Quantum efficiencies of organic-inorganic hybrid lead halide perovskite light-emitting devices (LEDs) have increased significantly, but poor device operational stability still impedes their further development and application. All-inorganic perovskites show better stability than the hybrid counterparts, but the performance of their respective films used in LEDs is limited by the large perovskite grain sizes, which lowers the radiative recombination probability and results in grain boundary related trap states. We realize smooth and pinhole-free, small-grained inorganic perovskite films with improved photoluminescence quantum yield by introducing trifluoroacetate anions to effectively passivate surface defects and control the crystal growth. As a result, efficient green LEDs based on inorganic perovskite films achieve a high current efficiency of 32.0 cd A-1 corresponding to an external quantum efficiency of 10.5%. More importantly, our all-inorganic perovskite LEDs demonstrate a record operational lifetime, with a half-lifetime of over 250 h at an initial luminance of 100 cd m-2.

Oxytocin is a neuropeptide involved in animal and human reproductive and social behavior. Three oxytocin signaling genes have been frequently implicated in human social behavior: OXT (structural gene for oxytocin), OXTR (oxytocin receptor), and CD38 (oxytocin secretion). Here, we characterized the distribution of OXT, OXTR, and CD38 mRNA across the human brain by creating voxel-by-voxel volumetric expression maps, and identified putative gene pathway interactions by comparing gene expression patterns across 20,737 genes. Expression of the three selected oxytocin pathway genes was enriched in subcortical and olfactory regions and there was high co-expression with several dopaminergic and muscarinic acetylcholine genes, reflecting an anatomical basis for critical gene pathway interactions. fMRI meta-analysis revealed that the oxytocin pathway gene maps correspond with the processing of anticipatory, appetitive, and aversive cognitive states. The oxytocin signaling system may interact with dopaminergic and muscarinic acetylcholine signaling to modulate cognitive state processes involved in complex human behaviors.

A fundamental step in membrane protein biogenesis is their integration into the lipid bilayer with a defined orientation of each transmembrane segment. Despite this, it remains unclear how cells detect and handle failures in this process. Here we show that single point mutations in the membrane protein connexin 32 (Cx32), which cause Charcot-Marie-Tooth disease, can cause failures in membrane integration. This leads to Cx32 transport defects and rapid degradation. Our data show that multiple chaperones detect and remedy this aberrant behavior: the ER-membrane complex (EMC) aids in membrane integration of low-hydrophobicity transmembrane segments. If they fail to integrate, these are recognized by the ER-lumenal chaperone BiP. Ultimately, the E3 ligase gp78 ubiquitinates Cx32 proteins, targeting them for degradation. Thus, cells use a coordinated system of chaperones for the complex task of membrane protein biogenesis, which can be compromised by single point mutations, causing human disease.

How innate T cells (ITC), including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells, maintain a poised effector state has been unclear. Here we address this question using low-input and single-cell RNA-seq of human lymphocyte populations. Unbiased transcriptomic analyses uncover a continuous 'innateness gradient', with adaptive T cells at one end, followed by MAIT, iNKT, γδ T and natural killer cells at the other end. Single-cell RNA-seq reveals four broad states of innateness, and heterogeneity within canonical innate and adaptive populations. Transcriptional and functional data show that innateness is characterized by pre-formed mRNA encoding effector functions, but impaired proliferation marked by decreased baseline expression of ribosomal genes. Together, our data shed new light on the poised state of ITC, in which innateness is defined by a transcriptionally-orchestrated trade-off between rapid cell growth and rapid effector function.

Permafrost warming has the potential to amplify global climate change, because when frozen sediments thaw it unlocks soil organic carbon. Yet to date, no globally consistent assessment of permafrost temperature change has been compiled. Here we use a global data set of permafrost temperature time series from the Global Terrestrial Network for Permafrost to evaluate temperature change across permafrost regions for the period since the International Polar Year (2007-2009). During the reference decade between 2007 and 2016, ground temperature near the depth of zero annual amplitude in the continuous permafrost zone increased by 0.39 ± 0.15 °C. Over the same period, discontinuous permafrost warmed by 0.20 ± 0.10 °C. Permafrost in mountains warmed by 0.19 ± 0.05 °C and in Antarctica by 0.37 ± 0.10 °C. Globally, permafrost temperature increased by 0.29 ± 0.12 °C. The observed trend follows the Arctic amplification of air temperature increase in the Northern Hemisphere. In the discontinuous zone, however, ground warming occurred due to increased snow thickness while air temperature remained statistically unchanged.

