Notes

Different useful aspects inside RNA forecast transcriptome-wide simply by orthogonal RNA construction probing.
Dielectric metasurfaces support resonances that are widely explored both for far-field wavefront shaping and for near-field sensing and imaging. Their design explores the interplay between localised and extended resonances, with a typical trade-off between Q-factor and light localisation; high Q-factors are desirable for refractive index sensing while localisation is desirable for imaging resolution. Here, we show that a dielectric metasurface consisting of a nanohole array in amorphous silicon provides a favourable trade-off between these requirements. We have designed and realised the metasurface to support two optical modes both with sharp Fano resonances that exhibit relatively high Q-factors and strong spatial confinement, thereby concurrently optimizing the device for both imaging and biochemical sensing. For the sensing application, we demonstrate a limit of detection (LOD) as low as 1 pg/ml for Immunoglobulin G (IgG); for resonant imaging, we demonstrate a spatial resolution below 1 µm and clearly resolve individual E. coli bacteria. The combined low LOD and high spatial resolution opens new opportunities for extending cellular studies into the realm of microbiology, e.g. for studying antimicrobial susceptibility.The interplay of genetic and environmental factors behind cognitive development has preoccupied multiple fields of science and sparked heated debates over the decades. Here we tested the hypothesis that developmental genes rely heavily on cognitive challenges-as opposed to natural maturation. Starting with a polygenic score (cogPGS) that previously explained variation in cognitive performance in adults, we estimated its effect in 344 children and adolescents (mean age of 12 years old, ranging from 6 to 25) who showed changes in working memory (WM) in two distinct samples (1) a developmental sample showing significant WM gains after 2 years of typical, age-related development, and (2) a training sample showing significant, experimentally-induced WM gains after 25 days of an intense WM training. We found that the same genetic factor, cogPGS, significantly explained the amount of WM gain in both samples. And there was no interaction of cogPGS with sample, suggesting that those genetic factors are neutral to whether the WM gains came from development or training. These results represent evidence that cognitive challenges are a central piece in the gene-environment interplay during cognitive development. We believe our study sheds new light on previous findings of interindividual differences in education (rich-get-richer and compensation effects), brain plasticity in children, and the heritability increase of intelligence across the lifespan.Otitis media (OM), known as a middle ear infection, is the leading cause of antibiotic prescriptions for children. With wide-spread use of antibiotics in OM, resistance to antibiotics continues to decrease the efficacy of the treatment. Furthermore, as the presence of a middle ear biofilm has contributed to this reduced susceptibility to antimicrobials, effective interventions are necessary. A miniaturized 3D-printed microplasma jet array has been developed to inactivate Pseudomonas aeruginosa, a common bacterial strain associated with OM. The experiments demonstrate the disruption of planktonic and biofilm P. aeruginosa by long-lived molecular species generated by microplasma, as well as the synergy of combining microplasma treatment with antibiotic therapy. In addition, a middle ear phantom model was developed with an excised rat eardrum to investigate the antimicrobial effects of microplasma on bacteria located behind the eardrum, as in a patient-relevant setup. These results suggest the potential for microplasma as a new treatment paradigm for OM.Bacterial processes necessary for adaption to stressful host environments are potential targets for new antimicrobials. Here, we report large-scale transcriptomic analyses of 32 human bacterial pathogens grown under 11 stress conditions mimicking human host environments. The potential relevance of the in vitro stress conditions and responses is supported by comparisons with available in vivo transcriptomes of clinically important pathogens. Calculation of a probability score enables comparative cross-microbial analyses of the stress responses, revealing common and unique regulatory responses to different stresses, as well as overlapping processes participating in different stress responses. We identify conserved and species-specific 'universal stress responders', that is, genes showing altered expression in multiple stress conditions. Non-coding RNAs are involved in a substantial proportion of the responses. The data are collected in a freely available, interactive online resource (PATHOgenex).In peripheral nerves, Schwann cells form myelin and provide trophic support to axons. We previously showed that the mitochondrial protein prohibitin 2 can localize to the axon-Schwann-cell interface and is required for developmental myelination. Whether the homologous protein prohibitin 1 has a similar role, and whether prohibitins also play important roles in Schwann cell mitochondria is unknown. Here, we show that deletion of prohibitin 1 in Schwann cells minimally perturbs development, but later triggers a severe demyelinating peripheral neuropathy. Moreover, mitochondria are heavily affected by ablation of prohibitin 1 and demyelination occurs preferentially in cells with apparent mitochondrial loss. Furthermore, in response to mitochondrial damage, Schwann