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Novel Fluconazole Derivatives With Promising Antifungal Activity, Nishad Thamban Chandrika, Sanjib K. Shrestha, Huy X. Ngo, Kaitlind C. Howard, Sylvie Garneau-Tsodikova Feb 2018

Novel Fluconazole Derivatives With Promising Antifungal Activity, Nishad Thamban Chandrika, Sanjib K. Shrestha, Huy X. Ngo, Kaitlind C. Howard, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

The fungistatic nature and toxicity concern associated with the azole drugs currently on the market have resulted in an increased demand for new azole antifungal agents for which these problematic characteristics do not exist. The extensive use of azoles has resulted in fungal strains capable of resisting the action of these drugs. Herein, we report the synthesis and antifungal activities of novel fluconazole (FLC) analogues with alkyl-, aryl-, cycloalkyl-, and dialkyl-amino substituents. We evaluated their antifungal activity by MIC determination and time-kill assay as well as their safety profile by hemolytic activity against murine erythrocytes as well as cytotoxicity against …

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Minocycline Protects Developing Brain Against Ethanol-Induced Damage, Xin Wang, Kai Zhang, Fanmuyi Yang, Zhenhua Ren, Mei Xu, Jacqueline A. Frank, Zun-Ji Ke, Jia Luo Feb 2018

Minocycline Protects Developing Brain Against Ethanol-Induced Damage, Xin Wang, Kai Zhang, Fanmuyi Yang, Zhenhua Ren, Mei Xu, Jacqueline A. Frank, Zun-Ji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Fetal alcohol spectrum disorders (FASD) are caused by ethanol exposure during the pregnancy and is the leading cause of mental retardation. Ethanol exposure during the development results in the loss of neurons in the developing brain, which may underlie many neurobehavioral deficits associated with FASD. It is important to understand the mechanisms underlying ethanol-induced neuronal loss and develop appropriate therapeutic strategies. One of the potential mechanisms involves neuroimmune activation. Using a third trimester equivalent mouse model of ethanol exposure, we demonstrated that ethanol induced a wide-spread neuroapoptosis, microglial activation, and neuroinflammation in C57BL/6 mice. Minocycline is an antibiotic that inhibits …

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Kruppel-Like Factor 4-Dependent Staufen1-Mediated Mrna Decay Regulates Cortical Neurogenesis, Byoung-San Moon, Jinlun Bai, Mingyang Cai, Chunming Liu, Jiandang Shi, Wange Lu Jan 2018

Kruppel-Like Factor 4-Dependent Staufen1-Mediated Mrna Decay Regulates Cortical Neurogenesis, Byoung-San Moon, Jinlun Bai, Mingyang Cai, Chunming Liu, Jiandang Shi, Wange Lu

Molecular and Cellular Biochemistry Faculty Publications

Kruppel-like factor 4 (Klf4) is a zinc-finger-containing protein that plays a critical role in diverse cellular physiology. While most of these functions attribute to its role as a transcription factor, it is postulated that Klf4 may play a role other than transcriptional regulation. Here we demonstrate that Klf4 loss in neural progenitor cells (NPCs) leads to increased neurogenesis and reduced self-renewal in mice. In addition, Klf4 interacts with RNA-binding protein Staufen1 (Stau1) and RNA helicase Ddx5/17. They function together as a complex to maintain NPC self-renewal. We report that Klf4 promotes Stau1 recruitment to the 3′-untranslated region of neurogenesis-associated mRNAs, …

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Behavioral And Transcriptomic Analysis Of Trem2-Null Mice: Not All Knockout Mice Are Created Equal, Silvia S Kang, Aishe Kurti, Kelsey E Baker, Chia-Chen Liu, Marco Colonna, Jason D Ulrich, David M Holtzman, Guojun Bu, John D Fryer Jan 2018

Behavioral And Transcriptomic Analysis Of Trem2-Null Mice: Not All Knockout Mice Are Created Equal, Silvia S Kang, Aishe Kurti, Kelsey E Baker, Chia-Chen Liu, Marco Colonna, Jason D Ulrich, David M Holtzman, Guojun Bu, John D Fryer

