Machine learning for data-driven discovery in solid Earth geoscience ()
Understanding the behavior of Earth through the diverse fields of the solid Earth geosciences is an increasingly important task. It is made challenging by the complex, interacting, and multiscale processes needed to understand Earth’s behavior and by the inaccessibility of nearly all of Earth’s subsurface to direct observation. Substantial increases in data availability and in the increasingly realistic character of computer simulations hold promise for accelerating progress, but developing a deeper understanding based on these capabilities is itself challenging. Machine learning will play a key role in this effort. We review the state of the field and make recommendations for how progress might be broadened and accelerated.
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Comment on "Insulator-metal transition in dense fluid deuterium" ()
Celliers et al. (Reports, 17 August 2018, p. 677), in an attempt to reconcile differences in inferred metallization pressures, provide an alternative temperature analysis of the Knudson et al. experiments (Reports, 26 June 2015, p. 1455). We show that this reanalysis implies an anomalously low specific heat for the metallic fluid that is clearly inconsistent with first-principles calculations.
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The future of science in film ()

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News at a glance ()

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Humans may sense Earth's magnetic field ()

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White House details proposed cuts to science agencies ()

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Rapid apple decline has researchers stumped ()

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Tests identify HIV's final redoubt ()

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Elite advisers to help NSF navigate security concerns ()

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For these intrepid crickets, lava is home sweet home ()

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Clever math enables MRI to map biomolecules ()

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The reef builders ()

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Science at Sundance ()

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Volcanic threats to global society ()

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Evolving resistance to pathogens ()

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Sodium channels caught in the act ()

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Dampening oncogenic RAS signaling ()

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Making more from methane ()

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Stem cell-based options to preserve male fertility ()

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A treasure trove of Cambrian fossils ()

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Wallace Broecker (1931-2019) ()

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Adversarial attacks on medical machine learning ()

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Racial profiling harms science ()

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Response ()

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Empowering young innovators ()

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Locating myxomatosis resistance ()

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A treasure trove of Cambrian secrets ()

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Targeting a common eye cancer ()

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Boron brings nitrogen together ()

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Solving equations with waves ()

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Elucidating the sources of nightglow ()

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Targeting sodium channels ()

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Methane oxidation on the plus side ()

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A sweetener's not-so-sweet effects ()

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Automating geoscience analysis ()

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How activation leads to gating ()

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Sequencing and the single sperm ()

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Rapid response to tissue damage ()

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Preserving male fertility ()

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Swarming in parallel toward sociality ()

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Preparing for the next supereruption ()

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Targeting RAS regulation ()

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Learning from one tumor to help another ()

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Getting immune cells home ()

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Leadership from behind ()

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Naked droplets for culturing cells ()

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Turtles and tortoises in decline ()

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A core-shell silver cluster ()

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Careers in STEM start early ()

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Lysosome repositioning ()

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Reproducible instability ()

