Browse Articles

Socio-technical determinants of explainable artificial intelligence for infrastructure decision support

Phosphatidylinositol diphosphate binding by ESCRT-III filaments

Different inositol phospholipids (PIPs) distribute to distinct subcellular organelles, creating an addressing system that dictates the sites of action of PIP-binding proteins, including components of the Endosomal Sorting Complexes Required for Transport (ESCRT). The ESCRT machinery is recruited to remodel many different cellular membranes through combinatorial binding interactions made by the early-acting ESCRT-I and ESCRT-II complexes with PIPs, ubiquitin modifications, and membrane-specific adaptors. Membrane remodeling, constriction, and fission are then mediated by membrane-associated filaments formed by subunits of the late-acting ESCRT-III complexes, together with their associated VPS4 AAA ATPases. Here, we describe two different classes of helical ESCRT-III filaments that can surround and tubulate membranes containing PIP 2 lipids. Cryo-EM reconstructions revealed that protofilaments comprising closed IST1 subunits formed 8-stranded nanotubes that encase membrane monolayers. The nanotube coordinates exposed PI(4,5)P 2 or PI(3,5)P 2 headgroups within a basic pocket formed at the junction of three IST1 subunits, and our structures reveal how the pocket can accommodate either PIP 2 isomer with minimal adjustment. In contrast, protofilaments comprising open CHMP1A subunits formed one start helices that encase membrane bilayers and bind exposed PI(4,5)P 2 headgroups across a basic surface that spans adjacent subunits of the CHMP1A protofilament. These two different structures extend the known plasticity of ESCRT-III polymers, reveal how PIP 2 lipids can promote ESCRT-III filament assembly and membrane remodeling, and define the molecular contacts that underlie specific ESCRT-III/PIP 2 interactions.

Buried soils from the Holocene Humid Period in Wadi Shuwayhi, Al-Khashbah (Oman)

Abstract The paleosol horizons on the lower terrace of Wadi Shuwayhi are the first buried soils from the Holocene Humid Period in Central Oman have been studied; they occur in alluvial sediments (terrace fill) deposited approximately 11.5 to 7 ka, with radiocarbon ages of soil organic matter range from 10,600 to 5300 cal BP (8700–3500 cal BC). The youngest buried soil horizon in profile KS3 show disturbances in soil structure, consistent with Early Bronze Age cultivation at 4800–4400 cal BP (2800–2500 cal BC). Pedogenic features in the buried A and B horizons of all paleosols show subangular blocky or crumb macro- and microstructure, bioturbation features, and secondary calcification within root channels. In two soils, tabular and lenticular gypsum is particularly pronounced. Although the organic carbon content is low at all sites, soil formation suggests earlier vegetation establishment during the Early Holocene as is also known from other arid areas. Alternating phases of alluvial aggradation and lateral erosion, i.e. stability and instability of the wadi terraces, are reflected in the preserved, albeit relic paleosol horizons. The study describes and classifies the buried soils, place them within a stratigraphic framework, and evaluates their significance as proxies of the Holocene Humid Period as well as early human–environment interactions in Southern Arabia.

Female reproductive dysfunction and transgenerational consequences following prolonged spaceflight exposure

Spaceflight presents unique gravitational, radiation, and isolation hazards for human exploration of the Moon, Mars, and beyond, yet its impact on the female reproductive system and successive generations has been largely unassessed. In the NASA Rodent Research 20 mission, we examined the impact of a 42-d spaceflight on the female reproductive axis including ovulatory capacity, implantation rate, and fecundity as well as behavioral, metabolic, and functional outcomes in F1 and F2 offspring. Females bred 5 d after return to Earth became pregnant but only exhibited a slight decline in fecundity compared to ground controls. In contrast, F1 offspring from spaceflight dams exhibited marked growth, functional, and behavioral differences compared to F1 offspring from control dams. Moreover, F1 female offspring from spaceflight dams exhibited decreased ovarian reserves as evidenced by reduced anti-Mullerian hormone levels early in life (21 d of age) and premature ovarian failure or an early loss in fertility, as indicated by reduced numbers of litters and total number of pups born to females over a 9-mo period. Strikingly, transgenerational metabolic and reproductive disturbances were also observed in F2 pups of spaceflight granddams, including persistent reductions in ovarian reserve, suggesting germline-level effects. Together these findings reveal significant short- and long-term impacts of spaceflight on the female reproductive system and on their offspring across generations, demonstrating biological transmission of reproductive vulnerability following maternal spaceflight exposure, and raising concerns for space travelers and colonization missions.

