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SARS-CoV-2 seroprevalence surveys aim to estimate the proportion of the population that has been infected, but their accuracy depends on the characteristics of the test assay used. Here, the authors use statistical models to assess the impact of the use of different assays on estimates of seroprevalence in the United States.

Whether mRNA SARS-CoV-2 vaccines promote T cells within the nasal mucosa of vaccine recipients is not known. Here the authors show that after mRNA SARS-CoV-2 vaccination, antigen specific T cells can be measured in the nasal mucosa and that these T cells may be localised to respond to a subsequent virus infection.

Clinical trial registration NCT04713163

Tacrolimus is a critical immunosuppressant for liver transplant recipients, but its dosing is challenging due to individual variability. Here, the authors show that a phenotypic personalized medicine approach improves tacrolimus dosing precision, reducing large deviations from target levels and shortening hospital stays in a Phase 2 randomized trial.

Genomic epidemiology studies have indicated southern Africa as likely sources of emergence of six Omicron lineages since November 2021. Here, the authors trace the geographic origins and dispersion patterns of these six lineages and highlight Gauteng province in South Africa as likely to have played a key role.

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

A20, encoded by TNFAIP3, is a negative-feedback inhibitor of NF-κB. Grey and colleagues identify natural human variants of TNFAIP3, which lower A20 activity and increase autoinflammatory responses. These alleles were inherited by descendants of Denisovans who crossed the Wallace Line to inhabit Oceania.

A central problem in the COVID-19 pandemic is that there is not enough testing to prevent infectious spread of SARS-CoV-2, causing surges and lockdowns with human and economic toll. Here, the authors evaluate an alternative strategy based on the monitoring of olfactory dysfunction with a mathematical model.

Blockade of intrahepatic accumulation and function of platelets represents a potential approach to treat non-alcoholic steatohepatitis (NASH) and prevent subsequent progression to hepatocellular carcinoma

Bone marrow-derived epithelial cells can be recruited to sites of chronic inflammation. Here, the authors using allogenic bone marrow transplantation in a multistage murine cutaneous carcinogenesis model show that bone marrow-derived epithelial cells and hair follicle stem cells are recruited to cutaneous neoplasms during tumor promotion of carcinogen-exposed skin and bone marrow.

Disentangling the impacts of non-pharmaceutical interventions on COVID-19 transmission is challenging as they have been used in different combinations across time and space. This study shows that, early in the epidemic, school/daycare closures and stopping nursing home visits were associated with the biggest reduction in transmission in the United States.

Bispecific antibodies can bind to two distinct targets though the fusion of two different Fv regions. In this study, the authors develop DutaFabs that present two separated and independent antigen binding sites within the same Fv region, giving rise to bispecific Fab fragments.

How the 22q11.2 deletion predisposes to psychiatric disease is unclear. Here, the authors examine living human neuronal cells and show that 22q11.2 regulates the expression of genes linked to autism during early development, and genes linked to schizophrenia and synaptic biology in neurons.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

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.

Chemical force microscopy measurements show that the immobilization of specific cationic groups near non-polar domains produces pronounced changes in the domains’ hydrophobic interaction strengths: charged ammonium groups double interaction strengths, whereas guanidinium groups eliminate measurable interactions.

Mincle is a pattern recognition receptor that senses danger signals in innate immune cells. Here authors show in an experimental autoimmune encephalomyelitis mouse model that tissue damage triggers Mincle signaling on inflammatory helper T cells, leading to inflammasome-mediated IL-1β production and reinforced inflammation.

Genome-wide analysis identifies 30 loci associated with bipolar disorder, allowing for comparisons of shared genes and pathways with other psychiatric disorders, including schizophrenia and depression.

Here, the human immune response to infection with Mycobacterium tuberculosis has been characterized by transcriptional profiling. The results show that active tuberculosis correlates with a particular transcriptional signature that is dominated by a neutrophil-driven interferon-inducible gene profile. The study provides a broad range of transcriptional biomarkers with potential as diagnostic and prognostic tools to combat the tuberculosis epidemic.

In macrophages, IL-1β secretion is mediated by N-GSDMD pores in the plasma membrane (PM). Here the authors show that in neutrophils, IL-1β secretion occurs in the absence of PM pores, via autophagosomes; N-GSDMD does not traffic to PM but to azurophilic granules, thereby releasing neutrophil elastase which cleaves further N-GSDMD into alternative fragments.

Targeting of mitochondrial metabolism in combination with BCL-2 inhibition eradicates leukemia stem cells and induces long-lasting responses in patients with acute myeloid leukemia.

A breakthrough in metamaterial-based spatial light modulator design makes single-pixel real-time imaging practical by using compressive sensing to dispense with slow mechanical scanning.

In a randomized phase 2 trial, sotigalimab, a CD40 agonist, did not significantly improve overall survival in patients with previously untreated metastatic pancreatic cancer when combined with chemotherapy or with nivolumab and chemotherapy. Multi-omic exploratory analyses provide insights into immunologic features associated with clinical benefit.

A multiancestry genome-wide association study of chronic alanine aminotransferase elevation identifies candidate risk loci for nonalcoholic fatty liver disease, with replication in external cohorts defined by histology or imaging.

A microfluidic CRISPR-based platform enables multiplexed and high-throughput identification of a wide range of respiratory viruses, including the ability to identify specific SARS-CoV-2 variants such as Delta and Omicron.

Dziedzic et al. show that the ubiquitin-binding protein ABIN-1 is recruited into TNFR1 signalling complex in a manner dependent on Met1 -ubiquitinating complex LUBAC to regulate K63 de-ubiquitination to activate RIPK1.

The deubiquitinase A20 limits excessive cytokine expression by shutting down activation of the transcription factor NF-κB. Harhaj and colleagues show that the kinase IKKα activates the A20 ubiquitin-editing complex by phosphorylating the regulatory molecule TAX1BP1.

Paul Thompson and colleagues report a genome-wide association study for hippocampal, intracranial and total brain volume. They identify a locus at 12q24 associated with hippocampal volume and a locus at 12q14 associated with intracranial volume.

With a comprehensive analysis of sequencing data, DNA copy number, gene expression and DNA methylation in a large number of human glioblastomas, The Cancer Genome Atlas project initiative provides a broad overview of the genes and pathways that are altered in this cancer type.

Genomic characterization of the SARS-CoV-2 Omicron lineages BA.4 and BA.5, responsible for the fifth COVID-19 pandemic wave in South Africa, shows continued viral diversification and provides insights into the potential mechanisms underlying the ability of the new lineages to outcompete their predecessors.

This Review Article examines the development of physical unclonable functions, which exploit inherent randomness to give a physical entity a unique ‘fingerprint’ or trust anchor, considering the various potential applications of these devices and the security issues that they must confront.

Fouladzadeh, Dorraki and colleagues investigate the development of angiogenic networks for in vitro cancer cell lines. They demonstrate that during the growth stages of vasculogenic mimicry, the number of edges and vertices decreases but the edge length increases resulting in improved network efficiency.

The authors propose a new conceptual model of critical illness that moves away from the current syndrome-based framework in favor of more precise biological descriptors—spurred by mounting translational evidence and insights from Coronavirus Disease 2019 (COVID-19) research.