Browse Articles

Spatial scale of indentation explains shift in ratio between spinal cord gray and white matter stiffness

Abstract The structural integrity of spinal cord tissue and the transmission of mechanical stimuli across the different levels of tissue microarchitecture and varying spatial scales of mechanical loading challenge experimental and computational efforts to accurately model, simulate and interpret tissue mechanics, leading to conflicting findings in existing literature. Here, we demonstrate that the bead size used in spherical indentation tests significantly affects the stiffness ratio of spinal cord gray to white matter, a dependence which we only observe on the transverse plane and not the coronal plane of the tissue. Our study reveals a shift in stiffness ratio such that for smaller spherical indenters gray matter is stiffer than white matter, while for larger indenters, white matter is stiffer than gray matter. The mean relative change from the 100  $$\upmu$$ m bead to the 500  $$\upmu$$ m bead differed between anatomical planes, with transverse sections showing a decrease in gray matter ( $$-13.3\%$$ ) and an increase in white matter stiffness ( $$+26.9\%$$ ), accompanied by a reduction in the gray-to-white matter stiffness ratio from 1.07 to 0.76, whereas coronal sections exhibited increases in both gray ( $$+21.0\%$$ ) and white matter ( $$+33.8\%$$ ), along with a change in the ratio from 0.99 to 1.14. These findings contribute to explaining previously contradictory results in the literature and underscore the relevance of spatial scales in mechanical characterization studies.

Room-temperature multistage metastability in a moiré superstructure

Abstract Charge density waves (CDWs) offer versatile platforms for accessing metastable states due to their sensitivity to external stimuli. However, most metastable CDW states are stabilized only at low temperatures, limiting their practical utility. In this study, we report the observation of electrically driven, room-temperature, nonvolatile metastable states in the bulk form of EuTe 4 , a recently discovered compound that hosts an innate moiré superlattice characterized by the stacking of incommensurate monolayer and bilayer CDWs. Systematic transport measurements reveal discrete resistivity plateaus and strong electric-field sensitivity, with a large number of metastable states readily induced across a wide temperature window within a giant hysteresis loop, making them well-suited for high-temperature, multi-bit memory applications. By integrating photoemission spectroscopy, diffraction, and in-situ transport measurements, we uncover that these metastable states are characterized by a suppression of the original CDW amplitude and a reduction in correlation length, pointing to a unique electric-field-induced switching of out-of-plane CDW phases in the moiré superstructure. Our findings provide critical insights into metastable phenomena in moiré systems with stacked electronic orders and establish EuTe 4 as a promising platform for developing room-temperature, multi-bit memory devices.

NF1 and SPRED1/2 cooperate through RAS-MAPK-independent functions

Neurofibromin, the protein product of the neurofibromatosis type 1 ( NF1 ) gene, requires the direct binding interaction with SPRED to negatively regulate the RAS-MAPK pathway. Although the region of neurofibromin that stimulates the intrinsic GTPase activity of RAS represents only a small percentage of the entire protein, a large degree of the NF1 structural domains and their correlating mechanistic functions remain elusive. Here, we demonstrate RAS-independent biochemical and signaling functions regulated by the coordinate control of NF1 and SPRED1/2. Utilizing CRISPR-Cas9 methods to ablate NF1 or SPRED1/2 in isogenic “RASless” mouse embryonic fibroblast (MEF) cell lines expressing either the KRAS4b wild-type variant or an oncogenic KRAS -mutation, we show loss of SPRED1/2 phenocopies NF1 loss and their cooperation is required to modulate MAPK-AKT signaling. Moreover, NF1 or SPRED1/2 loss also resulted in a potent suppression of the RAS family GTPases, RRAS and RRAS2, occurring independently of RAS or AKT pathway activation. A transcriptome microarray analysis of the NF1 or SPRED1/2 knockout MEF cells revealed a specific subset of RAS-independent, NF1–SPRED1/2-dependent gene signatures, in which these same genes were also directly regulated by the RAS-GTPase function of neurofibromin. The modulation of these NF1–SPRED1/2-dependent downstream signaling effectors were further corroborated in Schwann cell models derived from Neurofibromatosis type I patients that consisted of either plexiform neurofibroma cells or unaffected nerve cells abrogated of NF1 or neurofibromin RAS-GAP activity. Taken together, this study provides RAS-independent functions that are dependent on the cooperation of NF1 and SPRED1/2 in a manner that is uncoupled from canonical MAPK signaling.

