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Open Access Publications from the University of California

Scholarly Works (82 results)

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

One main issue in protein-protein docking is to filter or score the putative docked structures. Unlike many popular scoring functions that are based on geometric and energetic complementarity, we present a set of scoring functions that are based on the consideration of local balance and tightness of binding of the docked structures. These scoring functions include the force and moment acting on one component (ligand) imposed by the other (receptor) and the second order spatial derivatives of protein-protein interaction potential. The scoring functions were applied to the docked structures of 19 test targets including enzyme/inhibitor, antibody/antigen and other classes of protein complexes. The results indicate that these scoring functions are also discriminative for the near-native conformation. For some cases, such as antibody/antigen, they show more discriminative efficiency than some other scoring functions. such as desolvation free energy (DeltaG(des)) based on pail-wise atom-atom contact energy (ACE). The correlation analyses between present scoring functions and the energetic functions also show that there is no clear correlation between them; therefore, the present scoring functions are not essentially the same as energy functions.

    Cover page: Scoring protein-protein docked structures based on the balance and tightness of binding
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2006)

    Background: Previous studies indicate that light information reaches the suprachiasmatic nucleus (SCN) through a subpopulation of retinal ganglion cells that contain both glutamate and pituitary adenylyl cyclase activating peptide (PACAP). While the role of glutamate in this pathway has been well studied, the involvement of PACAP and its receptors are only beginning to be understood. Speculating that PACAP may function to modulate how neurons in the suprachiasmatic nucleus respond to glutamate, we used electrophysiological and calcium imaging tools to examine possible cellular interactions between these co-transmitters. Results: Exogenous application of PACAP increased both the amplitude and frequency of spontaneous excitatory postsynaptic currents recorded from SCN neurons in a mouse brain slice preparation. PACAP also increased the magnitude of AMPA-evoked currents through a mechanism mediated by PAC1 receptors and the adenylyl cyclase-signalling cascade. This enhancement of excitatory currents was not limited to those evoked by AMPA as the magnitude of NMDA currents were also enhanced by application of PACAP. Furthermore, PACAP enhanced AMPA and NMDA evoked calcium transients while PACAP alone produced very little change in resting calcium in most mouse SCN neurons. Finally, in rat SCN neurons, exogenous PACAP enhanced AMPA evoked currents and calcium transients as well evoked robust calcium transients on its own. Conclusion: The results reported here show that PACAP is a potent modulator of glutamatergic signalling within the SCN in the early night.

      Cover page: Regulation of glutamatergic signalling by PACAP in the mammalian suprachiasmatic nucleus
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2015)
      Rapid urbanization and economic development in East Asia in past decades has led to photochemical air pollution problems such as excess photochemical ozone and aerosol formation. Asian megacities such as Seoul, Tokyo, Shanghai, Guangzhou, and Beijing are surrounded by densely forested areas, and recent research has consistently demonstrated the importance of biogenic volatile organic compounds (VOCs) from vegetation in determining oxidation capacity in the suburban Asian megacity regions. Uncertainties in constraining tropospheric oxidation capacity, dominated by hydroxyl radical, undermine our ability to assess regional photochemical air pollution problems. We present an observational data set of CO, NOx, SO2, ozone, HONO, and VOCs (anthropogenic and biogenic) from Taehwa research forest (TRF) near the Seoul metropolitan area in early June 2012. The data show that TRF is influenced both by aged pollution and fresh biogenic volatile organic compound emissions. With the data set, we diagnose HOx (OH, HO2, and RO2) distributions calculated using the University of Washington chemical box model (UWCM v2.1) with near-explicit VOC oxidation mechanisms from MCM v3.2 (Master Chemical Mechanism). Uncertainty from unconstrained HONO sources and radical recycling processes highlighted in recent studies is examined using multiple model simulations with different model constraints. The results suggest that (1) different model simulation scenarios cause systematic differences in HOx distributions, especially OH levels (up to 2.5 times), and (2) radical destruction (HO2 + HO2 or HO2 + RO2) could be more efficient than radical recycling (RO2 + NO), especially in the afternoon. Implications of the uncertainties in radical chemistry are discussed with respect to ozone-VOC-NOx sensitivity and VOC oxidation product formation rates. Overall, the NOx limited regime is assessed except for the morning hours (8 a.m. to 12 p.m. local standard time), but the degree of sensitivity can significantly vary depending on the model scenarios. The model results also suggest that RO2 levels are positively correlated with oxygenated VOCs (OVOCs) production that is not routinely constrained by observations. These unconstrained OVOCs can cause higher-than-expected OH loss rates (missing OH reactivity) and secondary organic aerosol formation. The series of modeling experiments constrained by observations strongly urge observational constraint of the radical pool to enable precise understanding of regional photochemical pollution problems in the East Asian megacity region.
        Cover page: Impact of isoprene and HONO chemistry on ozone and OVOC formation in a semirural South Korean forestCreative Commons 'BY' version 4.0 license
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2015)
        © 2015 Macmillan Publishers Limited. All rights reserved.Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis
          • Article
          • Peer Reviewed
          LBL Publications (2011)
            • Article
            • Peer Reviewed
            LBL Publications (2016)
              • Article
              • Peer Reviewed
              UC San Francisco Previously Published Works (2021)

              Study design

              Retrospective review of a multicenter prospective registry.

              Objectives

              Our goal was to develop a method to risk-stratify adult spinal deformity (ASD) patients on the basis of their accumulated health deficits. We developed a novel comorbidity score (CS) specific to patients with ASD based on their preoperative health state and investigated whether it was associated with major complications, length of hospital stay (LOS), and self-reported outcomes after ASD surgery.

