In science news around the world, China's largest research funding agency expresses support for the goals of Plan S, the push by European science funders for immediate open access to research publications. For the second year in a row, carbon dioxide emissions from fossil fuels are projected to hit a new high, growing 2.7% this year. NASA's Voyager 2 probe becomes only the second humanmade object to enter interstellar space. Empathy expert Tania Singer resigns as director of the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, Germany, after a commission confirmed allegations of bullying. Dozens of African researchers are denied visas for an artificial intelligence (AI) meeting in Montreal, Canada, even as the Canadian government takes steps to advance the country's standing in AI. Sue the Tyrannosaurus rex, the most complete and largest T. rex fossil known, returns to display at the Field Museum in Chicago, Illinois, after a makeover. Researchers publish the first detailed analyses of Little Foot, the world's most complete fossil skeleton of an early hominin.

In Ireland, peat—a carbon-rich soil harvested from drained bogs—has been used for centuries to warm homes and fire whiskey distilleries. For a country with little coal, oil, and gas, peat—deep layers of partially decayed moss and other plant matter—is also a ready fuel for power plants. Peat power peaked in the 1960s, providing 40% of Ireland's electricity. But peat is particularly polluting. Burning it for electricity emits more carbon dioxide than coal, and nearly twice as much as natural gas. In 2016, peat generated nearly 8% of Ireland's electricity, but was responsible for 20% of that sector's carbon emissions. Peat power is now being phased out. By the end of 2019, the Irish government will eliminate all of the roughly €100 million in annual industry subsidies it now pays for peat-generated electricity. Bord na Móna, a company that supplies peat to the three remaining power stations burning it for electricity, announced in October that it would cut its peat supply for electricity by a third by 2020 and end it completely by 2027. Ireland will need to find alternative, lower carbon sources of electricity. And the approximately 60 bogs no longer needed for fuel will undergo rehabilitation, some converted back to wetlands and others put to commercial uses such as land for wind farms.

U.S. President Donald Trump's administration is taking steps to limit the use of human fetal tissue from elective abortions in biomedical research. Last week, administration officials told researchers at one California university that their contract work involving fetal tissue would not receive the usual 1-year extension. And Science has learned that this past September, officials quietly ordered scientists employed by the U.S. National Institutes of Health (NIH) to stop acquiring new human fetal tissue for experiments. Both moves come as the Trump administration has launched a review of all federally funded research with fetal tissue, which is used to study several diseases. The actions have prompted fears that NIH-funded university scientists who work with fetal tissue could face a broader clampdown.

An independent panel that evaluated sexual harassment, bullying, and abuses of power at the Joint United Nations Programme on HIV/AIDS (UNAIDS) issued a blistering report that called for a change in leadership to address what it called a "vacuum of accountability." UNAIDS, based in Geneva, Switzerland, is the global command center in the fight against HIV/AIDS, issuing authoritative epidemiological updates and staging campaigns to improve prevention and treatment—and, ironically, to promote human rights. But the panel report says there's a "boy's club" culture at UNAIDS, and it strongly faults the executive director, Michel Sidibé, for fostering a patriarchal environment that is marred further by nepotism and retaliation against employees who complain. Sidibé requested that the panel convene after two staffers were accused of sexual harassment and there was criticism of his handling of the incidents. The Programme Coordinating Board that oversees UNAIDS is meeting this week and reviewing the panel's recommendations.

There's growing concern about an Ebola outbreak in the Democratic Republic of the Congo (DRC) that surfaced in August and, despite a coordinated response that has included vaccinating more than 40,000 people, persists. Although it's not being formally evaluated, the vaccine appears to be having an impact, says Peter Salama, who coordinates the response for the World Health Organization in Geneva, Switzerland. But the outbreak in the northeastern region of the country is taking place in an area that has long suffered from armed conflict, which repeatedly has brought Ebola response teams to a halt. The outbreak has had some 500 cases, about half of which have resulted in death, making it the second largest Ebola outbreak on record. The largest, which took place in West Africa from 2014 to 2016, was considerably larger—28,000 cases, 11,000 deaths—but there is fear that if the international community does not do more to help the DRC by sending experienced personnel and more money, the outbreak could continue its spread—and could easily breach borders to neighboring countries. Editorials in two leading medical journals urge the United States government in particular to change a policy that, for safety reasons, bars staff from the U.S. Centers for Disease Control and Prevention from traveling to the DRC and helping in the affected region.

