Medicine and Health Sciences Commons^™

Sexual Dimorphism In Rat Vascular Function Of Type I And Type Ii Diabetes: Role Of Edrfs, Roshanak Rahimian

Science Seminar Series

Dr. Roshanak Rahimian, professor of physiology and pharmacology in the Thomas J. Long School of Pharmacy and Health Sciences will tell us about her work on understanding the mechanisms underlying the interaction of sex and diabetes in vasculature.

Over the past decade, diabetes and obesity have reached epidemic levels in developed countries, and has become one of the most serious and challenging health problems in the 21st century. Several studies suggest that diabetes affects male and female vascular beds differently. However, the mechanisms underlying the interaction of sex and diabetes in vasculature remain to be investigated. We have shown that …

Nucleoside-Diphosphate-Kinase Of P. Gingivalis Is Secreted From Epithelial Cells In The Absence Of A Leader Sequence Through A Pannexin-1 Interactome, Kalina Atanasova, Jungnam Lee, Joann Roberts, Kyulim Lee, David M. Ojcius, Özlem Yilmaz

All Dugoni School of Dentistry Faculty Articles

Nucleoside-diphosphate-kinases (NDKs) are leaderless, multifunctional enzymes. The mode(s) of NDK secretion is currently undefined, while extracellular translocation of bacterial NDKs is critical for avoidance of host pathogen clearance by opportunistic pathogens such as Porphyromonas gingivalis. P. gingivalis-NDK during infection inhibits extracellular-ATP (eATP)/P2X7-receptor mediated cell death in gingival epithelial cells (GECs) via eATP hydrolysis. Furthermore, depletion of pannexin-1-hemichannel (PNX1) coupled with P2X7-receptor blocks the infection-induced eATP release in GECs, and P. gingivalis-NDK impacts this pathway. Ultrastructural and confocal microscopy of P. gingivalis-co-cultured GECs or green-fluorescent-protein (GFP)-P. gingivalis-NDK transfected GECs revealed a perinuclear/cytoplasmic localization of NDK. eATP stimulation induced NDK recruitment to …

An Iron Detection System Determines Bacterial Swarming Initiation And Biofilm Formation, Chuan-Sheng Lin, Yu-Huan Tsai, Chih-Jung Chang, Shun-Fu Tseng, Tseng-Ru Wu, Chia-Chen Lu, Ting-Shu Wu, Jang-Jih Lu, Jim-Tong Horng, Jan Martel, David M. Ojcius, Hsin-Chih Lai, John Ding-E. Young

All Dugoni School of Dentistry Faculty Articles

Iron availability affects swarming and biofilm formation in various bacterial species. However, how bacteria sense iron and coordinate swarming and biofilm formation remains unclear. Using Serratia marcescens as a model organism, we identify here a stage-specific iron-regulatory machinery comprising a two-component system (TCS) and the TCS-regulated iron chelator 2-isocyano-6,7-dihydroxycoumarin (ICDH-Coumarin) that directly senses and modulates environmental ferric iron (Fe3+) availability to determine swarming initiation and biofilm formation. We demonstrate that the two-component system RssA-RssB (RssAB) directly senses environmental ferric iron (Fe³⁺) and transcriptionally modulates biosynthesis of flagella and the iron chelator ICDH-Coumarin whose production requires the pvc cluster. …

Pyk2 Activates The Nlrp3 Inflammasome By Directly Phosphorylating Asc And Contributes To Inflammasome-Dependent Peritonitis, I-Che Chung, Chun-Nan Ouyang, Sheng-Ning Yuan, Hsin-Pai P. Li, Jeng-Ting Chen, Hui-Ru Shieh, Yu-Jen Chen, David M. Ojcius, Ching-Liang Chu, Jau-Song Yu, Yu-Sun Chang, Lih-Chyang Chen

All Dugoni School of Dentistry Faculty Articles

The inflammasome adaptor protein, ASC, contributes to both innate immune responses and inflammatory diseases via self-oligomerization, which leads to the activation of the protease, caspase-1. Here, we report that the cytosolic tyrosine kinases, FAK and Pyk2, are differentially involved in NLRP3 and AIM2 inflammasome activation. The inhibition of FAK and Pyk2 with RNA interference or chemical inhibitors dramatically abolished ASC oligomerization, caspase-1 activation, and IL-1β secretion in response to NLRP3 or AIM2 stimulation. Pyk2 is phosphorylated by the kinase Syk and relocalizes to the ASC specks upon NLRP3 inflammasome activation. Pyk2, but not FAK, could directly phosphorylate ASC at Tyr146, …

Danger Signals, Inflammasomes, And The Intricate Intracellular Lives Of Chlamydiae, M. A. Pettengill, A. A. Sater, R. Coutinho-Silva, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