Multi-phantom SAR-assessed ultra-compact dual-band millimeter-wave (mmWave) antenna optimised for 5G smartphones

This paper presents an ultra-compact millimetre-wave antenna designed to support 28 GHz and 38 GHz 5G smartphone applications. To ensure safe and reliable integration, a comprehensive specific absorption rate (SAR) evaluation was carried out using three anatomically realistic head phantoms: a full-head, a skeletal skull, and an isolated brain model. The fabricated prototype demonstrated robust dual-band performance with close agreement between simulated and measured results. Importantly, SAR levels remained well below international safety limits, confirming both compliance and user safety. These results highlight the antenna’s strong potential for enabling next-generation high-data-rate communications in compact mobile devices.

Characterization and antimicrobial assessment of phytogenic synthesized selenium nanoparticles using leaf extract of Abies spectabilis (D. Don) Spach

Learned statistical regularity modulates anticipatory micro-saccades toward suppressed distractor locations

Force loading on molecular clutches governs the stability of cell lamellipodia

Cells use lamellipodia, thin actin-rich membrane protrusions, to probe the mechanical properties of their microenvironment. During mechanosensing, lamellipodia often exhibit dynamic instability in the form of protrusion-retraction cycles. However, how this mechanical instability arises during mechanotransduction remains poorly understood. Here, we develop a minimal mechanochemical model for lamellipodial dynamics that integrates membrane deformation, myosin contractility, and binding kinetics of adhesion molecules (molecular clutches). Through stochastic simulations and analytical mean-field analysis, we demonstrate that both loading rate and force magnitude applied by myosin-driven retrograde flow control the clutch binding kinetics, governing lamellipodial stability and cellular mechanosensing. Specifically, a slow loading rate promotes sustained clutch engagement and traction buildup, while a high force magnitude ruptures bound clutches. Their temporal interplay gives rise to protrusion-retraction cycles in lamellipodia. Furthermore, the model predicts a biphasic response to myosin perturbation, consistent with quantitative experimental observations. Overall, the theoretical model highlights force loading as the key mechanical input driving lamellipodial instability and cellular mechanosensing, advancing our understanding of mechanotransduction during cell spreading.

A Rras2–BMPR2 feedback loop sustains osteogenesis and represents a therapeutic target for osteoporosis

An engineered closed-shell, two-component, 480-subunit nucleocapsid

Self-assembling protein cages are valuable nanoscale containers for biotechnology and medical applications. Two-component systems are especially attractive due to their potential for functional complexity. In this study, we demonstrate that the subunits of the 240-subunit nucleocapsid NC-4, which was previously evolved to package and protect its encoding mRNA, can be split into two fragments without disrupting cage assembly or structure, generating a two-component, 480-subunit capsid. This modification introduces additional termini on the cage’s exterior surface, creating opportunities for functionalization. We exploited these new sites by genetically appending peptide and protein tags to the exterior surface of split NC-4 (spNC-4), enabling site-specific glycosylation via posttranslational modification and cell-specific delivery by targeted antibody recruitment. Our findings broaden the utility of the NC-4 nucleocapsid. By extension, splitting related protein compartments that bind diverse cargoes could offer a robust platform for biotechnological applications requiring simultaneous encapsulation and customizable surface modification.

