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Urinary albumin-to-creatinine ratio (UCAR) is associated with various clinical outcomes such as kidney disease and cardiovascular disease. Here, the authors report genome-wide meta-analysis in over 500,000 individuals and find 68 UACR loci, followed by statistical fine-mapping, gene prioritization and experimental validation in flies.

Bacterial genomes still contain many hidden and uncharacterized genes. Using complementary Ribo-seq approaches, Froschauer, Svensson et al. here annotate start and stop codons of Campylobacter jejuni, reporting a high-resolution translatome and identifying several novel small ORFs in this foodborne pathogen.

Sarah Robey examines two books that together trace the birth and evolution of the nuclear age.

Aging-related Meibomian gland shrinkage is associated with dry eye disease. Here, the authors identify Meibomian gland stem cell populations and identify regulatory pathways altered in aging, suggesting new therapeutic targets for Meibomian gland dysfunction.

The authors present a characterization of complex X-linked lncRNA loci with sex- and allele-specific epigenetic signatures that serve as a platform for the largest chromatin structures in mammals, thereby elucidating diverse phenotypes and combinatorial effects on autosomes.

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.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Experiments show that olivine is transparent at high pressure and temperature, with radiative heat transport representing 40% of olivine’s thermal conductivity. Heat radiation enhances slab’s heating rate and affects subduction dynamics.

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.

Reduced central corneal thickness (CCT) is observed in common eye diseases as well as in rare Mendelian disorders. Here, in a cross-ancestry GWAS, the authors identify 19 novel genetic loci associated with CCT, a subset of which is involved in rare corneal or connective tissue disorders.

When applied in large scale to electronic medical record data, the PheWAS approach replicates GWAS associations and reveals potentially new pleiotropic associations.

Anti-TRBC1 antibody–drug conjugates may offer a more potent T cell cancer therapy by bypassing the fratricide that may be limiting the efficacy of anti-TRBC1 CAR T cells in the clinical trial for patients with T cell cancers.

A paper reports the development of a universal tool for studying cellular interactions in biological systems, and demonstrates its coupling with single-cell transcriptomics methods to provide insights into the biology of the interactions.

Drug and target discovery for advanced liver disease are hampered by a lack of suitable models for clinical translation. Here the authors present a human liver cell-based system modeling a clinical prognostic signature allowing to propose nizatidine for treatment of advanced liver fibrosis and hepatocellular carcinoma prevention.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

Steve Brown and colleagues report an analysis of 20 phenotyping tests, including 413 data parameters, across 449 mutant mouse alleles. They identify widespread pleiotropy and assign putative functions to genes that lacked previous phenotypic annotation.

Rebound virus in the cerebrospinal fluid of a human cohort is a possible HIV-1 reservoir.

Hair follicle stem cells have increased resistance to DNA damage-induced cell death. This is due to higher expression of Bcl2 and to a faster non-homologous end-joining (NHEJ) DNA repair activity, which attenuates p53 activation.

Thomas Sander and colleagues identify 15q13.3 microdeletions in 1% of individuals with idiopathic generalized epilepsy (IGE). The majority of these individuals do not show intellectual disability, schizophrenia or other neuropsychiatric phenotypes, thus extending the phenotypic spectrum associated with 15q13.3 microdeletions.

Scolaro et al. identify the enzyme cytidine deaminase (CDA) as upregulated in immunotherapy-resistant tumors and find it contributes to the UDP pool, which in turn modulates tumor-associated macrophages to instruct an immune-evasive TME.

Here, Jacobsen et al show that Varicella zoster virus glycoprotein C binds interferon gamma and induces biased signalling through its receptor, leading to higher expression of adhesion molecules, more T cell adhesion and viral spread from epithelial cells.

Artificial compartments have been expressed in prokaryotes and yeast, but similar capabilities have been missing for mammalian cell engineering. Here the authors use bacterial encapsulins to engineer genetically controlled multifunctional orthogonal compartments in mammalian cells.

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology.

This Review provides an overview of the pathogenesis, classification and diagnosis of and treatment strategies for adult and paediatric rheumatology patients with uveitis. The authors highlight the importance of collaborations between ophthalmologists and rheumatologists to provide optimal treatment of uveitis, improve patient care and enhance future research.

The regulatory role of calcitonin in bone homeostasis is well studied, yet its molecular activity is poorly understood. The authors show that calcitonin regulates bone cells function by inhibiting the osteoclast secretion of sphingosine 1-phosphate, a lipid mediator of osteoclast–osteoblast crosstalk.

Identification and characterization, using a comprehensive embryonic phenotyping pipeline, of 410 lethal alleles during the generation of the first 1,751 of 5,000 unique gene knockouts produced by the International Mouse Phenotyping Consortium.

The genome of the gibbon, a tree-dwelling ape from Asia positioned between Old World monkeys and the great apes, is presented, providing insights into the evolutionary history of gibbon species and their accelerated karyotypes, as well as evidence for selection of genes such as those for forelimb development and connective tissue that may be important for locomotion through trees.

Ric-8A is guanine nucleotide exchange factor (GEF) that also acts as a folding chaperone for its Gα subunit. Here, the authors present the structure of Ric-8A bound to nucleotide-free Gαi1, revealing the mechanism by which Ric-8A exerts both GEF and chaperone activity.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

The full extent of the genetic basis for hearing impairment is unknown. Here, as part of the International Mouse Phenotyping Consortium, the authors perform a hearing loss screen in 3006 mouse knockout strains and identify 52 new candidate genes for genetic hearing loss.

The lateral entorhinal cortex computes and transfers olfactory information from the olfactory bulb to the hippocampus and supports associative multimodal memories. Leitner et al. characterize the activity of odor-responsive cell types in this brain area and identify upstream and downstream brain areas to which olfactory information is conveyed.

Intermediate-depth earthquakes (30-300 km) occur in subducting oceanic slabs, but their generation mechanism remains enigmatic. Here, the authors show through high-pressure and dehydration experiments of antigorite that dehydration-driven stress transfer triggers intermediate-depth earthquakes.

Mature desmosomes are the main adhesive junctions in epithelia and cardiac muscle. Now new work shows that the desmosomal protein desmoplakin is also essential for the maturation of adherens junctions. Desmoplakin clamps down on the transient zippering courtship of the classical cadherins, promoting the maturation of puncta adherens junctions and cortical actin remodelling, steps that are essential for cell adhesion.