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Here the authors show that DNA damage induced RNA m5C in R-loops competes with PARP1- mediated PARylation in transcribed genomes to promote cell survival which could be targeted be in cancer therapy.

Here the authors spatially map tuberculosis granulomas from nonhuman primates to link structure and immune organization with bacterial control. They find that a conserved hypoxic myeloid core is associated with dysfunctional immunity, restricted lymphocyte access and increased bacterial burden.

The authors show that changes in nuclear dynamics of p75^NTR by γ-secretase cleavage are a novel molecular switch that determines TGF-β signaling in astrocytes. Cleaved p75^NTR acts as a component of the nuclear pore complex, regulating nuclear import of Smad-2 in astrocytes. The authors find that p75^NTR is required in mice for TGF-β-induced glial scar formation and reduced neuronal activity.

Surface association and quorum sensing regulate bacterial community behaviours such as biofilm formation and motility. Here, Chuang et al. show that surface association promotes stronger quorum-sensing responses in Pseudomonas aeruginosa by upregulating the master regulator LasR.

In this paper, a CRISPR-based gene addition strategy at the CX3CR1 locus of human hematopoietic stem cells is proposed to efficiently generate microglia engineered for the regulated expression of therapeutic genes for the treatment of neurodegenerative disorders.

Inborn errors of metabolism are a diverse group of disorders that can mimic rheumatological disease, often presenting with progressive joint and systemic involvement. This Review serves as a primer for rheumatologists, covering clinical aspects and potential mechanisms by which these metabolic alterations cause immune dysregulation.

SPEN is a key player in initiation of X chromosome inactivation. Here, the authors show that SPEN is required for Xist-mediated silencing of its own antisense regulator Tsix.

Behavioural and genetic experiments in mice reveal gut-to-brain circuits driving the development of fat preference, one responding to intestinal sugar and fat using cholecystokinin signalling, and the other responding only to fat.

Mutations in the mitochondrial kinase PINK1 result in familial Parkinson’s disease. Here the authors show that LETM1, a mitochondrial inner membrane protein, is a substrate of PINK1 that regulates Ca²⁺ handling in mitochondria in response to mitochondrial toxins.

Here, the authors identify a novel regulator of autophagy, skeletal muscle mass and integrity named MYTHO. Silencing MYTHO protects against muscle atrophy in a wide range of acute catabolic conditions, while prolonged silencing causes a severe myopathy.

The Drosophila tumour necrosis factor (TNF) system comprises a single ligand Eiger (Egr) and two receptors. The structure of Egr in complex with the extracellular domain of the receptor Grindelwald and accompanying data suggest that distinct affinities of TNF ligand for its receptors mediate non-redundant functions.

Illness signals from the gut reactivate and strengthen flavour representations in the amygdala to support learning from delayed postingestive feedback.

The Drosophilahomologue of the vertebrate cell surface glycoprotein Cdon binds Hedgehog ligand and thereby prevents its diffusion. Here, the authors provide evidence for a similar mechanism during vertebrate optic vesicle patterning, where Cdon acts as a negative regulator of Hedgehog signalling to define the boundary between the optic stalk and the retina.

A new MAP4K4–moesin–talin–β1-integrin pathway regulating endothelial cell motility was discovered through chemical and siRNA screens; loss of Map4k4 or inhibition of MAP4K4 kinase activity altered the sprout morphology of endothelial cells during angiogenesis by blocking moesin phosphorylation, which regulates the disassembly of focal adhesions, demonstrating that this pathway is involved in both normal and pathological angiogenesis.

Polycystin-2 (PC2) is an ion channel commonly found mutated in autosomal dominant polycystic kidney disease. Here Arhatte et al. identify transmembrane protein 33 (TMEM33) as a regulator of PC2 function at the endoplasmic reticulum, and find that deletion of TMEM33 protects mice from acute kidney injury.

