Data security experts say increased oversight is needed, but researchers are struggling to comply.Data security experts say increased oversight is needed, but researchers are struggling to comply.
Liang L, Zhang S, Wang Z
… +18 more, Zhang H, Li C, Thapa C, Oh EK, Sirkin D, Sun X, Barishman A, McCarroll A, Duhe AC, Qian S, Zhong X, Jamison B, Wood W, Kozlova A, Pang ZP, Sanders AR, He X, Duan J
Most causal variants for neuropsychiatric disorders (NPD) remain unknown. A major hurdle is that disease variants may act in specific contexts, such as during neuronal activation, which is difficult to study in vivo at t...Most causal variants for neuropsychiatric disorders (NPD) remain unknown. A major hurdle is that disease variants may act in specific contexts, such as during neuronal activation, which is difficult to study in vivo at the population level. We profiled single-nucleus neuron-activation multiomics in human induced pluripotent stem cell-derived neurons from 100 donors, revealing the NPD-relevant transcriptomic and epigenomic landscape of neuronal activation. We identified abundant genetic variants associated with activity-dependent gene expression and chromatin accessibility, the latter explaining larger proportions of NPD heritability. Integrating multiomics data with genome-wide association studies further revealed NPD risk variants and genes with effects detected only upon stimulation, such as activity-dependent cholesterol metabolism. Our work highlights the power of cell stimulation to reveal context-specific "hidden" genetic effects.
Stewart JD, Bisot C, Cargill RIM
… +21 more, Van Nuland ME, Hawkins HJ, Oyarte Galvez L, Klein M, van Son M, Terry V, Paré L, Banchini C, Stefani F, Kahane F, Lin KK, Braghiere RK, Field KJ, Soudzilovskaia NA, Elhance J, Kokkoris V, Sheldrake M, Weedon JT, Shimizu TS, West S, Kiers ET
Arbuscular mycorrhizal fungi form symbioses with ~70% of plant species, building hyphal networks that exchange nutrients for host-derived carbon. These tubular networks move ~1 billion metric tons of carbon per year into...Arbuscular mycorrhizal fungi form symbioses with ~70% of plant species, building hyphal networks that exchange nutrients for host-derived carbon. These tubular networks move ~1 billion metric tons of carbon per year into Earth's soils. However, we have no quantitative understanding of the hyphal infrastructure required to carry out this resource transfer. We assembled data from 322 studies representing more than 16,000 soil cores across nine biomes and developed machine-learning models to predict hyphal densities globally. With robotic imaging of more than 300,000 hyphae, we calibrated a biomass model from our spatial predictions. We estimate that global topsoils contain 1.10 × 10 ± 0.13 × 10 SD kilometers of living hyphae, weighing ~300 ± 60 SD megatons, ~4- to 6-fold the biomass of humans. Our uncertainty analyses identified undersampled ecosystems that require additional empirical attention.
United States seeks to debar Ralph Baric for misleading NIAID on old coronavirus studies, which he disputes.United States seeks to debar Ralph Baric for misleading NIAID on old coronavirus studies, which he disputes.
The uneven global distribution of plant diversity remains a fundamental question in biogeography. Using dated phylogenies of >300,000 plant species and ancestral biogeographical stochastic mapping, we show that in situ s...The uneven global distribution of plant diversity remains a fundamental question in biogeography. Using dated phylogenies of >300,000 plant species and ancestral biogeographical stochastic mapping, we show that in situ speciation is the predominant process underlying extant plant diversity and accounts for 78% of biogeographic events across realms. The Neotropic contributed 37% of in situ speciation, likely owing to its role as a center of species diversification. Dispersal between realms was less frequent (16% of events) but facilitated floristic exchanges, especially in the Eastern Hemisphere. Extinction was least frequent but more pronounced in East Asia. These findings support the tropical conservatism hypothesis in which many clades originated in the tropics and only recently expanded into temperate zones, where limited time and biome conservatism have restricted speciation and diversity.
Timmy, a humpback stranded in Germany 6 weeks ago, was freed after a media outcry. But the whale was in poor health and may already be dead.Timmy, a humpback stranded in Germany 6 weeks ago, was freed after a media outcry. But the whale was in poor health and may already be dead.
