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Decreased brain coenzyme Q₁₀ levels cause encephalopathy and are associated with neurodegeneration; supplementation with 4-HMA or 4-HB restores coenzyme Q₁₀ synthesis in mice and humans with HPDL variants, improving survival and neurological symptoms in HPDL-driven mitochondrial encephalopathy.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Gold has a vital role in human society and the global economy, but its production currently causes high levels of environmental pollution. This work reports an approach that can effectively produce gold from both primary and secondary resources without the use of toxic substances such as mercury or cyanide.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Real-time joint motion feedback during exercise interventions can enhance hand and wrist rehabilitation. Here, the authors introduce electrogoniometry systems that accurately monitor target joint angles in fingers and wrists in real-time for use in medical and physical activity settings.

Preventing axon breakdown is key to treating neurodegeneration. Here, the authors show that after axotomy, DLK kinase drives apoptotic mitochondrial fission in axons. Blocking this reduces axon degeneration and neuron death in both human and mouse models.

Graphene oxide could potentially be used for numerous applications, particularly in electronics. Understanding its structural stability in an ambient atmosphere is essential for the realization of devices. A new study shows that multilayer graphene oxide is in fact metastable at room temperature.

Leveraging on large-scale data collection through a smartphone app, Donegan et al show that the association between model-based planning and compulsivity can be estimated with as few as 25 trials

ThiH is a radical SAM L-tyrosine lyase involved in the biosynthesis of the thiazole ring of vitamin B1. Here, the authors report the crystal structure of ThiH in complex with its L-tyrosine substrate, revealing an unexpected protonation state and tunneling effect that lowers the reaction energy barrier.

Polθ has been recently identified as a therapeutic target in cancer but specific inhibitors are currently unavailable. Here, the authors identify small molecule inhibitors of Polθ’s polymerase activity which elicit BRCA1/2 synthetic lethality, enhance the effect of PARP inhibitors and target PARP inhibitor resistance caused by 53BP1/Shieldin pathway defects.

Compression is a common densification method for solid-state materials, but the structural evolution of compressed non-equilibrium oxide materials such as glasses and zeolites remains somewhat elusive. Here, the authors show that siliceous zeolite single-crystals cold-compressed at 20 GPa yield permanently densified glassy silica, while cold-compressed siliceous zeolite powder and glassy silica are metastable.

The immune synapse at the interface between T cells and antigen-presenting cells manifests intense vesicular trafficking, but how the vesicles are sorted is still unclear. Here the authors show that, in activated T cells, the Golgin GMAP210 specifically conveys LAT⁺ vesicles to immune synapse allowing proper T cell activation.

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.

Spatial proteomics allows studying cellular protein localisations at system-wide scale. Here, the authors show that combining the previously developed hyperLOPIT method with differential centrifugation yields protein localisation maps at suborganellar resolution while reducing analysis time and input material.

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.

The contributions of women to the development of the periodic table have long been overlooked. Claire Murray relates how the recent ‘Setting their table’ conference set out to highlight their prominent role in element discovery and use.

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 a first-in-human phase 1 trial, HER2-specific CAR macrophages were feasible to manufacture and well tolerated, with no dose-limiting toxicities in patients with HER2-overexpressing solid tumors.

This protocol describes a substantially redeveloped approach for the localization of organelle proteins by isotope tagging (LOPIT) to enable subcellular localization of thousands of proteins per experiment (hyperLOPIT).

Fructose consumption has greatly increased in recent years and has been linked to the development of hepatic steatosis. Here, the authors show that fructose promotes gut-barrier deterioration and subsequent endotoxaemia that in turn induces hepatic lipogenesis by activation TLR signalling in liver macrophages.

“Protein relocalisation plays a major role in the innate immune response but remains incompletely characterised. Here, the authors combine temporal proteomics with LOPIT, a spatial proteomic workflow, in a fully Bayesian framework to elucidate spatiotemporal proteomic changes during the LPS-induced immune response in THP-1 cells.

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.

Changes in penguin populations on the Antarctic Peninsula in recent decades have been linked to environmental factors such as sea ice. Here, the authors show that penguin colony change on Ardley Island, NW Antarctic Peninsula during the last 8,500 years was primarily driven by volcanic activity.

