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Scholz omitted crucial parts of the the recent history of the seismic gap forecast and test. He remarked that our test of the gap theory was 'flawed' because it used earthquakes 'smaller than system-sized'. This was also asserted in a published comment by Nishenko & Sykes¹ and answered by Jackson & Kagan². But 'system-sized' was never defined in the original seismic gap model³.

In this study, the authors present optimization and efficacy testing of apolipoprotein-based lipid nanoparticles for delivering various nucleic acid therapeutics in vivo to immune cells and their progenitors in the bone marrow.

In CHIP, somatic mutations in a hematopoietic stem cell lead to a clonal subpopulation of blood cells. Here, the authors perform a CHIP meta-EWAS to establish its epigenetic features and age-related outcomes.

Modifying the polyethylene glycol lipid ratio and phospholipids in the lipid nanoparticle component of nucleoside-modified mRNA–lipid nanoparticle vaccines is shown to have an impact on the elicited cellular and humoral immune responses.

Shared inter-brain neural dynamics, reflecting aspects of social interaction including self and other’s behaviours, arise in GABAergic neurons of the dorsomedial prefrontal cortex of socially interacting mice, as well as in the neurons of socially interacting artificial intelligence agents.

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

Neural networks fundamentally dictate function. Here, the authors show thirteen uniquely connected neuron populations within the anterior thalamic nuclei, suggesting multiple parallel subnetworks support its emotional and cognitive functions.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

A population of TRAIL-positive astrocytes in glioblastoma contributes to an immunosuppressive tumour microenvironment and this mechanism can be targeted with an engineered oncolytic virus to improve outcomes.

Using viral barcode tracing to detect interactions between glioblastoma cells and non-malignant astrocytes in patient samples, investigators discovered a pathway that reduces tumour-specific immunity and identified potential therapeutic targets.

Candida auris is a fungal pathogen notorious for persistent skin colonization and transmission in healthcare settings. Here, Zhao et al. explore the mechanisms driving pathogen’s adherence to skin, involving a conserved adhesin, as well as the potential of collagen coatings as a strategy to reduce C. auris adherence to abiotic surfaces.

Inactivating PPP2R1A mutations correlate with better survival after immune checkpoint blockade in patients with ovarian clear cell carcinoma, suggesting that targeting the phosphatase 2A (PP2A) pathway may represent an effective startegy for improving responses to immunotherapy.

Colobomatous microphthalmia often lacks a genetic diagnosis despite its developmental complexity. Here, the authors show that rare variants in NR6A1 cause a syndromic form with eye, kidney, and vertebral defects, supported by zebrafish functional validation.

The mechanisms underlying neurological complications of monkeypox virus infection remain unclear. Here, the authors investigate its neurotropic potential and show that neuritic transport of viral particles drives neuronal degeneration.

Malnutrition during pregnancy has lasting effects on maternal and offspring health. Its adverse impacts are modified by the maternal microbiome and attenuated by gestational treatment with select microbial metabolites.

Neural circuit mechanisms underlying feeding behavior regulation are not fully understood. Here authors provide quantitative mapping of the brain-wide input and output configuration of tuberal nucleus somatostatin neurons, a key player of feeding regulation, in mouse brain for a deeper understanding of the feeding regulation network.

A distinct population of CD4 T cells resides in specific regions of the steady-state brain, and these T cells are programmed in the periphery by the microbiome to coordinate adaptive behaviour.

End-of-life nonhuman primates can be used to screen pools of lipid nanoparticles for clinical safety studies.

Monomethylation of histone H4 lysine 20 (H4K20me1) contributes to DNA replication but the mechanism is not well understood. Here, the authors identify a conserved tandem Tudor ___domain of BAHCC1 as a H4K20me1-specific reader, which promotes the recruitment of MCM complex to chromatin for efficient DNA replication.

The mechanism of macrophage cytotoxicity against cancer cells requires further illustration. By employing CRISPR screening in CAR-macrophage and cancer cell co-culture system, the authors identify depletion of ATG9A on cancer cells sensitizes them to macrophage-mediated killing, which can be synergic with CSF1R inhibition in cancer treatment.

Pocock et al. reveal that transient activation of 5′ AMP-activated protein kinase and estrogen-related receptor drives robust maturation of multicellular human cardiac organoids, enabling modeling of desmoplakin cardiomyopathy dysfunction, which could be rescued using the bromodomain and extra-terminal inhibitor INCB054329.

Certain antimetabolites used to treat cancer are more neurotoxic than others, and it is now shown that this is due to their greater tendency to generate DNA double-stranded breaks, whereas less neurotoxic agents induce single-stranded breaks.

Zhang et al. provide evidence that, during meiosis, recombination proteins assemble into active droplets, the coarsening of which partially explains the phenomenon of crossover interference.

