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Two programs, GRAPE and GARLIC, work together to first predict biosynthetic gene clusters responsible for the production of polyketides and nonribosomal peptides, then link sequenced gene clusters to known and unknown natural products.

A series of unexplained elephant mortalities occurred in northwest Zimbabwe in 2020. Here the authors show that six elephants died of bacterial septicaemia associated with a little-reported Pasteurella species.

Genome-wide association meta-analyses identify 26 risk loci for epilepsy, including 19 loci specific to genetic generalized epilepsy. Prioritized candidate genes implicate synaptic processes and overlap with targets of antiseizure medications.

Here, the authors perform a meta-analysis in 26,699 people with seizures and 492,324 controls to identify 25 genome-wide significant copy-number variants. The discovered loci point to known disease genes and associations with clinical annotations.

Identification of genes associated with resistance to hundreds of cancer therapeutics enabled the discovery of the serine hydrolases MGLL and CES1 as modifiers of sensitivity to GSK-J4 via direct enzymatic modification.

BET-bromodomain inhibitors could be used to treat medulloblastoma tumors with Myc amplifications. Here, the authors show that both the response and resistance to BET inhibitors in mice is mediated by bHLH/homeobox transcription factors.

In comparison with traditional surgery techniques, arthroscopic surgeries induce less tissue damage and can reduce morbidity and complications. In this Review, Carr and colleagues focus on the increased use of therapeutic arthroscopy as a tool for excision, reconstruction and replacement of damaged or abnormal tissue, and signal the need for additional studies to allow this surgical approach to reach its full potential.

Dust-borne nutrients can enhance productivity in the surface ocean. Two years of sediment trap data reveal that dust enhances carbon export to depth by increasing surface nitrogen fixation, productivity and carbon sinking rates in the North Atlantic.

Host metabolic reprogramming plays a role in functional responses against pathogens. Here, the authors characterise malonylated proteins in macrophages and show that malonylation of the glycolytic enzyme GAPDH impacts cytokine production by modulating both its enzymatic activity and RNA-binding capacity.

Joel Hirschhorn and colleagues report results of a large-scale genome-wide association and replication study for obesity-related traits. The newly discovered loci are enriched for genes expressed in the central nervous system, and may thus contribute to weight gain by modulating food intake. Similar results are reported in a related study by Gudmar Thorleifsson and colleagues.

The authors present evidence suggesting that amorphous Bi₂Se₃ displays topological properties, signalling a new regime for the pursuit of topological matter.

Richard Houlston and colleagues report a genome-wide association study for colorectal cancer. They report three loci newly associated with colorectal cancer, bringing the total number of common susceptibility loci to 20.

The International Strawberry Sequencing Consortium reports the draft genome of the woodland strawberry (Fragaria vesca). The genome of this diploid species should serve as a reference genome for the Fragaria genus, as the cultivated strawberry (Fragaria × ananassa) is an octoploid where F. vesca is predicted to be a subgenome donor.

SLIT-ROBO alterations arise in pancreatic ductal adenocarcinoma (PDAC), but their role in the pancreas is unclear. Here, the authors use mouse models to show that loss of epithelial Robo2 activates the neighbouring stroma via TGF-β signalling; findings  are relevant to PDAC patients, where ROBO expression correlates with survival outcomes.

This study presents the results of the second round of the Critical Assessment of Metagenome Interpretation challenges (CAMI II), which is a community-driven effort for comprehensively benchmarking tools for metagenomics data analysis.

The first phase 2 gene therapy trial for HIV-1 has shown some promising signs. There's a long way to go before this would be a viable approach in people with HIV—this trial did not show a statistically significant difference in viral load at the primary end point–but other analyses did reveal that the gene therapy seemed to have a modest, but statistically significant, effect at reducing viral load in the treated subjects versus the placebo arm. The study also provides some clues about what to improve in the future.

As phase 1 of the Earth Microbiome Project, analysis of 16S ribosomal RNA sequences from more than 27,000 environmental samples delivers a global picture of the basic structure and drivers of microbial distribution.

Chronic kidney disease affects approximately 10% of the Western population. Recent studies have elucidated some of the immune mechanisms that contribute to kidney injury and disease, which are described in this Review. In addition, the contribution of the kidneys to immune homeostasis and the effects of kidney failure on systemic immune functions are discussed.

This study synthesizes data from several published datasets to provide a global estimate of the impact of nitrification on oceanic new production.

In oxygen-redox intercalation cathodes, voltage hysteresis can be avoided by forming cathode materials with a ‘ribbon’ superstructure in the transition metal layers that suppresses transition metal migration.

Electrochemical technologies for ore refinement provide a unique opportunity to integrate with renewable energy sources but are impeded by the insulating properties of many ores. Here, the authors take inspiration from the lithium-ion battery field and fabricate hectorite–carbon black composite electrodes to enhance electron percolation into hectorite enabling lithium-ion release through a multi-step (electro)chemical mechanism.

Ligand efficiency metrics quantify the molecular properties required to gain binding affinity for a drug target. This article discusses the application of such metrics in the selection and optimization of fragments, hits and leads, highlighting how optimizing ligand efficiency metrics based on both molecular mass and lipophilicity, when set in the context of the specific target, has the potential to increase the quality of drug candidates.

Golub and colleagues tested thousands of drugs not originally developed for oncology across 578 human cancer cell lines, revealing growth-inhibitory effects and providing a resource to identify drugs with the potential to be repurposed for cancer.

α-Helix-mediated protein–protein interactions (PPIs) play a key role in the development of numerous infection and disease states. Modulating such interactions offers considerable therapeutic potential, however, identifying suitable inhibitors has proved challenging. This Review highlights recent and generic approaches for designing inhibitors of helix-mediated PPIs.

Power exhaust is one of the biggest challenges stopping fusion energy. This article shows experimental evidence for strategically shaping the power exhaust region as a solution to this challenge, utilising physics understanding to strike a balance between engineering complexity and power exhaust benefits, consistent with reduced models and simulations.

John Chambers and colleagues report a genome-wide association study for type 2 diabetes in individuals of south Asian ancestry. They identify six loci newly associated with type 2 diabetes.

Organic synthesis is a rate-limiting factor in drug discovery, so the pharmaceutical industry heavily relies on academic research. This Perspective highlights some of the most pressing challenges to be overcome from the industrial viewpoint — such as the development of reactions tolerating specific functionalities — and encourages stronger industry–academia relationships. Credit: Pills image: Profimedia.CZ a.s. / Alamy Stock Photo; Factory image: Diana Johanna Velasquez / Alamy Stock Vector; Graduate hat: Michael Burrell / Alamy Stock Photo; Conical flask: Astex.

Therapy-resistant cancer cell states identified across diverse contexts are selectively vulnerable to ferroptotic cell death induced by inhibition of lipid peroxidase pathways converging on GPX4.

Jeffrey Barrett, Tarjinder Singh and colleagues present a meta-analysis of rare coding variants and copy number variants in a large collection of schizophrenia cases and controls, combined with de novo mutation data from family trios. They find that rare, damaging variants contribute to risk of schizophrenia both with and without intellectual disability and that there is overlap between genetic risk for schizophrenia and other neurodevelopmental disorders.