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NMR structure determination is challenging for proteins with a molecular weight above 30 kDa and atomic-resolution structure determination from cryo-EM data is currently not the rule. Here the authors describe an integrated structure determination approach that simultaneously uses NMR and EM data and allows them to determine the structure of the 468 kDa dodecameric aminopeptidase TET2 complex.

Phosphate involvement in calcium carbonate biominerals raises questions on biomineralisation pathways. Here, the authors explore the presence of phosphate in the growing shell of the European abalone and suggest a shared mixed mineral ancestral precursor with final crystal phase being selected by mineral-associated proteins.

Cladodontomorph sharks are Palaeozoic stem chondrichthyans thought to have disappeared at the end-Permian mass extinction. Here, Guinot et al.report the finding of a shark tooth assemblage from the Early Cretaceous recovered from southern France, which shows that this group survived the mass extinction in deep-sea refuges.

Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

Results of the phase 2 trial of CD19 CAR T cell therapy lisocabtagene maraleucel in patients with relapsed or refractory follicular lymphoma, most of whom were treated in a third-line or later setting, show encouraging objective response rates in these high-risk patients.

This study reveals how the intrinsically disordered protein POSH undergoes stepwise folding upon binding to the GTPase Rac1. Each folding step is dependent on the successful completion of the previous one, revealing a hierarchical folding mechanism.

Little Red Dots (LRDs) are a high-redshift galaxy population with unclear nature. Here, authors show CANUCS-LRD-z8.6, a spectroscopically confirmed LRD, hosting an active galactic nucleus, and its properties provide insights for early black hole and galaxy formation.

Porous metal–organic frameworks (MOFs) can be used as sorbents in water-adsorption-driven chillers, but are currently limited in terms of stability and efficiency. Here the authors present a chemically and mechanically stable zirconium carboxylate MOF with a high coefficient of performance for refrigeration.

A method for cell-free synthesis of amyloid fibrils is reported that also allows for solid-state NMR analysis to characterize complex and pathological fibrillary assemblies.

A metal–organic framework membrane based on fumarate and mesaconate linkers is shown to have a pore aperture shape that enables efficient and cost-effective removal of nitrogen and carbon dioxide from methane.

Leder et al. show that the chaperones PDIA6, Hsp70 BiP, ERdj3, PDIA1 and Hsp90 form co-condensates within the endoplasmic reticulum, enhancing folding and preventing misfolding of client proteins.

Mas et al introduce in-cyclo NMR to quantify all states and kinetic steps of Hsp70 chaperones ATPase cycle. In-cyclo NMR will enable studies of other molecular machines at an unprecedented level of detail.

Genomic analyses of large population-based cohorts uncover the genetic determinants of perivascular space burden, an MRI marker of cerebral small vessel disease, across the lifespan, and reveal potential pathways implicated in the etiology of stroke and dementia.

A high-quality draft genome assembly of Musa balbisiana (the banana B-genome) is reported. Comparative genomic and gene functional analyses provide insights into the subgenome evolution and functional divergence between the A- and B-subgenomes.

Phenomic and genomic approaches are required to evaluate the progress of breeding strategies. Here, the authors analyse 65 years of genetic progress in maize, showing that breeders have selected traits with stable effects on yield whereas not for adaptive traits key for climate change adaptation.

Proteins from bone extracellular matrix are known to mediate the organization of apatite crystals in bone. Now, electron microscopy, X-ray scattering and nuclear magnetic resonance measurements of the structure and organization of apatite nanoparticles and intact bone samples show that water also plays a significant role in orienting the apatite crystals, and that such structuring is mediated by a disordered mineral layer that coats the crystalline core of bone apatite.

Porous framework material DUT-49 was recently demonstrated to exhibit a unique counterintuitive negative gas adsorption (NGA) behaviour. Here the authors identify framework DUT-50 as an additional pressure amplifying material that features distinct NGA transitions, and suggest structural design criteria to access other such materials.

Here, the authors show that physiological alpha-synuclein supports mitochondrial ATP homeostasis via interactions with ATP synthase and AK2, whereas its disease-linked mutants, truncated forms, and aggregates lose these interactions.

