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Here, the authors present an update to a widely used curatedMetagenomicData (cMD) database and use it to create a catalog of microbiome-phenotype associations (age, sex, body mass index), and develop an oral enrichment score in the gut microbiome independently of age.

iGluSnFR4f and iGluSnFR4s are the latest generation of genetically encoded glutamate sensors. They are advantageous for detecting rapid dynamics and large population activity, respectively, as demonstrated in a variety of applications in the mouse brain.

In this study, authors employ fragment-based lead discovery to identify WRN inhibitors. The fragment hits reveal an additional allosteric pocket and uncover a previously uncharacterized structural conformation of the WRN helicase domain with unique orientations of the ATPase domains

Here, the authors present archaeology of the Namorotukunan site in Kenya’s Turkana Basin that demonstrates adaptive shifts in hominin tool-making behaviour spanning 300,000 years and increasing environmental variability. They contextualize these findings with paleoenvironmental proxies, dating, and geological descriptions.

The authors provide a molecular explanation for how a plant stress hormone called ethylene suppresses root colonization by arbuscular mycorrhiza fungi. These fungi form symbioses with most land plants and increase their access to mineral nutrients.

A hybrid machine learning and atomistic modelling strategy enables one-shot design of efficient enzymes to catalyse diverse biological and non-biological chemical transformations.

Multi-ancestry genome-wide and transcriptome-wide association studies of aortic stenosis identify more than 200 independent risk loci and provide insights into its genetic architecture.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

A greater diversity of crops at the national level increases the temporal stability of total national harvest, reflecting markedly lower frequencies of years with sharp harvest losses.

PMTs are fungal O-mannosyltransferases embedded in the ER membrane. Here, structures of the Pmt4 homodimer reveal distinct features of this PMT family and uncover an additional cytosolic binding site for the Dol-P-Man substrate lipid.

A highly scalable approach is used to generate 3,000 genome-wide maps of transcription factor binding in ten flowering plants, along with multi-species single-nucleus RNA-seq atlases. Together, the results reveal both ancient regulation and key regulatory adaptations.

The effects of current protected areas on freshwater biodiversity are poorly understood. Here, the authors show that European protected areas have overall limited influence on changes in river biodiversity, underscoring the urgent need for improved effectiveness.

A method to label and visualize nascent RNA allows real-time study of transcriptional dynamics at single-cell resolution in vivo. The approach is used to study transcriptional repression of the SPX1 gene by phosphate in Arabidopsis roots.

Intrinsic capacity (IC) was introduced by the World Health Organization to promote healthy aging. Here, using data from the Longitudinal Ageing Study in India, the authors develop an IC measure for older Indian adults. Their analysis shows that higher IC scores are associated with better health and functioning and reveals regional and sociodemographic variations.

In this work, the authors show that the essential Mycoplasma pneumoniae protein P116 enables cholesterol acquisition from lipoproteins and various cell types. An antibody against its C-terminal domain inhibits lipid acquisition, growth, and plaque binding, linking M. pneumoniae to atherosclerotic lipid-rich tissue.

Multidrug efflux pumps help bacteria survive stress and promote antibiotic resistance. Here, authors define the molecular detail of an anaerobic-connected pump MdtF uncovering acid-responsive activity which may enable toxin control in certain niches.

Klose and colleagues show that the neuropeptide vasoactive intestinal peptide (VIP) acts on LGR5⁺ epithelial stem cells in the gut to restrain their proliferation and differentiation to secretory cell types. This VIP–VIPR1 interaction acts to limit type 2 immune responses.

An architecture inspired by Hopfield networks based on a programmable, stable, room-temperature optoelectronic oscillator-based photonics Ising machine is introduced that can be used to efficiently address optimization and combinatorics problems.

Existing methods for non-invasively monitoring water flow in plants have limited spatial/temporal resolution. Here, the authors report that Raman microspectroscopy, complemented by hydrodynamic modelling, can monitor hydrodynamics within living root tissues at cell- and sub-second-scale resolutions.

Although FZDs are promising drug targets, so far no small molecules targeting them were described. Here, the authors report the a FZD7 core-targeting small molecule negative allosteric modulators of WNT-induced signaling, confirmed by pharmacology, structure determination and MD simulations.

Paul and colleagues report the development and characterization of an antibody–drug conjugate targeting TRBC2 for the treatment of T cell malignancies.

Vaccine-derived poliovirus type 2 currently spreads similarly to historical poliovirus—unidirectionally across neighbouring countries at a median velocity of 2.3 km per day. International borders are associated with slower velocity when immunity is high.

