Neuropathology-based approach reveals novel Alzheimer's Disease genes and highlights female-specific pathways and causal links to disrupted lipid metabolism: insights into a vicious cycle.

Dementia refers to an umbrella phenotype of many different underlying pathologies with Alzheimer's disease (AD) being the most common type. Neuropathological examination remains the gold standard for accurate AD diagnosis, however, most that we know about AD genetics is based on Genome-Wide Association Studies (GWAS) of clinically defined AD. Such studies have identified multiple AD susceptibility variants with a significant portion of the heritability unexplained and highlighting the phenotypic and genetic heterogeneity of the clinically defined entity.

Stereoselective amino alcohol synthesis via chemoselective electrocatalytic radical cross-couplings.

Amino alcohols are vital in natural products, pharmaceuticals and agrochemicals, and as key building blocks for various applications. Traditional synthesis methods often rely on polar bond retrosynthetic analysis, requiring extensive protecting group manipulations that complicate direct access. Here we show a streamlined approach using a serine-derived chiral carboxylic acid in stereoselective electrocatalytic decarboxylative transformations, enabling efficient access to enantiopure amino alcohols.

Pan-phylum genomes of hornworts reveal conserved autosomes but dynamic accessory and sex chromosomes.

Hornworts, one of the three bryophyte phyla, show some of the deepest divergences in extant land plants, with some families separated by more than 300 million years. Previous hornwort genomes represented only one genus, limiting the ability to infer evolution within hornworts and their early land plant ancestors. Here we report ten new chromosome-scale genomes representing all hornwort families and most of the genera.

Hornworts reveal a spatial model for pyrenoid-based CO-concentrating mechanisms in land plants.

Pyrenoid-based CO-concentrating mechanisms (pCCMs) turbocharge photosynthesis by saturating CO around Rubisco. Hornworts are the only land plants with a pCCM. Owing to their closer relationship to crops, hornworts could offer greater translational potential than the green alga Chlamydomonas, the traditional model for studying pCCMs.

AND-gated protease-activated nanosensors for programmable detection of anti-tumour immunity.

The forward design of biosensors that implement Boolean logic to improve detection precision primarily relies on programming genetic components to control transcriptional responses. However, cell- and gene-free nanomaterials programmed with logical functions may present lower barriers for clinical translation. Here we report the design of activity-based nanosensors that implement AND-gate logic without genetic parts via bi-labile cyclic peptides.

Two decades of bacterial ecology and evolution in a freshwater lake.

Ecology and evolution are considered distinct processes that interact on contemporary time scales in microbiomes. Here, to observe these processes in a natural system, we collected a two-decade, 471-metagenome time series from Lake Mendota (Wisconsin, USA). We assembled 2,855 species-representative genomes and found that genomic change was common and frequent.

Unravelling viral ecology and evolution over 20 years in a freshwater lake.

As freshwater lakes undergo rapid anthropogenic change, long-term studies reveal key microbial dynamics, evolutionary shifts and biogeochemical interactions, yet the vital role of viruses remains overlooked. Here, leveraging a 20 year time series from Lake Mendota, WI, USA, we characterized 1.3 million viral genomes across time, seasonality and environmental factors.

Exploring transition states of protein conformational changes via out-of-distribution detection in the hyperspherical latent space.

Identifying transitional states is crucial for understanding protein conformational changes that underlie numerous biological processes. Markov state models (MSMs), built from Molecular Dynamics (MD) simulations, capture these dynamics through transitions among metastable conformational states, and have demonstrated success in studying protein conformational changes. However, MSMs face challenges in identifying transition states, as they partition MD conformations into discrete metastable states (or free energy minima), lacking description of transition states located at the free energy barriers.

Quantum Thermodynamics of Nonequilibrium Processes in Lattice Gauge Theories.

A key objective in nuclear and high-energy physics is to describe nonequilibrium dynamics of matter, e.g., in the early Universe and in particle colliders, starting from the standard model of particle physics.

