Browse Articles

Scoping review of artificial intelligence via mobile technology and social media for health in Africa

Zinc-oligoether carboxylate salts as electrolyte additives for aqueous Zn metal batteries

Gradient chaotropic regulation of Zn2+ solvation chemistry for low-temperature zinc metal batteries

A Plug-in system for reprogramming the editing patterns of base editors

Reconstructing the three-dimensional architecture of extrachromosomal DNA with ec3D

Abstract Extrachromosomal DNAs (ecDNAs) are circular DNA molecules prevalent in human cancers that drive tumor evolution and drug resistance. Their circular topology, which disrupts topological domains and rewires regulatory circuits, has typically been studied via pairwise interactions. Here we develop ec3D, a computational method for reconstructing three-dimensional ecDNA structures from Hi-C data. Given a candidate ecDNA sequence and whole-genome Hi-C data, ec3D reconstructs spatial structures by maximizing the Poisson likelihood of observed interactions. We validate ec3D using simulated structures, previously characterized cancer cell lines, and microscopy imaging. Our reconstructions reveal that ecDNAs occupy spherical configurations and mediate unique long-range regulatory interactions involved in gene regulation. Through algorithmic innovations, ec3D can resolve complex structures with duplicated segments, identify multi-way interactions, and identify potential intermolecular (trans) interactions. Our findings provide insights into how ecDNA’s spatial organization bypasses normal chromosomal constraints and contributes to increased oncogene expression.

Neisseria meningitidis filamentous phage MDA promotes colonisation by selecting hyperadhesive pili variants

Abstract Filamentous phages are non-lytic phages mutually beneficial to their bacterial hosts. In Neisseria meningitidis , the filamentous phage MDA is associated with invasive diseases thanks to its key role in the formation of biofilm during epithelium colonisation. The infection model for filamentous phages has been defined for phages Ff and CTX. These phages bind to the tips of bacterial pili before being translocated into the periplasm of their hosts. The aim of this study is to investigate the relationship between filamentous phage infection and type IV pili, using the bacterium Neisseria meningitidis and the bacteriophage MDA as model organisms. We show that MDAΦ rather binds to type IV pili along their entire length with preferential binding to positively charged variants of the major fibre-forming pilin, demonstrating a role for antigenic variation in phage infection. Strikingly, bacteria expressing the more positively charged pilin are also the most adhesive, suggesting that MDAΦ primarily target the most adhesive bacteria. Finally, we show that adhesion to human cells is sufficient to amplify the phage-positive meningococcal population. Overall, this study reveals how a filamentous phage can target hyperadhesive bacterial variants and promote their selection, thereby establishing a link between phage infection and bacterial colonisation.

Identifying grain boundary and intragranular pinning centres in Sm2(Co,Fe,Cu,Zr)17 permanent magnets to guide performance optimisation

Abstract Permanent magnets draw their properties from a complex interplay of chemical composition and phase, each with their associated intrinsic magnetic properties. Gaining an understanding of these interactions is the key to deciphering the origins of a permanent magnets’ magnetic performance and facilitate the engineering of much improved-performing magnets. Here, we use advanced multiscale microscopy and microanalysis on a bulk Sm 2 (Co,Fe,Cu,Zr) 17 pinning-type high-performance magnet with outstanding thermal and chemical stability. Comparison of the microstructure in regions of different composition, we demonstrate that the pinning of magnetic domains, imaged by nanoscale magnetic induction mapping, is controlled by the composition and atomic arrangement of copper. This is confirmed by micromagnetic simulations. Contrary to the belief that grain boundaries are “weak links” in magnetic materials, we demonstrate grain boundaries undergo magnetization reversal at relatively low fields (0.1-0.3 T), but this remains confined to these regions and does not significantly impact the magnet’s coercivity. Our results showcase that it is the optimal microstructure within the grain itself that is crucial for achieving the desired magnetic properties.

Structural basis for the assembly and energy transfer between the cyanobacterial PSI core and the double-layered IsiA proteins

Abstract Iron-limitation is a common stress factor in natural environments. To survive under iron-starved conditions, cyanobacteria overexpress iron stress-induced protein A (IsiA), which is crucial for light-harvesting and photoprotection. Multiple IsiA proteins form a single- or double-layered architecture encircling the photosystem I (PSI) core, forming various PSI-IsiA supercomplexes. The assembly and energy transfer mechanisms of double-layered PSI-IsiA supercomplexes remain unelucidated. Here, we present high-resolution structures of two PSI-IsiA supercomplexes isolated from the cyanobacterium Thermosynechococcus elongatus BP-1 cultured under iron-starved conditions. The PSI 3 -IsiA 43 complex contains a trimeric PSI core surrounded by 43 IsiA subunits assembled into a closed double-ring. The PSI 1 -IsiA 13 complex contains 13 IsiA proteins arranged in a double-layered architecture attached to the monomeric PSI core. Atomic force microscopy demonstrates the presence and distribution of different PSI-IsiA complexes within native thylakoid membranes isolated from iron-starved cells. Our findings provide insights into the structural variability and adaptive mechanisms of PSI-IsiA complexes.

