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Open Access Publications from the University of California

Scholarly Works (68 results)

  • Article
  • Peer Reviewed
UC Davis Previously Published Works (2017)
Metabolomics answers a fundamental question in biology: How does metabolism respond to genetic, environmental or phenotypic perturbations? Combining several metabolomics assays can yield datasets for more than 800 structurally identified metabolites. However, biological interpretations of metabolic regulation in these datasets are hindered by inherent limits of pathway enrichment statistics. We have developed ChemRICH, a statistical enrichment approach that is based on chemical similarity rather than sparse biochemical knowledge annotations. ChemRICH utilizes structure similarity and chemical ontologies to map all known metabolites and name metabolic modules. Unlike pathway mapping, this strategy yields study-specific, non-overlapping sets of all identified metabolites. Subsequent enrichment statistics is superior to pathway enrichments because ChemRICH sets have a self-contained size where p-values do not rely on the size of a background database. We demonstrate ChemRICH’s efficiency on a public metabolomics data set discerning the development of type 1 diabetes in a non-obese diabetic mouse model. ChemRICH is available at www.chemrich.fiehnlab.ucdavis.edu
    • Article
    • Peer Reviewed
    UC Davis Previously Published Works (2019)

    Background

    Blood chemicals are routinely measured in clinical or preclinical research studies to diagnose diseases, assess risks in epidemiological research, or use metabolomic phenotyping in response to treatments. A vast volume of blood-related literature is available via the PubMed database for data mining.

    Objectives

    We aimed to generate a comprehensive blood exposome database of endogenous and exogenous chemicals associated with the mammalian circulating system through text mining and database fusion.

    Methods

    Using NCBI resources, we retrieved PubMed abstracts, PubChem chemical synonyms, and PMC supplementary tables. We then employed text mining and PubChem crowdsourcing to associate phrases relating to blood with PubChem chemicals. False positives were removed by a phrase pattern and a compound exclusion list.

    Results

    A query to identify blood-related publications in the PubMed database yielded 1.1 million papers. Matching a total of 15 million synonyms from 6.5 million relevant PubChem chemicals against all blood-related publications yielded 37,514 chemicals and 851,999 publications records. Mapping PubChem compound identifiers to the PubMed database yielded 49,940 unique chemicals linked to 676,643 papers. Analysis of open-access metabolomics papers related to blood phrases in the PMC database yielded 4,039 unique compounds and 204 papers. Consolidating these three approaches summed up to a total of 41,474 achiral structures that were linked to 65,957 PubChem CIDs and to over 878,966 PubMed articles. We mapped these compounds to 50 databases such as those covering metabolites and pathways, governmental and toxicological databases, pharmacology resources, and bioassay repositories. In comparison, HMDB, the Human Metabolome Database, links 1,075 compounds to blood-related primary publications.

    Conclusion

    This new Blood Exposome Database can be used for prioritizing chemicals for systematic reviews, developing target assays in exposome research, identifying compounds in untargeted mass spectrometry, and biological interpretation in metabolomics data. The database is available at http://bloodexposome.org. https://doi.org/10.1289/EHP4713.
      Cover page: Generating the Blood Exposome Database Using a Comprehensive Text Mining and Database Fusion Approach
      • Thesis
      • Peer Reviewed
      UC Davis Electronic Theses and Dissertations (2024)