cells trigger the integrated stress response, but, contrary to what was previously suggested, this response is not detrimental in this context. These results identify a role for prohibitin 1 in myelin integrity and advance our understanding about the Schwann cell response to mitochondrial damage.Chinese goldthread (Coptis chinensis Franch.), a member of the Ranunculales, represents an important early-diverging eudicot lineage with diverse medicinal applications. Here, we present a high-quality chromosome-scale genome assembly and annotation of C. chinensis. Phylogenetic and comparative genomic analyses reveal the phylogenetic placement of this species and identify a single round of ancient whole-genome duplication (WGD) shared by the Ranunculaceae. We characterize genes involved in the biosynthesis of protoberberine-type alkaloids in C. chinensis. In particular, local genomic tandem duplications contribute to member amplification of a Ranunculales clade-specific gene family of the cytochrome P450 (CYP) 719. The functional versatility of a key CYP719 gene that encodes the (S)-canadine synthase enzyme involved in the berberine biosynthesis pathway may play critical roles in the diversification of other berberine-related alkaloids in C. chinensis. Alofanib Our study provides insights into the genomic landscape of early-diverging eudicots and provides a valuable model genome for genetic and applied studies of Ranunculales.Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke.Polar materials display a series of interesting and widely exploited properties owing to the inherent coupling between their fixed electric dipole and any action that involves a change in their charge distribution. Among these properties are piezoelectricity, ferroelectricity, pyroelectricity, and the bulk photovoltaic effect. Here we report the observation of a related property in this series, where an external electric field applied parallel or anti-parallel to the polar axis of a crystal leads to an increase or decrease in its second-order nonlinear optical response, respectively. This property of electric-field-modulated second-harmonic generation (EFM-SHG) is observed here in nanowires of the polar crystal ZnO, and is exploited as an analytical tool to directly determine by optical means the absolute direction of their polarity, which in turn provides important information about their epitaxy and growth mechanism. EFM-SHG may be observed in any type of polar nanostructures and used to map the absolute polarity of materials at the nanoscale.The limited availability of nasopharyngeal carcinoma-related progression biomarker array kits that offer physicians comprehensive information is disadvantageous for monitoring cancer progression. To develop a biomarker array kit, systematic identification and differentiation of a large number of distinct molecular surface-enhanced Raman scattering (SERS) reporters with high spectral temporal resolution is a major challenge. To address this unmet need, we use the chemistry of metal carbonyls to construct a series of unique SERS reporters with the potential to provide logical and highly multiplex information during testing. In this study, we report that geometric control over metal carbonyls on nanotags can produce 14 distinct barcodes that can be decoded unambiguously using commercial Raman spectroscopy. These metal carbonyl nanobarcodes are tested on human blood samples and show strong sensitivity (0.07 ng/mL limit of detection, average CV of 6.1% and >92% degree of recovery) and multiplexing capabilities for MMPs.Single-atom catalysts (SACs) have emerged as a frontier in heterogeneous catalysis due to the well-defined active site structure and the maximized metal atom utilization. Nevertheless, the robustness of SACs remains a critical concern for practical applications. Herein, we report a highly active, selective and robust Ru SAC which was synthesized by pyrolysis of ruthenium acetylacetonate and N/C precursors at 900 °C in N2 followed by treatment at 800 °C in NH3. The resultant Ru1-N3 structure exhibits moderate capability for hydrogen activation even in excess NH3, which enables the effective modulation between transimination and hydrogenation activity in the reductive amination of aldehydes/ketones towards primary amines. As a consequence, it shows superior amine productivity, unrivalled resistance against CO and sulfur, and unexpectedly high stability under harsh hydrotreating conditions compared to most SACs and nanocatalysts. This SAC strategy will open an avenue towards the rational design of highly selective and robust catalysts for other demanding transformations.The SARS-CoV-2 nsp16/nsp10 enzyme complex modifies the 2'-OH of the first transcribed nucleotide of the viral mRNA by covalently attaching a methyl group to it. The 2'-O methylation of the first nucleotide converts the status of mRNA cap from Cap-0 to Cap-1, and thus, helps the virus evade immune surveillance in host cells. Here, we report two structures of nsp16/nsp10 representing pre- and post-release states of the RNA product (Cap-1). We observe overall widening of the enzyme upon product formation, and an inward twisting motion in the substrate binding region upon product release. These conformational changes reset the enzyme for the next round of catalysis. The structures also identify a unique binding mode and the importance of a divalent metal ion for 2'-O methylation. We also describe underlying structural basis for the perturbed enzymatic activity of a clinical variant of SARS-CoV-2, and a previous SARS-CoV outbreak strain.
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