Tallying up the biomass in a forest—and monitoring changes to it—is no easy task. You can cordon off a patch of forest and use tape measures to assess tree growth, hoping your patch is representative of the wider forest. Or you can turn to aerial or satellite photography—if the pictures are available and sharp enough. But even the best cameras can't see past the forest canopy to the understory below. On 5 December, scientists gained a new tool for this tricky business when NASA's Global Ecosystem Dynamics Investigation instrument was launched on a SpaceX rocket. The instrument, the size of a large refrigerator, uses a laser to see below the treetops. It is now mounted on the International Space Station, where it will begin to gather data on the height and 3D structure of tropical and temperate forests. The campaign will help scientists understand whether forests are slowing or amplifying climate change and identify prime habitat for valued species.

The idea of electronic devices implanted in our bodies conveys images of cyborgs. But devices in use today, such as cardiac pacemakers, already save thousands of lives each year. Future devices aim to do even better, as material advances are making the new versions vanishingly small, often requiring no batteries, and even able to dissolve when no longer needed. New work presented at the recent Materials Research Society meeting in Boston showed how these devices can speed the healing of damaged nerves, quell tremors from Parkinson's and similar diseases, and even help obese patients lose weight. These new devices aren't ready for use in humans yet. But the trend is clear that novel bioelectronic devices are on their way to becoming an alternative to pharmaceuticals.

Neanderthals have odd heads, stretched from front to back like a football rather than round like a basketball, as in living people. But why our heads and those of our ice age cousins look different has long been a mystery. Now, researchers have found an ingenious way to identify genes that help explain the contrast. By analyzing traces of Neanderthal DNA that linger in Europeans from their ancestors' trysts, researchers have identified two Neanderthal gene variants linked to slightly less globular head shape in living people. The genes also influence brain organization, offering a clue to how evolution acting on the brain might have reshaped the skull.

This year, 68% of major scientific conferences held in North America provided child care support for parent attendees, Science has found. An even larger share—94%—made a lactation room available for nursing mothers. "That's good," a biologist and mother told Science. But those statistics should be 100%, she added. Science examined resources available to parents at 34 meetings, each attended by more than 1000 scientists. Of the conferences that supplied child care support, 83% arranged for licensed providers to operate at conference facilities and 22% offered child care grants.

Despite the two space telescopes at the top of astronomers' wish list—the James Webb Space Telescope (JWST) and the Wide Field Infrared Survey Telescope (WFIRST)—remaining firmly on the ground because of technical hitches and budget problems, it is time for astronomers to look skyward and dream even bigger dreams. The decadal survey in astrophysics, which sets priorities for future projects on the ground and in space, kicked off last month and it must decide which of four proposed successors to the JWST and WFIRST most deserves to launch as a NASA flagship observatory, sometime in the 2030s. On the following pages, Science examines those dream telescopes: the Large Ultraviolet Optical Infrared Surveyor, a 15-meter-wide giant with 40 times the light-collecting power of the Hubble Space Telescope; the smaller Habitable Exoplanet Observatory, which will scrutinize nearby stars for signs of life; the Lynx X-ray Observatory, which would gather photons the universe's first black holes; and the Origins Space Telescope, which will study the cool infrared light from the gas and dust that fuel star and planet formation.

The creation of nanoscale electronics, photonics, plasmonics, and mechanically robust metamaterials will benefit from nanofabrication processes that allow a designer full control in manipulating nanomaterial precursors in a programmable and volumetric manner. Despite decades of research, it remains challenging to design nanofabrication processes that can produce complex free-form three-dimensional (3D) objects at the scale of tens of nanometers. On page 1281 of this issue, Oran et al. (1) report on the photopatterning of reactive sites into water-swollen, chemically cross-linked acrylic gels for the subsequent site-specific deposition of nanomaterials and nanoparticles. After chemical and thermal dehydration, the gel scaffold holds the nanomaterials in a distinct 3D arrangement. This process, termed implosion fabrication (ImpFab) because the scaffold of the gel effectively “implodes” upon solvent removal, provides an opportunity to fabricate centimeter-scale assemblies of nanomaterials that possess multiple functionalities.

