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The authors model near-ground and within-canopy microclimates in a tropical montane rainforest. They show that short-distance shifts towards dense vegetation or vertically downwards in canopies reduce velocities, highlighting that structurally complex ecosystems may provide short-term climate refuges.

This study shows that animal-based high-fat diets accelerate tumour growth and impair anti-tumour response to melanoma in obese mice, whereas plant-based high-fat diets do not.

Eosinophils exist as a functionally heterogeneous population. Whether the heterogeneity is driven by cell-intrinsic or extrinsic factors is underexplored. Here, by leveraging single-cell transcriptomic data and epigenomic analysis, the authors propose that local environmental cues define the gene expression program of murine esophageal eosinophils and identify AP-1 family members, including ATF3, as key regulators of gene expression.

Long-distance migration and dispersion is a common characteristic of nearly all classes of telencephalic GABAergic neurons, which diversify extensively after birth in the cortex and striatum, but show limited postnatal changes in the septum, preoptic area and pallidum.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Targeted protein degradation has so far been rarely applied as an antiviral strategy. Here, the authors report that macrocycle-based PROTACs targeting host protein cyclophilin A, exploited during viral infection, show potent and isoform-selective degradation resulting in antiviral activity against HIV-1 and HCV.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Despite its prevalence, the function of dermal photoreception in color-changing animals remains poorly understood. Here, the authors describe an optical mechanism in hogfish skin, suggesting that one function is to obtain sensory feedback about color change performance.

Metformin is under clinical trial for brain neuroprotection but how it may work is poorly understood. Here, the authors show that metformin helps myelin formation by human oligodendrocytes and improves mitochondrial action in all brain cells.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Combined patch clamp recording, biocytin staining and single-cell RNA-sequencing of human neurocortical neurons shows an expansion of glutamatergic neuron types relative to mouse that characterizes the greater complexity of the human neocortex.

Todorova et al. characterize the strategies through which embryos secure amino acid supply during the early phases of development. Their findings show that, in the preimplantation phase, embryos uptake whole proteins through macropinocytosis and, over time, they shift towards soluble amino acid uptake. This strategy may contribute to protecting embryos from nutrient fluctuations.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

A high-resolution gene expression atlas of prenatal and postnatal brain development of rhesus monkey charts global transcriptional dynamics in relation to brain maturation, while comparative analysis reveals human-specific gene trajectories; candidate risk genes associated with human neurodevelopmental disorders tend to be co-expressed in disease-specific patterns in the developing monkey neocortex.

Fibroblasts play critical roles in tissue homeostasis, but in pathologic states they can drive fibrosis, inflammation, and tissue destruction. Here, Faust et al. find that healthy human synovial fibroblasts under the influence of adjacent adipocytes have altered lipid metabolism driven by cortisol signaling. Both adipocytes and these characteristics are lost in inflammatory arthritis.

Hong Kong experienced a large wave of COVID-19 in early 2022 driven by Omicron BA.2. Here, the authors describe the epidemiological dynamics of this wave and show discordant inferences based on genomic and epidemiological data that underscore the need to improve near real-time epidemic growth estimates.

Mutations in the NRF2-KEAP1 pathway is found to be related with therapeutic resistance and poor outcomes of non-small cell lung cancer (NSCLC). Here this group reports that cystine/glutamate antiporter system xc−, controlled by NRF2, can be non-invasively imaged by positron emission tomography thereby providing a sensitive and specific marker of NRF2 activation in advanced preclinical models of NSCLC.

Aarno Palotie and colleagues present results of a large genome-wide association study of migraine. They identified significant associations at 38 distinct loci and found enrichment for genes expressed in vascular and smooth muscle tissues.

A non-canonical tricarboxylic acid cycle is required for changes in cell state.

Remotely sensed NDVI data and contemporary field data from 84 grasslands on 6 continents show increasing divergence in aboveground plant biomass between sites in different bioclimatic regions.

Laser microdissection and microarrays are used to assess 900 precise subdivisions of the brains from three healthy men with 60,000 gene expression probes; the resulting atlas allows comparisons between humans and other animals, and will facilitate studies of human neurological and psychiatric diseases.

Daniel Benjamin, Meike Bartels, Philipp Koellinger and colleagues report a genome-wide association meta-analysis of subjective well-being, depressive symptoms and neuroticism. The study leverages a large sample size together with genetic correlations between the phenotypes to identify, with high confidence, loci associated with each phenotype.

The RNA for ALS- and frontotemporal dementia-associated C9ORF72 gene is exported from nucleus via an unknown mechanism. This study shows that reduction of nuclear export adaptor SRSF1 can alleviate neuronal cell death and nuclear export of C9ORF72 inDrosophilaand patient-derived induced motor neurons.

Recent estimates of sugar-sweetened beverages (SSBs) intake are generally unavailable. Here the authors show a global SSBs intake of 2.7 servings/week in 2018 in adults (range: 0.7 South Asia, 7.8 Latin America/Caribbean); intakes were higher among males, younger, more educated, and urban adults.

 A transcriptomic cell-type atlas of the whole adult mouse brain with ~5,300 clusters built from single-cell and spatial transcriptomic datasets with more than eight million cells reveals remarkable cell type diversity across the brain and unique cell type characteristics of different brain regions. 

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

A genome-wide association study in ~3 million individuals identifies 3,952 independent variants associated with educational attainment. A polygenic index explains 12–16% of variance for this trait and contributes to risk prediction for ten diseases.

Nutrient-starved tumour cells cooperate by secreting aminopeptidases that digest oligopeptides in the microenvironment, creating a shared pool of free amino acids.

The expression of each of the roughly 22,000 genes of the mouse genome has been mapped, at cellular resolution, across all major structures of the mouse brain, revealing that 80% of all genes appear to be expressed in the brain.

A spatially resolved transcriptional atlas of the mid-gestational developing human brain has been created using laser-capture microdissection and microarray technology, providing a comprehensive reference resource which also enables new hypotheses about the nature of human brain evolution and the origins of neurodevelopmental disorders.

Applying an in vivo bacterial-based system for monitoring the influence of small molecules on the aggregation of model amyloid proteins expressed in the periplasm identified dopamine as a new inhibitor of hIAPP aggregation, a protein involved in type 2 diabetes mellitus.

Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by a genetic mutation in the huntingtin gene (HTT). Here, cryo electron tomography provides insights into the morphology of the cells derived from patients with HD and mouse models of the disease.

Copy number signatures characterize different types of chromosomal instability and predict drug response.

White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.

It remains unclear whether exotic and native species are functionally different. Using a global grassland experiment, Seabloomet al. show that native and exotic species respond differently to two globally pervasive environmental changes, addition of mineral nutrients and alteration of herbivore density.

A genetic study identifies hundreds of loci associated with risk tolerance and risky behaviors, finds evidence of substantial shared genetic influences across these phenotypes, and implicates genes involved in neurotransmission.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Finley et al. show that Brd4 is dispensable for self-renewal and pluripotency in murine embryonic stem cells (ESCs). In metastable ESCs, Brd4 independence can be achieved by increasing the expression of the pluripotency transcription factors Oct4, Sox2 and Nanog as long as Tet1/2 are present.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

Genomic and cell-free DNA sequencing clarify the clinical diagnosis and inform treatment initiation in a cohort of 356 patients with vascular anomalies.