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Non-ribosomal peptide synthetases (NRPSs) are multi-modular enzymes assembling complex natural products. Here, the structures of a Thermobifida fusca NRPS condensation domain bound to the substrate-bearing peptidyl carrier protein (PCP) domain provide insight into the mechanisms of substrate selectivity and engagement within the catalytic pocket.

A selective inhibitor of the deubiquitinase USP7 binds an allosteric site to inhibit its MDM2-stabilizing activity, resulting in stabilization of p53 and p21, which confers hypersensitivity to cancer cells for killing by the compound.

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Scientists are beginning to track down the ‘mysterious’ orgnanism which caused a public health scare by killing thousands of fish in the Chesapeake Bay on America's mid Atlantic coast. (P317)

In Escherichia coli, outer membrane protein (OMP) cluster and form islands, but the origin and behaviour of those clusters remains poorly understood. Here authors use coarse grained molecular dynamics simulation and show that their mesoscale simulations recapitulate the restricted diffusion characteristics of OMPs.

Androgen receptor (AR) signalling regulates cellular metabolism in prostate cancer. Here, the authors perform a proteomics and metabolomics characterisation of prostate cancer cells adapted to long-term resistance to AR inhibition and show rewiring of glucose and lipid metabolism, and further identify a signature associated with resistance to AR inhibition.

Detailed insight into how the brain responds to Trypanosoma brucei infection is lacking. Here, single cell and spatial transcriptomics are integrated to characterise this response, identifying a unique crosstalk between microglia and plasma cells.

CD8 T cell activity or neutralizing antibodies might control HIV-1 viral rebound after cessation of anti-retroviral therapy.

Monolyso-cardiolipin (MLCL) accumulates in individuals with Barth syndrome, but this can be mitigated by stabilization of cardiolipin from metabolism to MLCL via assembly into supercomplexes of oxidative phosphorylation proteins. This process was found to be defective in subjects with Barth syndrome.

Acromyrmex ants cultivate fungus gardens that can be parasitized by Escovopsis sp., leading to colony collapse. Here, Heine et al. identify two secondary metabolites produced by Escovopsis that accumulate in Acromyrmex tissue, reduce behavioural defenses and suppress symbiotic Pseudonocardia bacteria.

Platypuses are monotremes and combine aspects of both reptilian and mammalian behaviour. An international consortium reports the genome sequence and analysis of Ornithorhynchus anatinus and as expected, parts of the genome look more like mammals, whereas other parts more like reptiles or even chickens.

In order to interpret non-coding variants, information about regulatory elements in the genome is essential. Here, the authors annotate regulatory elements in chicken, pig and cattle, and characterize conservation of these elements between species.

DNA hairpins with a conjugated fluorophore-quencher pair are attached to surfaces to monitor cellular traction forces at high spatial resolution.

Time of reproduction may be altered as the climate changes. For seabirds, it is shown that there has not been an adjustment in timing as the climate changes and the sea surface warms. This lack of plasticity could result in a mismatch with food resources.

The supply of CO₂ to large marine phytoplankton cells is potentially limited by their diffusive boundary layer. Here, using direct microelectrode measurements, the authors show that extracellular carbonic anhydrase acts to maintain the concentration of CO₂ at the cell surface to overcome this problem.

By comparing neural responses to diverse visual stimuli measured with a standardized two-photon imaging pipeline, the authors reveal response specializations within the mouse visual cortex.

Land-sea breezes lead to unexpected daily maxima in extreme humid heat - associated with heat-stress risk - in the evening or at night in the Arabian Peninsula, suggest analyses of multiple reanalysis and in situ data sets.

Is a vast undersea grid bringing wind-generated electricity from the North Sea to Europe a feasible proposition or an overpriced fantasy?

Using data from global run-on and sequencing (GRO-seq) or related methods, the dREG software identifies a new class of transcriptional regulatory elements with strong evidence for directing active transcription.

CD98 heavy chain (CD98) is identified as a reticulocyte-specific receptor for the Plasmodium vivax PvRBP2a ligand.

Bacterial dimethylsulfoniopropionate (DMSP) production was recently demonstrated in surface oceans. Here the authors show that bacterial production is higher in sediment from coastal areas and the deep ocean, and identify an alternative pathway for its synthesis, indicating that coastal and marine sediments are important sources of this climate-relevant metabolite.

AKR1A1-regulated protein S-nitrosylation protects against kidney injury through PKM2-mediated metabolic reprogramming.

Csp1, a novel copper-binding protein that is exported from the cytosol of the methanotroph Methylosinus trichosporium OB3b and stores copper ions for particulate methane monooxygenase, is identified and characterized.

Efforts to control climate change require the stabilization of atmospheric carbon dioxide concentrations. An assessment of the trends in sources and sinks of atmospheric carbon dioxide suggests that the sinks are not keeping up with the increase in carbon dioxide emissions, but uncertainties are still large.

Overfishing and warming ocean temperature have caused an increase in methylmercury concentrations in some Atlantic predatory fish, and this trend is predicted to continue unless stronger mercury and carbon emissions standards are imposed.

John Lis, Adam Siepel and colleagues map transcription start sites across the genome in two human cell lines using a nuclear run-on protocol called GRO-cap. They find a common architecture of initiation at both promoters and enhancers and that transcript elongation stability provides the strongest distinction between promoters and enhancers.

Extreme heat is increasing in magnitude and frequency, threatening human health. This Review assesses mortality risk associated with extreme heat, revealing that human thermal tolerances (that is, uncompensable thresholds) were crossed for ~2% and 21% of global land area for young adults and older adults, respectively, from 1994 to 2023.

Even though geologists have rejected the designation of an Anthropocene epoch, the idea of a major planetary transition in the mid-twentieth century remains useful across physical and social sciences, the humanities and policy.

Distinct groups of microorganisms have been thought to grow on methane and on short-chain alkanes; now, the methanotroph Methylocella silvestris is shown to express two distinct soluble di-iron centre monooxygenases that allow it to use either methane or propane as a carbon and energy source.

Zoonotic diseases present a substantial global health burden. In this Opinion article, Plowrightet al. present an integrative conceptual and quantitative model that reveals that all zoonotic pathogens must overcome a hierarchical series of barriers to cause spillover infections in humans.

Structures of the amino-terminal region of inositol-1,4,5-trisphosphate receptor 1 with and without InsP₃ bound reveal two discrete interfaces between the InsP₃-binding core and suppressor domain that are similar to and functionally interchangeable with those in the equivalent domains of ryanodine receptor 1.