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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.

In this single-arm phase 2 trial in patients with HR⁺HER2⁻ advanced breast cancer, treatment with the HER3-targeting antibody–drug conjugate paritumab deruxtecan led to encouraging objective response rates, and comprehensive exploratory analyses indicate potential biomarkers of response.

A ‘light switch’ ruthenium complex is known to show enhanced luminescence in the presence of DNA mismatches — emerging targets for cancer diagnostics and therapeutics — but the way it interacts with DNA has remained unclear. Now, metalloinsertion into and metallointercalation at the minor groove of the double helix have been unambiguously observed in a high-resolution crystal structure.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

The potential for using molecules as wires in nanoscale electronics is somewhat tempered by the challenges in making long and uniform structures. Now, it has been shown that DNA — which is easily synthesized to precise lengths — can conduct charge over 34 nm on multiplexed gold electrodes, a distance that surpasses most reports of molecular wires.

Optical pooled CRISPR screening is improved by combinatorial oligo hybridization for barcode detection.

ATG5 expression in neutrophils counters type I interferon signalling and downstream activation of neutrophil swarming and NET release to limit disease severity during Mycobacterium tuberculosis infection.

Large-scale efforts are put into the generation of knockout mutant mice for many individual genes. Here, the authors systematically screen skin from 538 mutant mice and identify 50 mutants with epidermal phenotypes, of which 9 are also associated with human skin defects.

Evolution of osmoregulation allowed photosynthetic organisms to transform the whole biosphere. Leveraging high-throughput techniques in the freshwater alga Chlamydomonas reinhardtii, the authors uncover evolutionary conservation and divergence of osmoregulatory pathways within the green lineage.

A dataset of 3D images from more than 200,000 human induced pluripotent stem cells is used to develop a framework to analyse cell shape and the location and organization of major intracellular structures.

GABA is the primary inhibitory neurotransmitter in the central nervous system. Using two-photon GABA imaging, Matsumoto et al. reveal over 40 GABA neuron types in the mouse retina, each uniquely filtering visual features.

Motazedian et al. examine human T-cell genesis in haematopoietic organoids and show that RAG1 marks multipotent T-cell progenitors that arise directly from the haemogenic endothelium.

A study presents a strategy based on human pluripotent stem cells for treating neurodegenerative disorders of the gastrointestinal tract.

The involvement of nuclear pore proteins in cellular mechanosensing and metastasis is unclear. Here the authors identify that nuclear pore protein NUP210 promotes metastasis through the interaction with mechanotransducer LINC complex protein and chromatin to regulate mechanosensitive genes.

Transcriptomic data and functional experiments on macaque retina are used to identify the ON-type direction-selective ganglion cells responsible for detecting moving images and initiating gaze-stabilization mechanisms.

Early alcohol drinking confers greater risk for alcohol use disorder in women than men. Here authors show that ovarian-derived estrogen rapidly drives binge alcohol drinking via signaling with membrane-associated estrogen receptors in the extended amygdala.

The emergence of long-range metabolic co-dependence within a biofilm drives oscillations in growth that resolve a social conflict between cooperation and competition, thereby increasing community-level fitness against chemical attack.

Phage and yeast display were used to generate variable heavy single-domain antibodies that bind and allosterically inhibit ectodomain phosphatase/phosphodiesterase-1 to increase the half-life of the immune-stimulant cyclic guanosine monophosphate adenosine monophosphate (cGAMP) in tumor microenvironments.

Chondroitinase injections into monkey spinal cords 4 weeks after hemisection injury increased corticospinal axon growth and corticospinal synapse formation and improved functional outcomes.

RUFY proteins are known to regulate autophagy, cytoskeletal dynamics, migration and endosomal trafficking. Here, Char et al. show that iRUFY3 plays a role in perinuclear positioning, phagocyte migration and antigen presentation during Salmonella infection.

