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Open Access Publications from the University of California

Scholarly Works (281 results)

  • Article
LBL Publications (1991)
    Cover page: Thermal Effects and Mirror Surface Figure Requirements for a Diagnostic Beamline at the Advanced Light Source (ALS)
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    • Peer Reviewed
    UCLA Previously Published Works (2005)

    Polypyrimidine tract binding protein (PTB) represses some alternatively spliced exons by direct occlusion of splice sites. In repressing the splicing of the c-src N1 exon, we find that PTB acts by a different mechanism. PTB does not interfere with U1 snRNP binding to the N1 5' splice site. Instead, PTB prevents formation of the prespliceosomal early (E) complex across the intervening intron by preventing the assembly of the splicing factor U2AF on the 3' splice site of exon 4. When the unregulated 5' splice site of the upstream exon 3 is present, U2AF binding is restored and splicing between exons 3 and 4 proceeds in spite of the N1 exon bound PTB. Thus, rather than directly blocking the N1 splice sites, PTB prevents the 5' splice site-dependent assembly of U2AF into the E complex. This mechanism likely occurs in many other alternative exons.

      Cover page: Polypyrimidine tract binding protein blocks the 5 ' splice site-dependent assembly of U2AF and the presplicelosomal E complex
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      • Peer Reviewed
      UCLA Previously Published Works (2006)
      Epstein-Barr virus-induced molecule 1 ligand chemokine (CCL19) is a CC chemokine that chemoattracts both dendritic cells (DC) and T lymphocytes. We evaluated the antitumour efficacy of CCL19 in a murine model of spontaneous bronchoalveolar cell carcinoma. These transgenic mice (CC-10 TAg) express the SV40 large T antigen under the Clara Cell promoter, develop bilateral, multifocal, pulmonary carcinomas and die at 4 months owing to progressive pulmonary tumour burden. To mimic therapy in late-stage disease, 3-month-old transgenic mice were treated with recombinant CCL19 (0.5 microg dose(-1)) by intranodal (axillary lymph node region) injection three times per week for 4 weeks. CCL19 treatment led to a marked reduction in tumour burden with extensive mononuclear infiltration of the tumours compared to diluent treated controls. Flow cytometric analyses showed significant increases in CD4 and CD8T cell subsets as well as DC in the lungs of CCL19-treated mice. Lung tissue cytokine profiles showed a shift towards immune stimulatory molecules with a decrease in the immunosuppressive cytokine TGF-beta. Our findings show that CCL19 may serve as a potential immune stimulator and provide a strong rationale for the evaluation of CCL19 in cancer immunotherapy.
        Cover page: CCL19 reduces tumour burden in a model of advanced lung cancer
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        • Peer Reviewed
        UC Irvine Previously Published Works (2019)
        The gyrokinetic toroidal code has been upgraded for global simulations by coupling the core and scrape-off layer regions across the separatrix with field-aligned particle-grid interpolations. A fully kinetic particle pusher for high frequency waves (ion cyclotron frequency and beyond) and a guiding center pusher for low frequency waves have been implemented using cylindrical coordinates in a global toroidal geometry. The two integrators correctly capture the particle orbits and agree well with each other, conserving energy and canonical angular momentum. As a verification and application of this new capability, ion guiding center simulations have been carried out to study ion orbit losses at the edge of the DIII-D tokamak for single null magnetic separatrix discharges. The ion loss conditions are examined as a function of the pitch angle for cases without and with a radial electric field. The simulations show good agreement with past theoretical results and with the experimentally observed feature in which high energy ions flow out along the ion drift orbits and then hit the divertor plates. A measure of the ion direct orbit loss fraction shows that the loss fraction increases with the ion energy for DIII-D in the initial velocity space. Finally, as a further verification of the capability of the new code, self-consistent simulations of zonal flows in the core region of the DIII-D tokamak were carried out. All DIII-D simulations were performed in the absence of turbulence.
          Cover page: Kinetic particle simulations in a global toroidal geometryCreative Commons 'BY' version 4.0 license
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          • Peer Reviewed
          The Proceedings of the International Plant Nutrition Colloquium XVI (2009)

          Most often yields of cauliflower remain low due to inadequate supply of micronutrients particularly of boron. Studies were therefore undertaken to optimize rate of B fertilization and evaluate efficiency of various sources for correcting its deficiency more economically in different agro-ecological zones of India. To correct B deficiency, eight field studies were conducted to evaluate the relative efficiency of B sources and optimize rates of B application needed for cauliflower crop grown in soils in different agro-ecological zones (AEZ) of India. Granular borax penta hydrate has been commercially made available for correcting B deficiencies in agricultural crops. Treatments comprising of borax at the rate of 75, 100 and 125% and Granubor II at 75, 100 and 125% of the recommended rate 1.00 kg B ha-1 were imposed along with one B control (NPK alone).

          The study covers major soils types like hill and mountainous (Alfisols) of the Himalayas, red sandy loam and lateritic soils (Alfisols) of central and eastern India and alluvial soils of Gujarat (Ustochrepts) and calcareous (Calciorthent) soils representing various agro-ecological zones of the India. Deficiency of boron ranged from 2-84% in certain soils and agro-ecological zones. Application of B significantly increased the biomass yield as well as economic benefits of cauliflower in different soils, crops and zones. Response of crops to 0.75 kg B ha-1 gave a significantly low yield. Increasing rates of boron added at 100 to 125% of the recommended dose gave significantly higher yields in different soils. Both the sources like Granubor II and borax significantly increased the yield over the control. Granubor II outperformed the crystalline borax in most of the soils in correcting B deficiency in cauliflower and gave higher benefit cost ratio. Thus preferential use of Granubor II at the rate of 1.25 kg B ha-1 was found to be beneficial to correct B deficiency in cauliflower over borax in different soils of India.