The domestication of plants and animals and their dispersal across the globe triggered a millennia-long process by which human activity has become the dominant influence on climate and the environment (1). Domestication was a watershed development that ushered in the Anthropocene (2). How, when, where, and why humans embarked on this path is central to understanding how we might chart our way in an uncertain future. On page 1309 of this issue, Kistler et al. (3) report on the dispersal of maize into and across northern South America. The study contributes to the growing appreciation of domestication as a complex, coevolutionary journey taken by humans and receptive plant and animal species over hundreds, if not thousands, of years. The study also joins others in showing how human populations incorporated dispersing domesticates into indigenous systems of exploitation and manipulation of local resources. More broadly, this research speaks to the promise of domestication research in assessing fundamental questions about evolution and the interface of natural and cultural systems that shape it.

Changes in the human environment and activities over the past few decades have caused an epidemic of food allergies (1). People suffering from allergies often feel that they live on a cliff edge, as the allergens to which they react are potentially fatal (2). For example, tiny amounts of peanut picked up on skin or contaminating other foods can be dangerous to peanut-sensitized individuals (2–4). Immunoglobulin E (IgE) antibodies mediate the allergic response. They bind to specific receptors on inflammatory immune cells: mast cells in mucosal tissues lining body surfaces and cavities, and basophils in the circulation. These cells mediate allergic responses triggered by specific antigens (allergens) that are recognized by IgE. B cells expressing IgG antibodies have long served as the paradigm for the development of B cells into antibody-secreting plasma cells in the immune response. Until recently, the far less abundant IgE-expressing B cells have proved to be elusive. On page 1306 of this issue, Croote et al. (5) have analyzed single B cells from six individuals with peanut allergy, which enabled the identification of the natural Ig heavy- and light-chain pairs from IgE-expressing B cells that are responsible for peanut allergy. With this information they produced recombinant antibodies, identified the peanut allergen–specific antibodies, and used site-directed mutagenesis to suppress their activity. The mutated antibodies could be used to treat peanut allergy.

Root parasitic weeds of the Orobanchaceae such as broomrapes and witchweeds form a serious threat to agriculture in many countries around the world (1). They cause large yield losses in crops such as sorghum, millet, maize, rapeseed, tomato, sunflower, and legumes (1). These obligate parasitic plants are dependent on a host for survival, using them to grow and reproduce on. Therefore, they only germinate in the presence of a germination stimulant exuded by the host root (2). On page 1301 of this issue, Uraguchi et al. (3) reveal the discovery of a potent synthetic germination stimulant. Their discovery provides the basis for the development of an agrochemical that may be used to germinate parasitic weeds in the absence of a host (so that they will die, called suicide germination) and gives insight into what may be determining host specificity of these parasites.

Seth Fletcher's Einstein's Shadow is the story of the Event Horizon Telescope (EHT)—an astrophysical endeavor on an extraordinary scale that knits radio telescopes at far-flung locations across the globe into what is, in effect, a single telescope the size of Earth.

Want to master your professional and social networks to maximize recognition? Want to learn how to build productive teams that create lasting impact? In his new book, The Formula: The Universal Laws of Success, Albert-László Barabási translates almost a decade of scholarly research on the science of success into a lively and compelling narrative woven together with captivating stories and his own deeply personal experiences.

Every cancer is a living, ever-evolving, mutated derivation of a body's own cells. This makes fighting a cancer like fighting the mythological many-headed hydra. Cut off one head, and two may grow in its place. In The Breakthrough, journalist Charles Graeber tells the story of how we may finally slay the beast.

