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Jones, V.

Publications and source records attributed to Jones, V..

7 recordsLinked to original sources

Systematic proteomics identifies a conserved mechanism for polar targeting of plant cortical proteins

Multicellular development is tightly coupled to the polarization of individual cells, which partitions polar proteins along the cell cortex and can control asymmetric cell division, anisotropic growth, local differentiation or physiology. Mechanisms driving cell polarization have been described in fungi and animals, but these lack counterparts in plants. While several polarized proteins have been identified in plants, the overall mechanisms guiding their polar localization are poorly characterized. Through iterative affinity proteomics on the recently identified SOSEKI polar proteins, we discovered a network of polar proteins that is conserved in the flowering plant Arabidopsis and the liverwort Marchantia. We next used this collection of novel polarized proteins for systematic proximity ligation proteomics in these two species to map their global polar proteome. We identified a subfamily of polarized Protein S-acyl transferase (PAT) enzymes that are required for membrane targeting of Arabidopsis SOSEKI proteins. Using human and fruit fly models, we showed that PAT19 is sufficient for membrane targeting of SOSEKI1, likely through direct palmitoylation. This work demonstrates a conserved mechanism for polar protein targeting in plants and offers a resource for studying polar protein localization.

plant biology↗

Operationalizing site-level conservation for migratory birds across the Americas flyways

Conserving migratory birds effectively requires full annual cycle strategies that identify where on-the-ground efforts can have the greatest impact. Here, we present a hemispheric spatial framework to identify priority areas for 112 migratory bird species across the Americas. Building on full annual cycle prioritizations, we defined finer-scale spatial planning units that reflect differences in migratory and congregational behaviors between shorebirds and landbirds. We compiled population data for each planning unit and focal species and applied conservation planning tools to design area-efficient portfolios of sites and landscapes that secure 10% of each species population within the Americas flyways. The resulting minimum area portfolios include 175 shorebird sites and 80 landbird landscapes optimized to meet the species-specific 10% representation targets across breeding, non-breeding, and passage seasons. We also identified a broader set of complementary solutions, ranked by an importance score, to provide decision-makers with flexible options for strategic resource allocation. This framework provides the scientific foundation for the Americas Flyways Initiative (AFI), which aims to catalyze investment in nature-based solutions and bird-friendly infrastructure to enhance the conservation of migratory birds and strengthen the resilience of the Americas flyways by 2050.

ecology↗

Guardian crypt-base-goblet-cells protect the human colonic stem cell niche by triggering cholinergic calcium signal-dependent MUC2 secretion and luminal flushing

Mucus secreting goblet cells play a vital role in the maintenance of tissue homeostasis. Here we report the discovery of an enigmatic mechanism for the generation of calcium signals that couple cholinergic input to secretion of hydrated mucus in the human colonic stem cell niche. Mechanistic insights for this study were derived from native human colonic crypts and crypt-like organoids expressing MUC2-mNEON. Importantly, we demonstrate that the human colonic stem cell niche is also a cholinergic niche, and that activation of muscarinic receptors initiates calcium signals at the apical pole of intestinal stem cells and neighbouring crypt-base-goblet-cells. The calcium signal trigger zone is defined by a microdomain of juxtaposed calcium stores expressing TPC1 and InsP3R3 calcium channels. Co-activation of TPC1 and InsP3R3 is required for generation of cholinergic calcium signals and downstream secretion of hydrated mucus, which culminates in the flushing of the colonic stem cell niche.

cell biology↗

The risk for insufficient chill accumulation: a climate change perspective for apple and cherry production in the United States

