Search

Patients with myelodysplastic syndromes (MDS) have limited therapeutic options. Here the authors show that functionally impaired NK cells contribute to immune escape of pre-malignant clones in early stage MDS and that NK adoptive cell therapy can be considered to prevent or delay the development of MDS.

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.

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.

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.

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.

Authors present results from a national surveillance in Japan that found MRSA strains causing bloodstream infections are predominantly from three clonal lineages. They also identified the emergence of highest 30-day-mortality MRSA clone ST764-SCCmecII and traced its evolutionary path.

Analysis of whole-genome sequencing data from hematopoietic stem and progenitor cells taken from patients with myeloma shows how treatment shapes clonal architecture and sheds light on the evolution of treatment-related myeloid neoplasms.

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.

A newly identified bacterial strain (YB328) isolated from the faeces of patients who responded to immune checkpoint blockade therapies can promote antitumour immunity through the activation of tumour-specific CD8⁺ T cells.

Resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) is prevalent. Here the authors establish a biobank of patient-derived EGFR-mutant lung cancer organoids and identify a subgroup of EGFR-TKI-resistant lung adenocarcinoma organoids, which exhibit a basal-shift phenotype and vulnerability to CDK4/6 inhibitors.

Mutational signature analysis of blood cells isolated from 23 chemotherapy-exposed samples and 9 nonexposed controls characterizes the effects of various drugs on mutational burden, signature exposure and cell types.

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.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

Long-range spin transport is essential for spintronics applications, but so far has only been achieved in magnets below their Curie temperature. Here, the authors report on efficient spin transport in paramagnetic insulator Gd₃Ga₅O₁₂ exposed to a moderate magnetic field exhibiting a spin diffusion length of 1.8 μm.

Myeloid malignancies vary significantly in their clinical outcomes and their genetic background. Here, the authors develop a network-based clustering method to predict subgroups of malignancies across disease subtypes.

Post-translational modifications, such as glycosylation and sialylation, are thought to confer disease modifying effects on autoimmune-associated antibodies, including anti-citrullinated protein antibodies in rheumatoid arthritis. Here the authors show that sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis in mice.

Yukinori Okada, Michiaki Kubo and colleagues report the construction of a new HLA imputation reference panel for the Japanese population. They apply this resource to analyze the association of the HLA region with Graves' disease and find that variants in multiple class I and class II HLA genes contribute independently to disease risk.

Koichi Matsuda and colleagues report a genome-wide association study for hepatitis C virus–induced hepatocellular carcinoma. They identify a susceptibility locus at MICA in individuals of Japanese ancestry.

Resistance to menin inhibitors often occurs in the initially sensitive MLL-rearranged (MLLr) leukemias. Here authors discover that inhibition of guanine nucleotide biosynthesis leads to myeloid differentiation and sensitization to menin inhibitors in leukemia stem cells of MLLr leukemia.

The Notch signalling pathway has important roles in embryonic development. Here the authors show that an evolutionarily conserved gene, mab21-l3, is inhibited by Notch signalling and regulates specification of developing multiciliate cells and ion-transporting ionocytes in frog embryos.

Sato and colleagues present a biobank of patient-derived SCLC organoids, conducting a comprehensive genome and transcriptome profiling that reveals the existence of NE and non-NE subtypes with distinct molecular dependencies.

The biosynthesis of goadvionins—hybrid lipopeptide antibiotics—is not fully understood. An unusual acyltransferase, GdvG, has now been identified and shown to catalyse a condensation reaction between an acyl-carrier-protein-tethered very-long-chain fatty acid and an eight-residue ribosomally synthesized and post-translationally modified peptide. The position of functional groups in the very-long acyl chain have been determined by tandem mass spectrometry.

Genome-wide analysis in 212,453 Japanese individuals identifies loci associated with 42 diseases. Comparative analysis with European populations identifies East Asian–specific associations.

Using more than 100 independent iPSC lines derived from patients with Alzheimer’s disease, the authors discovered loci associated with the neuronal production of amyloid β and confirmed their influence using RNA interference.

Rmg8 and Rmg7, genes for resistance to wheat blast, proved to be a homoeologue and an allele of Pm4, a gene for resistance to powdery mildew. Their functional homologues were also found in Aegilops spp., suggesting that their origin dates back to the time before differentiation of Triticum and Aegilops.

Retrons are bacterial genetic elements that, in combination with toxic effector proteins, can serve as antiphage defense systems. Here, the authors show that some phages can evade retrons and other defense systems by expressing specific tRNAs.

EGFR mutations in lung adenocarcinoma are more frequent in East Asians compared to other populations. Here, the authors carry out a genome-wide association study in EGFRmutant cancers and identify loci that are associated with risk of developing this molecular subtype of cancer.

Environmental exposures shape patterns of selection for mutations in clonal hematopoiesis. Cancer therapies promote the growth of clones with mutations that are strongly enriched in treatment-related myeloid neoplasms.

Pesticides must be evaluated for their exposure to honey bees across diverse landscapes. This study reveals that both agricultural lands and urban areas resulted in higher pesticide exposure of bees, whereas forests were considered pesticide mitigation areas.