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Open Access Publications from the University of California

Scholarly Works (6 results)

  • Thesis
  • Peer Reviewed
UC Riverside Electronic Theses and Dissertations (2024)

The strigolactone (SL) and karrikin (KAR) signaling pathways, two highly homologous pathways in plants, are not only essential in plant growth and development, symbiotic and parasitic interactions, and responses to environmental stresses, but also hold significant implications for the field of plant hormone biology. Understanding how these two complex pathways evolved to achieve specificity separate from one another while possibly maintaining a level of crosstalk has been a matter of great interest. The work in this dissertation, which aims to deepen knowledge of how receptors in each pathway interact with downstream protein partners.While there have been numerous technological advancements for analyzing strigolactone receptors, the processes, such as stable transformations, can be laborious and time-consuming. In the first chapter, I present an innovative and alternate approach to evaluate the functionality of the strigolactone receptor, DWARF14 (D14), in a transient assay in Nicotiana benthamiana. This approach, using CRISPR-cas9 to knock out the two endogenous N. benthamiana D14 genes, D14a and D14b, to analyze different strigolactone receptor functions in a transient system. The Nbd14a,b mutant displayed a typical d14 phenotype, short and highly branched. Using this mutant background and a ratiometric reporter system, I demonstrated how this system can evaluate D14 variants not previously investigated in a plant system. Most research on strigolactone receptors has concentrated on ligand binding and perception. Nevertheless, interactions with downstream protein partners, specifically SUPPRESSOR OF MAX2 LIKE (SMXLs) proteins, play a crucial role in strigolactone signal transduction. My second chapter focuses on identifying and mapping the D14 amino acids necessary for SMXL interaction. I determine highly conserved amino acids in D14 and analyze if these residues convey interaction towards the SMXL7 protein partner by mutational analysis in both the transient system described in Chapter One and stable Arabidopsis thaliana lines. The data indicates that altering specific D14 residues affects SMXL interaction, but there is no clear interaction interface. Additionally, variant D14D198A showed a defective interaction with SMXL. However, the data suggests that the D198 residue is crucial for the protein's structure and stability. Parasitic species in the Orobanchaceae family have evolved to sense host-derived SLs via the convergent evolution of karrikin receptors known as KAI2d proteins. In the last chapter, I used the transient N. benthamiana system to determine the functional roles of the seven KAI2d orthologs and the two SMAX1 orthologs found in the hemiparasite Phtheirospermum japonicum. The findings of this research, which discovered four PjKAI2d proteins are highly sensitive SL receptors, and two demonstrate inhibitory functions towards the sensitive receptors at low SL concentrations, hold great potential for further understanding and manipulation of plant-parasite interactions.

