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Mitochondrial networks are carefully positioned to facilitate energy distribution within muscle cells. Here they show that energetic demands and conserved transcription factors regulate mitochondrial network organization and contractile phenotypes independently in Drosophila.

Galanos and colleagues observe p21 accumulation in proliferating cancer cells, and show that in cultured p53-null cells, p21 can cause genomic instability by perturbing replication licensing through inhibition of the CRL4-CDT ubiquitin ligase.

Infection or chronic inflammation is a risk factor for childhood B-cell precursor acute lymphoblastic leukemia. Here, the authors show that the DNA editing enzyme AID is expressed in infected B cells but using genetic mouse models show that it does not contribute to leukemia pathogenesis.

Integrative analysis in patients with diffuse large B-cell lymphoma uncovers that biallelic mutations on TMEM30A are associated with a favorable outcome and enhanced sensitivity to CD47 blockade.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

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.

Female naked mole rats are long lived and show little or no decline in fertility over their lifespan. Here Brieño-Enríquez et al., demonstrate that naked mole-rats establish an exceptionally large ovarian reserve and undergo postnatal oogenesis.

This study identified a new class of skeletal stem cells in the endosteal space of bone marrow, which are abundant in young bone marrow, express Fgfr3 with osteoblast-chondrocyte transitional identities and can turn into bone tumor-making cells.

Monitor lizards have a high aerobic capacity and distinctive cardiovascular physiology. Here the authors sequence the genome of the Komodo dragon and reveal genetic changes associated with its unique sensory, cardiovascular and muscular systems.

Disruption of the millipede gut microbiome using inhibitors and labelling it using 13 C stable isotope probing demonstrate that microbial fermentation and methanogenesis are non-essential for the millipede’s nutrition.

Susan Slager and colleagues report a meta-analysis of genome-wide association studies for chronic lymphocytic leukemia (CLL). They identify nine loci newly associated with CLL.

Jorge Ferrer and colleagues have mapped regulatory SNP variants associated in GWAS with type 2 diabetes risk and glycemic traits to large clusters of enhancer elements regulating the transcriptional identity of pancreatic β cells via a highly connected transcription factor network.

Cryo-EM structures of assembly intermediates of the proteasome 20S core particle show how the coordinated activity of chaperones orchestrates early steps in proteasome biogenesis.

Miguel Moreno-Pelayo and colleagues report mutations in the seed region of human miR-96 segregating with progressive hearing loss in two families. In an accompanying paper, Karen Steel and colleagues show that the mouse diminuendo mutant, which also shows progressive hearing loss, carries a similar mutation in the seed region of mouse miR-96.

Karen Steel and colleagues report that the mouse diminuendo mutant, which shows progressive hearing loss, carries a mutation in the seed region of mouse miR-96. In an accompanying paper, Miguel Moreno-Pelayo and colleagues report similar mutations in the seed region of human miR-96 segregating with progressive hearing loss in two families.

The p38α protein kinase is an attractive druggable target for many human diseases. Here, the authors show how the structural plasticity of p38α can be leveraged to selectively inhibit a subset of the functions regulated by this kinase and aid in the development of therapeutic compounds.

Christopher Hammond and colleagues report a genome-wide association study for myopia and refractive error, identifying a susceptibility locus at 15q25.

Roger Milne and colleagues conduct a genome-wide association study for estrogen receptor (ER)-negative breast cancer combined with BRCA1 mutation carriers in a large cohort. They identify ten new risk variants and find high genetic correlation between breast cancer risk for BRCA1 mutation carriers and risk of ER-negative breast cancer in the general population.

The authors show that TET2 is recruited to chromatin by the RNA-binding protein PSPC1. PSPC1 and TET2 contribute to ERV and ERV-associated gene regulation by both transcriptional repression via histone deacetylases and post-transcriptional destabilization of ERV RNAs through 5hmC modification.

Diffuse large B-cell lymphoma is an aggressive heterogeneous tumour type with poorly understood aetiology. Here, Green et al. show that transient expression of Bcl6in haematopoietic stem cells is sufficient to induce mature B-cell lymphoma, indicating that it acts as a ‘hit-and-run’ oncogene.

Epigenetic drugs are emerging as a powerful therapeutic option for cancer treatment. Here, the authors synthesized selective chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity and demonstrate their anti-tumour activity usingin vitro and in vivomodels of haematological neoplasia.

Peinado and colleagues show that small extracellular vesicles and secreted NGFR cargo induce lymphangiogenesis and develop the lymph node pre-metastatic niche to promote melanoma metastasis, which could be targeted pre-clinically with NGFR inhibition.

The success of CAR-T cells for treating acute myeloid leukaemia (AML) is hampered by toxicity to normal cells and low CAR-T cell persistence. Here, the authors show that the demethylating compound 5′-Azacitdine increases anti-CD123 CAR-T cell cytotoxicity against AML.

Here, Andrade et al. assess the memory B cell (MBC) and antibody response to Zika virus (ZIKV) in individuals with and without prior dengue virus (DENV) infection and find that ZIKV infection elicits a robust and specific MBC response that is only modestly affected by the number of prior DENV infections.

A meta-analysis of associations between human genetic variation and gut microbial structural variations shows that ABO genotype differentially affects the presence of Faecalibacterium prausnitzii strains containing GalNAc utilization pathway in the gut.

OPR3 is required to reduce the JA-Ile precursor OPDA. Analyses of JA levels in a loss-of-function opr3-3 mutant identified an OPR3-independent pathway for JA-Ile biosynthesis, based on OPDA conversion to 4,5-ddh-JA and reduction to JA by OPR2.

Cancer therapy using systemically administrated 4-1BB-targeting antibodies is often associated with severe toxicity due to the nonspecific activation of autoreactive T cells. Here, the authors have developed a trimeric antibody targeting both 4-1BB and EGFR, which activates T cells effectively and shows negligible cytotoxicity.

Georgia Chenevix-Trench and colleagues report meta-analyses of genome-wide association studies identifying six loci newly associated with epithelial ovarian cancer (EOC). They also test variants at the 12 known and 6 new EOC susceptibility loci for association in BRCA1 and BRCA2 mutation carriers.

Bacteria of the genus Streptomyces form cellular filaments (hyphae) in which sporadic peptidoglycan cell walls separate multinucleate compartments. Here, Yagüe et al. show that young hyphae are further compartmentalized by cross-membranes lacking detectable peptidoglycan.

Mutations in BRCA1 are associated with an increased risk of breast and ovarian cancer. Here the authors show that EDC4, a component of P-bodies, is a member of the BRCA1 complex with roles in stimulating end resection at breaks.

Prophylactic subcutaneous administration of anakinra, an IL-1 receptor inhibitor, reduced severe immune effector cell-associated neurotoxicity syndrome incidence in patients with relapsed or refractory large B-cell and mantle cell lymphoma treated with anti-CD19 chimeric antigen receptor (CAR) T cells.

Understanding regulation of genes associated to disease can reveal insights into disease mechanisms. Here, the authors perform an airway epithelial transcriptome-wide association analysis to elucidate genetic determinants of airway dysfunction in asthma, identifying genetic mechanisms of mucus pathobiology.

MicroRNAs are increasingly recognized as important regulators of experience-dependent plasticity in the brain. Cristino et al.show that miR-932 targets actin mRNA in trained honeybees, and that loss of miR-932 impairs long-term memory formation.

A newly discovered benzoxaborole prodrug AN15368 cures Trypanosoma cruzi infection (the cause of Chagas disease) in mice and in naturally infected non-human primates.