Cuprate superconductors have long been thought of as having strong electronic correlations but negligible spin-orbit coupling. Using spin- and angle-resolved photoemission spectroscopy, we discovered that one of the most studied cuprate superconductors, Bi2212, has a nontrivial spin texture with a spin-momentum locking that circles the Brillouin zone center and a spin-layer locking that allows states of opposite spin to be localized in different parts of the unit cell. Our findings pose challenges for the vast majority of models of cuprates, such as the Hubbard model and its variants, where spin-orbit interaction has been mostly neglected, and open the intriguing question of how the high-temperature superconducting state emerges in the presence of this nontrivial spin texture.

Achieving high catalytic performance with the lowest possible amount of platinum is critical for fuel cell cost reduction. Here we describe a method of preparing highly active yet stable electrocatalysts containing ultralow-loading platinum content by using cobalt or bimetallic cobalt and zinc zeolitic imidazolate frameworks as precursors. Synergistic catalysis between strained platinum-cobalt core-shell nanoparticles over a platinum-group metal (PGM)–free catalytic substrate led to excellent fuel cell performance under 1 atmosphere of O2 or air at both high-voltage and high-current domains. Two catalysts achieved oxygen reduction reaction (ORR) mass activities of 1.08 amperes per milligram of platinum (A mgPt−1) and 1.77 A mgPt−1 and retained 64% and 15% of initial values after 30,000 voltage cycles in a fuel cell. Computational modeling reveals that the interaction between platinum-cobalt nanoparticles and PGM-free sites improves ORR activity and durability.

Lithographic nanofabrication is often limited to successive fabrication of two-dimensional (2D) layers. We present a strategy for the direct assembly of 3D nanomaterials consisting of metals, semiconductors, and biomolecules arranged in virtually any 3D geometry. We used hydrogels as scaffolds for volumetric deposition of materials at defined points in space. We then optically patterned these scaffolds in three dimensions, attached one or more functional materials, and then shrank and dehydrated them in a controlled way to achieve nanoscale feature sizes in a solid substrate. We demonstrate that our process, Implosion Fabrication (ImpFab), can directly write highly conductive, 3D silver nanostructures within an acrylic scaffold via volumetric silver deposition. Using ImpFab, we achieve resolutions in the tens of nanometers and complex, non–self-supporting 3D geometries of interest for optical metamaterials.

Primordial sequence signatures in modern proteins imply ancestral origins tracing back to simple peptides. Although short peptides seldom adopt unique folds, metal ions might have templated their assembly into higher-order structures in early evolution and imparted useful chemical reactivity. Recapitulating such a biogenetic scenario, we have combined design and laboratory evolution to transform a zinc-binding peptide into a globular enzyme capable of accelerating ester cleavage with exacting enantiospecificity and high catalytic efficiency (kcat/KM ~ 106 M−1 s−1). The simultaneous optimization of structure and function in a naïve peptide scaffold not only illustrates a plausible enzyme evolutionary pathway from the distant past to the present but also proffers exciting future opportunities for enzyme design and engineering.

Theory has established the importance of geometric phase (GP) effects in the adiabatic dynamics of molecular systems with a conical intersection connecting the ground- and excited-state potential energy surfaces, but direct observation of their manifestation in chemical reactions remains a major challenge. Here, we report a high-resolution crossed molecular beams study of the H + HD → H2 + D reaction at a collision energy slightly above the conical intersection. Velocity map ion imaging revealed fast angular oscillations in product quantum state–resolved differential cross sections in the forward scattering direction for H2 products at specific rovibrational levels. The experimental results agree with adiabatic quantum dynamical calculations only when the GP effect is included.

Paired measurements of 14C/12C and 230Th ages from two Hulu Cave stalagmites complete a precise record of atmospheric 14C covering the full range of the 14C dating method (~54,000 years). Over the last glacial period, atmospheric 14C/12C ranges from values similar to modern values to values 1.70 times higher (42,000 to 39,000 years ago). The latter correspond to 14C ages 5200 years less than calibrated ages and correlate with the Laschamp geomagnetic excursion followed by Heinrich Stadial 4. Millennial-scale variations are largely attributable to Earth’s magnetic field changes and in part to climate-related changes in the oceanic carbon cycle. A progressive shift to lower 14C/12C values between 25,000 and 11,000 years ago is likely related, in part, to progressively increasing ocean ventilation rates.

