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Bay et al. investigate upper respiratory mucosal transcriptomic profiles in critically ill COVID-19 patients infected with Omicron using an unsupervised clustering approach. Their study identifies two distinct immune response profiles, one characterised by enhanced innate and inflammatory activation compared with the other, highlighting the immune heterogeneity in severe COVID-19.

Patin and colleagues present a mineable Resource database for identifying demographic and genetic factors that impact antiviral antibody repertoires in humans.

In a randomized controlled trial in individuals with persistent atrial fibrillation, an individualized ablation procedure, in which areas with abnormal electrophysiological characteristics—as detected by an AI algorithm—were targeted for ablation, led to improved efficacy for reducing arrhythmia recurrence at 12 months following the ablation procedure.

SARS-CoV-2 variant Omicron has been suggested to cause less severe disease. This prospective study shows that the clinical phenotype in patients infected with Omicron differs from patients infected with Delta but no association between Delta and Omicron including sublineages and mortality was observed.

Cao et al. show that SPIN90 enhances formation of Arp2/3-mediated unbranched filaments and promotes a formin-based cortex by recruiting mDia1 or forming a ternary SPIN90–Arp2/3–mDia1 complex.

Microsatellite instability (MSI) due to alterations in DNA repair genes leads to carcinogenesis, but it also correlates with better prognosis and therapy response. Little is known of the contribution of altered noncoding sequences to MSI tumorigenesis. This report identifies a deletion in an MSI intronic region leading to the expression of a truncated chaperone, which shows dominant-negative effects on its wild-type counterpart. Acting as an endogenous inhibitor of a protumorigenic chaperone, the expression of the truncated variant associates with better prognosis in humans and may contribute to the overall limited malignancy of MSI tumors.

In a post-approval study including more than 17,000 patients on the safety of pulsed field ablation, a new method for treatment of atrial fibrillation, the procedure was found to have a low rate of adverse events but was associated with some unexpected rare complications that will need further study.

The Type 3 Secretion System (T3SS) of Pseudomonas aeruginosa injects effectors into host cells to promote infection. Here, the authors reveal a new regulatory role for the T3SS effector ExoY in modulating ExoT-induced cytotoxicity via cGMP signalling.

Whether and how cannabinoid type-1 receptors impact sensory functions in vivo is largely unknown. Here, authors show that their endogenous activity controls network dynamics in the olfactory piriform cortex and the ability of mice to detect odorants.

Mercier et al. demonstrate a role for endosomal membrane tension in modulating ESCRT-III polymerization, intra-lumenal vesicle formation and endosome trafficking.

The correct assembly of genomes from sequencing data remains a challenge due to difficulties in correctly assigning the location of repeated DNA elements. Here the authors describe GRAAL, an algorithm that utilizes genome-wide chromosome contact data within a probabilistic framework to produce accurate genome assemblies.

Osmotic pressure is thought to play a key role in many cellular and developmental processes, but remains challenging to measure it in cells and tissues. Here, the authors present a sensor based on double emulsion droplets that allows quantification of osmotic pressure in situ and in vivo.

By simulating the implementation of airport-based wastewater surveillance sites at the global level, a modeling study shows how this early warning system would perform in identifying sources of pandemic outbreaks, in time and space, and what the optimal location of monitoring sites would be.

‘Missing self’ is a mode of natural killer (NK) cell activation aimed to detect the lack of HLA-I molecules on infected or neoplastic cells. Here, the authors show that mismatch between donor HLA-I and cognate receptors on recipient NK cells mediates microvascular inflammation-associated graft rejection, a pathology that is preventable by mTOR inhibition.

Analysis of genomic data from 25 distantly related plant species shows signatures of selection on the same gene families and functions that repeatedly contributed to local adaptation to climate.

This Review details the epidemiological, mechanistic, clinical, biological and pathological features of nonalcoholic fatty liver disease—the liver manifestation of the metabolic syndrome that can progress to end-stage liver disease, and the commonest liver disease in Western countries. The article also describes the treatment options, which include dietary modification and exercise.

The virus HTLV-1 is thought to pass between cells through synapses formed when infected lymphocytes make contact with other T cells. Isabelle Thoulouze and her colleagues uncover an alternative mechanism for the cell-to-cell transmission of this virus. They show that HTLV-1 virions bud at the plasma membrane and are held at the cell surface in structures reminiscent of bacterial biofilms. When infected lymphocytes make contacts with other cells, the adhesive viral assemblies are rapidly transferred to to the surface of the new lymphocyte, from which the virions mediate a new round of infection.

Chromatin loops bridging distant loci within chromosomes can be detected by a variety of techniques such as Hi-C. Here the authors present Chromosight, an algorithm applied on mammalian, bacterial, viral and yeast genomes, able to detect various types of pattern in chromosome contact maps, including chromosomal loops.

Anthropogenic stressors affect many aspects of marine organismal health. Here, the authors expose surgeonfish to temperature and pesticide stressors and show that the stressors, separately and in combination, have adverse effects on thyroid signaling, which disrupts several sensory systems and important predation defenses.

ANME-1 archaea are important because of their ability to metabolize methane through anaerobic oxidation. Here the authors use metagenomics on hydrothermal samples from the Gulf of California to characterize a family of ANME-1 and its virome.

Genomic analyses of human populations in the Pacific provide insights into the peopling history of the region and reveal episodes of biological adaptation relating to the immune system and lipid metabolism through introgression from archaic hominins and polygenic adaptation.

CRISPR interference (CRISPRi) is a method for targeted silencing of transcription that requires the coexpression of protein dCas9 and a customized guide RNA. Here, Cui et al. show that certain guide RNAs induce toxicity in E. coli, and provide design rules to minimize off-target effects.

Crystallographic snapshots illustrate the catalytic cycle and illuminate the mechanism by which the enzyme Pdx1 shuttles intermediates between lysine residues in its two active sites during the biosynthesis of pyridoxal 5′-phosphate.