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Open Access Publications from the University of California

Scholarly Works (8 results)

  • Article
  • Peer Reviewed
UC San Diego Previously Published Works (1986)
H2(18)O isotope exchange into specifically 13C-labeled substrate was used to obtain information on the rate-limiting step in the action of the phospholipase A2 from the venom of the Indian cobra (Naja naja naja). Incorporation of 18O was detected by the effect of 18O on 13C chemical shifts in 13C NMR. The enzymatic hydrolysis of a micellar phosphatidylcholine analogue of platelet-activating factor 1-alkyl-2-[1-13C]lauroyl-sn-glycero-3-phosphorylcholine proceeds by an O-acyl cleavage of the sn-2 ester bond. The reaction was examined for simultaneous 18O incorporation into the substrate. No exchange was found, suggesting that the hydrolytic step is not followed by a higher energy transition state and that it or a step before it appears to be rate-limiting. Previous experiments on phosphatidylethanolamine activation indicate that kcat is altered but that the km remains the same upon activation, suggesting that the binding steps occurring before the hydrolytic step are not affected. This strongly suggests that the hydrolytic step is in fact the rate-limiting step under these conditions. The 13C, 18O NMR technique should be generally applicable to mechanistic questions of this type.
    Cover page: Rate-determining step in phospholipase A2 mechanism. 18O isotope exchange determined by 13C NMR.
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2023)
    Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of morbidity and mortality. Colonization by MRSA increases the risk of infection and transmission, underscoring the importance of decolonization efforts. However, success of these decolonization protocols varies, raising the possibility that some MRSA strains may be more persistent than others. Here, we studied how the persistence of MRSA colonization correlates with genomic presence of antibiotic resistance genes. Our analysis using a Bayesian mixed effects survival model found that genetic determinants of high-level resistance to mupirocin was strongly associated with failure of the decolonization protocol. However, we did not see a similar effect with genetic resistance to chlorhexidine or other antibiotics. Including strain-specific random effects improved the predictive performance, indicating that some strain characteristics other than resistance also contributed to persistence. Study subject-specific random effects did not improve the model. Our results highlight the need to consider the properties of the colonizing MRSA strain when deciding which treatments to include in the decolonization protocol.
      Cover page: Bayesian modeling of the impact of antibiotic resistance on the efficiency of MRSA decolonization.
      • Article
      • Peer Reviewed
      Dermatology Online Journal, Volume 10, Issue 2 (2004)
        • Article
        • Peer Reviewed
        UC Berkeley Previously Published Works (2017)
        Cellular receptor-mediated signaling pathways play critical roles during the initial immune response to Human Cytomegalovirus (HCMV) infection. However, the involvement of type-I transmembrane glycoprotein CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) in the antiviral response to HCMV infection is still unknown. Here, we demonstrated the specific knockdown of CD147 significantly decreased HCMV-induced activation of NF-κB and Interferon-beta (IFN-β), which contribute to the cellular antiviral responses. Next, we confirmed that HCMV-encoded miR-US25-1-5p could target the 3' UTR (Untranslated Region) of CD147 mRNA, and thus facilitate HCMV lytic propagation at a low multiplicity of infection (MOI). The expression and secretion of Cyclophilin A (sCyPA), as a ligand for CD147 and a proinflammatory cytokine, were up-regulated in response to HCMV stimuli. Finally, we confirmed that CD147 mediated HCMV-triggered antiviral signaling via the sCyPA-CD147-ERK (extracellular regulated protein kinases)/NF-κB axis signaling pathway. These findings reveal an important HCMV mechanism for evading antiviral innate immunity through its encoded microRNA by targeting transmembrane glycoprotein CD147, and a potential cause of HCMV inflammatory disorders due to the secretion of proinflammatory cytokine CyPA.
          Cover page: Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response
          • Article
          • Peer Reviewed
          Western Journal of Emergency Medicine: Integrating Emergency Care with Population Health, Volume 21, Issue 3 (2020)

          Introduction: Hurricanes have increased in severity over the past 35 years, and climate change has led to an increased frequency of catastrophic flooding. The impact of floods on emergency department (ED) operations and patient health has not been well studied. We sought to detail challenges and lessons learned from the severe weather event caused by Hurricane Harvey in Houston, Texas, in August 2017.

