Conspectus With nearly 20% of global electricity consumed by lighting, more efficient illumination sources can enable massive energy savings. However, effectively creating the high-quality white ...light required for indoor illumination remains a challenge. To accurately represent color, the illumination source must provide photons with all the energies visible to our eye. Such a broad emission is difficult to achieve from a single material. In commercial white-light sources, one or more light-emitting diodes, coated by one or more phosphors, yield a combined emission that appears white. However, combining emitters leads to changes in the emission color over time due to the unequal degradation rates of the emitters and efficiency losses due to overlapping absorption and emission energies of the different components. A single material that emits broadband white light (a continuous emission spanning 400–700 nm) would obviate these problems. In 2014, we described broadband white-light emission upon near-UV excitation from three new layered perovskites. To date, nine white-light-emitting perovskites have been reported by us and others, making this a burgeoning field of study. This Account outlines our work on understanding how a bulk material, with no obvious emissive sites, can emit every color of the visible spectrum. Although the initial discoveries were fortuitous, our understanding of the emission mechanism and identification of structural parameters that correlate with the broad emission have now positioned us to design white-light emitters. Layered hybrid halide perovskites feature anionic layers of corner-sharing metal-halide octahedra partitioned by organic cations. The narrow, room-temperature photoluminescence of lead-halide perovskites has been studied for several decades, and attributed to the radiative recombination of free excitons (excited electron–hole pairs). We proposed that the broad white emission we observed primarily stems from exciton self-trapping. Here, the exciton couples strongly to the lattice, creating transient elastic lattice distortions that can be viewed as “excited-state defects”. These deformations stabilize the exciton affording a broad emission with a large Stokes shift. Although material defects very likely contribute to the emission width, our mechanistic studies suggest that the emission mostly arises from the bulk material. Ultrafast spectroscopic measurements support self-trapping, with new, transient, electronic states appearing upon photoexcitation. Importantly, the broad emission appears common to layered Pb–Br and Pb–Cl perovskites, albeit with a strong temperature dependence. Although the emission is attributed to light-induced defects, it still reflects changes in the crystal structure. We find that greater out-of-plane octahedral tilting increases the propensity for the broad emission, enabling synthetic control over the broad emission. Many of these perovskites have color rendering abilities that exceed commercial requirements and mixing halides affords both “warm” and “cold” white light. The most efficient white-light-emitting perovskite has a quantum efficiency of 9%. Improving this value will make these phosphors attractive for solid-state lighting, particularly as large-area coatings that can be deposited inexpensively. The emission mechanism can also be extended to other low-dimensional systems. We hope this Account aids in expanding the phase space of white-light emitters and controlling their exciton dynamics by the synthetic, spectroscopic, theoretical, and engineering communities.
Layered halide perovskites offer a versatile platform for manipulating light through synthetic design. Although most layered perovskites absorb strongly in the ultraviolet (UV) or near-UV region, ...their emission can range from the UV to the infrared region of the electromagnetic spectrum. This emission can be very narrow, displaying high color purity, or it can be extremely broad, spanning the entire visible spectrum and providing high color rendition (or accurately reproducing illuminated colors). The origin of the photoluminescence can vary enormously. Strongly correlated electron–hole pairs, permanent lattice defects, transient light-induced defects, and ligand-field transitions in the inorganic layers and molecular chromophores in the organic layers can be involved in the emission mechanism. In this review, we highlight the different types of photoluminescence that may be attained from layered halide perovskites, with an emphasis on how the emission may be systematically tuned through changes to the bulk crystalline lattice: changes in composition, structure, and dimensionality.
Through structural and optical studies of a series of two-dimensional hybrid perovskites, we show that broadband emission upon near-ultraviolet excitation is common to (001) lead-bromide perovskites. ...Importantly, we find that the relative intensity of the broad emission correlates with increasing out-of-plane distortion of the Pb-(μ-Br)-Pb angle in the inorganic sheets. Temperature- and power-dependent photoluminescence data obtained on a representative (001) perovskite support an intrinsic origin to the broad emission from the bulk material, where photogenerated carriers cause excited-state lattice distortions mediated through electron-lattice coupling. In contrast, most inorganic phosphors contain extrinsic emissive dopants or emissive surface sites. The design rules established here could allow us to systematically optimize white-light emission from layered hybrid perovskites by fine-tuning the bulk crystal structure.
