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Which combination of current genome sequencing and assembly approaches results in high-quality, complete diploid genome assemblies is determined.

Dysfunction in dorsal striatum, a brain region important for reward and habits, is linked to opioid use disorder (OUD). Here, authors delineate diverse cell populations in human dorsal striatum, revealing altered inflammatory and DNA damage signaling in OUD.

Zhao et al. used single-cell and spatial multiomics data analysis of human and mouse lung adenocarcinoma tumors and cell lines to reveal TP53 mutation-associated changes in cancer cells and their microenvironment.

RNA-interacting proteome can be identified by RNA affinity purification followed by mass spectrometry. Here the authors developed a different RNA-centric technology that combines high-throughput immunoprecipitation of RNA binding proteins and luciferase-based detection of their interaction with the RNA.

Past intestinal distress is associated with diminished social behavior in mice. Here, the authors show that treatment with microbiota members that are enriched in neurotypical people versus people with ASD can ameliorate colitis severity and associated sociability deficits.

ExFISH extends expansion microscopy to single-molecule RNA imaging, enabling super-resolution imaging of diverse RNAs in cells and tissues on conventional microscopes. The method enables multiplexed imaging of RNA and improved RNA quantitation.

Autophagy-mediated control of Mycobacterium tuberculosis acute infection in mice is uncovered by more complete knockouts in autophagy pathway genes.

ABCB6 has been implicated in dyschromatosis universalis hereditaria, a condition that can present with hearing loss. Here, the authors use zebrafish and mice to perform experiments suggesting that ABCB6 plays a role in inner ear development.

Few aerobic hyperthermophilic microorganisms are known to degrade polysaccharides. Here, Nou et al. use genomic information to enrich and optical tweezers to isolate an aerobic hyperthermophilic bacterium that can grow at 65–87.5 °C using polysaccharides as sole carbon sources.

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.

There is a need for development of efficient delivery vehicles for the treatment of inherited retinal degeneration with gene therapy. Here, Gautam et al., show that surface modifications of lipid nanoparticles with PEG variants alters their cellular tropism allowing gene editing in diverse retinal cell types in mice.

The transcription factor, serum response factor, SRF regulates critical smooth muscle (SM) contractile gene expression but what else controls SM differentiation is unclear. Here, Horita et al. demonstrate that nuclear PTEN acts with SRF at the transcriptional level to maintain the differentiated SM phenotype.

It is unclear why certain tissues are more susceptible to the consequences of aneuploidy. Here, in Drosophila, Gogendeau et al.identify aneuploidy as the cause of lengthened G1 and premature differentiation in both neural and adult intestinal stem cells, which prevents cells with abnormal genomes from cycling.

Anerillas et al. provide a strategy to eliminate senescent cells that leverages on their secretory needs. Inhibiting YAP–TEAD triggers endoplasmic reticulum stress that eliminates senescent cells from several tissues, improving age-related fibrosis.

The organization of gut microbes in lumen and mucosa and the microbial genes regulating this organization remain poorly understood. Here, using in vitro cultures incorporating a complex gut microbial community in mucin-hydrogel carriers, the authors show greater richness and strain-specific spatial organization, enabling discovery of associated genes.

Subduction of oceanic crust and sediments contributes to heterogeneities in the mantle, which are sampled by mantle plumes. Here, the authors find that extreme isotopic heterogeneity in Samoan clinopyroxenes can help constrain the composition of mantle sources containing sediment recycled into the Earth’s mantle.

Analysis of genomes, epigenomes and transcriptomes of developing sea urchins with divergent life histories shows how natural selection can reshape developmental gene regulatory networks.

Bulk or pooled epigenomic profiling in the heterogenous brain obscures cell-type-specificity and individual subject variability in gene regulation. Here the authors optimized a hybrid protocol, ICuRuS, to profile epigenetic features in neuronal subtypes from a single mouse.

Meng et al. show that ZBTB43 alters Z-DNA structures to prevent deleterious double-strand breaks and promote DNA methylation at purine–pyrimidine repeats in the mouse germ line.

Simultaneous electrophysiological recordings are obtained from multiple brain regions using Neuropixels probes. The procedure covers the implantation of a headframe, the targeted positioning of probes and their insertion through a perforated imaging window.

An ex vivo 3D culture model of mycobacterial granulomas recapitulates the in vivo physiology of these structures and enables longitudinal imaging studies. The platform allows genetic and pharmacological manipulation of this key structure.

Naturally occurring genetic variation between inbred mouse strains is used as a mutagenesis strategy to investigate mechanisms responsible for the selection and function of cis-regulatory elements in macrophages; lineage-determining transcription factors are proposed to select enhancer-like regions in the genome in a collaborative fashion and facilitate the binding of signal-dependent factors.

Previous methods for functionalizing hydrocarbons with CO₂ to form carboxylic acid derivatives have required stoichiometric energy-intensive reagents such as strong bases or electrophilic activators. Now, a simple solid base has been developed that transforms aromatic hydrocarbons, CO₂ and methanol into aromatic esters via a two-step cycle requiring no additional reagents.

