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Tackling the loss of expensive cofactors is a key challenge in continuous-flow biocatalysis. This work reports immobilized enzymes with a tethered cofactor that is channelled between a recycling and a catalysis module facilitating total turnover numbers of NAD⁺ and ATP exceeding 10,000 in biocatalytic flow systems.

Targeted protein degradation (TPD) is a promising strategy for drug development. In this proof-of-concept study, the authors use telaprevir, which binds hepatitis C virus (HCV) NS3/4A protease, to target the protease for protein degradation, and show inhibition of wildtype as well as drug resistant HCV.

Glutamine is an energetic source required for the proliferation of cancer cells. Here, the authors show that soft tissue sarcomas expressing high levels of glutaminase (GLS) are particularly sensitive to glutamine starvation and GLS inhibition in tumour-bearing allograft and autochthonous mouse models.

The development of reliable measures of health in ageing organisms is a need in ageing research. Using atomic force microscopy, here, the authors assess whole body stiffness of worms and show that it reflects organismal fitness.

Protein aggregation remains a significant challenge for manufacturing of protein biopharmaceuticals. Here, the authors demonstrate the use of directed evolution and an assay for in vivo innate protein aggregation-propensity to generate aggregation-resistant scFv fragments.

Crystal structures of the CLC^F proton-coupled fluoride antiporter Eca in two conformations capture two rotamers of the gating glutamate and reveal simultaneous accessibility of F^– and H⁺ ions via separate pathways on opposite sides of the membrane.

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.

Genetic association studies have identified loci including the choline transporter SLC44A2 as a potential regulator of thrombosis. Here the authors report that loss of SLC44A2 impairs platelet activation and thrombosis in mice via a reduction of mitochondrial ATP production.

Over 60 years of hydrographic data from southeast of Bermuda show the temporal variability of North Atlantic subtropical mode water. Between 2010 and 2018, there was an 86–93% loss of thickness, suggesting weaker production of mode water that is expected to continue with warming.

The lack of deep mixing in the subpolar North Atlantic Ocean for over a decade has raised concerns that climate warming may already be affecting the ocean circulation. A vigorous convection event last winter shows that the system holds some surprises yet.

Characterization of clinical isolates of the cryptic fungal pathogen Aspergillus latus revealed traits that distinguish it from other species. Steenwyck et al show that A. latus originated via allodiploid hybridization with both parental subgenomes actively expressed.

BamA carries out the essential process of folding outer membrane β-barrels in Gram-negative bacteria and is a potential antibiotic target. Here, the authors discover macrocyclic peptide inhibitors that trap BamA in distinct structural conformations.

Golub and colleagues tested thousands of drugs not originally developed for oncology across 578 human cancer cell lines, revealing growth-inhibitory effects and providing a resource to identify drugs with the potential to be repurposed for cancer.

Amyloid cascades leading to peptide β-sheet fibrils are central to many diseases. Intermediate assemblies were recently identified as the toxic agents, but obtaining structural details of these early oligomers has largely been unsuccessful with traditional techniques. Here, ion mobility methods provide evidence for structural transitions from random to β-sheet assembly.

UM171 promotes corepressor degradation by acting as a molecular glue to induce KBTBD4–HDAC1/2 interactions with the help of inositol hexakisphosphate.

A study identifies public neoantigens generated by tumor-wide aberrant mRNA splicing activity across distinct cancer types.

The AMOC is crucial for the global ocean overturning circulation and controls the climate around the North Atlantic. Here, the authors use 24 Earth System Models from the CMIP6 to demonstrate that air-sea heat flux anomalies north of any given latitude in the North Atlantic between 25.6°N and 50°N are linked to the AMOC at that latitude on decadal and centennial timescales. Based on this relationship, they find that the decadal averaged AMOC at 26.5° has not weakened from 1963 to 2017.

One of the questions for prebiotic chemistry is the formation of complementary base pairing systems. Here, the authors show that plausible two prebiotic heterocycles can form glycosidic bonds with ribose in water and that these spontaneously base-pair in aqueous solution.

TFIIIC is a RNA polymerase III-specific general transcription factor complex essential for tRNA synthesis. Here the authors combine chemical crosslinking/mass spectrometry and X-ray crystallography to define the architecture of TFIIIC and suggest a model for the assembly of pre-initiation complexes at tRNA genes.

Evolutionary distinctness is used as a metric to determine conservation priorities across all Chondrichthyes, identifying 21 countries with the highest richness, endemism and evolutionary distinctness of threatened species as targets.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Human activities have altered the production, transport and fate of mud and associated organic carbon, with important implications for global carbon cycling.

