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Fingerprints of supersymmetric spin and charge dynamics observed by inelastic neutron scattering
Abstract Supersymmetry is an algebraic property of a quantum Hamiltonian that, by giving every boson a fermionic superpartner and vice versa, may underpin physics beyond the Standard Model. Fractional bosonic and fermionic quasiparticles are familiar in condensed matter, as in the spin and charge excitations of the t-J model describing electron dynamics in one-dimensional materials, but this type of symmetry is almost unknown. However, the triplet excitations of a quantum spin ladder in an applied magnetic field provide a supersymmetric analogue of the t-J chain. Here we perform neutron spectroscopy on the spin-ladder compounds (C5D12N)2CuBr4 and (C5D12N)2CuCl4 over a range of applied fields and temperatures, and apply matrix-product-state methods to the ladder and equivalent chain models. From the momentum-resolved dynamics of a single charge-like excitation in a bath of fractional spins, we find essential differences in thermal broadening between the supersymmetric and non-supersymmetric sectors. The persistence of a strict zone-centre pole at all temperatures constitutes an observable consequence of supersymmetry that marks the beginning of supersymmetric studies in experimental condensed matter.
Optimization and scaling-up of porous solid electrolyte electrochemical reactors for hydrogen peroxide electrosynthesis
Development of N-centered radical scavengers that enables photoredox-catalyzed transition-metal-free radical amination of alkyl pinacol boronates
Lactate activates trained immunity by fueling the tricarboxylic acid cycle and regulating histone lactylation
A blood- and brain-based EWAS of smoking
Abstract DNA methylation offers an objective method to assess the impact of smoking. In this work, we conduct a Bayesian EWAS of smoking pack years ( n = 17,865, ~850k sites, Illumina EPIC array) and extend it by analysing whole genome data of smokers and non-smokers from Generation Scotland ( n = 46, ~4–21 million sites via TWIST and Oxford Nanopore sequencing). We develop mCigarette, an epigenetic biomarker of smoking, and test it in two British cohorts. Results of brain- and blood-based EWAS (n brain =14, n blood = 882, >450k sites, Illumina arrays) reveal several loci with near-perfect discrimination of smoking status, but which do not overlap across tissues. Furthermore, we perform a GWAS of epigenetic smoking, identifying several smoking-related loci. Overall, we improve smoking-related biomarker accuracy and enhance the understanding of the effects of smoking by integrating DNA methylation data from multiple tissues and cohorts.
Low melt viscosity enables melt doublets above the 410-km discontinuity
Abstract Seismic and magnetotelluric studies suggest hydrous silicate melts atop the 410 km discontinuity form 30–100 km thick layers. Importantly, in some regions, two layers are observed. These stagnant layers are related to their comparable density to the surrounding mantle, but their formation mechanisms and detailed structures remain unclear. Here we report a large decrease of silicate melt viscosity at ~14 GPa, from 96(5) to 11.7(6) mPa⋅s, as water content increases from 15.5 to 31.8 mol% H₂O. Such low viscosities facilitate rapid segregation of melt, which would typically prevent thick layer accumulation. Our 1D finite element simulations show that continuous dehydration melting of upwelling mantle material produces a primary melt layer above 410 km and a secondary layer at the depth of equal mantle-melt densities. These layers can merge into a single thick layer under low density contrasts or high upwelling rates, explaining both melt doublets and thick single layers.
Macroscale-area patterning of three-dimensional DNA-programmable frameworks
The Futile Creatine Cycle powers UCP1-independent thermogenesis in classical BAT
Abstract Classical brown adipose tissue (BAT) is traditionally viewed as relying exclusively on uncoupling protein 1 (UCP1) for thermogenesis via inducible proton leak. However, the physiological significance of UCP1-independent mechanisms linking substrate oxidation to ATP turnover in classical BAT has remained unclear. Here, we identify the Futile Creatine Cycle (FCC), a mitochondrial-localized energy-wasting pathway involving creatine phosphorylation by creatine kinase b (CKB) and phosphocreatine hydrolysis by tissue-nonspecific alkaline phosphatase (TNAP), as a key UCP1-independent thermogenic mechanism in classical BAT. Reintroducing mitochondrial-targeted CKB exclusively into interscapular brown adipocytes in vivo restores thermogenesis and cold tolerance in mice lacking native UCP1 and CKB, in a TNAP-dependent manner. Furthermore, mice with inducible adipocyte-specific co-deletion of TNAP and UCP1 exhibit severe cold-intolerance. These findings challenge the view that BAT thermogenesis depends solely on UCP1 because of insufficient ATP synthase activity and establishes the FCC as a physiologically relevant thermogenic pathway in classical BAT.
