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Here authors identify GluN2D-containing NMDA receptors on interneurons as a specific target for rapid antidepressant action. Blocking GluN2D restores stress-impaired plasticity and mimics the effects of ketamine with fewer side effects.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Pathology-oriented multiplexing (PathoPlex) represents a framework for widespread access to multiplexed imaging and computational image analysis of clinical specimens at a relatively high throughput and subcellular resolution.

This article presents NAPstars, a family of genetically-encoded biosensors that enable real-time monitoring of NADP redox dynamics across species. The sensors reveal robust NADP redox regulation, cell-cycle-linked NADP oscillations, and glutathione as the major conduit for anti-oxidative electron flux.

Dehingia, Milewska-Puchała and colleagues find a pervasive lncRNA-mediated increase in interactions between CTCF and RNA-binding proteins during embryonic stem cell differentiation. These interactions reinforce chromatin architecture in neural cells.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Here, using multi-omics, the authors reconstruct metabolic models and uncover how disrupted metabolic interactions between gut microbes and the host contribute to IBD, together suggesting that dietary modulation of the microbiome may help restore metabolic balance.

The functional relevance of neural timescales is not fully understood. Here the authors demonstrate that neural timescales change with behavioral demands in freely moving macaques.

A species-level phylogenetic analysis of the high-elevation flora of the European Alps reveals that the flora is young and colonist rich. Its assembly was primarily driven by the Pleistocene climatic cycles, rather than ancient orogenic events.

A multi-omics approach reveals host–microbiome interactions in aging in mice.

Alternative stable states in forests have implications for the biosphere. Here, the authors combine forest biodiversity observations and simulations revealing that leaf types across temperate regions of the NH follow a bimodal distribution suggesting signatures of alternative forest states.

The rhesus macaque is an important model species in several branches of science, but the utility of this model would be enhanced by the ability to measure behaviour throughout pose. Here, the authors describe a deep learning-based markerless motion capture system for estimating 3D pose in freely moving macaques.

Choice-relevant computations across the medial prefrontal cortex differ only quantitatively between areas. Here the authors suggest these computations may be organized along a functional gradient.

Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.

The bacterial second messenger c-di-GMP is important for host association of microbes in C. elegans and beyond.

Jean-Pierre Bourquin, Martin Stanulla and colleagues report whole genome, whole exome and transcriptome sequencing of TCF3-HLF fusion–positive acute lymphoblastic leukemia. Drug response profiling in patient-derived xenografts identified sensitivity to the BCL2-specific inhibitor ABT-199 (venetoclax) as a new option for treating this fatal disease.

Linking structural variants to gene expression information identifies aberrant signaling pathways.

Trained on 1.5 million whole-slide images from 100,000 patients, a pathology foundation model is shown to improve performance of specialized models in detection of rare cancers.

Here, the authors use full-plastome phylogenomics and multiclade comparative models to reconstruct the tempo and drivers of six European Alpine angiosperm lineages before and during the Pleistocene. They find that geographic divergence and bedrock shifts drive speciation events, while diversification rates remained steady.

Complex structural variations in single cells are detected by integrating read depth, template strand and haplotype phase information.

Climatic variables are useful but often weak predictors of plant functional trait variation across ecosystems. Here the authors investigate how assigning plant communities to a habitat hierarchy improves the explanatory power of climate-trait relationships at the continental scale.

By modelling the distribution of the entire Swiss flora using deep learning and citizen science data, this study demonstrates a method that predicts flowering phenology and potentially dominant tree species more accurately than commonly used approaches. This approach could enable investigation of understudied aspects of ecology and refine our understanding of plant distributions.

The prognostic value of OCT in progressive vs relapsing multiple sclerosis (MS) is not clear. Analyzing 2651 OCTs of 407 MS patients, OCT predicted activity in all MS subtypes cross sectionally but longitudinal changes were not predictive in a multicenter setting.

A microfluidics method to generate giant, copolymer-stabilized liposomes is presented. These vesicles are functionalized with distinct proteins to recapitulate cellular processes.

Glucocorticoids reprogram the mitochondrial metabolism of macrophages, resulting in increased and sustained production of the anti-inflammatory metabolite itaconate and, as a consequence, inhibition of the inflammatory response.

Site-specific recombinases such as the Cre-LoxP system are routinely used for genome engineering in both prokaryotes and eukaryotes. Here the authors develop 63 symmetrical LoxP variants and test 1192 pairwise combinations to determine their cross-reactivity and specificity upon Cre activation.

Fine-tuning the expression of biosynthetic pathway genes is crucial to improve microbial production titres. Here, the authors present GEMbLeR, an optimization strategy to balance the expression of multiple genes simultaneously over a wide range.

The neural mechanisms underpinning phase precession remain poorly understood. Here, the authors demonstrate that exogenously generated oscillatory electric fields in the brain can induce phase precession-like effects on cortical excitability and neural firing.

European forests are threatened by climate change with impacts on the distribution of tree species. Previous discussions on the consequences of biome shifts have concentrated only on ecological issues; however, research now shows that under forecasted changes in temperature and precipitation there could be a decline of economically valuable species, which would lead to a loss in the value of European forest land.

Authors carry out an immunogenetic and virologic analysis of nasopharyngeal and peripheral blood samples, finding that early nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways and reduced systemic inflammation before seroconversion.

Previous work has shown that the neural representation of value adapts to the recent history of rewards. Here, the authors report that a computational model based on divisive normalization over multiple timescales can explain changes in value coding driven by changes in the reward statistics.

In vivo mutagenesis allows improving cell factories through directed evolution. Here, the authors present CoMuTER, a tool for targetable random mutagenesis of complete biosynthetic pathways using a Cas3 enzyme fused to a cytidine deaminase.

Functional MRI studies across ages show that the classic homunculus of the motor cortex in humans is in fact discontinuous, alternating with action control-linked regions termed the somato-cognitive action network.

A spatial taxonomic framework integrating genomic, morphological, ecological, life history and acoustic data is used to clarify the cryptic evolution of the taxonomically controversial mouse lemur complex, with a view to aiding future conservation of this and other similarly cryptic clades.

Mitochondria import most of their proteins posttranslationally. Here, Dewar et al. characterize the mitochondrial quality control mechanism of Trypanosoma brucei. Through proteomics and functional studies, they show that only ablation of ATOM69, one of the seven subunits of its mitochondrial protein translocase, triggers a unique quality control pathway resulting in TbUbL1 release from the nucleus and subsequent proteasomal degradation of non-imported mitochondrial proteins.

In a prospective, double-blind, randomized, placebo-controlled trial, supplementation with a combination of conventional and gut-targeted nicotinamide was safe and effective in ameliorating COVID-19 symptoms.

The competition between the formation of different phases and their kinetics need to be clearly understood to make materials with on-demand and multifaceted properties. Here, the authors reveal, by a combination of complementary in situ techniques, the mechanism of a Cu-Zr-Al metallic glass’s high propensity for metastable phase formation, which is partially through a kinetic mechanism of Al partitioning.