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Structures of human Nav1.7 channel in complex with auxiliary subunits and animal toxins ()
Voltage-gated sodium channel Nav1.7 represents a promising target for pain relief. Here we report the cryo–electron microscopy structures of the human Nav1.7-β1-β2 complex bound to two combinations of pore blockers and gating modifier toxins (GMTs), tetrodotoxin with protoxin-II and saxitoxin with huwentoxin-IV, both determined at overall resolutions of 3.2 angstroms. The two structures are nearly identical except for minor shifts of voltage-sensing domain II (VSDII), whose S3-S4 linker accommodates the two GMTs in a similar manner. One additional protoxin-II sits on top of the S3-S4 linker in VSDIV. The structures may represent an inactivated state with all four VSDs "up" and the intracellular gate closed. The structures illuminate the path toward mechanistic understanding of the function and disease of Nav1.7 and establish the foundation for structure-aided development of analgesics.
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Molecular basis for pore blockade of human Na+ channel Nav1.2 by the {mu}-conotoxin KIIIA ()
The voltage-gated sodium channel Nav1.2 is responsible for the initiation and propagation of action potentials in the central nervous system. We report the cryo–electron microscopy structure of human Nav1.2 bound to a peptidic pore blocker, the μ-conotoxin KIIIA, in the presence of an auxiliary subunit, β2, to an overall resolution of 3.0 angstroms. The immunoglobulin domain of β2 interacts with the shoulder of the pore domain through a disulfide bond. The 16-residue KIIIA interacts with the extracellular segments in repeats I to III, placing Lys7 at the entrance to the selectivity filter. Many interacting residues are specific to Nav1.2, revealing a molecular basis for KIIIA specificity. The structure establishes a framework for the rational design of subtype-specific blockers for Nav channels.
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Autologous grafting of cryopreserved prepubertal rhesus testis produces sperm and offspring ()
Testicular tissue cryopreservation is an experimental method to preserve the fertility of prepubertal patients before they initiate gonadotoxic therapies for cancer or other conditions. Here we provide the proof of principle that cryopreserved prepubertal testicular tissues can be autologously grafted under the back skin or scrotal skin of castrated pubertal rhesus macaques and matured to produce functional sperm. During the 8- to 12-month observation period, grafts grew and produced testosterone. Complete spermatogenesis was confirmed in all grafts at the time of recovery. Graft-derived sperm were competent to fertilize rhesus oocytes, leading to preimplantation embryo development, pregnancy, and the birth of a healthy female baby. Pending the demonstration that similar results are obtained in noncastrated recipients, testicular tissue grafting may be applied in the clinic.
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Parallel adaptation of rabbit populations to myxoma virus ()
In the 1950s the myxoma virus was released into European rabbit populations in Australia and Europe, decimating populations and resulting in the rapid evolution of resistance. We investigated the genetic basis of resistance by comparing the exomes of rabbits collected before and after the pandemic. We found a strong pattern of parallel evolution, with selection on standing genetic variation favoring the same alleles in Australia, France, and the United Kingdom. Many of these changes occurred in immunity-related genes, supporting a polygenic basis of resistance. We experimentally validated the role of several genes in viral replication and showed that selection acting on an interferon protein has increased the protein’s antiviral effect.
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Activation of methane to CH3+: A selective industrial route to methanesulfonic acid ()
Direct methane functionalization to value-added products remains a challenge because of the propensity for overoxidation in many reaction environments. Sulfonation has emerged as an attractive approach for achieving the necessary selectivity. Here, we report a practical process for the production of methanesulfonic acid (MSA) from only two reactants: methane and sulfur trioxide. We have achieved >99% selectivity and yield of MSA. The electrophilic initiator based on a sulfonyl peroxide derivative is protonated under superacidic conditions, producing a highly electrophilic oxygen atom capable of activating a C–H bond of methane. Mechanistic studies support the formation of CH3+ as a key intermediate. This method is readily scalable with reactors connected in series for prospective production of up to 20 metric tons per year of MSA.
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The reductive coupling of dinitrogen ()
The coupling of two or more molecules of dinitrogen (N2) occurs naturally under the radiative conditions present in the ionosphere and may be achieved synthetically under ultrahigh pressure or plasma conditions. However, the comparatively low N–N single-bond enthalpy generally renders the catenation of the strongly triple-bonded N2 diatomic unfavorable and the decomposition of nitrogen chains a common reaction motif. Here, we report the surprising organoboron-mediated catenation of two N2 molecules under near-ambient conditions to form a complex in which a [N4]2– chain bridges two boron centers. The reaction entails reductive coupling of two hypovalent-boron-bound N2 units in a single step. Both this complex and a derivative protonated at both ends of the chain were characterized crystallographically.
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Inverse-designed metastructures that solve equations ()
Metastructures hold the potential to bring a new twist to the field of spatial-domain optical analog computing: migrating from free-space and bulky systems into conceptually wavelength-sized elements. We introduce a metamaterial platform capable of solving integral equations using monochromatic electromagnetic fields. For an arbitrary wave as the input function to an equation associated with a prescribed integral operator, the solution of such an equation is generated as a complex-valued output electromagnetic field. Our approach is experimentally demonstrated at microwave frequencies through solving a generic integral equation and using a set of waveguides as the input and output to the designed metastructures. By exploiting subwavelength-scale light-matter interactions in a metamaterial platform, our wave-based, material-based analog computer may provide a route to achieve chip-scale, fast, and integrable computing elements.
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The Qingjiang biota--A Burgess Shale-type fossil Lagerstätte from the early Cambrian of South China ()
Burgess Shale–type fossil Lagerstätten provide the best evidence for deciphering the biotic patterns and magnitude of the Cambrian explosion. Here, we report a Lagerstätte from South China, the Qingjiang biota (~518 million years old), which is dominated by soft-bodied taxa from a distal shelf setting. The Qingjiang biota is distinguished by pristine carbonaceous preservation of labile organic features, a very high proportion of new taxa (~53%), and preliminary taxonomic diversity that suggests it could rival the Chengjiang and Burgess Shale biotas. Defining aspects of the Qingjiang biota include a high abundance of cnidarians, including both medusoid and polypoid forms; new taxa resembling extant kinorhynchs; and abundant larval or juvenile forms. This distinctive composition holds promise for providing insights into the evolution of Cambrian ecosystems across environmental gradients.
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Social genes are selection hotspots in kin groups of a soil microbe ()
The composition of cooperative systems, including animal societies, organismal bodies, and microbial groups, reflects their past and shapes their future evolution. However, genomic diversity within many multiunit systems remains uncharacterized, limiting our ability to understand and compare their evolutionary character. We have analyzed genomic and social-phenotype variation among 120 natural isolates of the cooperative bacterium Myxococcus xanthus derived from six multicellular fruiting bodies. Each fruiting body was composed of multiple lineages radiating from a unique recent ancestor. Genomic evolution was concentrated in selection hotspots associated with evolutionary change in social phenotypes. Synonymous mutations indicated that kin lineages within the same fruiting body often first diverged from a common ancestor more than 100 generations ago. Thus, selection appears to promote endemic diversification of kin lineages that remain together over long histories of local interaction, thereby potentiating social coevolution.
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High-fructose corn syrup enhances intestinal tumor growth in mice ()
Excessive consumption of beverages sweetened with high-fructose corn syrup (HFCS) is associated with obesity and with an increased risk of colorectal cancer. Whether HFCS contributes directly to tumorigenesis is unclear. We investigated the effects of daily oral administration of HFCS in adenomatous polyposis coli (APC) mutant mice, which are predisposed to develop intestinal tumors. The HFCS-treated mice showed a substantial increase in tumor size and tumor grade in the absence of obesity and metabolic syndrome. HFCS increased the concentrations of fructose and glucose in the intestinal lumen and serum, respectively, and the tumors transported both sugars. Within the tumors, fructose was converted to fructose-1-phosphate, leading to activation of glycolysis and increased synthesis of fatty acids that support tumor growth. These mouse studies support the hypothesis that the combination of dietary glucose and fructose, even at a moderate dose, can enhance tumorigenesis.
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New Products ()

