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While the emergence of immune checkpoint inhibitors has improved outcomes in patients with small cell lung cancer (SCLC), tumour that develop means of immune evasion become resistant. Here, the authors report that ERBB2 signalling induces loss of MHC Class I expression and subsequently immune evasion in preclinical models of SCLC.

Reliable prediction of bacterial abundance dynamics in microbial communities is still unresolved. Here, the authors built a graph neural network-based model trained on historical relative abundance data to predict species abundance dynamics for weeks to months for any longitudinal microbial dataset.

The crystal structures and cryo-electron microscopy reconstructions of eEF3 on its own and attached to the ribosome are resolved, providing an insight into how eEF3 functions as a translation factor on the A and E sites on a ribosome.

The immune response is key in determining disease severity of COVID19. Here Nouailles et al., apply bulk proteomics and scRNA-Seq of lung and blood samples of SARS-CoV-2 infected Syrian hamsters and provide a temporal atlas of the systemic and pulmonary cellular responses.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

The transcription factor PU.1 is an essential regulator of the pro-fibrotic gene expression program in fibroblasts; PU.1 expression is upregulated in various fibrotic diseases, whereas inactivation of PU.1 induces regression of fibrosis in a number of organs.

The interaction of membrane-resident proteins plays an essential role in biological processes. Here the authors describe cellular biosensors based on chimeric receptors, as a tool to study the interaction of receptor-ligand pairs such as immune checkpoint molecules or virus attachment proteins and their receptors.

Pancreatitis often develops as a consequence of ductal obstruction. Here, the authors show that bicarbonate ions initiate the release of neutrophil extracellular traps (NETs) that form pancreatic ductal aggregates and occlude the ducts, thereby driving pancreatitis in mice and humans.

A multi-ancestry genome-wide association study for age at menarche followed by fine mapping and downstream analysis implicates 665 pubertal timing genes, such as the G-protein-coupled receptor 83 (GPR83) and other genes expressed in the ovaries involved in the DNA damage response.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

Innate immune responses to mRNA vaccines are less well understood than adaptive immunity. Here, the authors comprehensively characterize the innate and adaptive immune responses to mRNA-1273 vaccinations in rhesus macaques and show how the vaccine activates interactions among components of the two systems.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

Oestrogen negative breast cancer is associated with a poor prognosis. In this study, the authors perform a meta-analysis of 11 breast cancer genome-wide association studies and identify four new loci associated with oestrogen negative breast cancer risk. These findings may aid in stratifying patients in the clinic.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Thalidomide and its derivatives lenalidomide and pomalidomide, which are used to treat multiple myeloma and del(5q) myelodysplastic syndrome, have antitumor and teratogenic effects through a mechanism involving destabilization of the CD147 and MCT1 proteins.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

The structure of a recombinant 20-subunit version of human Mediator bound to the transcription pre-initiation complex is determined, providing insight into the regulation of RNA polymerase II initiation.

Using cryo-EM, here the authors structurally delineate the Elongin–RNA polymerase II holocomplex. They show that Elongin allosterically regulates the transcribing RNA polymerase II via a latch that affects its conformational mobility.

Neutrophils can release S100A8/S100A9 as an alarmin via gasdermin D pores. Here, the authors untangle the regulatory mechanisms driving this pathway and show that active repair processes make these pores transient, which can prevent the usual lytic cell death.

The cryo-electron microscopy structure of the 16-subunit yeast SWI/SNF complex RSC in complex with a nucleosome substrate provides insights into the chromatin-remodelling function of this family of protein complexes.

This study presents an analytic framework to link imaging-derived brain phenotypes to gene expression. In the future, this approach may facilitate in vivo pharmacotranscriptomics and the development of personalized (pharmacological) interventions.

Irradiation of chiral Al-salen complexes with violet light demonstrates efficient deracemization of cyclopropanes, enabling reactivity and enantioselectivity to be regulated simultaneously, negating the requirement for tailored catalyst–substrate recognition motifs.

