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Neutralizing nanobodies (Nb) are of considerable interest as therapeutic agents for COVID-19 treatment. Here, the authors functionally and structurally characterize Nbs that bind with high affinity to the receptor binding domain of the SARS-CoV-2 spike protein and show that an engineered homotrimeric Nb prevents disease progression in a Syrian hamster model of COVID-19 when administered intranasally.

Ultrathin layers of liquid water confined in nanoporous membranes enable fast, selective, and stable separation of carbon dioxide from other gases.

Genomic studies of canine tumours have been done for individual cancer types or dog breeds. Here the authors analyse canine tumour genomics data across multiple breeds and cancer types, finding that mutational burden is associated with TP53 mutations and that Golden Retrievers are enriched for particular signatures.

Synthetic receptors are a powerful approach for engineering cell-based therapies that can sense and respond to their environment. Here cytokine receptor domains have been repurposed to develop engineered T cells that can sense and respond to cues associated with cancer or immune dysfunction.

Engineering mammalian cellular functions requires a toolkit of orthogonal and well-characterized genetic components. Here the authors develop COMET: an ensemble of transcription factors, promoters, and accompanying models for the design and construction of genetic programs.

Superior mechanical properties in natural composites are frequently achieved by the inclusion of locally orientated reinforcing particles. Here, the authors implement this design strategy synthetically by employing a 3D magnetic printing protocol to create programmable composite architectures.

In this work, the authors reveal that three non-ribosomal peptides targeting a common protein quality system differentially alter the Mycobacterium tuberculosis proteome, providing new insight into the molecular mechanisms behind their antimycobacterial activity.

ProDomino is a machine leaning-based method, trained on a semisynthetic domain insertion dataset, to guide the engineering of protein domain recombination.

Microplastics (MPs) represent an environmental hazard which must be resolved by efficient, cheap, and sustainable remediation technology. Here the authors use an engineered algae to capture MPs and treat wastewater, the captured algae-plastic mix is upcycled into a tougher bioplastic composite.

Geminin regulates DNA replication by binding CDT1 and preventing MCM helicase loading. Using a reconstituted system and structural modelling, the authors find geminin inhibits via steric clash with MCM, not by blocking the CDT1–MCM interface. Combined with CDK activity, it fully halts licensing.

NEIL2, a mammalian DNA repair enzyme, has been reported to suppress infection induced inflammation. Here, the authors characterize its role in modulating the severity of SARS-CoV-2 infection.

Here, the authors isolate a SARS-CoV-2 mutant that has developed decreased sensitivity to Paxlovid and remdesivir from an immunocompromised patient, show that drug resistance can be overcome by simultaneous treatment with both drugs in vitro, and demonstrate that the drug resistant virus can efficiently transmit in the hamster model.

The co-evolution of oxygenation of the Earth’s atmosphere and lithosphere is still poorly constrained. However, the oxidation state of manganese minerals reveals that the redox state of Earth’s crust responds to changes in atmospheric oxygen following a ~66 million-year time lag.

The variability in clinical outcomes of SARS-CoV-2 infection is partly due to deficiencies in production or response to type I interferons (IFN). Here, the authors describe a FIP200-dependent lysosomal degradation pathway, independent of canonical autophagy and type I IFN, that restricts SARS-CoV-2 replication, offering insights into critical COVID-19 pneumonia mechanisms.

Base-editing screens of primary T cells reveal genetic variants beneficial to immunotherapies.

Yelland et al. use yeast genetics and cryo-EM to show how 2′-O-methylation on a single rRNA base gates the assembly of the ribosome via regulating interaction with the essential GTPase Nog2.

An Fe^III/V redox mechanism in Li₄FeSbO₆ on delithiation without Fe^IV or oxygen formation with resistance to aging, high operating potential and low voltage hysteresis is demonstrated, with implications for Fe-based high-voltage applications.

After RNA release, Escherichia coli RNA polymerase (RNAP) stays on DNA in a post-termination complex (PTC). PTCs can initiate RNA synthesis but produce cytotoxic R-loops. RapA induces an RNAP conformational change, dissociating PTCs and controlling R-loop formation.

The combination of synthetic biology and materials engineering enabled the development of biosensors that produce electrical readouts and real-time detection capabilities.

Invasive brown treesnakes decimated the forest bird community on the island of Guam. Now, Rogers and colleagues document the indirect effects of the snake on trees, linking snake-initiated bird loss to reduced seed dispersal and plant recruitment on Guam compared to nearby uninvaded islands.

A study integrating single-cell RNA-sequencing and electrophysiology data shows that in mouse, the cellular repertoire of the thalamic reticular nucleus is characterized by a transcriptomic gradient defined at its extremes by mutually exclusive expression of Spp1 and Ecel1, providing insights into the organizational principles underlying the divergent functions of this brain region.

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).

