Dias and Silvera (Research Article, 17 February 2017, p. 715) report on the observation of the Wigner-Huntington transition to metallic hydrogen at 495 gigapascals at 5.5 and 83 kelvin. Here, we show that the claim of metallic behavior is not supported by the presented data, which are scarce, contradictory, and do not prove the presence of hydrogen in the high-pressure cavity.

To resolve cellular heterogeneity, we developed a combinatorial indexing strategy to profile the transcriptomes of single cells or nuclei, termed sci-RNA-seq (single-cell combinatorial indexing RNA sequencing). We applied sci-RNA-seq to profile nearly 50,000 cells from the nematode Caenorhabditis elegans at the L2 larval stage, which provided >50-fold "shotgun" cellular coverage of its somatic cell composition. From these data, we defined consensus expression profiles for 27 cell types and recovered rare neuronal cell types corresponding to as few as one or two cells in the L2 worm. We integrated these profiles with whole-animal chromatin immunoprecipitation sequencing data to deconvolve the cell type–specific effects of transcription factors. The data generated by sci-RNA-seq constitute a powerful resource for nematode biology and foreshadow similar atlases for other organisms.

Mussels are opportunistic macrofouling organisms that can attach to most immersed solid surfaces, leading to serious economic and ecological consequences for the maritime and aquaculture industries. We demonstrate that lubricant-infused coatings exhibit very low preferential mussel attachment and ultralow adhesive strengths under both controlled laboratory conditions and in marine field studies. Detailed investigations across multiple length scales—from the molecular-scale characterization of deposited adhesive proteins to nanoscale contact mechanics to macroscale live observations—suggest that lubricant infusion considerably reduces fouling by deceiving the mechanosensing ability of mussels, deterring secretion of adhesive threads, and decreasing the molecular work of adhesion. Our study demonstrates that lubricant infusion represents an effective strategy to mitigate marine biofouling and provides insights into the physical mechanisms underlying adhesion prevention.

We synthesized a two-dimensional (2D) crystalline covalent organic framework (sp²c-COF) that was designed to be fully -conjugated and constructed from all sp² carbons by C=C condensation reactions of tetrakis(4-formylphenyl)pyrene and 1,4-phenylenediacetonitrile. The C=C linkages topologically connect pyrene knots at regular intervals into a 2D lattice with conjugations extended along both x and y directions and develop an eclipsed layer framework rather than the more conventionally obtained disordered structures. The sp²c-COF is a semiconductor with a discrete band gap of 1.9 electron volts and can be chemically oxidized to enhance conductivity by 12 orders of magnitude. The generated radicals are confined on the pyrene knots, enabling the formation of a paramagnetic carbon structure with high spin density. The sp² carbon framework induces ferromagnetic phase transition to develop spin-spin coherence and align spins unidirectionally across the material.

We fabricated a C₆₀ fullerene–based molecular spin-photovoltaic device that integrates a photovoltaic response with the spin transport across the molecular layer. The photovoltaic response can be modified under the application of a small magnetic field, with a magnetophotovoltage of up to 5% at room temperature. Device functionalities include a magnetic current inverter and the presence of diverging magnetocurrent at certain illumination levels that could be useful for sensing. Completely spin-polarized currents can be created by balancing the external partially spin-polarized injection with the photogenerated carriers.

Subluminous Type Ia supernovae, such as the Type Iax–class prototype SN 2002cx, are described by a variety of models such as the failed detonation and partial deflagration of an accreting carbon-oxygen white dwarf star or the explosion of an accreting, hybrid carbon-oxygen-neon core. These models predict that bound remnants survive such events with, according to some simulations, a high kick velocity. We report the discovery of a high proper motion, low-mass white dwarf (LP 40-365) that travels at a velocity greater than the Galactic escape velocity and whose peculiar atmosphere is dominated by intermediate-mass elements. Strong evidence indicates that this partially burnt remnant was ejected following a subluminous Type Ia supernova event. This supports the viability of single-degenerate supernova progenitors.