Large-scale implementation of electrochemical hydrogen production requires several fundamental issues to be solved, including understanding the mechanism and developing inexpensive electrocatalysts that work well at high current densities. Here we address these challenges by exploring the roles of morphology and surface chemistry, and develop inexpensive and efficient electrocatalysts for hydrogen evolution. Three model electrocatalysts are flat platinum foil, molybdenum disulfide microspheres, and molybdenum disulfide microspheres modified by molybdenum carbide nanoparticles. The last catalyst is highly active for hydrogen evolution independent of pH, with low overpotentials of 227 mV in acidic medium and 220 mV in alkaline medium at a high current density of 1000 mA cm-2, because of enhanced transfer of mass (reactants and hydrogen bubbles) and fast reaction kinetics due to surface oxygen groups formed on molybdenum carbide during hydrogen evolution. Our work may guide rational design of electrocatalysts that work well at high current densities.

Despite their discovery over 25 years ago, the Marine Group II Euryarchaea (MGII) remain a difficult group of organisms to study, lacking cultured isolates and genome references. The MGII have been identified in marine samples from around the world, and evidence supports a photoheterotrophic lifestyle combining phototrophy via proteorhodopsins with the remineralization of high molecular weight organic matter. Divided between two clades, the MGII have distinct ecological patterns that are not understood based on the limited number of available genomes. Here, I present a comparative genomic analysis of 250 MGII genomes, providing a comprehensive investigation of these mesophilic archaea. This analysis identifies 17 distinct subclades including nine subclades that previously lacked reference genomes. The metabolic potential and distribution of the MGII genera reveals distinct roles in the environment, identifying algal-saccharide-degrading coastal subclades, protein-degrading oligotrophic surface ocean subclades, and mesopelagic subclades lacking proteorhodopsins, common in all other subclades.

Triboelectric charging of insulators, also known as contact charging in which electrical charges develop on surfaces upon contact, is a significant problem that is especially critical for various industries such as polymers, pharmaceuticals, electronics, and space. Several methods of tribocharge mitigation exist in practice; however, none can reach the practicality of using light in the process. Here we show a light-controlled manipulation of triboelectric charges on common polymers, in which the tribocharges are mitigated upon illumination with appropriate wavelengths of light in presence of a mediator organic dye. Our method provides spatial and temporal control of mitigation of static charges on common polymer surfaces by a mechanism that involves photoexcitation of organic dyes, which also allows additional control using wavelength. This control over charge mitigation provides a way to manipulate macroscopic objects by tribocharging followed by light-controlled discharging.

Macrophages serve multiple functions including immune regulation, morphogenesis, tissue homeostasis and healing reactions. The current paradigm holds that mammary gland macrophages first arise postnatally during the prepubertal period from the bone marrow-derived monocytes. Here we delineate the origins of tissue-resident mammary gland macrophages using high-dimension phenotypic analyses, cell-fate mapping experiments, gene-deficient mice lacking selective macrophage subtypes, and antibody-based depletion strategies. We show that tissue-resident macrophages are found in mammary glands already before birth, and that the yolk sac-derived and fetal liver-derived macrophages outnumber the adult-derived macrophages in the mammary gland also in the adulthood. In addition, fetal-derived mammary gland macrophages have a characteristic phenotype, display preferential periductal and perivascular localization, and are highly active in scavenging. These findings identify fetal-derived macrophages as the predominant leukocyte type in the adult mammary gland stroma, and reveal previously unknown complexity of macrophage biology in the breast.

The many-body quantum nature of molecules determines their static and dynamic properties, but remains the main obstacle in their accurate description. Ultrashort extreme ultraviolet pulses offer a means to reveal molecular dynamics at ultrashort timescales. Here, we report the use of time-resolved electron-momentum imaging combined with extreme ultraviolet attosecond pulses to study highly excited organic molecules. We measure relaxation timescales that increase with the state energy. High-level quantum calculations show these dynamics are intrinsic to the time-dependent many-body molecular wavefunction, in which multi-electronic and non-Born-Oppenheimer effects are fully entangled. Hints of coherent vibronic dynamics, which persist despite the molecular complexity and high-energy excitation, are also observed. These results offer opportunities to understand the molecular dynamics of highly excited species involved in radiation damage and astrochemistry, and the role of quantum mechanical effects in these contexts.

