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The replicative helicase CMG is targeted for removal or proteolysis by the E3 ubiquitin ligase TRAIP. This study describes how the de-ubiquitylating enzyme USP37 protects genome stability by preventing premature TRAIP-dependent CMG unloading when replication stress impedes timely termination.

Activity-dependent oligodendroglial plasticity contributes to neuronal functions. Here the authors show that adaptive oligodendrocyte progenitor cell responses are disrupted in neurofibromatosis 1, impairing oligodendroglial dynamics and resulting in motor learning deficits in Nf1-deficient and Nf1-mutant mice.

Winged bean is a tropical legume that can produce similar level of seed protein to soybean. Here, the authors report the genome assembly, population genetics, QTL mapping of the plant architecture, protein content and phytonutrients for this species.

This Review discusses multiomic approaches for the characterization and biological understanding of cellular senescence, including detailed case studies on skeletal muscle and adipose tissue that highlight current outstanding issues in the field.

Here, the authors leverage whole-genome sequencing from >88,000 diverse individuals to uncover 18 BMI-related genetic signals, including novel variants in participants of African genetic ancestry, highlighting the value of diversity in genetic discovery.

Genome-wide association analysis in over one million individuals of European ancestry identifies 2,103 independent genetic signals (including 113 new loci) associated with blood pressure traits.

The Pliocene–early Pleistocene interval was characterized by climatic fluctuations. Here, the authors apply a bipartite network analysis to a database of planktic foraminifera, finding localized community restructuring through this interval.

A place to remember.

Interlocked molecules represent some of the most challenging synthetic targets in terms of non-natural products. It has now been demonstrated how a cyclic [3]catenane composed of three mutually interpenetrating rings can be prepared in two stages using a selective imine exchange reaction on a self-assembled triangular precursor.

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.

A remora-inspired mechanical underwater adhesive device adheres securely to a range of soft substrates and maintains performance under extreme pH and moisture conditions, with potential applications in biosensing and drug delivery.

A well-tolerated rAAV vector-mediated gene therapy in normotensive Brown Norway rats is used to reduce intraocular pressure in a dose dependent manner, encouraging further evaluations on pre-clinical models of glaucoma.

Aspartoacylase expression in white adipose tissue regulates circulating levels of N-acetylaspartate, which in turn modulates plasma pyrimidine levels and regulates postprandial body temperature.

A deep learning model trained on raw pixel data in hundreds of thousands of echocardiographic videos for the prediction of one-year all-cause mortality outperforms clinical scores and improves predictions by cardiologists.

Small genes have been ignored for years in the genome of every organism due to experimental and computational limitations. Here, the authors describe a computational tool named Rp3 that integrates two high throughput approaches to identify microproteins encoded by these short genes.

Here the authors use mRNA display to discover peptide inhibitors of BamA, an essential factor that catalyzes the membrane insertion of bacterial outer membrane proteins. They show that three peptides are antibacterial and inhibit BamA activity by a unique mechanism.

The cell of origin for high-grade serous carcinoma (HGSC) remains to be determined. Here, the authors characterize the different cell types and states of the mouse uterine tube and identify transitional pre-ciliated cells as a cancer-prone cell state, which could be targeted therapeutically.

Single-cell transcriptomics can allow detailed analyses of paediatric leukaemias. Here, the authors integrate single-cell data from 159 paediatric leukaemia and healthy bone marrow samples, identify a leukaemia-enriched gene expression signature, and develop the integrative online Paediatric Single-cell Cancer Atlas to explore and analyse this harmonised dataset.

Genome-wide association analyses identify new risk loci for heart failure and its subtypes, extending understanding of the underlying biological pathways and disease mechanisms.

Siglec-glycolipid interactions are often studied outside the context of a lipid bilayer. Here, the authors combine a variety of chemical biology techniques to demonstrate a unique and physiologically relevant ability of Siglec-6 to recognize glycolipids in a membrane.

A study reveals that Fusobacterium nucleatum subspecies animalis is bifurcated into two distinct clades, and shows that only one of these dominates the colorectal cancer niche, probably through increased colonization of the human gastrointestinal tract.

Chromatophores in cephalopod skin are known for fast changes in coloration due to light-scattering pigment granules. Here, authors demonstrate structural coloration facilitated by reflectin in sheath cells and offer insights into the interplay between structural and pigmentary coloration elements.

The archaeological site Shinfa-Metema 1 in the lowlands of northwest Ethiopia provides early evidence of intensive riverine-based foraging aided by the likely adoption of the bow and arrow.

RNA-guided CRISPR-associated transposases (CAST) are natural systems with broad potential in biotechnology. Here, the authors report compact type V-K CAST discovered from genome-resolved metagenomics and demonstrate targeted integration of a large transgene to a safe-harbor site in the human genome.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

Lipophilic siRNA conjugates exert therapeutic activity in the mouse CNS.

The underlying mechanism of electroconvulsive therapy remains not fully understood. Here, the authors use optical neuroimaging in mice and humans to show that electroconvulsive therapy elicits a second brain event after seizure—spreading depolarization—a previously hidden phenomenon that may help to understand and optimize this treatment.

Glutaredoxins are a family of essential enzymes divided into two major classes with either a CGFS or a CxxC active site, of which only the latter exhibits oxidoreductase activity. Here the authors address the structural basis for the functional difference between the two classes of glutaredoxins.

piggyBat is the only known DNA transposon active in mammals. Here the authors used cellular assays and 3D structure to show that sequences within the transposon ends restrict activity, and also how transposition activity can be substantially increased.

The neurochemical basis of compulsive behaviour is not well understood. Here, the authors show that levels of glutamate and GABA in the supplementary motor area and anterior cingulate cortex relate to compulsive behaviour in healthy controls and individuals with OCD.

Archaeological discoveries from Malta suggest that humans were present on the Maltese islands from around 8,500 years ago, providing evidence that Mesolithic hunter-gatherers made sea crossings as long as 100 km.

Tecovirimat forces dimerization of the poxvirus phospholipase F13 blocking virus spread. Clinical monkeypox virus strains resistant to tecovirimat show mutations in the F13 dimer interface.

This work presents GōMartini 3, an improved coarse-grained protein model combining physics- and structure-based approaches. It boosts computational efficiency and accuracy for structured soluble and membrane as well as disordered peptides/proteins.

VRC01-class bNAbs against the CD4 binding site of HIV-1 Env are targets of vaccine design. Here, the authors structurally characterized germline versions of the VRC01-class bNAb, BG24, bound to Env. They reveal mechanisms of germline binding, informing the design of VRC01-class targeting immunogens.

FXR regulates the levels of ACE2 in tissues of the respiratory and gastrointestinal systems that are affected by COVID-19, and inhibiting FXR with ursodeoxycholic acid downregulates ACE2 and reduces susceptibility to SARS-CoV-2 infection.

Ocampo et al. present several structures and the biochemical characterization of a compact Cas9 nuclease, shedding light on how these enzymes function and evolve.

Small structural distortions may lead to dramatic modification in the electronic states in strong correlated materials. Here, Yim et al. image a strain-stabilized smectic electronic order in LiFeAs with both broken rotational symmetry and reduced translational symmetry.

In wildlife tagging, stress from capture and handling can alter post- release behavior and potentially study interpretations. This study of 42 mammal species shows that these effects diminish within 4–7 days, and quicker for animals in high human activity areas indicating adaptation to disturbance.

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.