      Plants’ innate immunity is composed of two intricate immune networks: pattern-triggered immunity (PTI) and effector-triggered immunity (ETI). PTI is activated upon the recognition of pathogen-associated molecular patterns (PAMPs) by a pattern recognition receptor (PRRs). The outcomes of PTI are considered broad spectrum but can be easily suppressed by effectors from the adapted pathogens. Perception of the pathogen effectors by a nucleotide-binding leucine-rich (NLR) receptor activates ETI, which leads to a robust response in the form of localized programmed cell death at the site of infection. NLRs are classified into different classes based on protein structures: coiled-coil NLRs (CNLs) and Toll/interleukin-1 NLRs (TNLs). Both types deploy common and unique mechanisms to achieve immunity. CNLs can function as singletons, linked pairs or complex networks. Meanwhile, TNLs rely on the downstream immune modulator, ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1). EDS1 coordinates with RPW8-like NLRs (RNLs) to attain the defense response. In this dissertation, I describe the current knowledge and perspectives about the major types of NLRs in plants, including their discovery and functions, and various mechanisms they utilize to establish immunity. I also present findings of my studies, in which the regulation of EDS1 immune signaling is elucidated by TurboID-based proximity labeling proteomics. A unique NLR, belonging to the NLR-requirement for cell death (NRC) family, is identified as a negative regulator of TNL-mediated immunity. The connection between autophagy and TNL immune network is revealed in this work from the demonstration of interactions between autophagy-related gene 6 (ATG6) and the EDS1 complexes. Overall, this dissertation contributes to a better understanding of EDS1 immune signaling in plants and highlights the interplays amongst different classes of NLRs, and also autophagy as ways to fine-tune TNL-mediated immunity.

        • Article
        • Peer Reviewed
        UC Davis Previously Published Works (2014)
        Plant innate immune response against viruses utilizes intracellular Nucleotide Binding domain Leucine Rich Repeat (NLR) class of receptors. NLRs recognize different viral proteins termed elicitors and initiate diverse signaling processes that induce programmed cell death (PCD) in infected cells and restrict virus spread. In this review we describe the recent advances made in the study of plant NLRs that detect viruses. We describe some of the physical and functional interactions these NLRs undertake. We elaborate on the intra-molecular and homotypic association of NLRs that function in self-regulation and activation. Nuclear role for some viral NLRs is discussed as well as the emerging importance of the RNAi pathway in regulating the NLR family.
          • Article
          • Peer Reviewed
          UC Davis Previously Published Works (2014)
          Macroautophagy (hereafter autophagy) is a regulated intracellular process during which cytoplasmic cargo engulfed by double-membrane autophagosomes is delivered to the vacuole or lysosome for degradation and recycling. Atg8 that is conjugated to phosphatidylethanolamine (PE) during autophagy plays an important role not only in autophagosome biogenesis but also in cargo recruitment. Conjugation of PE to Atg8 requires processing of the C-terminal conserved glycine residue in Atg8 by the Atg4 cysteine protease. The Arabidopsis plant genome contains 9 Atg8 (AtATG8a to AtATG8i) and 2 Atg4 (AtATG4a and AtATG4b) family members. To understand AtATG4's specificity toward different AtATG8 substrates, we generated a unique synthetic substrate C-AtATG8-ShR (citrine-AtATG8-Renilla luciferase SuperhRLUC). In vitro analyses indicated that AtATG4a is catalytically more active and has broad AtATG8 substrate specificity compared with AtATG4b. Arabidopsis transgenic plants expressing the synthetic substrate C-AtAtg8a-ShR is efficiently processed by endogenous AtATG4s and targeted to the vacuole during nitrogen starvation. These results indicate that the synthetic substrate mimics endogenous AtATG8, and its processing can be monitored in vivo by a bioluminescence resonance energy transfer (BRET) assay. The synthetic Atg8 substrates provide an easy and versatile method to study plant autophagy during different biological processes.
            • Article
            • Peer Reviewed
            UC Davis Previously Published Works (2014)