Cryo-EM analyses unveil details of mechanism and targocil-II mediated inhibition of S. aureus WTA transporter TarGH
Abstract Wall teichoic acid (WTA) is a polyol phosphate polymer that covalently decorates peptidoglycan of gram-positive bacteria, including Staphylococcus aureus. Central to WTA biosynthesis is flipping of lipid-linked precursors across the cell membrane by TarGH, a type V ABC transporter. Here, we present cryo-EM structures of S. aureus TarGH in the presence of targocil-II, a promising small-molecule lead with β-lactam antibiotic synergistic action. Targocil-II binds to the extracellular dimerisation interface of TarG, we suggest mimicking flipped but not yet released substrate. In absence of targocil-II and in complex with ATP analogue ATPγS, determined at 2.3 Å resolution, the ATPase active site is allosterically inhibited. This is due to a so far undescribed D-loop conformation, potentially minimizing spurious ATP hydrolysis in the absence of substrate. Targocil-II binding comparatively causes local and remote conformational changes through to the TarH active site, with the D-loop now optimal for ATP hydrolysis. These structures suggest an ability to modulate ATP hydrolysis in a WTA substrate dependent manner and a jammed ATPase cycle as the basis of the observed inhibition by targocil-II. The molecular insights provide an unprecedented basis for development of TarGH targeted therapeutics for treatment of multidrug-resistant S. aureus and other gram-positive bacterial infections.
Spatial transcriptomics of the aging mouse brain reveals origins of inflammation in the white matter
Abstract To systematically understand age-induced molecular changes, we performed spatial transcriptomics of young, middle-aged, and old mouse brains and identified seven transcriptionally distinct regions. All regions exhibited age-associated upregulation of inflammatory mRNAs and downregulation of mRNAs related to synaptic function. Notably, aging white matter fiber tracts showed the most prominent changes with pronounced effects in females. The inflammatory signatures indicated major ongoing events: microglia activation, astrogliosis, complement activation, and myeloid cell infiltration. Immunofluorescence and quantitative MRI analyses confirmed physical interaction of activated microglia with fiber tracts and concomitant reduction of myelin in old mice. In silico analyses identified potential transcription factors influencing these changes. Our study provides a resourceful dataset of spatially resolved transcriptomic features in the naturally aging murine brain encompassing three age groups and both sexes. The results link previous disjointed findings and provide a comprehensive overview of brain aging identifying fiber tracts as a focal point of inflammation.
Nanopore sensing of protein and peptide conformation for point-of-care applications
Abstract The global population’s aging and growth will likely result in an increase in chronic aging-related diseases. Early diagnosis could improve the medical care and quality of life. Many diseases are linked to misfolding or conformational changes in biomarker peptides and proteins, which affect their function and binding properties. Current clinical methods struggle to detect and quantify these changes. Therefore, there is a need for sensitive conformational sensors that can detect low-concentration analytes in biofluids. Nanopore electrical detection has shown potential in sensing subtle protein and peptide conformation changes. This technique can detect single molecules label-free while distinguishing shape or physicochemical property changes. Its proven sensitivity makes nanopore sensing technology promising for ultra-sensitive, personalized point-of-care devices. We focus on the capability of nanopore sensing for detecting and quantifying conformational modifications and enantiomers in biomarker proteins and peptides and discuss this technology as a solution to future societal health challenges.
Electron correlation and incipient flat bands in the Kagome superconductor CsCr3Sb5
Enzymatic Birch reduction via hydrogen atom transfer at [4Fe-4S]-OH2 and [8Fe-9S] clusters
Abstract The alkali metal- and ammonia-dependent Birch reduction is the classical synthetic method for achieving dihydro additions to arenes, typically yielding 1,4-cyclodienes. A mild biological alternative to this process are 1,5-dienoyl-coenzyme A (CoA)-forming class I and II benzoyl-CoA reductases (BCRs), widely abundant key enzymes in the biodegradation of aromatic compounds at anoxic environments. To obtain a comprehensive mechanistic understanding of class I BCR catalysis, we produced the active site subunits from a denitrifying bacterium and determined the X-ray structure of its substrate and product complexes at 1.4 Å revealing non-canonical double-cubane [8Fe-9S] and active site aqua-[4Fe-4S] clusters. Together with kinetic, spectroscopic and QM/MM studies, we provide evidence for a radical mechanism with a [4Fe-4S] cluster-bound water molecule acting as hydrogen atom and electron donor at potentials beyond the biological redox window. An analogous Birch-like radical mechanism is applied by class II BCRs with the catalytic water bound to a tungsten-bis-metallopterin cofactor. The use of activated, metal-bound water ligands as hydrogen atom donor serves as a basic blueprint for future enzymatic or biomimetic Birch reduction processes.
Author Correction: A fast approach for structural and evolutionary analysis based on energetic profile protein comparison
Epidermal electronic-tattoo for plant immune response monitoring
Abstract Real-time monitoring of plant immune responses is crucial for understanding plant immunity and mitigating economic losses from pathogen and pest attacks. However, current methods relying on molecular-level assessment are destructive and time-consuming. Here, we report an ultrathin, substrate-free, and highly conductive electronic tattoo (e-tattoo) designed for plants, enabling immune response monitoring through non-invasive electrical impedance spectroscopy (EIS). The e-tattoo’s biocompatibility, high conductivity, and sub-100 nm thickness allow it to conform to leaf tissue morphology and provide robust impedance data. We demonstrate continuous EIS analysis of live transgenic Arabidopsis thaliana plants for over 24 h, capturing the onset of NLR-mediated acute immune responses within three hours post-induction, prior to visible symptoms. RNA-seq and tissue ion leakage tests validate that EIS data accurately represent the physiological and molecular changes associated with immune activation. This non-invasive tissue-assessment technology has the potential to enhance our comprehension of immune activation mechanisms in plants and paves the way for real-time monitoring for plant health management.