The platinum-based drug cisplatin is a widely used first-line therapy for several cancers. Cisplatin interacts with DNA mainly in the form of Pt-d(GpG) di-adduct, which stalls cell proliferation and activates DNA damage response. Although cisplatin shows a broad spectrum of anticancer activity, its utility is limited due to acquired drug resistance and toxicity to non-targeted tissues. Here, by integrating genome-wide high-throughput Damage-seq, XR-seq, and RNA-seq approaches, along with publicly available epigenomic data, we systematically study the genome-wide profiles of cisplatin damage formation and excision repair in mouse kidney, liver, lung and spleen. We find different DNA damage and repair spectra across mouse organs, which are associated with tissue-specific transcriptomic and epigenomic profiles. The framework and the multi-omics data we present here constitute an unbiased foundation for understanding the mechanisms of cellular response to cisplatin. Our approach should be applicable for studying drug resistance and for tailoring cancer chemotherapy regimens.

A major challenge in genomics is the knowledge gap between sequence and its encoded function. Gain-of-function methods based on gene overexpression are attractive avenues for phenotype-based functional screens, but are not easily applied in high-throughput across many experimental conditions. Here, we present Dual Barcoded Shotgun Expression Library Sequencing (Dub-seq), a method that uses random DNA barcodes to greatly increase experimental throughput. As a demonstration of this approach, we construct a Dub-seq library with Escherichia coli genomic DNA, performed 155 genome-wide fitness assays in 52 experimental conditions, and identified overexpression phenotypes for 813 genes. We show that Dub-seq data is reproducible, accurately recapitulates known biology, and identifies hundreds of novel gain-of-function phenotypes for E. coli genes, a subset of which we verified with assays of individual strains. Dub-seq provides complementary information to loss-of-function approaches and will facilitate rapid and systematic functional characterization of microbial genomes.

DNA methylation is an essential epigenetic process in mammals, intimately involved in gene regulation. Here we address the extent to which genetics, sex, and pregnancy influence genomic DNA methylation by intercrossing 2 inbred mouse strains, C57BL/6N and C3H/HeN, and analyzing DNA methylation in parents and offspring using whole-genome bisulfite sequencing. Differential methylation across genotype is detected at thousands of loci and is preserved on parental alleles in offspring. In comparison of autosomal DNA methylation patterns across sex, hundreds of differentially methylated regions are detected. Comparison of animals with different histories of pregnancy within our study reveals a CpG methylation pattern that is restricted to female animals that had borne offspring. Collectively, our results demonstrate the stability of CpG methylation across generations, clarify the interplay of epigenetics with genetics and sex, and suggest that CpG methylation may serve as an epigenetic record of life events in somatic tissues at loci whose expression is linked to the relevant biology.

Antibiotic resistance represents a growing health crisis that necessitates the immediate discovery of novel treatment strategies. One such strategy is the identification of collateral sensitivities, wherein evolution under a first drug induces susceptibility to a second. Here, we report that sequential drug regimens derived from in vitro evolution experiments may have overstated therapeutic benefit, predicting a collaterally sensitive response where cross-resistance ultimately occurs. We quantify the likelihood of this phenomenon by use of a mathematical model parametrised with combinatorially complete fitness landscapes for Escherichia coli. Through experimental evolution we then verify that a second drug can indeed stochastically exhibit either increased susceptibility or increased resistance when following a first. Genetic divergence is confirmed as the driver of this differential response through targeted and whole genome sequencing. Taken together, these results highlight that the success of evolutionarily-informed therapies is predicated on a rigorous probabilistic understanding of the contingencies that arise during the evolution of drug resistance.

Human skin constructs (HSCs) have the potential to provide an effective therapy for patients with significant skin injuries and to enable human-relevant drug screening for skin diseases; however, the incorporation of engineered skin appendages, such as hair follicles (HFs), into HSCs remains a major challenge. Here, we demonstrate a biomimetic approach for generation of human HFs within HSCs by recapitulating the physiological 3D organization of cells in the HF microenvironment using 3D-printed molds. Overexpression of Lef-1 in dermal papilla cells (DPC) restores the intact DPC transcriptional signature and significantly enhances the efficiency of HF differentiation in HSCs. Furthermore, vascularization of hair-bearing HSCs prior to engraftment allows for efficient human hair growth in immunodeficient mice. The ability to regenerate an entire HF from cultured human cells will have a transformative impact on the medical management of different types of alopecia, as well as chronic wounds, which represent major unmet medical needs.

