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Giacomo Cavalli, Frédéric Bantignies and colleagues report the establishment of stable and isogenic Drosophila lines carrying alternative epialleles, defined by different levels of H3K27me3. They show that environmental changes modulate the expressivity of the epialleles and that epilines can be reset to a naive state, thus indicating that the inheritance of this phenotypic variability is epigenetic.

The barren plateau problem represents one of the major bottlenecks for parametrized quantum circuits algorithms. Here, the authors study the known sources of BP using the lens of Lie algebraic theory, finding an expression of the variance of the loss function depending on the dynamical Lie algebra of the circuit.

Seventeen molecular clouds are identified in a Milky Way progenitor at z = 1.036, with higher masses, surface densities and supersonic turbulence than present-day analogues. Their properties reflect the hostile ambient interstellar conditions prevalent in distant galaxies and suggest they formed by fragmentation of a turbulent galactic gas disk.

Aquaporins have diverse roles in various homeostatic and physiological systems beyond their role in renal water handling. This Review describes the role of mammalian aquaporins in the transport of solutes other than water and their involvement in processes such as metabolism, cellular migration, cell adhesion, cell polarity and cell signalling.

How fMRI resting-state functional connectivity (rs-FC) in fronto-limbic circuits relates to neural activity is unclear. Here the authors show that rs-FC in these circuits is related to local field potential coherency in the alpha band.

The authors seek to understand the precise roles of microglia in the early human brain by coculturing brain organoids with primitive-like macrophages generated from the same human induced pluripotent stem cells (iMac).

Light sheet fluorescence microscopy (LSFM) is a technique that uses a thin sheet of light for illumination, allowing optical sectioning of the sample. In this Primer, Stelzer et al. outline the fundamental concepts behind LSFM, discuss the different experimental set-ups for light sheet microscopes and detail steps for processing LSFM images. The Primer also describes the range of applications for this technique across the biological sciences and concludes by discussing advances for enhancing imaging depth and resolution.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

Using resonance Raman spectroscopy and serial femtosecond X-ray crystallography, the authors show the heme a₃ iron and Cu_B in the resting oxidized form of Cytochrome c Oxidase are coordinated by a hydroxide ion and a water molecule, respectively.

The R138Q mutation in the Fragile X Mental Retardation 1 (FMR1) gene has been associated with Fragile X syndrome (FXS). Here, the authors present a Fmr1^R138Q Knock-In mouse model and show that R138Q mutation results in impaired long-term potentiation and socio-cognitive performance in these mice.

Skyrmions are spin textures which have integer topological charge. Typically they are very stable. Here, the authors observe the spontaneous creation and annihilation of skyrmions in regions of high exchange energy density, suggesting a limit to skyrmion stability.

Fibroblastic reticular cells (FRCs) provide structural support and soluble factors necessary for proper lymph node organization and function. Turley and colleagues use scRNA-seq to identify a unique Gremlin1-expressing FRC subset that is found in T cell zones. Grem1⁺ FRCs support the survival of resident cDCs and are necessary to promote T cell immunity.

In this work, Louros et al. uncover a rule book for interactions of amyloids with other proteins. This grammar was shown to promote cellular spreading of tau aggregates in cells, but can also be harvested to develop structure-based aggregation blockers.

Fragile X syndrome patients display intellectual disability and autism, caused by mutations in the RNA-binding protein fragile X mental retardation protein (FMRP). Here, the authors show that FMRP sumoylation is required for regulating spine density and maturation.

A phage-derived peptide selectively binds to the Frizzled 7 CRD resulting in disruption of the dimer interface and impairing Wnt/β-catenin stem signaling in intestinal organoids.

Triggered therapeutics are of interest but currently suffer from limited penetration depth of light sources. Here, the authors report on the development of a system, called radioswitch, that uses ionising irradiation to switch an azobenzene modified drug to an active form for deep tissue triggered therapeutic application.

An environmentally safe means of mosquito control is the application of Bacillus thuringiensis israelensis, which produces a cocktail of four naturally crystalline proteins exclusively toxic to mosquito. Here the authors report the atomic-resolution structures of Bti Cry11Aa and related Btj Cry11Ba solved de novo through Serial Femtosecond Crystallography on naturally-occurring nanocrystals.

The spatial organization of the genome within the nucleus impacts many processes. Here the authors combine oligo-based DNA FISH with single-molecule super-resolution microscopy to image single-copy genomic regions and, taking advantage of SNPs, distinguish allelic regions of homologous chromosomes.

Sumoylation plays key roles in neurotransmission but the mechanisms regulating this post-translational system in neurons remain unclear. Here the authors show that synaptic diffusion of the sole SUMO-conjugating enzyme Ubc9 is regulated by synaptic activity via an mGlu5R-dependent signalling pathway.

Phosphatidylinositol 5-phosphate (PtdIns5P) is known to induce actin depolymerisation and cell migration; however, the mechanisms by which this occurs remain unclear. Viaud et al.show that PtdIns5P regulates actin dynamics and invasiveness by recruiting and activating the Rac-GTPase exchange factor Tiam1.