Impact evaluation of labor force transfer motivation identification in forest areas based on fuzzy control algorithm

The centrosomal hub unifies regulatory factors of NLRP3 inflammasome activation

The NLRP3 inflammasome is central to host defense and sterile inflammation and forms condensates at the microtubule-organizing center (also known as the centrosome), although the mechanisms regulating this process remain unclear. Here we define a functional relationship among microtubule transport, the centrosomal kinase NEK7, priming, and NLRP3 abundance. We show that microtubule-dependent transport is required for NEK7-dependent NLRP3 activation and promotes NEK7 to the pericentriolar material (PCM). Microtubules, priming, and NEK7 synergistically converge on PCM abundance, thereby creating a permissive centrosomal environment for NLRP3 condensation and inflammasome assembly. Elevated NLRP3 expression compensates for limited PCM abundance, rendering K + efflux-induced activation independent of both NEK7 and priming in human and mouse macrophages. By contrast, NLRP3 overexpression only partially bypasses NEK7 dependence in response to the K + efflux-independent stimulus imiquimod, likely due to its activation of a non-trans-Golgi network pool of NLRP3 that is quantitatively limited. Together, these findings define a conserved spatial mechanism in which microtubule transport, NEK7 localization, priming, and NLRP3 abundance integrate at the PCM to establish the activation threshold and magnitude of NLRP3 inflammasome signaling across species and stimuli.

Repairing Atp10D in C57Bl/6J mice restores protein expression but does not mitigate metabolic stress from high fat diet

Single-shot wide-field biochemical imaging at 1 kHz frame rate

Vibrational microspectroscopy, including both Raman-based and infrared-based techniques, can map the chemical distribution of samples based on molecular vibrations without labeling. However, imaging fast dynamics in living organisms remains challenging. To address this, we propose a wide-field infrared microspectroscopy capable of single-shot imaging, where each image is captured with a single pair of laser pulses lasting approximately one picosecond. It minimizes motion blur and allows observing fast dynamic processes at frame rates up to the laser repetition rate. This approach is based on the infrared-resonant third-order sum-frequency process, which converts infrared light to visible signals. We demonstrate the capability through single-shot in vivo imaging of alive Caenorhabditis elegans worms in water, achieving a spatial resolution of approximately 400 nm. Additionally, 1,000 Hz single-shot videos of moving worms are shown by using a kHz laser system. This approach opens more possibilities for imaging chemicals involved in fast dynamic processes, offering diverse applications in both chemistry and biology.

Differential effects of plyometric training loads on jump and sprint performance reveal optimal strategies

Lhcf2 in the peripheral antenna is essential for nonphotochemical quenching and Lhcx1 accumulation in the diatom <i>Chaetoceros gracilis</i>

Photosynthetic organisms must continuously balance efficient light harvesting with protection against excess excitation energy, a challenge met by nonphotochemical quenching (NPQ). Although the molecular components involved in NPQ have been extensively studied, how the essential energy-quenching site is assembled remains poorly understood, particularly in marine diatoms. Here, we show that in the centric diatom Chaetoceros gracilis , which belongs to one of the most abundant and diverse genera in marine phytoplankton, the light-harvesting complex (LHC) protein Lhcf2 is required for energy-dependent quenching (qE). Targeted knockout of Lhcf2 abolished qE by preventing the stable accumulation of Lhcx1, a core component of the NPQ effectors in this species. Lhcf2 localizes to the peripheral antenna system and associates with Lhcx1 in a higher-order complex suggested by biochemical and functional analyses. In contrast, other established NPQ-related factors, including the trans-thylakoid proton gradient and the accumulation of diatoxanthin, were not affected by the loss of Lhcf2. These results identify a non-Lhcx-type LHC protein as an essential structural component for qE-NPQ and establish a general design principle for the cooperative assembly of photoprotective energy-quenching sites in eukaryotic photosynthesis, with implications for marine carbon fixation.

A baseline-oriented dynamic aggregation approach for demand-side heterogeneous controllable resources

Monitoring major biodiversity stronghold in war zones: Model predicts Lake Chad remains Africa’s most important wetland for waterbirds

