Brochlundsgaard0776

High-index dielectric materials are in great demand for nanophotonic devices and applications, from ultrathin optical elements to metal-free sub-diffraction light confinement and waveguiding. Here we show that chalcogenide topological insulators are particularly apt candidates for dielectric nanophotonics architectures in the infrared spectral range, by reporting metamaterial resonances in chalcogenide crystals sustained well inside the mid-infrared, choosing Bi2Te3 as case study within this family of materials. Strong resonant modulation of the incident electromagnetic field is achieved thanks to the exceptionally high refractive index ranging between 7 and 8 throughout the 2-10 μm region. Analysis of the complex mode structure in the metamaterial allude to the excitation of circular surface currents which could open pathways for enhanced light-matter interaction and low-loss plasmonic configurations by coupling to the spin-polarized topological surface carriers, thereby providing new opportunities to combine dielectric, plasmonic and magnetic metamaterials in a single platform.Gentamicin is a nephrotoxic antibiotic that causes acute kidney injury (AKI) primarily by targeting the proximal tubule epithelial cell. The development of an effective therapy for gentamicin-induced renal cell injury is limited by incomplete mechanistic insight. To address this challenge, we propose that RNAi signal pathway screening could identify a unifying mechanism of gentamicin-induced cell injury and suggest a therapeutic strategy to ameliorate it. Computational analysis of RNAi signal screens in gentamicin-exposed human proximal tubule cells suggested the cross-organelle stress response (CORE), the unfolded protein response (UPR), and cell chaperones as key targets of gentamicin-induced injury. To test this hypothesis, we assessed the effect of gentamicin on the CORE, UPR, and cell chaperone function, and tested the therapeutic efficacy of enhancing cell chaperone content. Early gentamicin exposure disrupted the CORE, evidenced by a rise in the ATPADP ratio, mitochondrial-specific H2O2 accumulation, Drp-1-mediated mitochondrial fragmentation, and endoplasmic reticulum-mitochondrial dissociation. CORE disruption preceded measurable increases in whole-cell oxidative stress, misfolded protein content, transcriptional UPR activation, and its untoward downstream effects CHOP expression, PARP cleavage, and cell death. Geranylgeranylacetone, a therapeutic that increases cell chaperone content, prevented mitochondrial H2O2 accumulation, preserved the CORE, reduced the burden of misfolded proteins and CHOP expression, and significantly improved survival in gentamicin-exposed cells. We identify CORE disruption as an early and remediable cause of gentamicin proteotoxicity that precedes downstream UPR activation and cell death. Preserving the CORE significantly improves renal cell survival likely by reducing organelle-specific proteotoxicity during gentamicin exposure.Environmental and epigenetic factors often play an important role in polygenic disorders. However, how such factors affect disease-specific tissues at the molecular level remains to be understood. Here, we address this in pulmonary arterial hypertension (PAH). We obtain pulmonary arterial endothelial cells (PAECs) from lungs of patients and controls (n = 19), and perform chromatin, transcriptomic and interaction profiling. Overall, we observe extensive remodeling at active enhancers in PAH PAECs and identify hundreds of differentially active TFs, yet find very little transcriptomic changes in steady-state. We devise a disease-specific enhancer-gene regulatory network and predict that primed enhancers in PAH PAECs are activated by the differentially active TFs, resulting in an aberrant response to endothelial signals, which could lead to disturbed angiogenesis and endothelial-to-mesenchymal-transition. We validate these predictions for a selection of target genes in PAECs stimulated with TGF-β, VEGF or serotonin. Our study highlights the role of chromatin state and enhancers in disease-relevant cell types of PAH.When learning about dynamic and uncertain environments, people should update their beliefs most strongly when new evidence is most informative, such as when the environment undergoes a surprising change or existing beliefs are highly uncertain. Here we show that modulations of surprise and uncertainty are encoded in a particular, temporally dynamic pattern of whole-brain functional connectivity, and this encoding is enhanced in individuals that adapt their learning dynamics more appropriately in response to these factors. The key feature of this whole-brain pattern of functional connectivity is stronger connectivity, or functional integration, between the fronto-parietal and other functional systems. Our results provide new insights regarding the association between dynamic adjustments in learning and dynamic, large-scale changes in functional connectivity across the brain.High-resolution soil moisture (SM) information is essential to many regional applications in hydrological and climate sciences. Many global estimates of surface SM are provided by satellite sensors, but at coarse spatial resolutions (lower than 25 km), which are not suitable for regional hydrologic and agriculture applications. Here we present a 16 years (2000-2015) high-resolution spatially and temporally consistent surface soil moisture reanalysis (ESSMRA) dataset (3 km, daily) over Europe from a land surface data assimilation system. Coarse-resolution satellite derived soil moisture data were assimilated into the community land model (CLM3.5) using an ensemble Kalman filter scheme, producing a 3 km daily soil moisture reanalysis dataset. Validation against 112 in-situ soil moisture observations over Europe shows that ESSMRA captures the daily, inter-annual, intra-seasonal patterns well with RMSE varying from 0.04 to 0.06 m3m-3 and correlation values above 0.5 over 70% of stations. The dataset presented here provides long-term daily surface soil moisture at a high spatiotemporal resolution and will be beneficial