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

Scholarly Works (9 results)

  • Article
  • Peer Reviewed
Himalayan Linguistics, Volume 16, Issue 1 (2017)
This paper presents the grammatical systems that are used for the concepts of space in the Cogtse dialect of Rgyalrong. Cogtse is noted for the way it lexicalizes a rich set of orientations (up-down, east-west, upstream-downstream) in terms of nominals, pronominals, verbs, and adverbials. Together with locative postpositions and the relator-noun construction, they constitute the three primary kinds of grammatical devices to incorporate notions of space. Despite the fact that Cogtse lexicalizes the intrinsic, relative, and absolute (based on the six orientations) frames of reference; no occurrence of ‘left’ and ‘right’ has been observed in the discourse data, spontaneous or preplanned. Speakers clearly prefer the absolute references that take the above-mentioned orientations as the basis. Finally, this paper illustrates from two socio-cultural perspectives how entrenched the orientation system is in Rgyalrong. The selection of semantically-dependent perfectivizer reveals the way Rgyalrong speakers conceptualize events in orientational terms; while the seating arrangement in the Rgyalrong house demonstrates that in assigning orientation terms to refer to various indoor spaces, cultural conceptions override natural geographical settings.
    Cover page: How Grammar Encodes Space in Cogtse RgyalrongCreative Commons 'BY-NC-ND' version 4.0 license
    • Thesis
    • Peer Reviewed
    UC Irvine Electronic Theses and Dissertations (2019)

    Acute kidney injury (AKI) is a significant public health issue with high morbidity and mortality. Recent evidences suggest that renal tubular dysfunction may modulate glomerular function; however, its mechanism remains unknown. We hypothesized that mitochondrial AKT1 signaling could play a protective role in the pathogenesis of AKI and subsequent kidney failure. We have generated novel renal tubular cell-specific transgenic mice harboring an inducible mitochondria-targeting dominant negative AKT1 (KMDAKT) or constitutively active AKT1 (KMCAKT) with Cre-lox strategy. AKI was induced by ischemia-reperfusion injury (IRI). IRI induced greater renal injury with increased Jablonski score (p=0.018), an index of overall renal tubular injuries, in the tamoxifen (TAM)-injected KMDAKT mice. Renal fibrosis areas (%) by Masson’s trichrome stain was significantly larger in the KMDAKT mice as compared to the control mice (p<0.001). Marker for renal tubule injury (kidney injury molecule-1, KIM-1) was significantly increased in the KMDAKT mice (p=0.002). Grades of Periodic acid Schiff (PAS) stain of glomerulosclerosis were significantly higher on day 45 post AKI in the TAM-KMDAKT (p<0.001). Creatinine (Cr.) was significantly higher in the TAM-KMDAKT group 45 days post AKI (p<0.001). Survival rate was significantly lower in the TAM-MDAKT mice 7 days post ischemia (46.67%) as compared to the controls (85.71%) (p=0.0013). To study whether enhancing tubule mitochondrial AKT1 signaling can further protect kidney injury, we used KMCAKT mice as our experimental model. Histology analysis confirmed lesser renal injury with decreased Jablonski score after AKI (p=0.038). Renal fibrosis areas (%) was significantly smaller when compared to the control mice (p=0.002). KIM-1 were decreased in the KMCAKT mice (p<0.001). PAS stain of glomerulosclerosis were significantly lower in the TAM injected KMCAKT mice45 days post AKI (p<0.001). Survival rate in the TAM-KMCAKT mice after AKI was improved (p<0.001). Mitochondria respiration was investigated and the results showed increased basal respiration (p<0.001), spare respiration (p<0.001), adenosine triphosphate (ATP) dependent respiration (p<0.001), and proton leak in the KMDAKT tubule cells. Activation of mitochondrial AKT1 signaling protected kidney injury from glomerulosclerosis after IRI through attenuating renal tubular damage, therefore, mitochondrial AKT1 is a novel target for therapeutic intervention to prevent AKI and subsequent development of CKD.

