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Stereotactic needle biopsies are currently performed for diagnosis only in glioblastoma; this study highlights the depth of information available through multi-omics analysis.

A set of neurons in the peri-locus coeruleus region controls arousal and avoidance states, providing an understanding of the neurobiological basis of arousal and exploratory behaviours.

Modulation of the myosin molecular motor has emerged as a potential therapeutic target for both heart disease and heart failure. Here, the authors use AI-based virtual high throughput screening to identify compounds that acts as a cardiac-specific myosin modulators.

Using a novel assay, Ellis et al. show that stem cell-derived neurons from individuals with autism carrying SHANK2 mutations are hyperconnected, have impaired activity-dependent dendrite extension, and have perturbed transcription of ASD gene modules.

Cox and colleagues develop PXS-5505, a first-in-class selective pan-lysyl oxidase inhibitor and show that it reduces chemotherapy-induced desmoplasia and stiffness, thereby improving chemotherapy response and survival in pancreatic cancer models.

Cell-free gene expression systems are an attractive platform for biomanufacturing and synthetic biology. Here the authors characterize native membrane vesicles in E. coli extracts for improved glycoengineering.

Type-1 innate lymphoid cells have been shown to drive intestinal epithelial proliferation and extracellular matrix remodelling through TGF-β1 secretion, which could exacerbate inflammatory bowel disease comorbidities such as cancer and fibrosis.

Cryo-electron-microscopy reconstructions of eukaryotic and archaeal ribosomes bound by ABCE1 and Pelota suggest a conserved mechanism for ribosome recycling.

The acid-sensing ion channel, ASIC1a, is known to play a role in synaptic transmission and plasticity. Here, the authors demonstrate a role for ASIC1a in regulating plasticity in the insular cortex and find that extinction of conditioned taste aversion memory is disrupted in the ASIC1a knockout mice.

Enzymes that form a metabolic pathway in which the product of one enzyme is the substrate for the next have now been shown to associate through a process of sequential, directed chemotactic movement. The extent of enzyme migration is proportional to the exposure time to the substrate gradient.

Compound MMV006833 inhibits ring-stage development of Plasmodium falciparum. Here, the authors show that it targets lipid transfer enzyme PfSTART1 and prevents PfSTART1 from expanding the vacuole membrane encasing the parasite after red blood cell invasion, thereby blocking parasite growth.

Loss of HLA-I gene expression in prostate cancer is associated with repressive chromatin states, which can be reversed by pharmacological DNMT and HDAC inhibition leading to increased activation of co-cultured tumor-specific CD8+ T-cells.

Dysregulation of protein degradation by the ubiquitin-proteasome system is a feature commonly associated with cancer. Here, the authors develop an orally available small molecule that inhibits CSN5, the proteolytic subunit of the COP9 signalosome, and blocks tumour growth in a xenograft model.

Isotopically labeled amino acids are useful in pharmacology and for medical imaging. In this protocol, C1-labeled α-amino acids are prepared via late-stage carboxylate exchange of unprotected α-amino acids with [*C]CO₂ where *C is ¹³C, ¹¹C or ¹⁴C.

The functional role of synaptotagmin-17 (syt-17) has remained unanswered. In this study, authors demonstrate that syt-17 exists in two distinct pools in hippocampal neurons (Golgi complex and early endosomes), where it served two completely independent functions: controlling neurite outgrowth and synaptic physiology

It has been hypothesized that the steroidal alkaloid dendrogenin A (DDA) is a natural metabolite. de Medina et al.show that DDA is produced in mammalian tissues from 5,6α-epoxy-cholesterol and histamine metabolism, and that the compound displays cell differentiation and anti-tumour activities.

Hepatic bone morphogenetic protein 8b expression is shown to be induced in NASH to drive wound healing responses and NASH progression by promoting inflammatory pathways in hepatic stellate cells and, more broadly, in the liver parenchyma.