Clear cell renal cell carcinoma (ccRCC) bears the hallmark loss of VHL but remains incurable. Here, the authors identify the SLC1A1 dicarboxylic amino acid transporter as an actionable, oncogenic, HIF-independent, metabolic dependency in VHL-deficient ccRCCs.

The evolutionary diversification of an exocyst subunit was enabled by electrostatic shifts leading to its dissociation from the ancestral complex.

Efficient lead optimization in drug discovery requires improving potency, synthetic accessibility, and physicochemical properties. Here, the authors utilize machine learning to screen large chemical spaces, demonstrating automated selection of optimized molecules to improve cycle times.

Water-vapor interfaces have been studied with many techniques, yet open questions persist about their electronic and molecular structure. Here, the authors demonstrate the application of soft x-ray second harmonic generation to study the water surface by leveraging attosecond pulses at the LCLS and a flat liquid sheet microjet, providing insights on the H-bond structure.

In correlated materials, new phases emerge when the balance between many-body interactions is perturbed. Here, Ma et al. induce a mosaic charge-density-wave phase out of Mott insulating state in layered 1T-TaS₂by voltage pulses, which reveals a dominating role of interlayer stacking order.

Large-scale analyses of bird species traits reveal that land-use change reduces resilience of key ecological functions more than previously thought.

Giehl et al. describe a method for simultaneous quantification of up to 11 mineral elements in different root cell types, explore the consequences of perturbed xylem loading and identify a cell type-specific constraint for metal sequestration in roots.

The hippocampus can replay long spatial sequences without ripples. When present, ripples cluster in spatially restricted zones as a function of replayed location that remap with barrier changes, implying a tagging role in consolidation.

Here, the authors show that two residues in FDX1 control both protein lipoylation and copper-induced cell death, suggesting these roles are interconnected. They also identify DLD as an upstream regulator that strengthens FDX1’s link to the lipoylation pathway.

Fossil tooth development suggests an extended human growth phase occurred at least 1.77 million years ago, possibly reflecting a shift towards extended parenting and reproductive success, rather than increasing brain size.

Carbon dioxide enrichment of a mature forest resulted in the emission of the excess carbon back into the atmosphere via enhanced ecosystem respiration, suggesting that mature forests may be limited in their capacity to mitigate climate change.

Trends in global H₂ sources and sinks are analysed from 1990 to 2020, and a comprehensive budget for the decade 2010–2020 is presented.

A generative artificial intelligence-powered method enables de novo design of highly active enzymes based on information about the geometry of residues in the active site, without requiring protein backbone or sequence information.

A deep-learning-based de novo design strategy was developed that enables simultaneous scaffolding of three distinct epitopes derived from respiratory syncytial virus within small single-domain immunogens. Crystallographic analyses confirmed precise presentation of the designed motifs. The multiepitope constructs elicited enhanced cross-reactive and neutralizing antibody responses, demonstrating the potential of generative models for complex multisite protein engineering.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

This study uncovers a mechanism for innate immune memory in neurons, demonstrated by a more silent epigenetic structure of the Herpes Simplex Virus genome, resulting in a deep form of latent infection that is restricted for reactivation of the virus.

Phylogenetic reconstructions with conserved protein markers from the 11 known DPANN phyla reveal their monophyletic placement within the Euryarchaeota.

Visualizing cellular Pi distribution is crucial for the understanding of Pi signalling and homeostasis in plants. Here Guo et al. developed a rapid colorimetric Pi imaging method to reveal the intracellular Pi distribution and related regulators.

This study demonstrates that growth arrest under stress in Arabidopsis protects meristem cells from DNA damage, challenging the idea that it is merely due to energy trade-offs and highlighting its role as an active defense strategy.

Here, using samples from ~1,100 individuals, the authors define the nasal microbiome linked to Staphylococcus aureus colonization, identifying seven communities- either S. aureus-dominated or dominated by other bacteria.

Soil-borne fungal pathogens use chemotropism and extracellular pH alkalinisation to reach and penetrate plant roots. Here, Palmieri et al. show that soil endophytic bacteria swim along fungal hyphae to colonize plant roots and protect host plants by modulating the pH of the rhizosphere.

Multi-plane light converters (MPLCs) rely on complex nonlinear design optimisation and are challenging to physically realise with high fidelity. Here the authors develop a self-configuring free-space MPLC for linear optical information processing.