          Methods: This report combines narrative data from interviews with retrospective data on patient volumes, mode of arrival, and ED lengths of stay (LOS). We compared the five-week peri-storm period for the 2017 hurricane to similar periods in 2015 and 2016.

          Results: For five days, flooding limited access to the hospital, with a consequent negative impact on provider staffing availability, disposition and transfer processes, and resource consumption. Interruption of patient transfer capabilities threatened patient safety, but flexibility of operations prevented poor outcomes. The total ED patient census for the study period decreased in 2017 (7062 patients) compared to 2015 (7665 patients) and 2016 (7770) patients). Over the five-week study period, the arrival-by-ambulance rate was 12.45% in 2017 compared to 10.1% in 2016 (p < 0.0001) and 13.7% in 2015 (p < 0.0001). The median ED length of stay (LOS) in minutes for admitted patients was 976 minutes in 2015 (p < 0.0001) compared to 723 minutes in 2016 and 591 in 2017 (p < 0.0001). For discharged patients, median ED LOS was 336 minutes in 2016 compared to 356 in 2015 (p < 0.0001) and 261 in 2017 (p < 0.0001). Median boarding time for admitted ED patients was 284 minutes in 2016 compared to 470 in 2015 (p < 0.0001) and 234.5 in 2017 (p < 0.001). Water damage resulted in a loss of 133 of 179 inpatient beds (74%). Rapid and dynamic ED process changes were made to share ED beds with admitted patients and to maximize transfers post-flooding to decrease ED boarding times.

          Conclusion: A number of pre-storm preparations could have allowed for smoother and safer ride-out functioning for both hospital personnel and patients. These measures include surplus provisioning of staff and supplies to account for limited facility access. During a disaster, innovative flexibility of both ED and hospital operations may be critical when disposition and transfer capibilities or bedding capacity are compromised.

            Cover page: Impact of Hurricane Harvey on Healthcare Utilization and Emergency Department OperationsCreative Commons 'BY' version 4.0 license
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (2022)
            Immunoglobulin family and carbohydrate vascular addressins encoded by Madcam1 and St6gal1 control lymphocyte homing into intestinal tissues, regulating immunity and inflammation. The addressins are developmentally programmed to decorate endothelial cells lining gut post-capillary and high endothelial venules (HEV), providing a prototypical example of organ- and segment-specific endothelial specialization. We identify conserved NKX-COUP-TFII composite elements (NCCE) in regulatory regions of Madcam1 and St6gal1 that bind intestinal homeodomain protein NKX2-3 cooperatively with venous nuclear receptor COUP-TFII to activate transcription. The Madcam1 element also integrates repressive signals from arterial/capillary Notch effectors. Pan-endothelial COUP-TFII overexpression induces ectopic addressin expression in NKX2-3+ capillaries, while NKX2-3 deficiency abrogates expression by HEV. Phylogenetically conserved NCCE are enriched in genes involved in neuron migration and morphogenesis of the heart, kidney, pancreas and other organs. Our results define an NKX-COUP-TFII morphogenetic code that targets expression of mucosal vascular addressins.
              Cover page: An NKX-COUP-TFII morphogenetic code directs mucosal endothelial addressin expression.
              • Article
              • Peer Reviewed
              UC San Francisco Previously Published Works (2022)
              Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD.
                Cover page: A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials
                • Article
                • Peer Reviewed
                LBL Publications (2017)
                The 2014-2016 JET results are reviewed in the light of their significance for optimising the ITER research plan for the active and non-active operation. More than 60 h of plasma operation with ITER first wall materials successfully took place since its installation in 2011. New multi-machine scaling of the type I-ELM divertor energy flux density to ITER is supported by first principle modelling. ITER relevant disruption experiments and first principle modelling are reported with a set of three disruption mitigation valves mimicking the ITER setup. Insights of the L-H power threshold in Deuterium and Hydrogen are given, stressing the importance of the magnetic configurations and the recent measurements of fine-scale structures in the edge radial electric. Dimensionless scans of the core and pedestal confinement provide new information to elucidate the importance of the first wall material on the fusion performance. H-mode plasmas at ITER triangularity (H = 1 at β N ∼ 1.8 and n/n GW ∼ 0.6) have been sustained at 2 MA during 5 s. The ITER neutronics codes have been validated on high performance experiments. Prospects for the coming D-T campaign and 14 MeV neutron calibration strategy are reviewed.
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