Single crystalline perovskites exhibit high optical absorption, long carrier lifetime, large carrier mobility, low trap-state-density and high defect tolerance. Unfortunately, all single crystalline perovskites attained so far are limited to bulk single crystals and small area wafers. As such, it is impossible to design highly demanded flexible single-crystalline electronics and wearable devices including displays, touch sensing devices, transistors, etc. Herein we report a method of induced peripheral crystallization to prepare large area flexible single-crystalline membrane (SCM) of phenylethylamine lead iodide (C6H5C2H4NH3)2PbI4 with area exceeding 2500 mm2 and thinness as little as 0.6 μm. The ultrathin flexible SCM exhibits ultralow defect density, superior uniformity and long-term stability. Using the superior ultrathin membrane, a series of flexible photosensors were designed and fabricated to exhibit very high external quantum efficiency of 26530%, responsivity of 98.17 A W-1 and detectivity as much as 1.62 × 1015 cm Hz1/2 W-1 (Jones).

Spatial mapping is a promising strategy to investigate the mechanisms underlying the incidence of psychosis. We analyzed a case-cohort study (n = 24,028), drawn from the 1.47 million Danish persons born between 1981 and 2005, using a novel framework for decomposing the geospatial risk for schizophrenia based on locale of upbringing and polygenic scores. Upbringing in a high environmental risk locale increases the risk for schizophrenia by 122%. Individuals living in a high gene-by-environmental risk locale have a 78% increased risk compared to those who have the same genetic liability but live in a low-risk locale. Effects of specific locales vary substantially within the most densely populated city of Denmark, with hazard ratios ranging from 0.26 to 9.26 for environment and from 0.20 to 5.95 for gene-by-environment. These findings indicate the critical synergism of gene and environment on the etiology of schizophrenia and demonstrate the potential of incorporating geolocation in genetic studies.

The propensity of viruses to acquire genetic material from relatives and possibly from infected hosts makes them excellent candidates as vectors for horizontal gene transfer. However, virus-mediated acquisition of host genetic material, as deduced from historical events, appears to be rare. Here, we report spontaneous and surprisingly efficient generation of hybrid virus/host DNA molecules in the form of minicircles during infection of Beta vulgaris by Beet curly top Iran virus (BCTIV), a single-stranded DNA virus. The hybrid minicircles replicate, become encapsidated into viral particles, and spread systemically throughout infected plants in parallel with the viral infection. Importantly, when co-infected with BCTIV, B. vulgaris DNA captured in minicircles replicates and is transcribed in other plant species that are sensitive to BCTIV infection. Thus, we have likely documented in real time the initial steps of a possible path of virus-mediated horizontal transfer of chromosomal DNA between plant species.

Nanocarrier-based drug delivery is a promising therapeutic approach that offers unique possibilities for the treatment of various diseases. However, inside the blood stream, nanocarriers' properties may change significantly due to interactions with proteins, aggregation, decomposition or premature loss of cargo. Thus, a method for precise, in situ characterization of drug nanocarriers in blood is needed. Here we show how the fluorescence correlation spectroscopy that is a well-established method for measuring the size, loading efficiency and stability of drug nanocarriers in aqueous solutions can be used to directly characterize drug nanocarriers in flowing blood. As the blood is not transparent for visible light and densely crowded with cells, we label the nanocarriers or their cargo with near-infrared fluorescent dyes and fit the experimental autocorrelation functions with an analytical model accounting for the presence of blood cells. The developed methodology contributes towards quantitative understanding of the in vivo behavior of nanocarrier-based therapeutics.

There is growing interest in bioenergy with carbon capture and storage (BECCS) as a possible technology for removing CO2 from the atmosphere. In the first study of its kind, we investigate whether and how different forms of incentivisation impact on public perceptions of this technology. We develop a new experimental method to triangulate perceptions of BECCS in different policy scenarios through quantitative measurement and qualitative elicitation. Here we show that the type of policy instrument used to incentivise BECCS significantly affects perceptions of the technology itself. While we find approval of coercive and persuasion-based policy scenarios for incentivisation, supportive instruments proved polarising. Payments based on the amount of CO2 removed from the atmosphere were approved, but guarantees of higher prices for producers selling energy derived from BECCS were strongly opposed. We conclude that public support for BECCS is inextricably linked to attitudes towards the policies through which it is incentivised.