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My mix-and-match career ()

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Response to Comment on "Insulator-metal transition in dense fluid deuterium" ()
In their comment, Desjarlais et al. claim that a small temperature drop occurs after isentropic compression of fluid deuterium through the first-order insulator-metal transition. We show that their calculations do not correspond to the experimental thermodynamic path, and that thermodynamic integrations with parameters from first-principles calculations produce results in agreement with our original estimate of the temperature drop.
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Damage on plants activates Ca2+-dependent metacaspases for release of immunomodulatory peptides ()
Physical damage to cells leads to the release of immunomodulatory peptides to elicit a wound defense response in the surrounding tissue. In Arabidopsis thaliana, the plant elicitor peptide 1 (Pep1) is processed from its protein precursor, PRECURSOR OF PEP1 (PROPEP1). We demonstrate that upon damage, both at the tissue and single-cell levels, the cysteine protease METACASPASE4 (MC4) is instantly and spatiotemporally activated by binding high levels of Ca2+ and is necessary and sufficient for Pep1 maturation. Cytosol-localized PROPEP1 and MC4 react only after loss of plasma membrane integrity and prolonged extracellular Ca2+ entry. Our results reveal that a robust mechanism consisting of conserved molecular components links the intracellular and Ca2+-dependent activation of a specific cysteine protease with the maturation of damage-induced wound defense signals.
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Structural basis of {alpha}-scorpion toxin action on Nav channels ()
Fast inactivation of voltage-gated sodium (Nav) channels is essential for electrical signaling, but its mechanism remains poorly understood. Here we determined the structures of a eukaryotic Nav channel alone and in complex with a lethal α-scorpion toxin, AaH2, by electron microscopy, both at 3.5-angstrom resolution. AaH2 wedges into voltage-sensing domain IV (VSD4) to impede fast activation by trapping a deactivated state in which gating charge interactions bridge to the acidic intracellular carboxyl-terminal domain. In the absence of AaH2, the S4 helix of VSD4 undergoes a ~13-angstrom translation to unlatch the intracellular fast-inactivation gating machinery. Highlighting the polypharmacology of α-scorpion toxins, AaH2 also targets an unanticipated receptor site on VSD1 and a pore glycan adjacent to VSD4. Overall, this work provides key insights into fast inactivation, electromechanical coupling, and pathogenic mutations in Nav channels.
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Factors influencing meiotic recombination revealed by whole-genome sequencing of single sperm ()
Recombination is critical to meiosis and evolution, yet many aspects of the physical exchange of DNA via crossovers remain poorly understood. We report an approach for single-cell whole-genome DNA sequencing by which we sequenced 217 individual hybrid mouse sperm, providing a kilobase-resolution genome-wide map of crossovers. Combining this map with molecular assays measuring stages of recombination, we identified factors that affect crossover probability, including PRDM9 binding on the non-initiating template homolog and telomere proximity. These factors also influence the time for sites of recombination-initiating DNA double-strand breaks to find and engage their homologs, with rapidly engaging sites more likely to form crossovers. We show that chromatin environment on the template homolog affects positioning of crossover breakpoints. Our results also offer insights into recombination in the pseudoautosomal region.
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