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Diabetes results in part from a deficiency of functional pancreatic beta cells. Here, the authors study the genomic and epigenetic landscapes of human insulinomas to gain insight into possible pathways for therapeutic beta cell regeneration, highlighting epigenetic genes and pathways.

The authors show long-term potentiation at the hippocampal CA3–CA1 synapse is modulated by EphA4 in the postsynaptic CA1 neuron and by ephrin-A3, an EphA4 ligand, in astrocytes, through their regulation of glial glutamate transporters. These results suggest EphA4/ephrin-A3 signaling as a mechanism for astrocytic regulation of synaptic plasticity.

Dietary restriction can extend the life of various model organisms. Here, Xie et al. show that intermittent periods of fasting achieved through every-other-day feeding protect mice against neoplastic disease but do not broadly delay organismal aging in animals.

A meta-analysis across ten pediatric autoimmune diseases reveals shared genetic architecture and novel susceptibility loci.

Bacillus subtilis withstands starvation by forming dormant spores that revive when nutrients become available. Here, Mutlu et al. show that sporulation timing controls spore revival through a phenotypic ‘memory’ that arises from the carry-over of a metabolic enzyme from the vegetative cell into the spore.

Several protein quality control mechanisms are in place to trigger the rapid degradation of aberrant polypeptides and mRNAs. Here the authors describe a mechanism of ribosome-mediated quality control that involves the ubiquitination of ribosomal proteins by the E3 ubiquitin ligase Hel2/RQT1.

The intestinal microbiota signals through epithelial cells to activate calcineurin and NFAT, driving proliferation of cancer stem cells and the development of colorectal cancer.

Genome-wide association studies are used to identify common genetic variants that affect the structure of selected subcortical regions of the human brain; their identification provides insight into the causes of variability in brain development and may help to determine mechanisms of neuropsychiatric dysfunction.

The existence and properties of tetraquark states with two heavy quarks and two light antiquarks have been widely debated. Here, the authors use a unitarized model to study the properties of an exotic narrow state compatible with a doubly charmed tetraquark.

The link between conspiracy beliefs and reactionary movements that promote intolerance and undermine democracy was investigated in 21 countries. Economic prosperity and democratic functioning moderated the positive link between anti-migration conspiracy beliefs and commitment to reactionary action.

A high-resolution reference panel based on whole-genome sequencing data enables accurate imputation of HLA alleles across diverse populations and fine-mapping of HLA association signals for HIV-1 host response.

The co-transcriptional processing of RNA depends on the precisely timed recruitment of different factors to the elongating transcript, which depends on the phosphorylation state of the C-terminal domain (CTD) of RNA polymerase II. Varani and coworkers show that two transcription termination factors, Rtt103 and Pcf1, bind specifically and cooperatively to Ser2-phosphorylated CTD. This provides a way to ensure that proper polyadenylation occurs only where Ser2 phosphorylation density is highest.

Mitochondria and chloroplasts import the vast majority of their proteins across two membranes. Although the import and initial sorting of precursor proteins is mediated by translocases that are functionally similiar in the outer membrane of both organelles, they each have a unique mode of translocation.

The LHCb collaboration reports an improved measurement of the oscillation frequency of mesons consisting of a bottom quark and strange quark, which is then combined with previous results.

The Large Hadron Collider beauty collaboration reports a test of lepton flavour universality in decays of bottom mesons into strange mesons and a charged lepton pair, finding evidence of a violation of this principle postulated in the standard model.

Schubnel, Nel and colleagues present the first Carboniferous representative of Titanoptera, Theiatitan azari. Specially modified wing zones suggest that Titanoptera were capable of wing-based communication using light or sound, as seen in modern species.

Integrated assessment modelling backed by expert judgement indicates that the existence of future multiple interacting climate tipping points, with irreversible economic damages, greatly increases the social cost of carbon.

STAAR is a powerful rare variant association test that incorporates variant functional categories and complementary functional annotations using a dynamic weighting scheme based on annotation principal components. STAAR accounts for population structure and relatedness and is scalable for analyzing large whole-genome sequencing studies.

Before a honeybee can start to go out foraging, it must get to know the area around the hive. Bees do this by taking ‘orientation flights’, which apparently allow them to learn local landmarks. These flights are shaped like a hairpin — straight out and straight back — and get longer and faster as the bee becomes more familiar with the area.

An analysis of 16 health-related quantitative traits in approximately 350,000 individuals reveals statistically significant associations between genome-wide homozygosity and four complex traits (height, lung function, cognitive ability and educational attainment); in each case increased homozygosity associates with a decreased trait value, but no evidence was seen of an influence on blood pressure, cholesterol, or ten other cardio-metabolic traits.

Snyder and colleagues present a comprehensive multiomic atlas of normal mucosal, benign polyps and dysplastic polyps from six persons with familial adenomatous polyposis, comprising transcriptomic, proteomic, metabolomic and lipidomic datasets.

Using TEA-seq, Thomson et al. detail transcriptional and epigenetic alterations in the T cell compartment between healthy children and older adults, leading to the discovery of a novel pediatric CD8αα⁺ population poised for rapid effector responses.

James Cerhan and colleagues report genome-wide association and meta-analysis studies to identify genetic susceptibility loci for diffuse large B cell lymphoma. They identify four loci that influence genetic susceptibility to this B cell malignancy.

Analysis of the uncertainty associated with the timing of climate tipping points suggests that carbon taxes need to be increased by a minimum of 50%. If considering a rapid, high-impact tipping event, these taxes should be more than 200% higher. This implies that the discount rate to delay stochastic tipping points is much lower than that for deterministic climate damages.

Solveig Gretarsdottir, Kari Stefansson and colleagues report a genome-wide association study for abdominal aortic aneurysm. They identified a variant located within the DAB2IP gene on 9q33 associated with risk of developing abdominal aortic aneurysm.

The thermal state of the Earth’s surface is usually influenced more by climate than by heating from the Earth’s interior. Numerical models show that in the oldest and thickest part of the Greenland Ice Sheet, geothermal heat flux through an anomalously thin lithosphere leads to strong regional variations in basal melting.

Philippe Amouyel, Julie Williams, Gerard Schellenberg, Sudha Seshadri and colleagues report a meta-analysis of genome-wide association studies for late-onset Alzheimer's disease in 17,008 cases and 37,154 controls with replication in an additional 8,572 cases and 11,312 controls. They identify 11 loci newly associated with Alzheimer's disease.

Antisense oligonucleotides against ATXN2 improved motor neuron function and restored firing frequency in cerebellar Purkinje cells in mouse models of spinocerebellar ataxia type 2.