Browsing by Author "Wang, Ting"
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Item 3D Protein structure prediction with genetic tabu search algorithm(BMC, 2010-05-28) Zhang, Xiaolong; Wang, Ting; Luo, Huiping; Yang, Jack Y.; Deng, Youping; Tang, Jinshan; Yang, Mary Qu; Medicine, School of MedicineBackground Protein structure prediction (PSP) has important applications in different fields, such as drug design, disease prediction, and so on. In protein structure prediction, there are two important issues. The first one is the design of the structure model and the second one is the design of the optimization technology. Because of the complexity of the realistic protein structure, the structure model adopted in this paper is a simplified model, which is called off-lattice AB model. After the structure model is assumed, optimization technology is needed for searching the best conformation of a protein sequence based on the assumed structure model. However, PSP is an NP-hard problem even if the simplest model is assumed. Thus, many algorithms have been developed to solve the global optimization problem. In this paper, a hybrid algorithm, which combines genetic algorithm (GA) and tabu search (TS) algorithm, is developed to complete this task. Results In order to develop an efficient optimization algorithm, several improved strategies are developed for the proposed genetic tabu search algorithm. The combined use of these strategies can improve the efficiency of the algorithm. In these strategies, tabu search introduced into the crossover and mutation operators can improve the local search capability, the adoption of variable population size strategy can maintain the diversity of the population, and the ranking selection strategy can improve the possibility of an individual with low energy value entering into next generation. Experiments are performed with Fibonacci sequences and real protein sequences. Experimental results show that the lowest energy obtained by the proposed GATS algorithm is lower than that obtained by previous methods. Conclusions The hybrid algorithm has the advantages from both genetic algorithm and tabu search algorithm. It makes use of the advantage of multiple search points in genetic algorithm, and can overcome poor hill-climbing capability in the conventional genetic algorithm by using the flexible memory functions of TS. Compared with some previous algorithms, GATS algorithm has better performance in global optimization and can predict 3D protein structure more effectively.Item Analysis of Lipid Contents in Human Trabecular Meshwork Cells by Multiple Reaction Monitoring (MRM) Profiling Lipidomics(Springer, 2023) Wang, Ting; Pattabiraman, Padmanabhan Paranji; Ophthalmology, School of MedicineLipids are among the major constituents of cells and play many important cellular functions. Lipid levels in the trabecular meshwork (TM) aqueous humor outflow pathway play an important role in the maintenance of aqueous humor drainage and intraocular pressure (IOP) homeostasis. Therefore, it is important to characterize the changes in the lipid contents in the aqueous humor outflow pathway tissues to better understand their functional significance in the maintenance of IOP. The multiple reaction monitoring (MRM)-based profiling aids in the analysis of the metabolome as a collection of functional groups and is utilized as an exploratory metabolomics and lipidomics approach. The MRM-based profiling utilizes tandem mass spectrometry experiments carried out on a commercial triple quadrupole mass spectrometer with three aligned quadrupole mass filters (Q1, Q2, and Q3). This screening methodology can be utilized for targeted lipidomics screening. This chapter focuses on the methodology for isolation and culturing of the TM cells, lipid extraction, and the MRM-based lipidomics approach with data analysis.Item Cathepsin K