Diverse plant RNAs coat leaves and are distinct from apoplastic RNAs.

Transgenic expression of a double-stranded RNA in plants can induce silencing of homologous mRNAs in fungal pathogens. Although such host-induced gene silencing is well documented, the molecular mechanisms by which RNAs can move from the cytoplasm of plant cells across the plasma membrane of both the host cell and fungal cell are poorly understood. Indirect evidence suggests that this RNA transfer may occur at a very early stage of the infection process, prior to breach of the host cell wall, suggesting that silencing RNAs might be secreted onto leaf surfaces.

The proteome is a terminal electron acceptor.

Microbial metabolism is impressively flexible, enabling growth even when available nutrients differ greatly from biomass in redox state. , for example, rearranges its physiology to grow on reduced and oxidized carbon sources through several forms of fermentation and respiration. To understand the limits on and evolutionary consequences of this metabolic flexibility, we developed a coarse-grained mathematical framework coupling redox chemistry with principles of cellular resource allocation.

Deriving a genetic regulatory network from an optimization principle.

Many biological systems operate near the physical limits to their performance, suggesting that aspects of their behavior and underlying mechanisms could be derived from optimization principles. However, such principles have often been applied only in simplified models. Here, we explore a detailed mechanistic model of the gap gene network in the embryo, optimizing its 50+ parameters to maximize the information that gene expression levels provide about nuclear positions.

Sub-terahertz metamaterial stickers for non-invasive fruit ripeness sensing.

Fruits and vegetables account for around a third of all food loss and waste. Post-harvest, retail and consumer losses and waste could be reduced with better ripeness assessment methods. Here we develop a sub-terahertz metamaterial sticker (called Meta-Sticker) that can be attached to a fruit to provide insights into the edible mesocarp's ripeness without cutting into the produce.

Programming scheduled self-assembly of circadian materials.

Active biological molecules present a powerful, yet largely untapped, opportunity to impart autonomous regulation of materials. Because these systems can function robustly to regulate when and where chemical reactions occur, they have the ability to bring complex, life-like behavior to synthetic materials. Here, we achieve this design feat by using functionalized circadian clock proteins, KaiB and KaiC, to engineer time-dependent crosslinking of colloids.

Orthologous marker groups reveal broad cell identity conservation across plant single-cell transcriptomes.

Single-cell RNA sequencing (scRNA-seq) is widely used in plant biology and is a powerful tool for studying cell identity and differentiation. However, the scarcity of known cell-type marker genes and the divergence of marker expression patterns limit the accuracy of cell-type identification and our capacity to investigate cell-type conservation in many species. To tackle this challenge, we devise a novel computational strategy called Orthologous Marker Gene Groups (OMGs), which can identify cell types in both model and non-model plant species and allows for rapid comparison of cell types across many published single-cell maps.

Overlapping qubits from non-isometric maps and de Sitter tensor networks.

The emergence of a local effective theory from a more fundamental theory of quantum gravity with seemingly fewer degrees of freedom is a major puzzle of theoretical physics. A recent approach to this problem is to consider general features of the Hilbert space maps relating these theories. In this work, we construct approximately local observables, or overlapping qubits, from such non-isometric maps.

Demonstration of high-reconfigurability and low-power strong physical unclonable function empowered by FeFET cycle-to-cycle variation and charge-domain computing.

Physical unclonable functions (PUFs) are of immense potential in authentication scenarios for Internet of Things (IoT) devices. For creditable and lightweight PUF applications, key attributes, including low power, high reconfigurability and large challenge-response pair (CRP) space, are desirable. Here, we report a ferroelectric field-effect transistor (FeFET)-based strong PUF with high reconfigurability and low power, which leverages the FeFET cycle-to-cycle variation throughout the workflow and introduces charge-domain in-memory computing.

Moiré band structure engineering using a twisted boron nitride substrate.