2010-2019 OA Pubs

It is clear that innate immune system status is altered in numerous neurodegenerative diseases. Human genetic studies have demonstrated that triggering receptor expressed in myeloid cells 2 (TREM2) coding variants have a strong association with Alzheimer's disease (AD) and other neurodegenerative diseases. To more thoroughly understand the impact of TREM2 in vivo, we studied the behavioral and cognitive functions of wild-type (WT) and Trem2-/- (KO) mice during basal conditions and brain function in the context of innate immune stimulation with peripherally administered lipopolysaccharide (LPS). Early markers of neuroinflammation preceded Aif1 and Trem2 upregulation that occurred at later stages (24-48 h …

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Beta-Catenin Cleavage Enhances Transcriptional Activation, Tatiana Goretsky, Emily M. Bradford, Qing Ye, Olivia F. Lamping, Tomas Vanagunas, Mary Pat Moyer, Patrick C. Keller, Preetika Sinh, Josep M. Llovet, Tianyan Gao, Qing-Bai She, Linheng Li, Terrence A. Barrett Jan 2018

Beta-Catenin Cleavage Enhances Transcriptional Activation, Tatiana Goretsky, Emily M. Bradford, Qing Ye, Olivia F. Lamping, Tomas Vanagunas, Mary Pat Moyer, Patrick C. Keller, Preetika Sinh, Josep M. Llovet, Tianyan Gao, Qing-Bai She, Linheng Li, Terrence A. Barrett

Internal Medicine Faculty Publications

Nuclear activation of Wnt/β-catenin signaling is required for cell proliferation in inflammation and cancer. Studies from our group indicate that β-catenin activation in colitis and colorectal cancer (CRC) correlates with increased nuclear levels of β-catenin phosphorylated at serine 552 (pβ-Cat552). Biochemical analysis of nuclear extracts from cancer biopsies revealed the existence of low molecular weight (LMW) pβ-Cat552, increased to the exclusion of full size (FS) forms of β-catenin. LMW β-catenin lacks both termini, leaving residues in the armadillo repeat intact. Further experiments showed that TCF4 predominantly binds LMW pβ-Cat552 in the nucleus of inflamed and …

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Zinc Inhibits Trpv1 To Alleviate Chemotherapy-Induced Neuropathic Pain, Jialie Luo, Alexis Bavencoffe, Pu Yang, Jing Feng, Shijin Yin, Aihua Qian, Weihua Yu, Shenbin Liu, Xuan Gong, Tao Cai, Edgar T. Walters, Carmen W. Dessauer, Hongzhen Hu Jan 2018

Zinc Inhibits Trpv1 To Alleviate Chemotherapy-Induced Neuropathic Pain, Jialie Luo, Alexis Bavencoffe, Pu Yang, Jing Feng, Shijin Yin, Aihua Qian, Weihua Yu, Shenbin Liu, Xuan Gong, Tao Cai, Edgar T. Walters, Carmen W. Dessauer, Hongzhen Hu

Open Access Publications

Zinc is a transition metal that has a long history of use as an anti-inflammatory agent. It also soothes pain sensations in a number of animal models. However, the effects and mechanisms of zinc on chemotherapy-induced peripheral neuropathy remain unknown. Here we show that locally injected zinc markedly reduces neuropathic pain in male and female mice induced by paclitaxel, a chemotherapy drug, in a TRPV1-dependent manner. Extracellularly applied zinc also inhibits the function of TRPV1 expressed in HEK293 cells and mouse DRG neurons, which requires the presence of zinc-permeable TRPA1 to mediate entry of zinc into the cytoplasm. Moreover, TRPA1 …

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Microscale Gene Expression Analysis Of Tumor-Associated Macrophages, Kuldeep S. Attri, Kamiya Mehla, Surendra K. Shukla, Pankaj K. Singh Jan 2018

Microscale Gene Expression Analysis Of Tumor-Associated Macrophages, Kuldeep S. Attri, Kamiya Mehla, Surendra K. Shukla, Pankaj K. Singh

