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A single-cell multiomic immune cell atlas from 235 Japanese, including patients with COVID-19 and healthy individuals, linked with host genetics including germline and somatic mutation, plasma proteomics and metagenomics data reveals that immune cells are dynamically regulated in a cell state-dependent manner.

Analysis of the blood DNA virome in patients with COVID-19 and autoimmune disease associates endogenous HHV-6 (eHHV-6) and high anellovirus load with increased disease risk, most notably for systemic lupus erythematosus. eHHV-6 carriers show a distinct immune response.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

A genome-wide association study highlights a variant in DOCK2, which is common in East Asian populations but rare in Europeans, as a host genetic risk factor for severe COVID-19.

In many sexually reproducing animals, the oocyte fuses with only one sperm during fertilization. Here, the authors show that C. elegans MARC-3, a membrane-associated RING-CH-type ubiquitin ligase, regulates polyspermy block after fertilization and maternal membrane protein degradation during the oocyte-to-embryo transition.

Small cell lung cancer presents high and multi-site metastatic potential. Here, the authors discover that FOXA2, regulated by ASCL1, promotes multi-site metastasis in small cell lung cancer by inducing a fetal neuroendocrine gene expression program.

Peripheral blood mononuclear cells from 73 Japanese patients with coronavirus disease 2019 (COVID-19) and 75 healthy controls were analyzed using single-cell transcriptomics. Combining these data with genotyping data highlights the interplay between host genetics and the immune response in modulating disease severity.

Tamagawa, Fujii et al. demonstrate that squamous differentiation in human pancreatic cancer can be attributed to TP63-mediated lineage conversion and epigenetic reprogramming that depends upon a hypoxic and Wnt-defective niche.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Inducible promoters that control gene expression in response to small molecules are essential in synthetic biology. Here, the authors describe a simple and reliable approach for constructing strongly inducible synthetic yeast promoters, which are validated for use in large-scale protein production.

Nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme for NAD synthesis, has been proposed as a potential target for cancer therapy. Here, the authors show synthetic lethality when combining NAMPT inhibition with Niacin restriction in neuroendocrine-type cancer.

Whether and how the non-lesional sensorimotor cortex contributes to the post-injury recovery are not fully understood. The authors, show that the interhemispheric pathway between the premotor cortices contributed to hand movements in early recovery after damage to the corticospinal tract in primates.

Proliferation of cancer cells leads to replication stress through incompletely understood mechanisms. Here, the authors show that the long noncoding RNA TUG1 resolves R-loops and reduces replication stress in cancer cells.

The structure of the Golgi and the localization of glycosylation enzymes remain largely elusive. Here, the authors use super-resolution microscopy to show that the Golgi is composed of small dynamic units which have rapidly moving zones of glycosylation enzymes.

Whole-exome sequencing of colon organoids derived from patients with ulcerative colitis identifies somatic mutations in components of the IL-17 signalling pathway, which may confer a growth advantage to cells under inflammatory conditions.

A close-up look at the action of space weathering on carbonaceous asteroids, provided by Ryugu’s returned samples, highlights its role on the dehydration of the first micrometre-thick layer of the surface, possibly hiding a water-rich interior. The depth of the 2.7 µm hydration band may be an indication of the level of space weathering withstood by a C-type asteroid.

Eukaryotic genetic switches are more complex than prokaryotic ones, complicating their design. Here the authors present a workflow for parallel screening, selection and evolution of yeast genetic switches.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

While measurement of an electron spin commonly destroys it, the quantum non-demolition measurement implemented here for an electron spin qubit in a semiconductor quantum dot preserves the measured spin and allows for exponential suppression of readout errors by repeated measurements.

Effective chemical catalysts can artificially control intracellular metabolism, however, driving catalysts in living cells remains challenging. Here, the authors develop Ca²⁺-responsive artificial allosteric redox catalysts that resist the redox imbalance induced by the reactive oxygen species generated by Ca²⁺-stimulated mitochondria.

Neuroendocrine neoplasms (NENs), which can develop in almost any organ and range from indolent neuroendocrine tumours (NETs) to rapidly progressive and fatal neuroendocrine carcinomas (NECs), have historically been approached in a siloed manner according to their specific tissue of origin. However, NETs and NECs across different sites of origin often share genomic and phenotypic characteristics. In this Review, the authors discuss both the clinical and biological commonalities as well as key organ-specific differences of NENs, with a focus on those of the gastrointestinal system and lung. Moreover, they advocate for a cross-cutting, tissue-agnostic approach to drug development for these rare tumours that might enable advances in one disease entity to accelerate research in others, ultimately improving patient care.

This paper reports the genome sequence of domesticated tomato, a major crop plant, and a draft sequence for its closest wild relative; comparative genomics reveal very little divergence between the two genomes but some important differences with the potato genome, another important food crop in the genus Solanum.

Craig Albertson et al. report a study of the genetic basis of scale shape variation in cichlids from Lake Malawi. They find 40 QTL for scale development, most of which are specific to distinct body locations, and a role for Fgf signaling in shaping cichlid scales.