    • Article
    • Peer Reviewed
    UC Davis Previously Published Works (2023)
    PURPOSE: Outdoor light at night (LAN) can result in circadian disruption and hormone dysregulation and is a suspected risk factor for some cancers. Our study is the first to evaluate the association between LAN and risk of endometrial cancer, a malignancy with known relationship to circulating estrogen levels. METHODS: We linked enrollment addresses (1996) for 97,677 postmenopausal women in the prospective NIH-AARP cohort to satellite imagery of nighttime radiance to estimate LAN exposure. Multivariable Cox models estimated hazard ratios (HR) and 95% confidence intervals (95% CI) for LAN quintiles and incident endometrial cancer overall (1,669 cases) and endometrioid adenocarcinomas (991 cases) through follow-up (2011). We tested for interaction with established endometrial cancer risk factors. RESULTS: We observed no association for endometrial cancer overall (HRQ1vsQ5 0.92; 95% CI 0.78-1.08; p trend = 0.67) or endometrioid adenocarcinoma (HRQ1vsQ5 1.01; 95% CI 0.82-1.24; p trend = 0.36). Although body mass index and menopause hormone therapy were both associated with risk, there was no evidence of interaction with LAN (p interactions = 0.52 and 0.50, respectively). CONCLUSION: Our study did not find an association between outdoor LAN and endometrial cancer risk, but was limited by the inability to account for individual-level exposure determinants. Future studies should consider approaches to improve characterization of personal exposures to light.
      Cover page: Outdoor light at night and risk of endometrial cancer in the NIH-AARP diet and health study.
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2024)
      STUDY OBJECTIVE: To examine the association between light at night (LAN) and multiple sleep health dimensions. METHODS: Among 47 765 Sister Study participants, indoor LAN (TV on in the room, light(s) on in room, light from outside the room, nightlight, no light) and sleep dimensions were self-reported at baseline (2003-2009). We used Poisson regression with robust variance to estimate adjusted prevalence ratios (PR) and 95% confidence intervals (CI) for the cross-sectional associations between LAN and short sleep duration (<7 hours/night), insomnia symptoms (difficulty falling or staying asleep), frequent napping (≥3 naps/week), inconsistent sleep/wake time (differed day-to-day and week-to-week), sleep debt (≥2 hours between longest and shortest duration), recent sleep medication use, and a cumulative poor sleep score (≥3 poor sleep dimensions). Population-attributable risks (PARs) were determined for any light exposure vs. none by race/ethnicity. RESULTS: Compared to sleeping with no light in the bedroom, sleeping with a TV on was associated with a higher prevalence of most dimensions of poor sleep (e.g. short sleep duration: PR = 1.38, 95% CI: 1.32 to 1.45; inconsistent sleep/wake time: PR = 1.55, 95% CI: 1.44 to 1.66; sleep debt: PR = 1.36, 95% CI: 1.29 to 1.44; poor sleep score: PR = 1.58, 95% CI: 1.48-1.68). PARs tended to be higher for non-Hispanic black women compared to non-Hispanic white women. CONCLUSIONS: Sleeping with a TV on was associated with poor sleep health among US women, and non-Hispanic black women may be disproportionately burdened.
        Cover page: Exposure to indoor light at night in relation to multiple dimensions of sleep health: findings from the Sister Study.
        • Article
        • Peer Reviewed
        UC Davis Previously Published Works (2022)
        BACKGROUND: Light at night (LAN) may alter estrogen regulation through circadian disruption. High levels of outdoor LAN may increase breast cancer risk, but studies have largely not considered possible residual confounding from correlated environmental exposures. We evaluated the association between indoor and outdoor LAN and incident breast cancer. METHODS: In 47,145 participants in the prospective Sister Study cohort living in the contiguous U.S., exposure to outdoor LAN was determined using satellite-measured residential data and indoor LAN was self-reported (light/TV on, light from outside the room, nightlight, no light). We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between outdoor and indoor LAN and breast cancer risk. Models were adjusted for age, race/ethnicity, educational attainment, annual household income, neighborhood disadvantage, latitude, and population density as a proxy for urbanicity. To evaluate the potential for residual confounding of the outdoor LAN and breast cancer relationship by factors associated with urbanicity, we considered further adjustment for exposures correlated with outdoor LAN including NO2 [Spearman correlation coefficient, rho (ρ) = 0.78], PM2.5 (ρ = 0.36), green space (ρ =  - 0.41), and noise (ρ = 0.81). RESULTS: During 11 years of follow-up, 3,734 breast cancer cases were identified. Outdoor LAN was modestly, but non-monotonically, associated with a higher risk of breast cancer (Quintile 4 vs 1: HR = 1.10, 95% CI: 0.99-1.22; Quintile 5 vs 1: HR = 1.04, 95% CI: 0.93-1.16); however, no association was evident after adjustment for correlated ambient exposures (Quintile 4 vs 1: HR = 0.99, 95% CI: 0.86-1.14; Quintile 5 vs 1: HR = 0.89, 95% CI: 0.74-1.06). Compared to those with no indoor LAN exposure, sleeping with a light or TV on was associated with a HR = 1.09 (95% CI: 0.97-1.23) in the adjusted model. CONCLUSIONS: Outdoor LAN does not appear to increase the risk of breast cancer after adjustment for correlated environmental exposures.
          Cover page: Light at night and the risk of breast cancer: Findings from the Sister study.
          • Article
          • Peer Reviewed
          UC Berkeley Previously Published Works (2016)
          Mechanisms underlying the poor breast cancer prognosis among obese women are unresolved. DNA methylation levels are linked to obesity and to breast cancer survival. We hypothesized that obesity may work in conjunction with the epigenome to alter prognosis. Using a population-based sample of women diagnosed with first primary breast cancer, we examined modification of the obesity-mortality association by DNA methylation. In-person interviews were conducted approximately 3 months after diagnosis. Weight and height were assessed [to estimate body mass index (BMI)], and blood samples collected. Promoter methylation of 13 breast cancer-related genes was assessed in archived tumor by methylation-specific PCR and Methyl Light. Global methylation in white blood cell DNA was assessed by analysis of long interspersed elements-1 (LINE-1) and with the luminometric methylation assay (LUMA). Vital status among 1308 patients (with any methylation biomarker and complete BMI assessment) was determined after approximately 15 years of follow-up (N = 194/441 deaths due to breast cancer-specific/all-cause mortality). We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) using two-sided p values of 0.05. Breast cancer-specific mortality was higher among obese (BMI ≥ 30) patients with promoter methylation in APC (HR = 2.47; 95 % CI = 1.43-4.27) and TWIST1 (HR = 4.25; 95 % CI = 1.43-12.70) in breast cancer tissue. Estimates were similar, but less pronounced, for all-cause mortality. Increased all-cause (HR = 1.81; 95 % CI = 1.19-2.74) and breast cancer-specific (HR = 2.61; 95 % CI = 1.45-4.69) mortality was observed among obese patients with the lowest LUMA levels. The poor breast cancer prognosis associated with obesity may depend on methylation profiles, which warrants further investigation.
            Cover page: DNA methylation modifies the association between obesity and survival after breast cancer diagnosis
            • Article
            • Peer Reviewed
            UC Berkeley Previously Published Works (2019)