Regulates Intraocular Pressure by Modulating Extracellular Matrix Remodeling and Actin-Bundling in the Trabecular Meshwork Outflow Pathway(MDPI, 2021-10-24) Soundararajan, Avinash; Ghag, Sachin Anil; Vuda, Sai Supriya; Wang, Ting; Pattabiraman, Padmanabhan Paranji; Ophthalmology, School of MedicineThe homeostasis of extracellular matrix (ECM) and actin dynamics in the trabecular meshwork (TM) outflow pathway plays a critical role in intraocular pressure (IOP) regulation. We studied the role of cathepsin K (CTSK), a lysosomal cysteine protease and a potent collagenase, on ECM modulation and actin cytoskeleton rearrangements in the TM outflow pathway and the regulation of IOP. Initially, we found that CTSK was negatively regulated by pathological stressors known to elevate IOP. Further, inactivating CTSK using balicatib, a pharmacological cell-permeable inhibitor of CTSK, resulted in IOP elevation due to increased levels and excessive deposition of ECM-like collagen-1A in the TM outflow pathway. The loss of CTSK activity resulted in actin-bundling via fascin and vinculin reorganization and by inhibiting actin depolymerization via phospho-cofilin. Contrarily, constitutive expression of CTSK decreased ECM and increased actin depolymerization by decreasing phospho-cofilin, negatively regulated the availability of active TGFβ2, and reduced the levels of alpha-smooth muscle actin (αSMA), indicating an antifibrotic action of CTSK. In conclusion, these observations, for the first time, demonstrate the significance of CTSK in IOP regulation by maintaining the ECM homeostasis and actin cytoskeleton-mediated contractile properties of the TM outflow pathway.Item Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms(Association for Research in Vision and Ophthalmology, 2022) McDowell, Colleen M.; Kizhatil, Krishnakumar; Elliott, Michael H.; Overby, Darryl R.; van Batenburg-Sherwood, Joseph; Millar, J. Cameron; Kuehn, Markus H.; Zode, Gulab; Acott, Ted S.; Anderson, Michael G.; Bhattacharya, Sanjoy K.; Bertrand, Jacques A.; Borras, Terete; Bovenkamp, Diane E.; Cheng, Lin; Danias, John; De Ieso, Michael Lucio; Du, Yiqin; Faralli, Jennifer A.; Fuchshofer, Rudolf; Ganapathy, Preethi S.; Gong, Haiyan; Herberg, Samuel; Hernandez, Humberto; Humphries, Peter; John, Simon W.M.; Kaufman, Paul L.; Keller, Kate E.; Kelley, Mary J.; Kelly, Ruth A.; Krizaj, David; Kumar, Ajay; Leonard, Brian C.; Lieberman, Raquel L.; Liton, Paloma; Liu, Yutao; Liu, Katy C.; Lopez, Navita N.; Mao, Weiming; Mavlyutov, Timur; McDonnell, Fiona; McLellan, Gillian J.; Mzyk, Philip; Nartey, Andrews; Pasquale, Louis R.; Patel, Gaurang C.; Pattabiraman, Padmanabhan P.; Peters, Donna M.; Raghunathan, Vijaykrishna; Rao, Ponugoti Vasantha; Rayana, Naga; Raychaudhuri, Urmimala; Reina-Torres, Ester; Ren, Ruiyi; Rhee, Douglas; Chowdhury, Uttio Roy; Samples, John R.; Samples, E. Griffen; Sharif, Najam; Schuman, Joel S.; Sheffield, Val C.; Stevenson, Cooper H.; Soundararajan, Avinash; Subramanian, Preeti; Sugali, Chenna Kesavulu; Sun, Yang; Toris, Carol B.; Torrejon, Karen Y.; Vahabikashi, Amir; Vranka, Janice A.; Wang, Ting; Willoughby, Colin E.; Xin, Chen; Yun, Hongmin; Zhang, Hao F.; Fautsch, Michael P.; Tamm, Ernst R.; Clark, Abbot F.; Ethier, C. Ross; Stamer, W. Daniel; Ophthalmology, School of MedicineDue to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings.Item Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms(ARVO, 2022-02) McDowell, Colleen M.; Kizhatil, Krishnakumar; Elliott, Michael H.; Overby, Darryl R.; Van Batenburg-Sherwood, Joseph; Millar, J. Cameron; Kuehn, Markus H.; Zode, Gulab; Acott, Ted S.; Anderson, Michael G.; Bhattacharya, Sanjoy K.; Bertrand, Jacques A.; Borras, Terete; Bovenkamp, Diane E.; Cheng, Lin; Danias, John; De Ieso, Michael Lucio; Du, Yiqin; Faralli, Jennifer A.; Fuchshofer, Rudolf; Ganapathy, Preethi S.; Gong, Haiyan; Herberg, Samuel; Hernandez, Humberto; Humphries, Peter; John, Simon