for many hydrological applications over regional and continental scales.For the sake of energy preservation, bacteria, upon transition to stationary phase, tone down their protein synthesis. This process is favored by the reversible binding of small stress-induced proteins to the ribosome to prevent unnecessary translation. One example is the conserved bacterial ribosome silencing factor (RsfS) that binds to uL14 protein onto the large ribosomal subunit and prevents its association with the small subunit. Here we describe the binding mode of Staphylococcus aureus RsfS to the large ribosomal subunit and present a 3.2 Å resolution cryo-EM reconstruction of the 50S-RsfS complex together with the crystal structure of uL14-RsfS complex solved at 2.3 Å resolution. The understanding of the detailed landscape of RsfS-uL14 interactions within the ribosome shed light on the mechanism of ribosome shutdown in the human pathogen S. aureus and might deliver a novel target for pharmacological drug development and treatment of bacterial infections.Cyanobacteria are model organisms for photosynthesis and are attractive for biotechnology applications. To aid investigation of genotype-phenotype relationships in cyanobacteria, we develop an inducible CRISPRi gene repression library in Synechocystis sp. PCC 6803, where we aim to target all genes for repression. We track the growth of all library members in multiple conditions and estimate gene fitness. The library reveals several clones with increased growth rates, and these have a common upregulation of genes related to cyclic electron flow. We challenge the library with 0.1 M L-lactate and find that repression of peroxiredoxin bcp2 increases growth rate by 49%. Transforming the library into an L-lactate-secreting Synechocystis strain and sorting top lactate producers enriches clones with sgRNAs targeting nutrient assimilation, central carbon metabolism, and cyclic electron flow. In many examples, productivity can be enhanced by repression of essential genes, which are difficult to access by transposon insertion.The laurel family within the Magnoliids has attracted attentions owing to its scents, variable inflorescences, and controversial phylogenetic position. Here, we present a chromosome-level assembly of the Litsea cubeba genome, together with low-coverage genomic and transcriptomic data for many other Lauraceae. Phylogenomic analyses show phylogenetic discordance at the position of Magnoliids, suggesting incomplete lineage sorting during the divergence of monocots, eudicots, and Magnoliids. Sulfatinib CSF-1R inhibitor An ancient whole-genome duplication (WGD) event occurred just before the divergence of Laurales and Magnoliales; subsequently, independent WGDs occurred almost simultaneously in the three Lauralean lineages. The phylogenetic relationships within Lauraceae correspond to the divergence of inflorescences, as evidenced by the phylogeny of FUWA, a conserved gene involved in determining panicle architecture in Lauraceae. Monoterpene synthases responsible for production of specific volatile compounds in Lauraceae are functionally verified. Our work sheds light on the evolution of the Lauraceae, the genetic basis for floral evolution and specific scents.Charge ordering creates a spontaneous array of differently charged ions and is associated with electronic phenomena such as superconductivity, colossal magnetoresistances (CMR), and multiferroicity. Charge orders are usually suppressed by chemical doping and site selective doping of a charge ordered array has not previously been demonstrated. Here we show that selective oxidation of one out of eight distinct Fe2+ sites occurs within the complex Fe2+/Fe3+ ordered structure of 2%-doped magnetite (Fe3O4), while the rest of the charge and orbitally ordered network remains intact. This 'charge order within a charge order' is attributed to the relative instability of the trimeron distortion surrounding the selected site. Our discovery suggests that similar complex charge ordered arrays could be used to provide surface sites for selective redox reactions, or for storing information by doping specific sites.Pyrazinamide is a sterilizing first-line tuberculosis drug. Genetic, metabolomic and biophysical analyses previously demonstrated that pyrazinoic acid, the bioactive form of the prodrug pyrazinamide (PZA), interrupts biosynthesis of coenzyme A in Mycobacterium tuberculosis by binding to aspartate decarboxylase PanD. While most drugs act by inhibiting protein function upon target binding, we find here that pyrazinoic acid is only a weak enzyme inhibitor. We show that binding of pyrazinoic acid to PanD triggers degradation of the protein by the caseinolytic protease ClpC1-ClpP. Thus, the old tuberculosis drug pyrazinamide exerts antibacterial activity by acting as a target degrader, a mechanism of action that has recently emerged as a successful strategy in drug discovery across disease indications. Our findings provide the basis for the rational discovery of next generation PZA.Cardiovascular diseases lead to 31.5% of deaths globally, and particularly myocardial infarction (MI) results in 7.4 million deaths per year. Diagnosis of MI and monitoring for prognostic use are critical for clinical management and biomedical research, which require advanced tools with accuracy and speed. Herein, we developed a plasmonic gold nano-island (pGold) chip assay for diagnosis and monitoring of MI. On-chip microarray analysis of serum biomarkers (e.g., cardiac troponin I) afforded up to 130-fold enhancement of near-infrared fluorescence for ultra-sensitive and quantitative detection within controlled periods, using 10 μL of serum only. The pGold chip assay achieved MI diagnostic sensitivity of 100% and specificity of 95.54%, superior to the standard chemiluminescence immunoassay in cardiovascular clinics. Further, we monitored biomarker concentrations regarding percutaneous coronary intervention for prognostic purpose. Our work demonstrated a designed approach using plasmonic materials for enhanced diagnosis and monitoring for prognostic use towards point-of-care testing.