Browse Articles

Value of lung ultrasound scores in assessing extravascular lung water in septic shock patients

Damping behavior of olive trees under trunk shaking

Thermal and desalination performance enhancement of single slope solar still using phase change material

Abstract The study that is being presented focused on the numerical analysis of the melting regime for various phase change materials (PCMs) in order to select an optimal material that would enhance the desalination efficiency of single-slope solar stills. While choosing the PCMs, the following factors were considered, availability, economic viability, environmental friendliness, and thermophysical properties. The study utilised ANSYS Fluent 18.1 to conduct a comparative analysis based on the melting of five different PCMs at different time stamps. The models and results showed that at 5000 s, Fe3O4 nanoparticle-enhanced PCM is the most effective of all the PCMs that were studied. This is because it melted completely before the other PCMs, which included RT35, Lauric Acid, CaCl2·6H2O, and n-octadecane. The best inorganic PCM was discovered to be CaCl2·6H2O, which had a maximum liquid fraction of around 68%. The best organic PCM was determined to be n-octadecane, which had a liquid fraction of nearly 57%. Lauric acid and RT35 achieved maximum liquid fractions of approximately 49% and 41%, respectively.

Reliability analysis of subsea pipeline system based on fuzzy polymorphic bayesian network

Synthesis of new DFNS/ZnTiO3 nanoparticles as a nanocatalyst for the reaction of quinazoline-2, 4(1H, 3H)-dione with CO2

K-mer analysis of long-read alignment pileups for structural variant genotyping

Defying the oxidative-addition prerequisite in cross-coupling through artful single-atom catalysts

Probing the subtle differences between promethium and curium

Abstract Curium and promethium share similar chemical and physical properties thereby complicating their separation. Co-located processing at Oak Ridge National Laboratory results in curium contamination of the fission product stream containing promethium. To gain insight into the difficulty of this separation, the fundamental properties of these elements are experimentally and computationally probed in a 2,2’:6’,2”-terpyridine crystal system. Analysis of the isostructural compounds via single crystal X-ray diffraction and quantum theory of atoms in molecules reveals that bonding between promethium and curium is quite similar in this particular structure type. The small differences in the analysis of these two elements in this isostructural series sheds light on the difficulty required to separate the elements from each other. More so, this study develops the fundamental chemistries of two rare elements in the solid state and experimentally portrays the often-omitted position of promethium within the lanthanide series.

A human model to deconvolve genotype-phenotype causations in lung squamous cell carcinoma

Abstract Tractable, patient-relevant models are needed to investigate cancer progression and heterogeneity. Here, we report an alternative in vitro model of lung squamous cell carcinoma (LUSC) using primary human bronchial epithelial cells (hBECs) from three healthy donors. The co-operation of ubiquitous alterations (TP53 and CDKN2A loss) and components of commonly deregulated pathways including squamous differentiation (SOX2), PI3K signalling (PTEN) and the oxidative stress response (KEAP1) is investigated by generating hBECs harbouring cumulative alterations. Our analyses confirms that SOX2-overexpression initiates early preinvasive LUSC stages, and co-operation with the oxidative stress response and PI3K pathways to drive more aggressive phenotypes, with expansion of cells expressing LUSC biomarkers and invasive properties. This cooperation is consistent with the classical LUSC subtype. Importantly, we connect pathway dysregulation with gene expression changes associated with cell-intrinsic processes and immunomodulation. Our approach constitutes a powerful system to model LUSC and unravel genotype-phenotype causations of clinical relevance.

Role of charges in a dynamic disordered complex between an IDP and a folded domain

Abstract Protein complexes involving intrinsically disordered proteins (IDPs) cover a continuum from IDPs that fully fold upon binding to IDPs that remain fully disordered in the complex. Here we demonstrate a case of charge-driven interactions of a folded domain with an oppositely charged IDP that remains completely disordered in the complex. Using the negatively charged and fully disordered prothymosin α and the positively charged and folded globular domain of histone H1.0, we show that they form a low-micromolar-affinity complex without fixed relative orientations or persistent contacts between specific residues. Using 25 charge variants of the globular domain, we find that the binding affinity can be modulated both by net charge and charge clustering on the folded domain, indicating some selectivity in highly charged complexes. Our results highlight that a folded protein can provide a charged surface onto which an oppositely charged IDP can bind while retaining disorder. We expect that more such complexes exist.

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.