W. M.; Kaufman, Paul L.; Keller, Kate E.; Kelley, Mary J.; Kelly, Ruth A.; Krizaj, David; Kumar, Ajay; Leonard, Brian C.; Lieberman, Raquel L.; Liton, Paloma; Liu, Yutao; Liu, Katy C.; Lopez, Navita N.; Mao, Weiming; Mavlyutov, Timur; McDonnell, Fiona; McLellan, Gillian J.; Mzyk, Philip; Nartey, Andrews; Pasquale, Louis R.; Patel, Gaurang C.; Pattabiraman, Padmanabhan P.; Peters, Donna M.; Raghunathan, Vijaykrishna; Rao, Ponugoti Vasantha; Rayana, Naga; Raychaudhuri, Urmimala; Reina-Torres, Ester; Ren, Ruiyi; Rhee, Douglas; Chowdhury, Uttio Roy; Samples, John R.; Samples, E. Griffen; Sharif, Najam; Schuman, Joel S.; Sheffield, Val C.; Stevenson, Cooper H.; Soundararajan, Avinash; Subramanian, Preeti; Sugali, Chenna Kesavulu; Sun, Yang; Toris, Carol B.; Torrejon, Karen Y.; Vahabikashi, Amir; Vranka, Janice A.; Wang, Ting; Willoughby, Colin E.; Xin, Chen; Yun, Hongmin; Zhang, Hao F.; Fautsch, Michael P.; Tamm, Ernst R.; Clark, Abbot F.; Ethier, C. Ross; Stamer, W. Daniel; Ophthalmology, School of MedicineDue to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings.Item Effects of traditional Chinese medicinal herbal extracts on HIV-1 replication(2011-03-16) Wang, Ting; He, Johnny J.; Yu, Andy; Schloemer, Robert H.Background: The current treatment for HIV/AIDS is called highly active antiretroviral therapy (HAART) and is a combination of anti-HIV reverse transcriptase inhibitors and protease inhibitors. HAART is capable of suppressing HIV replication and subsequently improving the patients’ survival. However, the issues associated with use of HARRT such as the high cost, severe side-effects, and drug resistance have called for development of alternative anti-HIV therapeutic strategies. In this study, we screened several traditional Chinese medicinal herbal extracts for their anti-HIV activities and determined their anti-HIV mechanisms. Methods: Nine traditional Chinese medicinal (TCM) herbal plants and their respective parts derived from Hainan Island, China were extracted using a series of organic solvents, vacuum dried, and dissolved in dimethyl sulfoxide. Initial anti-HIV activity and cytotoxicity of these extracts were evaluated in HIV-infected human CD4+ T lymphocytes Jurkat. Extracts of higher anti-HIV activities and lower cytotoxicity were selected from the initial screening, and further examined for their effects on HIV-1 entry, post-entry, reverse transcriptase, gene transcription and expression using combined virology, cell biology and biochemistry techniques. Results: Four extracts derived from two different herbal plants completely blocked HIV-1 replication and showed little cytotoxicity at a concentration of 10 g/ml. None of these four extracts had any inhibitory effects on HIV-1 long terminal repeat promoter. Two of them exhibited direct inhibitory activity against HIV-1 reverse transcriptase (RT). All four extracts showed significant blocking of HIV-1 entry into target cells. Conclusions: These results demonstrated that four TCM extracts were capable of preventing HIV-1 infection and replication by blocking viral entry and/or directly inhibiting the RT activity. These results suggest the possibility of developing these extracts as potential anti-HIV therapeutic agents.Item Epigenetic contribution of the myosin light chain kinase gene to the risk for acute respiratory distress syndrome(Elsevier, 2017-02) Szilágyi, Keely L.; Liu, Cong; Zhang, Xu; Wang, Ting; Fortman, Jeffrey D.; Zhang, Wei; Garcia, Joe G.N.; Medicine, School of MedicineAcute respiratory distress syndrome (ARDS) is a devastating clinical syndrome with a considerable case fatality rate (∼30%-40%). Health disparities exist with African descent (AD) subjects exhibiting greater mortality than European descent (ED) individuals. Myosin light chain kinase is encoded by MYLK, whose genetic variants are implicated in ARDS