Because all known living organisms are made from at least 20 canonical amino acids, the feasibility of life using a more simplified alphabet remains unclear. In this work, we leveraged computational design and synthetic...Because all known living organisms are made from at least 20 canonical amino acids, the feasibility of life using a more simplified alphabet remains unclear. In this work, we leveraged computational design and synthetic biology to explore building a cell from a 19-amino acid alphabet. Initial analyses suggested that isoleucine (Ile) may be dispensable, which we confirmed by directly replacing Ile residues in essential proteins in . Critically, protein language models and structure-based models were necessary to redesign functional Ile-less proteins in most cases. We systematically replaced all 382 Ile residues from the ribosome and combined 21 redesigned subunits at a native genomic locus to produce a viable, evolutionarily stable cell. This work provides a roadmap to create the first 19-amino acid organism since early evolution.
Researchers encode the tiny hepatitis D virus in an early step toward "quantum genomics".Researchers encode the tiny hepatitis D virus in an early step toward "quantum genomics".
At the blood-tissue interface, vasculature luminal surface is critical for molecular transport, signaling transduction, and cell extravasation. Here, we present a method for proteomic profiling of the vasculature luminal...At the blood-tissue interface, vasculature luminal surface is critical for molecular transport, signaling transduction, and cell extravasation. Here, we present a method for proteomic profiling of the vasculature luminal surface in vivo, broadly applicable to any vertebrate. Quantitative mass spectrometry revealed the luminal surface proteome of the mouse brain vasculature and its temporal evolution from development to aging. In vivo genetic perturbation found that the arginine transporter SLC7A1 and the nitric oxide synthase NOS3 are needed for blood-brain barrier integrity in neonatal but not adult mice, whereas the hyaluronan degradation enzyme HYAL2 safeguards the barrier throughout the lifespan. By characterizing the proteomic dynamics of the vasculature luminal surface, the study links the metabolism of nitric oxide and hyaluronan to blood-brain barrier integrity.
The bacterial pangenome contains a vast diversity of antiphage systems, whose overall extent is still unknown. In this study, we developed complementary machine learning approaches to systematically predict antiphage fun...The bacterial pangenome contains a vast diversity of antiphage systems, whose overall extent is still unknown. In this study, we developed complementary machine learning approaches to systematically predict antiphage function from genomic context, protein sequence, or their combination, achieving up to 99% precision and 92% recall. We validated these models experimentally in and with the discovery of 12 antiphage systems. Applied to over 32,000 bacterial genomes, these models expand the predicted antiphage repertoire, with ~1.5% of bacterial genomes devoted to defense and more than 85% of predicted protein families remaining uncharacterized. We provide an interactive catalog of more than 19,000 candidate operon families for experimental follow-up. Together, these findings show that most molecular diversity in bacterial immunity remains uncharacterized and provide a foundation for its systematic exploration.
Tennessen JA, Brosula R, Chabanol E
… +21 more, Bickersmith S, Early AM, Laws M, Kelley KA, Grillet ME, Gamboa D, Lucas ER, Duchemin JB, Quiñones ML, Sallum MAM, Bergo ES, Moreno JE, Nagi S, Arisco NJ, Sooklall M, Niles-Robin R, Castro MC, Cox H, Gendrin M, Conn JE, Neafsey DE
Malaria in South America remains a serious public health problem. () is the most important malaria vector across tropical Latin America. Vector-targeted disease control efforts require a thorough understanding of mosqu...Malaria in South America remains a serious public health problem. () is the most important malaria vector across tropical Latin America. Vector-targeted disease control efforts require a thorough understanding of mosquito demographic and evolutionary patterns. We present and analyze whole genomes of 1094 (median depth 18x) from six South American countries. We observe deep geographic population structure, high genetic diversity including 13 putative segregating inversions, and no evidence for sympatric cryptic taxa despite high interpopulation divergence. Strong signals of selection are plausibly driven by insecticides, especially on cytochrome P450 genes. Our results will facilitate effective mosquito surveillance and control while highlighting ongoing challenges that a diverse vector poses for malaria elimination in the Western hemisphere.