Generative modelling of inorganic materials with explicit electronic structure

Flipping plankton

Sudden, global reversals in shell coiling direction are a striking and recurrent feature in the fossil record of planktonic foraminifera (marine zooplankton), yet their evolutionary significance has been a mystery. Because coiling direction is a simple, binary character, such shifts have often been interpreted as environmentally induced phenotypic responses rather than indicators of evolutionary change, although it is increasingly evident that genetic variants can have different coiling preferences. Here, we synthesize recent evidence from multiple case studies spanning the Eocene to the Recent (the last 56 Mya). Coiling flips occur on timescales of thousands of years or less, across diverse taxa and ocean basins, far too abruptly to be explained by gradual trait evolution. Instead, these rapid, synchronous coiling reversals may signal cryptic speciation and episodic population sweeps, associated with distinct habitat preferences and water mass distributions. In most cases such replacements would leave little trace in the fossil record, but when competing groups differ in coiling preference, a dramatic and geologically abrupt coiling reversal becomes visible. These findings challenge the assumption that reproductive isolation alone delimits species in planktonic foraminifera and instead supports a model of ecological speciation mediated by habitat partitioning in the open ocean. Shell coiling direction thus serves not as an adaptive trait, but as a fortuitous marker of hidden evolutionary dynamics shaping marine microplankton diversity.

Tailoring polymers of intrinsic microporosity as photoredox catalysts for continuous-flow reaction–separation processes

Ultraslow conformational dynamics and catch bond formation of a bacterial adhesin revealed by a single-domain variant of FimH

Bacterial fimbrial adhesins such as FimH are critical for host colonization and persistence under the mechanical forces encountered at sites of infection such as the urinary tract. The molecular mechanisms by which FimH, a key virulence factor of uropathogenic Escherichia coli , regulates its binding to host cell surface mannose moieties through conformational switching remain incompletely understood. FimH operates across a range of conformations that includes low- (LAS), intermediate-, and high-affinity (HAS) states and forms catch bonds that paradoxically strengthen under force. The allosteric pathways governing these transitions remain poorly defined due to experimental limitations that restrict understanding of key dynamic phenomena that underlie ligand-triggered conformational shifts and force-induced long-lived interactions. Such understanding is central to drug discovery efforts to target bacterial adhesion. Here, we present a model system that fully recapitulates the conformational repertoire of FimH in the absence of its pilin domain. Our findings demonstrate that a single mutation in the lectin domain stabilizes the LAS while allowing for ligand-binding-induced transition to a HAS-like conformation and catch bond formation, mirroring the behavior of the native FimH adhesin. We propose a dynamic allosteric mechanism that involves ultraslow, low-frequency dynamics for the ability of FimH to sustain long-lived interactions with mannose, under both static and force conditions.

HPV16 genetic variation provides evidence of positive natural selection driven by HLA class I

Abstract Human papillomavirus type 16 (HPV16) causes more cancer than any other virus. However, most HPV16 infections are controlled by the host’s immune system and it remains unclear how viral and host genetic variation contribute to infection outcomes. Here, we analyze 4704 HPV16 whole genomes to identify 56 viral codons putatively under positive natural selection to change their amino acids, with evidence including d N / d S  > 1, evolutionary convergence, and structural importance in the protein. We find that codons under positive selection disproportionately overlap known HPV16 immune epitopes recognized by cytotoxic T lymphocytes, particularly those restricted by the previously reported risk allele HLA-B*07:02 (odds ratio [OR] = 4.9; 95%CI = 2.1–10.3; P Fisher  = 0.00015), exemplified by position 10 of the E6 oncoprotein. Positively selected codons also disproportionately overlap 158 nucleotide sites at which the evolutionary sub/lineages of HPV16 have diverged (OR = 19.1; 95%CI = 10.5–34.7; P Fisher  < 2.2×10 −16 ), and show more rare variation in cervical precancers/cancers than controls (benign or cleared HPV16 infections) in the E1 protein (OR = 9.34, 95%CI = 1.4–402.5; P Fisher  = 0.0084). Our results suggest that a small subset of HPV16 variants can improve viral persistence through escape of HLA-related immune recognition. The interaction of HPV16 and HLA variation may help to explain how similar or identical viral isolates can have such disparate infection outcomes.

