Browse Articles

Liver steatosis mediates the association between metabolic score for insulin resistance and obstructive sleep apnea

Reply to Loh and Ren: Motivating action among climate change believers

Correction: Alleviating head-mounted weight burden for neural imaging in freely-behaving rodents

Correction for Ninomiya and Isoda, Dynamic spatial representation of self and others’ actions in the macaque frontal cortex

RO8191, a new compound for initiating embryo implantation in mice

HLA-B*15:01-positive severe COVID-19 patients lack CD8 ⁺ T cell pools with highly expanded public clonotypes

Understanding host factors driving asymptomatic versus severe disease outcomes is of key importance if we are to control emerging and re-emerging viral infections. HLA-B*15:01 has been associated with asymptomatic SARS-CoV-2 infection in nonhospitalized individuals of European ancestry, with protective immunity attributed to preexisting cross-reactive CD8 + T-cells directed against HLA-B*15:01-restricted Spike-derived S 919-927 peptide (B15/S 919 + CD8 + T-cells). However, fundamental questions remained on the abundance and clonotypic nature of CD8 + T-cell responses in HLA-B*15:01-positive patients who succumbed to life-threatening COVID-19. Here, we analyzed B15/S 919 + CD8 + T-cell responses in COVID-19 patients from independent HLA-typed COVID-19 patient cohorts across three continents, Australia, Asia and Europe. We assessed B15/S 919 + CD8 + T-cells in COVID-19 patients across disease outcomes ranging from asymptomatic to hospitalized critical illness. We found that severe/critical COVID-19 patients mounted B15/S 919 + CD8 + T-cell responses lacking a highly expanded key public B15/S 919 + CD8 + T-cell receptor (TCR; TRAV9-2/TRBV7-2) which recurred across multiple individuals in COVID-19 patients with a mild disease. Instead, B15/S 919 + CD8 + T-cell responses in life-threatening disease had a prevalence of an alternate TCR clonotypic motif (TRAV38-2/DV8/TRBV20-1), potentially contributing, at least in part, to why B15/S 919 + CD8 + T-cells in severe COVID-19 patients were less protective. Interestingly, the frequency, memory phenotype, and activation profiles of circulating B15/S 919 + CD8 + T-cells did not differ across disease severity. Moreover, B15/S 919 + CD8 + T-cells were better maintained into convalescence compared to other SARS-CoV-2-specificities. Our study thus provides evidence on the differential nature of the TCR clonal repertoire in 22.37% of HLA-B*15:01-positive COVID-19 patients who developed severe or critical disease in our cohorts, comparing to HLA-B*15:01-expressing individuals with mild COVID-19.

A prediction nomogram for mild cognitive impairment in type 2 diabetes mellitus based on the Chinese visceral adiposity index

8,000 years of wild and domestic animal body size data reveal long-term synchrony and recent divergence due to intensified human impact

The long-term evolution of domestic mammal body size in Western Europe since the Early Neolithic is mainly attributed to human selection. However, the relative influence of environmental and anthropogenic factors in animal body size evolution, and the coevolution of wild and domestic species remain poorly understood. In the Northwestern Mediterranean, abundant archaeozoological data from well-contextualized sites and reliable paleoenvironmental reconstructions provide a unique opportunity to explore long-term morphological changes and their drivers over time. This study analyzes 81,211 biometric measurements from 311 archaeological sites in Mediterranean France, spanning the past 8,000 y. It examines body size evolution in key wild (red deer, red fox, brown hare, rabbit) and domestic (sheep, goat, cattle, pig, chicken) species alongside vegetation, climate, and human activity changes. Our analyses reveal a long-standing synchrony between wild and domestic species until the last millennium, both influenced by a complex interplay of environmental and anthropogenic factors. From the Early Neolithic to the Roman period, environmental conditions exerted comparable effects on wild and domestic species, though the magnitude and timing of changes varied, reflecting species-specific interactions with humans. From the Middle Ages onward, evolutionary trajectories diverged. Domestic species experienced intensified human selection, while human activities increasingly impacted wild populations and their habitat. These findings highlight the dynamic and interwoven roles of environmental and anthropogenic factors in shaping animal morphological evolution, emphasizing the importance of environmental factors in the evolution of domestic species, and illustrating the growing impact of human activities on wild populations.

Correction: Cell-specific expression biases in human cortex of genes associated with neurodevelopmental disorders

Vacuum tunneling of vortices in two-dimensional ⁴ He superfluid films

At low temperature T we expect vacuum tunneling processes to occur in superfluid 4 He films. We distinguish between extrinsic processes, in which single vortices nucleate by tunneling off boundaries in the system, and intrinsic processes, in which vortex/anti-vortex pairs nucleate far from boundaries. It is crucial to incorporate the varying effective mass of the vortex in tunneling calculations. The intrinsic processes are the superfluid analogue of the Schwinger mechanism in quantum field theory; here they appear as a quantum phase transition at T = 0, driven by an external supercurrent. We calculate the tunneling rate for these processes, and describe a means of testing the predictions using a specific “vortex counting” experiment.

