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Open Access Publications from the University of California

Scholarly Works (21 results)

  • Article
  • Peer Reviewed
UC San Francisco Previously Published Works (2004)

Initiation and maintenance of infection by mycobacteria in susceptible hosts are not well understood. A screen of Mycobacterium marinum transposon mutant library led to isolation of eight mutants that failed to cause haemolysis, all of which had transposon insertions in genes homologous to a region between Rv3866 and Rv3881c in Mycobacterium tuberculosis, which encompasses RD1 (Rv3871-Rv3879c), a known virulence gene cluster. The M. marinum mutants showed decreased virulence in vivo and failed to secrete ESAT-6, like M. tuberculosis RD1 mutants. M. marinum mutants in genes homologous to Rv3866-Rv3868 also failed to accumulate intracellular ESAT-6, suggesting a possible role for those genes in synthesis or stability of the protein. These transposon mutants and an ESAT-6/CFP-10 deletion mutant all showed reduced cytolysis and cytotoxicity to macrophages and significantly decreased intracellular growth at late stages of the infection only when the cells were infected at low multiplicity of infection, suggesting a defect in spreading. Direct evidence for cell-to-cell spread by wild-type M. marinum was obtained by microscopic detection in macrophage and epithelial monolayers, but the mutants all were defective in this assay. Expression of M. tuberculosis homologues complemented the corresponding M. marinum mutants, emphasizing the functional similarities between M. tuberculosis and M. marinum genes in this region that we designate extRD1 (extended RD1). We suggest that diminished membranolytic activity and defective spreading is a mechanism for the attenuation of the extRD1 mutants. These results extend recent findings on the genomic boundaries and functions of M. tuberculosis RD1 and establish a molecular cellular basis for the role that extRD1 plays in mycobacterial virulence. Disruption of the M. marinum homologue of Rv3881c, not previously implicated in virulence, led to a much more attenuated phenotype in macrophages and in vivo, suggesting that this gene plays additional roles in M. marinum survival in the host.

    Cover page: A mycobacterial virulence gene cluster extending RD1 is required for cytolysis, bacterial spreading and ESAT-6 secretion
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2017)
      Cover page: Ultrastructural characterization of hyperactive endothelial cells, pericytes and fibroblasts in hypertrophic and nodular port‐wine stain lesionsCreative Commons 'BY' version 4.0 license
      • Article
      • Peer Reviewed
      UC Berkeley Previously Published Works (2024)
      【Objective】 To develop a sustainable management plan for Larix gmelinii, which is influenced by climate change, it is crucial to understand the dynamic relationship between radial growth and climate in forests with different tree densities.【Method】Based on the stand density index, nine plots with three density levels (low, middle, high) were established in the central and northern Greater Khingan Mountains. Tree cores of L. gmelinii were collected during a field investigation. The Mann-Kendall test method was used to determine the turning point of temperature in the study area. To examine the radial growth trend of L. gmelinii, negative exponential function detrending and a linear function fitting were applied. Then, a Pearson correlation and sliding correlation were used to analyze whether the relationship between the radial growth and climate factors under each stand density remained stable after the temperature turning point.【Result】The radial growth of L. gmelinii displayed trends of both enhancement and decline after the temperature turning point. The proportion of declining trees increased with increasing stand density. The growth of L. gmelinii was strongly inhibited when the stand density was high. Its average growth change rate reached -25% during 1988-1990, indicating a serious growth decline. Instead, the L. gmelinii trees in low density plots maintained a 54% growth enhancement ratio. Stand density may also influence the response of L. gmelinii growth to climate. Under a high stand density, the L. gmelinii growth of the decline group was positively correlated with the standardized precipitation evapotranspiration index in August (P<0. 05) and negatively correlated with summer temperature (P<0. 05), but under a low stand density, the growth of L. gmelinii was positively correlated with temperature. With the warming and drying trend in the study area, the relationship between tree growth and temperature shifted from positive to negative with increasing stand density. 【Conclusion】 The proportion of declining trees increased with increasing stand density after the significant change of temperature. The impact of water limitation on growth was alleviated at a low stand density, while the trees in high density plots were more sensitive to climate factors. Reducing the stand density could mitigate the negative impacts of climate warming on the growth of L. gmelinii. Therefore, adjusting stand density is a necessary management operation to slow the declining trend of L. gmelinii.
        Creative Commons 'BY' version 4.0 license
        • Article
        • Peer Reviewed
        UC Berkeley Previously Published Works (2019)
        [Objective] Carbon content is one of the key factors when estimating carbon storage. Accurate measurement of carbon content and finding its influencing factors can improve the accuracy of the prediction of carbon storage. [Method]Tree cores collected in the plots of mature forests in the broardleaved Korean pine forest of Jiaohe, northeastern China were taken as samples in this study. Carbon content of frozen, oven-dried and natural air drying samples of Pinus koraiensis from 1987 to 2016 were attained in order to qualify the volatile carbon content and to compare the characteristics of the interannual variation of the carbon content attained by different drying methods. In this passage, volatile carbon content was qualified with frozen and oven-dried carbon content considering the relative stability of them. The relationship between volatile carbon content and three climate factors as well as size class and annual growth was developed. [Result](1)The results showed that significant difference among carbon content of different drying methods was only found in trees of large diameter class.(2)The fluctuation characteristics of volatile carbon contribution differed in small and large class and the interannual variations were more remarkable in small class. The volatile carbon contribution reached 24.46% in small class and 9.72% in large class. Also, the volatile carbon contribution in large class lagged behind that of small class. (3)The volatile carbon contribution was mainly limited by the temperature in winter. In small class, the volatile carbon contribution showed negative response to temperature in December of that very year, while in large class, it responsed negatively to the temperature in last December. (4)The precipitation of this January had positive influence in volatile carbon contribution of large class and the volatile carbon contribution of small class showed positive response to PDSI of this June, which inspired us that the effect of volatile carbon may be related to trees' dormancy or other defensive mechanisms. [Conclusion]Therefore, it is necessary to take volatile carbon content into account while estimating the forest carbon storage without ignoring the influence of size class. It is also necessary to make a deep analysis of the influencing factors of volatile carbon contribution.
          Cover page: Dynamic characteristics and its influencing factors of the volatile carbon content of Pinus koraiensis at different diameter classesCreative Commons 'BY' version 4.0 license
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2013)
          Recent genetic association studies have implicated several candidate susceptibility variants for schizophrenia among general populations. Rs1344706, an intronic SNP within ZNF804A, was identified as one of the most compelling candidate risk SNPs for schizo
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (2017)