      Cover page: Mechanistic Role of Mitochondrial AKT1 in Acute Kidney Injury
      • Thesis
      • Peer Reviewed
      UC San Francisco Electronic Theses and Dissertations (2011)

      The control of cell number depends on the balance between pro- and anti-death signals. The Drosophila PDGF/VEGF Receptor (PVR) provides an anti-apoptotic signal that is necessary for the survival of both embryonic hemocytes and the hemocyte-like Kc cell line, thus providing a model system for uncovering other mammalian PDGF/VEGF receptors regulated signaling pathways for hematopoietic cell survival. RNAi silencing of PVR in Kc cell leads to inactivation of both Ras/Erk and Akt/Tor, and reactivation of one of these pathways or inhibiting a pro-death regulator, leads to restoration of cell numbers. To identify other pathways, which involved in hemocyte survival, a genome-wide RNAi screen to identify suppressors and enhancers of the PVR RNAi-mediated cell number reduction had been conducted previously. The screen provided the basis for this thesis project, as we subsequently characterized the biological and molecular roles of genes identified in the screen. Among the suppressors identified are many known tumor suppressors and negative regulators of the Akt/Tor and Ras/Erk pathways, and as well as heterodimeric nuclear hormone receptor- ecdysone receptor (EcR) and ultraspiracle (usp). Loss of EcR or usp suppresses cell death in a PVR-silenced background, and expression of dominant negative EcR rescues hemocyte survival in PVR null mutant embryos. Ecdysone stimulation in Kc cells triggers cell death, possibly by the induction of reaper and E93. When trying to assess the relationship of EcR/usp or ecdysone signaling with the PVR signaling pathway, biochemistry data suggest that both function in a parallel fashion. Interestingly, PVR is required for ecdysone-induced upregulation of EcR, suggesting a regulatory balance between pro-survival PVR- and pro-death ecdysone signaling that stabilizes cell lifespan. These studies suggest a novel role of ecdysone signaling in Drosophila embryonic development and blood cell survival, and emphasize parallels with the homologous vertebrate rexinoid receptor (RXR) that acts in pro-death signaling and tumor suppression. In addition, novel PVR suppressors identified in the screen, and their mammalian counterparts, may play a role in cell number control and tumor suppression.

        Cover page: Characterization of regulators of blood cell number identified in a Drosophila genome-wide RNAi screen.
        • Article
        • Peer Reviewed
        Himalayan Linguistics, Volume 23, Issue 1 (2024)

        This issue of Himalayan Linguistics marks twenty years for the journal. We reflect on the early history of Himalayan Linguistics, its contribution to the field, and the future of the journal.

          Cover page: Twenty years of Himalayan LinguisticsCreative Commons 'BY-NC-ND' version 4.0 license
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2014)

          Background

          The major cancer related mortality is caused by metastasis and invasion. It is important to identify genes regulating metastasis and invasion in order to curtail metastatic spread of cancer cells.

          Methods

          This study investigated the association between RUNX2 and miR-10a/miR-10b and the risk of breast cancer relapse. Expression levels of RUNX2 and miR-10a/b in 108 pairs of tumor and non-tumor tissue of breast cancer were assayed by quantitative PCR analysis and evaluated for their prognostic implications.

          Results

          The median expression levels of RUNX2 and miR-10b in tumor tissue normalized using adjacent non-tumor tissue were significantly higher in relapsed patients than in relapse-free patients. Higher expression of these three genes were significantly correlated with the hazard ratio for breast cancer recurrence (RUNX2: 3.02, 95% CI = 1.50 ~ 6.07; miR-10a: 2.31, 95% CI = 1.00 ~ 5.32; miR-10b: 3.96, 95% CI = 1.21 ~ 12.98). The joint effect of higher expression of all three genes was associated with a hazard ratio of 12.37 (95% CI = 1.62 ~ 94.55) for relapse. In a breast cancer cell line, RUNX2 silencing reduced the expression of miR-10a/b and also impaired cell motility, while RUNX2 overexpression elicited opposite effects.

