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Advances in electron cryo-microscopy hardware allow proteins to be studied at atomic resolution.

In contrast to their clinical success as inhibitors and targeting agents, antibodies have generally been ineffective as receptor agonists. Here, Romei et al. leverage a natural homotypic interface to tune antibody geometry, enabling optimization of agonist activity for multiple therapeutic targets.

By leveraging paired microbiome and human gene expression data from pediatric patients who underwent hematopoietic cell transplantation, distinct lung–immune system–microorganism interactions were identified as important drivers of fatal lung injury.

Glucagon is hormone that signals via a dedicated g-protein coupled receptor, but downstream signaling is poorly understood. Here, Wu et al. uncover liver glucagon signaling using phosphoproteomics and define a role for the vesicle trafficking protein SEC22B in distinct metabolic actions.

The severity of ulcerative colitis, and response to treatment, is highly variable. Here, the authors examine rectal gene expression signatures and faecal microbiomes of children and adults with the disease and provide new insights in to pathogenesis.

The authors propose Detect, a browser-based anomaly detection framework for diffusion magnetic resonance imaging tractometry data. The tool leverages normative microstructural brain features derived from healthy participants using deep autoencoders to detect anomalies at the individual level.

Deep learning-based methods to generate new molecules can require huge amounts of data to train. Skinnider et al. show that models developed for natural language processing work well for generating molecules from small amounts of training data, and identify robust metrics to evaluate the quality of generated molecules.

Identifying a complex panel of bias dimensions to be evaluated, a framework is proposed to assess how prone large language models are to biased reasoning, with possible consequences on equity-related harms, and is applied to a large-scale and diverse user survey on Med-PaLM 2.

Design of a two-component protein array enables robust formation of complex large-scale ordered biologically active materials.

Nature Biotechnology asks a selection of researchers about the most exciting frontier in their field and the most needed technologies for advancing knowledge and applications.

Through a community-driven competition, the PANDA challenge provides a curated diverse dataset and a catalog of models for prostate cancer pathology, and represents a blueprint for evaluating AI algorithms in digital pathology.

In mammals, de novo DNA methyltransferase DNMT3B is essential for establishing DNA methylation patterns during embryonic development. Here the authors provide a structure-function characterization of homo-oligomeric DNMT3B, revealing the molecular basis for its vulnerability to ICF mutations.

Spectroscopy of a gravitationally lensed galaxy at a redshift of 2.7 with spatially resolved maps of two foreground damped Lyman α systems indicates a vast mass of neutral hydrogen gas, consistent with a star-forming region.

Description of four new species of Xenoturbella and phylogenomic analyses, aligning Xenacoelomorpha as sister group to the rest of Bilateria, or as sister to Protostomia.

Certain delafossite materials are the most conductive oxides known, for poorly understood reasons. This work elucidates this finding by uncovering a sublattice purification mechanism that enables ultrapure conductive planes even in impure crystals.

A protein has been engineered so that 24 identical copies self-assemble into a cube-shaped hollow cage 23 nm in diameter and containing a 130-Å-diameter inner cavity. This represents the largest and most porous structure of its type so far.

Breeding has increased crop productivity, but whether it has also changed phenotypic plasticity is unclear. Here, the authors find maize genomic regions selected for high productivity show reduced contribution to genotype by environment variation and provide evidence for regulatory control of phenotypic stability.

Optical spectroscopy based on nonlinear effects usually requires coherent, ultrafast light sources such as femtosecond lasers. Here Turneret al.measure coherent multidimensional optical spectra of molecular systems using incoherent light.

Targeted protein degradation (TPD) is a key modality for drug discovery. Here the authors present the discovery and analysis of reversible DCAF1-PROTACs, which show efficacy in cellular environments resistant to VHL-PROTACs or with acquired resistance to CRBN-PROTACs.

Thermal triggering of rock exfoliation has long been discounted as relevant to the evolution of rock domes. Here, the authors documented and measured recent fracturing events in California, USA to show that hot summer periods can lead to thermal stresses and cause seemingly spontaneous rock exfoliation.

Antibody-drug conjugates targeting high expression receptors can suffer from poor tumour penetration. Here, the authors use unconjugated antibody to improve the penetration of an antibody-dye conjugate in a clinical study, supporting further clinical investigation of the co-administration strategy.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

A conserved network of bacteria and fungi underpins cadaver decomposition despite selection effects of location, climate and season.

Deep-learning models trained on external eye photographs can detect diabetic retinopathy, diabetic macular oedema and poor blood glucose control more accurately than models relying on demographic and medical history data.

Emerging SARS-CoV-2 variants of concern were detected early and multiple cases of virus spread not captured by clinical genomic surveillance were identified using high-resolution wastewater and clinical sequencing.

