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BindCraft, an open-source, automated pipeline for de novo protein binder design with experimental success rates of 10–100%, leverages AlphaFold2 weights to generate binders with nanomolar affinity without the need for high-throughput screening.

Here, a combination of forward genetics and genome-wide association analyses has been used to show that variation at a single genetic locus in Arabidopsis thaliana underlies phenotypic variation in vegetative growth as well as resistance to infection. The strong enhancement of resistance mediated by one of the alleles at this locus explains the allele's persistence in natural populations throughout the world, even though it drastically reduces the production of new leaves.

The authors identify a single main-chain hydrogen bond required to keep GABA_A receptors closed in the absence of neurotransmitter. Electrophysiology and molecular dynamics simulations suggest disruption of this bond is a key component of channel opening during inhibitory synaptic signaling in the brain.

The functions of small nucleolar RNAs (snoRNAs) in cancer remain to be studied. Here the authors show that the snoRNA Snord67 promotes lymph node metastasis of breast cancer cells through guiding modifications of the spliceosome and regulating the splicing landscape.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

Peanut oral immunotherapy (POIT) can treat peanut allergy, but only a subset of patients achieve lasting remission. Here, the authors show that POIT efficacy is associated with the gut microbiome’s functional capacity, specifically bile and amino acid metabolism and protein degradation.

The Staufen family of RNA-binding proteins are conserved microtubule dependent mRNA transporter factors. Here the authors use biochemical and functional approaches to characterize the RNA-binding properties of mouse Staufen 2 and study the mRNA binding capacity of its two domains dsRBDs 1 and 2.

SOX9 titration in neural crest cells identifies regulatory elements and genes with sensitive or buffered responses. Sensitive genes are enriched for craniofacial disorder genes phenocopying SOX9, suggesting differential sensitivity contributes to phenotypic specificity.

To understand malaria symptoms, several studies investigate association between parasite’s transcriptome and disease severity. Here, Thomson-Luque et al. reanalyze available transcriptomic data of P. falciparum and find that longer circulation of infected erythrocytes without sequestering to endothelial cells associates with decreasing parasitaemia and less severe disease.

Bacterial Type I polyketide synthases are responsible for producing both lifesaving medicines and virulence factors, yet their stepwise mechanism remains elusive. Here, Burkart et al. characterize acyl carrier protein bound states of mycocerosic acid synthase from Mycobacterium tuberculosis through crosslinking and cryo-EM.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Here, the authors characterize the neutralization capacity of post-Sputnik V vaccination sera against SARS-CoV-2 variants of concern B.1.1.7 (alpha) and B.1.351 (beta), showing the latter to exhibit resistance to neutralization in vitro.

Climate surveys are common in the global north but remain limited in the global south. Through a large-scale survey in seven global south countries, this study examines public climate knowledge and identifies their most trusted information sources and preferred climate policies.

Resonant inelastic X-ray scattering can be used to measure the spin current carried by magnons in the presence of temperature gradients across a magnetic insulator.

Sperm–egg adhesion is crucial for mammalian reproduction. Here, authors report the human Izumo1:Juno complex, a key regulator of sperm-egg adhesion, forms an unusually strong bond through a secondary binding site, which is impaired in an infertility-associated Juno mutant.

Flores et al. show that brain-penetrant eIF2B agonists suppress ISR activation in cellular and mouse models of ALS and reduce ISR biomarkers in humans, enabling further clinical studies of ISR inhibition in individuals with neurological diseases

Layered feedback is an optimization strategy in feedback control designs widely used in engineering. Here, combining simulation and experimentation, the authors apply layered control - a powerful optimization strategy in engineering - to synthetic biomolecular networks in living bacteria to show layered control overcomes performance trade-offs in biology.

Append editing of ADP-ribosyl to thymine is used for precise modifications in bacteria and eukaryotes.

This Perspective celebrates the scientific legacy of W. G. Hill and highlights his various important contributions to the field of genetics.

The fungal pathogen Candida auris can acquire amphotericin B resistance through clinically rare mutations in sterol biosynthesis genes but at a certain fitness cost, which reduces its infection potential. Compensatory evolution can, however, mitigate this cost.

The dynamic behavior of supramolecular polymers in aqueous environments remains poorly understood due to the assembly pathway complexity. Here, the authors present a combinatorial titration methodology to probe in situ a binary assembly mechanism between spheroidal micelles and β-sheet polymers of peptide amphiphiles, which collectively govern supramolecular dynamics.

Analysing strontium isotope ratios for individuals of 18 bovid and equid species dating to the Last Glacial Period (115–11.7 ka), the authors find that 16 of these species lack definitive evidence of migration, even those species that are long-distance migrants today.

The role of wild and domesticated animals on alpine ecosystems is unclear. Here, the authors use sedaDNA from 14 European alpine lakes to demonstrate a positive association between wild and domesticated animal and plant diversity through the past 14 thousand years.

Managing power exhaust in fusion reactors is a key challenge, especially in compact designs for cost-effective commercial energy. This study shows how alternative divertor configurations improve exhaust control, enhance stability, absorb transients and enable independent plasma regulation.

The transcription factors TCF1 and LEF1 promote self-renewal and regulatory functions in B-1a cells.

The complex electronic motion in the quantum Hall regime in semiconductors has so far eluded analysis of its microscopic structure. Here, the authors use scanning gate microscopy to measure the spatial structure of transport inside a metal in this regime, opening the way for localized manipulation of the electronic states.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Using optogenetics in the fly embryo, this study investigates how a transcriptional repressor drives switch-like, rapidly reversible repression by modulating transcriptional burst frequency, offering insights into gene regulation dynamics in development.

Time-series data from tropical forests tracking weather and declines in arthropod diversity and function show that fluctuations in species were largely dependent on their El Niño sensitivity and ecological specialization.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Ventures focusing on gene therapy, adoptive T-cell therapy, protein homeostasis and the microbiome are among those selected by the editors in 2013's crop of startups.

Two-dimensional semiconducting transition metal dichalcogenides strongly absorb visible light. Kozawa et al.study the photocarrier relaxation in mono- and bilayer MX2 samples and find that loss of photocarriers by direct recombination becomes a second-order process when excitation is in resonance with band nesting.

The analysis of radial velocity variations of O-type stars in the Small Magellanic Cloud reveals a large fraction of close binaries, suggesting that binary physics also plays a prominent role in the low-metallicity environment of the distant Universe.

The primary entry route of vanilloid ligands to the vanilloid-binding site in transient receptor potential vanilloid 1 (TRPV1) is found to be a distinct and targetable hydrophobic pathway at the TRPV1–cell membrane interface rather than through direct membrane penetration.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Perovskite morphology dictates carriers’ behaviors and defect states, and thus the ultimate performance of the material. Here, the authors investigate micro-wrinkle formation in film by varying composition and deposition condition, and further implement the optimized structure for solar cells, achieving 23% efficiency.

A post hoc analysis of a multicentre, randomised trial showed that prediabetes remission is possible without total weight loss—providing weight is distributed to subcutaneous deposits as opposed to visceral ones.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.