Integrated acoustic identification of a petit-spot volcanic field in the oldest Pacific plate

Abstract Petit-spot volcanism plays a critical role in the metasomatism of oceanic plates prior to subduction and in their recycling into the deep mantle. The extent of metasomatism depends on the number and volume of petit-spot volcanic edifices and intrusions, making precise identification of petit-spot volcanic fields essential. However, conventional methods based on seafloor topography and acoustic backscatter intensity alone have limitations in accurately delineating these features. Here we compiled acoustic survey data obtained using subbottom profilers mounted on both research vessels and submersibles in the region southeast of Minamitorishima (Marcus) Island, the oldest part of the Pacific plate. Analysis of the subbottom profiler data revealed three main stratigraphic facies: O-type (opaque), T-type (transparent), and L-type (layered). Among these types, OL-type facies, characterized by low slope gradients and high backscatter intensity, indicate petit-spot lava flows. Additionally, M-type facies, marked by multiple discontinuous reflections, occur at boundaries between OL-type and other facies, representing transitional zones formed by intrusive activity. High-resolution acoustic stratigraphy and ground-truth observations from submersible dives confirmed that M-type facies reflect petit-spot lava intrusions. Integrating seafloor backscatter with subseafloor stratigraphy provides a robust and reliable method for delineating petit-spot volcanism and assessing its geological impact on the abyssal seafloor.

The RNA-binding protein TRIM71 is essential for hearing in humans and mice and times auditory sensory organ development

The RNA-binding protein TRIM71 is essential for brain development, and recent genetic studies in humans have identified TRIM71 as a risk gene for congenital hydrocephal-us (CH). Here, we show that monoallelic missense mutations in TRIM71 are associated with hearing loss (HL) and inner ear aplasia in humans. Utilizing conditional Trim71 knockout mice carrying a CH and HL-associated mutation, we demonstrate that loss of TRIM71 function during early otic development (embryonic day 9 to 10) causes severe HL. While inner ear morphogenesis occurs normally in Trim71 knockout mice, we find that early otic loss of TRIM71 function disrupts the highly stereotyped timing of cell cycle exit and differentiation within the inner ear auditory sensory organ (cochlea), resulting in the premature formation and innervation of mechanosensory hair cells. Transcriptomic profiling of Trim71 -deficient cochlear progenitor cells identifies Inhba and Tgfbr2 as targets of TRIM71 repression, and our analysis of Inhba-Tgfbr1 double knockout mice indicates that TRIM71 maintains hair cell progenitors in a proliferative and undifferentiated state by restricting TGFβ-type signaling. Characterization of hair cells and their associated neurons in adult Trim71 knockout mice revealed reduced presynaptic terminals and neuronal degeneration in the outer hair cell region, providing a basis for the observed hearing deficits in Trim71 knockout mice.

Retraction Note: Ulinastatin attenuates renal fibrosis by regulating AMPK/HIF-1α signaling pathway-mediated glycolysis

Identification of AMOTL2 as an antiviral factor that enhances the human type I interferon response against Zika virus

Zika virus (ZIKV) has caused multiple human outbreaks, with more recent epidemics associated with severe outcomes in infants. Today, ZIKV is endemic to many countries and presents a persistent threat for future epidemics. The host innate immune proteins that regulate ZIKV replication are incompletely defined. We developed a CRISPR knockout screen to identify host factors that impact ZIKV replication, resulting in the finding of angiomotin-like protein 2 (AMOTL2), a protein that inhibits ZIKV by regulating the host type I interferon (IFN) response. AMOTL2 affects IFN signaling by modulating STAT1 levels and activation in response to type I IFN. Thus, AMOTL2, which has largely been studied for its role in cancer, represents an antiviral protein that interacts with the IFN signaling pathway to promote downstream expression of IFN stimulated genes, resulting in restriction of ZIKV.

Retraction Note: Facile Synthesis of Mesoporous α-Fe2O3@g-C3N4-NCs for Efficient Bifunctional Electro-catalytic Activity (OER/ORR)

Unprecedented suppression of Panama’s Pacific upwelling in 2025

The Gulf of Panama’s (GOP) seasonal upwelling system has consistently delivered cool, nutrient-rich waters via northerly trade winds every January–April for at least 40 y. Here, we document the failure of this normally highly predictable phenomenon in 2025. Data suggest that the cause was a reduction in Panama wind-jet frequency, duration, and strength, possibly related to the Intertropical Convergence Zone (ITCZ) position during the 2024–2025 La Niña, though the mechanisms remain unclear. Nevertheless, the consequences are likely significant, including decreases in fisheries productivity and exacerbated thermal stress on corals that typically benefit from upwelling’s cooling. This event underscores how climate disruption can threaten wind-driven tropical upwelling systems, which remain poorly monitored and studied despite their importance to ecology and coastal economies.