The role of IFI16 as a DNA sensor is highly controversial. With support from a Nature Communications back-to-back publication from Almineet al. the authors here provide functional evidence that IFI16 is required for DNA sensing via the cGAS-STING pathway in human macrophages.

A range of blood-based biomarkers have shown high specificity for Alzheimer’s disease (AD) pathophysiology with phosphorylated-tau (p-tau) being the most promising test. Here, the authors show the utility of plasma p-tau212 in autopsy-confirmed AD and memory clinic patient cohorts.

This study develops a wide-ranging index to assess the many factors that contribute to the health and benefits of the oceans, and the scores for all costal nations are assessed.

Snakebite is a life-threatening neglected tropical disease that is currently treated using different antibody-based antivenoms, each effective against bites of specific snake species, but not others. Here, the authors show that a combination of two toxin-inhibiting repurposed drugs provides broad protection in experimental animals against the lethal effects of snakebites from multiple snake species.

H9T, an engineered IL-2 partial agonist, promotes the expansion of T cells while maintaining a stem-cell-like state, leading to improved efficacy of adoptive cell therapy in mouse models of melanoma and acute lymphoblastic leukaemia.

Entomopathogenic nematodes carrying Xenorhabdus and Photorhabdus bacteria prey on insect larvae in the soil. Now, a comprehensive analysis of the bacterial genome has revealed ubiquitous and unique families of biosynthetic gene clusters. Evaluation of the bioactivity of the natural products expressed by the most prevalent cluster families explains the functional basis of bacterial natural products involved in bacteria–nematode–insect interactions.

The mechanism of CGRP-evoked peripheral pain is unclear. Here, the authors show that the CGRP-mediated neuronal/Schwann cell pathway mediates allodynia associated with neurogenic inflammation, contributing to the algesic action of CGRP in mice.

It may have taken only a decade to repeatedly destabilize the Antarctic Ice Sheet after the last Ice Age as shown by a new data-model study. The ice sheet lost ice for centuries each time before it abruptly re-stabilized again.

Resources reporting RNA editing sites from brain tissue have been published. Here, the authors provide an atlas of RNA editing events found in the aged and Alzheimer’s disease human brain tissue resulting in changes at protein level.

Severe sepsis has a high mortality rate. Here, the authors provide genomic, transcriptomic, proteomic and metabolomic data across four sepsis-causing pathogens and identify a signature of global increase in fatty acid and lipid biosynthesis as well as cholesterol acquisition.

A number of natural occurring small-molecule splicing modulators are known. Here, the authors combine chemogenomic, structural and biochemical methods and show that these compounds also target the spliceosome-associated protein PHF5A and propose a potential modulator binding site in the PHF5A–SF3B1 complex.

Evolutionarily conserved gene modules mediate neurodegenerative dementia in a variety of mouse models and in postmortem brain tissue from patients.

Cognitive abilities tend to decline over time in advanced age, yet some individuals experience stable abilities or rapid decline. Here the authors present a proteome-wide association study of cognitive trajectory, and identify 38 proteins associated with cognitive resilience.

Enzymes from two discrete biosynthetic gene clusters in the entomopathogenic bacterium Xenorhabdus szentirmaii cooperate to produce a diverse array of phenazine natural products, including phenazine–peptide and phenazine–polyketide derivatives.

Black carbon produced by the burning of biomass and fuels is the most stable carbon compound in nature, yet its path from land to the deep ocean where it persists for thousands of years remains mysterious. Here Coppola and colleagues characterize the black carbon exported by the Amazon River, the largest river in the world.

Pacific sub-decadal sea surface temperature (SST) variations have dominantly driven Antarctic atmospheric circulation changes through tropical–polar teleconnections and contributed to recent rapid Antarctic sea ice extent (SIE) decline trends and Southern Ocean subsurface warming.

Studying changes in the metabolic properties of kidney cancer in patients reveals an increased need for mitochondrial metabolism as tumors metastasize from the kidney to distant organs.

In this study using an adult-onset mouse model of Alzheimer’s pathology, we uncovered a neuron-type-specific mechanism responsible for region-specific circuit dysfunction. Short-term expression of human amyloid precursor protein (hAPP) led to hyperexcitability in the entorhinal cortex, but not in isocortex, due to a distinct vulnerability of PV interneurons in the entorhinal region.

Our knowledge of the distribution and evolution of deep-sea life is limited, impeding our ability to identify priority areas for conservation.

Proteomic analysis of cerebrospinal fluid from individuals with autosomal dominant Alzheimer’s disease reveals how this complex and chronic disease evolves over many decades.