By comparing the genome-wide profile of H4K16ac in AD with younger and elder controls, the authors propose a mechanism for how age is a risk factor for AD: a histone modification, whose accumulation is associated with aging, is dysregulated in AD.

It is unclear whether climate driven phenological shifts of tundra plants are consistent across the plant growing season. Here the authors analyse data from a network of field warming experiments in Arctic and alpine tundra, finding that warming differentially affects the timing and duration of reproductive and vegetative phenology.

Cells exhibit exceptional chemical sensitivity, yet we haven’t fully understood how they achieve it. Here the authors consider the mutual information between signals and two coupled sensors as a proxy for sensing performance and show its optimisation depending on noise level and signal statistics.

Metal-catalysed prebiotic reactions have been proposed as forerunners of modern metabolism. Now, an abiotic pathway resembling the reverse tricarboxylic acid cycle has been shown to proceed without metal catalysis. The reaction of glyoxylate and pyruvate produces a series of α-ketoacid tricarboxylic acid analogues, and provides a route to generate α-amino acids by transamination.

Fibroblastic reticular cells support lymph-node function and adaptive immunity. McGeachy and colleagues show that the cytokine IL-17 is needed to trigger metabolic changes required for the proliferation and survival of these cells in reactive lymph nodes.

A Free Ocean Carbon Enrichment study on the Great Barrier Reef finds that elevated carbon dioxide impairs net calcification of living corals and may accelerate dissolution of dead corals.

Visual input received by photoreceptors is relayed to retinal ganglion cells (RGCs), which have selectivity for inputs of certain orientations. Here, the authors show that gap junction-mediated input onto one type of RGC contributes to its orientation selectivity.

Halophilic organisms thrive in high salt conditions and express proteins that display desirable characteristics for industrial applications. Here, the authors use a rational design approach to transform wild-type carbonic anhydrase into a strongly halophilic enzyme.

A phase-separation mechanism is proposed for the dominance of the surface tension effect over the solute effect in the observed activation of ultrafine cloud condensation nuclei.

How microglia sense amyloid plaques in Alzheimer’s disease has remained mysterious. Lemke and colleagues report that TAM receptor kinases are absolutely required for normal microglial recognition of, response to and phagocytosis of Aβ plaques. Surprisingly, TAM-mediated microglial phagocytosis of Aβ material does not constrain, but rather promotes, the formation of dense-core plaques.

The mechanisms underlying drought-induced tree mortality are not fully resolved. Here, the authors show that, across multiple tree species, loss of xylem conductivity above 60% is associated with mortality, while carbon starvation is not universal.

Spatial proteomic data serve to provide cell-level location information for the extraction of biological features from tissues, but analyzing such data can be difficult. Here the authors report the development of SPIAT for data analyses and spaSim for simulation and validation of methods to help bridge the gap between the technology and its translation.

Protein-truncating variants (PTVs) are predicted to significantly affect a gene’s function and, thus, human traits. Here, DeBoever et al. systematically analyze PTVs in more than 300,000 individuals across 135 phenotypes and identify 27 associations between PTVs and medical conditions.

A high-resolution reference panel based on whole-genome sequencing data enables accurate imputation of HLA alleles across diverse populations and fine-mapping of HLA association signals for HIV-1 host response.

The growth factor NELL-1 induces bone formation during development, but its role in osteoporosis is unknown. This study shows that NELL-1 binding to integrin ß1 induces Wnt/ß-catenin signalling in the bone and restores bone mineral density in osteoporotic mice and sheep, suggesting the therapeutic potential of NELL-1 for the treatment of bone loss.

Competing phases in layered complex oxides are believed to be relevant for emergent phenomena, which still await to be witnessed. Here, Stone et al. report direct atomic-scale imaging of a multitude of polar phases in Ruddlesden-Popper oxide thin films, exhibiting diverse phenomena in a single structure.

The chimeric cytokine IC7Fc combines the beneficial effects of the cytokines IL-6 and CNTF on weight loss and metabolism in mice, with no obvious side effects in mice and non-human primates.

‘Cooperative redox enhancement (CORE) effects, which arise through the coupling of oxidative dehydrogenation and oxygen reduction reactions, can lead to increased rates of reaction over spatially separated bimetallic heterogeneous catalysts.

In 653,790 individuals, this multi-ancestral meta-analysis of tobacco use disorder finds 461 potential risk genes and hundreds of associations with health outcomes, showcasing the utility of electronic health records for genetic research.

We have developed an automated and high-throughput, three-dimensional, vision-controlled inkjet deposition process that enables the high-resolution, contactless printing of a range of materials with varying elastic moduli to create complex structures and robots.