolmogorov-Arnold networks utilize a superposition of finite basis functions to implement variable continuous univariate activation functions, offering greater flexibility and adaptability. However, the hardware implementation of its basis functions remains costly, making it challenging to achieve complex computations with minimal equipment. Here, we designed the device defined as Gaussian-like memory cell, composed of a Gaussian transistor and a memristor, to ensure the tunable Gaussian-like current-voltage responses. Furthermore, we constructed the circuits based on Gaussian-like memory cells to accommodate the parallel inference computation of Kolmogorov-Arnold networks. This study demonstrates that the proposed architecture based on Gaussian-like memory cells can effectively maintain the algorithmic advantages across various tasks including one-dimensional function regression, image recognition, partial differential equation solving, and time-series forecasting. Notably, the proposed architecture achieves significant improvements in energy efficiency. The results provide a promising avenue for computing-in-memory architecture for Kolmogorov-Arnold networks, and expand the flexibility and efficiency of the neuromorphic computing paradigm.

Separation of large droplets from an oil-in-water emulsion using a deterministic lateral displacement (DLD) microfluidic chip

Precision engineering chiral interfaces for efficient spin injection in metal halide heterostructures

Phosphoglycerate dehydrogenase-mediated serine reprogramming aggravates macrophage hyperinflammation in murine Pseudomonas aeruginosa pneumonia

Stress pinch points from glacial loading modulate magma ascent and storage in continental arcs

Five ways increased militarization could change scientific careers

Competing hydrogen-bond orders drive water’s anomalous surface tension

Correlative molecular-to-mesoscale evolution in conjugated polymers for intrinsically stretchable organic photovoltaics

Abstract Conjugated polymer thin films offer a unique combination of tunable optoelectronic properties and mechanical flexibility, making them as promising materials for intrinsically stretchable optoelectronic devices. However, achieving both mechanical robustness and high device performance remains a key challenge. Addressing this requires a fundamental understanding of how molecular and mesoscale structures evolve under mechanical strain. Here, we employ a comprehensive suite of X-ray spectroscopy and scattering techniques to investigate the multiscale structural evolution of conjugated polymer thin films during uniaxial deformation. We uncover a two-stage morphological response: an initial stage characterized by polymer chain alignment and rapid crystallite disruption, followed by continued chain orientation accompanied by intrachain torsion at higher strains. These correlative structural adaptations govern key material properties, including stress dissipation, optical absorption, and photovoltaic performance. Our findings establish a mechanistic framework for understanding deformation in semiconducting polymers and provide design principles for developing mechanically robust, high-performance stretchable electronics.

Cross-domain metabolic interactions link Methanobrevibacter smithii to colorectal cancer microbial ecosystems

Abstract The human gut is colonized by trillions of microbes that influence the health of their human host. Whereas many bacterial species have now been linked to a variety of different diseases, the involvement of Archaea, an evolutionarily distinct group of microbes, in human disease remains elusive. By analyzing 19 independent clinical studies, we demonstrate that associations between Archaea and human diseases are widespread yet highly heterogeneous, with a pronounced and consistent enrichment of Methanobrevibacter smithii in colorectal cancer (CRC) patients. Metabolic modelling and in vitro co-culture identified distinct mutualistic interactions of M. smithii with CRC-causing bacteria such as Fusobacterium nucleatum , including metabolic enhancement. Metabolomics further reveal archaeal-derived compounds with tumor-modulating properties. Together, our results provide mechanistic insights into how the human gut archaeome may participate in CRC-associated microbial networks through metabolic cooperation with bacteria.

Briefing Chat: How hovering bumblebees keep their cool

A nutrient bottleneck controls antibiotic efficacy in structured bacterial populations

Abstract Antibiotic resistance is a growing global health threat. Although antibiotic activity is well studied in homogeneous liquid cultures, many infections are caused by spatially structured multicellular populations where consumption of scarce nutrients establishes strong spatial variations in their abundance. These nutrient variations have long been hypothesized to help bacterial populations tolerate antibiotics, since liquid culture studies link antibiotic tolerance to metabolic activity, and thus, local nutrient availability. Here, we test this hypothesis by visualizing cell death in structured Escherichia coli populations exposed to select nutrients and antibiotics. We find that nutrient availability acts as a bottleneck to antibiotic killing, causing death to propagate through the population as a traveling front. By integrating our measurements with biophysical theory and simulations, we establish quantitative principles that explain how collective nutrient consumption can limit the progression of this “death front,” protecting a population from a nominally deadly antibiotic dose. While increasing nutrient supply can overcome this bottleneck, in some cases, excess nutrient unexpectedly promotes the regrowth of resistant cells. Altogether, this work provides a key step toward predicting and controlling antibiotic treatment of spatially structured bacterial populations, yielding biophysical insights into collective behavior and guiding strategies for effective antibiotic stewardship.

Sensory coding of borneol repellency in culicine mosquitoes via the Or49 pathway