Applying long wavelength periodic potentials on quantum materials has recently been demonstrated to be a promising pathway for engineering novel quantum phases of matter. Here, we utilize twisted bilayer boron nitride (BN) as a moiré substrate for band structure engineering. Small-angle-twisted bilayer BN is endowed with periodically arranged up and down polar domains, which imprints a periodic electrostatic potential on a target two-dimensional (2D) material placed on top.

Evolutionary origins of archaeal and eukaryotic RNA-guided RNA modification in bacterial IS110 transposons.

Transposase genes are ubiquitous in all domains of life and provide a rich reservoir for the evolution of novel protein functions. Here we report deep evolutionary links between bacterial IS110-family transposases, which catalyse RNA-guided DNA recombination using bridge RNAs, and archaeal/eukaryotic Nop5-family proteins, which promote RNA-guided RNA 2'-O-methylation using C/D-box snoRNAs. On the basis of conservation of protein sequence, domain architecture, three-dimensional structure and non-coding RNA features, alongside phylogenetic analyses, we propose that programmable RNA modification emerged through the exaptation of components derived from IS110-like transposons.

Stakeholder diversity matters: employing the wisdom of crowds for data-poor fisheries assessments.

Embracing local knowledge is vital to conserve and manage biodiversity, yet frameworks to do so are lacking. We need to understand which, and how many knowledge holders are needed to ensure that management recommendations arising from local knowledge are not skewed towards the most vocal individuals. Here, we apply a Wisdom of Crowds framework to a data-poor recreational catch-and-release fishery, where individuals interact with natural resources in different ways.

Repairing a deleterious domestication variant in a floral regulator gene of tomato by base editing.

Crop genomes accumulate deleterious mutations-a phenomenon known as the cost of domestication. Precision genome editing has been proposed to eliminate such potentially harmful mutations; however, experimental demonstration is lacking. Here we identified a deleterious mutation in the tomato transcription factor SUPPRESSOR OF SP2 (SSP2), which became prevalent in the domesticated germplasm and diminished DNA binding to genome-wide targets.

Surface remodeling and inversion of cell-matrix interactions underlie community recognition and dispersal in Vibrio cholerae biofilms.

Biofilms are ubiquitous surface-associated bacterial communities embedded in an extracellular matrix. It is commonly assumed that biofilm cells are glued together by the matrix; however, how the specific biochemistry of matrix components affects the cell-matrix interactions and how these interactions vary during biofilm growth remain unclear. Here, we investigate cell-matrix interactions in Vibrio cholerae, the causative agent of cholera.

Towards non-blinking and photostable perovskite quantum dots.

Surface defect-induced photoluminescence blinking and photodarkening are ubiquitous in lead halide perovskite quantum dots. Despite efforts to stabilize the surface by chemically engineering ligand binding moieties, blinking accompanied by photodegradation still poses barriers to implementing perovskite quantum dots in quantum emitters. To date, ligand tail engineering in the solid state has rarely been explored for perovskite quantum dots.

A higher order PUF complex is central to regulation of C. elegans germline stem cells.

PUF RNA-binding proteins are broadly conserved stem cell regulators. Nematode PUF proteins maintain germline stem cells (GSCs) and, with key partner proteins, repress differentiation mRNAs, including gld-1. Here we report that PUF protein FBF-2 and its partner LST-1 form a ternary complex that represses gld-1 via a pair of adjacent FBF binding elements (FBEs) in its 3'UTR.

Single-molecule two- and three-colour FRET studies reveal a transition state in SNARE disassembly by NSF.

SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins are the minimal machinery required for vesicle fusion in eukaryotes. Formation of a highly stable four-helix bundle consisting of SNARE motif of these proteins, drives vesicle/membrane fusion involved in several physiological processes such as neurotransmission. Recycling/disassembly of the protein machinery involved in membrane fusion is essential and is facilitated by an AAA+ ATPase, N-ethylmaleimide sensitive factor (NSF) in the presence of an adapter protein, α-SNAP.