The Early Miocene fossil record documenting hominoid evolution has long been restricted primarily to sites in East Africa, whereas contemporaneous North African sites have only yielded remains of cercopithecoid monkeys....The Early Miocene fossil record documenting hominoid evolution has long been restricted primarily to sites in East Africa, whereas contemporaneous North African sites have only yielded remains of cercopithecoid monkeys. Here, we describe a fossil ape from North Africa, a new genus () from the Early Miocene (~17 million to 18 million years) of northern Egypt, on the basis of mandibular remains. A combined molecular-morphological Bayesian tip-dating analysis positions closer to crown hominoids than coeval fossil apes from East Africa, thereby filling a phylogenetic and biogeographic gap in the evolution of stem hominoids. This evidence suggests that crown Hominoidea might have originated during the Early Miocene in the underexplored northeastern part of Afro-Arabia, rather than in eastern Africa or Eurasia.
Early mammals were nocturnal while dinosaurs dominated the daytime. Mammalian transition to daytime activity accelerated after the Cretaceous-Paleogene extinction, but the underlying mechanisms remain unclear. We identif...Early mammals were nocturnal while dinosaurs dominated the daytime. Mammalian transition to daytime activity accelerated after the Cretaceous-Paleogene extinction, but the underlying mechanisms remain unclear. We identified a conserved cell-intrinsic, thermodynamic mechanism that likely facilitated this shift. In cells from diurnal mammals, protein synthesis, phosphorylation, and circadian timing were less sensitive to temperature changes than were cells from nocturnal mammals. Comparative genomics revealed accelerated evolution within essential signaling pathways, including mechanistic target of rapamycin (mTOR), that increase the robustness of diurnal cellular clocks to thermal and osmotic perturbation. In nocturnal mice, mTOR inhibition shifted cells, tissues, and behavior toward diurnal activity. These findings uncover a genetic and biochemical basis for nocturnal-diurnal switching, emphasizing how cellular signaling networks can encode complex phenotypes such as temporal niche selection.
More than a century after two introduced pathogens killed billions of American chestnut trees, introgression of resistance alleles from Chinese chestnuts has contributed to the recovery of self-sustaining populations. Ho...More than a century after two introduced pathogens killed billions of American chestnut trees, introgression of resistance alleles from Chinese chestnuts has contributed to the recovery of self-sustaining populations. However, progress has been slow because of the complex genetic architecture of resistance. To better understand blight resistance, we compared reference genomes, gene expression responses, and stem metabolite profiles of the resistant Chinese and susceptible American chestnut species. To accelerate resistance breeding, we conducted large-scale phenotyping and genotyping in hybrids of these species. Simulation and inoculation experiments suggest that significant resistance gains are possible through selectively breeding trees with an average of 70 to 85% American chestnut ancestry. The resources developed in this work are foundational for breeding to create diverse restoration populations with sufficient disease resistance and competitive growth.
Huang Y, Zhang Y, Zhang Q
… +17 more, Zhuang G, Li C, Wang B, Gao R, Xu Y, Qi Y, Hua X, Shi H, Xu Q, Yao W, Liu X, Qi Y, Chen B, Zhang M, Ming R, Tang H, Zhang J
The sugarcane genus is characterized by complex genomes with diverse ploidy levels. We developed a multiscale graph-based pangenome representation, which integrates nine genome assemblies into a unified reference, repre...The sugarcane genus is characterized by complex genomes with diverse ploidy levels. We developed a multiscale graph-based pangenome representation, which integrates nine genome assemblies into a unified reference, representing modern cultivars and founding species. Each homo(eo)logous (encompasses both homologous and homeologous relationships) chromosome set retains 47 to 57 haplotypes and ~74,000 to 271,000 gene alleles. This framework enables multiomics exploration, encompassing homo(eo)log systems and epigenomic signatures. The pangenome facilitates population genomics analyses of 417 mixed-ploidy accessions, revealing convergent selection and identifying the Andropogoneae homolog linked to tillering as a promising gene-editing target to boost cane yield. Additionally, the pangenome supports dosage-informed genome-wide association study, improving heritability estimates and identification of sugar or leaf-angle-associated loci, including and . Our analytical framework establishes a foundation for graph-based genetic studies in sugarcane and other polyploid genomes.
