The quantum-level interplay between geometry, topology and correlation is at the forefront of fundamental physics1-15. Kagome magnets are predicted to support intrinsic Chern quantum phases owing to ...their unusual lattice geometry and breaking of time-reversal symmetry14,15. However, quantum materials hosting ideal spinorbit-coupled kagome lattices with strong out-of-plane magnetization are lacking16-21. Here, using scanning tunnelling microscopy, we identify a new topological kagome magnet, TbMn6Sn6, that is close to satisfying these criteria. We visualize its effectively defect-free, purely manganese-based ferromagnetic kagome lattice with atomic resolution. Remarkably, its electronic state shows distinct Landau quantization on application of a magnetic field, and the quantized Landau fan structure features spin-polarized Dirac dispersion with a large Chern gap. We further demonstrate the bulk-boundary correspondence between the Chern gap and the topological edge state, as well as the Berry curvature field correspondence of Chern gapped Dirac fermions. Our results point to the realization of a quantum-limit Chern phase in TbMn6Sn6, and may enable the observation of topological quantum phenomena in the RMn6Sn6 (where R is a rare earth element) family with a variety of magnetic structures. Our visualization ofthe magnetic bulk-boundary-Berry correspondence covering real space and momentum space demonstrates a proof-of-principle method for revealing topological magnets.
Bacterial biosensors, or bactosensors, are promising agents for medical and environmental diagnostics. However, the lack of scalable frameworks to systematically program ligand detection limits their ...applications. Here we show how novel, clinically relevant sensing modalities can be introduced into bactosensors in a modular fashion. To do so, we have leveraged a synthetic receptor platform, termed EMeRALD (Engineered Modularized Receptors Activated via Ligand-induced Dimerization) which supports the modular assembly of sensing modules onto a high-performance, generic signaling scaffold controlling gene expression in E. coli. We apply EMeRALD to detect bile salts, a biomarker of liver dysfunction, by repurposing sensing modules from enteropathogenic Vibrio species. We improve the sensitivity and lower the limit-of-detection of the sensing module by directed evolution. We then engineer a colorimetric bactosensor detecting pathological bile salt levels in serum from patients having undergone liver transplant, providing an output detectable by the naked-eye. The EMeRALD technology enables functional exploration of natural sensing modules and rapid engineering of synthetic receptors for diagnostics, environmental monitoring, and control of therapeutic microbes.
Kagome-nets, appearing in electronic, photonic and cold-atom systems, host frustrated fermionic and bosonic excitations. However, it is rare to find a system to study their fermion-boson many-body ...interplay. Here we use state-of-the-art scanning tunneling microscopy/spectroscopy to discover unusual electronic coupling to flat-band phonons in a layered kagome paramagnet, CoSn. We image the kagome structure with unprecedented atomic resolution and observe the striking bosonic mode interacting with dispersive kagome electrons near the Fermi surface. At this mode energy, the fermionic quasi-particle dispersion exhibits a pronounced renormalization, signaling a giant coupling to bosons. Through the self-energy analysis, first-principles calculation, and a lattice vibration model, we present evidence that this mode arises from the geometrically frustrated phonon flat-band, which is the lattice bosonic analog of the kagome electron flat-band. Our findings provide the first example of kagome bosonic mode (flat-band phonon) in electronic excitations and its strong interaction with fermionic degrees of freedom in kagome-net materials.
Protein-protein interactions are critical determinants in biological systems. Engineered proteins binding to specific areas on protein surfaces could lead to therapeutics or diagnostics for treating ...diseases in humans. But designing epitope-specific protein-protein interactions with computational atomistic interaction free energy remains a difficult challenge. Here we show that, with the antibody-VEGF (vascular endothelial growth factor) interaction as a model system, the experimentally observed amino acid preferences in the antibody-antigen interface can be rationalized with 3-dimensional distributions of interacting atoms derived from the database of protein structures. Machine learning models established on the rationalization can be generalized to design amino acid preferences in antibody-antigen interfaces, for which the experimental validations are tractable with current high throughput synthetic antibody display technologies. Leave-one-out cross validation on the benchmark system yielded the accuracy, precision, recall (sensitivity) and specificity of the overall binary predictions to be 0.69, 0.45, 0.63, and 0.71 respectively, and the overall Matthews correlation coefficient of the 20 amino acid types in the 24 interface CDR positions was 0.312. The structure-based computational antibody design methodology was further tested with other antibodies binding to VEGF. The results indicate that the methodology could provide alternatives to the current antibody technologies based on animal immune systems in engineering therapeutic and diagnostic antibodies against predetermined antigen epitopes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Quantum geometry in condensed-matter physics has two components: the real part quantum metric and the imaginary part Berry curvature. Whereas the effects of Berry curvature have been observed through ...phenomena such as the quantum Hall effect in two-dimensional electron gases and the anomalous Hall effect (AHE) in ferromagnets, the quantum metric has rarely been explored. Here, we report a nonlinear Hall effect induced by the quantum metric dipole by interfacing even-layered MnBi
Te
with black phosphorus. The quantum metric nonlinear Hall effect switches direction upon reversing the antiferromagnetic (AFM) spins and exhibits distinct scaling that is independent of the scattering time. Our results open the door to discovering quantum metric responses predicted theoretically and pave the way for applications that bridge nonlinear electronics with AFM spintronics.
