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A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

DuMPLING (dynamic μ-fluidic microscopy phenotyping of a library before in situ genotyping) enables screening of dynamic phenotypes in strain libraries and was used here to study genes that coordinate replication and cell division in Escherichia coli.

Intestinal homeostasis is maintained by interactions between the gut-associated lymphoid tissue and the resident flora. Here Montorsi et al use multiplexed single cell omics to describe double negative type 2 B cells and DNASE1L3-expressing dendritic cells that interact and associate with microbiota on the human gut antigenic front line.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Excessive activity of matrix metalloproteinases (MMPs) occurs in many diseases; however, the systemic administration of MMP inhibitors can cause undesirable, off-target effects and hence, clinical translation has been hampered. Now, injectable polysaccharide-based hydrogels are shown to enable the localized delivery of an inhibitor of MMP following the hydrogels’ degradation in response to MMP activity. This targeted approach shows efficacy in a myocardial infarction model in large animals.

Remote tumours cause liver dysfunction by releasing extracellular vesicles and particles containing palmitic acid, which induces TNF signalling in Kupffer cells, resulting in inflammation, fatty deposits and metabolic dysregulation, thus both reducing the efficacy and increasing the toxicity of chemotherapies.

Tissue resident macrophages are intricately involved in homeostatic processes but also in tissue repair. Here Lee and colleagues show dermis-resident macrophages are a source of thymic stromal lymphopoietin and CCL24, which act on type 2 innate lymphoid cells and eosinophils respectively, to maintain their M2 properties and promote non-healing cutaneous leishmaniasis.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

A first-in-human phase I clinical trial demonstrates the feasibility and safety of non-viral precision genome-engineering of a personalized adoptive cell transfer anticancer therapeutic.

The validation and analysis of X-ray crystallographic data is essential for reproducibility and the development of crystallographic methods. Here, the authors describe a repository for crystallographic datasets and demonstrate some of the ways it could serve the crystallographic community.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

The effects of different choices on preprocessing pipelines for functional connectomics remain unclear. Here, the authors systematically evaluate a multitude of pipelines on resting-state fMRI, revealing a number of optimal pipelines for functional brain network analysis.

The signaling-specific inhibitor AEF0117 selectively inhibits CB₁ activation by THC and reduces self-administration and subjective effects of cannabis in clinical trials, making it a potential treatment for cannabis use disorder.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

This large integrated analysis of the KRAS^G12C inhibitor sotorasib clinical efficacy biomarkers from the phase 2 CodeBreaK 100 and phase 3 CodeBreaK 200 trials shows that low expression of TTF-1 and high expression of NRF2 determine anti-tumor efficacy of sotorasib in non–small-cell lung cancer.

Melanoma patients harbouring BRAF^V600E mutation generally develop resistance to targeted therapy. In this study, the authors demonstrate that SREBP-1-mediated induction of lipid biosynthesis contributes to therapy resistance in BRAF mutant melanoma.

The authors developed a small molecule targeting the circadian regulator BMAL1, enabling dose-dependent modulation of gene expression for circadian-controlled genes and downregulation of inflammatory pathways in macrophages.

Increasing excitability in the peri-infarct area enhances motor recovery after stroke. Here the authors show that expressing CREB, a transcription factor known for its role in synaptic plasticity, or increasing activity of CREB-expressing cells near the stroke site improves recovery in an effect that is strong enough that it can be used to turn on and off motor recovery after stroke.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Spontaneous parthenogenesis in sunflower has been used to develop a scalable doubled haploid breeding system.

Resorption of myocardial scar and subsequent regeneration may be influenced by the extent of irreversible pyridinoline and deoxypyridinoline collagen cross-links that develop in the scar. Hydroxylation of lysine in collagen may regulate this process.

Venous tumour thrombus can occur within renal cell carcinoma, and can require complex additional surgery and treatment. Here, the authors analyse multiparametric data from patients treated with axitinib and develop a machine learning model to predict neoadjuvant treatment response.

The imaging of tumour-draining lymph nodes is important for cancer diagnosis and therapy. Here, Thorek et al. report a nanoparticle that allows for the combined imaging of deep-tissue lymph nodes by positron emission tomography and magnetic resonance imaging in cancer-bearing mice.

Human memory and marginal zone B cells share some features including CD27 expression and somatic hypermutation, but their lineage relationship is still unclear. Here the authors use mass cytometry and sequential clustering methods to show that, despite their shared features, memory and marginal zone B cells represent distinct lineage choices.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.