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A chromosome-level genome assembly for the Ninu (greater bilby) and genome sequences for the extinct Yallara (lesser bilby), together with resequenced genomes, shed light on the demographic history of Ninu and inform conservation plans for this culturally and ecologically important marsupial.

Here the authors show that gut metagenomes of Indigenous Australian infants living remotely, display greater diversity and abundance of bacteria, viruses and fungi, compared to non-Indigenous infants living in urban Australia, suggesting that while having access to Western foods, the infants start life with a gut microbiome that retains key features of pre-industrialized societies.

Faecal microbiota transplantation (FMT) can be used to treat established colitis. Here the authors profile transcriptional changes in humans after FMT and how this relates to colitis remission identifying a role for GBP5, and this protein is validated in a loss-of-function mouse model.

MYCN-amplified neuroblastoma remains an aggressive childhood cancer with its core regulatory circuits less understood. Here, the authors identify that the transcriptional corepressor Runx1t1 is indispensable for MYCN-driven neuroblastoma tumorigenesis.

African ancestry is a known risk factor for prostate cancer development, but the genetic determinants of this are incompletely understood. Here, the authors identify 172 potentially pathogenic variants which are enriched in an African population.

Methylotrophic metabolism enables growth on methanol, an alternative to sugar fermentation. Here the authors use adaptive laboratory evolution to uncover native methylotrophy capacity in Saccharomyces cerevisiae.

Extracting functional information from 16S rRNA data surveys would provide a valuable tool for large-scale functional ecology. Here, the authors use PICRUSt2 to infer metabolic functions from bacterial marker gene data across the South Pacific Ocean, and compare them with rate data, biomass estimators and predictions based on shotgun metagenomes.

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.

A prospective analysis of gut microbiome signatures in patients treated with neoadjuvant immunocheckpoint blockade for high risk resectable metastatic melanoma identifies new links between microbiota signatures, dietary intake and systemic inflammation in shaping the response and toxicity to immunotherapy.

Here the authors report a that sprint interval exercise triggers mitochondrial stress and quality control in skeletal muscle in young healthy men, promoting enhanced mitochondrial function and a remodelling after 8 weeks of training.

Stromal cell recruitment, activation and crosstalk with cancer cells is poorly understood. Here, the authors demonstrate that cancer cell-derived Hedgehog ligand  triggers stromal remodeling that in turn induces a cancer-stem-cell like, drug-resistant phenotype of nearby cancer cells while treatment with smoothened inhibitors reverses these phenotypes.

Little is known about the selection of regulatory mechanisms for plant microRNAs. Now a Dicer partnering protein, DRB2, is reported to determine translational inhibition and repress transcript cleavage, allowing the selection of the two mechanisms.

The architectural protein CTCF is a mediator of chromatin conformation, but how CTCF binding to DNA is regulated remains poorly understood. Here the authors find that there is a shared subset of CTCF-bound sites resistant to protein depletion in different cell lines, which are enriched at domain boundaries and chromatin loops constitutive to all cell types.

Shen et al. identify a noncanonical role for the inflammasome protein NLR family CARD domain-containing protein 4 (NLRC4) to attenuate tumor development. NLRC4 forms a scaffold to assemble the ataxia telangiectasia and Rad3-related DNA repair complex and the repair kinase checkpoint kinase-1 to promote repair of DNA breaks.

Here, the authors show that high alpha diversity, differences in beta diversity, and a high abundance of Bacteroides in the gut microbiome are associated with positive vaccine take and stool shedding following administration of RV3-BB vaccine in the neonatal schedule, but not in the infant schedule or placebo groups, suggesting that the early-life gut microbiome provides a gut environment that optimizes the potential for a positive vaccine response.

CD8⁺ memory T cells appear during infection via a process of selection and differentiation that remains poorly understood. Using a fluorescent indicator of cell cycle progression, Kinjyo et al. show that slow-cycling memory precursors are derived from fast-cycling-activated T cells in influenza-infected mice.

In this study, the authors generated iPSC lines from more than 100 sporadic ALS cases, which recapitulated key disease phenotypes and enabled large-scale drug screening, identifying a promising combination therapy of baricitinib, memantine and riluzole.

Assessing microbial water quality is an important approach to monitor potential risks to human and environmental health. The use of two human faecal bacteria as molecular indicators is shown to be more sensitive than conventional measures for detecting contamination on an extensive set of data.

Injectable biomimetic hydrogels hold significant promise for tissue engineering applications. Here, the authors present a hybrid myoglobin:peptide hydrogel to overcome a critical oxygen shortage following neural stem cell transplantation, thus increasing cell survival and integration.

Joyce, Pascual et al. identify luminal progenitors as likely cells-of-origin in BRCA2-mutant breast cancer, exhibiting dysregulated proteostasis and translation, which may be therapeutically targeted via mTORC1 inhibition.

