Precise densities of red dwarf exoplanets help distinguish potential "water worlds".Precise densities of red dwarf exoplanets help distinguish potential "water worlds".
Webb telescope discovery offers clue to planet formation and promises insights on planetary habitability.Webb telescope discovery offers clue to planet formation and promises insights on planetary habitability.
Humans have cultivated grasses for food, feed, beverages, and construction materials for millennia. Grasses also dominate the landscape in vast parts of the world, where they have adapted morphologically and physiologica...Humans have cultivated grasses for food, feed, beverages, and construction materials for millennia. Grasses also dominate the landscape in vast parts of the world, where they have adapted morphologically and physiologically, diversifying to form ~12,000 species. Sequences of hundreds of grass genomes show that they are essentially collinear; nonetheless, not all species have the same complement of genes. Here, we focus on the molecular, cellular, and developmental bases of grain yield and dispersal-traits that are essential for domestication. Distinct genes, networks, and pathways were selected in different crop species, reflecting underlying genomic diversity. With increasing genomic resources becoming available in nondomesticated species, we anticipate advances in coming years that illuminate the ecological and economic success of the grasses.
Our understanding of the physical principles organizing the genome in the nucleus is limited by the lack of tools to directly exert and measure forces on interphase chromosomes in vivo and probe their material nature. He...Our understanding of the physical principles organizing the genome in the nucleus is limited by the lack of tools to directly exert and measure forces on interphase chromosomes in vivo and probe their material nature. Here, we introduce an approach to actively manipulate a genomic locus using controlled magnetic forces inside the nucleus of a living human cell. We observed viscoelastic displacements over micrometers within minutes in response to near-piconewton forces, which are consistent with a Rouse polymer model. Our results highlight the fluidity of chromatin, with a moderate contribution of the surrounding material, revealing minor roles for cross-links and topological effects and challenging the view that interphase chromatin is a gel-like material. Our technology opens avenues for future research in areas from chromosome mechanics to genome functions.
Pekar JE, Magee A, Parker E
… +26 more, Moshiri N, Izhikevich K, Havens JL, Gangavarapu K, Malpica Serrano LM, Crits-Christoph A, Matteson NL, Zeller M, Levy JI, Wang JC, Hughes S, Lee J, Park H, Park MS, Ching Zi Yan K, Lin RTP, Mat Isa MN, Noor YM, Vasylyeva TI, Garry RF, Holmes EC, Rambaut A, Suchard MA, Andersen KG, Worobey M, Wertheim JO
Understanding the circumstances that lead to pandemics is important for their prevention. We analyzed the genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease...Understanding the circumstances that lead to pandemics is important for their prevention. We analyzed the genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease 2019 (COVID-19) pandemic. We show that SARS-CoV-2 genomic diversity before February 2020 likely comprised only two distinct viral lineages, denoted "A" and "B." Phylodynamic rooting methods, coupled with epidemic simulations, reveal that these lineages were the result of at least two separate cross-species transmission events into humans. The first zoonotic transmission likely involved lineage B viruses around 18 November 2019 (23 October to 8 December), and the separate introduction of lineage A likely occurred within weeks of this event. These findings indicate that it is unlikely that SARS-CoV-2 circulated widely in humans before November 2019 and define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported. As with other coronaviruses, SARS-CoV-2 emergence likely resulted from multiple zoonotic events.
To accelerate the translation of cancer nanomedicine, we used an integrated genomic approach to improve our understanding of the cellular processes that govern nanoparticle trafficking. We developed a massively parallel...To accelerate the translation of cancer nanomedicine, we used an integrated genomic approach to improve our understanding of the cellular processes that govern nanoparticle trafficking. We developed a massively parallel screen that leverages barcoded, pooled cancer cell lines annotated with multiomic data to investigate cell association patterns across a nanoparticle library spanning a range of formulations with clinical potential. We identified both materials properties and cell-intrinsic features that mediate nanoparticle-cell association. Using machine learning algorithms, we constructed genomic nanoparticle trafficking networks and identified nanoparticle-specific biomarkers. We validated one such biomarker: gene expression of , which inversely predicts lipid-based nanoparticle uptake in vitro and in vivo. Our work establishes the power of integrated screens for nanoparticle delivery and enables the identification and utilization of biomarkers to rationally design nanoformulations.
Species' geographic ranges are limited by climate and species interactions. Climate is the prevailing explanation for why species live only within narrow elevational ranges in megadiverse biodiverse tropical mountains, b...Species' geographic ranges are limited by climate and species interactions. Climate is the prevailing explanation for why species live only within narrow elevational ranges in megadiverse biodiverse tropical mountains, but competition can also restrict species' elevational ranges. We test contrasting predictions of these hypotheses by conducting a global comparative test of birds' elevational range sizes within 31 montane regions, using more than 4.4 million citizen science records from eBird to define species' elevational ranges in each region. We find strong support that competition, not climate, is the leading driver of narrow elevational ranges. These results highlight the importance of species interactions in shaping species' ranges in tropical mountains, Earth's hottest biodiversity hotspots.