Sodium channel Nav1.7 is essential for acute human pain but its role in chronic neuropathic pain is unclear. Minett and colleagues show that Nav1.7 expression specifically in sympathetic neurons, rather than sensory neurons, is required for the development of chronic neuropathic pain after injury.

Structural and biochemical studies reveal how the antimicrobial peptide Onc112 binds to bacterial ribosomes and show that Onc112 blocks and destabilizes the translation-initiation complex.

Transient overexpression of the transcription factors NKX2-1 and PAX8 in a murine cell model is shown to direct the differentiation of embryonic stem cells towards a thyroid follicular cell lineage; the resulting three-dimensional thyroid follicles created by subsequent thyrotropin treatment show hallmarks of thyroid function in vitro and rescue thyroid function in vivo when transplanted into athyroid mice, adding to our understanding of the molecular mechanisms underlying thyroid development.

When the antibiotic erythromycin is bound to the ribosomal exit tunnel, ErmBL peptide translation stalls and allows translation of the downstream methyltransferase ErmB. Here the authors combine cryo-EM and molecular dynamics simulations to identify the underlying basis for the inhibition of peptide bond formation that results in ribosome stalling.

High-resolution cryo-EM density maps are used to present the structures of Drosophila and human 80S ribosomes in complex with eEF2, E-site transfer RNA and Stm1-like proteins, and reveal the presence of two additional structural layers in the ribosomes of metazoan eukaryotes.

Marginal zone B (MZB) cells shuttle between the marginal zone and lymphoid follicle to capture and present peripheral blood antigens. Here the authors show that shear force, such as blood flow from the sinus around the follicle, is a directional cue that induces MZB migration on ICAM-1, and that S1P signaling inhibits this directional migration.

Application of the founder principle from population genetics to variant selection after recombineering allows the isolation of rare unselected recombinants.

Ribosome-associated quality control (RQC) pathways monitor and respond to stalling of the translating ribosome. Here the authors show that the ribosome associated RQC factor Hel2/ZNF598, an E3 ubiquitin ligase, generally interacts with mRNAs in the vicinity of stop codons.

Receptor-mediated signaling occurs at nanoscale. Understanding this requires nanopatterning and imaging techniques compatible at this scale. Rapid functionalization of Ti nanopatterns allows nanoscale visualization of early steps in cell signaling.

Advances in crystallographic methods, the rise of nuclear magnetic resonance, and the blossoming of global structural genomics initiatives have helped to fuel a renaissance in the development of methods for high-resolution protein structural biology. Michael Eisenstein reports.

More and more scientists now see advantages in automating some of their more repetitive or error-prone tasks. Michael Eisenstein takes a look at systems that are helping to bring robotics into the academic and clinical research laboratory.

The discovery of peptide substrates for enzymes with selective activities is a central goal in chemical biology. Here, the authors develop a hybrid method combining machine learning and experimental testing for fast optimization of peptides for specific, orthogononal functions.

Type II DNA topoisomerases (Top2s) direct the passage of one DNA duplex through another, which is important for resolving DNA entanglements. Here the authors combine X-ray crystallography and MD simulations and present the structure of the human Top2 DNA-gate in an open conformation and discuss mechanistic implications.

Analysis of antigen-specific B cells in lymph nodes of individuals vaccinated with BNT162b2 reveals lasting germinal centre responses, explaining the robust humoral immunity induced by SARS-CoV-2 mRNA-based vaccines.

Cells with a single short telomere and lacking telomerase mount a damage response consisting of recruitment of DNA damage checkpoint proteins, Cdc13, RPA and Rad52, many generations before senescence and in addition show tethering of the short telomere to the nuclear pore complex.

An extinction-risk assessment of reptiles shows that at least 21.1% of species are threatened by factors such as agriculture, logging, urban development and invasive species, and that efforts to protect birds, mammals and amphibians probably also benefit many reptiles.

Bacterial growth can be monitored by following the incorporation of fluorescent D-amino acids (FDAA) into the peptidoglycan cell walls. This protocol covers the synthesis of FDAAs and their use in monitoring spatiotemporal bacterial growth.