Lake Chad is both one of the largest transboundary wetlands in Africa and a major biodiversity hotspot. As such, Lake Chad would require sound and long-term biodiversity monitoring, but it is also a war zone. Using several mitigation measures, we succeeded in surveying a major part of it in 2022 to estimate the abundance of wildlife. This study marked the first comprehensive population estimates for some species. Compared to previous total count approaches, we introduced an aerial distance sampling methodology to improve survey safety, repeatability, estimate uncertainty, and reduce detection bias. Due to strong security concerns, a portion of the lake was inaccessible. To overcome this limitation and estimate temporal trends, density surface modeling was applied to estimate species abundance over the entire lake. Locations of conflict events emerged as sites of higher densities for several species, suggesting a “refuge effect,” a rare positive outcome of conflict zones on wildlife. Indeed, we also noted the persistence of endangered large mammal populations, possibly due to reduced anthropogenic pressure from displaced communities. Results indicated that Lake Chad hosts approximately 2.48 million waterbirds, to our knowledge the most important known wetland bird concentration in Africa. Updated population estimates revealed that some species may have experienced positive trends. However, a few species, including transcontinental ones, showed signs of reduced abundance. The study urges actions to protect this ecosystem of major importance for global biodiversity, recommending the establishment of a protected area and World Heritage status for Lake Chad.

Prefrontal EEG spectral and nonlinear signatures of subthreshold depression during resting state and affectively valenced picture/video viewing: a participant-level analysis

Force-responsive symmetric cell divisions orient stomata along global tissue axes

Stomata, microscopic pores that regulate gas exchange in plants, are patterned according to conserved pathways that regulate their physiology. Here, we identify a mode of stomatal patterning that depends on previously unrecognized regulation of the final symmetric cell division (SCD) that creates paired guard cells. SCDs are aligned by tensile stress at both the subcellular and supracellular scales, creating a globally polarized stomatal field that tracks the major axes of tissue growth. By identifying KATANIN 1 as a critical regulator of symmetric division orientation, we show that stress-based division orientation is required to prepattern stomatal morphology and pore creation. We find that expansion of neighboring cells nonautonomously controls symmetric division orientation, linking stomatal alignment to overall leaf shape. Finally, we show that polarized stomatal fields are widespread across plant genera and their species-specific alignment patterns are consistent with the force-based mechanism we identify in Arabidopsis . This force-responsive pathway provides a unifying model that explains long-standing observations of stomatal organization across species.

Effect of control frequency on closed-loop electrical muscle stimulation for biceps–triceps in healthy participants: a pilot study

Abstract The bandwidth of voluntary upper-limb movement is constrained by the inherent transmission and processing delays of the central nervous system (CNS). While spinal reflexes exhibit shorter latencies, the maximum achievable closed-loop control bandwidth of the musculoskeletal system remains poorly defined. We address this by introducing a high-speed closed-loop electrical muscle stimulation (EMS) system. By integrating high-speed machine vision with antagonistic stimulation of the biceps and triceps via a fuzzy logic controller, this platform enables closed-loop elbow joint actuation that bypasses voluntary CNS pathways to probe the fundamental limits of neuromuscular response. In this study, the feedback control frequency was synchronized with the electrical stimulation frequency. We evaluated the system using a dynamic target-tracking task (sinusoidal reference target with $$12^\circ$$ amplitude and frequency from 0.2 to 0.4 Hz) involving six healthy participants across four feedback and stimulation frequencies (10, 33, 100, and 333 Hz). Performance was quantified using Dynamic Target Tracking Accuracy (DTTA-MAE) and a Neural Biceps–Triceps Response model’s mapping accuracy (NBTR-MAE). Our results show that both metrics improve with increasing feedback frequency. However, tracking accuracy (DTTA-MAE) exhibits no further improvement at 333 Hz compared to 100 Hz, whereas the mapping accuracy of the neural response model (NBTR-MAE) continues to improve up to 333 Hz. These findings suggest that the human neuromuscular system may adapt to and benefit from high-frequency feedback control far exceeding the rates of natural voluntary movement, providing critical insights for future applications of functional electrical stimulation (FES) systems.

Three-stage melting of a macroscopic continuous spacetime crystal

A spacetime crystal is a phase of matter that spontaneously develops periodic order in both space and time. Spacetime crystals have been experimentally observed in microscopic quantum many-body systems and, very recently, in a mesoscopic nematic liquid crystal. However, the melting process of a spacetime crystal and its underlying physical mechanisms have not yet been experimentally reported. Here, we present a direct observation of a classical continuous spacetime crystal melting in a table-top experiment with macroscopic active granular disks in 2 + 1 spacetime dimensions. The spacetime crystal is characterized by the spontaneous formation of a coherent, rigid-body rotation of a 2D triangular lattice that persists for almost a day and remains remarkably robust to noise. By tuning the disk packing fraction, we observe a complex three-stage melting process involving a spatially hexatic phase and multiple coexistence regions. Importantly, we show that spatial and temporal crystalline orders melt separately through distinct mechanisms: Spatial order is destroyed by the proliferation of topological defects, while temporal order is lost through the decay of directional persistence caused by the progressive weakening of many-body interactions. Our results demonstrate that the spontaneous breaking of spatial and temporal translational symmetries can be decoupled, leading to the emergence of exotic out-of-equilibrium classical phases of matter.