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.

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.

Multi-modal analysis of genomically unstable ovarian tumours characterizes the contribution of anatomical sites and mutational processes to evolutionary phenotypic divergence and immune resistance mechanisms.

The bacterium Brucella abortus is an intracellular pathogen that modulates autophagy in host cells. Here, the authors identify two B. abortus effectors that interact with host protease SENP3, thus promoting cytoplasmic accumulation of nucleolar proteins associated with ribosomal biogenesis and facilitating intracellular replication of the pathogen

Im7 is a small Escherichia coli colicin binding protein that uses a remarkably complex folding pathway. Analysis of the Im7 folding landscape reveals details of the earliest transition state in its folding pathway and indicates that the formation of non-native contacts that result in intermediate folding states is necessary to maintain elements essential to the protein's function.

Cell therapy requires the targeting of cells to specific sites in the body. Here Muthana et al.use a standard MRI scanner to direct oncolytic macrophages, labelled with magnetic nanoparticles, to primary and metastatic tumour sites in mice, and demonstrate that this leads to reduced tumour growth.

Aerobic energy metabolism is driven by proton-pumping respiratory supercomplexes. The study reports the structural basis for energy conversion in such supercomplex. It may aid metabolic engineering and drug design against diphtheria and tuberculosis.

Mechanochemistry is a promising technology to tackle current and future polymer waste streams for a sustainable future. With this review, we take into account synthetic, computational, technical, and engineering perspectives to converge trituration and polymer mechanochemistry with a particular focus on the fate of commodity polymers and potential technologies to monitor mechanochemical reactions while they occur. We highlight the need for future transdisciplinary research to tackle the high-leverage parameters governing an eventually successful mechanochemical polymer degradation approach for a circular economy.

The fate of soil carbon is controlled by plant inputs, microbial activity, and the soil matrix. Here the authors extend the notion of plant-derived particulate organic matter, from an easily available and labile carbon substrate, to a functional component at which persistence of soil carbon is determined.

Organoids have improved disease modeling. Here, the authors generate human sensorimotor organoids derived from hiPSCs of individuals with ALS. These organoids contain skeletal muscle, sensory and motor neurons as well as astrocytes, microglia, and vasculature and form neuromuscular junctions.

A multicore analogue in-memory computing chip that is designed and fabricated in 14 nm complementary metal–oxide–semiconductor technology with backend-integrated phase-change memory can be used for deep neural network inference.

The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.

Controlling the rotation direction of individual molecular machines requires precise design and manipulation. Here, the authors describe a surface-adsorbed molecular propeller that, upon excitation with a scanning tunneling microscope tip, can rotate clockwise or anticlockwise depending on its chirality, and directly visualize its stepwise rotation with STM images.

When excitons in light-harvesting materials meet, they recombine and dissipate their energy. Here, the authors show that pairs of excitons can co-exist in aggregated materials and only annihilate when the aggregates are chemically connected.

Edwin Cuppen, Gijs van Haaften and colleagues report the identification of mutations in ABCC9 in individuals with Cantú syndrome, which is characterized by congenital hypertrichosis, distinctive facial features, cardiomegaly and osteochondrodyplasia. ABCC9 encodes an ATP-dependent potassium channel.

The ASAP complex is emerging as an assembly of proteins at the interface between transcription, pre-mRNA splicing and mRNA quality control. Structural analysis of the ASAP core complex reveals macromolecular interactions between the subunits and their assembly into ASAP. In addition, ASAP subunits SAP18 and RNPS1 are shown to bind Pinin, forming a novel complex called PSAP.

Delineating the neurobiology of pathological anxiety remains challenging. In this Review, Akiki et al. synthesize task-based functional MRI evidence for how vulnerabilities within circuits that mediate acute, distant and sustained threat, reward processing, cognitive control and social processing can lead to its emergence and maintenance.

The spatial location of proteins within a cell is a key element of protein function. Here the authors describe hyperLOPIT—a proteomics workflow that allows the simultaneous assignment of thousands of proteins to subcellular niches with high resolution—and apply it to mouse pluripotent stem cells.