pathogenesis and may influence ARDS mortality. As baseline population-specific epigenetic changes, that is, cytosine modifications, have been observed between AD and ED individuals, epigenetic variations in MYLK may provide insights into ARDS disparities. We compared methylation levels of MYLK cytosine-guanine dinucleotides (CpGs) between ARDS patients and intensive care unit (ICU) controls overall and by ethnicity in a nested case-control study of 39 ARDS cases and 75 non-ARDS ICU controls. Two MYLK CpG sites (cg03892735 and cg23344121) were differentially modified between ARDS subjects and controls (P < 0.05; q < 0.25) in a logistic regression model, where no effect modification by ethnicity or age was found. One CpG site was associated with ARDS in patients aged <58 years, cg19611163 (intron 19, 20). Two CpG sites were associated with ARDS in EDs only, gene body CpG (cg01894985, intron 2, 3) and CpG (cg16212219, intron 31, 32), with higher modification levels exhibited in ARDS subjects than controls. Cis-acting modified cytosine quantitative trait loci (mQTL) were identified using linear regression between local genetic variants and modification levels for 2 ARDS-associated CpGs (cg23344121 and cg16212219). In summary, these ARDS-associated MYLK CpGs with effect modification by ethnicity and local mQTL suggest that MYLK epigenetic variation and local genetic background may contribute to health disparities observed in ARDS.Item Functional connectivity in frontostriatal networks differentiate offspring of parents with substance use disorders from other high-risk youth(Elsevier, 2021) Kwon, Elizabeth; Hummer, Tom; Andrews, Katharine D.; Finn, Peter; Aalsma, Matthew; Bailey, Allen; Hanquier, Jocelyne; Wang, Ting; Hulvershorn, Leslie; Psychiatry, School of MedicineBackground: Family history (FH) of substance use disorders (SUDs) is known to elevate SUD risk in offspring. However, the influence of FH SUDs has been confounded by the effect of externalizing psychopathologies in the addiction risk neuroimaging literature. Thus, the current study aimed to assess the association between parental SUDs and offspring functional connectivity in samples matched for psychopathology and demographics. Methods: Ninety 11-12-year-old participants with externalizing disorders were included in the study (48 FH+, 42 FH-). We conducted independent component analyses (ICA) and seed-based analyses (orbitofrontal cortex; OFC, nucleus accumbens (NAcc), dorsolateral prefrontal cortex) with resting state data. Results: FH+ adolescents showed stronger functional connectivity between the right lateral OFC seed and anterior cingulate cortex compared to FH- adolescents (p < 0.05, corrected). Compared to FH-, FH+ adolescents showed stronger negative functional connectivity between the left lateral OFC seed and right postcentral gyrus and between the left NAcc seed and right middle occipital gyrus (p < 0.05, corrected). Poorer emotion regulation was associated with more negative connectivity between right occipital/left NAcc among FH+ adolescents based on the seed-based analysis. FH- adolescents had stronger negative functional connectivity between ventral attention/salience networks and dorsal attention/visuospatial networks in the ICA. Conclusions: Both analytic methods found group differences in functional connectivity between brain regions associated with executive functioning and regions associated with sensory input (e.g., postcentral gyrus, occipital regions). We speculate that families densely loaded for SUD may confer risk by altered neurocircuitry that is associated with emotion regulation and valuation of external stimuli beyond what would be explained by externalizing psychopathology alone.Item Higher blood selenium level is associated with lower risk of hyperhomocysteinemia in the elderly(Elsevier, 