Repetitive head impacts from contact sports are associated with brain inflammation, vascular damage and neuron loss that are independent of hyperphosphorylated tau pathology.

Macrophages densely populate the arterial wall, yet their origin and homeostasis are poorly understood. Robbins and colleagues show that arterial macrophages arise from CX3CR1⁺ embryonic precursors and adult bone marrow–derived monocytes that colonize the tissue immediately after birth.

Glioblastoma tumours expressing oncogenic PIK3CA variants secrete the glycan GPC3, which promotes the formation of neural synapses, brain synaptic hyperexcitability and gliomagenesis.

Glutamatergic neurons in the parvocellular part of the medial vestibular nucleus mediate motion-induced hypothermia and can be targeted to prevent diet-induced obesity.

Yap and colleagues identify an extramitotic role for the centralspindlin complex, a Rho signalling regulator during cytokinesis. They show that centralspindlin interacts with α-catenin, and promotes epithelial junctional integrity by recruiting the ECT2 RhoGEF to the zonula adherens, as well as by inhibiting the junctional localization of the p190 B RhoGAP.

In vivo imaging of mammary carcinoma cells reveals that activation of a TGFβ-induced transcriptional response induces the motility of individual cells, allowing them to spread through the blood stream. In the absence of TGFβ, cells migrate as groups and can only metastasize through the lymphatic system.

The hormone Dipl8 regulates organ growth inDrosophila whereas the Hippo pathway controls organ size. Here, the authors show that the expression of Dipl8 is regulated by the Hippo pathway, thus linking organ growth or organ size in Drosophila.

El-Shennawy et al. report that ACE2⁺ circulating extracellular vesicles (evACE2) are associated with COVID-19 severity and that evACE2 inhibits the infection of SARS-CoV-2 variants of concern at a higher efficacy than soluble ACE2.

Nixon-Abell et al. show that ANXA11 condensation on lysosomal membranes causes a coupled phase transition of the underlying lipids and mechanical stiffening of the overall ensemble involved in RNP granule-lysosome tethering and co-trafficking.

Little is known regarding migration of Th17 cells that produce distinct cytokines implicated in protection and pathology. Kara et al. show that a switch from CCR6 to CCR2 by Th17 cells defines a signature (CCR6⁻CCR2⁺) of GM-CSF⁺Th17 cells and drives pathology in a mouse model of autoimmunity.

Arterial development relies on the timely and MYC-dependent suppression of endothelial metabolism and the cell cycle in pre-arterial endothelial cells through Notch signalling.

A reinforcement learning-based virtual reality system, implementing a series of sport sessions with coaching, was as effective as standard physical activity in reducing fat mass in adolescents, with positive effects on cognition.

Transcription-coupled homologous recombination (TC-HR) is activated by reactive oxygen species-induced DNA damage to maintain transcribed genome stability. The authors demonstrate that R loops are induced by ROS at the transcribed genome, triggering a CSB-RAD52- dependent but BRCA1/2-independent RAD51 loading for repair.

CherryML is a method to scale up maximum likelihood estimation for general phylogenetic models of molecular evolution, providing several orders of magnitude speedup over traditional methods.

CLOCK (CLK) is essential for the development and maintenance of circadian rhythms in Drosophila. Here, the authors show that Clk mRNA is regulated by miRNA bantam, and deletion of bantambinding site leads to stochastic CLK-driven transcription and development of the circadian neurons.

In cancer, the impact on cellular fitness of copy-number gains affecting collaterally-amplified genes remains poorly understood compared to oncogenes. Here, the authors integrate genomic data from tumours and cell lines and identify a class of ‘Amplification-Related Gain Of Sensitivity’ (ARGOS) genes, with potential therapeutic applications.

Kirchhausen and colleagues show that actin is required for clathrin-mediated endocytosis at membranes under tension—such as apical surfaces of polarized cells. Actin engages with Hip1R bound to clathrin light chain to complete the deformation of a clathrin-coated pit into an endocytic vesicle.