Skip to main content
eScholarship
Open Access Publications from the University of California

Scholarly Works (128 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2016)

Previous studies show mammalian cardiomyocytes will undergo depressed proliferation and induced apoptosis shortly after birth, but vary to different degrees in two ventricles. p38 MAP kinase (p38) was indicated to be a contributor to this variation, but with unclear functioning mechanism. For a better understanding, we conducted in vivo study using p38α/β cardiac specific conditional knockout mice model, and in vitro experiments in neonatal rat ventricular cardomyocytes. Both models show inhibiting p38α/β causes an increased expression of inositol-requiring protein 1 alpha (IRE1α) and x-box binding protein 1 (XBP1) splicing in cardiomyocytes, but different pro-survival responses at different postnatal days: elevated mitosis at P3 while reduced apoptosis at P1, while both responses were found in vitro. Overexpressing IRE1α in vitro generates similar pro-survival effect to p38 inhibition, whereas knocking down XBP1 significantly blunts p38-inhibition-induced proliferation. Thus, we raise a chamber-specific model in which p38 regulates postnatal heart proliferation/apoptosis via inhibiting IRE1α.

    Cover page: p38 MAP Kinase Regulates Remodeling of Heart via IRE1α During Early Postnatal Development
    • Article
    • Peer Reviewed
    UC Davis Previously Published Works (2020)
    The ubiquitin-proteasome system (UPS) governs the protein degradation process and balances proteostasis and cellular homeostasis. It is a well-controlled mechanism, in which removal of the damaged or excessive proteins is essential in driving signal pathways for cell survival or death. Accumulation of damaged proteins and failure in removal may contribute to disease initiation such as in cancers and neurodegenerative diseases. In this notion, specific protein-protein interaction is essential for the recognition of targeted proteins in UPS. WW domain plays an indispensable role in the protein-protein interactions during signaling. Among the 51 WW domain-containing proteins in the human proteomics, near one-quarter of them are involved in the UPS, suggesting that WW domains are crucial modules for driving the protein-protein binding and subsequent ubiquitination and degradation. In this review, we detail a broad spectrum of WW domains in protein-protein recognition, signal transduction, and relevance to diseases. New perspectives in dissecting the molecular interactions are provided.
      Cover page: Functional role of WW domain‐containing proteins in tumor biology and diseases: Insight into the role in ubiquitin‐proteasome system
      • Article
      • Peer Reviewed
      UC Santa Barbara Previously Published Works (2016)
      Adenosine deaminases acting on double-stranded RNA (ADARs) catalyze the deamination of adenosine (A) to produce inosine (I) in double-stranded (ds) RNA structures, a process known as A-to-I RNA editing. dsRNA is an important trigger of innate immune responses, including interferon (IFN) production and action. We examined the role of A-to-I RNA editing by two ADARs, ADAR1 and ADAR2, in the sensing of self-RNA in the absence of pathogen infection, leading to activation of IFN-induced, RNA-mediated responses in mouse embryo fibroblasts. IFN treatment of Adar1(-/-) cells lacking both the p110 constitutive and p150 IFN-inducible ADAR1 proteins induced formation of stress granules, whereas neither wild-type (WT) nor Adar2(-/-) cells displayed a comparable stress granule response following IFN treatment. Phosphorylation of protein synthesis initiation factor eIF2α at serine 51 was increased in IFN-treated Adar1(-/-) cells but not in either WT or Adar2(-/-) cells following IFN treatment. Analysis by deep sequencing of mouse exonic loci containing A-to-I-editing sites revealed that the majority of editing in mouse embryo fibroblasts was carried out by ADAR1. IFN treatment increased editing in both WT and Adar2(-/-) cells but not in either Adar1(-/-) or Adar1(-/-) (p150) cells or Stat1(-/-) or Stat2(-/-) cells. Hyper-edited sites found in predicted duplex structures showed strand bias of editing for some RNAs. These results implicate ADAR1 p150 as the major A-to-I editor in mouse embryo fibroblasts, acting as a feedback suppressor of innate immune responses otherwise triggered by self-RNAs possessing regions of double-stranded character.
        Cover page: Editing of Cellular Self-RNAs by Adenosine Deaminase ADAR1 Suppresses Innate Immune Stress Responses*
        • Article
        • Peer Reviewed
        LBL Publications (2015)
        Arbuscular mycorrhizal fungi (AMF) are considered as a potential biotechnological tool for improving phytostabilization efficiency and plant tolerance to heavy metal-contaminated soils. However, the mechanisms through which AMF help to alleviate metal toxicity in plants are still poorly understood. A greenhouse experiment was conducted to evaluate the effects of two AMF species (Funneliformis mosseae and Rhizophagus intraradices) on the growth, Pb accumulation, photosynthesis and antioxidant enzyme activities of a leguminous tree (Robinia pseudoacacia L.) at Pb addition levels of 0, 500, 1000 and 2000 mg kg(-1) soil. AMF symbiosis decreased Pb concentrations in the leaves and promoted the accumulation of biomass as well as photosynthetic pigment contents. Mycorrhizal plants had higher gas exchange capacity, non-photochemistry efficiency, and photochemistry efficiency compared with non-mycorrhizal plants. The enzymatic activities of superoxide dismutase (SOD), ascorbate peroxidases (APX) and glutathione peroxidase (GPX) were enhanced, and hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents were reduced in mycorrhizal plants. These findings suggested that AMF symbiosis could protect plants by alleviating cellular oxidative damage in response to Pb stress. Furthermore, mycorrhizal dependency on plants increased with increasing Pb stress levels, indicating that AMF inoculation likely played a more important role in plant Pb tolerance in heavily contaminated soils. Overall, both F. mosseae and R. intraradices were able to maintain efficient symbiosis with R. pseudoacacia in Pb polluted soils. AMF symbiosis can improve photosynthesis and reactive oxygen species (ROS) scavenging capabilities and decrease Pb concentrations in leaves to alleviate Pb toxicity in R. pseudoacacia. Our results suggest that the application of the two AMF species associated with R. pseudoacacia could be a promising strategy for enhancing the phytostabilization efficiency of Pb contaminated soils.