              Methods

              We identified 273 operatively treated ASD patients with 2-year follow-up. We assessed associations between major complications and age, comorbidities, Charlson Comorbidity Index score, and Oswestry Disability Index score. Significant factors were used to construct the ASD-CS. Associations of ASD-CS with major complications, LOS, and patient-reported outcomes were analyzed.

              Results

              Major complications increased significantly with ASD-CS (P < .01). Compared with patients with ASD-CS of 0, the odds of major complications were 2.8-fold higher (P = .068) in patients with ASD-CS of 1 through 3; 4.5-fold higher (P < .01) in patients with ASD-CS of 4 through 6; and 7.5-fold higher (P < .01) in patients with ASD-CS of 7 or 8. Patients with ASD-CS of 7 or 8 had the longest mean LOS (10.7 days) and worst mean Scoliosis Research Society-22r total score at baseline; however, they experienced the greatest mean improvement (0.98 points) over 2 years.

              Conclusions

              The ASD-CS is significantly associated with major complications, LOS, and patient-reported outcomes in operatively treated ASD patients.
                Cover page: Development of a Preoperative Adult Spinal Deformity Comorbidity Score That Correlates With Common Quality and Value Metrics: Length of Stay, Major Complications, and Patient-Reported Outcomes.Creative Commons 'BY-NC-ND' version 4.0 license
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2018)
                Both inflammatory processes and glutamatergic systems have been implicated in the pathophysiology of mood-related disorders. However, the role of caspase-1, a classic inflammatory caspase, in behavioral responses to chronic stress remains largely unknown. To address this issue, we examined the effects and underlying mechanisms of caspase-1 on preclinical murine models of depression. We found that loss of caspase-1 expression in Caspase-1-/- knockout mice alleviated chronic stress-induced depression-like behaviors, whereas overexpression of caspase-1 in the hippocampus of wild-type (WT) mice was sufficient to induce depression- and anxiety-like behaviors. Furthermore, chronic stress reduced glutamatergic neurotransmission and decreased surface expression of glutamate receptors in hippocampal pyramidal neurons of WT mice, but not Caspase-1-/- mice. Importantly, pharmacological inhibition of caspase-1-interleukin-1β (IL-1β) signaling pathway prevented the depression-like behaviors and the decrease in surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in stressed WT mice. Finally, the effects of chronic stress on both depression- and anxiety-like behaviors can be mimicked by exogenous intracerebroventricular (i.c.v.) administration of IL-1β in both WT and Caspase-1-/- mice. Taken together, our findings demonstrate that an increase in the caspase-1/IL-1β axis facilitates AMPAR internalization in the hippocampus, which dysregulates glutamatergic synaptic transmission, eventually resulting in depression-like behaviors. These results may represent an endophenotype for chronic stress-induced depression.
                  Cover page: Gene deficiency and pharmacological inhibition of caspase-1 confers resilience to chronic social defeat stress via regulating the stability of surface AMPARs.Creative Commons 'BY-NC-SA' version 4.0 license
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2016)

                  Study design

                  Prospective, cross-sectional study.

                  Objective

                  The aim of the study was to determine which radiographic parameters drive patient-reported outcomes (PROs) in primary presentation adult symptomatic lumbar scoliosis (ASLS).

                  Summary of background data

                  Previous literature suggests correlations between PROs and sagittal plane deformity (sagittal vertical axis [SVA], pelvic incidence-lumbar lordosis [PI-LL] mismatch, pelvic tilt [PT]). Prior work included revision and primary adult spinal deformity patients. The present study addresses only primary presentation ASLS.

                  Methods

                  Prospective baseline data were analyzed on 286 patients enrolled in an NIH RO1 clinical trial by nine centers from 2010 to 2014.

                  Inclusion criteria

                  40 to 80 years old, lumbar Cobb (LC) 30° or higher and Scoliosis Research Society-23 score 4.0 or less in Pain, Function or Self-Image domains, or Oswestry Disability Index (ODI) 20 or higher. Patients were primary presentation (no prior spinal deformity surgery) and had complete baseline data: standing coronal/sagittal 36" radiographs and PROs (ODI, Scoliosis Research Society-23, Short Form-12). Correlation coefficients were calculated to evaluate relations between radiographic parameters and PROs for the study population and a subset of patients with ODI 40 or higher. Analysis of variance was used to identify differences in PROs for radiographic modifier groups.

                  Results

                  Mean age was 60.3 years. Mean spinopelvic parameters were: LL = -39.2°; SVA = 3.1 cm; sacral slope = 32.5°; PT = 23.9°; PI-LL mismatch = 16.8°. Only weak correlations (0.2-0.4) were identified between population sacral slope, SVA and SVA modifiers, and SRS function. SVA and SVA modifiers were weakly associated with ODI. Although there were more correlations in subset analysis of high-symptom patients, all were weak. Analysis of variance identified significant differences in ODI reported by SVA modifier groups.

                  Conclusion

                  In primary presentation patients with ASLS and a subset of "high-symptom" patients (ODI ≥ 40), only weak associations between baseline PROs and radiographic parameters were identified. For this patient population, these results suggest regional radiographic parameters (LC, LL, PT, PI-LL mismatch) are not drivers of PROs and cannot be used to extrapolate effect on patient-perceived pathology.

                  Level of evidence

                  2.
                    Cover page: Baseline Patient-Reported Outcomes Correlate Weakly With Radiographic Parameters
                    • Article
                    • Peer Reviewed
                    UCLA Previously Published Works (2011)
                    A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients' lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology.
                      Cover page: Integrated genomic analyses of ovarian carcinoma
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