Severe sepsis has a high mortality rate. Here, the authors provide genomic, transcriptomic, proteomic and metabolomic data across four sepsis-causing pathogens and identify a signature of global increase in fatty acid and lipid biosynthesis as well as cholesterol acquisition.

Here, the authors characterise Acinetobacter baumanii and Klebsiella pneumoniae isolated from a single human lung infection and proceed to define their interactions to shed light on how this impacts their evolution, growth parameters, metabolism and antimicrobial responses.

This study provides insights into the functional roles of microbial symbionts within the reef-building coral Acropora kenti. The findings reveal molecular mechanisms underpinning coral health and adaptation to local environmental stressors, which may support host resilience in the face of anthropogenic climate change and pollution.

Although the gain in chromosome 17q21-ter is commonly associated with neuroblastoma, it is not clear which gene of this region mediates tumorigenesis. Here, the authors are showing that JMJD6, which locates in that region, is a neuroblastoma tumorigenic factor.

Age-related macular degeneration (AMD) is a leading cause of vision loss, and there is no approved treatment for AMD with geographic atrophy. Here, the authors used transcriptomic and proteomic analyses of patient induced pluripotent stem cell-derived retinal pigment epithelium to better understand disease mechanisms.

Simpson and colleagues systematically interrogate the influence of dietary carbohydrate type and quality on the obesogenic impact of protein-diluted diets in mice.

Here it is shown that the consumption of a high-fat diet by male rats has an intergenerational effect: it leads to the dysfunction of pancreatic β-cells in female offspring. Relative to controls, these offspring showed an early onset of impaired insulin secretion and glucose tolerance, which worsened with time. The results add to our understanding of the complex genetic and environmental factors that are leading to the global epidemic of obesity and type 2 diabetes.

Roquin is an RNA-binding protein that promotes the degradation of specific mRNAs and is crucial for the maintenance of peripheral immune tolerance. Here the authors show that, in addition to its target mRNAs, Roquin can bind miR-146a and the RISC component Ago2 to control homeostasis of both RNA species.

The M₅ muscarinic acetylcholine receptor represents a promising therapeutic target for neurological disorders. Here, the authors reveal a 2.1 Å cryo-EM structure of the M₅ bound to a selective positive allosteric modulator site that enables structure-based drug design.

Successful human-AI collaboration could greatly contribute to breast cancer mammographic screening. Here, the authors use a large-scale retrospective mammography dataset to simulate and compare five plausible AI-integrated screening pathways, finding optimal ways in which human-AI collaboration could be implemented in real-world settings.

Epidemiological evidence has identified associations among obesity, Alzheimer’s disease, and cardiovascular disease. Here, the authors report that adipose tissue releases amyloid beta 42 (Aβ42) and that antagonizing Aβ42 protects cardiac function in obesity murine models.

The first large, high-coverage whole-genome sequencing study of melanomas from cutaneous, acral and mucosal sites.

The membrane attack complex is a heteromeric assembly of complement proteins where multiple copies of C9 are recruited by the C5b678 complex to form lytic pores in pathogen membranes. Here the authors present the structure of a soluble pore-like form of the C9 component that reveals details of the oligomerization interfaces.

Cryo-electron microscopy structures of the human lysosomal transmembrane protein LYCHOS show that it comprises a transporter-like domain fused to a G-protein-coupled receptor, and that the transporter domain is similar to the plant PIN family.

A genome-wide screen using human gut epithelial organoids combined with transposon-directed insertion sequencing identifies over 100 Shigella flexneri genes required for epithelial colonization.

The authors previously identified a family of viral insulin-like peptides (VILPs) with high homology to human insulin/IGF−1. Here, they report that one of these VILPs exhibits antagonist properties associated with a unique conformation of the IGF1R.

Colorectal cancer cell lines accurately recapitulate the histological and transcriptional properties of low-grade and high-grade colorectal cancers.

Bond et al. show that inducible PolG mutation in muscle causes mtDNA damage and muscle wasting. This is driven by the integrated stress response (ISR) and reduction in folate intermediates, linking impaired folate metabolism with ISR/disease induction.

Cryo-EM, X-ray crystallography and crosslinking mass spectrometry are harnessed to solve the structure of the full-length Rho-GEF P-Rex1, uncovering a two-layered mechanism of autoinhibition released upon Gβγ and PI(3,4,5)P3 binding.

Cryo-EM and three-dimensional variability analyses reveal the structure of the autoinhibited 640-kDa NF1 dimer, providing a long-sought-after molecular explanation for the extreme sensitivity of the NF1 gene to loss-of function mutation in disease.

Metagenomic and biochemical analyses of soil samples from Antarctic desert regions provides evidence that bacteria in these soils derive carbon and energy from atmospheric CO, H₂ and CO₂.

The recovery of metagenome-assembled genomes from the coral Porites lutea, its dinoflagellate symbiont, and its bacterial and archaeal populations, enabled comparative genomic identification of functions important for host–microbe interactions and nutritional associations.