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Together with a companion paper, molecular details of immune responses in a pig-to-human xenotransplantation are identified through dense longitudinal multi-omics profiling of the xenograft and the host recipient, across the 61-day procedure.

CRISPR activators are powerful tools for controlling gene expression, but they suffer from inconsistent efficacy and high toxicity. Here, authors develop a high-throughput method to test thousands of CRISPR activators, revealing distinct principles of activator biology and delivering improved tools.

ENTRAP-seq systematically links protein sequence to transcriptional output in a native plant context.

Here, the authors show that two residues in FDX1 control both protein lipoylation and copper-induced cell death, suggesting these roles are interconnected. They also identify DLD as an upstream regulator that strengthens FDX1’s link to the lipoylation pathway.

Kathiriya et al. identify a cardiac progenitor lineage with expression of Tbx5 and anterior heart field-specific expression of Mef2c that bisects the intraventricular septum during development and show that alterations in this lineage lead to congenital heart defects in mice.

BRCA2 is a well-characterized central player in homologous recombination in which it functions as the RAD51 loader. Here the authors identify an N-terminal region of BRCA2 that binds DNA and promotes efficient DNA repair.

González-Delgado et al. developed retron-based editors termed multitrons, which can modify multiple sites on a single genome simultaneously. This technology is compatible with recombineering in prokaryotes and CRISPR editing in eukaryotes with applications in molecular recording, genome minimization and metabolic engineering.

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.

The STAR experiment at the Relativistic Heavy Ion Collider at Brookhaven National Laboratory demonstrates evidence of spin correlations in \(\Lambda \bar{\Lambda }\) hyperon pairs inherited from virtual spin-correlated strange quark–antiquark pairs during QCD confinement.

ARGONAUTE (AGO) is the core protein component of small RNA-guided silencing complexes. Free, but not RNA-bound, AGO turns over rapidly. The authors identify a structural AGO switch whose accessibility only in the free state confers rapid degradation.

A metabolic system of engineered biocatalysts using the noncanonical cofactor nicotinamide mononucleotide is established for biomanufacturing in cell-free systems and in Escherichia coli without interference from nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate.

Cell movements are achieved by the spatio-temporal coordination of local membrane protrusions and retractions. Here, the authors identify a mechanism by which these protrusion and retraction events are coupled and how this affects the directionality of cell movements.

Limited experimental platforms exist for assessing quantitative sequence-function relationships for multiple antibodies. Here, authors develop a deep-sequencing based technology called MAGMA-seq, that determines the quantitative properties of antibody libraries.

Staphylococcus epidermidis induces a potent, durable and specific antibody response that is conserved in humans and non-human primates, and which could be redirected against pathogens as a new form of topical vaccination.

Florfenicol amine hijacks intrinsic resistance in Mycobacterium abscessus, highlighting that antimicrobial resistance mechanisms can be harnessed for antibiotic activation.

Non-canonical amino acids can be incorporated into proteins through translation of orthogonal mRNAs. Now, automating the design of orthogonal mRNAs—which are more selectively and efficiently translated—in combination with compact orthogonal aminoacyl-tRNA synthetase/tRNA expression systems, enables the incorporation of four distinct non-canonical monomers via a 68-codon genetic code.

The ferroptosis suppressor protein FSP1 has a critical role in ferroptosis protection of tumours across multiple in vivo models and is linked to worse prognosis in human lung adenocarcinoma, suggesting its potential as a therapeutic target in lung cancer.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

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.

Wei et al. show that the primary function of m⁶A on the nuclear long noncoding RNA Xist, a master regulator of X inactivation, is to promote RNA degradation. Xist turnover is mediated by the nuclear exosome targeting complex and occurs independently of the nuclear m⁶A reader YTHDC1.

This study maps out the diversity and evolution of the bacterial order Caulobacterales, including the model organism C. crescentus, which reveals widespread phototrophy and illuminates the evolution of bacterial cell shapes and lifecycle complexity.

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.

Coagulase-negative staphylococci secrete natural products that prevent pathogen colonization. Here, the authors identify hominicin, a daptide bacteriocin produced by Staphylococcus hominis that has antimicrobial activity against a skin pathogen.

Ultrasound imaging with acoustic reporter genes has been limited to a single ‘tone’, restricting the types of experiments that can be achieved. This work introduces two acoustic reporter genes that enable multiplexed imaging in vitro and in mice.

