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Dense calcium imaging combined with co-registered high-resolution electron microscopy reconstruction of the brain of the same mouse provide a functional connectomics map of tens of thousands of neurons of a region of the primary cortex and higher visual areas.

Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) is a deadly tick-borne virus and a growing global health threat. In this study, Petit et al. used a multi-omics approach on SFTSV-infected tick cells to study its impact and reveal host antiviral responses and key restriction factors.

Auxotrophic metabolic sensors (AMS) are vital for bioengineering but are often time-consuming to develop. Here, the authors present a workflow for designing versatile AMS, demonstrating their use for sensing glyoxylate and glycolate, with applications in pathway engineering and environmental monitoring.

Pathology-oriented multiplexing (PathoPlex) represents a framework for widespread access to multiplexed imaging and computational image analysis of clinical specimens at a relatively high throughput and subcellular resolution.

A de novo–designed protein, Syn-F4, hydrolyzes the siderophore ferric enterobactin both in vitro and in Escherichia coli cells, enabling a bacterial strain lacking the essential natural enterobactin esterase to grow in iron-limited medium.

In Escherichia coli, the UvrAB damage sensor recognizes helix-distorting lesions by itself or via Mfd bound to stalled RNA polymerase. Here authors use single-molecule fluorescence imaging to quantify the kinetic signatures of interactions of UvrA with Mfd and UvrB in live cells.

Community-associated Staphylococcus aureus strains show heightened wall teichoic acid production, which correlates with virulence and abscess formation.

Enteric pathogens such as Salmonella depend on propanediol-utilising microcompartments (Pdu MCP), which self-assemble from cytosolic proteins. Using mass spectrometry-based absolute quantification, the authors here define the protein stoichiometry and propose an organizational model of a Salmonella Pdu MCP.

The efficacy of the antibiotic trimethoprim, which inhibits bacterial dihydrofolate reductase (DHFR), is limited by the rapid emergence of resistant bacteria. Here, Manna et al. show that 4’-desmethyltrimethoprim inhibits DHFR and a common TMP-resistant variant, and impedes evolution of antibiotic resistance by selecting against the emergence of this variant.

Wanner et al. demonstrate SARS-CoV-2 liver tropism and identify transcriptional and proteomic profiles of SARS-CoV-2 liver samples that show similarities to previously characterized hepatotropic viruses.

Gene expression is inherently dynamic, due to complex regulation and stochastic biochemical events. Here the authors train a deep neural network to predict and dynamically control gene expression in thousands of individual bacteria in real-time which they then apply to control antibiotic resistance and study single-cell survival dynamics.

How DNA cytosine methylation affects gene expression inEscherichia coli is poorly understood. Here, the first genome-wide study of cytosine methylation in E. coliat single-base resolution reveals that cytosine methylation controls the expression of genes during the stationary growth phase.

Reengineering of the lac operon in E. coli from a ligand-inducible to a blue-light-regulated gene expression system facilitates optogenetic control of biotechnological applications including metabolic engineering and protein expression.

Ribo-T is a tethered ribosome complex capable of orthogonal ribosome-mRNA functionality, but has low activity. Here the authors evolve new tether designs that support faster growth and increased protein expression.

In participants with obesity and chronic kidney disease without diabetes, once-weekly administration of semaglutide 2.4 mg led to a reduction in albuminuria, body weight and systolic blood pressure compared with placebo, with no changes to creatinine or cystatin-C estimated glomerular filtration rate or measured glomerular filtration rate during the 24-week follow-up period.

The factors varying mutation rate at a particular site in a single genotype remain elusive. Here, Krašovec et al. show that mutation rates at sites conferring resistance to rifampicin in Escherichia coli decrease with population density, and that mutation-rate plasticity is controlled by the luxSgene.

Sexual recombination and mutation rate may play different roles in adaptive evolution depending on the fitness landscape. Here, Peabody et al. examine how the two factors affect the rate of adaptation of an E. coli strain capable of sexual recombination, under different conditions during experimental evolution.

The mechanisms of action of the antibacterial metalloid tellurite are unclear. Here, the authors show that tellurite induces an accumulation of hydroxyl radical and intermediates of heme biosynthesis inE. coli, and that the heme precursor 5-aminolevulinic acid potentiates tellurite toxicity.

2,4-Dihydroxybutyric acid has potential to be a precursor to a range of industrially important products, however a natural metabolic pathway for its synthesis does not exist. Here the authors rationally design a synthetic pathway inE. coliby engineering enzymes from malate metabolism.

In this Review, participants in the 7^thInternational Fabry Nephropathy Roundtable, which was convened in Barcelona, Spain in June 2007, propose guidelines and recommendations for the diagnosis and management of Fabry nephropathy in adults. The roles of enzyme replacement and antiproteinuric therapy are emphasized. The authors suggest that these organ-specific recommendations could have a greater impact on clinical practice than general Fabry disease guidelines.

Although ABC-F proteins represent a ubiquitously distributed type of ATP-binding cassette (ABC) family member across phyla, their biological functions remain poorly characterized. A new study now shows that the bacterial ABC-F protein YjjK (EttA) gates ribosome entry into the translational cycle in an energy-dependent manner.

The authors report a tripling in the speed of serial section transmission electron microscopy using a beam deflecting mechanism. This innovation enables the acquisition of multiple image tiles for each stage motion, yielding a net imaging rate of 0.3 gigapixels per second for millimeter-scale areas.

Here the authors present a framework for estimating disease risk using PGS accounting for country, age and sex. They find that PGSs have a significant sex-specific effect on common diseases, and their effect is typically larger in young individuals.

Bacterially encoded environmental sensor proteins are potentially a rich source of transcriptional control but only a few have been harnessed for biotechnological applications. Here the authors develop a general strategy for designing custom-made monogenic synthetic sensors and validate the approach by designing two sense-and-respond regulators for benzoate.

In a randomized clinical trial, treatment using a monoclonal antibody targeting interleukin-6 (IL-6) in patients with cardiovascular disease and/or diabetes who were receiving maintenance kidney dialysis reduced levels of inflammatory biomarkers at 12 weeks, including C-reactive protein, paving the way for a phase 3 trial.

Moderate flooding in the European Alps declined during past warmer periods, whereas extreme floods both increased and decreased, according to an analysis of palaeoflood records.

Magnetic nanoparticles are synthesized in a foreign host after gene transfer from magnetotactic bacteria.

An array-based high-throughput approach, genetic interaction analysis technology for Escherichia coli (GIANT-coli), now allows comprehensive genetic interaction screens in bacteria. The method uses bacterial conjugation and robotic technology to generate double mutants on a genome-wide scale. In this issue another paper presents eSGA, a very similar approach.