Brown dwarfs are massive analogs of extrasolar giant planets and may host types of atmospheric circulation not seen in the solar system. We analyzed a long-term Spitzer Space Telescope infrared monitoring campaign of brown dwarfs to constrain cloud cover variations over a total of 192 rotations. The infrared brightness evolution is dominated by beat patterns caused by planetary-scale wave pairs and by a small number of bright spots. The beating waves have similar amplitudes but slightly different apparent periods because of differing velocities or directions. The power spectrum of intermediate-temperature brown dwarfs resembles that of Neptune, indicating the presence of zonal temperature and wind speed variations. Our findings explain three previously puzzling behaviors seen in brown dwarf brightness variations.

At the final stage of the ventral visual stream, perirhinal neurons encode the identity of memorized objects through learning. However, it remains elusive whether and how object percepts alone, or concomitantly a nonphysical attribute of the objects ("learned"), are decoded from perirhinal activities. By combining monkey psychophysics with optogenetic and electrical stimulations, we found a focal spot of memory neurons where both stimulations led monkeys to preferentially judge presented objects as "already seen." In an adjacent fringe area, where neurons did not exhibit selective responses to the learned objects, electrical stimulation induced the opposite behavioral bias toward "never seen before," whereas optogenetic stimulation still induced bias toward "already seen." These results suggest that mnemonic judgment of objects emerges via the decoding of their nonphysical attributes encoded by perirhinal neurons.

Patient genomes are interpretable only in the context of other genomes; however, genome sharing enables discrimination. Thousands of monogenic diseases have yielded definitive genomic diagnoses and potential gene therapy targets. Here we show how to provide such diagnoses while preserving participant privacy through the use of secure multiparty computation. In multiple real scenarios (small patient cohorts, trio analysis, two-hospital collaboration), we used our methods to identify the causal variant and discover previously unrecognized disease genes and variants while keeping up to 99.7% of all participants’ most sensitive genomic information private.

Although itch sensation is an important protective mechanism for animals, chronic itch remains a challenging clinical problem. Itch processing has been studied extensively at the spinal level. However, how itch information is transmitted to the brain and what central circuits underlie the itch-induced scratching behavior remain largely unknown. We found that the spinoparabrachial pathway was activated during itch processing and that optogenetic suppression of this pathway impaired itch-induced scratching behaviors. Itch-mediating spinal neurons, which express the gastrin-releasing peptide receptor, are disynaptically connected to the parabrachial nucleus via glutamatergic spinal projection neurons. Blockade of synaptic output of glutamatergic neurons in the parabrachial nucleus suppressed pruritogen-induced scratching behavior. Thus, our studies reveal a central neural circuit that is critical for itch signal processing.

In methanogenic archaea, the carbon dioxide (CO₂) fixation and methane-forming steps are linked through the heterodisulfide reductase (HdrABC)–[NiFe]-hydrogenase (MvhAGD) complex that uses flavin-based electron bifurcation to reduce ferredoxin and the heterodisulfide of coenzymes M and B. Here, we present the structure of the native heterododecameric HdrABC-MvhAGD complex at 2.15-angstrom resolution. HdrB contains two noncubane [4Fe-4S] clusters composed of fused [3Fe-4S]-[2Fe-2S] units sharing 1 iron (Fe) and 1 sulfur (S), which were coordinated at the CCG motifs. Soaking experiments showed that the heterodisulfide is clamped between the two noncubane [4Fe-4S] clusters and homolytically cleaved, forming coenzyme M and B bound to each iron. Coenzymes are consecutively released upon one-by-one electron transfer. The HdrABC-MvhAGD atomic model serves as a structural template for numerous HdrABC homologs involved in diverse microbial metabolic pathways.

Vinculin is an actin-binding protein thought to reinforce cell-cell and cell-matrix adhesions. However, how mechanical load affects the vinculin–F-actin bond is unclear. Using a single-molecule optical trap assay, we found that vinculin forms a force-dependent catch bond with F-actin through its tail domain, but with lifetimes that depend strongly on the direction of the applied force. Force toward the pointed (–) end of the actin filament resulted in a bond that was maximally stable at 8 piconewtons, with a mean lifetime (12 seconds) 10 times as long as the mean lifetime when force was applied toward the barbed (+) end. A computational model of lamellipodial actin dynamics suggests that the directionality of the vinculin–F-actin bond could establish long-range order in the actin cytoskeleton. The directional and force-stabilized binding of vinculin to F-actin may be a mechanism by which adhesion complexes maintain front-rear asymmetry in migrating cells.

