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Engineered mucus-tethering bispecific nanobodies neutralize and entrap viruses to enhance mucosal immunity, preventing influenza infection and limiting SARS-CoV-2 transmission.

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.

Fragile X syndrome is a neurodevelopmental disorder with altered neuronal excitability and behavior. Here, the authors show that dysfunction of astroglial Kir4.1 potassium channels drives neuronal and behavioral impairments in a fragile X mouse model.

Extracellular vesicles encapsulating mRNA encoding for extracellular-matrix collagen and delivered intradermally via microneedles led to the replacement of collagen in the dermis of mice with photoaged skin.

Analysis of medulloblastomas in humans and mice shows that the functional consequences of ZIC1 mutations are exquisitely dependent on the cells of origin that give rise to different subgroups of medulloblastoma.

Using unique barcodes for tumour cells, the authors explore the dynamics of human glioblastoma subpopulations, and suggest that clonal heterogeneity emerges through stochastic fate decisions of a neutral proliferative hierarchy.

The largest harmonized proteomic dataset of plasma, serum and cerebrospinal fluid samples across major neurodegenerative diseases reveals both disease-specific and transdiagnostic proteomic signatures, including a robust plasma profile associated with the APOEε4 genotype.

Sonic Hedgehog medulloblastoma (Shh-MB) comprises four subtypes each with distinct clinical traits. Here the authors characterize the genome, transcriptome, and methylome of Shh-MB subtypes, revealing a complex fusion landscape and the molecular convergence of MYCN and cAMP signaling pathways.

In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.

Professional antigen presenting cells (APCs) are deterred from phagocytosing cancer cells that express CD47. Here, the authors show that in glioblastoma mouse models, temozolomide improves the phagocytosis effect of CD47 blockade in APCs and results in the activation of adaptive anti-tumour responses.

Proteogenomic analysis of human cerebrospinal fluid by measuring 6,361 proteins in 3,506 individuals identifies new protein QTLs and highlights genetic regulation involved in neurological processes.

Derailed differentiation of human-specific progenitors of the developing cerebellar rhombic lip is the cause of group 4 medulloblastoma, the most common childhood brain tumour. 

Medulloblastoma is the most common malignant brain tumour in children; having assembled over 1,000 samples the authors report that somatic copy number aberrations are common in medulloblastoma, in particular a tandem duplication of SNCAIP, a gene associated with Parkinson’s disease, which is restricted to subgroup 4α, and translocations of PVT1, which are restricted to Group 3.

Sequencing data from the developing cerebellum are compared with bulk sequencing data from paediatric tumours, providing insights into their potential origins and suggesting that many cerebellar tumours have their origins early in utero.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Highly recurrent hotspot r.3A>G mutations are identified in U1 splicesomal small nuclear RNAs in about 50% of Sonic hedgehog medulloblastomas, which result in disrupted RNA splicing and the activation of oncogenes.

In a prespecified 3-year analysis of the KEN SHE trial, single-dose HPV vaccination was shown to be well tolerated and provided durable protection against cervical HPV infection in Kenyan women aged 15–20 years.

Patterned organoids and bioprinted tissues can be generated by simultaneously co-differentiating pluripotent stem cells into distinct cell types via the forced overexpression of transcription factors, independently of culture-media composition.

Graft-versus-leukemia reactions are required for the eradication of myeloid malignancies after allogeneic hematopoietic cell transplantation. However, treatment efficacy is variable, depending on the immunological response. Here the authors show that dysfunction of HLA heterogeneity is associated with post-transplant leukemia relapse.

This Resource describes genetic tools for microbial eukaryotes, providing a roadmap for developing genetically tractable organisms.

The N-end rule pathway targets substrate proteins for proteasomal degradation. Here, Whiteet al. show that ArabidopsisPLANT CYSTEINE OXIDASEs show dioxygenase activity producing Cys-sulfinic acid at the N-terminus of target proteins, which then act as direct substrates for arginyl transferase.

To address the question of whether a recurrent tumour is genetically similar to the tumour at diagnosis, the evolution of medulloblastoma has been studied in both an in vivo mouse model of clinical tumour therapy as well as in humans with recurrent disease; targeted tumour therapies are usually based on targets present in the tumour at diagnosis but the results from this study indicate that post-treatment recurring tumours (compared with the tumour at diagnosis) have undergone substantial clonal divergence of the initial dominant tumour clone.

The cost and cost-effectiveness of dialysis therapy for patients with end-stage renal disease is a key consideration for health-care providers, particularly given the increasing prevalence of chronic kidney disease worldwide. Here, Klarenbach and colleagues discuss available data comparing the relative cost and cost-effectiveness of various dialysis modalities, including variations in the intrinsic costs of the different modalities and other factors, such as economic differences between high-income and low–middle-income nations.

Super enhancers regulate oncogenes and other molecular targets in ependymomas, and identification of these genes provides potential therapeutic targets.

The Impact of Genomic Variation on Function Consortium is combining single-cell mapping, genomic perturbations and predictive modelling to investigate relationships between human genomic variation, genome function and phenotypes and will provide an open resource to the community.

Michael Taylor, Marco Marra and colleagues analyze spatial tumor heterogeneity in 9 medulloblastomas, 16 high-grade gliomas and 10 renal cell carcinomas, using a combination of transcriptomic and genomic profiling of multiregional biopsies. They find that medulloblastomas have spatially homogeneous transcriptomes, whereas somatic mutations that affect genes suitable for targeted therapeutics are spatially heterogeneous.

A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.

Azevedo et al. conduct a machine learning-based analysis of structural MRI data from multiple cohorts. The authors identify Alzheimer’s disease-like neuroimaging phenotypes associated with poorer cognitive performance in a healthy UK Biobank cohort, potentially highlighting a population at risk of Alzheimer’s disease.

Inglese et al. develop a predictive model that computes multi-regional statistical morpho-functional mesoscopic traits from T1-weighted magnetic resonance imaging scans. Their model reliably discriminates people with Alzheimer’s disease-related pathologies from those without.