Adoptive transfer of regulatory T (Treg) cells holds promise for the treatment of inflammatory diseases, but maintaining a therapeutic capacity is challenging. Here, the authors show that engineering Tregs to express an IL-2 partial agonist enhances Treg persistence and suppression of inflammation in mouse models, representing a potential optimization for Treg therapy.

Konturek-Ciesla et al show that low intensity conditioning with antibody mediated haematopoietic stem cell (HSC) depletion coupled to HSC transplantation boosts blood cell and immune cell generation in aging mice, slowing disease. This approach may help treat age-related blood disorders in humans.

ADP-heptose binds to ALPK1, triggering transcriptional reprogramming and NF-κB activation, endowing pre-leukaemic cells with a competitive advantage due to excessive clonal proliferation.

Every spring, Bogong moths use the starry night sky as a compass to navigate up to 1,000 km towards their alpine migratory goal.

Neurons in the median preoptic nucleus that express the prostaglandin EP3 receptor produce prolonged hypothermic responses or hyperthermic responses, respectively, following brief activation or inhibition.

Tacto et al. uncover a key marker that enables the selection of functional, transplantable human islets derived from stem cells, potentially paving the way for more precise and effective diabetes cell therapy.

Optimized SORT LNPs enable precise and long-lasting base editing in dual organs in a disease mouse model.

Birds have an excellent ability to learn to discriminate harmless insects from those that they mimic on the basis of subtle differences in appearance.

Total cell cycle duration is a key hallmark of cancer initiation, and determines whether defects in apoptosis, senescence, immune surveillance, angiogenesis, DNA repair, polarity and proliferation lead to cancer development.

The homeostasis and function of adipose tissue are tightly regulated by immune cells, with macrophages playing a pivotal role. Here the authors show that PpargHIGH macrophages positively enhance brown adipose tissue thermogenesis through GDF15.

Rashan, Bartlett and colleagues show that mammalian 4-hydroxy fatty acids are primarily catabolized by ACAD10 and ACAD11 (atypical mitochondrial and peroxisomal acyl-CoA dehydrogenases, respectively) that use phosphorylation in their reaction mechanisms.

Targeting a non-natural micropeptide ‘killswitch’ to several biomolecular condensates altered condensate compositions and revealed condensate functions in human cells

How signaling pathways recruit SWI/SNF chromatin remodeling complexes is not known. Here the authors suggest a ubiquitin directed mechanism targeting SWI/SNF for Wnt pathway dependent transcription, important for development and cancer.

The antiviral protein SP140 negatively regulates Ifnb1 mRNA stability by directly repressing the expression of the immune regulator RESIST.

Transferrin receptor (TfR) and CD98hc are increasingly used to enable more effective drug delivery to the central nervous system. Here, the authors reveal comprehensive and distinct brain cellular and whole body biodistribution patterns of TfR- and CD98hc-binding molecules.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

In this study, the authors performed single-cell RNA-sequencing across various isogenic mutant FUS and TDP43 neurons. Mitochondrial dysfunction emerged as pathway unique to motor neurons demonstrating shared toxic gain of-function mechanisms, uncoupled from protein mislocalization.

Goel et al. examine why some factually correct news articles are often shared by users who also shared fake news articles on social media.

A study of human and mouse models of pancreatic cancer finds that inhibiting the lipid kinase PIKfyve interferes with the cancer’s lipid homeostasis, making it a potential target for drug development.

In a 6-week randomized phase 1 trial, tirzepatide led to reduced caloric intake during a meal test at week 3 compared with placebo and liraglutide in people with overweight or obesity.

Gradients of cell recognition molecules wire a sensorimotor interface in Drosophila.

Olfactory perception shows marked sexual dimorphism, yet its genetic basis remains underexplored. Here, the authors show sex-specific and shared genetic loci for odour identification, implicating olfactory receptor clusters and links to Alzheimer’s disease risk.

The neuronal composition of the intestinal submucosal plexus is incompletely understood. Here Li et al. define their neuron classes, connectome and stepwise acquisition of identities.

Here the authors engineer a bispecific antibody (Ab) for HIV-1 by combining a gp41 N-heptad repeat targeting Ab with a CD4 binding Ab. Prepositioning via CD4 binding results in high neutralization breadth and potency, and experiments in HIV infected humanized male mice show reduction of viral load.

Glucose uptake in astrocytes is thought to rely on GLUT1. Here, the authors show that adult mice tolerate astrocyte-specific GLUT1 deletion, which increases astrocytic glucose metabolism and confers neuroprotection in a model of stroke.

The transcription factor CREM is a pivotal regulator of NK cell function, making CREM a valuable target to increase the efficacy of anticancer immunotherapies based on this cell population and chimeric antigen receptors.