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Sawada et al. show simultaneous activation of the STING and lymphotoxin beta receptor signaling induces B cell-activating germinal center responses within tumor environment and enhances antitumor responses.

The highest tensile strength biomaterial known exists in limpet teeth and replicating this material is of interest. Here, the authors report on the ex vivo growth of teeth and use of isolated limpet tissue and cells providing foundations for the development of this high-tensile biomaterial.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Cyanide-releasing defence systems in plants and animals are important to the evolution of plant–herbivore interactions. The authors identify the enzymes responsible for biosynthesis of cyanogenic glucosides by Six-spot Burnet moth caterpillars, which have evolved independently from the known plant pathway.

Analysis of pottery made and used by hunter-gatherers in northeastern Europe in the sixth millennium bc supports the existence of super-regional networks enabling cultural transmission long before the arrival of farming.

Pan-genomes provide useful resources for evolutionary studies, functional genomics and breeding of cultivated plants. Here, the authors report a new rice pan-genome including 73 Asian rice and two wild relatives (Oryza rufipogon and O. punctata), and reveal the prevalence and scale of large inversions across the pan-genome.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

Medulloblastomas lacking p53 do not express surface class I major histocompatibility complex (MHC-I) and are resistant to immune rejection. Tumor necrosis factor rescues MHC-I expression and synergizes with immune checkpoint inhibitors to promote rejection.

GWAS have identified more than 500 genetic loci associated with blood lipid levels. Here, the authors report a genome-wide analysis of interactions between genetic markers and physical activity, and find that physical activity modifies the effects of four genetic loci on HDL or LDL cholesterol.

Alternative lengthening of telomeres (ALT) is associated with a poor outcome in neuroblastoma. Here, the authors find that ALT is associated with mutated ATRX and/or reduced protein abundance, frequent telomeric repeat loci and heterochromatic telomeric chromatin.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

A robust signature of circulating inflammatory proteins is causally associated with 10-year risk of progression to end-stage renal disease in diabetic patients

Chronic inflammation of the airways is associated with remodeling and fibrosis, leading to a progressive decline in lung function in people with severe asthma. Michael Croft and his colleagues report that in mouse models of allergic lung inflammation expression of the TNF family member LIGHT is induced. Blockade of LIGHT prevents remodeling, providing a therapeutic strategy to prevent asthmatic airway remodeling.

Clear and harmonized regulatory guidelines are needed to realize the potential of new approach methodologies for improving the predictivity of nonclinical drug candidate assessment.

Targeted DNase Hi-C uses DNase I instead of restriction enzymes for chromatin fragmentation and improves the resolution of chromatin interaction maps.

Lupus erythematosus is a debilitating autoimmune disease, a feature of which is the presence of hyperactive B cells. The discovery of a new pathway that stimulates B-cell proliferation provides insight into the biology of this disease, and allowed the construction of antagonists of the pathway that halt disease progression in mice.

A high-quality sequence assembly of the zebrafish genome reveals the largest gene set of any vertebrate and provides information on key genomic features, and comparison to the human reference genome shows that approximately 70% of human protein-coding genes have at least one clear zebrafish orthologue.

The function of TRAF3, a member of the family of tumor necrosis factor receptor–associated factors, has remained an enigma. Two recent Nature papers now show that TRAF3 regulates interferon and interleukin 10 production.

The clinical success of inhibitors of tumour necrosis factor (TNF) in the treatment of autoimmune diseases has generated interest in the therapeutic potential of targeting other members of the TNF superfamily (TNFSF) of cytokines and their receptors. Here, Croft and colleagues review the current developmental status of biologics targeting these molecules in a range of disorders, highlighting key challenges and emerging therapeutic targets.

Herpesviruses have evolved numerous strategies to outsmart the host and establish persistent infection. Important targets of viral entry and immunomodulation are the tumour-necrosis factor superfamily proteins. This Review describes the central role of these proteins in both virus survival and host defence.

A large-scale epigenome-wide association study identifies changes in DNA methylation associated with body mass index in blood and adipose tissue, and correlates DNA methylation sites with high risk of incident type 2 diabetes.

Members of the TNF superfamily (TNFSF) of ligands and their receptors have emerged as promising targets in the treatment of autoimmune diseases and cancer, with several biologics gaining FDA approval. However, there are still many hurdles to realizing the true potential of targeting these superfamilies. This Review assesses past and ongoing clinical trials of agents modulating TNFSF ligands or receptors, highlighting ongoing challenges and future opportunities.

Molecules that recognize pathogens and activate the immune response are being discovered at a rapid rate. RIG-I, a new protein in this category, recognizes viral RNA. Recent studies show that RIG-I operates independently of Toll-like receptors and that it is targeted for inactivation by the hepatitis C virus.

This paper reports the genome sequence of domesticated tomato, a major crop plant, and a draft sequence for its closest wild relative; comparative genomics reveal very little divergence between the two genomes but some important differences with the potato genome, another important food crop in the genus Solanum.

The first structure of fully active HOIP of the RBR family of RING-type E3 ligases in its transfer complex with an E2~ubiquitin conjugate provides insights into its mechanism of action, including the ideal alignment of the E2 and E3 catalytic centres for ubiquitin transfer and the allosteric regulation of the RBR family.