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Retraction Note: Kynurenine promotes neonatal heart regeneration by stimulating cardiomyocyte proliferation and cardiac angiogenesis
Heparan sulfate regulates amphiregulin programming of tissue reparative lung mesenchymal cells during influenza A virus infection in mice
Abstract Amphiregulin (Areg), a growth factor produced by regulatory T (Treg) cells to facilitate tissue repair, contains a heparan sulfate (HS) binding domain. How HS, a highly sulfated glycan subtype that alters growth factor signaling, influences Areg repair functions is unclear. Here we report that inhibition of HS in various cell lines and primary lung mesenchymal cells (LMC) qualitatively alters Areg downstream signaling. Utilization of a panel of cell lines with targeted deletions in HS synthesis–related genes identifies the glypican family of HS proteoglycans as critical for Areg signaling. In the context of influenza A virus (IAV) infection in vivo, an Areg-responsive subset of reparative LMC upregulate glypican-4 and HS; conditional deletion of HS primarily within this LMC subset results in reduced repair characteristics following IAV infection. This study demonstrates that HS on a specific lung mesenchymal population is a mediator of Treg cell–derived Areg reparative signaling.
Origin and evolution of the North Atlantic Oscillation
Distinct horizontal gene transfer potential of extracellular vesicles versus viral-like particles in marine habitats
The Hydractinia cell atlas reveals cellular and molecular principles of cnidarian coloniality
Abstract Coloniality is a widespread growth form in cnidarians, tunicates, and bryozoans, among others. Colonies function as single physiological units despite their modular structure of zooids and supporting tissues. A key question is how structurally and functionally distinct colony parts are generated. In the cnidarian Hydractinia symbiolongicarpus, colonies consist of zooids (polyps) interconnected by stolons attached to the substrate. Using single-cell transcriptomics, we profiled ~200,000 Hydractinia cells, including stolons and two polyp types, identifying major cell types and their distribution across colony parts. Distinct colony parts are primarily characterised by unique combinations of shared cell types and to a lesser extent by part-specific cell types. We identified cell type-specific transcription factors (TFs) and gene sets expressed within these cell types. This suggests that cell type combinations and occasional innovations drive the evolution of coloniality in cnidarians. We uncover a novel stolon-specific cell type linked to biomineralization and chitin synthesis, potentially crucial for habitat adaptation. Additionally, we describe a new cell type mediating self/non-self recognition. In summary, the Hydractinia cell atlas provides insights into the cellular and molecular mechanisms underpinning coloniality.
Meiosis-specific distal cohesion site decoupled from the kinetochore
Abstract Primary constriction of the M-phase chromosome serves as a marker for the kinetochore position. Underlying this observation is the concept that the kinetochore is spatially linked with the pericentromere where sister-chromatids are cohered. Here, we find an unconventional chromatid-cohesion pattern in Peromyscus oocytes, with sister chromatids cohered at a chromosome end, spatially separated from the kinetochore. This distal locus enriches cohesin protectors specifically during meiosis, and chromosomes with this additional cohesion site exhibit enhanced cohesin protection at anaphase I compared to those without it, implying an adaptive evolution to ensure cohesion during meiosis. The distal locus corresponds to an additional centromeric satellite block, located far from the satellite block building the kinetochore. Analyses on three Peromyscus species reveal that the internal satellite consistently assembles the kinetochore in mitosis and meiosis, whereas the distal satellite selectively enriches cohesin protectors in meiosis to promote cohesion. Our study demonstrates that cohesion regulation is flexible, controlling chromosome segregation in a cell-type dependent manner.
Cortical processing of discrete prosodic patterns in continuous speech
Author Correction: Electron diffraction of deeply supercooled water in no man’s land
The role of water molecules in the dissociation of an electron-molecule contact pair
Abstract The hydrated electron, e– (aq), is a potent reducing agent and a prototypical quantum solute. Reactions of e– (aq) often involve a contact pair comprised of a molecule and electron that are hydrated within a single sphere. However, a molecular-level understanding of the solvent-driven coordinate that links the contact pair to the free dissociated e– (aq) remains elusive. Here, we study this coordinate by kinetically trapping representative metastable intermediates as gas-phase clusters and probing them using photoelectron spectroscopy. We apply this methodology to uracil-water anion clusters, where key intermediates are identified with supporting quantum chemical calculations. Just a single water molecule drives the parent molecule and non-valence electron apart, thereby inhibiting geminate recombination to form the more stable valence-bound uracil anion. The electron-water binding is akin to bare water cluster anions, highlighting the link to larger clusters and e– (aq). Our results provide a molecular-level view of quantum solute hydration and, more broadly, of how water-driven electron-transfer reactions proceed.
Identification of plasma proteomic markers underlying polygenic risk of type 2 diabetes and related comorbidities
Abstract Genomics can provide insight into the etiology of type 2 diabetes and its comorbidities, but assigning functionality to non-coding variants remains challenging. Polygenic scores, which aggregate variant effects, can uncover mechanisms when paired with molecular data. Here, we test polygenic scores for type 2 diabetes and cardiometabolic comorbidities for associations with 2,922 circulating proteins in the UK Biobank. The genome-wide type 2 diabetes polygenic score associates with 617 proteins, of which 75% also associate with another cardiometabolic score. Partitioned type 2 diabetes scores, which capture distinct disease biology, associate with 342 proteins (20% unique). In this work, we identify key pathways (e.g., complement cascade), potential therapeutic targets (e.g., FAM3D in type 2 diabetes), and biomarkers of diabetic comorbidities (e.g., EFEMP1 and IGFBP2) through causal inference, pathway enrichment, and Cox regression of clinical trial outcomes. Our results are available via an interactive portal ( https://public.cgr.astrazeneca.com/t2d-pgs/v1/ ).
Controlled macroscopic shape evolution of self-growing polymeric materials
Regulatory variation controlling architectural pleiotropy in maize
Abstract An early event in plant organogenesis is establishment of a boundary between the stem cell containing meristem and differentiating lateral organ. In maize ( Zea mays ), evidence suggests a common gene network functions at boundaries of distinct organs and contributes to pleiotropy between leaf angle and tassel branch number, two agronomic traits. To uncover regulatory variation at the nexus of these two traits, we use regulatory network topologies derived from specific developmental contexts to guide multivariate genome-wide association analyses. In addition to defining network plasticity around core pleiotropic loci, we identify new transcription factors that contribute to phenotypic variation in canopy architecture, and structural variation that contributes to cis -regulatory control of pleiotropy between tassel branching and leaf angle across maize diversity. Results demonstrate the power of informing statistical genetics with context-specific developmental networks to pinpoint pleiotropic loci and their cis -regulatory components, which can be used to fine-tune plant architecture for crop improvement.