Deep learning based solar forecasting for optimal PV BESS sizing in ultra fast charging stations

Abstract Ultra-fast charging stations (UFCS) present a significant challenge due to their high power demand and reliance on grid electricity. This paper proposes an optimization framework that integrates deep learning-based solar forecasting with a Genetic Algorithm (GA) for optimal sizing of photovoltaic (PV) and battery energy storage systems (BESS). A Gated Recurrent Unit (GRU) model is employed to forecast PV output, while the GA maximizes the Net Present Value (NPV) by selecting optimal PV and BESS sizes tailored to weekday and weekend demand profiles. The results show that PV integration alone improves the NPV by €6.19 million, while combining PV and BESS increases it to €33.97 million. With projected cost reductions, the system achieves a peak NPV of €34.05 million. Reliability analysis using Energy Sufficiency Ratio (ESR) and Autonomy Ratio (AR) confirms enhanced self-sufficiency and reduced grid dependency. This study demonstrates the techno-economic potential of hybrid renewable-powered UFCS using intelligent forecasting and evolutionary optimization.

Metabolic rewiring of isoniazid sensitivity in <i>Mycobacterium tuberculosis</i>

Isoniazid (INH) inhibits mycolic acid synthesis in Mycobacterium tuberculosis ( Mtb ) and is a cornerstone of treatment regimens against this deadly pathogen. However, over 10% of Mtb infections are INH-resistant. The compound C10 can sensitize clinically relevant INH-resistant mutants to killing by INH. Thus, understanding the mechanism of action for C10 could aid in designing new strategies for circumventing drug resistance. We find that C10 treatment reroutes carbon flux toward valine, drawing carbon away from gluconeogenesis and the TCA cycle. As a result, C10 decreases cell envelope capsule thickness and blocks an accumulation of peptidoglycan precursors that occurs in response to INH treatment in an INH-resistant Mtb katG mutant. In this altered metabolic state induced by C10, INH treatment of the INH-resistant Mtb katG mutant inhibits peptidoglycan synthesis, precipitating collapse of cell envelope integrity. Pyruvate supplementation relieves the C10-induced requirement for carbon flux toward valine, enhancing carbon assimilation into cell envelope precursors and restoring resistance to INH. In addition, we identify the formation of isoniazid-pyruvate in INH-treated katG W328L Mtb , where pyruvate sequesters INH, lowering the concentration of INH available to inhibit Mtb . Together, our findings reveal a bactericidal activity for INH in Mtb that can function in INH-resistant mutants independently of INH-mediated inhibition of mycolic acid synthesis. This activity for INH can be elicited by shifting carbon flux toward valine and away from cell envelope precursor synthesis, highlighting a metabolic vulnerability that can be exploited to kill INH-resistant Mtb .

Flexible use of multimodal communicative strategies in adult chimpanzees

Abstract Human communication is remarkable for its flexibility, a trait largely reflected in its multimodal nature and shared to some extent with nonhuman primates. Although individual differences in social behaviour are known to have evolutionary implications, their role in shaping primate communication remains largely unexplored. This study adopts a multimodal framework to partition variation in chimpanzees’ use of multicomponent and multisensory communicative strategies into socio-environmental, between-individual, and within-individual sources. Results showed that research setting and signaller’s sex affected communicative expression. Importantly, we also detected consistent between-individual differences in both strategies, independent of age, sex, or setting. While only multicomponent signal use was predicted by behavioural context at the population level, individuals varied in how they adjusted to context only in their use of multisensory acts. These findings reveal substantial flexibility in chimpanzee communication, highlighting individual-specific patterns and supporting a gradual evolutionary pathway toward the complexity of human multimodal communication.

Structural insights into the substrate uptake and inhibition of the human creatine transporter (hCRT)

Creatine plays a vital role in cellular energy production and adenosine triphosphate (ATP) homeostasis and has also been identified as a neurotransmitter in the mammalian brain. Creatine is transported into cells by the human creatine transporter (hCRT) (SLC6A8), an Na + /Cl − -dependent symporter encoded on the X chromosome. Mutations in hCRT cause cerebral creatine deficiency syndrome 1, a neurological disorder marked by intellectual disability, speech delay, and seizures. Beyond its role in the brain and muscle, hCRT is highly expressed in metabolically active tumors. Many cancer cells, including colorectal cancer and glioblastoma, upregulate hCRT to sustain intracellular creatine levels and buffer ATP under energy stress. Pharmacological blockade of hCRT by RGX202 has been shown to impair tumor growth by disrupting energy homeostasis. Here, we report the high-resolution cryo-Electron Microscopy (cryo-EM) structures of human hCRT in three states: apo, creatine-bound, and RGX202-bound. hCRT adopts a canonical LeuT-fold with 12 transmembrane helices and two pseudosymmetric inverted repeats. Creatine is coordinated in the central substrate-binding site through interactions with transmembrane helices TM1, TM3, TM6, and TM8, while the inhibitor RGX202 occupies the same binding pocket, engaging in overlapping contacts that competitively block creatine access. Our structural and mechanistic findings clarify substrate recognition and inhibitory binding of hCRT, providing a molecular rationale for targeting hCRT in both inherited metabolic diseases and cancer therapy.