Insights into the underlying neuronal circuitry of the Drosophila song production system are provided using song patterning of males near versus far from the female.

Using single-molecule super-resolution microscopy, researchers revealed that Tau controls the recycling pool of synaptic vesicles in hippocampal neurons by forming nanoscale biomolecular condensates that are dynamically regulated by neuronal activity.

Methicillin-resistant strains of Staphylococcus aureus appeared in European hedgehogs in the pre-antibiotic era as a co-evolutionary adaptation to antibiotic-producing dermatophytes and have spread within the local hedgehog populations and between hedgehogs and secondary hosts.

Current treatments for age-related neovascular macular degeneration (nAMD) suffer from limited efficacy. Here, Zhao et al. show that pharmacological inhibition or genetic deletion of the mineralocorticoid receptor (MR) limits choroidal neovascularisation in rodents, and show in a pilot clinical study that targeting the MR pathway may provide clinical benefits in nAMD patiens.

An analogy between wave propagation in hydrodynamics and in optics has yielded new insights into the mechanisms leading to the formation of giant rogue waves on the ocean. We review experimental progress and field measurements in this area.

RBM39 is an essential splicing factor for several cancer cells. Here, the authors described how RBM39 selects RNA at atomic level and autoregulates at the mRNA level by selecting the 3’-splice site of a poison exon.

Confocal optical microscopy is used to visualize—at high speed—solid (particle volume changes and phase-front velocities) and liquid electrolyte (concentration polarization gradients) dynamics inside operating batteries.

p53 isoform Δ133p53β is reported to promote intrinsic oncogenic functions. Here the authors show Δ133p53β is sequestered as aggregates in an inactive form, while association with interacting partners including p63 isoforms and the CCT chaperone complex promotes Δ133p53β activity, resulting in enhanced cancer cell migration and invasion.

Sarcopenia is the loss of muscle mass and strength associated with physical disability during ageing. Here, the authors analyse muscle biopsies from 119 patients with sarcopenia and age-matched controls of different ethnic groups and find transcriptional signatures indicating mitochondrial dysfunction, associated with reduced mitochondria numbers and lower NAD⁺ levels in older individuals with sarcopenia.

Multiple-quantum-well semiconductors can provide one of the largest known nonlinear material responses, which is, however, geometrically limited to light beams polarized perpendicular to the semiconductor layers; by coupling a plasmonic metasurface to the semiconductor heterostructure, this limitation can be lifted, opening a new path towards ultrathin planarized components with large nonlinear response.

Environmental metabarcoding of soil samples suggests that protists comprise the greatest eukaryotic diversity in tropical rainforests, and are dominated by phyla that parasitise arthropods and other animals.

Secretory vesicles must cross a dense cortical actin network to dock and fuse with the plasma membrane. Papadopulos et al. reveal that, in neurosecretory cells, relaxation of this network acts as a 'casting net', driving tethered vesicles towards the plasma membrane.

The cellular and molecular mechanisms underlying food texture detection are poorly understood. Here the authors show thatDrosophilacan discriminate food texture when feeding, and that this ability depends on NOMPC, a mechanosensory channel expressed in gustatory sensilla neurons.

The optimal disambiguation of similar sensory stimuli by neuronal networks is essential to adapt animal behavior. Gschwend and colleagues show that the olfactory bulb network acts as a pattern separator, increasing slight differences between highly related odors. Inhibitory interneuron activation causally improves pattern separation and facilitates odor discrimination learning.

Many organelles in the cell are not encapsulated in a membrane—they are liquid-like domains formed through phase separation. The liquid-like nature of such domains leads to adhesive interactions between the cytoskeleton filaments and organelles.

Local activity of the DNA methylation machinery remains poorly understood. Here, the authors present a theoretical and experimental framework to infer methylation and demethylation rates at genome scale in mouse embryonic stem cells, finding that maintenance methylation activity is reduced at transcription factor binding sites, while methylation turnover is elevated in transcribed gene bodies.

As more intersection points between platelets and the immune system are found, the role of platelets for vessel growth in the adult organism remains unclear. The authors demonstrate that platelets negatively modulate revascularization through CXCL4 secretion induced by activation C5aR1 on their surface.

Using cryo-electron microscopy, the authors describe the structure and function of a molecular motor powering both the Bacteroidetes type 9 protein secretion system and the associated gliding motility apparatus.

In a rat model of spinal cord injury, calpain-dependent cleavage of motoneuron sodium channels can be pharmacologically targeted to achieve long-lasting amelioration of spasticity.

Microsporidia contain a tiny mitochondrial remnant called a mitosome, but the function of this organelle is unknown. Microsporidian genomes encode several components of the mitochondrial iron–sulphur-cluster machinery. This paper describes the cloning, characterization and subcellular localization of several Fe–S-cluster components for two microsporidia. Although some components localize to the mitosome, others are cytosolic, raising questions about how their function is coordinated.