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Cas12a3 nucleases constitute a distinct clade of type V CRISPR–Cas bacterial immune systems that preferentially cleave the 3′ tails of tRNAs after recognition of target RNA to induce growth arrest and block phage dissemination.

Ryan et al. report a highly conserved mechanism by which arginine induces changes in hypervirulent Klebsiella pneumoniae bacterial cell surface capsule. K. pneumoniae arginine sensing is critical for full virulence potential.

New field measurements and modeling show meltwater refreezing in Greenland’s bare ice may reduce runoff to surrounding oceans, highlighting a process climate models can incorporate for improved predictions of future sea-level rise.

Mehl and colleagues present a protocol for selecting aminoacyl-tRNA synthetase (RS)/tRNA pairs from a publicly available MaPylRS active site mutant library for specific and efficient incorporation of noncanonical amino acids into proteins.

The surface types that comprise the dark zone of the Greenland Ice Sheet, an area of bare ice with low albedo, are unknown. Here, the authors use UAV imagery to show that, during the melt-season, biologically active surface impurities are responsible for spatial albedo patterns and the dark zone itself.

As synthetic biology expands, creating “drag-and-drop” regulatory tools that can achieve diverse regulatory outcomes are paramount. In this work, the Carbon Storage Regulatory Network of Escherichia coli is rewired to create synthetic post-transcriptional genetic circuits that leverage the native interactions and are composed to achieve complex bacterial computation.

In a trial involving 45 clinics and 15,596 visits, the use of an AI-based screening tool applied to ECG for opportunistic detection of advanced chronic liver disease led to a significant increase in new diagnoses compared to the standard workflow.

The width of rod bacteria depends on the balance between the activities of the Rod complex and aPBPs: the Rod complex reduces cell diameter, whereas aPBPs increase it.

Aromatic amino acids in proteins support ligand binding and protein stability. To parse the physiocochemical roles of aromatic interactions, here Galles, Infield and co-authors identify pyrrolysine-based aminoacyl-tRNA synthetases that enable the encoding of fluorinated phenylalanine amino acids.

Multi-subunit Cullin (CUL)-RING ligases (CRL) form the largest family of E3 ligases and are composed of a substrate receptor, a CUL, and a RING-box (RBX) protein. Here, the authors use cryo-EM and HDX-MS to characterise the ASB9 CUL-RING E3 ligase and present the structure of ASB9-ELOB/C bound to the substrate creatine kinase and the full-length CUL5 structure in complex with RBX2, and they propose a revised allosteric mechanism for CUL-E3 ligase function.

Mutations in an RNA polymerase fragment, frequently found in lab adaptation, cluster in two modules favoring growth or maintenance via loss of interactions. Combining mutations in both modules enhances both traits, promoting compensatory evolution.

An approach called TRACE enables mapping of millions of mutations in engineered cell populations.

Synechococcus elongatus PCC 7942 was modified to import and use monosaccharides, which allows it to grow on lignocellulosic lysate and produce 2,3-butanediol.

This study presents a splice-based selection method that enriches actively editing cells in base editing screening at target loci, reducing the number of unedited cells from over 40% to less than 10%.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

RNA targeting by the Sulfuricurvum type V single-effector nuclease SuCas12a2 drives abortive infection through non-specific cleavage of double-stranded DNA—after recognition of an RNA target through an activating protospacer-flanking sequence, SuCas12a2 efficiently degrades ssRNA, ssDNA and dsDNA.

Zhu et al. discover that in human brain there is widespread anatomic distribution of low-frequency somatic, mosaic L1 insertions, using deep whole-genome sequencing of neuronal and glial fractions and machine-learning analysis.

Levulinic acid (LA) is a value-added chemical easily obtained from biomass. The pathway enabling LA degradation in Pseudomonas putida requires five enzymes and can be engineered into Escherichia coli, which could enable further biotechnological applications.

Discovery of a near-complete colchicine biosynthetic pathway enables the engineered production of the tropolone-containing alkaloid N-formyldemecolcine from amino acid precursors in Nicotiana benthamiana.

We show how neuroactive alkaloids from clubmosses are biosynthesized, which reveals an unexpected role for carbonic anhydrase-like enzymes in alkaloid scaffold formation.

Shark antibodies (Variable New Antigen Receptors, VNARs) are the smallest naturally occurring antibody fragments. Here, the authors screen a VNAR phage display library against the SARS-CoV2 receptor binding domain (RBD) and identify VNARs that neutralize the SARSCoV-2 virus and discuss their mechanisms of viral neutralization.

Nano et al. introduce a pipeline to generate meta-atlases of the human brain from existing single-cell datasets and extract gene modules linked to cell fate specification. Perturbing these programs in human cortical chimeroids validated their roles in cell type specification.

Minichromosome maintenance protein 10 (MCM10) is critical for eukaryotic DNA replication. Here, by modelling MCM10 variants in human cell lines, the authors reveal a mechanism of MCM10-associated disease, finding that loss of MCM10 function constrains telomerase activity.

Synthetic biology offers the ability to explore new ways of manipulating gene expression and function. Here the authors demonstrate an electrogenetic device that allows control of transcription by an exogenous electrical signal.

Using a gain-of-function method, this work identified 14 plant proteins that can repress gene expression via diverse epigenetic pathways, including DNA methylation, histone modifications and interference of RNA polymerase II transcription.

Hundreds of RNAs and proteins are imaged in fixed tissue at subcellular resolution.

Evolutionary modelling and expert review are applied to integrate experimentally supported knowledge accumulated in the Gene Ontology knowledgebase to create a draft human gene ‘functionome’.

Dietary restriction can extend the life of various model organisms. Here, Xie et al. show that intermittent periods of fasting achieved through every-other-day feeding protect mice against neoplastic disease but do not broadly delay organismal aging in animals.

MAGE is a rapid in vivo method for introducing mutations into E. coli genomes. Libraries of synthetic ssDNA are used in iterative MAGE cycles to target multiple genomic sites. About five cycles can be carried out by one person in one day.

Analysis of microbiome data from feral swine, coyotes, domesticated cattle, and the surrounding environment reveals that wild animals harbor more abundant antibiotic-resistant organisms than livestock, and might act as a source of antibiotic-resistant microbes in outbreaks.

A large-scale GWAS provides insight on diabetes-dependent genetic effects on the glomerular filtration rate, a common metric to monitor kidney health in disease.