            Background

            Port-wine stain (PWS) is a vascular malformation characterized by progressive dilatation of postcapillary venules, but the molecular pathogenesis remains obscure.

            Objectives

            To illustrate that PWS endothelial cells (ECs) present a unique molecular phenotype that leads to pathoanatomical PWS vasculatures.

            Methods

            Immunohistochemistry and transmission electron microscopy were used to characterize the ultrastructure and molecular phenotypes of PWS blood vessels. Primary culture of human dermal microvascular endothelial cells and in vitro tube formation assay were used for confirmative functional studies.

            Results

            Multiple clinicopathological features of PWS blood vessels during the development and progression of the disease were shown. There were no normal arterioles and venules observed phenotypically and morphologically in PWS skin; arterioles and venules both showed differentiation impairments, resulting in a reduction of arteriole-like vasculatures and defects in capillary loop formation in PWS lesions. PWS ECs showed stemness properties with expression of endothelial progenitor cell markers CD133 and CD166 in non-nodular lesions. They also expressed dual venous/arterial identities, Eph receptor B1 (EphB1) and ephrin B2 (EfnB2). Co-expression of EphB1 and EfnB2 in normal human dermal microvascular ECs led to the formation of PWS-like vasculatures in vitro, for example larger-diameter and thick-walled capillaries.