Preeclampsia (PE) is a gestational hypertensive syndrome affecting between 5 and 8% of all pregnancies. Although PE is the leading cause of fetal and maternal morbidity and mortality, its molecular etiology is still unclear. Here, we show that ELABELA (ELA), an endogenous ligand of the apelin receptor (APLNR, or APJ), is a circulating hormone secreted by the placenta. Elabela but not Apelin knockout pregnant mice exhibit PE-like symptoms, including proteinuria and elevated blood pressure due to defective placental angiogenesis. In mice, infusion of exogenous ELA normalizes hypertension, proteinuria, and birth weight. ELA, which is abundant in human placentas, increases the invasiveness of trophoblast-like cells, suggesting that it enhances placental development to prevent PE. The ELA-APLNR signaling axis may offer a new paradigm for the treatment of common pregnancy-related complications, including PE.

Contractile injection systems mediate bacterial cell-cell interactions by a bacteriophage tail–like structure. In contrast to extracellular systems, the type 6 secretion system (T6SS) is defined by intracellular localization and attachment to the cytoplasmic membrane. Here we used cryo-focused ion beam milling, electron cryotomography, and functional assays to study a T6SS in Amoebophilus asiaticus. The in situ architecture revealed three modules, including a contractile sheath-tube, a baseplate, and an anchor. All modules showed conformational changes upon firing. Lateral baseplate interactions coordinated T6SSs in hexagonal arrays. The system mediated interactions with host membranes and may participate in phagosome escape. Evolutionary sequence analyses predicted that T6SSs are more widespread than previously thought. Our insights form the basis for understanding T6SS key concepts and exploring T6SS diversity.

The sexual differentiation paradigm contends that the female pattern of the reproductive system is established by default because the male reproductive tracts (Wolffian ducts) in the female degenerate owing to a lack of androgen. Here, we discovered that female mouse embryos lacking Coup-tfII (chicken ovalbumin upstream promoter transcription factor II) in the Wolffian duct mesenchyme became intersex—possessing both female and male reproductive tracts. Retention of Wolffian ducts was not caused by ectopic androgen production or action. Instead, enhanced phosphorylated extracellular signal-regulated kinase signaling in Wolffian duct epithelium was responsible for the retention of male structures in an androgen-independent manner. We thus suggest that elimination of Wolffian ducts in female embryos is actively promoted by COUP-TFII, which suppresses a mesenchyme-epithelium cross-talk responsible for Wolffian duct maintenance.

Managing ecosystems is challenging because of the high number of stakeholders, the permeability of man-made political and jurisdictional demarcations in relation to the temporal and spatial extent of biophysical processes, and a limited understanding of complex ecosystem and societal dynamics. Given these conditions, collaborative governance is commonly put forward as the preferred means of addressing environmental problems. Under this paradigm, a deeper understanding of if, when, and how collaboration is effective, and when other means of addressing environmental problems are better suited, is needed. Interdisciplinary research on collaborative networks demonstrates that which actors get involved, with whom they collaborate, and in what ways they are tied to the structures of the ecosystems have profound implications on actors’ abilities to address different types of environmental problems.

Cancer is one of the leading causes of death, and there is great interest in understanding the underlying molecular mechanisms involved in the pathogenesis and progression of individual tumors. We used systems-level approaches to analyze the genome-wide transcriptome of the protein-coding genes of 17 major cancer types with respect to clinical outcome. A general pattern emerged: Shorter patient survival was associated with up-regulation of genes involved in cell growth and with down-regulation of genes involved in cellular differentiation. Using genome-scale metabolic models, we show that cancer patients have widespread metabolic heterogeneity, highlighting the need for precise and personalized medicine for cancer treatment. All data are presented in an interactive open-access database (www.proteinatlas.org/pathology) to allow genome-wide exploration of the impact of individual proteins on clinical outcomes.

We evaluated a program of payments for ecosystem services in Uganda that offered forest-owning households annual payments of 70,000 Ugandan shillings per hectare if they conserved their forest. The program was implemented as a randomized controlled trial in 121 villages, 60 of which received the program for 2 years. The primary outcome was the change in land area covered by trees, measured by classifying high-resolution satellite imagery. We found that tree cover declined by 4.2% during the study period in treatment villages, compared to 9.1% in control villages. We found no evidence that enrollees shifted their deforestation to nearby land. We valued the delayed carbon dioxide emissions and found that this program benefit is 2.4 times as large as the program costs.