            Autophagy is a highly conserved biological process during which double membrane bound autophagosomes carry intracellular cargo material to the vacuole or lysosome for degradation and/or recycling. Autophagosome biogenesis requires Autophagy 4 (Atg4) cysteine protease-mediated processing of ubiquitin-like Atg8 proteins. Unlike single Atg4 and Atg8 genes in yeast, the Arabidopsis genome contains two Atg4 (AtAtg4a and AtAtg4b) and nine Atg8 (AtAtg8a-AtAtg8i) genes. However, we know very little about specificity of different AtAtg4s for processing of different AtAtg8s. Here, we describe a unique bioluminescence resonance energy transfer-based AtAtg8 synthetic substrate to assess AtAtg4 activity in vitro and in vivo. In addition, we developed a unique native gel assay of superhRLUC catalytic activity assay to monitor cleavage of AtAtg8s in vitro. Our results indicate that AtAtg4a is the predominant protease and that it processes AtAtg8a, AtAtg8c, AtAtg8d, and AtAtg8i better than AtAtg4b in vitro. In addition, kinetic analyses indicate that although both AtAtg4s have similar substrate affinity, AtAtg4a is more active than AtAtg4b in vitro. Activity of AtAtg4s is reversibly inhibited in vitro by reactive oxygen species such as H2O2. Our in vivo bioluminescence resonance energy transfer analyses in Arabidopsis transgenic plants indicate that the AtAtg8 synthetic substrate is efficiently processed and this is AtAtg4 dependent. These results indicate that the synthetic AtAtg8 substrate is used efficiently in the biogenesis of autophagosomes in vivo. Transgenic Arabidopsis plants expressing the AtAtg8 synthetic substrate will be a valuable tool to dissect autophagy processes and the role of autophagy during different biological processes in plants.
              • Article
              • Peer Reviewed
              UC Davis Previously Published Works (2019)
              In unstressed conditions, the cap-binding protein, eIF4E, binds the 5' cap structure (m7G) on mRNA and recruits other translation initiation factors to bring the ribosome to the mRNA. Bruns et al. show that, in plants, phosphorylation of eIF4E by the master metabolic regulatory protein, sucrose nonfermenting-related kinase 1 (SnRK1), reduces translation globally. This negative regulation of translation inhibits geminivirus infection and is speculated to be a response to various abiotic stresses.
                Cover page: A new mechanism for translational control in plants
                • Article
                • Peer Reviewed
                UC Davis Previously Published Works (2021)
                RNAi is a major plant antiviral strategy. However, the mechanisms triggering RNAi are unknown. In this issue of Cell Host & Microbe, Wang et al. (2021) demonstrate that wound-induced calcium signaling induces RNAi activation. As a counter-defense, a viral suppressor of RNAi (VSR) interferes with players in calcium signaling.
                  Cover page: Ca2+ kickstarts antiviral RNAi
                  • Article
                  • Peer Reviewed
                  UC Davis Previously Published Works (2014)
                    • Thesis
                    • Peer Reviewed
                    UC Davis Electronic Theses and Dissertations (2023)

                    AbstractDuring the immune response there is a significant increase in the number of protrusions of the chloroplast stroma known as stromules. These stromules were reported over 100 years ago; however, their function has remained elusive. Recently, it was shown that chloroplast stromules are induced during the plant innate immune response and serve as positive regulators of the immune response. Toward this, we wanted to identify genetic components required for stromule formation. Using a candidate approach, we found a kinesin containing a calponin homology domain, Kinesin required for Inducing Stromules 1 (KIS1) which induces constitutive stromule formation when overexpressed and is required for N-TNL mediated stromule formation and immunity to Tobacco mosaic virus (TMV). Further, we used pathogen effectors as a probe to identify proteins which are required for stromule formation and subsequent perinuclear chloroplast clustering during the N-mediated immune response. Using TurboID-based proximity labeling we identified four proteins which interact with the Type 3 secretion system (T3SS) effector SH9 and are required for immunity to TMV. Toward this, we showed that one SH9 interactor, Sh9 interactor 1 is required for perinuclear chloroplast clustering during the N-mediated immune response. Our results with KIS1 represent the first known component required for stromule formation. Further, our initial characterization of Sh9 interactor 1 suggests that perinuclear chloroplast clustering is required for immunity to TMV and is specifically inhibited by the effector Sh9.

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