Bacteria and fungi behind cheese, soy, and more share genomic traits wth domesticated plants and animals.Bacteria and fungi behind cheese, soy, and more share genomic traits wth domesticated plants and animals.
Rivers support indispensable ecological functions and human health and infrastructure. Yet limited river sampling hinders our understanding of consequential changes to river systems. Satellite-based estimates of suspende...Rivers support indispensable ecological functions and human health and infrastructure. Yet limited river sampling hinders our understanding of consequential changes to river systems. Satellite-based estimates of suspended sediment concentration and flux for 414 major rivers reveal widespread global change that is directly attributable to human activity in the past half-century. Sediment trapping by dams in the global hydrologic north has contributed to global sediment flux declines to 49% of pre-dam conditions. Recently, intensive land-use change in the global hydrologic south has increased erosion, with river suspended sediment concentration on average 41 ± 7% greater than in the 1980s. This north-south divergence has rapidly reconfigured global patterns in sediment flux to the oceans, with the dominant sources of suspended sediment shifting from Asia to South America.
Global-scale surveys of plankton communities using "omics" techniques have revolutionized our understanding of the ocean. Lipidomics has demonstrated the potential to add further essential insights on ocean ecosystem fun...Global-scale surveys of plankton communities using "omics" techniques have revolutionized our understanding of the ocean. Lipidomics has demonstrated the potential to add further essential insights on ocean ecosystem function but has yet to be applied on a global scale. We analyzed 930 lipid samples across the global ocean using a uniform high-resolution accurate-mass mass spectrometry analytical workflow, revealing previously unknown characteristics of ocean planktonic lipidomes. Focusing on 10 molecularly diverse glycerolipid classes, we identified 1151 distinct lipid species, finding that fatty acid unsaturation (i.e., number of carbon-carbon double bonds) is fundamentally constrained by temperature. We predict substantial declines in the essential fatty acid eicosapentaenoic acid over the next century, which are likely to have serious deleterious effects on economically critical fisheries.
INTRODUCTION The eukaryotic nucleus pro-tects the genome and is enclosed by the two membranes of the nuclear envelope. Nuclear pore complexes (NPCs) perforate the nuclear envelope to facilitate nucleocytoplasmic transpor...INTRODUCTION The eukaryotic nucleus pro-tects the genome and is enclosed by the two membranes of the nuclear envelope. Nuclear pore complexes (NPCs) perforate the nuclear envelope to facilitate nucleocytoplasmic transport. With a molecular weight of ∼120 MDa, the human NPC is one of the larg-est protein complexes. Its ~1000 proteins are taken in multiple copies from a set of about 30 distinct nucleoporins (NUPs). They can be roughly categorized into two classes. Scaf-fold NUPs contain folded domains and form a cylindrical scaffold architecture around a central channel. Intrinsically disordered NUPs line the scaffold and extend into the central channel, where they interact with cargo complexes. The NPC architecture is highly dynamic. It responds to changes in nuclear envelope tension with conforma-tional breathing that manifests in dilation and constriction movements. Elucidating the scaffold architecture, ultimately at atomic resolution, will be important for gaining a more precise understanding of NPC function and dynamics but imposes a substantial chal-lenge for structural biologists. RATIONALE Considerable progress has been made toward this goal by a joint effort in the field. A synergistic combination of complementary approaches has turned out to be critical. In situ structural biology techniques were used to reveal the overall layout of the NPC scaffold that defines the spatial reference for molecular modeling. High-resolution structures of many NUPs were determined in vitro. Proteomic analysis and extensive biochemical work unraveled the interaction network of NUPs. Integra-tive modeling has been used to combine the different types of data, resulting in a rough outline of the NPC scaffold. Previous struc-tural models of the human NPC, however, were patchy and limited in accuracy owing to several challenges: (i) Many of the high-resolution structures of individual NUPs have been solved from distantly related species and, consequently, do not comprehensively cover their human counterparts. (ii) The scaf-fold is interconnected by a set of intrinsically disordered linker NUPs that are not straight-forwardly accessible to common structural biology techniques. (iii) The NPC scaffold intimately embraces the fused inner and outer nuclear membranes in a distinctive topol-ogy and cannot be studied in isolation. (iv) The conformational dynamics of scaffold NUPs limits the resolution achievable in structure determination. RESULTS In this study, we used artificial intelligence (AI)-based prediction to generate an exten-sive repertoire of structural models of human NUPs and their subcomplexes. The resulting models cover various domains and interfaces that so far remained structurally uncharac-terized. Benchmarking against previous and unpublished x-ray and cryo-electron micros-copy structures revealed unprecedented accu-racy. We obtained well-resolved cryo-electron tomographic maps of both the constricted and dilated conformational states of the hu-man NPC. Using integrative modeling, we fit-ted the structural models of individual NUPs into the cryo-electron microscopy maps. We explicitly included several linker NUPs and traced their trajectory through the NPC scaf-fold. We elucidated in great detail how mem-brane-associated and transmembrane NUPs are distributed across the fusion topology of both nuclear membranes. The resulting architectural model increases the structural coverage of the human NPC scaffold by about twofold. We extensively validated our model against both earlier and new experimental data. The completeness of our model has enabled microsecond-long coarse-grained molecular dynamics simulations of the NPC scaffold within an explicit membrane en-vironment and solvent. These simulations reveal that the NPC scaffold prevents the constriction of the otherwise stable double-membrane fusion pore to small diameters in the absence of membrane tension. CONCLUSION Our 70-MDa atomically re-solved model covers >90% of the human NPC scaffold. It captures conforma-tional changes that occur during dilation and constriction. It also reveals the precise anchoring sites for intrinsically disordered NUPs, the identification of which is a prerequisite for a complete and dy-namic model of the NPC. Our study exempli-fies how AI-based structure prediction may accelerate the elucidation of subcellular ar-chitecture at atomic resolution. [Figure: see text].