East Africa has provided the earliest known evidence for Oldowan stone artifacts and hominin-induced stone tool cutmarks dated to ~2.6 million years (Ma) ago. The ~1.8-million-year-old stone artifacts from Ain Hanech (Algeria) were considered to represent the oldest archaeological materials in North Africa. Here we report older stone artifacts and cutmarked bones excavated from two nearby deposits at Ain Boucherit estimated to ~1.9 Ma ago, and the older to ~2.4 Ma ago. Hence, the Ain Boucherit evidence shows that ancestral hominins inhabited the Mediterranean fringe in northern Africa much earlier than previously thought. The evidence strongly argues for early dispersal of stone tool manufacture and use from East Africa or a possible multiple-origin scenario of stone technology in both East and North Africa.

The parasitic plant Striga hermonthica has been causing devastating damage to the crop production in Africa. Because Striga requires host-generated strigolactones to germinate, the identification of selective and potent strigolactone agonists could help control these noxious weeds. We developed a selective agonist, sphynolactone-7, a hybrid molecule originated from chemical screening, that contains two functional modules derived from a synthetic scaffold and a core component of strigolactones. Cooperative action of these modules in the activation of a high-affinity strigolactone receptor ShHTL7 allows sphynolactone-7 to provoke Striga germination with potency in the femtomolar range. We demonstrate that sphynolactone-7 is effective for reducing Striga parasitism without impinging on host strigolactone-related processes.

Immunoglobulin E (IgE) antibodies protect against helminth infections but can also cause life-threatening allergic reactions. Despite their role in human health, the cells that produce these antibodies are rarely observed and remain enigmatic. We isolated single IgE B cells from individuals with food allergies and used single-cell RNA sequencing to elucidate the gene expression and splicing patterns unique to these cells. We identified a surprising example of convergent evolution in which IgE antibodies underwent identical gene rearrangements in unrelated individuals. Through the acquisition of variable region mutations, these IgE antibodies gained high affinity and unexpected cross-reactivity to the clinically important peanut allergens Ara h 2 and Ara h 3. These findings provide insight into IgE B cell transcriptomics and enable biochemical dissection of this antibody class.

Domesticated maize evolved from wild teosinte under human influences in Mexico beginning around 9000 years before the present (yr B.P.), traversed Central America by ~7500 yr B.P., and spread into South America by ~6500 yr B.P. Landrace and archaeological maize genomes from South America suggest that the ancestral population to South American maize was brought out of the domestication center in Mexico and became isolated from the wild teosinte gene pool before traits of domesticated maize were fixed. Deeply structured lineages then evolved within South America out of this partially domesticated progenitor population. Genomic, linguistic, archaeological, and paleoecological data suggest that the southwestern Amazon was a secondary improvement center for partially domesticated maize. Multiple waves of human-mediated dispersal are responsible for the diversity and biogeography of modern South American maize.

To explore the developmental reorganization of the three-dimensional genome of the brain in the context of neuropsychiatric disease, we monitored chromosomal conformations in differentiating neural progenitor cells. Neuronal and glial differentiation was associated with widespread developmental remodeling of the chromosomal contact map and included interactions anchored in common variant sequences that confer heritable risk for schizophrenia. We describe cell type–specific chromosomal connectomes composed of schizophrenia risk variants and their distal targets, which altogether show enrichment for genes that regulate neuronal connectivity and chromatin remodeling, and evidence for coordinated transcriptional regulation and proteomic interaction of the participating genes. Developmentally regulated chromosomal conformation changes at schizophrenia-relevant sequences disproportionally occurred in neurons, highlighting the existence of cell type–specific disease risk vulnerabilities in spatial genome organization.