          Cover page: The Combined Effects of Arbuscular Mycorrhizal Fungi (AMF) and Lead (Pb) Stress on Pb Accumulation, Plant Growth Parameters, Photosynthesis, and Antioxidant Enzymes in Robinia pseudoacacia L.
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2018)
          Heart failure is associated with induction of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). The serine/threonine protein kinase/endoribonuclease IRE1α is a key protein in ER stress signal transduction. IRE1α activity can induce both protective UPR and apoptotic downstream signaling events, but the specific role for IRE1α activity in the heart is unknown. A major aim of this study was to characterize the specific contribution of IRE1α in cardiac physiology and pathogenesis. We used both cultured myocytes and a transgenic mouse line with inducible and cardiomyocyte-specific IRE1α overexpression as experimental models to achieve targeted IRE1α activation. IRE1α expression induced a potent but transient ER stress response in cardiomyocytes and did not cause significant effects in the intact heart under normal physiological conditions. Furthermore, the IRE1α-activated transgenic heart responding to pressure overload exhibited preserved function and reduced fibrotic area, associated with increased adaptive UPR signaling and with blunted inflammatory and pathological gene expression. Therefore, we conclude that IRE1α induces transient ER stress signaling and confers a protective effect against pressure overload-induced pathological remodeling in the heart. To our knowledge, this report provides first direct evidence of a specific and protective role for IRE1α in the heart and reveals an interaction between ER stress signaling and inflammatory regulation in the pathologically stressed heart.
            Cover page: The serine/threonine-protein kinase/endoribonuclease IRE1α protects the heart against pressure overload–induced heart failure
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (2012)
            Previous research reported that a rare serotonin receptor 2B gene (HTR2B) stop codon mutation predisposes subjects to severe impulsivity and novelty seeking. In this study, we expanded this previous work by testing six single nucleotide polymorphisms (SNPs) within the HTR2B gene for potential associations with the behavioral inhibition system (BIS) and the three components of the behavioral approach systems (BAS: fun seeking, drive, and reward responsiveness) in a Han Chinese sample (N= 478). Association analysis for individual SNPs indicated that four of the six SNPs (i.e., rs6437000, rs10194776, rs16827801, and rs1549339) were significantly associated with BAS fun seeking (p= 0003-0022). Haplotype-based association analysis revealed that fun seeking was positively associated with haplotype A-A-G-A for SNPs rs6437000- rs10194776- rs16827801- rs1549339 (p= 0002), which survived Bonferroni correction. Except for the association between BAS reward responsiveness and rs16827801 (p= 005), no other association was found for BAS drive, BAS reward responsiveness, or BIS. This study provides the first evidence for the involvement of the HTR2B gene in BAS fun seeking. A better understanding of the genetic basis of the BIS and BAS would allow us to develop more effective diagnosis, treatment, and prevention of impulsive behavioral problems. © 2012 Elsevier Ltd.
              Cover page: Association between the HTR2B gene and the personality trait of fun seekingCreative Commons 'BY' version 4.0 license
              • Article
              • Peer Reviewed
              UC Irvine Previously Published Works (2013)
                Cover page: Genotypes over-represented among college students are linked to better cognitive abilities and socioemotional adjustmentCreative Commons 'BY' version 4.0 license
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2013)
                Previous functional neuroimaging studies have shown that the left mid-fusiform cortex plays a critical role in reading. However, there is very limited research relating this region's anatomical structure to reading performance either in native or second language. Using structural MRI and three reading tasks (Chinese characters, English words, and alphabetic pseudowords) and a non-reading task (visual-auditory learning), this study investigated the contributions of the left mid-fusiform cortical thickness to reading in a large sample of 226 Chinese subjects. Results showed that the cortical thickness in the left mid-fusiform gyrus was positively correlated with performance on all three reading tasks but not with the performance on the non-reading task. Our findings provide structural evidence for the left mid-fusiform cortex as the "gateway" region for reading Chinese and English. The absence of the association between the left mid-fusiform cortical thickness and non-reading performance implied the specific role of this area in reading skills, not in general language skills.
                  Cover page: The contribution of the left mid-fusiform cortical thickness to Chinese and English reading in a large Chinese sampleCreative Commons 'BY' version 4.0 license
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2011)
                  Background

