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Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Staphylococcus aureus can aggregate within human synovial fluid and lead to joint infections. Here, the authors reveal that the fatty acid kinase system and its downstream saeRS regulator control S. aureus aggregation within synovial fluid.

Here the authors perform longitudinal sampling of lymphoid organs along with fate mapping and matched single-cell RNA sequencing and TCR sequencing to define the developmental dynamics of follicular regulatory T (T_FR) cells. They find that T_FR cells undergo clonal expansion and progressive differentiation in a process that requires follicular helper T cells.

Dendritic cells (DCs) are required to establish thymic central tolerance. Here Srinivasan et al. use single-cell transcriptomics to define thymic conventional dendritic cell (cDC) subsets and find that CD8⁺ single-positive thymocytes modulate the thymus environment to regulate plasmacytoid DC and cDC2 homeostasis and interferon signatures in DCs, while CD4⁺ single-positive thymocytes regulate cDC1 activation via cognate and CD40L–CD40 interactions.

In Streptococcus pneumoniae, competence for genetic transformation is accompanied by a pause in growth. Here, Bergé et al. show that this pause is linked to the cell cycle via at least two pathways that impair peptidoglycan synthesis and preserve genomic integrity during transformation.

Two-dimensional polyaramid polymers are synthesized to form nanofilms that exhibit the lowest gas permeability of any polymer by orders of magnitude, despite lacking crystallinity, enabling molecular-scale nanomechanical resonators and barrier materials.

Genome-wide association studies (GWAS) of deep learning-derived measurements of aortic valve function, along with multitrait analyses incorporating disease-based GWAS, identify 166 genetic loci associated with aortic valve function or aortic stenosis.

Staphylococcus epidermidis is a frequent cause of medical implant-associated biofilm infections. Here, studying a patient with pacemaker-associated endocarditis, the authors report in-host evolution of S. epidermidis leading to phenotypes exhibiting increased biofilm formation and antibiotic tolerance.

Coagulase-negative staphylococci and Staphylococcus aureus colonize similar niches in mammals. Here, Chin et al. show that a coagulase-negative staphylococcus secretes 6-thioguanine, a purine analog that suppresses S. aureus growth and virulence by inhibiting de novo purine biosynthesis and toxin production.

During SARS-CoV-2 infection caspase-8 fuels harmful inflammation independent of apoptosis. Genetic loss of caspase-8 reduces cytokine levels, lowers viral load and mitigates disease severity, revealing non-apoptotic caspase-8 as a key driver of severe COVID-19.

ATP depletion is associated with induction of antibiotic tolerance in Staphylococcus aureus.

Analyses of newly discovered hand and foot bones of a Paranthropus boisei specimen provide insight into possible tool use and other palaeobiology characteristics among Plio-Pleistocene hominin species.

CAR-T cell therapy has been shown to be effective in immunotherapy for treatment of several different tumours. Here the authors show pre-specified interim outcomes from a P-BCMA-ALLO1 trial with BCMA targeted CAR-T therapy in multiple myeloma.

Unlike other halogen atoms, the ability for fluorine to exist in a [C–X–C]⁺ connectivity pattern has only been shown in spectroscopic studies. Here the authors present a single crystal structure of a fluoronium cation, characterized by X-ray diffraction.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

Eutrophication and chlorophyll-rich algal blooms occurred at high concentrations of the thermoplastic polyurethane, but only occasionally with bioplastics, suggests a three-month experiment exposing plankton in experimental ponds.

Future quantum communication technologies require entanglement between stationary and flying qubits, in systems that are inherently scalable. To this end, De Greveet al.present full state tomography of a qubit pair formed by entangling a quantum dot spin and a photon, with a fidelity of over 90%.

In this Review, Gerdes and colleagues discuss the multifaceted alarmones guanosine tetraphosphate and guanosine pentaphosphate (collectively referred to as (p)ppGpp) and their functions in the regulation of bacterial physiology, including their synthesis and degradation, as well as their role in transcriptional regulation, in GTP biosynthesis and in the formation of bacterial persisters.

The treatment potential of psilocybin for postpartum depression was investigated in a preclinical mouse model. Here the authors show both acute and long-term effects of psilocybin in mothers and their offspring who were exposed via lactation.

A 50 microRNA-based dynamic risk score for stratifying individuals with and without type 1 diabetes was developed using samples obtained from multicenter and multiethnic cohorts.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

A novel antiviral targeting the SARS-CoV-2 PLpro protease shows strong efficacy in a mouse model, preventing lung pathology and reducing brain dysfunction. The study provides proof-of-principle that PLpro inhibition may be a viable strategy for preventing and treating long COVID.

Silver (Ag) has been used as an antimicrobial agent since a long time, but its molecular mechanism of action was not elucidated due to technical challenges. Here, the authors develop a mass spectrometric approach to identify the Ag-proteome in Staphylococcus aureus, and capture a molecular snapshot of the dynamic bactericidal mode of action of Ag through targeting multiple biological pathways.

Cheese fermentation and flavour formation are the result of complex biochemical reactions driven by the activity of multiple microorganisms. Here, the authors identify microbial interactions as a mechanism underlying flavour formation in Cheddar cheese.

The development of catalytic systems for sequestering anthropogenic methane emissions from the atmosphere could potentially reduce global warming. Now, coupling the enzyme alcohol oxidase with an inorganic zeolite generates formaldehyde from methane under ambient conditions with 90% selectivity.

T_FH cells that express IL-13 are associated with high-affinity IgE responses, but factors controlling their development, transcriptional programming and exact function have remained unclear. Here, Chandrakar et al. find that the transcription factor JunB is required for T_FH13 cell maintenance and that T_FH13 cells producing IL-21 drive broad germinal center responses to allergen-specific IgG and IgE.

Organic sulfur compounds are vital to life but often overlooked in the sulfur cycle, especially in the subsurface. Subsurface microbes can metabolize diverse organosulfur compounds, hinting at a more complex sulfur cycle than previously thought.

Here, Nelson et al. use amplicon next-generation sequencing of two P. falciparum polymorphic gene regions to investigate the genetic similarity of parasite populations across time and space in a pediatric cohort in Kenya. They identify both micro- and macro-scale structuring of malaria parasites in this high-transmission setting, which could inform future intervention strategies.

Analysis of more than 95% of each diploid human genome of a four-generation, twenty-eight-member family using five complementary short-read and long-read sequencing technologies provides a truth set to understand the most fundamental processes underlying human genetic variation.

Obesity changes the characteristics of the immune response induced in a mouse model of atopic dermatitis, suggesting therapies that could be used against immune dysregulation in obesity.

SARS-CoV-2 variants with spike (S)-protein D614G mutations currently predominate globally. Here, Zhang et al. hypothesize that D614G variant may increase infectivity by increasing S protein abundance on the virion since pseudoviruses carrying S-G614 incorporate higher amounts of S protein and enter cells more efficiently than those carrying S-D614.

Using forward genetics, the authors identified the cholesterol regulator Ptchd1, which controls opioid tolerance by affecting desensitization and trafficking of opioid receptors.