Whole-genome sequencing (WGS) has facilitated the first genome-wide evaluations of the contribution of de novo noncoding mutations to complex disorders. Using WGS, we identified 255,106 de novo mutations among sample genomes from members of 1902 quartet families in which one child, but not a sibling or their parents, was affected by autism spectrum disorder (ASD). In contrast to coding mutations, no noncoding functional annotation category, analyzed in isolation, was significantly associated with ASD. Casting noncoding variation in the context of a de novo risk score across multiple annotation categories, however, did demonstrate association with mutations localized to promoter regions. We found that the strongest driver of this promoter signal emanates from evolutionarily conserved transcription factor binding sites distal to the transcription start site. These data suggest that de novo mutations in promoter regions, characterized by evolutionary and functional signatures, contribute to ASD.

Genes implicated in neuropsychiatric disorders are active in human fetal brain, yet difficult to study in a longitudinal fashion. We demonstrate that organoids from human pluripotent cells model cerebral cortical development on the molecular level before 16 weeks postconception. A multiomics analysis revealed differentially active genes and enhancers, with the greatest changes occurring at the transition from stem cells to progenitors. Networks of converging gene and enhancer modules were assembled into six and four global patterns of expression and activity across time. A pattern with progressive down-regulation was enriched with human-gained enhancers, suggesting their importance in early human brain development. A few convergent gene and enhancer modules were enriched in autism-associated genes and genomic variants in autistic children. The organoid model helps identify functional elements that may drive disease onset.

To broaden our understanding of human neurodevelopment, we profiled transcriptomic and epigenomic landscapes across brain regions and/or cell types for the entire span of prenatal and postnatal development. Integrative analysis revealed temporal, regional, sex, and cell type–specific dynamics. We observed a global transcriptomic cup-shaped pattern, characterized by a late fetal transition associated with sharply decreased regional differences and changes in cellular composition and maturation, followed by a reversal in childhood-adolescence, and accompanied by epigenomic reorganizations. Analysis of gene coexpression modules revealed relationships with epigenomic regulation and neurodevelopmental processes. Genes with genetic associations to brain-based traits and neuropsychiatric disorders (including MEF2C, SATB2, SOX5, TCF4, and TSHZ3) converged in a small number of modules and distinct cell types, revealing insights into neurodevelopment and the genomic basis of neuropsychiatric risks.

Human nervous system development is an intricate and protracted process that requires precise spatiotemporal transcriptional regulation. We generated tissue-level and single-cell transcriptomic data from up to 16 brain regions covering prenatal and postnatal rhesus macaque development. Integrative analysis with complementary human data revealed that global intraspecies (ontogenetic) and interspecies (phylogenetic) regional transcriptomic differences exhibit concerted cup-shaped patterns, with a late fetal-to-infancy (perinatal) convergence. Prenatal neocortical transcriptomic patterns revealed transient topographic gradients, whereas postnatal patterns largely reflected functional hierarchy. Genes exhibiting heterotopic and heterochronic divergence included those transiently enriched in the prenatal prefrontal cortex or linked to autism spectrum disorder and schizophrenia. Our findings shed light on transcriptomic programs underlying the evolution of human brain development and the pathogenesis of neuropsychiatric disorders.

Most genetic risk for psychiatric disease lies in regulatory regions, implicating pathogenic dysregulation of gene expression and splicing. However, comprehensive assessments of transcriptomic organization in diseased brains are limited. In this work, we integrated genotypes and RNA sequencing in brain samples from 1695 individuals with autism spectrum disorder (ASD), schizophrenia, and bipolar disorder, as well as controls. More than 25% of the transcriptome exhibits differential splicing or expression, with isoform-level changes capturing the largest disease effects and genetic enrichments. Coexpression networks isolate disease-specific neuronal alterations, as well as microglial, astrocyte, and interferon-response modules defining previously unidentified neural-immune mechanisms. We integrated genetic and genomic data to perform a transcriptome-wide association study, prioritizing disease loci likely mediated by cis effects on brain expression. This transcriptome-wide characterization of the molecular pathology across three major psychiatric disorders provides a comprehensive resource for mechanistic insight and therapeutic development.

Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource for the adult brain across 1866 individuals. The PsychENCODE resource contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles for many cell types; expression quantitative-trait loci (QTLs); and further QTLs associated with chromatin, splicing, and cell-type proportions. Integration shows that varying cell-type proportions largely account for the cross-population variation in expression (with >88% reconstruction accuracy). It also allows building of a gene regulatory network, linking genome-wide association study variants to genes (e.g., 321 for schizophrenia). We embed this network into an interpretable deep-learning model, which improves disease prediction by ~6-fold versus polygenic risk scores and identifies key genes and pathways in psychiatric disorders.

