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This paper presents TDAC-seq, a targeted chromatin-accessibility-profiling method using cytidine deaminases and long-read sequencing, to resolve the effects of CRISPR edits on single chromatin fibers.

Plasma proteomics plays a key role in advancing clinical research and biomarker discovery. Here, the authors show in a large MSCoreSys multicenter benchmark study that DIA outperforms DDA, delivering robust, precise, and reproducible label-free protein quantification across sites.

Researchers working outside their home country should be careful to brush up on local customs.

Alfajaro et al identify that a bat MERS-like coronavirus HKU5 uses ACE2 as a receptor from its natural bat reservoir Pipistrellus abramus and American mink. Structural analyses demonstrate a unique interaction between the HKU5 receptor binding domain and bat ACE2. This highlights the receptor flexibility of merbecoviruses and identifies mink as potential intermediate hosts, informing viral surveillance and countermeasure development.

Pyramidal cells in superficial layers of neocortex form a lateral network of synaptic bouton clusters, but its functional implication remains unclear. Here the authors overlaid activity maps of orientation preference in cat visual cortex with single-cell anatomy and observed projections to multiple functional domains.

Human leukocyte antigen (HLA) class I peptide ligands (HLAIps) are targets for developing vaccines and immunotherapies. Here the authors report Thunder-DDA-PASEF, an immunopeptidomics method which enhances the identification of vital HLAIps crucial for vaccine and immunotherapy development.

Here, the authors provide guidance on the prevention, diagnosis and management of anticancer therapy nephrotoxicity in adult patients. They also define a research agenda focused on preventing and mitigating anticancer therapy toxicity, maximizing early detection of nephrotoxicity and enabling optimal drug dosing in patients with kidney disease.

This article by Zepeda-Gómez and Baron discusses the principles of endoscopic therapy for benign biliary strictures, different endoscopic approaches and their respective outcomes, and varied etiologies and their appropriate management. Data on newer therapies, such as the placement of self-expandable metal stents, and the treatment of biliary–enteric anastomotic strictures is also discussed.

Harvest from inland recreational fisheries are estimated, demonstrating the importance of this food source for nutrition and economic value in food systems that are vulnerable to climate change.

Large sequences are integrated site specifically into the human genome without double-strand DNA cleavage.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

The synaptic mechanisms underlying cortical postnatal development are largely unexplored. Here, the authors reveal how spine calcium activity impacts turnover and organization of synaptic inputs on neurons in the mouse binocular visual cortex.

The common vampire bat (Desmodus rotundus) is one of only three obligate blood-feeding mammals. By sequencing both its genome and gut metagenome, the authors provide a holistic view of the evolutionary adaptations that underlie this unusual diet.

Proteomic, transcriptomic, and genomic analysis has shown osteosarcoma (OS) to be a complex and heterogenous disease but revealed little about its carcinogenesis or potential therapeutic targets. Here, the authors profile the RNA interactome, transcriptome and proteome of cells derived from OS patients, identifying a targetable vulnerability to translation inhibition.

The spike protein of the Omicron variant of SARS-CoV-2 has a higher affinity for ACE2 than Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic and vaccine-elicited neutralizing antibodies.

Pseudovirus assays and surface plasmon resonance show that the Omicron receptor-binding domain binds to human ACE2 with increased affinity relative to the ancestral virus, and that most neutralizing antibodies are considerably less potent against Omicron.

Here, Forster et al. compare 1354 cultured commensal strains (540 species) to 45,403 pathogen strains (12 species), identifying 64,188 MGE-mediated antibiotic resistance gene transfer events between the two groups, and show that 15 broad host range MGEs are able to transfer between phyla.

The timing of NAD + supply determines its efficacy to treat metabolic disease. Here, the authors show that increasing NAD + at the early active phase maximizes weight loss and glucose regulation in mice. NAD + can displace the phase of the liver clock which can cause circadian misalignment.

Polycomb Repressive Complexes PRC1 and PRC2 catalyse distinct chromatin modifications to promote gene silencing. Here the authors use reversible tethering of Polycomb proteins to ectopic sites in mouse ESCs and find that canonical but not variant PRC1 can trigger sequence-independent propagation of Polycomb-mediated transcriptional repression.

The human monoclonal antibody S2X259 cross-reacts with spike proteins from all clades of sarbecovirus, and provides prophylactic and therapeutic protection in vivo against parental SARS-CoV-2 and emerging variants of concern.

A major challenge in coronavirus vaccination and treatment is to counteract rapid viral evolution and mutations. Here the authors show that CRISPR-Cas13d can be used as a broad-spectrum antiviral to inhibit human coronaviruses, including new SARS-CoV-2 variants, combined with small molecule drugs for an enhanced antiviral effect in human primary cells.

Phytophthora infestanscaused the potato famine in the nineteenth century. Martinet al. sequence the nuclear genomes of five archival samples of the pathogen and compare these to extant specimens allowing the reconstruction of the evolutionary history of P. infestans.

Nanostructured high-surface-area materials capable of converting energy into mechanical work are promising for use as actuation devices. Surface-chemistry-induced changes of the surface stress in nanoporous gold are now observed on alternate exposure to ozone and carbon monoxide.

Protein methyltransferases (PMTs) are epigenetic regulatory enzymes with significant therapeutic relevance. Here the authors describe a collection of chemical inhibitors and antagonists to modulate most of the key methylation marks on histones H3 and H4, and use the collection to study of the role of PMTs in mouse and human T cell differentiation.

Immunopeptidomics is crucial for the discovery of potential immunotherapy and vaccine candidates. Here, the authors generate a ground truth timsTOF dataset to fine-tune the deep learning model Prosit, improving peptide-spectrum match rescoring by up to 3-fold during immunopeptide identification.

In contrast with conventional views, ultra-large-scale atomistic simulations show that the staged character of strain hardening of metals originates from crystal rotation, whereas the dislocation behaviours remain the same across all the stages.

Michael Talkowski and colleagues analyze balanced chromosomal abnormalities in 273 individuals by whole-genome sequencing. Their findings suggest that sequence-level resolution improves prediction of clinical outcomes for balanced rearrangements and provides insight into pathogenic mechanisms such as altered gene regulation due to changes in chromosome topology.

The vapour–liquid–solid method is used to produce semiconducting nanowires but the fundamental processes involved are poorly understood. Wang et al.use atomic-scale simulations to elucidate the mechanisms involved in the growth and stability of gold-catalysed silicon nanowires.

As melanoma progresses, it evolves. Here, in advanced melanoma the authors study genomic evolution, highlighting trunk mutations dominated by the ultraviolet damage signature, common late truncal whole-genome duplication events, as well as selective copy number gain of mutant BRAF.

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.