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This study reveals how temporally restricted enhancers control gene expression over time, highlighting their role in transcription dynamics and enhancer–promoter interactions during mouse limb development.

Neuroimmune communication in Alzheimer’s disease (AD) is poorly understood. Here, the authors show that CD103–CD8+ resident memory T cells induce neurotoxicity and neuroinflammation in AD via the granzyme K–PAR-1 axis.

Experimental models of breast cancer reveal the phosphoinositide-phosphatases PIPP and PTEN play non-redundant roles in suppressing mouse mammary epithelial cell transformation, and disease progression in a subset of human breast cancers.

Type I interferons have been described to have protumor or antitumor functions depending on context. Here the authors show a protumor function for type I interferons in that they promote cancer stem cells by upregulating the chromatin remodeling factor KDM1B.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

This study highlights the biocompatibility, tropism, antioxidant and anti-inflammatory properties of nanoalgosomes, extracellular vesicles (EVs) derived from the marine microalga Tetraselmis chuii, suggesting their potential for EV-based therapies.

Disruptions to the ER-Golgi network can lead to neurodevelopmental disorders, though our understanding of these Golgipathies remains incomplete. Here Lauri, Tartaglia and colleagues show that ARF3 mutations cause a rare pediatric neurological disorder and perform detailed molecular characterization in fish.

S-layers form continuous protein lattices on the surface of bacteria. Here, authors use S-layer depolymerizing nanobodies to solve the structure of the EA1 S-layer in the pathogen Bacillus anthracis and show its role as cell wall supportive structure”

Jose Florez, Claudia Langenberg, Erik Ingelsson, Inga Prokopenko, Inês Barroso and colleagues perform large-scale association analyses using the Metabochip to gain further insights into the genetic architecture of glucose regulation. They identify 38 new loci influencing 1 or more glycemic traits and show that many of these loci also modify risk of type 2 diabetes.

A head-to-head double-ring complex of the human multifunctional DNA repair protein RAD52 mediates protection of stalled replication forks during replication stress, protecting them from reversal by SMARCAL1 motor.

SKP2 is an oncogenic E3-ubiquitin ligase. Here the authors show that SKP2 is epigenetically regulated by the muscle lineage transcription factor MYOD, supports tumorigenesis in the Fusion Negative (FN) subtype of rhabdomyosarcoma (RMS) and impairs differentiation promoting degradation of p57^Kip2.

Pubertal timing in mammals depends on the function of GnRH neurons that innervate the median eminence (ME) of the hypothalamus. Here, the authors show that Semaphorin 6A regulates GnRH innervation and puberty onset by tuning vascular permeability at the ME.

Metastatic cells can mimic many of the phenotypic behaviors of embryonic cells. Here, the authors generate a melanoblast-specific transcriptome using a genetically engineered mouse model and identify KDELR3 as a pro-metastasis gene in melanoma.

The enzyme nicotinate phosphoribosyltransferase (NAPRT) mediates the rate-limiting step in NAD salvage pathway starting from nicotinic acid. Here the authors show that NAPRT can be detected extracellularly, binds to Toll like receptor 4, and activates NF-kB signaling and cytokine production in macrophage via NAD synthesis-independent pathways.

Brain cytoplasmic (BC1) RNA is a non-coding RNA that has been implicated in translational regulation, seizure, and anxiety. Here, the authors show that in the cortex, BC1 RNA is required for sensory deprivation-induced structural plasticity of dendritic spines, as well as for correct sensory learning and social behaviors.

In vivo gene delivery to haematopoietic stem and progenitor cells in newborn mice using engineered lentiviral vectors shows promise as an effective treatment for genetic diseases.

Chondrocyte differentiation controls skeleton development and stature. Here, the authors map mouse fetal chondrocyte enhancers, highlighting their role in controlling bone genes and connecting stature to non-coding variants overlapping these enhancers.

Advances in animal magnetoreception have been limited by a lack of tractable vertebrate laboratory models. Here, the authors demonstrate light-independent magnetoreception in mature zebrafish and medaka, as well as magnetosensitive locomotion in juvenile medaka associated with neuronal activation in the lateral hindbrain.

Mutations in the RHO GTPase CDC42 have been associated with autoinflammatory diseases. In this study, the authors investigate how two distinct mutations, which trap CDC42 in the Golgi apparatus, are specifically associated with hyperactivation of the STING pathway and the type I interferon response, as well as the induction of endoplasmic reticulum stress.

DNA methyltransferase 3 A (DNMT3A) is involved in DNA methylation, and genetic variants in the DNMT3 locus have been associated with inflammatory bowel disease. Here the authors report that DNMT3A controls intestinal epithelial barrier function and restoration of the gut barrier function after intestinal epithelial perturbation.