The Sec61 protein-conducting channel mediates transport of many proteins, such as secretory proteins, across the endoplasmic reticulum (ER) membrane during or after translation. Posttranslational transport is enabled by two additional membrane proteins associated with the channel, Sec63 and Sec62, but its mechanism is poorly understood. We determined a structure of the Sec complex (Sec61-Sec63-Sec71-Sec72) from Saccharomyces cerevisiae by cryo-electron microscopy (cryo-EM). The structure shows that Sec63 tightly associates with Sec61 though interactions in cytosolic, transmembrane, and ER-luminal domains, prying open Sec61’s lateral gate and translocation pore and thus activating the channel for substrate engagement. Furthermore, Sec63 optimally positions binding sites for cytosolic and luminal chaperones in the complex to enable efficient polypeptide translocation. Our study provides mechanistic insights into eukaryotic posttranslational protein translocation.

Using a mid-infrared emission spectrometer based on a superconducting nanowire single-photon detector (SNSPD), we observe the dynamics of vibrational energy pooling of CO adsorbed at the surface of a NaCl crystal. After exciting a majority of the CO molecules to their first vibrationally excited state (v = 1), we observe infrared emission from states up to v = 27. Kinetic Monte Carlo simulations show that vibrational energy collects in a few CO molecules at the expense of those up to eight lattice sites away by selective excitation of NaCl’s transverse phonons. The vibrating CO molecules behave like classical oscillating dipoles, losing their energy to NaCl lattice-vibrations via the electromagnetic near-field. This is analogous to Sommerfeld’s description of the Earth’s influence on radio transmission by ground waves.

Forgetting is important. Without it, the relative importance of acquired memories in a changing environment is lost. We discovered that Synaptotagmin-3 (Syt3) localizes to post-synaptic endocytic zones and removes AMPA receptors from synaptic plasma membranes in response to stimulation. AMPA receptor internalization, long-term-depression (LTD), and decay of long-term-potentiation (LTP) of synaptic strength required calcium-sensing by Syt3, and were abolished by Syt3 knockout. In spatial memory tasks Syt3 knockout mice learned normally, but exhibited a lack of forgetting. Disrupting Syt3:GluA2 binding in a wild-type background mimicked the lack of LTP decay and lack of forgetting, and these effects were occluded in the Syt3 knockout background. Our findings provide evidence for a molecular mechanism whereby Syt3 internalizes AMPA receptors to depress synaptic strength and promote forgetting.

A wide-range of human diseases result from haploinsufficiency, where the function of one of the two gene copies is lost. Here, we targeted the remaining functional copy of a haploinsufficient gene using CRISPR-mediated activation (CRISPRa) in Sim1 and Mc4r heterozygous mouse models to rescue their obesity phenotype. Transgenic-based CRISPRa targeting of the Sim1 promoter or its distant hypothalamic enhancer upregulated its expression from the endogenous functional allele in a tissue-specific manner, rescuing the obesity phenotype in Sim1 heterozygous mice. To evaluate the therapeutic potential of CRISPRa, we injected CRISPRa-rAAV into the hypothalamus, which led to reversal of the obesity phenotype in Sim1 and Mc4r haploinsufficient mice. Our results suggest that endogenous gene upregulation could be a potential strategy to treat altered gene dosage diseases.

We assess scientific evidence that has emerged since the U.S. Environmental Protection Agency’s 2009 Endangerment Finding for six well-mixed greenhouse gases, and find that this new evidence lends increased support to the conclusion that these gases pose a danger to public health and welfare. Newly available evidence about a wide range of observed and projected impacts strengthens the association between risk of some of these impacts and anthropogenic climate change; indicates that some impacts or combinations of impacts have the potential to be more severe than previously understood; and identifies substantial risk of additional impacts through processes and pathways not considered in the endangerment finding.

