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PCNA–PAF15 has a key role in determining replisome dynamics during genome replication and protecting against genome instability.

A deep learning–based tool, Prosit, predicts high-quality peptide tandem mass spectra, improving peptide-identification performance compared with that of traditional proteomics analysis methods.

Microflora Danica—an atlas of Danish environmental microbiomes—reveals that although human-disturbed habitats have high alpha diversity, species reoccur, revealing hidden homogeneity.

Iceberg calving can act as a submarine melt amplifier through excitation of transient internal waves.

Wastewater-based surveillance tends to focus on specific pathogens. Here, the authors mapped the wastewater virome from 62 cities worldwide to identify over 2,500 viruses, revealing city-specific virome fingerprints and showing that wastewater metagenomics enables early detection of emerging viruses.

Co-delivery of TLR7/8 agonists and TGF-β inhibitors (TGFβi) has the potential to overcome immunosuppression in the tumor microenvironment. Here the authors describe the application of the CarboCell technology for the sustained intratumoral release of a TLR7/8 agonist alone or in combination with a TGFβi, promoting anti-tumor immune responses in preclinical cancer models.

Time-resolved cryo-EM captured transient intermediates during E. coli RNAP promoter melting, revealing conformational changes affecting stepwise transcription bubble opening. Results inform how DNA sequence controls bacterial transcription initiation.

Korn and colleagues demonstrate that the site of T cell priming (gut versus skin draining lymph nodes) dictates their effector phenotypes and homing to distal sites of immunopathology.

Comparative chromosome-scale genome sequencing and transcriptomic and epigenomic profiling of three different species of annelid provide insight into the evolutionary origin of larvae.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

The identification of HLA peptides by mass spectrometry is non-trivial. Here, the authors extended and used the wealth of data from the ProteomeTools project to improve the prediction of non-tryptic peptides using deep learning, and show their approach enables a variety of immunological discoveries.

A benchmarking competition improves tools that predict how regulatory regions control gene expression.

Using the FANTOM5 CAGE expression atlas, the authors show that bidirectional capped RNAs are a signature feature of active enhancers and identify over 40,000 enhancer candidates from over 800 human cell and tissue samples across the whole human body.

Dietary protein restriction in healthy, lean men elicits an increased energy intake to maintain body weight, which is driven, at least in part, by FGF21-mediated alterations to adipose tissue mitochondria.

Human endogenous retroviruses (HERV) normally remain quiescent, but can be reactivated by malignant transformation. Here the authors find, via HERV peptide library testing and tetramer validation, more profound HERV transcription and associated T cell recognition in myeloid cancer patients to implicate HERVs as potential therapeutic targets.

A device architecture based on indium arsenide–aluminium heterostructures with a gate-defined superconducting nanowire allows single-shot interferometric measurement of fermion parity and demonstrates an assignment error probability of 1%.

Seronegative healthcare workers with an innate signature of infection preferentially expand pre-existing T cells targeting the conserved replication transcription complex of SARS-CoV-2 in abortive infection.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

The genetic basis of atopic dermatitis is not fully understood. Here, the authors find 91 genetic loci associated with atopic dermatitis in a GWAS of >1million individuals, which highlight the importance of systemic immune regulation.

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.

Georgia Chenevix-Trench and colleagues report meta-analyses of genome-wide association studies identifying six loci newly associated with epithelial ovarian cancer (EOC). They also test variants at the 12 known and 6 new EOC susceptibility loci for association in BRCA1 and BRCA2 mutation carriers.

The PSA (KLK3) genetic variant rs17632542 is associated with reduced prostate cancer risk and lower serum PSA levels, although the underlying reasons are unclear. Here, the authors show that this PSA variant reduced proteolytic activity and leads to smaller tumours, but also increases invasion and bone metastasis, indicating its dual risk association depending on tumour context; the variant is associated with both lower risk and poor clinical outcomes.