Bioluminescence microscopy with deep learning enables subsecond exposures for timelapse and volumetric imaging with denoising and yields high signal-to-noise ratio images of cells.

Cotton fibre grows in a protective boll that becomes a barrier for researchers when tracking the growth dynamics. Now, the cytoskeleton in elongating cotton fibres has been visualized by live-cell imaging. The cytoskeleton organization and dynamics shed light on the elongation mode of cotton fibre.

Multiciliogenesis requires activation of transcriptional and protein assembly programs; however, the mechanisms that initiate the formation of these multiprotein complexes are unclear. Here the authors show that after inducing centriole biogenesis genes, the transcription factor E2f4 is required in the cytoplasm for assembly and nucleation of deuterosomes.

Ubiquitination factors play crucial roles in DNA repair. The authors show that deubiquitinase OTUD5 facilitates ATM-dependent DNA damage signalling via the UBR5-ATMIN axis. OTUD5 loss results in DNA repair defects at heterochromatin and deprotected telomeres due to insufficient KAP1^S824 phosphorylation.

Plasmonics and metamaterials enable ptychographic coherent diffractive imaging with improved reconstructed phase and amplitude. The approach may be particularly useful for imaging of extremely thin or highly transparent objects.

DEAD-box ATPases are important regulators of RNA metabolism and are involved in all stages of RNA biogenesis. Here, the authors identify Dbp2 as a key ribonucleoprotein remodelling enzyme required for transcript release after 3’-end formation by the cleavage and polyadenylation complex.

RNA base editing enables a precise, reversible and doseable change of genetic information. Here, authors propose base editing as a method to control post-translational modifications via removal of regulatory phosphorylation and acetylation sites, applying the approach to modulation of the JAK/STAT pathway via editing of wildtype alleles.

January 2022 saw the first observations of a tsunami resulting from a large emergent volcanic eruption (Hunga Tonga) captured using modern instrumentation, with broad implications for hazard management in similar geophysical settings.

The order and variability of bacterial chromosome organization, contained within the distribution of chromosome conformations, are unclear. Here, the authors develop a fully data-driven maximum entropy approach to extract single-cell 3D chromosome conformations from Hi-C experiments on the model organism Caulobacter crescentus.

MC4R colocalizes with ADCY3 at primary cilia in hypothalamic neurons, and MC4R mutations associated with human obesity impair this localization. Inhibition of adenylyl cyclase signaling at primary cilia of neurons leads to increased body weight in mice.

Atypical teratoid/rhabdoid brain tumours are characterized by loss of chromatin remodelling complex member SMARCB1. Here, using a genetic screen in Drosophila, the authors identify a number of genes involved in the detrimental effects of SMARCB1 deficiency.

Demyelination results in impairments in oligodendrocyte progenitor cell recruitment. Here the authors identify sulfatase 1/2 as a potential modulator of myelination by modulating the microenvironment around oligodendrocyte progenitor cells.

Marrs et al. show that the serine hydrolase α/β-hydrolase domain 6 (ABHD6) controls the accumulation and efficacy of the endocannabinoid 2-arachidonoylglycerol at cannabinoid receptors. ABHD6 is located post-synaptically and its selective inhibition permits the induction of cannabinoid receptor–dependent long-term depression by otherwise subthreshold stimulations.

Montbretin A is a potent inhibitor of amylase, an enzyme critical in starch digestion and thus of relevance for diabetes and obesity. Structural and biochemical analyses now show that a minimal core of the glycoside π-stacks on itself to fit into the active site.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

A human SARS-CoV-2 challenge study in individuals without previous exposure to the virus or vaccines provides detailed profiles of local and systemic epithelial and immune cell response dynamics over time and infection status.

Some viruses are spherical particles in which protein components are organized with well-defined icosahedral and local symmetries. Here, Gipson et al. describe a unique arrangement of proteins, breaking all expected local symmetries, in particles of a marine bacterial virus.