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A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

In rare-earth intermetallics, interaction between localized 4f electrons and itinerant electrons can result in exotic states of matter. Here, the authors use photoemission spectroscopy to reveal and study this interaction in the bulk and at the surface of the Kondo lattice antiferromagnet CeRh₂Si₂.

Structural analysis of the human choline and ethanolamine transporters FLVCR1 and FLVCR2 clarifies the mechanisms of transport, the conformational dynamics of these proteins and the disease-associated mutations that interfere with these processes.

Proton pump inhibitors (PPIs) are prodrugs that are activated by protonation in the highly acidic environment of the stomach lining. Now, coordination of PPIs to protein-bound zinc ions is revealed as another pathway to PPI activation. Acting as a Lewis acid, the zinc ion facilitates conjugation of the drug to zinc-coordinating cysteine residues.

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.

A systematic analysis of 115 mammalian genomes, including 10 new bat genomes, reveals prevalent positive selection in immune genes in bats and shows key adaptations in the antiviral gene ISG15 that aid disease resistance in bats, including to coronaviruses.

The molecular diversity and spatial organization of the mouse basolateral amygdala are unclear. Here, the authors classify 11 glutamatergic cell clusters and describe the roles of distinct neuron populations in different valence-specific behaviors.

Dynamic disorder reduces the carrier mobility in organic semiconductors (OSs) to an extent that depends on their specific electronic band structure. Here the authors study the temperature-dependent hole mobility of two structurally similar OSs and find that thermal access to transiently delocalized states enhances hole mobility in C8-DNTT-C8 compared to DNTT.

Bacillus subtilis withstands starvation by forming dormant spores that revive when nutrients become available. Here, Mutlu et al. show that sporulation timing controls spore revival through a phenotypic ‘memory’ that arises from the carry-over of a metabolic enzyme from the vegetative cell into the spore.

A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Single-cycle and sub-cycle field transients are typically generated by external pulse compression where a combination of nonlinear broadening followed up by dispersion compensation is used. Here, Balciunas et al. use self-compression in a Kagome fibre to generate phase-controlled single-cycle pulses.

Titin is considered an integrator of muscle cell proteins but direct evidence is limited. Here, titin is inactivated in adult mouse muscles, which causes sarcomere disassembly, protein mis-expression and force impairment, recapitulating key alterations in critical illness myopathy patient muscles.

A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.

The trans-Tango genetic strategy, which mediates signaling across synapses, was adapted to identify neural connections in a vertebrate nervous system, with synaptic partners confirmed in the retina and spinal cord of larval zebrafish.

16p11.2 CNVs are associated with neurodevelopmental disorders. Here, the authors show that 16p11.2 deletion is associated with hyperactivation of human iPSC-derived dopaminergic neuron networks and is rescued by RHOA inhibition in vitro.

Tabletop quantum simulators have arisen as a powerful and highly configurable tool to study dynamics in quantum many-body systems. In this work, the authors propose an advancement of an existing optical-lattice setup for simulating lattice quantum electrodynamics to two spatial dimensions, and demonstrate its fidelity using numerical simulations.

Evidence for light-induced superconductivity in K₃C₆₀ was limited to optical methods due to the short lifetime of the phase. Extending the lifetime from picoseconds to nanoseconds now allows measurement of its negligible electrical resistance.

Swarm Learning is a decentralized machine learning approach that outperforms classifiers developed at individual sites for COVID-19 and other diseases while preserving confidentiality and privacy.

iTango confers access to neuromodulation-sensitive subsets of neurons in a functionally defined and temporally controlled manner. The tool allows for manipulating the subset of neurons that are activated by dopamine during a behavior of interest.

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.

The authors present a method for the conversion of full-length tau protein into seeding-competent amyloid fibrils without heparin or other negatively charged co-factors, which could be useful for studying the effects of post-translational modifications on Tau aggregation as well as to identify potential inhibitors of tau aggregation. Biochemical experiments and solid-state NMR spectroscopy measurements show that these co-factor-free tau fibrils have similar properties as amyloid fibrils isolated from brain tissue but differ from those of commonly used heparin-induced tau fibrils.