Here, Miranda-Cervantes et al. identified pantothenate kinase 4 (PanK4) as a key regulator of muscle metabolism. Deleting PanK4 impairs fatty acid oxidation and glucose uptake, leading to glucose intolerance, while increasing PanK4 enhances glucose metabolism, highlighting its potential in promoting metabolic health.

Both rare and common variants contribute to the aetiology of complex traits such as type 2 diabetes (T2D). Here, the authors examine the effect of coding variation on glycaemic traits and T2D, and identify low-frequency variation in GLP1Rsignificantly associated with these traits.

Muscle mass is lost in patients with diabetes, which is associated with mitochondrial disfunction. Here they show that SLIRP maintains muscle mitochondria and that exercise training can compensate for SLIRP loss, improving mitochondrial function and quality control in muscle.

Biologics are delivered by a pill that pricks the stomach wall.

This Consensus Statement presents the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines.

Paul Pharoah, Joellen Schildkraut, Thomas Sellers and colleagues report a meta-analysis of genome-wide association studies for epithelial ovarian cancer and genotyping using the iCOGS array in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. They identify three new ovarian cancer susceptibility loci, including one specific to the serous subtype, and their integrated molecular analysis of genes and regulatory regions at these loci suggests disease mechanisms.

The human RNA exosome contains a nuclear co-factor MTR4, which unwinds structural RNAs and recruits adaptors for different RNA processing and decay pathways. Here the authors uncover new variations of the arch-interacting motif (AIM) in NVL and ZCCHC8 and characterise their interaction with MTR4.

The gut microbiota is involved in the development of colorectal cancer. Here, the authors analyse the faecal microbiomes of healthy subjects and of patients with colorectal cancer or benign adenoma, revealing microbial genes, strains and functions enriched in each group.

In magneto-ionics, ion migration through the material is used to change the materials magnetic properties. Typically oxygen is used as the mobile ion. In this manuscript, the authors demonstrate controlled migration of nitrogen in a CoN film, expanding the possibilities of magneto-ionics.

Rapid extracellular antigen profiling of a cohort of 194 individuals infected with SARS-CoV-2 uncovers diverse autoantibody responses that affect COVID-19 disease severity, progression and clinical and immunological characteristics.

A challenge for any machine learning system is to continually adapt to new data. While methods to address this issue are developed, their performance is hard to compare. A new framework to facilitate benchmarking divides approaches into three categories, defined by whether models need to adapt to new tasks, domains or classes.

Late-stage functionalization of complex drug molecules is challenging. To address this problem, a discovery platform based on geometric deep learning and high-throughput experimentation was developed. The computational model predicts binary reaction outcome, reaction yield and regioselectivity with low error margins, enabling the functionalization of complex molecules without de novo synthesis.

The physiological role of GDF15 remains poorly defined. Here, the authors show that circulating GDF15 increases in response to prolonged exercise, but that this exercise-induced GDF15, unlike pharmacological GDF15, does not affect post-exercise food intake or exercise motivation.

Sander and colleagues show that antigen-presenting cells detect bacterial RNA from live bacteria via TLR8 and promote T_FH cell differentiation and vaccine responses through the induction of a specific cytokine profile.

Most confirmed susceptibility variants for epithelial ovarian cancer lie in non-protein-coding sequences. Here Permuth-Wey and colleagues investigate variants in 3′ untranslated regions (UTRs) and uncover a new susceptibility locus.

Whole-genome bisulphite sequencing data from diverse human cell and tissue types shows that only about 22% of CpGs change their methylation state across these cell types; most of these CpGs are located at gene regulatory elements, particularly enhancers and transcription-factor-binding sites, and these selected regions with dynamic DNA methylation patterns could help to define putative regulatory elements further.

Genome-wide association studies have identified regions which confer risk of high-grade serous epithelial ovarian cancer. Here the authors use expression quantitative train locus analysis to identify candidate genes and functionally characterise them, identifying a role for HOXD9 in ovarian cancer.