Libraries of well-characterised components regulating gene expression levels are essential to many synthetic biology applications. While widely available for the Gram-negative model bacterium ...Escherichia coli, such libraries are lacking for the Gram-positive model Bacillus subtilis, a key organism for basic research and biotechnological applications. Here, we engineered a genetic toolbox comprising libraries of promoters, Ribosome Binding Sites (RBS), and protein degradation tags to precisely tune gene expression in B. subtilis We first designed a modular Expression Operating Unit (EOU) facilitating parts assembly and modifications and providing a standard genetic context for gene circuits implementation. We then selected native, constitutive promoters of B. subtilis and efficient RBS sequences from which we engineered three promoters and three RBS sequence libraries exhibiting ∼14 000-fold dynamic range in gene expression levels. We also designed a collection of SsrA proteolysis tags of variable strength. Finally, by using fluorescence fluctuation methods coupled with two-photon microscopy, we quantified the absolute concentration of GFP in a subset of strains from the library. Our complete promoters and RBS sequences library comprising over 135 constructs enables tuning of GFP concentration over five orders of magnitude, from 0.05 to 700 μM. This toolbox of regulatory components will support many research and engineering applications in B. subtilis.
Summary
Living cells have evolved to detect and process various signals and can self‐replicate, presenting an attractive platform for engineering scalable and affordable biosensing devices. Microbes ...are perfect candidates: they are inexpensive and easy to manipulate and store. Recent advances in synthetic biology promise to streamline the engineering of microbial biosensors with unprecedented capabilities. Here we review the applications of microbially‐derived biosensors with a focus on environmental monitoring and healthcare applications. We also identify critical challenges that need to be addressed in order to translate the potential of synthetic microbial biosensors into large‐scale, real‐world applications.
Living cells have evolved to detect and process various signals and can self‐replicate, presenting an attractive platform for engineering scalable and affordable biosensing devices. Here we review the applications of microbial‐derived biosensors to environmental monitoring and healthcare applications. We also discuss the challenges to address in order to accelerate the transition of these technologies into real‐world applications.
Background
We hypothesized that food sensitization (FS) in children could be linked to specific gut microbiota. The aim of our study is to quantify and evaluate differences in gut microbiota ...composition between children with FS and healthy controls.
Methods
A case–control study of 23 children with FS and 22 healthy children was performed. Individual microbial diversity and composition were analyzed via parallel barcoded 454 pyrosequencing targeting the 16S rRNA gene hypervariable V3–V5 regions.
Results
The children with FS exhibited lower diversity of both the total microbiota (p = 0.01) and the bacterial phylum Bacteroidetes (p = 0.02). In these children, the number of Bacteroidetes bacteria was significantly decreased and that of Firmicutes were significantly increased compared with the healthy children. At the genus level, we observed significant increases in the numbers of Sphingomonas, Sutterella, Bifidobacterium, Collinsella, Clostridium sensu stricto, Clostridium IV, Enterococcus, Lactobacillus, Roseburia, Faecalibacterium, Ruminococcus, Subdoligranulum, and Akkermansia in the FS group. We also found significant decreases in the numbers of Bacteroides, Parabacteroides, Prevotella, Alistipes, Streptococcus, and Veillonella in this group. Furthermore, linear discriminant analysis (LDA) coupled with effect size measurements revealed the most differentially abundant taxa (increased abundances of Clostridium IV and Subdoligranulum and decreased abundances of Bacteroides and Veillonella), which could be used to identify FS.
Conclusions
Our results showed that FS is associated with compositional changes in the gut microbiota. These findings could be useful for developing strategies to control the development of FS or atopy by modifying the gut microbiota.
Engineered bacteria are promising candidates for in situ detection and treatment of diseases. The female uro-genital tract presents several pathologies, such as sexually transmitted diseases or ...genital cancer, that could benefit from such technology. While bacteria from the gut microbiome are increasingly engineered, the use of chassis isolated from the female uro-genital resident flora has been limited. A major hurdle to implement the experimental throughput required for efficient engineering in these non-model bacteria is their low transformability. Here we report an optimized electrotransformation protocol for Lactobacillus jensenii, one the most widespread species across vaginal microflora. Starting from classical conditions, we optimized buffers, electric field parameters, cuvette type and DNA quantity to achieve an 80-fold improvement in transformation efficiency, with up to 3.5·103 CFUs/μg of DNA in L. jensenii ATCC 25258. We also identify several plasmids that are maintained and support reporter gene expression in L. jensenii. Finally, we demonstrate that our protocol provides increased transformability in three independent clinical isolates of L. jensenii. This work will facilitate the genetic engineering of L. jensenii and enable its use for addressing challenges in gynecological healthcare.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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