          Conclusions

          These findings indicate that higher expression of RUNX2 and miR-10a/b was associated with adverse outcome of breast cancer. Expression levels of RUNX2 and miR-10a/b individually or jointly are potential prognostic factors for predicting breast cancer recurrence. Data from in vitro studies support the notion that RUNX2 promoted cell motility by upregulating miR-10a/b.
            Cover page: The prognostic significance of RUNX2 and miR-10a/10b and their inter-relationship in breast cancer
            • Article
            • Peer Reviewed
            UC San Diego Previously Published Works (2013)
            It has been shown that imprecise cleavage of a primary or precursor RNA by Drosha or Dicer, respectively, may yield a group of microRNA (miRNA) variants designated as "isomiR". Variations in the relative abundance of isoforms for a given miRNA among different species and different cell types beg the question whether these isomiRs might regulate target genes differentially. We compared the capacity of three miR-31 isoforms (miR-31-H, miR-31-P, and miR-31-M), which differ only slightly in their 5'- and/or 3'-end sequences, to regulate several known targets and a predicted target, Dicer. Notably, we found isomiR-31s displayed concordant and discordant regulation of 6 known target genes. Furthermore, we validated a predicted target gene, Dicer, to be a novel target of miR-31 but only miR-31-P could directly repress Dicer expression in both MCF-7 breast cancer cells and A549 lung cancer cells, resulting in their enhanced sensitivity to cisplatin, a known attribute of Dicer knockdown. This was further supported by reporter assay using full length 3'-untranslated region (UTR) of Dicer. Our findings not only revealed Dicer to be a direct target of miR-31, but also demonstrated that isomiRs displayed similar and disparate regulation of target genes in cell-based systems. Coupled with the variations in the distribution of isomiRs among different cells or conditions, our findings support the possibility of fine-tuning gene expression by miRNAs.
              Cover page: Concordant and Discordant Regulation of Target Genes by miR-31 and Its IsoformsCreative Commons 'BY' version 4.0 license
              • Article
              • Peer Reviewed
              UC Davis Previously Published Works (2019)
              Williams syndrome (WS) and 7q11.23 duplication syndrome (Dup7q11.23) are neurodevelopmental disorders caused by the deletion and duplication, respectively, of ~ 25 protein-coding genes on chromosome 7q11.23. The general transcription factor 2I (GTF2I, protein TFII-I) is one of these proteins and has been implicated in the neurodevelopmental phenotypes of WS and Dup7q11.23. Here, we investigated the effect of copy number alterations in Gtf2i on neuronal maturation and intracellular calcium entry mechanisms known to be associated with this process. Mice with a single copy of Gtf2i (Gtf2i+/Del) had increased axonal outgrowth and increased TRPC3-mediated calcium entry upon carbachol stimulation. In contrast, mice with 3 copies of Gtf2i (Gtf2i+/Dup) had decreases in axon outgrowth and in TRPC3-mediated calcium entry. The underlying mechanism was that TFII-I did not affect TRPC3 protein expression, while it regulated TRPC3 membrane translocation. Together, our results provide novel functional insight into the cellular mechanisms that underlie neuronal maturation in the context of the 7q11.23 disorders.
                Cover page: Transcription Factor 2I Regulates Neuronal Development via TRPC3 in 7q11.23 Disorder Models.
                • Article
                • Peer Reviewed
                Abstract Background The black tiger shrimp (Penaeus monodon) is one of the most important aquaculture species in the world, representing the crustacean lineage which possesses the greatest species diversity among marine invertebrates. Yet, we barely know anything about their genomic structure. To understand the organization and evolution of the P. monodon genome, a fosmid library consisting of 288,000 colonies and was constructed, equivalent to 5.3-fold coverage of the 2.17 Gb genome. Approximately 11.1 Mb of fosmid end sequences (FESs) from 20,926 non-redundant reads representing 0.45% of the P. monodon genome were obtained for repetitive and protein-coding sequence analyses. Results We found that microsatellite sequences were highly abundant in the P. monodon genome, comprising 8.3% of the total length. The density and the average length of microsatellites were evidently higher in comparison to those of other taxa. AT-rich microsatellite motifs, especially poly (AT) and poly (AAT), were the most abundant. High abundance of microsatellite sequences were also found in the transcribed regions. Furthermore, via self-BlastN analysis we identified 103 novel repetitive element families which were categorized into four groups, i.e., 33 WSSV-like repeats, 14 retrotransposons, 5 gene-like repeats, and 51 unannotated repeats. Overall, various types of repeats comprise 51.18% of the P. monodon genome in length. Approximately 7.4% of the FESs contained protein-coding sequences, and the Inhibitor of Apoptosis Protein (IAP) gene and the Innexin 3 gene homologues appear to be present in high abundance in the P. monodon genome. Conclusions The redundancy of various repeat types in the P. monodon genome illustrates its highly repetitive nature. In particular, long and dense microsatellite sequences as well as abundant WSSV-like sequences highlight the uniqueness of genome organization of penaeid shrimp from those of other taxa. These results provide substantial improvement to our current knowledge not only for shrimp but also for marine crustaceans of large genome size.
                • 5 supplemental files
                Cover page: Fosmid library end sequencing reveals a rarely known genome structure of marine shrimp Penaeus monodon
                • Article
                • Peer Reviewed
                UC Berkeley Previously Published Works (2021)
                This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange-correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear-electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an "open teamware" model and an increasingly modular design.
                  Cover page: Software for the frontiers of quantum chemistry: An overview of developments in the Q-Chem 5 package
                  Top