Protein structure is conserved beyond sequence, making multiple structural alignment (MSTA) essential for analyzing distantly related proteins. Computational prediction methods have vastly extended our repository of avai...Protein structure is conserved beyond sequence, making multiple structural alignment (MSTA) essential for analyzing distantly related proteins. Computational prediction methods have vastly extended our repository of available protein structures, requiring fast and accurate MSTA methods. We introduce FoldMason, a progressive MSTA method that leverages the pairwise structural aligners Foldseek and TM-align for the multiple alignment of hundreds of thousands of protein structures, matching or exceeding the alignment quality of state-of-the-art MSTA methods while being two orders of magnitude faster. Using glycoproteins, we demonstrate that FoldMason's MSTAs support phylogenetic analysis beyond the "twilight zone." FoldMason computes confidence scores, offers interactive visualizations, and provides essential speed and accuracy for large-scale protein structure analysis in the era of accurate structure prediction. FoldMason is free, open-source software.
Recent studies suggest that microbes inhabit tree bark, yet little is known about their identities, functions, and environmental roles. Here we reveal, through gene-centric and genome-resolved metagenomics, that the bark...Recent studies suggest that microbes inhabit tree bark, yet little is known about their identities, functions, and environmental roles. Here we reveal, through gene-centric and genome-resolved metagenomics, that the bark of eight common Australian tree species hosts abundant and specialized microbial communities. The predominant bacteria are hydrogen-cycling facultative anaerobes adapted to dynamic redox and substrate conditions. Furthermore, bark-associated methanotrophs are abundant and can coexist with hydrogenotrophic methanogens. Microcosm experiments showed that bark microorganisms aerobically consume methane, hydrogen, and carbon monoxide at in planta concentrations and produce these gases under anoxia. Combined with in situ field measurements, we show that tree-dwelling microbiota metabolize multiple climate-active gases at marked rates within tree stems, highlighting a potentially substantial role in global atmospheric cycles.
Paint traps a rich stew of biomolecules that can reveal artworks' history-and authenticity.Paint traps a rich stew of biomolecules that can reveal artworks' history-and authenticity.
Yin J, Zheng Y, Huang Z
… +54 more, Zhou W, Yuan Y, Cai P, Bai Y, Yang S, Gao Y, Duan S, Wang Y, Xu Z, Zhang W, Zhang X, Wei Y, Huang Y, Liu Y, Wang W, Yang T, Zhang Z, Chen X, Zhang X, Lv J, Li F, Zhang Y, Zeng G, Wang X, Ma W, Hou G, Hao S, Liu C, Lai Y, Liu P, Wang B, Li Y, Zhang W, Gao P, Xie J, Esteban MA, Gu Y, Liu X, Ji J, Qi T, Liu B, Wang H, Zhao Y, Yang X, Wang X, Chen R, Yang J, Yin Y, Wang J, Cao Y, Xu X, Liu L, Jin X, Liu C
Human peripheral blood exhibits molecular and cellular heterogeneity across populations, yet the underlying mechanisms remain unclear. We present the Chinese Immune Multi-Omics Atlas (CIMA), characterizing molecular vari...Human peripheral blood exhibits molecular and cellular heterogeneity across populations, yet the underlying mechanisms remain unclear. We present the Chinese Immune Multi-Omics Atlas (CIMA), characterizing molecular variations linked to sex, age, and genetic variants through multi-omics analysis of more than 10 million circulating immune cells from 428 Chinese adults. CIMA established an enhancer-driven gene regulatory network comprising 237 robust regulons; identified 9600 eGenes and 52,361 caPeaks at cell type resolution; and revealed pleiotropic associations among immune-related disease risk loci, cis-expression quantitative trait loci (QTLs), and chromatin accessibility QTLs. Furthermore, the cell language model CIMA-CLM predicted chromatin accessibility and evaluated the effects of noncoding variants from chromatin sequences and gene expression. CIMA provides a comprehensive reference for immune-related disease research.