Evolution induced state shifts in a long-term microbial community experiment

Biological communities are complex, dynamic systems that underpin ecosystem functionality, yet their long-term dynamics and predictability remain poorly understood. Understanding how Darwinian evolution shapes these systems through eco-evolutionary feedback is a central challenge in ecology and evolution. Experimental studies using simplified microbial assemblages have yielded important insights into the ecological principles governing community states. However, an important knowledge gap is how selection within member species drives changes of community state in multispecies systems. Here, we present a four-year evolution experiment involving a 23-species synthetic bacterial community propagated in two environments: a control medium and the same medium supplemented with the antibiotic streptomycin. Through combined analyses of community composition and genome evolution, we quantified the temporal changes in species abundances and the evolutionary trajectories of individual community members. The extended duration of the experiment enabled the detection of adaptive mutations and community state shifts that occur only over long evolutionary timescales. We show that community dynamics are environment dependent and reproducible across replicates and that evolution of streptomycin resistance in a previously streptomycin-sensitive species on its own can induce abrupt community state shifts. Our results provide a direct demonstration of eco-evolutionary feedbacks within a multispecies community, revealing how a single adaptive mutation can reorganize complex ecological networks.

An agent-based platform for simulating the impact of chlamydia vaccine in the US population

Tuning mitotic recombination with patterned DNA nicks for precision mosaic analysis

CRISPR/Cas9-based mosaic analysis is a powerful tool for in vivo genetics but is limited by cytotoxicity and mutagenesis associated with DNA double-strand breaks. Here, we establish Cas9-derived nickases as safer and more reliable alternatives for inducing mitotic recombination in Drosophila . We demonstrate that single-strand nicks are sufficient to generate mosaic clones and systematically dissect the parameters governing this process. We find that clone frequency can be controlled by the gRNA nicking pattern, with two distant nicks on the same DNA strand synergistically enhancing recombination by over ninefold compared to a single nick. Based on these findings, we propose a mechanistic model for nick-induced crossover and provide a versatile toolkit for generating tissue-specific nickases. This work establishes nickase-based mosaic analysis by gRNA-induced crossing-over as a superior method for high-fidelity clonal analysis, enabling more precise investigation of gene function in development and disease.

Competing structural orders frustrate crystallization in a metallic glass

Peer influence on West Point cadets’ Civil War allegiances

Do social networks and peer influence shape major life decisions in polarized settings? We explore this question by examining how peers influenced the allegiances of West Point cadets during the American Civil War. Leveraging quasi-random variations in the proportion of cadets from Free States, we analyze how cadets’ decisions about which army to join depended on the composition of their peers. We have three main findings. First, there was a strong and significant peer effect: a higher proportion of classmates from Free States significantly increased the likelihood that cadets from Slave States joined the Union Army. Second, the peer effect varies with geography, most notably with the slave population share in cadets’ home states or counties, and with cadets’ own slave ownership in 1860. Third, peer effects were amplified by shared experiences such as having served together in the Mexican-American War, continuous military service, and belonging to the same cohort, suggesting that sustained interaction is important.

An intelligent feedback loop for sustaining self-lubrication and wear resistance

Abstract Intelligent materials that self-sense and self-adjust are an emerging frontier in sustainable technology. Here we introduce a Cu/C nanocomposite film that acts as a self-adjusting intelligent lubricant. In this film, frictional heating triggers melting and migration of Cu nanoparticles along nanopores to the friction interface, where the Cu catalyzes the in-situ formation of ordered carbon nanostructures. Real-time monitoring of friction coefficient ( μ ), electrical resistance ( R ), and metal release confirms a feedback loop: high friction generates enough heat, melting the metal nanoparticles; the migrating metal then lowers friction by creating low-friction nanostructures, which reduces heat and arrests further migration until friction rises again. This self-limiting feedback enables stable ultra-low friction ( μ  ~ 0.04) and an exceptional wear life (>40 km) even in high vacuum. By utilizing friction-derived heat as an intrinsic activation signal, our system establishes a general paradigm for intelligent, self-adjusting materials with applications extending beyond tribology.