Interferons (IFN) are essential antiviral cytokines that establish the cellular antiviral state through upregulation of hundreds of interferon-stimulated genes (ISGs), most of which have ...uncharacterized functions and mechanisms. We identified cholesterol-25-hydroxylase (CH25H) as a broadly antiviral ISG. CH25H converts cholesterol to a soluble antiviral factor, 25-hydroxycholesterol (25HC). 25HC treatment in cultured cells broadly inhibited growth of enveloped viruses including VSV, HSV, HIV, and MHV68 and acutely pathogenic EBOV, RVFV, RSSEV, and Nipah viruses under BSL4 conditions. It suppressed viral growth by blocking membrane fusion between virus and cell. In animal models, Ch25h-deficient mice were more susceptible to MHV68 lytic infection. Moreover, administration of 25HC in humanized mice suppressed HIV replication and reversed T cell depletion. Thus, our studies demonstrate a unique mechanism by which IFN achieves its antiviral state through the production of a natural oxysterol to inhibit viral entry and implicate membrane-modifying oxysterols as potential antiviral therapeutics.
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► CH25H inhibits viral growth by production of an oxysterol, 25-hydroxycholesterol ► 25HC inhibits replication of VSV, HSV, HIV, MHV68, EBOV, NiV, RSSEV, and RVFV ► 25HC inhibits viral fusion of VSV and HIV ► In vivo, 25HC suppresses HIV growth and Ch25h is required for antiviral immunity
A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern ...of G614 increase at multiple geographic levels: national, regional, and municipal. The shift occurred even in local epidemics where the original D614 form was well established prior to introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to a higher titer as pseudotyped virions. In infected individuals, G614 is associated with lower RT-PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, but not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus and support continuing surveillance of Spike mutations to aid with development of immunological interventions.
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•A SARS-CoV-2 variant with Spike G614 has replaced D614 as the dominant pandemic form•The consistent increase of G614 at regional levels may indicate a fitness advantage•G614 is associated with lower RT PCR Cts, suggestive of higher viral loads in patients•The G614 variant grows to higher titers as pseudotyped virions
Korber et al. present evidence that there are now more SARS-CoV-2 viruses circulating in the human population globally that have the G614 form of the Spike protein versus the D614 form that was originally identified from the first human cases in Wuhan, China. Follow-up studies show that patients infected with G614 shed more viral nucleic acid compared with those with D614, and G614-bearing viruses show significantly higher infectious titers in vitro than their D614 counterparts.
Multiple sclerosis (MS) lesions that do not resolve in the months after they form harbour ongoing demyelination and axon degeneration, and are identifiable in vivo by their paramagnetic rims on MRI ...scans
. Here, to define mechanisms underlying this disabling, progressive neurodegenerative state
and foster development of new therapeutic agents, we used MRI-informed single-nucleus RNA sequencing to profile the edge of demyelinated white matter lesions at various stages of inflammation. We uncovered notable glial and immune cell diversity, especially at the chronically inflamed lesion edge. We define 'microglia inflamed in MS' (MIMS) and 'astrocytes inflamed in MS', glial phenotypes that demonstrate neurodegenerative programming. The MIMS transcriptional profile overlaps with that of microglia in other neurodegenerative diseases, suggesting that primary and secondary neurodegeneration share common mechanisms and could benefit from similar therapeutic approaches. We identify complement component 1q (C1q) as a critical mediator of MIMS activation, validated immunohistochemically in MS tissue, genetically by microglia-specific C1q ablation in mice with experimental autoimmune encephalomyelitis, and therapeutically by treating chronic experimental autoimmune encephalomyelitis with C1q blockade. C1q inhibition is a potential therapeutic avenue to address chronic white matter inflammation, which could be monitored by longitudinal assessment of its dynamic biomarker, paramagnetic rim lesions, using advanced MRI methods.
Adipose tissue is an essential regulator of metabolic homeostasis. In contrast with white adipose tissue, which stores excess energy in the form of triglycerides, brown adipose tissue is thermogenic, ...dissipating energy as heat via the unique expression of the mitochondrial uncoupling protein UCP1. A subset of UCP1+ adipocytes develops within white adipose tissue in response to physiological stimuli; however, the developmental origin of these “brite” or “beige” adipocytes is unclear. Here, we report the identification of a BMP7-ROCK signaling axis regulating beige adipocyte formation via control of the G-actin-regulated transcriptional coactivator myocardin-related transcription factor A, MRTFA. White adipose tissue from MRTFA–/– mice contains more multilocular adipocytes and expresses enhanced levels of brown-selective proteins, including UCP1. MRTFA–/– mice also show improved metabolic profiles and protection from diet-induced obesity and insulin resistance. Our study hence unravels a central pathway driving the development of physiologically functional beige adipocytes.
