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Open Access Publications from the University of California

Scholarly Works (4 results)

  • Article
  • Peer Reviewed
Frontiers of Biogeography, Volume 11, Issue 2 (2019)

Arthropods are a major component of ecosystems, in terms of both their biomass and the variety of functional roles they play. Yet we lack a clear understanding of how arthropod abundance changes along environmental gradients. We compiled published literature on overall arthropod abundances (number of individuals) along elevational gradients and performed a formal meta-analysis on the role of latitude, climatic variables, and interactions with ants in shaping the pattern. Specifically, we asked if patterns of arthropod abundance along different elevational gradients are associated with gradients of seasonality and precipitation and whether ant abundance affects other arthropods. Arthropod abundance peaks at higher elevations at mid-latitudes than low latitudes; hence, the correlation between arthropod abundance and elevation shifts from negative to positive with an increase in latitude. We suggest these patterns reflect a steep elevational gradient in the length of growing season at mid-latitudes, with the short growing season at high elevations in mid-latitudes leading to synchronous emergence and reproduction of arthropods generating a sharp increase in abundance. Precipitation and ant abundance do not have a consistent effect on arthropod abundance along most elevational gradients. However, on gradients with a very dry base and sharp increase in precipitation with elevation, arthropod abundance peaks at higher elevations. Overall, our results suggest that future changes in the length of growing season will impact the elevation at which summer arthropod abundance peaks and the sharpness of the peak, likely affecting diversity and distribution of other taxa that interact with arthropods.

  • 2 supplemental ZIPs
Cover page: Analysis of tropical and temperate elevational gradients in arthropod abundanceCreative Commons 'BY' version 4.0 license
  • Article
  • Peer Reviewed
UCLA Previously Published Works (2023)
A parallel series of general chemistry courses for Life Science Majors was created in an effort to support students and improve general chemistry outcomes. We created a two-quarter enhanced general chemistry course series that is not remedial, but instead implements several evidence-based teaching practices including Process Oriented Guided Inquiry Learning (POGIL), Peer-Led Team Learning (PLTL), and the Learning Assistant (LA) model. We found that students who took enhanced general chemistry had higher persistence to the subsequent first organic chemistry course, and performed equally well in the organic course compared to their peers who took standard general chemistry. Students in the first enhanced general chemistry course also reported significantly higher belonging, although we were unable to determine if increased belonging was associated with the increased persistence to organic chemistry. Rather we found that the positive association between taking the enhanced general chemistry course and persistence to organic chemistry was mediated by higher grades received in the enhanced general chemistry course. Our findings highlight the responsibility we have as educators to carefully consider the pedagogical practices we use, in addition to how we assign student grades.
    Cover page: Participation in a High-Structure General Chemistry Course Increases Student Sense of Belonging and Persistence to Organic Chemistry.
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2016)

    Unlabelled

    Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver bile duct malignancy exhibiting frequent isocitrate dehydrogenase (IDH1/IDH2) mutations. Through a high-throughput drug screen of a large panel of cancer cell lines, including 17 biliary tract cancers, we found that IDH mutant (IDHm) ICC cells demonstrate a striking response to the multikinase inhibitor dasatinib, with the highest sensitivity among 682 solid tumor cell lines. Using unbiased proteomics to capture the activated kinome and CRISPR/Cas9-based genome editing to introduce dasatinib-resistant "gatekeeper" mutant kinases, we identified SRC as a critical dasatinib target in IDHm ICC. Importantly, dasatinib-treated IDHm xenografts exhibited pronounced apoptosis and tumor regression. Our results show that IDHm ICC cells have a unique dependency on SRC and suggest that dasatinib may have therapeutic benefit against IDHm ICC. Moreover, these proteomic and genome-editing strategies provide a systematic and broadly applicable approach to define targets of kinase inhibitors underlying drug responsiveness.

    Significance

    IDH mutations define a distinct subtype of ICC, a malignancy that is largely refractory to current therapies. Our work demonstrates that IDHm ICC cells are hypersensitive to dasatinib and critically dependent on SRC activity for survival and proliferation, pointing to new therapeutic strategies against these cancers. Cancer Discov; 6(7); 727-39. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 681.
      Cover page: Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and SRC Dependence in Intrahepatic Cholangiocarcinoma
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2019)
      ATP-competitive fibroblast growth factor receptor (FGFR) kinase inhibitors, including BGJ398 and Debio 1347, show antitumor activity in patients with intrahepatic cholangiocarcinoma (ICC) harboring activating FGFR2 gene fusions. Unfortunately, acquired resistance develops and is often associated with the emergence of secondary FGFR2 kinase domain mutations. Here, we report that the irreversible pan-FGFR inhibitor TAS-120 demonstrated efficacy in 4 patients with FGFR2 fusion-positive ICC who developed resistance to BGJ398 or Debio 1347. Examination of serial biopsies, circulating tumor DNA (ctDNA), and patient-derived ICC cells revealed that TAS-120 was active against multiple FGFR2 mutations conferring resistance to BGJ398 or Debio 1347. Functional assessment and modeling the clonal outgrowth of individual resistance mutations from polyclonal cell pools mirrored the resistance profiles observed clinically for each inhibitor. Our findings suggest that strategic sequencing of FGFR inhibitors, guided by serial biopsy and ctDNA analysis, may prolong the duration of benefit from FGFR inhibition in patients with FGFR2 fusion-positive ICC. SIGNIFICANCE: ATP-competitive FGFR inhibitors (BGJ398, Debio 1347) show efficacy in FGFR2-altered ICC; however, acquired FGFR2 kinase domain mutations cause drug resistance and tumor progression. We demonstrate that the irreversible FGFR inhibitor TAS-120 provides clinical benefit in patients with resistance to BGJ398 or Debio 1347 and overcomes several FGFR2 mutations in ICC models.This article is highlighted in the In This Issue feature, p. 983.
        Cover page: TAS-120 Overcomes Resistance to ATP-Competitive FGFR Inhibitors in Patients with FGFR2 Fusion–Positive Intrahepatic Cholangiocarcinoma
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