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Electron cryo-microscopy and image analysis of frozen-hydrated, two-dimensional crystals of gap junction membrane channels formed by recombinant α₁ connexin (Cx43) reveal a ring of transmembrane α-helices that lines the aqueous pore and a second ring of α-helices in close contact with the membrane lipids.

The HIV virion has a cone-shaped core composed of capsid proteins, which take either pentameric or hexameric form. The crystal structure of the capsid hexamer had been solved previously. Now the structure of the pentamer is provided, which allows the proposal of the first atomic-level model of the mature HIV capsid.

Single particle cryo-electron microscopy of membrane proteins is limited by their small size and difficulty to orient. Here the authors generate recombinant antibodies against the 12 kDa fusion partner BRIL domain from apocytochrome b562 to use them as plug and play fiducial marks for structure determination of BRIL fused membrane proteins.

Over one hundred loci have been identified to be associated with the familial risk of prostate cancer but the functional effects are poorly understood. Here the authors use single-nucleotide variant and epigentic data to show an underlying genetic architecture marked by histone modification.

A multi-ancestry genome-wide association meta-analysis of kidney cancer identifies 63 regions associated with disease susceptibility including one locus that was associated with increased risk in individuals with African ancestry.

Human proteins SERINC3 and SERINC5 are HIV-1 restriction factors that reduce viral infectivity. Here, the authors show that SERINC3 has architecture resembling non-ATP dependent lipid transporters and induces loss of membrane asymmetry correlated with changes in envelope conformation and loss of infectivity.

The structural basis of integrin signaling in health and disease is not fully understood. Here, the authors determine the cryoEM structure of full-length platelet integrin αIIbβ3 in its apo and eptifibatide-bound conformations in a native membrane environment.

Montserrat Garcia-Closas and colleagues report a genome-wide association study for bladder cancer. They identify three new susceptibility loci on chromosomes 22q13.1, 19q12 and 2q37.1.

Advances in climate prediction mean that the state of the ocean and the drivers of shifts can be skilfully forecast up to a decade ahead. This study applies decadal-scale climate predictions to forecast shifts in the habitat and distribution of marine fish species, providing information relevant to stakeholders and a tool to foresee and adapt to the challenges of a changing climate.

Invasive cervical cancer is caused by HPV infection, but the disease itself is highly variable. Here, the authors use deep targeted sequencing to identify hotspot mutations in routine screening samples prior to diagnosis, which differed depending on HPV type.

Risk for renal cell carcinoma (RCC) is higher when there are first-degree family members with the disease. Here, Scelo and colleagues perform a genome-wide association meta-analysis and new genome-wide scan to identify seven new loci with significant RCC association.

Tirofiban is an inhibitor of platelet αIIbβ3 which may contribute to venous thrombosis. Here the authors developed a non-agonizing modified tirofiban, defined by its cryo-EM structure bound to platelet αIIbβ3 and elucidated the pathogenic role of αIIbβ3 in venous thrombogenesis.

Genetic and functional studies implicate allele-specific regulation of OAS1 splicing and nonsense-mediated decay in COVID-19 severity. The OAS1 risk haplotype is also associated with reduced SARS-CoV-2 clearance in a clinical trial with pegIFN-λ1.

Luis Pérez-Jurado, Stephen Chanock and colleagues detect clonal chromosomal abnormalities in peripheral blood or buccal samples from individuals in the general population. They show that the frequency of such events increases with age and is associated with elevated risk of developing subsequent hematological cancers.

Chronic lymphocytic leukemia is a highly inheritable cancer. Here the authors conduct a metaanalysis of four genome-wide association studies and identify three novel loci located near EOMES, SERPINB6 and LPPassociated with risk of this disease.

Marginal zone lymphoma (MZL) is a common subtype of B-cell non-Hodgkin lymphoma. Here the authors carry out a two-stage genome-wide association study in over 8,000 Europeans and identify two new MZL risk loci at chromosome 6p, implicating the major histocompatibility complex in the disease for the first time.

Susan Slager and colleagues report a meta-analysis of genome-wide association studies for chronic lymphocytic leukemia (CLL). They identify nine loci newly associated with CLL.

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

Intercellular signalling can be mediated by gap junction channels, and calcium blocks this signally during tissue injury. Here, the authors use X-ray crystallography and molecular dynamics to show that the calcium forms an electrostatic barrier to prevent transport of cations.

Genetic variants associated with susceptibility to pancreatic cancer have been identified using genome wide association studies (GWAS). Here, the authors combine data from over 9000 patients and perform a meta-analysis to identify five novel loci linked to pancreatic cancer.

Injectable biomaterial vaccines designed to magnetically capture pathogen-associated molecular patterns protect mice and pigs against septic shock from lethal bacterial infections.

The APOBEC mutational signature is prevalent in different tumour types. Here, using HPV16- positive cervical samples, the authors show that the signature is more prevalent in the viral genome of benign or clearing HPV16 infections compared to the viral genomes of the more advanced precancerous lesions or cervical cancer.

Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a non-Hodgkin-type B cell lymphoma. Here, the authors identify two risk loci for WM/LPL in a two-stage GWAS involving a family-oversampling approach and provide evidence for a functional role of the non-coding SNP rs116446171.

Significant morphological changes occur during the conversion of the immature HIV virion into a mature infectious form. Here the authors use coarse-grained molecular dynamics simulations to model HIV-1 capsid self-assembly and disassembly events that suggests several metastable capsid intermediates sensitive to local conditions.

Pannexins are oligomeric plasma membrane channels that allow permeation of ions and large molecules. Here the authors show that human Pannexin 1 activation is a multistep event, where modification of each monomer opens the channel to a unique conductance state and fine tunes its activity.

Sexually selected traits primarily drive reproductive success, but their secondary functions are less well studied. Here, the authors show that antler retention among male elk involves a trade-off between predator deterrence and reproductive success in the next breeding season.

Paul Brennan, Stephen Chanock and colleagues performed a genome-wide association study for renal carcinoma. They identified two genetic susceptibility loci.

Beatrice Melin, Richard Houlston, Melissa Bondy and colleagues report results of a large-scale genome-wide association study of glioma. They identify five new risk loci for glioblastoma and eight new risk loci for non-glioblastoma tumors, highlighting distinct genetic etiologies for these two glioma subtypes.

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.

Sharon Savage and colleagues report the results of a genome-wide association study of osteosarcoma. They identify two susceptibility loci for this primary bone malignancy, including variants within the metabotropic glutamate receptor gene GRM4.

Maria Teresa Landi and colleagues identify a rare missense variant in POT1 shared by five melanoma-prone families from Italy and associated with increased telomere length and telomere fragility. They also identify additional familial melanoma cases with rare missense variants in POT1 and find a significant excess of rare exonic POT1 variants in melanoma cases compared to controls, implicating POT1 variants in melanoma susceptibility.

Katherine Nathanson and colleagues report four new susceptibility loci for testicular germ cell tumor identified through a meta-analysis of genome-wide association studies with follow-up replication. The newly discovered risk regions include genes important for male germ cell development, chromosomal segregation and the DNA damage response.