Chlamydiae are obligate intracellular bacterial pathogens, and as such are sensitive to alterations in the cellular physiology of their hosts. Chlamydial infections often cause pathologic consequences due to prolonged localized inflammation. Considerable advances have been made in the last few years regarding our understanding of how two key inflammation-associated signaling pathways influence the biology of

The Relationship Between Basic Psychological Need Satisfaction, Behavioral Regulation, And Participation In Crossfit, Melissa J. Davies, Lyndsie Coleman, Megan Babkes Stellino

College of the Pacific Faculty Articles

CrossFit can be described as a relatively new fitness training method that is based on a variety of high-intensity weight training, body weight movements, and cardiovascular exercise. Given the recent rise in CrossFit establishments, the purpose of this study was to explore the relationships between basic need satisfaction (autonomy, relatedness, competence), behavioral regulation toward CrossFit, and actual participation behaviors within the framework of Self-Determination Theory. CrossFit participants (N = 206; Mage = 37.6 years), majority Caucasian (76%), females (58%), who reported attending three (n = 91; 44.2%) and five (n = 78; 37.9%) CrossFit sessions per week completed online surveys …

Purinergic Signaling During Porphyromonas Gingivalis Infection, C. Silva, A. C. Morandini, David M. Ojcius, R. Coutinho-Silva,

All Dugoni School of Dentistry Faculty Articles

Despite recent advances unraveling mechanisms of host–pathogen interactions in innate immunity, the participation of purinergic signaling in infection-driven inflammation remains an emerging research field with many unanswered questions. As one of the most-studied oral pathogens, Porphyromonas gingivalis is considered as a keystone pathogen with a central role in development of periodontal disease. This pathogen needs to evade immune-mediated defense mechanisms and tolerate inflammation in order to survive in the host. In this review, we summarize evidence showing that purinergic signaling modulates P. gingivalis survival and cellular immune responses, and discuss the role played by inflammasome activation and cell death during …

Hepatitis C Virus Frameshift/Alternate Reading Frame Protein Suppresses Interferon Responses Mediated By Pattern Recognition Receptor Retinoic-Acid-Inducible Gene-I, Seung Bum Park, Scott Seronello, Wasima Mayer, David M. Ojcius

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Hepatitis C virus (HCV) actively evades host interferon (IFN) responses but the mechanisms of how it does so are not completely understood. In this study, we present evidence for an HCV factor that contributes to the suppression of retinoic-acid-inducible gene-I (RIG-I)-mediated IFN induction. Expression of frameshift/alternate reading frame protein (F/ARFP) from HCV -2/+1 frame in Huh7 hepatoma cells suppressed type I IFN responses stimulated by HCV RNA pathogen-associated molecular pattern (PAMP) and poly(IC). The suppression occurred independently of other HCV factors; and activation of interferon stimulated genes, TNFα, IFN-λ1, and IFN-λ2/3 was likewise suppressed by HCV F/ARFP. Point mutations in …

Alternative Functions For The Multifarious Inflammasome, J. Martel, H. C. Lai, Y. F. Ko, J. D. Young, David M. Ojcius

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The inflammasome has been mainly studied in innate immune cells in which it senses microbes and cellular damage, and induces secretion of pro-inflammatory cytokines. This process induces an inflammatory response that is critical for the resolution of infections and repair of tissue damage following injury. Recent studies indicate that inflammasome complex formation also participates in many other cellular and physiological processes beyond modulation of inflammation, such as autophagy, metabolism, eicosanoids production, and phagosome maturation.

Retigabine Holds Kv7 Channels Open And Stabilizes The Resting Potential, Aaron Corbin-Leftwich, Sayeed M. Mossadeq, Junghoon Ha, Iwona Ruchala, Audrey Han Ngoc Le, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

The anticonvulsant Retigabine is a KV7 channel agonist used to treat hyperexcitability disorders in humans. Retigabine shifts the voltage dependence for activation of the heteromeric KV7.2/KV7.3 channel to more negative potentials, thus facilitating activation. Although the molecular mechanism underlying Retigabine's action remains unknown, previous studies have identified the pore region of KV7 channels as the drug's target. This suggested that the Retigabine-induced shift in voltage dependence likely derives from the stabilization of the pore domain in an open (conducting) conformation. Testing this idea, we show that the heteromeric KV7.2/KV7.3 channel has at least two open states, which we named O1 …

Exploring The Information Source Preferences Among Canadian Adult Golf League Members, Melissa J. Davies, Dianna Gray

College of the Pacific Faculty Articles

With an aging demographic, and the abundance of physical inactivity in Canada, sport professionals need to understand how best to recruit and retain adults in sport and recreational activities, namely, golf leagues. Canadian golf league participants (N = 419; Mage = 62 years old) completed an online survey detailing their propensity to utilize a variety of information sources prior to making the decision to join a golf league. Results from a principal component analysis of a revised Information Sources Inventory, suggested that golfers in this sample were most likely to utilize Personal and Social sources of information associated with their …