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Several unusual features have been reported for bacteria of the phylum Planctomycetes, such as cytosolic compartmentalization and an endocytosis-like process. Here, Boedekeret al. provide evidence supporting a Gram-negative cell plan and the absence of endocytosis-like processes in these organisms.

The vascular stem cell niche regulates the proliferation and differentiation of neural stem cells (NSCs) in the adult subventricular zone. Here the authors identify EGFL7 as a neurovascular regulator of NSCsin vivo; EGFL7-knockout mice show reduced neurogenesis, and exhibit impaired olfactory perception and behaviour.

NAD(P)H-dependent enzymes are generally assumed to use a one-step hydride transfer mechanism owing to a lack of evidence for alternative proposals. Spectrophotometric and NMR data now call this assumption into question, defining a covalent substrate-cofactor species that is catalytically competent in three unrelated enzymes.

High binding affinities are usually obtained when ligands are rigidified. Here the authors present flexible peptides binding to Armadillo repeat proteins with femtomolar affinity. They demonstrate that the bound state is characterized by residual dynamics limiting entropic losses upon binding.

Manipulating the interactions of cells with their environment is usually done with cells in vitro, which does not reflect the complex in vivosystem. Here the authors demonstrate micromanipulation of microparticles, bacteria and immune cells within live zebrafish using optical tweezers.

Jayavelu, Samaha et al., apply machine learning models on hospital admission data, including antibody titers and viral load, to identify patients at high risk for Long COVID. Low antibody levels, high viral loads, chronic diseases, and female sex are key predictors, supporting early, targeted interventions.

The production of ribosomes is a precisely orchestrated energy consuming cellular process of highest priority. Here, the authors use cryo-EM to show that bacterial ribosomal subunits, self-assembled from their purified RNA and protein components, mature along parallel pathways.

Nature uses complex supramolecular reaction networks to regulate structure formation. Now, by creating a photolytic reaction cascade with competing redox pathways, different hierarchical assemblies can be tailored based on a single molecular identity.

Alveolar rhabdomyosarcoma is a clinically challenging disease due to the lack of druggable targets. Here the authors show preclinical evidence for ATR inhibitors as a therapeutic option for alveolar rhabdomyosarcoma.

Global ocean microbiome survey reveals the bacterial family ‘Candidatus Eudoremicrobiaceae’, which includes some of the most biosynthetically diverse microorganisms in the ocean environment.

Precise and reliable gene delivery remains technically challenging. Here, the authors show that rationally designed frameshifting splicing can be used to express genes only in targeted cell types, with the potential to enhance the specificity AAV gene delivery.

Stacked elastomeric arrays containing plasmonic nanoparticles show efficient chiral responses that can be fully controlled by mechanical compression and stack rotation. These simple layered materials may be useful modulators for photonic applications.

Tobacco smoking and cold exposure are environmental modulators of human energy metabolism suppressing appetite and increasing energy expenditure, respectively. Here, the authors develop a novel pharmacological strategy in which they simultaneously mimic the metabolic benefits of both phenomena through small-molecule combination therapy, and show that this treatment improves metabolic health of obese mice.

Drug and target discovery for advanced liver disease are hampered by a lack of suitable models for clinical translation. Here the authors present a human liver cell-based system modeling a clinical prognostic signature allowing to propose nizatidine for treatment of advanced liver fibrosis and hepatocellular carcinoma prevention.

Rapid extracellular antigen profiling of a cohort of 194 individuals infected with SARS-CoV-2 uncovers diverse autoantibody responses that affect COVID-19 disease severity, progression and clinical and immunological characteristics.

Hyper-activated STAT5B and its disease-causing variants are of interest as cancer drug targets. Here the authors combine cell based studies, X-ray crystallography, biophysical experiments and MD simulations to structurally and functionally characterize the STAT5B^N642H mutant found in aggressive T-cell leukemia and lymphomas and find that it has an increased affinity for self-dimerization.

Despite imaging advances, diagnosis of infective endocarditis is not simple, and uncertainty about whether a surgical or nonsurgical approach is best and the timing of intervention can hamper therapy. In this Review, Saptarsi Haldar and Patrick O'Gara discuss the major features of diagnosis and therapy and make recommendations based on the available data.

Toll-like receptor 4 (TLR4) is a key pattern recognition receptor that primarily responds to ligation of bacterial lipopolysaccharide. Here the authors suggest the intramembrane protease RHBDL4 as a regulator of TLR4 signaling.

de Jonckheere, Kollotzek, et al. report a quantitative proteomic and lipidomic map of different stages of megakaryopoiesis and find an anionic lipid membrane remodeling and concomitant relocalization of the CKIP-1/CK2α complex to the plasma membrane of maturing megakaryocytes, which appear to be essential for sufficient platelet biogenesis.

Insulin secretion adapts to metabolic needs, but how this happens over the short term is not clear. Here the authors show this involves upregulation of beta-cell exocytosis and requires the SUMO-protease SENP1, which responds to redox state in a zinc-dependent manner.

