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Host factors required for parechovirus entry are not well understood. Here, the authors identify MYADM as an essential host entry factor that directly binds human parechovirus 1 and that is required for PeV-A infection in cell lines and human gastrointestinal epithelial organoids.

We show that gain-of-function cancer mutations in the KBTBD4 E3 ligase promote neodegradation of substrates via a shape-complementarity-based mechanism, which converges with the mechanism of action of the UM171 molecular glue degrader and can be blocked by HDAC1/2 inhibitors.

The actin methyltransferase SETD3, by virtue of its ability to interact with the viral 2A protein and independently of its enzymatic activity, is necessary for RNA replication of several enteroviruses in cell culture and in vivo.

Systematic base-editing and computational screens identify specific cysteine residues on VPS35 in the retromer complex as key sensors that decrease mitochondrial translation in response to reactive oxygen species signals.

The ATPase CpaF from C. crescentus powers pilus dynamics in the bacterial Tad pilus system. Cryo-EM and light microscopy characterisation of CpaF uncovers a mechanism for how CpaF may drive both pilus extension and retraction.

UM171 promotes corepressor degradation by acting as a molecular glue to induce KBTBD4–HDAC1/2 interactions with the help of inositol hexakisphosphate.

Insecticide treated nets (ITNs) are an important part of malaria control in Africa and WHO targets aim for 80% coverage. This study estimates the spatio-temporal access and use of ITNs in Africa from 2000-2020, and shows that both metrics have improved over time but access remains below WHO targets.

Four distinct tuft cell states are identified by combining analysis of primary human intestinal resection material and organoids, and studying tuft cell development shows that they represent a damage-induced reserve intestinal stem cell pool in humans.

Mitophagy is an important quality control pathway. Here, the authors identify the mechanisms enabling the TBK1 adaptors NAP1 and SINTBAD to prevent hyperactivation of PINK1/Parkin mitophagy while promoting the pathway once set in motion.

Dai et al. show that the transcription factor ATFS-1 interferes with mitochondrial pre-initiation transcription complex assembly and promotes mitochondrial DNA repair, thereby reducing age-dependent mitochondrial DNA damage in Caenorhabditis elegans.

Insulin secretion adapts to metabolic needs, but how this happens over the short term is not clear. Here the authors show this involves upregulation of beta-cell exocytosis and requires the SUMO-protease SENP1, which responds to redox state in a zinc-dependent manner.

The bacterial Tight adherence (Tad) secretion system assembles surface pili that drive cell adherence and biofilm formation. Here, authors show the mechanism of assembly for the outer membrane secretin RcpA and how it recruits its pilotin TadD.

Dynamin-like proteins (DLPs) such as the mitofusins form homotypic and heterotypic oligomers that bridge and fuse opposing membranes. Here, Liu, Noel and Low present the crystal structure of a bacterial DLP heterotypic pair, providing insights into the mechanism behind long-range binding of opposing membranes.

Transancestral GWAS meta-analysis in 160,420 individuals identifies 139 loci associated with refractive error, including myopia. Newly identified genes implicate pathways involved in eye growth and light signaling cascades.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Bacterial type II secretion systems (T2SSs) translocate virulence factors, toxins and enzymes across the cell outer membrane. Here, Chernyatina and Low use negative stain and cryo-electron microscopy to reveal the core architecture of an assembled T2SS from the pathogen Klebsiella pneumoniae.

Programmable and reversible CRISPRi-based genetic circuits function in a variety of plants.

The molecular mechanisms that define the periodicity or rate of the circadian clock are not well understood. Here the authors use a multidisciplinary approach and identify a mechanism for period regulation that depends on the affinity of the core clock proteins for one another.

The ability to alter the genomes of living cells is key to understanding how genes influence the functions of organisms and will be critical to modify living systems for useful purposes. Here, the authors use computational design to discover Cas9 enzymes with increased activity.

Transcriptional activity in plants is controlled with a programmable gene circuit.

Patients with spinocerebellar ataxia type 1 express ataxin-1 with an extended polyglutamine (polyQ) tract that forms distinctive nuclear bodies. Here, the authors characterize the cellular pathways affected by polyQ-ataxin-1, showing that it disrupts multiple nuclear transport processes.

Gene correction in hematopoietic stem cells could be a powerful way to treat monogenic diseases of the blood and immune system. Here the authors develop a strategy using CRISPR-Cas9 and an aAdeno-Associated vVirus(AAV)-delivered IL2RG cDNA to correct X-linked sSevere Ccombined iImmunodeficiency (SCID-X1) with a high success rate.

Tungstate inhibits molybdenum-cofactor-dependent microbial respiratory pathways and shows potential as a selective treatment for microbial imbalances that occur during inflammation of the gastrointestinal tract.

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.

A subset of mitochondrial transcripts is not flanked by tRNAs and thus does not conform to the canonical mode of processing. Here, Clemente et al. demonstrate that phosphatase activity of ANGEL2 is required for correct processing of these transcripts.

Malaria on Bioko Island has been reduced substantially but many acquire malaria while traveling. Here, the authors use survey data, geostatistical and mathematical modeling to investigate malaria prevalence and mobility patterns and find that in some parts of the island a significant fraction of prevalence is attributable to malaria acquired while traveling.

Geospatial estimates of child growth failure in Africa provide a baseline for measuring progress and a precision public health platform to target interventions to those populations with the greatest need.

Human non-neuronal somatic cells can be converted into neurons; however, this is a low-efficiency process and the resulting neuronal subtypes are of low purity. Here the authors show that two small molecules enable NGN2 to efficiently convert human fibroblasts into pure cholinergic neurons.

Abnormal PR interval duration is associated with risk for atrial fibrillation and heart block. Here, van Setten et al. identify 44 PR interval loci in a genome-wide association study of over 92,000 individuals and find genetic overlap with QRS duration, heart rate and atrial fibrillation.

Here, a cross of Plasmodium vivax malaria parasites links a chloroquine resistance (CQR) phenotype to a 76 kb region of chromosome 1 and greater expression of pvcrt, an ortholog of the Plasmodium falciparum CQR transporter gene.

A genetic study identifies hundreds of loci associated with risk tolerance and risky behaviors, finds evidence of substantial shared genetic influences across these phenotypes, and implicates genes involved in neurotransmission.

A longitudinal analysis of viral expansion and clearance rates in 60 individuals sampled daily during acute infection reveals high inter-individual variation in infectious virus shedding, which may contribute to superspreading.

Despite the many recent developments in iron-catalysed cross-couplings, the mechanistic understanding of these reactions is lacking compared to the more studied palladium and nickel variants. Here, the authors find that during iron-catalysed Negishi reactions the diphosphine ligand predominately binds to the zinc—rather than the iron—centre.

Keith Ligon, Adam Resnick, Rameen Beroukhim and colleagues identify MYB-QKI fusions in angiocentric gliomas and show that these rearrangements promote tumorigenesis through activation of MYB by truncation, enhancer translocation driving aberrant MYB-QKI expression and hemizygous loss of QKI.

Stuart Macregor, Tien Wong and colleagues report meta-analyses that identify 16 new loci associated with central corneal thickness. They also identify two loci associated with risk of developing keratoconus, a common corneal ectasia.