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•BMP7 induces brown adipogenesis in mesenchymal stem cells•BMP7 inhibits ROCK and promotes F- to G-actin conversion•Overexpression of MRTFA or SRF inhibits brown adipogenesis•Loss of MRTFA promotes browning and resistance to obesity
A signaling axis driven by ROCK and the transcription factor MRTFA regulates the conversion of mesenchymal stem cells (MSCs) to brown-like (beige) adipocytes. Small molecule inhibitors or loss of MRTFA in mice leads to beige adipocyte formation, enhanced energy expenditure, and protection against diet-induced obesity.
Mechanisms of selective autophagy of the ER, known as ER-phagy, require molecular delineation, particularly in vivo. It is unclear how these events control ER proteostasis and cellular health. Here, ...we identify cell-cycle progression gene 1 (CCPG1), an ER-resident protein with no known physiological role, as a non-canonical cargo receptor that directly binds to core autophagy proteins via an LIR motif to mammalian ATG8 proteins and, independently and via a discrete motif, to FIP200. These interactions facilitate ER-phagy. The CCPG1 gene is inducible by the unfolded protein response and thus directly links ER stress to ER-phagy. In vivo, CCPG1 protects against ER luminal protein aggregation and consequent unfolded protein response hyperactivation and tissue injury of the exocrine pancreas. Thus, via identification of this autophagy protein, we describe an unexpected molecular mechanism of ER-phagy and provide evidence that this may be physiologically relevant in ER luminal proteostasis.
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•CCPG1 is an ER stress-inducible ER-phagy cargo receptor in mammals•CCPG1 binds directly to ATG8 proteins and FIP200 via distinct peptide motifs•CCPG1 lysosomal degradation and ER-phagy both require these interactions•CCPG1 maintains normal ER luminal proteostasis in pancreatic acinar cells in vivo
The mechanisms and physiological functions of ER autophagy (ER-phagy) are incompletely understood. Smith et al. show that the ER membrane-resident protein CCPG1 is an effector of ER stress responses, driving ER-phagy via interaction with ATG8 and FIP200. CCPG1 maintains ER luminal proteostasis within pancreatic acinar cells in vivo.
Placentas can exhibit chromosomal aberrations that are absent from the fetus
. The basis of this genetic segregation, which is known as confined placental mosaicism, remains unknown. Here we ...investigated the phylogeny of human placental cells as reconstructed from somatic mutations, using whole-genome sequencing of 86 bulk placental samples (with a median weight of 28 mg) and of 106 microdissections of placental tissue. We found that every bulk placental sample represents a clonal expansion that is genetically distinct, and exhibits a genomic landscape akin to that of childhood cancer in terms of mutation burden and mutational imprints. To our knowledge, unlike any other healthy human tissue studied so far, the placental genomes often contained changes in copy number. We reconstructed phylogenetic relationships between tissues from the same pregnancy, which revealed that developmental bottlenecks genetically isolate placental tissues by separating trophectodermal lineages from lineages derived from the inner cell mass. Notably, there were some cases with full segregation-within a few cell divisions of the zygote-of placental lineages and lineages derived from the inner cell mass. Such early embryonic bottlenecks may enable the normalization of zygotic aneuploidy. We observed direct evidence for this in a case of mosaic trisomic rescue. Our findings reveal extensive mutagenesis in placental tissues and suggest that mosaicism is a typical feature of placental development.
Oligodendrocyte precursor cells (OPCs) are abundant in the adult central nervous system, and have the capacity to regenerate oligodendrocytes and myelin. However, in inflammatory diseases such as ...multiple sclerosis (MS) remyelination is often incomplete. To investigate how neuroinflammation influences OPCs, we perform in vivo fate-tracing in an inflammatory demyelinating mouse model. Here we report that OPC differentiation is inhibited by both effector T cells and IFNγ overexpression by astrocytes. IFNγ also reduces the absolute number of OPCs and alters remaining OPCs by inducing the immunoproteasome and MHC class I. In vitro, OPCs exposed to IFNγ cross-present antigen to cytotoxic CD8 T cells, resulting in OPC death. In human demyelinated MS brain lesions, but not normal appearing white matter, oligodendroglia exhibit enhanced expression of the immunoproteasome subunit PSMB8. Therefore, OPCs may be co-opted by the immune system in MS to perpetuate the autoimmune response, suggesting that inhibiting immune activation of OPCs may facilitate remyelination.
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