            Cover page: Relative efficiency of boron sources in improving cauliflower (Brassica Oleracea L.) yield and its uptake in Indian soils
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            • Peer Reviewed
            UC Davis Previously Published Works (2015)

            Background

            RELM-β has been implicated in airways inflammation and remodelling in murine models. Its possible functions in human airways are largely unknown. The aim was to address the hypothesis that RELM-β plays a role in extracellular matrix deposition in asthmatic airways.

            Methods

            The effects of RELM-β gene deficiency were studied in a model of allergen exposure in mice sensitised and challenged with Aspergillus fumigatus (Af). RELM-β expression was investigated in bronchial biopsies from asthmatic patients. Direct regulatory effects of RELM-β on human lung fibroblasts were examined using primary cultures and the MRC5 cell line in vitro.

            Results

            Sensitisation and challenge of wild-type mice with Af-induced release of RELM-β with a time course coincident with that of procollagen in the airways. Af-induced expression of mRNA encoding some, but not all ECM in the lung parenchyma was attenuated in RELM-β-/- mice. RELM-β expression was significantly increased in the bronchial submucosa of human asthmatics compared with controls, and its expression correlated positively with that of fibronectin and α-smooth muscle actin. In addition to epithelial cells, macrophages, fibroblasts and vascular endothelial cells formed the majority of cells expressing RELM-β in the submucosa. Exposure to RELM-β increased TGF-β1, TGF-β2, collagen I, fibronectin, smooth muscle α-actin, laminin α1, and hyaluronan and proteoglycan link protein 1 (Hapl1) production as well as proliferation by human lung fibroblasts in vitro. These changes were associated with activation of ERK1/2 in MRC5 cells.

            Conclusion

            The data are consistent with the hypothesis that elevated RELM-β expression in asthmatic airways contributes to airways remodelling at least partly by increasing fibroblast proliferation and differentiation with resulting deposition of extracellular matrix proteins.
              Cover page: Resistin‐like molecule‐β (RELM‐β) targets airways fibroblasts to effect remodelling in asthma: from mouse to man
              • Article
              • Peer Reviewed
              UC San Francisco Previously Published Works (2015)
              © 2015 Elsevier Ireland Ltd.Abstract Background/objectives Earlier studies differ on whether serum leptin is associated with adverse or beneficial cardiac structure. We determined the association between serum leptin with subsequent cardiac structure and f
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2014)
                Purpose: Uncontrolled radiation exposure due to radiological terrorism, industrial accidents or military circumstances is a continuing threat for the civilian population. Age plays a major role in the susceptibility to radiation; younger children are at hi
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2014)
                  Cysteine proteases play a crucial role in the development of the human malaria parasites Plasmodium falciparum and Plasmodium vivax. Our earlier studies demonstrated that these enzymes are equipped with specific domains for defined functions and further su
                    • Article
                    • Peer Reviewed
                    UCLA Previously Published Works (2013)
                    Background: Interleukin-27 signaling is mediated by the JAK-STAT pathway via activation of STAT1 and STAT3, which have tumor suppressive and oncogenic activities, respectively. Epithelial-mesenchymal transition (EMT) and angiogenesis are key processes in carcinogenesis. Although IL-27 has been shown to have potent anti-tumor activity in various cancer models, the role of IL-27 in EMT and angiogenesis is poorly understood. In this study, we investigated the role of IL-27 in regulating EMT and angiogenesis through modulation of the STAT pathways in human non-small cell lung carcinoma (NSCLC) cells. Methods. STAT activation following IL-27 exposure was measured in human NSCLC cell lines. Expression of epithelial (E-cadherin, γ-catenin) and mesenchymal (N-cadherin, vimentin) markers were assessed by Western blot analysis. Production of pro-angiogenic factors (VEGF, IL-8/CXCL8, CXCL5) were examined by ELISA. Cell motility was examined by an in vitro scratch and transwell migration assays. Selective inhibitors of STAT1 (STAT1 siRNAs) and STAT3 (Stattic) were used to determine whether both STAT1 and STAT3 are required for IL-27 mediated inhibition of EMT and secretion of angiogenic factors. Results: Our results demonstrate that IL-27 stimulation in NSCLC resulted in 1) STAT1 and STAT3 activation in a JAK-dependent manner, 2) development of epithelial phenotypes, including a decrease in the expression of a transcriptional repressor for E-cadherin (SNAIL), and mesenchymal marker (vimentin) with a reciprocal increase in the expression of epithelial markers, 3) inhibition of cell migration, and 4) reduced production of pro-angiogenic factors. STAT1 inhibition in IL-27-treated cells reversed the IL-27 effect with resultant increased expression of Snail, vimentin and the pro-angiogenic factors. The inhibition of STAT3 activation had no effect on the development of the epithelial phenotype. Conclusion: IL-27 induces mesenchymal to epithelial transition and inhibits the production of pro-angiogenic factors in a STAT1-dominant pathway. These findings highlight the importance of STAT1 in repressing lung carcinogenesis and describe a new anti-tumor mechanism of IL-27. © 2013 Kachroo et al.; licensee BioMed Central Ltd.
                      Cover page: IL-27 inhibits epithelial-mesenchymal transition and angiogenic factor production in a STAT1-dominant pathway in human non-small cell lung cancer
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