Many optoelectronic properties have been reported for lead halide perovskite polycrystalline films. However, ambiguities in the evaluation of these properties remain, especially for long-range lateral charge transport, where ionic conduction can complicate interpretation of data. Here we demonstrate a new technique to measure the long-range charge carrier mobility in such materials. We combine quasi-steady-state photo-conductivity measurements (electrical probe) with photo-induced transmission and reflection measurements (optical probe) to simultaneously evaluate the conductivity and charge carrier density. With this knowledge we determine the lateral mobility to be ~ 2 cm2/Vs for CH3NH3PbI3 (MAPbI3) polycrystalline perovskite films prepared from the acetonitrile/methylamine solvent system. Furthermore, we present significant differences in long-range charge carrier mobilities, from 2.2 to 0.2 cm2/Vs, between films of contemporary perovskite compositions prepared via different fabrication processes, including solution and vapour phase deposition techniques. Arguably, our work provides the first accurate evaluation of the long-range lateral charge carrier mobility in lead halide perovskite films, with charge carrier density in the range typically achieved under photovoltaic operation.

We demonstrate exceptional performance for steam electrolysis at intermediate temperatures (500-650 °C) using protonic ceramic electrolyte cells comprised of the proton-permeable, high-activity mixed conductor PrBa0.5Sr0.5Co1.5Fe0.5O5+δ (PBSCF) as the air electrode, the highly proton-conductive and chemically stable perovskite oxide BaZr0.4Ce0.4Y0.1Yb0.1O3 (BZCYYb4411) as the electrolyte, and a composite of Ni-BZCYYb4411 as the fuel electrode. Cells constructed from this material set have been shown previously to function efficiently in fuel cell mode. We demonstrate here reversible operation, enabling hydrogen production when excess electricity is available and immediate electricity generation from stored hydrogen when power demand is high. The cells are stable under cyclic operation and also under prolonged continuous operation in electrolysis mode, undergoing minimal loss in electrochemical characteristics after 500 h at 550 °C. Microstructurally optimized cells yield a remarkable current density of -1.80 A cm-2 at 600 °C and an operating voltage of 1.3 V, of which, based on an electrochemically estimated Faradaic efficiency of 76%, -1.37 A cm-2 contributes to useful hydrogen.

A new, metal-free I2-catalyzed oxidative tandem annulation of 1,6-enynes by employing tert-butyl hydroperoxide (TBHP) as the oxidant and the oxygen atom resource for the synthesis of 1H-cyclopropa-[b]naphthalene-2,7-diones is developed. This reaction allows the formation of three new chemical bonds through selective radical addition across the C≡C bond and tandem cyclization cascades, which features a broad 1,6-enyne scope and excellent chemo- and diastereoselectivities.

The employment of an ancillary amine-substituted bisphosphonate ligand affords a dicobalt complex able to quantitate pH with a remarkably high sensitivity of 8.8(5) pH unit−1 at 37 °C through a ratiometric paramagnetic chemical exchange saturation transfer (PARACEST) approach, where the different pH dependences of amine and amide CEST peak intensities are utilized.

The organometallic complex (fac-Mn(apbpy)(CO)3Br) (apbpy = 4-(4-aminophenyl)-2,2’-bipyridine) grafted electrochemically onto carbon cloth performs as electrocatalyst for the aqueous reduction of CO2 to syngas. A faradaic efficiency of around 60% for CO and 40% for H2 at -1.35 V is achieved together with a productivity rate higher than 870NlCO h-1 gMn-1 at turnover numbers of up to 33200 during 10 hours of operation.

Herein we show that how metal–N,S-heterocyclic carbene intermediates are conveniently generated and utilized for the first time to construct N,S doubly-doped cationic conjugated tricyclic organic molecules which show tuneable emission. The chemistry proceeds via direct double C–H activation followed by annulative π-extension pathway.

A novel multicomponent coupling reaction involving the iridium-catalyzed 1,5-difunctionalization of 1,3-enynes with arylboronic acids and triazinanes is described. A key step in this 1,5-(aryl)aminomethylation reaction is the alkenyl-to-allyl 1,4-iridium(I) migration.