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This Resource paper presents a global SARS-CoV-2 phylogenetic tree of 4,471,579 high-quality genomes consistently constructed by Viridian, an efficient amplicon-aware assembler.

Circulating tumor cell (CTC) clusters are key drivers of metastasis, yet their formation in tumors lacking classical adhesion molecules is unclear. Here, the authors discover that hyaluronic acid promotes homotypic and heterotypic CTC clustering by initiating early cell contacts and stabilizing mature interactions.

Molecules arranged in close proximity to a surface form molecular layers, exhibiting distinct properties. However, the creation of these layers is challenging. Here, the authors present a technique for generating molecular layers through crystallization induced by gas blowing onto a surface.

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).

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.

Geminin regulates DNA replication by binding CDT1 and preventing MCM helicase loading. Using a reconstituted system and structural modelling, the authors find geminin inhibits via steric clash with MCM, not by blocking the CDT1–MCM interface. Combined with CDK activity, it fully halts licensing.

The role of impaired lung function in lung cancer etiology is complex due to the relation of cigarette smoking to both conditions. Here, supported by Mendelian randomization analysis the authors find a link between pulmonary function impairment and lung cancer risk beyond smoking, implicating immune-related pathways

Mepolizumab (anti-IL-5 therapy) has been shown to reduce type 2 inflammation in asthma. Here the authors use bulk transcriptomics from nasal samples before and after mepolizumab treatment to assess the changes and associations with treatment outcomes.

A long way from home.

Microglial states are dynamically regulated during development and disease. Here, the authors show that these changes are mediated by cell autonomous TGF-β signaling in microglia, which is developmentally regulated by ITGB8 in radial glia.

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.

The WHO’s designation of mpox as a public health emergency of international concern underscores the need for diagnostics to combat this escalating threat. Here, the authors present a portable POC molecular platform based on power-free DNA extraction and colourimetric LAMP.

Recognising cross-ecosystem linkages between terrestrial and aquatic ecosystems is vital for sustainable management and conservation of freshwater biota. Here, the authors show that land use activities are strongly linked to the reliance of benthic and pelagic consumers on terrestrial energy sources in boreal lake food webs.

A tweezer clock containing about 150 ⁸⁸Sr atoms achieves trapping and optical excited-state lifetimes exceeding 40 seconds, and shows relative fractional frequency stability similar to that of leading atomic clocks.

Nephrite jade is a semi-precious gemstone composed of tiny crystals and needles of amphibole. Here, Matthew Tarling and Steven Smith describe how its origins lead to inner toughness and beauty.

The expansion of agriculture and rangelands can cause ecological spillover effects across cultivated-natural ecosystem boundaries. Here, Luskin et al. show irruptions of oil palm-subsidized wild boar alter the abundance and diversity of understory trees >1 km into a primary forest reserve in Malaysia.

Wind patterns could enhance or hinder the ability of organisms reliant on wind-driven dispersal and pollination to shift their ranges under climate change. Organisms in the tropics and on the leeward side of mountains may be particularly at risk due to scarcity of suitable, wind-accessible sites.

Replenishing key extracellular matrix (ECM) proteins facilitate wound healing through unclear mechanisms. Here the authors report that injury-triggered Agrin, an ECM proteoglycan, tunes a mechanocompetent niche by engaging MMP-12, thereby enforcing efficient skin wound healing.

This work presents biotin-DNA affinity purification (DAP) sequencing, that is, an in vitro, clone-free workflow to profile transcription factor (TF) DNA binding, as well as multiDAP to simultaneously characterize TF DNA binding in multiple bacterial genomes.

A targeted protein stabilization platform termed deubiquitinase-targeting chimera (DUBTAC) was developed based on heterobifunctional small molecules consisting of a deubiquitinase OTUB1 recruiter linked to a protein-targeting ligand.

Analogue quantum simulators could provide insights into complex dynamics, but realizing them in a scalable way remains a technological challenge. Here, the authors demonstrate how two-dimensional arrays of three ions trapped in individually controlled wells could form a scalable platform for quantum simulation.

Asthma is characterized by abnormal airway hyperresponsiveness. Here the authors identify BPIFA1 as a factor secreted by airway epithelial cells, and show that it regulates contractility of airway smooth muscle cells by binding to and regulating the Orai1 Ca²⁺channel.

A bright patch in the Fermi bubbles, previously attributed to a jet launched by the Galaxy’s central black hole, is actually due to gamma-ray emission by millisecond pulsars in a background, satellite galaxy of the Milky Way.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Mimicking the molecular architecture of channel-forming membrane proteins of a target microbe can be used to design host defence peptides that specifically target a particular pathogen, as shown here for Mycobacterium tuberculosis.

Respiratory infections are the principal cause of asthma exacerbations in children. Altman and colleagues use a systems approach to describe the pathways associated with asthma exacerbations in a cohort of inner-city children.

Light-inducible dimerization tags are engineered to rapidly recruit proteins to precise points in living yeast and mammalian cells. The affinities and response time of the interactions are tunable, and the authors used the system to activate cell signaling and to direct cell polarization in yeast.

Determining the spatial and temporal activity patterns of enhancers remains a challenge in the functional annotation of the human genome. In this study, the genome-wide occupancy of the enhancer-associated protein p300 was determined in developing mouse tissues by using chromatin immunoprecipitation followed by massively parallel sequencing. Testing the p300-bound sequences in a transgenic mouse enhancer assay confirmed that p300 binding is a highly effective means to identify enhancers and to predict in which tissues they are active.

Foreign proteins in a cell are chopped up and presented to the immune system by molecules of the major histocompatibility complex. What enzymes are responsible for making these cuts? The enzyme that delivers the initial blow specifically to the tetanus toxin has now been identified as asparaginyl endopeptidase.

Transient electronics entails the capability of electronic components to dissolve or reabsorb in a controlled manner when used in biomedical implants. Here, the authors perform a systematic study of the processes of hydrolysis, bioabsorption, cytotoxicity and immunological biocompatibility of monolayer MoS₂.

Rajderkar et al. provide a genome-wide compendium of transcriptional enhancers active in human craniofacial development, along with single-cell resources for studies of mammalian craniofacial morphogenesis.

The month’s sharpest science shots — selected by Nature’s photo team.

Physicists hoping for signs of radically new particles get no joy from Large Hadron Collider.

LTT 9779 b is Neptune-sized planet rotating around its star with a period of 0.79 days and an equilibrium temperature of 2,000 K. It is not clear how it retained its atmospheric envelope, which contains ~10% of H/He, as it should have been photoevaporated by now.

A large-scale mutagenesis screen identifies mutant phenotypes for over 11,000 protein-coding genes in bacteria that had previously not been assigned a specific function.

Maxwell Scott et al. report the genome of the New World screwworm, a devastating livestock pest in South America and the Caribbean. Using transcriptomic analysis of the insect’s developmental stages combined with genomic analyses, the authors identify genes that may be important for its parasitic lifestyle.

This month’s Genome Watch discusses the application of spatial transcriptomics to investigate the arrangements of microbial communities and their effects on the host.

In order for quiescent galaxies to maintain their low-to-non-existent star formation, there must be a mechanism to remove or heat gas that would otherwise cool to form stars; now supermassive black hole winds that are sufficient to suppress star formation in such galaxies are reported.