Repurposed antiviral drugs present as a valuable resource in the defence during outbreaks, with rigorous evaluation in large animal models keys for translation to clinical implementation. Here, the authors explore the antiviral activity of favipiravir against Zika virus and SARS-CoV-2 in cynomolgus macaques, in order to support future clinical investigations into this RNA polymerase inhibitor.

Love and colleagues find an inhibitory function for CD3ζ ITAMs in response to low-affinity ligands, meaning that CD3ζ can perform a dual function in TCR signaling by playing a positive or negative role depending on the affinity of the TCR for its peptide ligand.

Martensitic transition is commonly seen in steel and shape memory alloys but rarely in organic materials. Chung et al. discover martensitic transitions in organic electronics and utilize it in designing field-effect transistors, leading to shape memory effect that in return modifies charge transport properties.

The basic five-digit limb of tetrapods has been altered many times during evolution, usually by the progressive loss of digits — this study tracks the molecular underpinnings of this change, showing that in comparison to mouse, the polarized gene expression in the bovine limb bud is progressively lost due to evolutionary alteration of the cis-regulatory sequences that control Ptch1 expression in response to SHH signalling in the digit-forming handplate.

Metal-organic frameworks are promising materials for proton exchange membrane fuel cells, but cumbersome ligand preparation and use of toxic metals or solvents hinders their application. Here, the authors report the green synthesis of a zirconium, amino acid-based MOF that displays high proton conductivity and excellent stability.

Early neural development is regulated by the neurotransmitter GABA acting through ionotropic GABA_A receptors; however, the function of metabotropic GABA_B receptors in this context is less clear. Here the authors show that GABA_Breceptors promote neuronal migration and maturation by activating cAMP signalling.

A massive star at a redshift of 6.2, corresponding to 900 million years after the Big Bang, is magnified greatly by lensing of the foreground galaxy cluster WH0137–08.

Laurent et al. develop a liver-targeted gene therapy using recombinant adeno-associated viral vector (rAAV) to effectively cure Lysosomal acid lipase deficiency. This occurs via correction of lipid accumulation and normalized gene expression patterns and mitochondrial function in Lipa^−/− mice.

Sarry and colleagues demonstrate that adaptive resistance to venetoclax + cytarabine therapy in acute myeloid leukemia relies on mitochondrial respiration and show that combination with electron transport chain complex inhibitors delays relapse in patient-derived xenograft models in vivo.

Structural analysis and functional assays of S. aureus LtaA reveal that it functions as a proton-coupled flippase of the lipoteichoic acid precursor and that it contributes to S. aureus survival under physiological acidic conditions.

Asthenozoospermia is a major cause of male infertility, and multiple morphological abnormalities of the flagella (MMAF) is a particularly severe form. Here, using whole-exome sequencing of 78 MMAF patients, the authors identify mutations in two WDR proteins, CFAP43 and CFAP44, and confirm that these proteins are required for flagellogenesis in mouse and Trypanosoma brucei.

Galhaut et al. evaluate the immunogenicity and efficacy of an inactivated whole virus COVID-19 vaccine in animal models. VLA2001 adjuvanted with alum and CpG 1018 generates polyfunctional Th1 cell responses and specific neutralizing antibodies to several SARS-CoV-2 variants of concern and protects macaques from viral replication and inflammation.

Jessop et. al. investigate the expression, activity, structure and supramolecular assembly of the arginine decarboxylase from Providencia stuartii, compare its polymers with those formed by the Escherichia coli lysine decarboxylase, and analyse the evolutionary conservation of the structural determinants of the polymerisation of these enzymes in enterobacteria.

Joana Carlevaro-Fita, Andrés Lanzós et al. present the Cancer LncRNA Census (CLC), a manually curated dataset of 122 long noncoding RNAs (lncRNAs) with experimentally-validated functions in cancer based on data from the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. CLC lncRNAs have unique gene features, and a number display evidence for cancer-driving functions that are conserved from humans to mice.