Anaplastic lymphoma kinase (ALK) inhibitors are currently being considered in neuroblastoma (NB), but its acquired resistance is reported in non-small cell lung cancers. Here, the authors have found PIM1 overexpression decreases sensitivity to ALK inhibitors in NB and combined ALK and PIM1 inhibition enhances anti-tumour efficacy in vitro and in PDX models.

Pairing an odor conditioned stimulus (CS) with an unconditioned stimulus (US) induces memory formation. Vetere et al. replace the real CS and US with direct optogenetic stimulation of the brain and create a fully artificial odor memory in mice.

This chromosome-engineering protocol generates heritable chromosomal rearrangements in A. thaliana; by combining SaCas9 with an egg-cell-specific promoter to facilitate heritable mutations, chromosomal rearrangements can be made and homozygous lines can be established.

Type IV-A CRISPR-Cas systems diverge from the general CRISPR-Cas mechanism. To understand this system, the authors determine cryo-EM structures of two evolutionarily distinct type IV-A complexes (types IV-A1 and IV-A3) bound to cognate DNA-targets in the presence and absence of the type IV-A signature DinG effector helicase.

The lysosomal aspartic protease Cathepsin D (CTSD) is associated with breast cancer progression. Here the authors show that selective inactivation of CTSD in mammary epithelium delays tumor onset due to impaired mTORC1 signaling, but resumes malignant growth due to compensatory oncogenic pathways

Inhibiting thrombosis without inducing bleeding is a major challenge for anticoagulant agents. Here the authors describe a synthetic FXIIa inhibitor able to efficiently prevent thrombosis in mice and suppress coagulation in artificial lungs in rabbits without increasing the risk of bleeding.

Diagnosis and classification of peripheral neuropathy (PN) is facilitated by nerve conduction (NC) studies. Here, Bjornsdottir et al. find a low-frequency PRPH splice-donor variant that associates with NC amplitude and neurological assessment of recalled PRPH variant carriers reveals increased risk of a mild sensory-negative PN.

Computational docking to the the μ-opioid-receptor identifies PZM21, a novel selective biased agonist that generates substantial affective analgesia in mice without altering respiration or inducing drug reinforcement.

Eukaryotic RNA polymerase I (Pol I) is responsible for the transcription of rRNA genes. Here the authors determine the cryo-EM structure of the Pol I-Rrn3 complex, providing insight into how Rrn3 stabilizes the monomeric initiation competent Pol I to drive pre-initiation complex formation.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Geochemical zonation of the Tristan-Gough hotspot track has been demonstrated for the conjugate Rio Grande Rise on the South American Plate, suggesting geochemically distinct Tristan and Gough plumelets existed since the plume head/tail transition.

The role of circular RNAs (circRNAs) in modulating gene expression in cancer remains to be investigated. Here, the authors perform whole transcriptome sequencing in 104 primary neuroblastomas and reveal the involvement of MYCN in regulating circRNAs.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

Transcription termination correlates with the loss of Tyr1 phosphorylation from the C-terminal domain (CTD) of Rpb1, an event thought to be necessary for the recruitment of termination factors. The phosphatase Glc7, an integral component of the cleavage-and-polyadenylation factor (CPF), is now shown to dephosphorylate Tyr1 and to contribute to termination in vivo.

Medulloblastoma in children is a difficult cancer to treat and the immune response to this tumour is not fully understood. Here the authors characterise and validate T cell epitopes from these cancers using an immunopeptidomics approach, comparing different molecular subtypes.

The authors present an in-depth investigation of excited state dynamics and molecular mechanism of the voltage sensing in microbial rhodopsins. Using a combination of spectroscopic investigations and molecular dynamics simulations, the study proposes the voltage-modulated deprotonation of the chromophore as the key event in the voltage sensing. Thus, molecular constraints that may further improve the fluorescence quantum yield and the voltage sensitivity are presented.

The study of tumour dormancy is limited by suitable in vivo models. Here the authors show that mammary intraductal breast cancer (BC) xenografts model estrogen receptor α-positive (ER+) BC dormancy and rapid metastatic progression characteristic of triple-negative (TN) BC. The dormant disseminated ER+ BC cells display characteristics of epithelial-mesenchymal plasticity and forced expression of E-cadherin allows them to overcome dormancy.

Skokowa et al. reconstruct the fold of a granulopoietic cytokine, resulting in de novo, hyperstable, highly active proteins with therapeutic potential for treating several neutropenia disorders.

Glucose is a key energy source for many organisms, efficiently transported in bacteria by specific systems. Here, the authors reveal cryo-EM structures of the glucose transporter IICB from E. coli, providing insights into its mechanism and dynamics.

Reactions at the interface between mineral surfaces and flowing liquids are ubiquitous in nature. Here the authors explore, using surface-specific sum frequency generation spectroscopy and numeric calculations, how the liquid flow affects the charging and dissolution rates leading to flow-dependent charge gradients along the surface.

The mechanosensitive ion channel PIEZO1 senses shear stress induced by collagen-fibre sliding in tendons, regulates their stiffness and influences jumping performance.

Sprenger et al. find that cytosolic pyrimidine levels regulate the release of mitochondrial DNA and activation of cGAS–STING.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

An oncometabolite produced by tumor cells acts as a paracrine immunosuppressant dampening antitumor T cell responses in glioma.