Multi-parameter metrology requires collective measurements on more than one copy of the same quantum state. Now, an optimal scheme for the estimation of qubit rotations has been demonstrated on superconducting and trapped-ion platforms.

Fewer than 100 wild Cat Ba langurs survive in Vietnam. Here, the authors use whole genome sequencing to demonstrate potential adaptations to saltwater consumption as well as maintenance of adaptive potential despite low levels of genetic diversity and high levels of inbreeding.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

How genetic and environmental factors contribute to the generation of various subtypes of inhibitory neurons called interneurons in the brain is unclear. A study in mice provides new insight into this process.

Skeletal muscle conveys the beneficial effects of physical exercise but due to its heterogeneity, studying the effects of exercise on muscle fibres is challenging. Here, the authors carry out proteomic analysis of myofibres from freeze-dried muscle biopsies, show fibre-type specific changes in response to exercise, and show that the oxidative and glycolytic muscle fibers adapt differentially to exercise training.

The mechanisms responsible for the strongly correlated insulating and superconducting phases in twisted bilayer graphene are still debated. The authors provide a theory for phonon-dominated transport that explains several experimental observations, and contrast it with the Planckian dissipation mechanism.

Abnormal cytoplasmic aggregates of FUS are a hallmark of some forms of amyotrophic lateral sclerosis (ALS). Here, using neurons derived from patients with FUS-ALS, the authors demonstrate that impairment of PARP-dependent DNA damage signaling is an event that occurs upstream of neurodegeneration and cytoplasmic aggregate formation in FUS-ALS.

Scientists demonstrate that strong single-cycle terahertz pulses can switch off interlayer superconductivity in a cuprate superconductor while leaving in-plane superconductivity unaltered. The effect may prove useful for studying and controlling the behaviour of future ultrafast nanoelectronics.

Biochemical, structural and genetic analysis of the shelterin complex reveal that by recruiting RAP1 to DNA, TRF2 directly inhibits DNA-dependent protein kinase to regulate classical non-homologous end joining at telomeres.

Investigation of premature mortality by seven emission sources of atmospheric pollutants shows that outdoor air pollution, mostly by fine particulate matter, leads to more than three million premature deaths per year worldwide, which could double by 2050.

The authors show that neural activity and synaptic plasticity in the orbitofrontal cortex mediate multiple timescales of reinforcement learning (RL) for meta-RL, which parallels a form of meta-RL in artificial intelligence.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

The CCR4-NOT complex is a key regulator of eukaryotic mRNA deadenylation. Here the authors identified the E3 ubiquitin ligase RNF219 as an acetylation-regulated cofactor of the complex, which inhibits mRNA decay through a direct interaction with NOT9.

There is a trade-off between increasing thickness of active layers in organic photovoltaic cells to be compatible with modern printing techniques and decreasing it to improve the device performance. Sun et al.report a nematic liquid crystalline molecular electron donor material used in thick layers.

Analysis of whole-genome doubling (WGD) by using cancer sequencing data combined with simulations of tumor evolution suggests that there is negative selection against homozygous loss of essential genes before WGD but not after.

The authors develop a closed-form expansion of the linear response associated with resonant non-Hermitian systems having exceptional points and demonstrate that the spectral response may involve different super Lorentzian lineshapes depending on the input/output channel configuration.

As in haematopoietic cells and platelets, agonist binding to protease-activated receptors PAR1 and PAR2 in non-haematopoietic cells also triggers signalling pathways that lead to α₅β₁-integrin-mediated cell adhesion.

The vibrational properties of fullerenes are incompletely understood, particularly with respect to the effect of molecular size. Here the vibrational density of states of fullerenes is shown by density functional theory to converge smoothly to that of graphene, hindered only by the presence of frequency compressed radial optic vibrations due to the pentagonal faces in the fullerene family.

Lipid bilayers feature an intricate interplay between membrane geometry and its chemical composition but lack of a model system with simultaneous control over membrane shape and composition prevented a fundamental understanding of curvature-induced effects. Here the authors demonstrate that the local substrate geometry and global chemical composition of the bilayer determine both the spatial arrangement and the sorting of lipid domains.