Hsp100 polypeptide translocases are conserved members of the AAA+ family (adenosine triphosphatases associated with diverse cellular activities) that maintain proteostasis by unfolding aberrant and toxic proteins for refolding or proteolytic degradation. The Hsp104 disaggregase from Saccharomyces cerevisiae solubilizes stress-induced amorphous aggregates and amyloids. The structural basis for substrate recognition and translocation is unknown. Using a model substrate (casein), we report cryo–electron microscopy structures at near-atomic resolution of Hsp104 in different translocation states. Substrate interactions are mediated by conserved, pore-loop tyrosines that contact an 80-angstrom-long unfolded polypeptide along the axial channel. Two protomers undergo a ratchet-like conformational change that advances pore loop–substrate interactions by two amino acids. These changes are coupled to activation of specific nucleotide hydrolysis sites and, when transmitted around the hexamer, reveal a processive rotary translocation mechanism and substrate-responsive flexibility during Hsp104-catalyzed disaggregation.

Lithium-ion batteries with ever-increasing energy densities are needed for batteries for advanced devices and all-electric vehicles. Silicon has been highlighted as a promising anode material because of its superior specific capacity. During repeated charge-discharge cycles, silicon undergoes huge volume changes. This limits cycle life via particle pulverization and an unstable electrode-electrolyte interface, especially when the particle sizes are in the micrometer range. We show that the incorporation of 5 weight % polyrotaxane to conventional polyacrylic acid binder imparts extraordinary elasticity to the polymer network originating from the ring sliding motion of polyrotaxane. This binder combination keeps even pulverized silicon particles coalesced without disintegration, enabling stable cycle life for silicon microparticle anodes at commercial-level areal capacities.

The conversion of widely available carboxylic acids into versatile boronic esters would be highly enabling for synthesis. We found that this transformation can be effected by illuminating the N-hydroxyphthalimide ester derivative of the carboxylic acid under visible light at room temperature in the presence of the diboron reagent bis(catecholato)diboron. A simple workup allows isolation of the pinacol boronic ester. Experimental evidence suggests that boryl radical intermediates are involved in the process. The methodology is illustrated by the transformation of primary, secondary, and tertiary alkyl carboxylic acids as well as a diverse range of natural-product carboxylic acids, thereby demonstrating its broad utility and functional group tolerance.

Quantum spin Hall materials hold the promise of revolutionary devices with dissipationless spin currents but have required cryogenic temperatures owing to small energy gaps. Here we show theoretically that a room-temperature regime with a large energy gap may be achievable within a paradigm that exploits the atomic spin-orbit coupling. The concept is based on a substrate-supported monolayer of a high–atomic number element and is experimentally realized as a bismuth honeycomb lattice on top of the insulating silicon carbide substrate SiC(0001). Using scanning tunneling spectroscopy, we detect a gap of ~0.8 electron volt and conductive edge states consistent with theory. Our combined theoretical and experimental results demonstrate a concept for a quantum spin Hall wide-gap scenario, where the chemical potential resides in the global system gap, ensuring robust edge conductance.

The flux of carbon into and out of Earth’s surface environment has implications for Earth’s climate and habitability. We compiled a global data set for carbon and helium isotopes from volcanic arcs and demonstrated that the carbon isotope composition of mean global volcanic gas is considerably heavier, at –3.8 to –4.6 per mil (), than the canonical mid-ocean ridge basalt value of –6.0. The largest volcanic emitters outgas carbon with higher ¹³C and are located in mature continental arcs that have accreted carbonate platforms, indicating that reworking of crustal limestone is an important source of volcanic carbon. The fractional burial of organic carbon is lower than traditionally determined from a global carbon isotope mass balance and may have varied over geological time, modulated by supercontinent formation and breakup.

Majorana fermion is a hypothetical particle that is its own antiparticle. We report transport measurements that suggest the existence of one-dimensional chiral Majorana fermion modes in the hybrid system of a quantum anomalous Hall insulator thin film coupled with a superconductor. As the external magnetic field is swept, half-integer quantized conductance plateaus are observed at the locations of magnetization reversals, giving a distinct signature of the Majorana fermion modes. This transport signature is reproducible over many magnetic field sweeps and appears at different temperatures. This finding may open up an avenue to control Majorana fermions for implementing robust topological quantum computing.

