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Geller and Jackson have both reproached me for not citing all of the Jackson and Kagan papers in my earlier statement. Space requirements did not allow for a fuller discussion it that time.

Physical activity has been linked to lower risks of colorectal and breast cancer. Here, the authors present a Mendelian randomisation analysis supporting a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer.

Production of reactive oxygen species is an ancient antimicrobial mechanism, but its role in antiviral defense in mammals is unclear. Here, To et al. show that virus infection activates endosomal NOX2 oxidase and restricts TLR7 signaling, and that an endosomal NOX2 inhibitor decreases viral pathogenicity.

It is important to understand the correlates of protection against SARS-CoV-2 and its variants for future vaccine design. Here, the authors show that the complement system enhances the antibody-mediated neutralisation of SARS-CoV-2 via increased inhibition of virus-host interactions.

Genome sequencing data can be used to infer transmission dynamics for pathogens of public health concern such as N. gonorrhoeae. Here, the authors sequence and analyse 5881 genomes from Victoria, Australia from 2017–2021, and assess impacts of COVID-19 restrictions on transmission.

Data collected from more than 2,000 taxa provide an unparalleled opportunity to quantify how extreme wildfires affect biodiversity, revealing that the largest effects on plants and animals were in areas with frequent or recent past fires and within extensively burnt areas.

The strength of the Antarctic Circumpolar Current, as traced in sediment cores from the Pacific Southern Ocean, shows no linear long-term trend over the past 5.3 Myr; instead, the strongest flow occurs consistently in warmer-than-present intervals.

Tool making has been considered to be an attribute of the genus Homo; this paper reports 3.3-million-year-old stone tools and the early timing of these tools provides evidence that the making and use of stone tools by hominins occurred before the evolution of our own genus.

There has been a recent recrudescence^1,2 of the long debate on the feasibility of short-term earthquake prediction, namely, the prediction, with a lead time of days to weeks, of the time, ___location and magnitude of a future event. This type of earthquake prediction is inherently difficult to research and has a chequered past, with many intriguing but fragmentary observations of possibly precursory phenomena but no scientifically based and verified successes³.

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.

Patagonian ice sheet changes largely mirrored those of the Northern Hemisphere over the last glacial cycle owing to displacements of the southern westerly winds, according to beryllium isotope constraints.

Lei et al. systematically characterized the epistasis among natural mutations in the neuraminidase of human influenza H3N2 virus, which provide insights into the biophysical constraints that shaped its evolution trajectory over the past half-century.

Genome-wide association analyses of prostate cancer in men from sub-Saharan Africa identify population-specific risk variants and regional differences in effect sizes. Founder effects contribute to continental differences in the genetic architecture of prostate cancer.

Understanding the effect of vaccination on emerging SARS-CoV-2 variants of concern is of increasing importance. Here, James et al. report that two doses of vaccination with the Pfizer-BioNTech vaccine induce more robust immune responses to the B.1.1.7 and B.1.351 SARS-CoV-2 lineages than does natural infection.

It is unclear how often genetic mosaicism of chromosome X arises. Here, the authors examine women with cancer and cancer-free controls and show that X chromosome mosaicism occurs more frequently than on autosomes, especially on the inactive X chromosome, but is not linked to non-haematologic cancer risk

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

The Southern Ocean is perhaps the only region where fluctuations in the global influence of North Atlantic Deep Water (NADW) can be monitored unambiguously in single deep-sea cores. A carbon isotope record from benthic foraminifera in a Southern Ocean core reveals large and rapid changes in the flux of NADW during the last deglaciation, and an abrupt increase in the NADW production rate which immediately preceded large-scale melting of the Northern Hemisphere ice sheets. This sudden strengthening of the NADW thermoha-line cell provides strong evidence for the importance of NADW in glacial-interglacial climate change.

Global syphilis prevalence has been increasing. Sequencing and analysis of a global collection of 726 Treponema pallidum samples reveal globally circulating lineages linked to a rapid expansion occurring since the end of the twentieth century.

Here the authors use single cell profiling of T cells across the human lifespan to show that a suboptimal TCR shift in T cells as we enter older age results in a molecular signature that resembles that of T cells from newborns and children.

The chromosome 15q25.1 locus is a leading susceptibility region for lung cancer. Here, the authors interrogate three GWAS cohorts with 42,901 individuals to investigate potential pathological pathways such as gated channel activity and neuroactive ligand receptor interaction in lung cancer etiology.

Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology.

Non-pharmaceutical interventions for COVID-19 also reduced incidence of respiratory pathogens such as respiratory syncytial virus (RSV). Here, the authors report the resurgence of RSV in Australia following lifting of some of the restrictions and describe reduction in genetic diversity in circulating clades.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

The ability to maintain blood stem cells (HSCs) in vitro would allow us to provide better therapies for blood diseases. Here, the authors report that polymer-organised extracellular proteins, coupled to soft environments mimicking bone marrow stiffness, allow stromal cells to maintain HSCs in vitro.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

Free-ranging domestic cats have major ecological impacts globally. Here, Lepczyk et al. compile records of the species consumed by cats, identifying thousands of species consumed, including hundreds of species that are of conservation concern.

A transparent and reproducible scientific framework is introduced to formalize how trillions in economic losses are attributable to the extreme heat caused by emissions from fossil fuel companies, which could inform climate liability claims.

The engagement of immunological memory is a key component to the protective anti-SARS-CoV-2 B and T cell responses. Here the authors assess the B and T cells of a cohort of UK healthcare workers in response to infection and longitudinally track the compartment showing distinct trajectories following early priming.

The immunology of Indigenous populations is generally understudied outside the context of diseases that are prevalent in these communities. Here the authors identify prevalence of influenza CD8⁺ T cell epitopes in an Indigenous Australian population expressing the susceptibility allomorph HLA A*24:02 and validate immunodominance of some of these epitopes in mice.

IgE antibodies have shown anti-tumor activity, even superior to IgG, in preclinical models. However, all monoclonal antibodies in clinical use for cancer therapy are members of the IgG class. Here the authors report the results of a phase I clinical trial of a chimeric monoclonal IgE antibody, specific for the folate receptor-alpha, in patients with advanced solid cancer.

It is unclear how reward and risk are temporally organized in the human brain. Here, the authors demonstrate both sequential and parallel encoding of decision variables, and the role of anterior insula in reward- and risk-prediction error.