2023-01) Wang, Ting; Su, Liqin; Chen, Xi; Wang, Sisi; Han, Xu; Cheng, Yibin; Lin, Shaobin; Ding, Liang; Liu, Jingyi; Chen, Chen; Unverzagt, Frederick W.; Hake, Ann M.; Jin, Yinlong; Gao, Sujuan; Biostatistics and Health Data Science, School of MedicineBackground and aims Earlier studies have reported inconsistent association between selenium (Se) and homocysteine (Hcy) levels, while no evidence could be found from Chinese population. To fill this gap, we investigated the association between blood Se and hyperhomocysteinemia (HHcy) of rural elderly population in China. Methods A cross-sectional study on 1823 participants aged 65 and older from four Chinese rural counties was carried out in this study. Whole blood Se and serum Hcy concentrations were measured in fasting blood samples. Analysis of covariance and restricted cubic spline models were used to examine the association between Se and Hcy levels. Logistic regression models were used to evaluate the risk of prevalent HHcy among four Se quartile groups after adjusting for covariates. Results For this sample, the mean blood Se concentration was 156.34 (74.65) μg/L and the mean serum Hcy concentration was 17.25 (8.42) μmol/L. A significant non-linear relationship was found between blood Se and serum Hcy, the association was inverse when blood Se was less than 97.404 μg/L and greater than 156.919 μg/L. Participants in the top three blood Se quartile groups had significantly lower risk of prevalent HHcy compared with the lowest quartile group. When defined as Hcy> 10 μmol/L, the odds ratios and 95% confidence interval of HHcy were 0.600 (0.390, 0.924), 0.616 (0.398, 0.951) and 0.479 (0.314, 0.732) for Q2, Q3, and Q4 Se quartile groups compared with the Q1 group, respectively. When defined as Hcy≥ 15 μmol/L, the odds ratios and 95% confidence interval of HHcy were 0.833 (0.633, 1.098) and 0.827 (0.626, 1.092), 0.647 (0.489, 0.857) for Q2, Q3, and Q4 Se quartile groups compared with Q1 group. Conclusions Our findings suggest that higher blood Se level could be a protective factor for HHcy in the elderlyItem HIV envelope protein gp120-induced apoptosis in lung microvascular endothelial cells by concerted upregulation of EMAP II and its receptor, CXCR3(American Physiological Society (APS), 2014-02-15) Green, Linden A.; Yi, Ru; Petrusca, Daniela; Wang, Ting; Elghouche, Alhasan; Gupta, Samir K.; Petrache, Irina; Clauss, Matthias; Department of Cellular & Integrative Physiology, IU School of MedicineChronic lung diseases, such as pulmonary emphysema, are increasingly recognized complications of infection with the human immunodeficiency virus (HIV). Emphysema in HIV may occur independent of cigarette smoking, via mechanisms that are poorly understood but may involve lung endothelial cell apoptosis induced by the HIV envelope protein gp120. Recently, we have demonstrated that lung endothelial apoptosis is an important contributor to the development of experimental emphysema, via upregulation of the proinflammatory cytokine endothelial monocyte-activating polypeptide II (EMAP II) in the lung. Here we investigated the role of EMAP II and its receptor, CXCR3, in gp120-induced lung endothelial cell apoptosis. We could demonstrate that gp120 induces a rapid and robust increase in cell surface expression of EMAP II and its receptor CXCR3. This surface expression occurred via a mechanism involving gp120 signaling through its CXCR4 receptor and p38 MAPK activation. Both EMAP II and CXCR3 were essentially required for gp120-induced apoptosis and exposures to low gp120 concentrations enhanced the susceptibility of endothelial cells to undergo apoptosis when exposed to soluble cigarette smoke extract. These data indicate a novel mechanism by which HIV infection causes endothelial cell loss involved in lung emphysema formation, independent but potentially synergistic with smoking, and suggest therapeutic targets for emphysema prevention and/or treatment.