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Results of an early-phase breast cancer prevention trial demonstrate the potential for breast cancer prevention in premenopausal women with anti-progestin therapy by inducing epithelial–stromal remodelling and suppression of luminal progenitors.

Systematic base-editing and computational screens identify specific cysteine residues on VPS35 in the retromer complex as key sensors that decrease mitochondrial translation in response to reactive oxygen species signals.

Kim et al. show that NAD⁺ kinase 2 serves as a source of mitochondrial NADPH to support mitochondrial fatty acid synthesis, protein lipoylation and mitochondrial oxidative metabolism.

Isolating and studying haematopoietic stem cells in young and aged mice demonstrates evolutionary processes related to blood production and provides a framework for interpreting future work using laboratory mice to study stem cell ageing.

Many bacteria use the second messenger cyclic diguanylate (c-di-GMP) to control motility, biofilm production and virulence. Here, the authors identify a thermosensitive enzyme that synthesizes c-di-GMP and modulates temperature-dependent motility, biofilm development and virulence in the opportunistic pathogen Pseudomonas aeruginosa.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

Samples from the asteroid (101955) Bennu, returned by the OSIRIS-REx mission, include sodium-bearing phosphates and sodium-rich carbonates, sulfates, chlorides and fluorides formed during evaporation of a late-stage brine.

The authors use artificial intelligence approaches to explore the predictive value of whole exome sequencing in forecasting clinical outcomes following surgery for congenital heart defects. Findings include that damaging genotypes in chromatin-modifying and cilia-related genes are associated with an increased risk of adverse post-operative outcomes such as mortality, cardiac arrest, and prolonged mechanical ventilation.

Hypoxia induces ·NO-dependent hydrogen sulfide (H₂S) biogenesis by inhibiting the transsulfuration pathway. H₂S oxidation promotes endothelial cell proliferation to support neovascularization in tissue injury and tumor xenograft models.

Wu, Harrison and colleagues visualize lactate production at subcellular resolution in migrating endothelial cells and identify hotspots of glycolytic activity, mediated by RhoA and the glucose transporter SLC2A3, that couple cellular energy metabolism with cytoskeleton remodelling and cell motility.

Feedback from active galactic nuclei (AGNs) remains controversial despite its wide acceptance as necessary to regulate massive galaxy growth. Consequently, we held a workshop in October 2017, at Leiden’s Lorentz Center, to distinguish between the reality and myths of feedback.

Newly formed endosomes mature into early endosomes by shedding one protein and acquiring another. Here, the authors describe a trigger-and-convert mechanism driven by endosomal collisions and fusions that govern timeliness in ensemble maturations.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Electron cryomicroscopy and cryotomography studies reveal that rotaviruses attach to a target cell through the outer-layer protein VP4, which—following cleavage—rearranges to enable perforation of the membrane and delivery of the viral genome into the host cell.

Wang and colleagues show that in skeletal muscle cells and cardiomyocytes, the glucose transporter GLUT4 is a negative regulator of RIG-I-like receptor signaling during viral infection by redistributing RIG-I and MDA5 to the plasma membrane and attenuating interferon responses.

Hernandez-Candia et al. introduce BTBolig, a chemical-based tool to manipulate biomolecular condensates, and CoSMo, a method for control of condensate maturation. When used together, the authors observe dynamic interactions of condensates with protein chaperones.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

City-level analysis of data from the SALURBAL project shows vast heterogeneity in life expectancy across cities within the same country, in addition to substantive differences in causes of death among nine Latin American countries, revealing modifiable factors that could be leveraged by municipal-level policies aimed toward improving health in urban environments.

By investigating key transcription factors in Drosophila, the authors show that pioneering activity is not an intrinsic, binary property. Instead, it is heavily influenced by the level of chromatin occupancy of the transcription factors, which is controlled by multiple protein domains and protein-extrinsic features.

The RIG-I like receptors sense RNA viruses and initiate antiviral immunity. Here the authors screen 375 definite ubiquitin ligases and propose UBR5 promotes RLR transcription by disengaging the TRIM28-imposed brake on the RLR promoters.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

The prognosis of cancer patients with lymph node (LN) metastasis is worse than those without. Here, the authors report that while histone deacetylase 11 (HDAC11) inhibition suppresses tumor growth within the LN, it also promotes cancer cell migration out of the LN to form distant metastasis, and therefore suggest caution with HDAC inhibitors.

Lung squamous carcinomas (LUSC) are poorly molecularly characterized, but sub-populations show promising response to immune checkpoint inhibitors. Here, the authors identify a subset of LUSC characterized by infiltration of inflammatory monocytes, where metastasis is linked to Factor XIIIA promoting fibrin cross-linking.

Here the authors perform a genome-wide CRISPR-Cas9 knockout screen to systematically identify and characterize essential and growth-restricting genes in human trophoblast cells. They identify TEAD1 as a key regulator that plays an important role in the specification, maintenance, and differentiation of the human trophoblast lineage by modulating chromatin architecture and gene expression.

Here the authors describe a simple reverse genetics method that relies on overlapping cDNA fragments for generation of positive-strand viruses including SARS-CoV-2 and characterize them in vitro and in vivo.

In a new study including 200 families who experienced perinatal death, adding genomic analyses to standard autopsies improved the identification of underlying pathogenic causes and informed genetic counseling.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Mutations in equilibrative nucleoside transporter 3 (ENT3), encoded by SLC29A3, cause a spectrum of human genetic disorders. Here, the authors show altered haematopoietic stem cell and mesenchymal stem cell fates in ENT3-deficient mice, due to misregulation of the AMPK-mTOR-ULK axis.

In Drosophila embryos, Piwi-interacting RNAs (piRNAs) loaded into the PIWI protein Aubergine target and destabilize maternal mRNAs. Here, the authors provide evidence that piRNAs and Aubergine cooperate with the Wispy poly(A) polymerase to stabilize these mRNAs in the germ plasm.