Charge transport in DNA is often described by either tunnelling or hopping, but recent results suggest that coherence is maintained over several bases. Now it is shown that nearest-neighbour interactions play an important role in determining the electronic properties of DNA and that, by utilizing these effects, higher-conductance sequences can be designed.

Fc engineering of a capsule-specific antibody identifies Fc variants which augment effector function and promote neutrophil-dependent control of Mycobacterium tuberculosis.

CRISPR-Cas12a is a programmable endonuclease used for genetic engineering. Here, the authors use real-time single-molecule measurements to show that Cas12a unwinds the target DNA site in dynamic and reversible steps to test for matches with its guide RNA molecule.

Understanding principles that govern protein association with extracellular vesicles should expand their potential as a therapeutic modality. Here, the authors show that by localizing proteins to the plasma membrane and lipid rafts, a variety of proteins can be preferentially loaded into extracellular vesicles.

Ising anyons are a promising platform for topological quantum computation, but braiding alone is not universal. Here, authors show that extending to non-semi simple TQFTs introduces new anyon types that enable universal quantum computation with Ising anyons.

Combinatorial CRISPR screens can be utilized to identify genetic interactions and functional redundancies of multiple genes. Here, the authors benchmark ten digenic CRISPR technologies and identify novel Cas9 tracrRNA combinations that show superior performance.

Agrobacterium-mediated transformation of plants and fungi is enhanced by plasmid copy number variants.

Analysis of large-scale CRISPR screening data, combined with experiments in patient-derived tumour organoid models, identifies PELO as a potential therapeutic target in chromosomal 9p21.3-deleted cancers and microsatellite-unstable cancers harbouring specific mutations.

Optical pooled screening is enhanced by amplification of barcodes before in situ sequencing.

The application of genome-wide CRISPR–Cas9 screening coupled with a fluorescent reporter to interrogate the microRNA pathway reveals that continual transient phosphorylation of Argonaute 2 is required to maintain the global efficiency of microRNA-mediated repression.

Alternative algorithms exploiting advantages of multidimensional mass spectrometry in untargeted metabolomics are needed. Here, the authors develop and demonstrate PeakDecoder for confident and accurate metabolite profiling in 116 microbial sample runs and using a library built from 64 standards.

High-entropy alloys (HEAs) have interesting properties, but the synthesis of uniform HEAs is challenging. Here design principles are established for the synthesis of core–shell nanoparticles, which can be thermally annealed to produce uniform HEA nanoparticles in a predictable manner.

Designed split ferredoxins, fused to protein fragments that associate under certain conditions such as the presence of rapamycin, enable transcriptional and post-translational control over electron transfer in Escherichia coli cells and lysates.

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.

Mutation of the nuclear envelope protein, barrier-to-autointegration factor 1 (Banf1), has previously been associated with the development of ageing associated diseases in a human progeria syndrome. Here, the authors reveal the functional link between Banf1-regulated, PARP1-directed repair of oxidative lesions.

The dihydrofolate reductase inhibitor, fluorofolin, shows potent activity against Pseudomonas aeruginosa and selectively eliminates P. aeruginosa from mixed-species bacterial cultures.

The process of protein crystallization is poorly understood and difficult to program through the primary sequence. Here the authors develop a computational approach to designing three-dimensional protein crystals with prespecified lattice architectures with high accuracy.

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.

Nanoplasmonic structures that can detect trace analytes via surface-enhanced Raman spectroscopy typically require sophisticated nanofabrication techniques. Self-assembly of gold nanoparticles into close-packed arrays at liquid/liquid and liquid/air interfaces is now used for the detection of multi-analytes from aqueous, organic or air phases.

A diverse, multidisciplinary panel of 386 experts in COVID-19 response from 112 countries provides health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

Here the authors report the formation of toxic clumps of protein, similar to amyloid assemblies found in Alzheimer’s disease and suggest their possible role for some of the neurological symptoms of long-COVID.

Chromatophores in cephalopod skin are known for fast changes in coloration due to light-scattering pigment granules. Here, authors demonstrate structural coloration facilitated by reflectin in sheath cells and offer insights into the interplay between structural and pigmentary coloration elements.

Past experiences and future predictions both shape our decisions. Here, the authors trained participants in a foraging task in which reward rates varied systematically over time and find the dACC tracks both recent and past reward rates, leading to opposing effects on decisions about whether to stay or leave a reward environment.

A framework for studying and engineering gene regulatory DNA sequences, based on deep neural sequence-to-expression models trained on large-scale libraries of random DNA, provides insight into the evolution, evolvability and fitness landscapes of regulatory DNA.

When an extrasolar planet passes in front of its star (transits), its radius can be measured from the decrease in starlight and its orbital period from the time between transits. This study reports Kepler spacecraft observations of a single Sun-like star that reveal six transiting planets, five with orbital periods between 10 and 47 days plus a sixth one with a longer period. The five inner planets are among the smallest for which mass and size have both been measured, and these measurements imply substantial envelopes of light gases.