Journal Articles: Eppley Institute

Macrophages, apart from being the key effector cells of the innate immune system, also play critical roles during the development and progression of various complex diseases, including cancer. Tumor-associated macrophages, infiltrate tumors during different stages of cancer progression to regulate motility, invasion, and intravasation to metastatic sites. Macrophages can exist in different polarization states associated with unique function in tumors. Since tumor-associated macrophages constitute a very small proportion of tumor cells, analysis of gene expression pattern using normal extraction buffer-based methods remains a challenging task. Therefore, it is imperative to develop low-throughput strategies to investigate transcriptional regulations from a small …

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Aminoglycosides Rapidly Inhibit Nad(P)H Metabolism Increasing Reactive Oxygen Species And Cochlear Cell Demise, Danielle E. Desa, Michael G. Nichols, Heather Jensen Smith Jan 2018

Aminoglycosides Rapidly Inhibit Nad(P)H Metabolism Increasing Reactive Oxygen Species And Cochlear Cell Demise, Danielle E. Desa, Michael G. Nichols, Heather Jensen Smith

Journal Articles: Eppley Institute

Despite causing permanent hearing loss by damaging inner ear sensory cells, aminoglycosides (AGs) remain one of the most widely used classes of antibiotics in the world. Although the mechanisms of cochlear sensory cell damage are not fully known, reactive oxygen species (ROS) are clearly implicated. Mitochondrial-specific ROS formation was evaluated in acutely cultured murine cochlear explants exposed to gentamicin (GM), a representative ototoxic AG antibiotic. Superoxide (O2·-) and hydrogen peroxide (H2O2) were measured using MitoSOX Red and Dihydrorhodamine 123, respectively, in sensory and supporting cells. A 1-h GM exposure significantly increased O2·- formation in IHCs and increased H2O2 formation in …

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Analogical Reasoning, Stella Christie Jan 2018

Analogical Reasoning, Stella Christie

Psychology Faculty Works

Analogical reasoning is the ability to perceive and use relational commonality between two situations. Most commonly, analogy involves mapping relational structures from a familiar (base situation to an unfamiliar situation (target). For example, solving the analogy “chicken is to chick like tiger is to___?” requires perceiving the relation parent–offspring in the base domain (chicken:chick) and mapping the same relation to the target (tiger:__?) to get to the answer cub. Relational similarity is the crux of analogical reasoning; what is crucial here is the sameness of the relation, not of other similarities—chickens and tigers do not look alike.

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3′,4′-Dihydroxyflavonol Ameliorates Endoplasmic Reticulum Stress-Induced Apoptosis And Endothelial Dysfunction In Mice, Y.S. Lau, Mohd Rais Mustafa, K.W. Choy, S.M.H. Chan, S. Potocnik, T.P. Herbert, O.L. Woodman Jan 2018

3′,4′-Dihydroxyflavonol Ameliorates Endoplasmic Reticulum Stress-Induced Apoptosis And Endothelial Dysfunction In Mice, Y.S. Lau, Mohd Rais Mustafa, K.W. Choy, S.M.H. Chan, S. Potocnik, T.P. Herbert, O.L. Woodman

Research Publications (2016 to 2020)

Endoplasmic reticulum (ER) stress has been implicated in the development of hypertension 3 through the induction of endothelial impairment. As 3′,4′-dihydroxyflavonol (DiOHF) 4 reduces vascular injury caused by ischaemia/reperfusion or diabetes, and flavonols have been demonstrated to attenuate ER stress, we investigated whether DiOHF can protect mice from ER stress-induced endothelial dysfunction. Male C57BLK/6 J mice were injected with tunicamycin to induce ER stress in the presence or absence of either DiOHF or tauroursodeoxycholic acid (TUDCA), an inhibitor of ER stress. Tunicamycin elevated blood pressure and impaired endothelium-dependent relaxation. Moreover, in aortae there was evidence of ER stress, oxidative stress …

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Acute And Sub-Acute Oral Toxicity Of Dracaena Cinnabari Resin Methanol Extract In Rats, N.A. Al-Afifi, A.M. Alabsi, M.M. Bakri, A. Ramanathan Jan 2018

