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Polycomb Repressive Complex 2 (PRC2) mediates epigenetic silencing of target genes in animals and plants. In Arabidopsis, PRC2 is required for the cold-induced epigenetic silencing of theFLCfloral repressor locus to align flowering with spring. During this process, PRC2 relies on VEL accessory factors, including the constitutively expressed VRN5 and the cold-induced VIN3. The VEL proteins are physically associated with PRC2, but their individual functions remain unclear. Here, we show an intimate association between recombinant VRN5 and multiple components within a reconstituted PRC2, dependent on a compact conformation of VRN5 central domains. Key residues mediating this compact conformation are conserved amongst VRN5 orthologs across the plant kingdom. By contrast, VIN3 interacts with VAL1, a transcriptional repressor that binds directly toFLC. These associations differentially affect their role in H3K27me deposition: both proteins are required for H3K27me3, but only VRN5 is necessary for H3K27me2. Although originally defined as vernalization regulators, VIN3 and VRN5 co-associate with many targets in the Arabidopsis genome that are modified with H3K27me3. Our work, therefore, reveals the distinct accessory roles for VEL proteins in conferring cold-induced silencing onFLC, with broad relevance for PRC2 targets generally.

Galectins are a group of carbohydrate-binding proteins with a presumed immunomodulatory role and an elusive function on antigen-presenting cells. Here we used an in-depth and dynamic proteomic and phosphoproteomic analysis of human macrophages stimulated with galectin-1 and show that galectin-1 induces a tolerogenic macrophage phenotype with increased expression of key immune checkpoint protein programmed cell death 1 ligand 1 (PD-L1/CD274) and immunomodulator indoleamine 2,3-dioxygenase-1 (IDO1). Galectin-1 induced IDO1 and its active metabolite kynurenine in a dose-dependent manner dependent on JAK/STAT signaling. Analyzing the expression of galectin-1 showed that galectin-1 is upregulated across multiple tumors and in a 3D organotypic model system equipped with genetically engineered tumorigenic epithelial cells we find that the tumor-associated galectin-1 is derived from both epithelial and stromal cells. Our results highlight the potential of targeting galectin-1 in immunotherapeutic treatment of human cancers.

Transcriptional silencing through the Polycomb silencing machinery utilizes a "read-write" mechanism involving histone tail modifications. However, nucleation of silencing and long-term stable transmission of the silenced state also requires P-olycomb Repressive Complex 2 (PRC2) accessory proteins, whose molecular role is poorly understood. The Arabidopsis VEL proteins are accessory proteins that interact with PRC2 to nucleate and propagate silencing at the FLOWERING LOCUS C (FLC) locus, enabling early flowering in spring. Here, we report that VEL proteins contain a domain related to an atypical four-helix bundle that engages in spontaneous concentration-dependent head-to-tail polymerization to assemble dynamic biomolecular condensates. Mutations blocking polymerization of this VEL domain prevent Polycomb silencing at FLC. Plant VEL proteins thus facilitate assembly of dynamic multivalent Polycomb complexes required for inheritance of the silenced state.

Rice blast is a devastating disease caused by the fungal pathogen Magnaporthe oryzae that threatens rice production around the world. The fungus produces a specialized infection cell, called the appressorium, that enables penetration through the plant cell wall in response to surface signals from the rice leaf. The underlying biology of plant infection, including the regulation of appressorium formation, is not completely understood. Here we report the identification of a network of temporally coregulated transcription factors that act downstream of the Pmk1 mitogen-activated protein kinase pathway to regulate gene expression during appressorium-mediated plant infection. We show that this tiered regulatory mechanism involves Pmk1-dependent phosphorylation of the Hox7 homeobox transcription factor, which regulates genes associated with induction of major physiological changes required for appressorium development—including cell-cycle control, autophagic cell death, turgor generation and melanin biosynthesis—as well as controlling a additional set of virulence-associated transcription factor–encoding genes. Pmk1-dependent phosphorylation of Mst12 then regulates gene functions involved in septin-dependent cytoskeletal re-organization, polarized exocytosis and effector gene expression, which are necessary for plant tissue invasion. Identification of this regulatory cascade provides new potential targets for disease intervention. Comparative RNA-seq, ChIP–seq and quantitative phosphoproteomics reveal how the blast fungus uses the Pmk1 MAP kinase to regulate a network of transcription factors that orchestrate the complex transcriptome changes necessary for infecting rice plants.

This paper reviews the literature on additive manufacturing (AM) technologies and equipment, and spare parts classification criteria to propose a systematic process for selecting spare parts which are suitable for AM. This systematic process identifies criteria that can be used to select spare parts that are suitable for AM. The review found that there is limited research that addresses identifying processes for spare parts selection for AM, even though companies have identified this to be a key challenge in adopting AM. Seven areas for future research are identified relating to the methodology of spare parts selection for AM, processes for cross-functional integration in selecting spare parts for AM, broadening the spare parts portfolio that is suitable for AM (by considering usage of AM in conjunction with conventional technologies), and potential impact of AM on product modularity and integrality.

Rice blast is a devastating disease caused by the fungal pathogen Magnaporthe oryzae that threatens rice production around the world. The fungus produces a specialized infection cell, called the appressorium, that enables penetration through the plant cell wall in response to surface signals from the rice leaf. The underlying biology of plant infection, including the regulation of appressorium formation, is not completely understood. Here we report the identification of a network of temporally coregulated transcription factors that act downstream of the Pmk1 mitogen-activated protein kinase pathway to regulate gene expression during appressorium-mediated plant infection. We show that this tiered regulatory mechanism involves Pmk1-dependent phosphorylation of the Hox7 homeobox transcription factor, which regulates genes associated with induction of major physiological changes required for appressorium development-including cell-cycle control, autophagic cell death, turgor generation and melanin biosynthesis-as well as controlling a additional set of virulence-associated transcription factor-encoding genes. Pmk1-dependent phosphorylation of Mst12 then regulates gene functions involved in septin-dependent cytoskeletal re-organization, polarized exocytosis and effector gene expression, which are necessary for plant tissue invasion. Identification of this regulatory cascade provides new potential targets for disease intervention.