            Background

            The authors hypothesized that epigenetic changes may help to clarify the underlying biologic mechanism linking aspirin use to breast cancer prognosis. To the authors' knowledge, this is the first epidemiologic study to examine whether global methylation and/or tumor promoter methylation of breast cancer-related genes interact with aspirin use to impact mortality after breast cancer.

            Methods

            Prediagnosis aspirin use was assessed through in-person interviews within a population-based cohort of 1508 women diagnosed with a first primary breast cancer in 1996 and 1997. Global methylation in peripheral blood was assessed by long interspersed elements-1 (LINE-1) and the luminometric methylation assay. Promoter methylation of 13 breast cancer-related genes was measured in tumor by methylation-specific polymerase chain reaction and the MethyLight assay. Vital status was determined by the National Death Index through December 31, 2014 (N = 202/476 breast cancer-specific/all-cause deaths identified among 1266 women with any methylation assessment and complete aspirin data). Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs, and the likelihood ratio test was used to evaluate multiplicative interactions.

            Results

            All-cause mortality was elevated among aspirin users who had methylated promotor of BRCA1 (HR, 1.67; 95% CI, 1.26-2.22), but not among those with unmethylated promoter of BRCA1 (HR, 0.99; 95% CI, 0.67-1.45; P for interaction ≤.05). Decreased breast cancer-specific mortality was observed among aspirin users who had unmethylated promotor of BRCA1 and PR and global hypermethylation of LINE-1 (HR, 0.60, 0.78, and 0.63, respectively; P for interaction ≤.05), although the 95% CIs included the null.

            Conclusions

            The current study suggests that the LINE-1 global methylation and promoter methylation of BRCA1 and PR in tumor may interact with aspirin use to influence mortality after breast cancer.
              Cover page: Prediagnosis aspirin use, DNA methylation, and mortality after breast cancer: A population‐based study
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