Acute And Sub-Acute Oral Toxicity Of Dracaena Cinnabari Resin Methanol Extract In Rats, N.A. Al-Afifi, A.M. Alabsi, M.M. Bakri, A. Ramanathan

Research Publications (2016 to 2020)

Background: Dracaena cinnabari (DC) is a perennial tree that located on the Southern coast of Yemen native to the Socotra Island. This tree produces a deep red resin known as the Dragon's blood, the Twobrother's Blood or Damm Alakhwain. The current study performed to evaluate the safety of the DC resin methanol extract after a single or 28 consecutive daily oral administrations. Methods: In assessing the safety of DC resin methanol extract, acute and sub-acute oral toxicity tests performed following OECD guidelines 423 and 407, respectively, with slight modifications. In acute oral toxicity test, DC resin methanol extract administered to …

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Ac-Sdkp Decreases Mortality And Cardiac Rupture After Acute Myocardial Infarction, Pablo Nakagawa, Cesar A. Romero, Xu Jiang, Martin D'Ambrosio, Ginette Bordcoch, Edward L. Peterson, Pamela Harding, Xiao-Ping Yang, Oscar A. Carretero Jan 2018

Ac-Sdkp Decreases Mortality And Cardiac Rupture After Acute Myocardial Infarction, Pablo Nakagawa, Cesar A. Romero, Xu Jiang, Martin D'Ambrosio, Ginette Bordcoch, Edward L. Peterson, Pamela Harding, Xiao-Ping Yang, Oscar A. Carretero

Hypertension and Vascular Research Articles

The natural peptide N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) decreases inflammation in chronic diseases such as hypertension and heart failure. However, Ac-SDKP effects on acute inflammatory responses during myocardial infarction (MI) are unknown. During the first 72 hours post-MI, neutrophils, M1 macrophages (pro-inflammatory), and M2 macrophages (pro-resolution) and release of myeloperoxidase (MPO) and matrix metalloproteinases (MMP) are involved in cardiac rupture. We hypothesized that in the acute stage of MI, Ac-SDKP decreases the incidence of cardiac rupture and mortality by preventing immune cell infiltration as well as by decreasing MPO and MMP expression. MI was induced by ligating the left descending coronary artery in …

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Altered Myelination As A Proposed Mechanism For Neurocognitive Dysfunction Observed In Mice With Tyrosinemia Type 1, Marissa E. Moore Jan 2018

Altered Myelination As A Proposed Mechanism For Neurocognitive Dysfunction Observed In Mice With Tyrosinemia Type 1, Marissa E. Moore

Theses

The exact mechanism behind the recent reports of impaired neurocognitive function in individuals with the rare genetic disorder Hereditary Tyrosinemia Type I (HT1) has yet to be determined. This disorder stems from lack of expression of the gene fumarylacetoacetate hydrolase (FAH), which is responsible for tyrosine catabolism. This subsequently leads to a buildup of tyrosine and associated harmful metabolites that will cause sever liver dysfunction and cancer if treatment is not provided. The drug 2-[2-nitro-4-(trifluoromethylbenzoyl) cyclohexane-1,3-dione (NTBC) has proven to be effective in stopping the negative consequences on the liver and kidneys by inhibiting an enzyme upstream in the metabolic …

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Cgas Drives Noncanonical-Inflammasome Activation In Age-Related Macular Degeneration, Nagaraj Kerur, Shinichi Fukuda, Daipayan Banerjee, Younghee Kim, Dongxu Fu, Ivana Apicella, Akhil Varshney, Reo Yasuma, Benjamin J. Fowler, Elmira Baghdasaryan, Kenneth M. Marion, Xiwen Huang, Tetsuhiro Yasuma, Yoshio Hirano, Vlad Serbulea, Meenakshi Ambati, Vidya L. Ambati, Yuji Kajiwara, Kameshwari Ambati, Shuichiro Hirahara, Ana Bastos-Carvalho, Yuichiro Ogura, Hiroko Terasaki, Tetsuro Oshika, Kyung Bo Kim, David R. Hinton, Norbert Leitinger, John C. Cambier, Joseph D. Buxbaum, M. Cristina Kenney, Bradley D. Gelfand, Jayakrishna Ambati Jan 2018