            Conclusions

            PWS ECs are differentiation-impaired, late-stage endothelial progenitor cells with a specific phenotype of CD133+ /CD166+ /EphB1+ /EfnB2+ , which form immature venule-like pathoanatomical vasculatures. The disruption of normal EC-EC interactions by coexistence of EphB1 and EfnB2 contributes to progressive dilatation of PWS vasculatures.
              Cover page: Coexistence of Eph receptor B1 and ephrin B2 in port-wine stain endothelial progenitor cells contributes to clinicopathological vasculature dilatation.
              • Article
              • Peer Reviewed
              UC Irvine Previously Published Works (2015)
              Background The recurrence of port-wine stain (PWS) blood vessels by pulsed dye laser (PDL)-induced angiogenesis is a critical barrier that must be overcome to achieve a better therapeutic outcome. Objectives To determine whether PDL-induced angiogenesis can be suppressed by topical axitinib. Methods The mRNA expression profiles of 86 angiogenic genes and phosphorylation levels of extracellular signal regulated kinases (ERKs), phosphorylated protein kinase B (AKT) and ribosomal protein S6 kinase (p70S6K) in rodent skin were examined with or without topical axitinib administration after PDL exposure. Results The PDL-induced increased transcriptional levels of angiogenic genes peaked at days 3-7 post-PDL exposure. Topical application of 0·5% axitinib effectively suppressed the PDL-induced increase in mRNA levels of the examined angiogenic genes and activation of AKT, P70S6K and ERK from days 1 to 7 post-PDL exposure. After topical administration, axitinib penetrated into rodent skin to an approximate depth of 929·5 μm. Conclusions Topical application of 0·5% axitinib can systematically suppress the PDL-induced early stages of angiogenesis via inhibition of the AKT/mammalian target of rapamycin/p70S6K and Src homology 2 domain containing transforming protein-1/mitogen-activated protein kinase kinase/ERK pathway cascades.
                Cover page: Topical axitinib suppresses angiogenesis pathways induced by pulsed dye laser
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2003)

                Mycobacterium tuberculosis infects one-third of the world's population and causes two million deaths annually. The unusually low permeability of its cell wall contributes to the ability of M. tuberculosis to grow within host macrophages, a property required for pathogenesis of infection. Mycobacterium marinum is an established model for discovering genes involved in mycobacterial infection. Mycobacterium marinum mutants with transposon insertions in the beta-ketoacyl- acyl carrier protein synthase B gene (kasB) grew poorly in macrophages, although growth in vitro was unaffected. Detailed analyses by thin-layer chromatography, nuclear magnetic resonance (NMR), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, infrared spectroscopy, and chemical degradations showed that the kasB mutants synthesize mycolic acids that are 2 - 4 carbons shorter than wild type; the defect was localized to the proximal portion of the meromycolate chain. In addition, these mutants showed a significant ( similar to 30%) reduction in the abundance of keto-mycolates, with a slight compensatory increase of both alpha- and methoxymycolates. Despite these small changes in mycolate length and composition, the kasB mutants exhibited strikingly altered cell wall permeability, leading to a marked increase in susceptibility to lipophilic antibiotics and the host antimicrobial molecules defensin and lysozyme. The abnormalities of the kasB mutants were fully complemented by expressing M. tuberculosis kasB, but not by the closely related gene kasA. These studies identify kasB as a novel target for therapeutic intervention in mycobacterial diseases.

                  Cover page: Requirement for kasB in Mycobacterium mycolic acid biosynthesis, cell wall impermeability and intracellular survival: implications for therapy
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2017)
                    Cover page: Pathological alterations involve the entire skin physiological milieu in infantile and early‐childhood port‐wine stain
                    • Article
                    • Peer Reviewed
                    UCLA Previously Published Works (2019)

                    Background

                    Neuroimaging studies have identified obesity-related differences in the brain's resting state activity. An imbalance between homeostatic and reward aspects of ingestive behaviour may contribute to obesity and food addiction. The interactions between early life adversity (ELA), the reward network and food addiction were investigated to identify obesity and sex-related differences, which may drive obesity and food addiction.

                    Methods

                    Functional resting state magnetic resonance imaging was acquired in 186 participants (high body mass index [BMI]: ≥25: 53 women and 54 men; normal BMI: 18.50-24.99: 49 women and 30 men). Participants completed questionnaires to assess ELA (Early Traumatic Inventory) and food addiction (Yale Food Addiction Scale). A tripartite network analysis based on graph theory was used to investigate the interaction between ELA, brain connectivity and food addiction. Interactions were determined by computing Spearman rank correlations, thresholded at q < 0.05 corrected for multiple comparisons.

                    Results

                    Participants with high BMI demonstrate an association between ELA and food addiction, with reward regions playing a role in this interaction. Among women with high BMI, increased ELA was associated with increased centrality of reward and emotion regulation regions. Men with high BMI showed associations between ELA and food addiction with somatosensory regions playing a role in this interaction.

                    Conclusions

                    The findings suggest that ELA may alter brain networks, leading to increased vulnerability for food addiction and obesity later in life. These alterations are sex specific and involve brain regions influenced by dopaminergic or serotonergic signalling.
                      Cover page: History of early life adversity is associated with increased food addiction and sex‐specific alterations in reward network connectivity in obesity
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