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Sensing of cytosolic RNA or DNA can lead to innate responses, but little information is available for RNA/DNA dual sensors. Here the authors find SAMD9 as a potential dual sensor linked to pro-inflammatory responses, interferon induction and resistance to viral infection, as evidenced by in vitro overexpression and in vivo knockout mouse data.

RNA-binding FBF proteins control germline stem cell differentiation. Here, the authors show that three long non-coding RNAs bind, condense, and thus inhibit FBFs to promote the transition of germline stem cells into meiosis.

Dietary n-6 PUFAs enhance adipose tissue expandability through the PPARγ–LPCAT3 membrane remodelling axis.

Genomic imprinting, manifested as monoallelic expression of genes according to parental origin, is linked to mammalian placentation and human diseases. The authors integrate single-nucleus transcriptomes and whole-genome variations to create a cell type-specific genomic imprinting atlas of pig placenta, highlighting the role of cell-cell communication in parent-of-origin effects on gene expression.

Myelosuppressive injuries lead to chronic MAPK activation and impair blood reconstitution. Here, the authors show that chronic activation endothelial MAPK impairs hematopoietic stem cell (HSC) function through NFkB signaling, and that post-myelosuppressive HSC defects can be reversed by administration of Stem Cell Growth Factor SCGFa.

This study reports the cryo-EM structures of AA amyloid fibrils from two patients with vascular AA amyloidosis. The findings imply that different disease variants in systemic amyloidosis are associated with different fibril structures.

Homologs are paired in Drosophila somatic cells from embryogenesis to adulthood. Using a computational approach for haplotype-resolved Hi-C, the authors reveal highly structured homolog pairing in Drosophila embryos during zygotic genome activation and demonstrate its application to mammalian embryos.

Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are a recently discovered class of biological lipids. This protocol describes their extraction from serum and tissue samples, followed by enrichment and analysis by LC-MS.

Here the authors investigate lipid nanodiscs as drug carriers for antitumour immunotherapy. They demonstrate that flexible lipid nanodiscs functionalized with STING-activating cyclic dinucleotides exhibit superior tumour penetration and tumour cell uptake compared with spherical liposomes, resulting in improved antitumour T-cell priming and tumour regression.

Germ layer specification during zygotic genome activation is regulated by chromatin state. Here, the authors use single-cell multiome profiling in Drosophila to show that H3K27me3 and H3K27ac at cis-regulatory elements control cell type-specific gene expression and developmental progression.

PUF proteins, conserved stem cell regulators, maintain germline stem cells with partner proteins in nematodes. Here, authors discover a complex of two FBF-2 PUF proteins and partner LST-1 that represses target mRNA via adjacent regulatory elements.

It has been shown that inhaling multiwalled carbon nanotubes does not lead to significant lung inflammation, but can suppress the immune function of mice. Now it is demonstrated that signals in the lung can activate signals in the spleen to inhibit the immune function of mice inhaling low levels of nanotubes.

Itkin et al. identify a role for Fli-1 in hematopoietic stem cell activation during regenerative hematopoiesis. They show that Fli-1 coordinates hematopoietic stem cells to stimulate niche-derived Notch1 feedback signals for demand-needed hematopoietic cell output.

The bacterium Helicobacter pylori, often found in the human stomach, can be classified into distinct subpopulations associated with the geographic origin of the host. Here, the authors provide insights into H. pylori population structure by collecting over 1,000 clinical strains from 50 countries and generating and analyzing high-quality bacterial genome sequences.

The complex microenvironmental signalling pathways that govern haematopoietic stem cell (HSC) activity remain poorly defined. Here, the authors identify endothelial NF-κB signalling as regulating regenerative HSC function, accelerating haematopoietic recovery following myelosuppressive injury in mice.

Cryptococcus neoformans is the leading cause of death by fungal meningoencephalitis. Here, the authors study the roles played by 129 putative kinases in the growth and virulence of C. neoformans, identifying potential targets for development of anticryptococcal drugs.

Using cross-areal mapping of axonal projections in the mouse neocortex, we identify the subtype-specific developmental dynamics of extratelencephalic neurons and show the functional transcriptional programs driving extratelencephalic neuron diversity.

Glucagon is hormone that signals via a dedicated g-protein coupled receptor, but downstream signaling is poorly understood. Here, Wu et al. uncover liver glucagon signaling using phosphoproteomics and define a role for the vesicle trafficking protein SEC22B in distinct metabolic actions.