Preimplantation genetic testing (PGT-M) awareness in BRCA-positive individuals in Türkiye: a dual physician–patient survey

Epigenetic regulation of mesenchymal BMP signaling directs postnatal organ innervation

Sensory innervation of developing organs is influenced by molecular cues secreted from surrounding tissues, yet the mechanisms coordinating this tissue–tissue communication are not well understood. Tooth innervation during root development provides a valuable model to investigate how local mesenchymal cues regulate axonal growth under physiological conditions, as innervation begins and progresses alongside tooth root formation. Here we identify the histone demethylase KDM6B, expressed in cranial neural crest-derived dental mesenchyme, as a critical extrinsic regulator of tooth sensory innervation. Loss of Kdm6b in dental mesenchyme severely impairs trigeminal axon entry and branching into the dental pulp, leading to tooth root development defects. Mechanistically, loss of Kdm6b reduces the expression of bone morphogenetic protein (BMP) pathway antagonist Bambi in the dental mesenchyme by modulating H3K27me3 chromatin marks, causing overactivation of BMP signaling, which then directly suppresses the expression of nerve growth factor ( Ngf ). Compromised NGF activity thereby diminishes mesenchymal support for sensory axon extension during tooth root development. Haploinsufficiency of Ezh2, which antagonizes Kdm6b , or Bmpr1a, a key BMP receptor, partially rescues Ngf expression, sensory innervation, and tooth root development defects in Kdm6b mutants. Together, these findings reveal that epigenetic regulation within mesenchymal cells governs sensory innervation during organogenesis, uncovering important regulatory mechanisms that may inform future strategies for restoring innervation in tissue regenerative approaches.

Reconstituting central nervous system niche cues partially restores homeostatic-like features in cultured murine primary microglia

Abstract Microglia rapidly lose their homeostatic phenotype after isolation, limiting the interpretability of in vitro studies. We systematically evaluated culture conditions that reconstitute central nervous system (CNS) niche inputs to better preserve microglial homeostatic features. Neonatal mouse microglia were isolated by fluorescence-activated cell sorting, Percoll gradients, or a shaking protocol and cultured with defined cytokines (TGF-β1, IL-34, CX3CL1), extracellular matrix (collagen IV), and metabolic support (cholesterol, insulin-transferrin-selenium) under serum-free or serum-containing conditions. RT-qPCR revealed rapid downregulation of seven homeostatic transcripts (Tmem119, P2ry12, Cx3cr1, Hexb, Fcrl2, Olfml3, Tgfbr1) within 24 h across isolation methods, with further decline for a subset over 7 days. A cytokine cocktail partially restored homeostatic gene expression, with collagen IV and cholesterol further enhancing selected transcripts. Serum-free conditions favored ramified, surveillant-like microglia, whereas serum promoted amoeboid, activated-like cells, and adding defined factors preserved ramification while improving transcriptional recovery. Transcriptomic analyses demonstrated that optimized conditions shifted global expression profiles toward neonatal ex vivo microglia, upregulated most microglia-specific homeostatic genes, and downregulated inflammatory effectors. These data define a scalable, serum-free, collagen IV-based culture system with defined CNS cues that partially preserves key aspects of microglial homeostatic transcriptional and morphological features compared with conventional serum-containing culture, providing more physiologically relevant conditions for mechanistic and disease-relevant studies.

People in more individualist cultures are more motivated to make others feel better

In many Western cultures, trying to make others feel better is considered critical for psychological health and social relationships. However, given that people think about emotions and relationships differently across cultures, the desirability, means, and benefits of making others feel better may also vary by culture. In two multicountry survey studies (Study 1: N = 3,154, 13 countries; Study 2: N = 3,503, 17 countries) and in a daily dairy study (Study 3: N = 243, 2 countries), we assessed motivation and strategies used for influencing others’ and one’s own emotions. To test whether potential cross-cultural differences in motivation and strategies in emotion regulation are unique to social interactions, we compared cultural differences in making others feel better to making oneself feel better. Across studies, cultural differences in influencing others’ emotions were greater than those in influencing one’s own emotions. Members of more individualist (vs. collectivist) cultures were more motivated to make others (but not themselves) feel better, were more likely to express care and less likely to encourage others to suppress their emotions or to ruminate. These patterns, in turn, were linked to an index of relationship closeness in an individualist (but not a collectivist) culture. These findings suggest that helping others feel better may not be equally desirable across cultures.