Harnessing multivalency and FcγRIIB engagement to augment anti-CD27 immunotherapy

Abstract Despite significant clinical progress, checkpoint blockade remains limited by variable response rates, resistance, and toxicity. Activating costimulatory receptors offers a promising alternative to enhance anti-tumor immunity. However, there is insufficient understanding of how to mimic physiological membrane-anchored costimulatory ligands. Here, we describe a strategy for developing effective agonists of the costimulatory receptor CD27 by increasing both antibody valency and FcγRIIB engagement. Engineered anti-CD27 antibodies capable of tetravalent binding to CD27 and selective FcγRIIB association exhibit potent T cell stimulatory activity and anti-tumor efficacy in pre-clinical models, compared to bivalent counterparts. The anti-tumor effects of the tetravalent antibody are mediated through CD8⁺ T cell activation without evidence of regulatory T cell depletion. Mechanistically, whereas the increase in avidity drives more efficient CD27 clustering, FcγRIIB engagement triggers polarization of receptor clusters to the cell-cell interface and reduces receptor internalization. This work provides a framework for developing more effective agonist-based T cell stimulatory therapies.

SETD1A regulates psychiatric gene networks involved in genomic stability and synaptic function in rare and sporadic schizophrenia

Chromosome-level haplotype-resolved assembly of highly heterozygous grass genomes with PhaseGrass

Abstract Current methods to generate haplotype-resolved assemblies for highly heterozygous genomes suffer from reference bias when relying on reference-based phasing or may generate imbalanced haplomes when relying on graph-based phasing. Here, we report PhaseGrass, an assembly, phasing and scaffolding workflow that is compatible with accurate or error-prone long reads, generating haplotype-resolved assemblies for highly heterozygous genomes. Requiring no parental data, PhaseGrass combines reference-based phasing with haplotype-specific k-mers to partition long reads or unitigs to corresponding haplotypes, thereby avoiding reference bias and uneven haplotype partitioning. Using PhaseGrass, we generated chromosome-level, haplotype-resolved assemblies for the highly heterozygous, allogamous grass species Lolium perenne L. and L. multiflorum Lam. We find that PhaseGrass can bin 20% more reads to haplotypes than WhatsHap and generated balanced haplomes compared to Hifiasm, which produced largely imbalanced haplomes for L. multiflorum due to abundant structural variations between haplotypes. PhaseGrass will facilitate routine generation of haplotype-resolved pangenomes for species with highly heterozygous genomes.

Single iron redox sites boost Methanol-SCR at low temperature

The importance of multiregional accounting for corporate carbon emissions

Abstract Corporations routinely use environmentally-extended input-output models to estimate and report greenhouse gas emissions upstream in their supply chains. However, the most widely used models assume that supply chains and emissions intensities of industries match those of a single region—usually the U.S. or the U.K. Here, we use a high-resolution multiregional input-output model to demonstrate the scale and pattern of emissions that may be missed by single-region models. We find that the upstream emissions of the companies reporting to CDP are together greater by 2.0 gigatons of CO 2 -equivalent emissions (~10%) when estimated by a multiregional model instead of a U.S.-based single-region model, with the largest differences in manufacturing sectors of moderate emissions intensity. Widespread adoption of multiregional models could thus improve the accuracy of corporate emissions inventories and help prioritize primary data collection and emissions reduction efforts, often by shifting focus to energy- and emissions-intensive sectors of industrializing nations.

Toward rational understanding of the hydrogen evolution polarization curves through multiscale simulations

Wearable AI for on-device frailty assessment

Factors associated with herbal usage among hypertensive and diabetic patients in Yogyakarta, Indonesia: A cross-sectional study

IndiVNet A region adaptive semantic image segmentation for autonomous driving in unstructured environments

A comparison of sperm parameters DNA fragmentation and telomere length in testicular versus ejaculated spermatozoa

Autophagy related biomarkers in ulcerative colitis revealed by bioinformatics analysis and immune correlation

Investigation of bentonite–goethite mixture as a novel material for low-level landfill liners

Abstract The safe containment of hazardous waste requires landfill liner materials with both effective radiation shielding and strong hydro-mechanical performance. This study investigates the potential of a bentonite-goethite mixture as a novel material for hazardous waste landfill liners. The study examines the radiation shielding of the mixtures, represented by the linear attenuation coefficient, through experimental (Na (Tl) spectrometer detector), numerical (MCNP code), and reference database (XCOM and PHY-X) approaches. Moreover, the hydraulic permeability and mechanical properties are evaluated experimentally. For this, the varying proportions of goethite from 10 to 50% were examined. The results show an increase of up to 20, 24, and 28 percent in the linear attenuation coefficient at gamma ray energies of Cs $$^{137}$$ (661.6 keV) and Co $$^{60}$$ (1173.2 and 1332.5 keV). Higher goethite percentages, correlating with density variations and enhancing radiation shielding effectiveness. Numerical and reference database results align closely with experimental findings, suggesting their utility for assessing other mixtures. The direct shear test reveals that with an increase of goethite proportion to 50 percent, the cohesion is reduced to half and the friction angle is inclined twice the pure bentonite values, attributed to bentonite reduction and goethite roughness. Unconfined compressive strength trends show 20% improvement at specific mixture composition with 30% goethite, while hydraulic conductivity inclines with goethite content to $$\mathrm { 8.8\times 10^{-10}}$$ m/s. In this study the bentonite-goethite mixture illustrates improving radiation shielding and maintaining hydro-mechanical properties for landfill liners. This may offer a sustainable alternative using waste materials from mineral processing, contributing to waste management and environmental sustainability.