Winter chill accumulation is critical for the productivity and profitability of perennial tree fruit systems. Several studies have quantified the impacts of global warming on chill accumulation in the warmer production regions of the world, where insufficient chill events occur and their frequency is increasing. In contrast, we focus on a region with relatively cold winters-the Pacific Northwest United States (PNW)-where insufficient chill events are currently absent, and quantify the potential for introduction of these risks under climate change. Results identified spatial variation within the PNW, with chill accumulation projected to increase in some areas but decrease in others. There was also spatiotemporal variation in the driving factors of changes to chill accumulation. Even with decreases in chill accumulations, there are likely minimal issues with insufficient chill accumulation. However, delayed chill accumulation in combination with advances in the onset of heat accumulation can potentially shift the region from one where spring phenology is primarily forcing-driven to one where the dynamic interplay between chilling and forcing processes become important. These interactions might create production risks for varieties with high chill requirements, post mid-21st-century under high emissions scenarios. Future work should focus on understanding, modeling, and projecting responses across these overlapping chilling and forcing processes. Additionally, given significant spatial differences across a relatively small geographic range, it is also critical to understand and model these dynamics at a local landscape resolution for regions such as the PNW.

plant biology↗

KDM6B promotes oncogenic CDK4/6-pRB-E2F pathway via maintaining enhancer activation in high-risk neuroblastoma

The H3K27me2/me3 histone demethylase KDM6B is over-expressed in neuroblastoma and is essential to neuroblastoma cell survival. While the KDM6B inhibitor, GSK-J4, has shown activity in in vitro and in vivo preclinical models, the mechanism of action remains poorly defined. We demonstrate that genetic and pharmacologic inhibition of KDM6B downregulates the pRB-E2F transcriptome and MYCN expression. Chemical genetic analyses show that high expression of the E2F transcriptome is positively correlated with sensitivity of cancer cells to GSK-J4. Mechanistically, inhibition of KDM6B activity 1) reduces the chromatin accessibility of E2F target genes and MYCN, 2) selectively leads to an increase of H3K27me3 but a decrease of the enhancer mark H3K4me1 at the CTCF and BORIS binding sites, which may, consequently, disrupt the long-range chromatin interaction of MYCN and E2F target genes, and 3) phenocopies the transcriptome induced by the specific CDK4/6 inhibitor palbociclib. Overexpression of CDK4/6 or Rb1 knockout confers neuroblastoma cell resistance to both palbociclib and GSK-J4. A gene signature targeted by KDM6B inhibition is associated with poor survival of patients with neuroblastoma regardless of the MYCN status. These data indicate that KDM6B activity promotes an oncogenic CDK4/6-pRB-E2F pathway in neuroblastoma cells via H3K27me3-dependent enhancer-promoter interactions, providing a rationale to target KDM6B for high-risk neuroblastoma.

cancer biology↗

Forensic microbial system for high-resolution object provenance

Mapping where an object has been is a fundamental challenge for human health, commerce, and food safety. Location-specific microbes offers the potential to cheaply and sensitively determine object provenance. We created a synthetic, scalable microbial spore system that identifies object provenance in under one hour at meter-scale resolution and near single spore sensitivity, and that can be safely introduced into and recovered from the environment. This system solves the key challenges in object provenance: persistence in the environment, scalability, rapid and facile decoding, and biocontainment. Our system is compatible with SHERLOCK, facilitating its implementation in a wide range of applications.

bioengineering↗

Cytokinin signaling alters acid-fast staining of Mycobacterium tuberculosis

It was reported the human-exclusive pathogen Mycobacterium (M.) tuberculosis secretes cytokinins, which previously had only been known as plant hormones. Cytokinins are adenine-based signaling molecules in plants that have never been shown to participate in signal transduction in other kingdoms of life. Here, we show that cytokinins induce the strong expression of the M. tuberculosis gene, Rv0077c. We found that a TetR-like transcriptional regulator, Rv0078, directly repressed expression of the Rv0077c gene. Strikingly, cytokinin-induced expression of Rv0077c resulted in a loss of acid-fast staining of M. tuberculosis. Although acid-fast staining is thought to be associated with changes in the bacterial cell envelope and virulence, Rv0077c-induced loss of acid-fastness did not affect antibiotic susceptibility or attenuate bacterial growth in mice. Collectively, these findings show cytokinins signal transcriptional changes that affect the M. tuberculosis cell envelope, and that cytokinin signaling is no longer limited to the kingdom plantae.

microbiology↗