Stretching polymer chains accelerates dissociation of a variety of internal covalent bonds, to an extent that correlates well with the force experienced by the scissile bond. Recent theory has also predicted scenarios in which applied force accelerates dissociation of unloaded bonds and kinetically strengthens strained bonds. We report here unambiguous experimental validation of this hypothesis: Detailed kinetic measurements demonstrate that stretching phosphotriesters accelerates dissociation of the unloaded phosphorus-oxygen bond orthogonal to the pulling axis, whereas stretching organosiloxanes inhibits dissociation of the aligned loaded silicon-oxygen bonds. Qualitatively, the outcome is determined by phosphoester elongation and siloxane contraction along the pulling axis in the respective rate-determining transition states. Quantitatively, the results agree with a simple mechanochemical kinetics model.

The advent of high-harmonic generation in gases 30 years ago set the foundation for attosecond science and facilitated ultrafast spectroscopy in atoms, molecules, and solids. We explore high-harmonic generation in the solid state by means of nanostructured and ion-implanted semiconductors. We use wavelength-selective microscopic imaging to map enhanced harmonic emission and show that the generation medium and the driving field can be locally tailored in solids by modifying the chemical composition and morphology. This enables the control of high-harmonic technology within precisely engineered solid targets. We demonstrate customized high-harmonic wave fields with wavelengths down to 225 nanometers (ninth-harmonic order of 2-micrometer laser pulses) and present an integrated Fresnel zone plate target in silicon, which leads to diffraction-limited self-focusing of the generated harmonics down to 1-micrometer spot sizes.

Molecular piezoelectrics are highly desirable for their easy and environment-friendly processing, light weight, low processing temperature, and mechanical flexibility. However, although 136 years have passed since the discovery in 1880 of the piezoelectric effect, molecular piezoelectrics with a piezoelectric coefficient d₃₃ comparable with piezoceramics such as barium titanate (BTO; ~190 picocoulombs per newton) have not been found. We show that trimethylchloromethyl ammonium trichloromanganese(II), an organic-inorganic perovskite ferroelectric crystal processed from aqueous solution, has a large d₃₃ of 185 picocoulombs per newton and a high phase-transition temperature of 406 kelvin (K) (16 K above that of BTO). This makes it a competitive candidate for medical, micromechanical, and biomechanical applications.

The lymphatic system in teleost fish has genetic and developmental origins similar to those of the mammalian lymphatic system, which is involved in immune response and fluid homeostasis. Here, we show that the lymphatic system of tunas functions in swimming hydrodynamics. Specifically, a musculo-vascular complex, consisting of fin muscles, bones, and lymphatic vessels, is involved in the hydraulic control of median fins. This specialization of the lymphatic system is associated with fish in the family Scombridae and may have evolved in response to the demand for swimming and maneuvering control in these high-performance species.

Bidirectional replication from eukaryotic DNA replication origins requires the loading of two ring-shaped minichromosome maintenance (MCM) helicases around DNA in opposite orientations. MCM loading is orchestrated by binding of the origin recognition complex (ORC) to DNA, but how ORC coordinates symmetrical MCM loading is unclear. We used natural budding yeast DNA replication origins and synthetic DNA sequences to show that efficient MCM loading requires binding of two ORC molecules to two ORC binding sites. The relative orientation of these sites, but not the distance between them, was found to be critical for MCM loading in vitro and origin function in vivo. We propose that quasi-symmetrical loading of individual MCM hexamers by ORC and directed MCM translocation into double hexamers acts as a unifying mechanism for the establishment of bidirectional replication in archaea and eukaryotes.

Chromatin and associated epigenetic mechanisms stabilize gene expression and cellular states while also facilitating appropriate responses to developmental or environmental cues. Genetic, environmental, or metabolic insults can induce overly restrictive or overly permissive epigenetic landscapes that contribute to pathogenesis of cancer and other diseases. Restrictive chromatin states may prevent appropriate induction of tumor suppressor programs or block differentiation. By contrast, permissive or "plastic" states may allow stochastic oncogene activation or nonphysiologic cell fate transitions. Whereas many stochastic events will be inconsequential "passengers," some will confer a fitness advantage to a cell and be selected as "drivers." We review the broad roles played by epigenetic aberrations in tumor initiation and evolution and their potential to give rise to all classic hallmarks of cancer.