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Multi-ancestry genome-wide analyses identify new risk loci for age-related macular degeneration. Ancestry-specific analyses identify distinct effects at major risk loci, including smaller effect sizes for CFH risk alleles in haplotypes of African ancestry.

Suppressed Dexter transfer is needed to achieve efficient and stable hyperfluorescence, but complex matrices must be involved. A molecular design strategy has been proposed where Dexter transfer can be substantially reduced by an encapsulated terminal emitter, leading to ‘matrix-free’ hyperfluorescence.

Akbar, Lanna and colleagues show that sestrin proteins bind to and coordinate the simultaneous activation of Erk, Jnk and p38 MAPKs in T lymphocytes and inhibit immunity during aging.

Reanalysis of bipedal trackways from Laetoli site A in Tanzania suggest that the footprints were made by a hominin that coexisted with at least one other hominin species.

A report of the optical discovery and follow-up observations of the type Ic supernova SN 2006aj associated with X-ray flash XRF 060218. SN 2006aj was intrinsically less luminous than the gamma-ray burst (GRB)–supernovae connection, but more luminous than many supernovae not accompanied by a GRB.

When exposed to chronic endoplasmic reticulum (ER) stress, cells downregulate protein synthesis by inhibiting mTOR signalling. Park et al.identify Sestrin2 as a transcriptional target of the ER stress pathway and an important mediator of this protective response in the liver.

Only about 15% of water cycle diagrams include human interaction with water, although human freshwater appropriation amounts to about half of global river discharge, according to an analysis of 464 water cycle diagrams and a synthesis of the global water cycle.

In cells with microsatellite instability, expanded TA-dinucleotide repeats form cruciform structures that stall replication forks and cause chromosome shattering in the absence of the WRN helicase.

The genetic basis of cataract is not well understood. Here, the authors perform a genome-wide association multiethnic meta-analysis of cataract, finding 37 new loci and replicating known and new loci. They additionally perform sex-specific analyses, identifying new associations specific to women.

Missense variants in RNA-binding proteins underlie many diseases. Here the authors report an oculopharyngeal muscular dystrophy caused by heterozygous frameshift mutations in HNRNPA2B1 that alter its nucleocytoplasmic transport dynamics and result in cytoplasmic accumulation of hnRNPA2 protein.

While the cellular recycling process autophagy has been linked to aging, the impact of selective autophagy on lifespan remains unclear. Here Kumsta et al. show that the autophagy receptor p62/SQSTM1 is required for hormetic benefits and p62/SQSTM1 overexpression is sufficient to extend C. elegans lifespan and improve proteostasis.

While genetic loci shared between cancer types have been identified, cross-cancer relationships for polygenic risk scores have not been well studied. Here, the authors have developed polygenic risk scores for 16 cancers in two large cohorts and identified positive and inverse cross-cancer associations.

Circulating DNA detected in plasma can be used for diagnostic purposes. Here, the authors show that the 5-hydroxymethyl cytosine biomarker from plasma-derived cell free DNA can be used to detect early stage pancreatic cancer.

Hydrogen is commonly produced during the high-temperature hydration of mafic and ultramafic rocks. Laboratory experiments suggest that water–rock reactions also generate hydrogen at lower temperatures, potentially fuelling microbial life in ultramafic aquifers in oceanic and terrestrial crust.

Forest conservation contributes to climate change mitigation and delivers a host of other benefits to society, but such benefits are usually assessed qualitatively at the project level. This study provides a quantitative assessment of multiple benefits from forest carbon projects across Southeast Asia.

An understanding of how fluid–solid interactions affect flow dynamics is essential for microfluidics design. Here the authors show how fluids in linear channels can be controlled by the degree of confinement when the contact-line slip length is comparable to the channel size.

Dynamic regulation of the cytoskeletal factor ABLIM3 controls the precision of memory representations in rodent models of post-traumatic stress disorder and age-related cognitive impairment.

Global tree restoration could cause substantial and regionally variable changes in water availability, according to an ensemble of Budyko models and moisture recycling data.

FoxO are commonly down-regulated transcription factors and tumor suppressors in renal cell cancer (RCC). Here, the authors show that upon energy stress FoxOs induce the expression of the long non-coding RNA FILNC1, which inhibits survival of RCC by downregulating c-Myc and c-Myc-dependent metabolic rewiring.

