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Open Access Publications from the University of California

Scholarly Works (7 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2013)

Remembering information based on its importance or value can help facilitate a person's quality of life by having them selectively prioritize specific information at the cost of being less likely to remember other, less important, information. My dissertation examines the cognitive mechanisms that are involved with this "value-directed remembering" (VDR), as well as how effectively learning information based on its value or importance can be applied to using memory practically in everyday life. Specifically, I tested whether value influences category learning (Chapter 2; Experiments 1-3) and the impact of value on remembering medication side effects (Chapter 3; Experiments 4-6). Generally speaking, the results from the present research suggest that VDR can occur in these paradigms under certain conditions, and that value influences memory performance in both younger and older adults. The findings show that that goal-directed learning occurs in the presence of high value information and that the selective encoding and/or rehearsal of important information during learning is a cognitively active and effortful process. This research illustrates how the importance or value we place on information can help us prioritize our learning and, in turn, facilitate our later retrieval for that information in both theoretically driven and practical memory tasks. The implications of this research range from assisting students to improve the quality of their learning and study habits, to helping doctors identify and classify tumors and broken bones, to improving overall quality of life in older adults.

    Cover page: The Importance of Selectivity in Memory: The Influence of Value on Monitoring, Learning, and Cognitive Aging
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2015)
    Older adults often experience memory impairments, but sometimes they can use selective processing and schematic support to remember important information. In the present experiments, we investigated the degrees to which younger and healthy older adults remembered medication side effects that were subjectively or objectively important to remember. Participants studied a list of common side effects and rated how negative these effects would be if they were to experience them, and they were then given a free recall test. In Experiment 1, the severity of the side effects ranged from mild (e.g., itching) to severe (e.g., stroke), and in Experiment 2, certain side effects were indicated as being critical to remember (i.e., "contact your doctor if you experience this"). We observed no age differences in terms of free recall of the side effects, and older adults remembered more severe side effects than mild effects. However, older adults were less likely to recognize the critical side effects on a later recognition test, relative to younger adults. These findings suggest that older adults can selectively remember medication side effects but have difficulty identifying familiar but potentially critical side effects, and this has implications for monitoring medication use in older age.
      Cover page: Memory for medication side effects in younger and older adults: The role of subjective and objective importance
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2017)
      Ageing typically leads to various memory deficits which results in older adults' tendency to remember more general information and rely on gist memory. The current study examined if younger and older adults could remember which of two comparable grocery items (e.g., two similar but different jams) was paired with a lower price (the "better buy"). Participants studied lists of grocery items and their prices, in which the two items in each category were presented consecutively (Experiment 1), or separated by intervening items (Experiment 2). At test, participants were asked to identify the "better buy" and recall the price of both items. There were negligible age-related differences for the "better buy" in Experiment 1, but age-related differences were present in Experiment 2 when there were greater memory demands involved in comparing the two items. Together, these findings suggest that when price information of two items can be evaluated and compared within a short period of time, older adults can form stable gist-based memory for prices, but that this is impaired with longer delays. We relate the findings to age-related changes in the use of gist and verbatim memory when remembering prices, as well as the associative deficit account of cognitive ageing.
        Cover page: Gist-based memory for prices and “better buys” in younger and older adults
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2016)
