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The reliance on natural plasmid replication mechanisms limits plasmid tunability, compatibility, and modularity. Here the authors refactor the natural pMB1 origin and create plasmids with customizable copy numbers with synthetic RNA regulators to implement independent copy control.

An alternative mating system, termed parasex, produces progeny with high levels of genotypic diversity and is able to fulfil the roles of meiosis when it is absent in the fungal pathobiont Candida albicans.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

Manipulation of spins in the solid state is a promising avenue for quantum information and field sensing applications. Bennett et al. demonstrate voltage tunability of single-spin states in a quantum dot as a step towards universal control of a single spin with a single electrical gate.

The discovery of a vast reservoir of primordial neutral hydrogen gas surrounding a young galaxy cluster just one billion years after the Big Bang offers new insight into how the first large cosmic structures assembled.

Models typically used to analyse climate–economy interactions have paradoxically ignored much of nature’s value. A new study explicitly addresses this issue and reveals feedback loops between nature and the climate system that make climate change more costly.

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).

Poly-ADP-ribose polymerase 1 (PARP1) plays key roles in DNA repair, transcription, and replication. Here, the authors used a single-molecule approach to reveal how PARP1 identifies DNA single-strand breaks in nucleosomes and how PARP1 activity regulates its DNA and chromatin binding kinetics.

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.

Synthetic microbial consortia are collections of strains which can segregate metabolic tasks for efficient use in biomaterials, biomanufacturing, and biotherapeutics. Here, the authors present a method to maintain and tune the ratio of two co-cultured bacterial strains via growth medium manipulation.

The existence of phosphatases specialized in regulating the axon initial segment (AIS) was unclear. Here, the authors show that a PP2A-B55 subunit is selectively enriched at the AIS and contributes to its local phospho-regulation.

The molecular composition of the axon initial segment (AIS) is not well defined. Here, the authors used a ratiometric immunoproximity labeling strategy on fixed wild-type rat neurons to identify the AIS proteome, including the scaffolding protein SCRIB.

For synthetic gene circuits to behave as designed, ligand-inducible promoters should display predictable ON/OFF characteristics. Here the authors design multi-input hybrid promoters to build transcriptional logic gates.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

The next generation of managers must be fit for a net-zero, nature-positive economy.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

This study presents a BRET biosensor that measures how anticancer drugs cooperatively engage PRMT5 complexes in cells, revealing how cellular metabolites such as SAM and MTA enhance drug action and enable precision therapies for MTAP-deleted tumors.

Microfluidic 'lab-on-a-chip' devices can be used to study the dynamics of gene networks in single cells. This Review discusses the various designs of these devices and the insights into modelling the complex dynamics of gene regulation that these new technologies have provided.

LIG3α forms a complex with XRCC1 during single strand break and base excision repair. Here, the authors show that LIG3α displays higher affinity for nicks than XRCC1 and binds with its N-terminal ZnF domain more avidly to an undamaged nucleosome.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

The human Shu complex promotes homologous recombination by regulating RAD51. Here the authors reveal that the Shu complex proteins, SWSAP1-SWS1, decorate the RAD51 filament on ssDNA and facilitate its strand exchange reaction by stimulating RPA diffusion on ssDNA. Lastly, that SWSAP1-SWS1 knockouts are Olaparib sensitive.

Viruses generally have compact genomes, resulting in many viral mRNAs with short 5’ untranslated regions. An antiviral complex exploits this feature of viral mRNAs to selectively inhibit viral protein synthesis and repress viral replication.

Profiling >200,000 live human microglia from 74 donors across neurological diseases reveals 12 subtypes of microglia that were validated in situ. Camptothecin is also identified as a compound reducing disease-enriched microglial subsets.

Protease containing ABC Transporters (PCAT) play a critical role in the translocation of polypeptides across membranes. Here, authors reveal the structural and energetic of the ATP-powered conformational cycle that enable this process.

The potential applications of bacterial cellulose (BC) have been limited by challenges in aligning nanofibrils at the macroscale and creating BC-based multifunctional nanosheets. Here, the authors report a strategy of using shear forces from fluid flow in a rotational culture device to biosynthesize strong BC sheets with aligned nanofibrils, and BC-based multifunctional hybrid nanosheets.

Genome-wide analyses identify common variants associated with 11 distinct neuropathology endophenotypes, providing insights into the mechanisms underlying the genetic risk of Alzheimer’s disease and related dementias.

Here the authors show that rehabilitating nuclear speckles, membraneless organelles involved in mRNA processing and gene regulation, can boost protein quality control and reduce toxic protein buildup, as well as ameliorate models of diseases like tauopathy and retinal degeneration.

Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.

The month’s sharpest science shots, selected by Nature’s photo team.

A comparison of alpha diversity (number of plant species) and dark diversity (species that are currently absent from a site despite being ecologically suitable) demonstrates the negative effects of regional-scale anthropogenic activity on plant diversity.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

Tools for gaining long-term genetic access to mu-opioid receptor (MOR) neural cell types are limited. Here, the authors develop a suite of adeno-associated viral tools allowing selective genetic access to MOR cell types, and showcase their use across species.

Mating of Candida albicans produces tetraploid products that return to the diploid state via a non-meiotic process known as concerted chromosome loss (CCL). Here, Anderson et al. show high recombination rates during CCL and identify factors that are essential for chromosome stability and recombination during CCL.

Hybrid metal halide semiconductors typically rely on chiral A-site ammonium cations for chiral induction in the lattice. Now it has been shown that chirality in low-dimensional achiral metal halide semiconductors can be induced by non-ammonium, non-A-site chiral molecules through remote stereocontrol of the inorganic framework.