                  Recent molecular genetics studies showed significant associations between dopamine-related genes (including genes for dopamine receptors, transporters, and degradation) and working memory, but little is known about the role of genes for dopamine modulation, such as those related to neurotensin (NT), in working memory. A recent animal study has suggested that NT antagonist administration impaired working memory in a learning task. The current study examined associations between NT genes and working memory among humans.

                  Methods

                  Four hundred and sixty healthy undergraduate students were assessed with a 2-back working memory paradigm. 5 SNPs in the NTSR1 gene were genotyped. 5 ANOVA tests were conducted to examine whether and how working memory differed by NTSR1 genotype, with each SNP variant as the independent variable and the average accuracy on the working memory task as the dependent variable.

                  Results

                  ANOVA results suggested that two SNPs in the NTSR1 gene (rs4334545 and rs6090453) were significantly associated with working memory. These results survived corrections for multiple comparisons.

                  Conclusions

                  Our results demonstrated that NTSR1 SNP polymorphisms were significantly associated with variance in working memory performance among healthy adults. This result extended previous rodent studies showing that the NT deficiency impairs the working memory function. Future research should replicate our findings and extend to an examination of other dopamine modulators.

                    Cover page: Neurotensin Receptor 1 Gene (NTSR1) Polymorphism Is Associated with Working MemoryCreative Commons 'BY' version 4.0 license
                    • Article
                    • Peer Reviewed
                    LBL Publications (2019)
                    Amine-functionalized polyhedral oligomeric silsesquioxane (POSS), the smallest, monodisperse cage-shaped silica cubic nanoparticle, is exceptionally interfacially active and can form assemblies that jam the toluene/water interface, locking in non-equilibrium shapes of one liquid phase in another. The packing density of the amine-functionalized POSS assembly at the water/toluene interface can be tuned by varying the concentration, the pH value, and the degree of POSS functionalization. Functionalized POSS gives a higher interface coverage, and hence a lower interfacial tension, than nanoparticle surfactants formed by interactions between functionalized nanoparticles and polymeric ligands. Hydrogen-bonded POSS surfactants are more stable at the interface, offering some unique advantages for generating Pickering emulsions over typical micron-sized colloidal particles and ligand-stabilized nanoparticle surfactants.
                      Cover page: Interfacial Activity of Amine‐Functionalized Polyhedral Oligomeric Silsesquioxanes (POSS): A Simple Strategy To Structure Liquids
                      Top