        Older adults often experience associative memory impairments but can sometimes remember important information. The current experiments investigate potential age-related similarities and differences associate memory for gains and losses. Younger and older participants were presented with faces and associated dollar amounts, which indicated how much money the person "owed" the participant, and were later given a cued recall test for the dollar amount. Experiment 1 examined face-dollar amount pairs while Experiment 2 included negative dollar amounts to examine both gains and losses. While younger adults recalled more information relative to older adults, both groups were more accurate in recalling the correct value associated with high-value faces compared to lower-value faces and remembered gist-information about the values. However, negative values (losses) did not have a strong impact on recall among older adults versus younger adults, illustrating important associative memory differences between younger and older adults.
          Cover page: I owe you: age-related similarities and differences in associative memory for gains and losses
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2016)
          Approximately 75% of melanomas have known driver oncogenic mutations in BRAF, NRAS, GNA11 or GNAQ, while the mutations providing constitutive oncogenic signaling in the remaining melanomas are not known. We established a melanoma cell line from a tumor with none of the common driver mutations. This cell line demonstrated a signaling profile similar to BRAF-mutants, but lacked sensitivity to the BRAF inhibitor vemurafenib. RNA-seq mutation data implicated CRAF R391W as the alternative driver mutation of this melanoma. CRAF R391W was homozygous and over expressed. These melanoma cells were highly sensitive to CRAF, but not BRAF knockdown. In reconstitution experiments, CRAF R391W, but not CRAF WT, transformed NIH3T3 cells in soft-agar colony formation assays, increased kinase activity in vitro, induced MAP kinase signaling and conferred vemurafenib resistance. MAP kinase inducing activity was dependent on CRAF dimerization. Thus, CRAF is a bona fide alternative oncogene for BRAF/NRAS/GNAQ/GNA11 wild type melanomas.
            Cover page: CRAF R391W is a melanoma driver oncogene
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2016)
            A prominent mechanism of acquired resistance to BRAF inhibitors in BRAF (V600) -mutant melanoma is associated with the upregulation of receptor tyrosine kinases. Evidences suggested that this resistance mechanism is part of a more complex cellular adaptation process. Using an integrative strategy, we found this mechanism to invoke extensive transcriptomic, (phospho-) proteomic and phenotypic alterations that accompany a cellular transition to a de-differentiated, mesenchymal and invasive state. Even short-term BRAF-inhibitor exposure leads to an early adaptive, differentiation state change-characterized by a slow-cycling, persistent state. The early persistent state is distinct from the late proliferative, resistant state. However, both differentiation states share common signaling alterations including JUN upregulation. Motivated by the similarities, we found that co-targeting of BRAF and JUN is synergistic in killing fully resistant cells; and when used up-front, co-targeting substantially impairs the formation of the persistent subpopulation. We confirmed that JUN upregulation is a common response to BRAF inhibitor treatment in clinically treated patient tumors. Our findings demonstrate that events shared between early- and late-adaptation states provide candidate up-front co-treatment targets.
              Cover page: JUN dependency in distinct early and late BRAF inhibition adaptation states of melanoma.
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2017)
              Copy number alteration (CNA) profiling of human tumors has revealed recurrent patterns of DNA amplifications and deletions across diverse cancer types. These patterns are suggestive of conserved selection pressures during tumor evolution but cannot be fully explained by known oncogenes and tumor suppressor genes. Using a pan-cancer analysis of CNA data from patient tumors and experimental systems, here we show that principal component analysis-defined CNA signatures are predictive of glycolytic phenotypes, including 18F-fluorodeoxy-glucose (FDG) avidity of patient tumors, and increased proliferation. The primary CNA signature is enriched for p53 mutations and is associated with glycolysis through coordinate amplification of glycolytic genes and other cancer-linked metabolic enzymes. A pan-cancer and cross-species comparison of CNAs highlighted 26 consistently altered DNA regions, containing 11 enzymes in the glycolysis pathway in addition to known cancer-driving genes. Furthermore, exogenous expression of hexokinase and enolase enzymes in an experimental immortalization system altered the subsequent copy number status of the corresponding endogenous loci, supporting the hypothesis that these metabolic genes act as drivers within the conserved CNA amplification regions. Taken together, these results demonstrate that metabolic stress acts as a selective pressure underlying the recurrent CNAs observed in human tumors, and further cast genomic instability as an enabling event in tumorigenesis and metabolic evolution.
                Cover page: Recurrent patterns of DNA copy number alterations in tumors reflect metabolic selection pressures
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