Topoisomerase 2 (Top2) is known to resolve DNA topological stress through double strand breaks (DSBs), yet Top2 inhibition has been reported to result in a significant amount of single-strand breaks (SSBs). Here the authors develop CC-seq—a method that allows direct mapping of both Top2-linked SSBs and DSBs—and reveal a significant impact of primary DNA sequence on Top2 directed cleavage.

Soft electronic patches worn on the skin of infants or children in intensive-care units have a wide range of capabilities in aiding critical care, including monitoring of hemodynamic parameters, cardiac activity, movement and crying.

Serum MMP8 is increased in stress-susceptible mice following chronic stress and leads to brain structure and behavioural changes in mice.

Combination of TCR or CAR T cells expressing the engineered CD47 variant 47_E with anti-CD47 antibody therapy results in synergistic antitumour efficacy due to T cell resistance to clearance by macrophages, while maintaining macrophage recruitment into the tumour microenvironment.

Functional brain imaging with two-photon microscopy is limited by a tradeoff between imaging area and acquisition speed. Here, the authors present Quadroscope, a flexible microscope which allows for simultaneous video rate acquisition of four independently targetable brain regions across 5 mm.

Using carbon nanotube transistors, stretchable temperature sensor circuits can be designed that suppress strain-dependent errors and achieve a measured inaccuracy of only ±1 °C within a uniaxial strain range of 0–60%

Quantum dots with different size emit light at different wavelengths but also different brightness, which complicates analysis of fluorescence images. Here, the authors synthesize multicolour brightness-equalized quantum dots by controlling the composition and structure of core-shell HgCdSeS-CdZnS nanocrystals.

The mechanism of U6 small nuclear ribonucleoprotein (snRNP) biogenesis is not well understood. Here the authors characterize the enzymatic activities and structures of yeast and human U6 RNA processing enzyme Usb1, reconstitute post-transcriptional assembly of yeast U6 snRNP in vitro, and propose a model for U6 snRNP assembly.

The liver is an important regulator of glucose homeostasis. Here, the authors provide insight into the molecular signalling pathways controlling hepatic gluconeogenesis by showing that SIK protein kinases suppress gluconeogenesis, and that glucagon—but not insulin—regulates phosphorylation of SIK2.

South Africa experienced a resurgence in COVID-19 in 2022 driven by Omicron subvariants BA.4 and BA.5. Here, the authors investigate the severity of infections caused by these subvariants, and find no difference in the risk of severe outcomes when compared to Omicron BA.1, whilst all Omicron subvariants were less severe than Delta.

Ali et al. show that, during heat shock, aggregation-prone orphan ribosomal proteins form nucleolar-associated condensates that are kept in a liquid-like and reusable state through Hsp70 and its co-chaperones.

Here the authors find that RNase J, the major ribonuclease of the gastric pathogen Helicobacter pylori is post-translationally modified by acetylation. They show that acetylation can control RNase J activity.

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.

Matrix stiffening is a quintessential feature of aged tissues. Authors show that an aged (stiff) matrix epigenetically represses the gene encoding the longevity factor, α-Klotho, resulting in chondrocyte dysfunction, a leading cause of osteoarthritis.

Expansion of the chemical diversity of glycopeptide antibiotics (GPAs) to deal with the emergence and spread of GPA resistance is challenging. Here, the authors report a GPA synthetic biology platform in Streptomyces coelicolor for Type IV–V glycopeptide antibiotic production and discovery.

A role and mechanism of action are identified for INSP3R1 in the stimulation of hepatic gluconeogenesis and mitochondrial oxidation by glucagon, suggesting that INSP3R1 may be a target for ameliorating dysregulation of hepatic glucose metabolism.

Microbiota composition fluctuates in response to changes in environmental and lifestyle factors. Here, Hicks et al. show that the faecal microbiota of wild gorillas and chimpanzees is temporally dynamic, with shifts that correlate with seasonal rainfall patterns and periods of high and low frugivory.

Resident microbiota contribute to HIV and EBV infection in a germ-free humanized mouse model.

The scarcity of targetable proteins broadly expressed on cancer cells, but not on healthy cells, is an obstacle for chimeric antigen receptor (CAR)-T cell therapy. Here the authors establish that a functionally impaired version of P2X purinoceptor 7, non-functional P2X7 (nfP2X7), fulfils these criteria, and demonstrate that CAR-T cells targeting nfP2X7 efficiently and selectively kill breast and prostate cancer cells in mouse models.

Bacteria and archaea use tripartite ATP-independent periplasmic (TRAP) transporters to import essential nutrients. Davies et al. report a high resolution structure of a TRAP and show that it uses an ‘elevator-with-an operator’ mechanism.

The Arctic is changing faster than anywhere else on Earth. Interactions between clouds and aerosols play a role in these changes. We report how the quantities and origins of aerosols that affect cloud ice formation change over a full sea ice cycle

The role of ciliary/centriolar components in the postnatal brain is unclear. Here, the authors show via ablation of Pcm1 in mice that degenerative ciliary/centriolar phenotypes induce neuroanatomical and behavioral changes. Sequencing of PCM1 in human cohorts and zebrafish in vivo complementation suggests PCM1 mutations can contribute to schizophrenia.

Researchers report an optical method to detect and image single proteins without using any labels.

A simple approach for making multilayer microfluidic devices should make this technology more accessible to biologists.