Characterizing complex microbial communities with single-cell resolution has been a long-standing goal of microbiology. We present Microbe-seq, a high-throughput method that yields the genomes of individual microbes from...Characterizing complex microbial communities with single-cell resolution has been a long-standing goal of microbiology. We present Microbe-seq, a high-throughput method that yields the genomes of individual microbes from complex microbial communities. We encapsulate individual microbes in droplets with microfluidics and liberate their DNA, which we then amplify, tag with droplet-specific barcodes, and sequence. We explore the human gut microbiome, sequencing more than 20,000 microbial single-amplified genomes (SAGs) from a single human donor and coassembling genomes of almost 100 bacterial species, including several with multiple subspecies strains. We use these genomes to probe microbial interactions, reconstructing the horizontal gene transfer (HGT) network and observing HGT between 92 species pairs; we also identify a significant in vivo host-phage association between crAssphage and one strain of . Microbe-seq contributes high-throughput culture-free capabilities to investigate genomic blueprints of complex microbial communities with single-microbe resolution.
Emerging resistance to currently used antibiotics is a global public health crisis. Because most of the biosynthetic capacity within the bacterial kingdom has remained silent in previous antibiotic discovery efforts, unc...Emerging resistance to currently used antibiotics is a global public health crisis. Because most of the biosynthetic capacity within the bacterial kingdom has remained silent in previous antibiotic discovery efforts, uncharacterized biosynthetic gene clusters found in bacterial genome-sequencing studies remain an appealing source of antibiotics with distinctive modes of action. Here, we report the discovery of a naturally inspired lipopeptide antibiotic called cilagicin, which we chemically synthesized on the basis of a detailed bioinformatic analysis of the biosynthetic gene cluster. Cilagicin's ability to sequester two distinct, indispensable undecaprenyl phosphates used in cell wall biosynthesis, together with the absence of detectable resistance in laboratory tests and among multidrug-resistant clinical isolates, makes it an appealing candidate for combating antibiotic-resistant pathogens.
Researchers should be aware of how sex-difference science is (mis)applied in legal and policy contexts.Researchers should be aware of how sex-difference science is (mis)applied in legal and policy contexts.
Suo C, Dann E, Goh I
… +25 more, Jardine L, Kleshchevnikov V, Park JE, Botting RA, Stephenson E, Engelbert J, Tuong ZK, Polanski K, Yayon N, Xu C, Suchanek O, Elmentaite R, Domínguez Conde C, He P, Pritchard S, Miah M, Moldovan C, Steemers AS, Mazin P, Prete M, Horsfall D, Marioni JC, Clatworthy MR, Haniffa M, Teichmann SA
Single-cell genomics studies have decoded the immune cell composition of several human prenatal organs but were limited in describing the developing immune system as a distributed network across tissues. We profiled nine...Single-cell genomics studies have decoded the immune cell composition of several human prenatal organs but were limited in describing the developing immune system as a distributed network across tissues. We profiled nine prenatal tissues combining single-cell RNA sequencing, antigen-receptor sequencing, and spatial transcriptomics to reconstruct the developing human immune system. This revealed the late acquisition of immune-effector functions by myeloid and lymphoid cell subsets and the maturation of monocytes and T cells before peripheral tissue seeding. Moreover, we uncovered system-wide blood and immune cell development beyond primary hematopoietic organs, characterized human prenatal B1 cells, and shed light on the origin of unconventional T cells. Our atlas provides both valuable data resources and biological insights that will facilitate cell engineering, regenerative medicine, and disease understanding.