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Despite large sequencing and data sharing efforts it often remains challenging to provide a genetic diagnosis for individuals with suspected Mendelian (single-gene) disorders. Here, the authors describe their experiences in identifying likely causal genetic variants in thousands of families and highlight the need to consider a wide range of challenges rather than a narrow focus on sequencing technologies.

In silico chemical prediction of a polyketide synthase gene cluster in the bacterium Gynuella sunshinyii has led to the discovery of a class of natural products called janustatins. The absolute configuration of the stereocentres in these compounds was determined by a combination of techniques including DFT calculations and 2D NMR experiments—and finally confirmed by total synthesis. Janustatins were found to cause delayed, synchronized cell death at subnanomolar concentrations.

Globally, new particle formation represents a major source of cloud condensation nuclei. Here, the authors present evidence of frequent occurrence of new particle formation in the upper part of remote marine boundary layer following cold front passages.

Prime editing uses Cas9 nickase fused to a reverse transcriptase to edit genetic information. Here, the authors prime edit primary adult stem cells in 3D organoid cultures to show functional correction of pathogenic mutations without genome-wide off-target effects.

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.

Constructing atomically flat surface in a single crystal ultrathin film is difficult owing to the coherent merging of trillions of clusters. Here the authors establish the initial growth mechanism of a single crystal Cu thin film with atomically flat surface using atomic sputtering epitaxy.

Wuidart et al. show that the mammary gland develops from embryonic multipotent progenitors that switch from multipotency to unipotency and express a unique gene signature. ΔNp63 promotes their basal fate and also reprograms adult luminal cells.

Various methods have been investigated to locally control atmospheric precipitation. In this study, field experiments show that laser-induced condensation is initiated when the relative humidity exceeds 70%, and that this effect is largely a result of photochemical HNO₃formation.

The acidic tumour microenvironment in melanoma drives immune evasion by cAMP in tumor-infiltrating monocytes. Here, the authors show that the release of an adenylate cyclase inhibitor from micelles restores antitumor immunity and, when combined with regulatory T cell depletion, leads to remission of established B16-F10-OVA tumors.

Pathogens secrete effectors to promote disease, symbionts might use them to confer benefits. Here, the authors identify 106 candidate effectors from the symbiont Serendipita indica, characterise their interactions, and reveal their roles in regulating phytohormone signalling and promoting growth.

Combining whole-transcriptome preindexing with standard droplet microfluidics, scifi-RNA-seq enables single-cell RNA-seq with massive throughput and built-in sample multiplexing.

Translation efficiency can be affected by mRNA stability and secondary RNA structures. Here the authors reveal that loss of DHX36 helicase activity leads to an accumulation of translationally inactive target mRNAs with G-rich structures in untranslated regions.

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

Azole antifungals are used to treat lung diseases caused by the pathogenic fungus Aspergillus fumigatus, but resistance is rising. Here, the authors generate a library of >100 protein kinase mutants of A. fumigatus, and show that loss of function or pharmacological inhibition of kinase YakA results in hypersensitivity to azoles and reduced pathogenicity.

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.

A study reports single-cell RNA-sequencing profiles for more than 1.6 million cell nuclei from 101 whole mouse embryos including 22 mutant and 4 wild-type genotypes, from one experiment.

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.

The re-epithelialization phase in skin wound repair involves epidermal cell migration into the wound, proliferation and differentiation. Here the authors describe a role for the transcription factor Tcf3 and its target, the secreted factor lipocalin2, in cell migration during wound healing in mice.

Magnetic reconnection acts as energy transfer process in plasma and induces processes like plasma heating, particle acceleration. Here the authors demonstrate the variation of magnetic reconnection between two flux tubes in the presence of external magnetic field.

A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.

Aerotaxis, chemotaxis towards oxygen, occurs in bacteria and likely in cancer cells. Here the authors find that confined cells from different tissues escape hypoxia by aerotaxis, a process independent of mitochondria and the HIF pathway, and dependent on EGF receptor interpretation of a ROS gradient in mammary cells.

Plasma turbulence is the main driver to deteriorate the performance of fusion power plants. This work presents an unprecedented comparison of plasma turbulence between experiment and simulation, proving that the gyrokinetic model GENE reached a high level of maturity to predict core turbulence.

Polymers commonly are semiconducting or insulating because of a sizable energy gap in the density of states around the Fermi level. Yet, the phase transition from topologically trivial to non-trivial in on-surface synthesized π-conjugated polymers, due to a change of resonant form, stabilizes narrow bandgaps and bears in-gap zero-energy edge states in the non-trivial phase.

The corneal endothelium is crucial for proper vision. Here, Ivarsdottir et al. perform genome-wide association studies for various corneal endothelial cell measurements and find that an intergenic variant near ANAPC1 explains 24% of the variance of endothelial cell density and associates with corneal hysteresis.

Innate lymphoid cells (ILC), including natural killer (NK) cells, are important innate immune regulators. Here the authors show that, in human infant intestines, CD103⁺Eomes⁺ NK cells are the predominant ILC population, but are replaced gradually by Eomes⁺ T cells, while NKp44⁺ NK cells persist in adult intestines.

While prime editing is a promising technique, some genomic sites remain difficult to edit. Here the authors present fluoPEER, fluorescent prime editing and enrichment reporter, to rank the efficiency of pegRNAs and prime editor variants.

During mammary gland involution, the organ undergoes extensive remodeling. Here, the authors explore the role of mammary gland adipose tissue (mgWAT) in this process and demonstrate that adipocyte hypertrophy and lipid trafficking underlie mgWAT expansion and epithelial regression.

FXR regulates the levels of ACE2 in tissues of the respiratory and gastrointestinal systems that are affected by COVID-19, and inhibiting FXR with ursodeoxycholic acid downregulates ACE2 and reduces susceptibility to SARS-CoV-2 infection.

Lithium metal penetration into solid-state electrolytes is a major drawback for developing all-solid-state batteries. Here, authors, via operando force microscopy, demonstrate that the trapping of electrons in garnet-type solid-state electrolyte grain boundaries is the origin of cell failure.