The PAM specificity of SpCas9 can be altered with positive selection during directed evolution. Here the authors use simultaneous positive and negative selection to improve activity on NAG PAMs while reducing activity on NGG PAMs.

Precise and scalable regulation of gene expression in mammalian cells is challenging. Here, the authors created a highly tunable CRISPR-based synthetic transcription system for programmable control of mammalian gene expression and cellular activity.

Khan et al. report a non-catalytic function of the methyltransferase SETD2 in regulating nuclear morphology and genome integrity. The SETD2 amino terminus functions as a scaffold helping CDK1 associate with lamins during nuclear-envelope disassembly

Despite effective vaccines against SARS-CoV-2, therapeutic options such as anti-virals and neutralizing antibodies are critical in treating disease, especially given the breakthrough infections of emerging VOCs. Here, Peng et al. generate two potent monoclonal antibodies and a bispecific antibody with two antigenrecognition variable regions targeting SARS-CoV-2 spike, provide CryoEM structures and show in vitro and in vivo efficacy of a humanized antibody against wildtype virus and delta variant.

Fine-tuning the expression of biosynthetic pathway genes is crucial to improve microbial production titres. Here, the authors present GEMbLeR, an optimization strategy to balance the expression of multiple genes simultaneously over a wide range.

B. thuringiensis spores contain uncharacterized protein filaments that extend from the surface of the exosporium. Here, the authors show that these filaments feature conserved β-barrel neck domains and promote spore clustering through protein contacts and filament bundling, and reveal a mechanism for biofilm-like spore aggregation.

In glioma, malignant synapses hijack mechanisms of synaptic plasticity to increase glutamate-dependent currents in tumour cells and the formation of neuron–glioma synapses, thereby promoting tumour proliferation and progression.

A mutant-selective AKT inhibitor shows potential as a targeted therapy for breast cancer, enabling enhanced target engagement and avoiding the dose-limiting toxicity associated with pan-AKT inhibitors.

Metelev et al. use single-molecule tracking to study kinetics of translation directly in E. coli cells, and how it is affected by translation inhibitors and rRNA mutations. Their results support widespread 70S re-initiation on mRNAs.

The Toxoplasma gondii effector TgROP1 mimics host factors to bind VAPA/B, thereby establishing parasite–host ER contact sites.

Application of highly specific Cas9 variants can be restricted by the design of the guide RNA. Here the authors present DeepHF, a gRNA activity prediction tool built from genome-scale screens of 50,000 guides covering 20,000 genes.

Barcoding microbial ribosomal RNA creates a recording of gene transfer events without requiring translation.

To date, brain gene therapies require high vector doses. Here, authors devised an AAV capsid screen and found variants with unprecedented potency for transduction of deep brain and cortical neurons and human iPSC-neurons with cell tropism relevant for Huntington’s and Parkinson’s disease.

This protocol outlines an extracellular vesicle detection approach in which reagent-loaded liposomes fuse with extracellular vesicles directly in patient blood to sensitively detect RNA within the extracellular vesicles.

Protein complexes are essential for cell function. Here, authors show that paired ribosomes can help each other’s nascent chains fold correctly, enabling proper dimer assembly and preventing misfolding, using lamin as a model system.

Santos et al found that the ubiquitin ligase adaptor Fbxo42 is a critical regulator of terminal Unfolded Protein Response signaling through its control of Ataxin-2 granules containing Xbp1 mRNA.

Detection of geoneutrinos from ⁴⁰K decay in the Earth would yield a wealth of information on Earth’s bulk chemical composition and radiogenic heat. By exploiting the positron identification ability of LiquidO to reject backgrounds, charged-current neutrino capture reactions on ⁶³Cu is proposed as the ideal way to observe potassium geoneutrinos

Several different genetic strategies have been reported for the modification of polyketide synthases but the highly repetitive modular structure makes this difficult. Here the authors report on an adapted Cas9 reaction and Gibson assembly to edit a target region of the polyketide synthases gene in vitro.

Targeting FSP1 in lymph nodes has considerable potential for blocking melanoma progression.

“Out of one, many”. The authors show that, despite binding to a common network of genes, two transcription factors each have their own set of direct targets (also known as their ‘regulon’). Thus, out of one bound network, many regulons are possible.