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Cluster states are a key resource in quantum technologies, but generation of large-scale 2D cluster states faces several difficulties. Here, the authors show how to generate a 2 × n ladder-like cluster state via sequential emission of time- and frequency multiplexed photonic qubits from a transmon-based device.

Pocock et al. reveal that transient activation of 5′ AMP-activated protein kinase and estrogen-related receptor drives robust maturation of multicellular human cardiac organoids, enabling modeling of desmoplakin cardiomyopathy dysfunction, which could be rescued using the bromodomain and extra-terminal inhibitor INCB054329.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

Whole genome sequences enable discovery of rare variants which may help to explain the heritability of common diseases. Here the authors find that ultra-rare variants explain ~50% of coronary artery disease (CAD) heritability and highlight several functional processes including cell type-specific regulatory mechanisms as key drivers of CAD genetic risk.

Apolipoprotein L1 genetic variants contribute to a subtype of proteinuric kidney disease referred to as APOL1-mediated kidney disease (AMKD). Here the authors report the discovery and characterization of potent and selective APOL1 ion channel inhibitors for the potential treatment of AMKD.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

Here, the authors perform a global analysis of over 3000 infant gut samples revealing a universal pattern of microbial changes over the first 1.5 years, with declines in Bifidobacterium and increases in Faecalibacterium, providing a standard for early gut development.

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.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

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.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

In a phase 2 trial of patients with untreated, recurrent and progressive brain metastases treated with an anti-programmed cell death protein 1 inhibitor, the overall intracranial benefit rate was 42.1%, which met the prespecified primary endpoint.

Real-time feedback control of quantum systems without relying on a description of the system itself is usually challenging. Here, the authors exploit deep reinforcement learning to realise feedback control for initialisation of a superconducting qubit on a submicrosecond timescale.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

Efforts to produce aromatic monomers through catalytic lignin depolymerization were focused on aryl–ether bond cleavage, while the carbon–carbon bonds of a large fraction of aromatic monomers in lignin are difficult to cleave. Here, the authors report a catalytic autoxidation method using manganese and zirconium salts as catalysts to cleave the C–C bonds in lignin-derived dimers and oligomers from pine and poplar.

Leptomeningeal metastases from solid tumors are a rare complication with a very poor prognosis. Here the authors report the efficacy and safety of combined ipilimumab and nivolumab in patients with leptomeningeal carcinomatosis.

Chromatin accessibility may be altered in disease states. Here the authors carry out ATAC-seq on a large number of samples of dorsolateral prefrontal cortex from individuals with schizophrenia, and healthy controls.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

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.

It remains unclear whether exotic and native species are functionally different. Using a global grassland experiment, Seabloomet al. show that native and exotic species respond differently to two globally pervasive environmental changes, addition of mineral nutrients and alteration of herbivore density.

Multi-inflammatory syndrome in children (MIS-C) can be associated with SARS-CoV-2 infection but can also be similar to other inflammatory syndromes. Here the authors characterise the plasma proteome phenotype in MIS-C and compare to other SARS-CoV-2 related syndromes and find disproportionately high IFN-γ responses in MIS-C patients.

The histone H3 variant CENP-A defines centromeric chromatin, but it has been unclear how CENP-A is stably maintained at centromeres. It has now been shown that the CENP-A licensing factor HsKNL2 and the small GTPases activating protein MgcRacGAP cooperate to promote the stability of newly loaded CENP-A at centromeres.

The beta variant (B.1.351) is to date the most resistant to neutralization of the SARS-CoV-2 variants. Using nonhuman primates, Seder and colleagues demonstrate that double vaccination with a high dose of the lipid nanoparticle vaccine mRNA-1273 protects against infection with the beta variant.

Viruses are isolated from the SAR11 bacterial clade, the most abundant group of bacteria in the ocean, that were thought to be resistant to viral infection; because of the essential role of SAR11 in carbon cycling these viruses are also an important factor in biogeochemical cycling.

This study demonstrates that bacteria use a ubiquitin transferase-like enzyme to prime cGAS/DncV-like nucleotidyltransferase activation and use a deubiquitinase-like enzyme to decrease activity.