Phosphorylation of the carboxy-terminal domain of RNA polymerase II is important for controlling gene transcription. In this study, the transcription elongation factor Tefb is shown to phosphorylate serine-5 and its activity is enhanced when the polymerase is already phosphorylated on serine-7.

Wastewater treatment plants (WWTPs) are thought to play a central role in the dissemination of antibiotic resistance genes. Here, the authors identify novel antibiotic resistance genes in WWTPs and show that only a few of the most abundant resistance genes are found outside the WWTP environment.

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

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.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.

The cryo-EM structure of the N-terminal acetyl transferase NatA in complex with the ribosome shows that NatA is dynamically positioned underneath the ribosomal exit tunnel to facilitate modification of the emerging nascent peptide chain.

A series of genetic studies have led to the discovery of novel independent loci and candidate genes associated with red blood cell phenotype; for a proportion of these genes potential single-nucleotide genetic variants are also identified, providing new insights into genetic pathways controlling red blood cell formation, function and pathology.

The authors pooled resources to identify best practices and develop a new standardized protocol for estimating functional connectivity in rats with magnetic resonance imaging.

Many genetic loci have been identified to be associated with kidney disease, but the molecular mechanisms are not well understood. Here, the authors perform epigenome-wide association studies on kidney function measures to identify epigenetic marks and pathways involved in kidney function.

The TOM and TIM23 complexes facilitate the transport of nuclear-encoded proteins into the mitochondrial matrix. Here, the authors use a stalled client protein to purify the translocation supercomplex and gain insight into the TOM-TIM23 interface and the mechanism of protein handover from the TOM to the TIM23 complex.

Understanding the molecular basis of leukaemia predisposition is essential for intervention. The authors here investigate germline genetic leukaemia predisposition by studying Shwachman-Diamond syndrome and report compensatory inactivating mutations in EIF6 and transforming biallelic TP53 alterations.

Serum urate concentration can be studied in large datasets to find genetic and epigenetic loci that may be related to cardiometabolic traits. Here the authors identify and replicate 100 urate-associated CpGs, which provide insights into urate GWAS loci and shared CpGs of urate and cardiometabolic traits.

A study of the functional microbiome in a mouse model of ALS shows that several gut bacteria may modulate the severity of the disease.

Here, using an integrative experimental and computational approach, Imle et al. show how cell motility and density affect HIV cell-associated transmission in a three-dimensional tissue-like culture system of CD4⁺ T cells and collagen, and how different collagen matrices restrict infection by cell-free virions.

The authors leveraged a large multimodal sample and combined normative modeling and linked independent component analysis to study a cross-modal signature of face processing within the fusiform gyrus in autism.

Depletion of chromosome-associated cohesin leads to loss of topologically associating domains in interphase chromosomes, without affecting segregation into compartments, and instead, it unmasks a finer compartment structure that reflects local chromatin and transcriptional activity.

A combination of scattering interferometry and single-molecule fluorescence microscopy allows visualization of both the position and orientation of single Simian virus 40 particles on lipid bilayers and provides evidence of viral interaction with receptors in membrane nanodomains.

The neurotransmitter transporter SERT counter transport K⁺ to transport serotonin. Here the authors show that the activity of the prokaryotic orthologue LeuT is also modulated by this cation, suggesting a general regulatory role for K⁺on neutrotrasmitter:sodium symporters function.

Using normative modeling and focusing on individual differences, the authors explore the link between copy number variations, brain structure and cognitive abilities.

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.

This study maps cerebellar anatomy across the lifespan using over 54,000 brain scans from 132 scanning sites and identifies that patients with autism spectrum disorder, mild cognitive impairment, Alzheimer disease, and schizophrenia are likely to have deviations in cerebellar anatomy.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

Ruth Loos and colleagues report a meta-analysis of genome-wide association studies in 181,171 individuals identifying 14 new loci associated with heart rate and test these for association with cardiac conduction, rhythm disorders and cardiovascular disease. Their experimental studies in Drosophila melanogaster and zebrafish models provide support for a role for 20 candidate genes at 11 of these loci in regulation of heart rate.