Human RNA editing enzymes ADAR1 and ADAR2 are required for innate immune functions and neurological functions, respectively. Here, the authors show that Drosophila Adar has both innate immune and brain functions, despite being the homolog of mammalian ADAR2.

UVRAG is involved in autophagy, which loses its tumour suppressor functions when in its truncated form in cancers. Here, the authors use a mouse model that inducibly express this truncated protein and show impaired autophagy, enhanced inflammation and β-catenin stabilisation, which promotes spontaneous tumorigenesis.

These two studies show that primary cilia can either mediate or suppress tumorigenesis in models of basal cell carcinoma and medulloblastoma, respectively, depending on the nature of the initial oncogenic event (pages 994–996) and (pages 1055–1061).

Mammographic density represents one the strongest predictors of breast cancer risk. Here the authors perform genome-wide association study meta-analysis of women screened with full-field digital mammography and identify 31 previously unreported loci associated with mammographic density phenotypes.

DNA single-strand breaks in neurons accumulate at high levelsin functional enhancers.

Fanconi anaemia (FA) is a genetic disease associated with low levels of blood stem cells. Here Liu et al.report an improved method to generate genetically corrected induced pluripotent stem cells from an FA patient, and perform a screening to identify drugs that improve their differentiation into blood stem cells.

PROTAC degrader–induced SWI/SNF inactivation abolishes DNA accessibility at enhancer elements of oncogenes and also tempers supra-physiologic expression of driver transcription factors, resulting in potent inhibition of tumour growth in mouse models.

Marine spatial planning is used to co-ordinate multiple ocean uses, and is frequently informed by tradeoffs and composite metrics. Here, Lester et al. introduce an approach that plans for multiple uses simultaneously whilst balancing individual objectives, using a case study of aquaculture development in California.

Increasing compositional uniqueness of the gut microbiome, and corresponding changes in microbial metabolites in the blood, are identified as a signature of healthy ageing in humans.

Direct neuronal conversion of skin fibroblasts from individuals with Huntington’s disease (HD) generates a population of medium spiny neurons that recapitulate hallmarks of HD, including aggregation of mutant huntingtin protein, DNA damage and spontaneous cell death.

Genome-wide association analysis using electronic health record data from >94,000 individuals identifies loci associated with plasma lipid concentrations. Longitudinal measurements allow for the calculation of genetic risk scores and increase the variance explained.

A cyclobutane compound competitively inhibits the activity of androgen receptors (AR) containing antiandrogen-resistant mutations through stabilization of the receptor in an apo-like conformation and preventing AR nuclear entry.

Endothelial cells at the inner surface of blood vessels are exposed to mechanical forces as a result of blood flow. Here the authors show that the interaction of extracellular matrix proteins with adhesion molecules on the endothelial cell surface determines cellular stiffness and sensitivity to mechanical forces.

Alzheimer’s disease (AD) is pathologically characterized by the accumulation of neuritic plaques and neurofibrillary tangles but it is not known whether the neuritic plaque is necessary to drive the conversion of wild-type tau. Here the authors developed a mouse model in which wild-type tau is converted into pathological tau in a neuritic plaque-dependent manner.

Closed-loop electrical stimulation of the internal capsule of participants undergoing intracranial epilepsy monitoring improved the participants’ performance on a cognitive conflict task, and performance could be decoded from electrode activity.

These two studies show that primary cilia can either mediate or suppress tumorigenesis in models of basal cell carcinoma and medulloblastoma, respectively, depending on the nature of the initial oncogenic event (pages 994–996) and (pages 1062–1065).

The authors show that inhibitory interneurons in cortical layer 1 integrate topographically organized thalamic and neuromodulatory inputs to sculpt sound frequency maps in primary auditory cortex during a developmental critical period.

ARLNC1 is a newly discovered lncRNA that is induced by androgen receptor (AR) and maintains AR signaling by stabilizing the AR transcript. Knockdown of ARLNC1 suppresses AR expression, AR signaling and prostate cancer growth in vitro and in vivo.

Ageing is associated with muscle atrophy, which negatively impacts quality of life. Here the authors show that expression of sestrins decreases during inactivity and that their overexpression prevents atrophy in mice via modulation of autophagy and protein degradation.