Analysis of DNA replication fork arrest is challenging due to lack of techniques that induce site-specific replication barriers in eukaryotic chromosomes. Here, Larsen et al. create a novel tool to trigger targeted replication fork pausing by engineering the bacterial Tus–Tersystem into the yeast genome.

Single-nucleus RNA-seq was used to profile 11 retinas with varying stages of age-related macular degeneration and 6 control retinas. The authors identified shared glial states across neurodegeneration, indicating that the retina provides a human system for investigating therapeutic approaches in neurodegeneration.

During female gametogenesis in plants, the Megaspore Mother Cell (MMC) accumulates β−1,3-glucan. Here Pinto et al. show that increased β−1,3-glucanase in the MMC delays β−1,3-glucan deposition, disrupts cell identity, and halts gametogenesis.

Damaged brains try to repair themselves by producing neurons in areas where neurogenesis does not normally occur. Here, the authors show that brain endothelial cells provide microvesicle-encased signals that convert parenchymal astrocytes into neural progenitors, thus improving outcomes after stroke.

This Brain Somatic Mosaicism Network analysis of 283 cases of malformations of cortical development identifies 69 candidate and known genes in 76 patients. Single-nucleus RNA sequencing and mouse modeling implicate radial glia and daughter excitatory neurons.

Lesnik, Kaletsky et al. show that in C. elegans branched-chain amino acid catabolism is important for maintaining oocyte quality with age.

Idiopathic Parkinson’s disease can be stratified according to the severity of neuronal respiratory complex I deficiency. The emerging disease subtypes show distinct molecular and clinical profiles.

p53 regulates signalling pathways involved in metabolic homeostasis. Here the authors show that O-GlcNAcylation of p53 in the liver plays a key role in the physiological regulation of glucose homeostasis, potentially via controlling the expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase.

The potassium channel selectivity filter is responsible for conduction and selectivity of K + over other cations. Here, the authors use a combination of single molecule FRET, non-canonical fluorescent amino acid incorporation, and single channel patch-clamp electrophysiology, to establish the generality of K + -induced SF conformational stability across the K + channel superfamily.

Dysfunction of the gastrointestinal system, and to the autophagy lysososmal pathway (ALP) have been reported in Parkinson’s disease. Here the authors report epigenetic disruption of ALP related genes in the appendix of individuals with Parkinson’s disease.

In a future quantum internet, entanglement or a secret key should be efficiently provided between two points via intermediate nodes connected by optical channels. Here the authors derive general rate-loss trade-off for such protocols, that is applicable to any network topology.

Fumarate metabolism regulates the innate immune response through a mechanism in which high levels of fumarate result in the generation of mitochondrial-derived vesicles and the release of mitochondrial DNA into the cytosol, which activates inflammatory pathways.

Resident microglia in the central nervous system are identified as the specific macrophage population that regulates myelin growth and integrity.

Arrigoni et al. present non-canonical voltage-gated ion channel pore domain (PD) structures demonstrating that the PD is an autonomously folded unit found in diverse proteins and show that PDs can adopt non-canonical forms in full-length channels.

Skate-specific changes in the epigenome and its three-dimensional organization contributed to the evolution of the batoid fin morphology.

A multidisciplinary approach, including genetics and behavioural assays, identifies a single gene, CYP4PC1, which integrates both sex differentiation and hormone signalling with sexual attractiveness in the German cockroach.

A comprehensive analysis of brain somatic mosaicism across the neocortex demonstrates the origins and distribution patterns of cells within the human brain.

The human-specific gene duplication SRGAP2C is identified as a modifier of structural and functional features of cortical circuits leading to improved behavioural performance that may have allowed the emergence of cognitive properties characterizing the human brain.

Microglia, the brain’s immune cells, suppress neuronal activity in response to synaptic ATP release and alter behavioural responses in mice.

We developed tissue-engineered neuromuscular organoids by combining decellularized skeletal muscle and hiPSCs. The provided ECM scaffolds improved cell maturation, enabling the study of (dys)functional skeletal muscle.

The hypoxia response pathway can counter pathological damage caused by low oxygen availability. Here the authors employ a multiomics approach to show how the pathway reprograms metabolism towards gluconeogenesis to combat oxidative stress.