Here the authors show that a strong enhancer sequence can be controlled by the chromatin environment provided by a topologically associated domain (TAD) located nearby. An enhancer relocated by homologous recombination takes all the hallmarks of its new neighboring enhancers located in the recipient TAD.

The infrared view of JWST has opened up the early Universe to study. This Perspective summarizes the key developments in our understanding of the high-redshift Universe from the first 18 months of JWST observations.

Exosome targeting for therapeutic needs remains a challenge. Here, the authors show that ferromagnetic-nanotube-passivated exosomes promote the transition of proinflammatory macrophages to an anti-inflammatory state and myogenic maturation of dystrophic muscle progenitors in a murine model.

The exact molecular mechanisms driving FUS-mediated toxicity remain unclear. Here, the authors demonstrate that muscleblind (Mbl) is a novel modifier of FUS-associated ALS, with knockdown of endogenous Mbl suppressing neuromuscular junction defects and motor dysfunctions associated with FUS expression in Drosophila, as well as restoring reduced SMN protein levels in mammalian neuronal and human iPSC-derived motor neurons.

Stabilisation of stalled replication forks prevents excessive fork reversal and genome instability. Here authors reveal a RAD52-dependent replication fork protection mechanism.

Therapeutic T cells bearing ligands engineered to optimize adhesion and transmigration through the blood–brain barrier can be targeted to brain tumours.

Hepatic precursor cells (HPCs) are known to be bipotent and to give rise to both new hepatocytes and cholangiocytes upon acute liver injury. Stuart J. Forbes and his colleagues now show that interactions of HPCs with local macrophages and myofibroblasts potentiate Wnt and Notch signaling, respectively, to determine fate specification of the HPCs. Together, these mechanisms help determine proper organ regeneration after liver injury.

The chemokine CXCL10 is associated with pathogenesis of cerebral malaria in Plasmodium falciparum infection. Here the authors show that P. falciparum produces extracellular vesicles laden with RNAs that are taken up by monocytes resulting in a RIG-I and HUR-1 mediated mechanism of inhibition of CXCL10 protein translation.

Rapid and spontaneous estimation of number is observed in many animals. Here the authors show that perceived number of items modulates the pupillary light response in humans, confirming its spontaneous nature, and introducing pupillometry as a tool to study numerical cognition.

The PI(3,4)P₂ 4-phosphatase, INPP4B, functions as a tumour suppressor in triple negative breast cancer. Here, the authors show that INPP4B enhances proliferation and growth of PIK3CA-mutant ER⁺ breast cancers by promoting PI3Kα-dependent late endosome formation and trafficking that leads to the activation of Wnt/β-catenin signalling.

The signals that enable endothelial cells to switch to hemogenic to generate hematopoietic stem cells are poorly understood. Here, the authors identify an intracellular sensor of pathogens as an inductive developmental cue that primes this switch.

NeuBtracker is an open-source platform that enables simultaneous imaging of behavior and neural activity in freely behaving zebrafish larvae. Its performance is demonstrated during several spontaneous or stimulus-induced behaviors.

Changes in the metabolic state of stem cells can trigger a shift from quiescence into cell cycle entry. Here Maryanovichet al. identify mitochondrial carrier homolog 2 (MCH2) as a negative regulator of mitochondrial oxidative phosphorylation in haematopoietic stem cells, maintaining their homeostasis.

The mechanisms underpinning neuronal death in Alzheimer's disease (AD) remain unclear. Caccamo and colleagues show that necroptosis contributes to neurodegeneration in AD. Blocking necroptosis reduced neuronal loss in a mouse model of AD, suggesting that necroptosis might be a therapeutic target in AD.

The use of nanobodies that inhibit the self-assembly of the S-layer protein Sap from B. anthracis enabled the elucidation of the structure of this protein. The nanobodies also trigger disintegration of assembled S-layers and attenuate both bacterial growth and anthrax pathology in animal models of infection.

Romani et al. report that cells on soft extracellular matrix have increased mitochondrial fission, with subsequent production of mitochondrial reactive oxygen species and NRF2, which may increase resistance to reactive oxygen species-dependent chemotherapy drugs in breast cancer cells in vitro and in mouse lungs.

Despite acral melanoma being the most common melanoma subtype in non-White individuals, its molecular drivers remain unknown. Here, the authors integrate genomic and clinical data from 104 patients and identify late-arising focal amplifications of chr22q11.21 and LZTR1 as a key tumour promoter in this region.

UNC5B is a Netrin-1 receptor expressed in endothelial cells that in the absence of ligand induces apoptosis. Here the authors identify an UNC5B splicing isoform that is insensitive to the pro-survival ligand Netrin-1 and is required for apoptosis-dependent blood vessel development.

It is difficult to synchronize the cell cycle in a population of yeast cells for extended periods of time. Here the authors use a cybergenetic system with inbuilt feedback to synchronize a population of modified yeast.