Cgas Drives Noncanonical-Inflammasome Activation In Age-Related Macular Degeneration, Nagaraj Kerur, Shinichi Fukuda, Daipayan Banerjee, Younghee Kim, Dongxu Fu, Ivana Apicella, Akhil Varshney, Reo Yasuma, Benjamin J. Fowler, Elmira Baghdasaryan, Kenneth M. Marion, Xiwen Huang, Tetsuhiro Yasuma, Yoshio Hirano, Vlad Serbulea, Meenakshi Ambati, Vidya L. Ambati, Yuji Kajiwara, Kameshwari Ambati, Shuichiro Hirahara, Ana Bastos-Carvalho, Yuichiro Ogura, Hiroko Terasaki, Tetsuro Oshika, Kyung Bo Kim, David R. Hinton, Norbert Leitinger, John C. Cambier, Joseph D. Buxbaum, M. Cristina Kenney, Bradley D. Gelfand, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Geographic atrophy is a blinding form of age-related macular degeneration characterized by retinal pigmented epithelium (RPE) death; the RPE also exhibits DICER1 deficiency, resultant accumulation of endogenous Alu-retroelement RNA, and NLRP3-inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human-cell-culture and mouse models is driven by a noncanonical-inflammasome pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β production and gasdermin D-dependent interleukin-18 secretion. Decreased DICER1 levels or Alu-RNA accumulation triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin …

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Gata4-Dependent Differentiation Of C-Kit+-Derived Endothelial Cells Underlies Artefactual Cardiomyocyte Regeneration In The Heart, Bryan D. Maliken, Onur Kanisicak, Jason Karch, Hadi Khalil, Xing Fu, Justin G. Boyer, Vikram Prasad, Yi Zheng, Jeffery D. Molkentin Jan 2018

Gata4-Dependent Differentiation Of C-Kit+-Derived Endothelial Cells Underlies Artefactual Cardiomyocyte Regeneration In The Heart, Bryan D. Maliken, Onur Kanisicak, Jason Karch, Hadi Khalil, Xing Fu, Justin G. Boyer, Vikram Prasad, Yi Zheng, Jeffery D. Molkentin

Faculty Publications

© 2018 The Authors. BACKGROUND: Although c-Kit+ adult progenitor cells were initially reported to produce new cardiomyocytes in the heart, recent genetic evidence suggests that such events are exceedingly rare. However, to determine if these rare events represent true de novo cardiomyocyte formation, we deleted the necessary cardiogenic transcription factors Gata4 and Gata6 from c-Kit-expressing cardiac progenitor cells. METHODS: Kit allele-dependent lineage tracing and fusion analysis were performed in mice following simultaneous Gata4 and Gata6 cell type-specifc deletion to examine rates of putative de novo cardiomyocyte formation from c-Kit+ cells. Bone marrow transplantation experiments were used to defne the contribution …

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Cell Circuits Between B Cell Progenitors And Il-7+ Mesenchymal Progenitor Cells Control B Cell Development, Chris Fistonich, Sandra Zehentmeier, Jeffrey J. Bednarski, Runfeng Miao, Hilde Schjerven, Barry P Sleckman, João P Pereira Jan 2018

Cell Circuits Between B Cell Progenitors And Il-7+ Mesenchymal Progenitor Cells Control B Cell Development, Chris Fistonich, Sandra Zehentmeier, Jeffrey J. Bednarski, Runfeng Miao, Hilde Schjerven, Barry P Sleckman, João P Pereira

Open Access Publications

B cell progenitors require paracrine signals such as interleukin-7 (IL-7) provided by bone marrow stromal cells for proliferation and survival. Yet, how B cells regulate access to these signals in vivo remains unclear. Here we show that proB and IL-7

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Cell Biological Analyses Of The Role Of The Vrk1 Protein Kinase In Mammary Epithelial Cells, Aye M. Mon Jan 2018

Cell Biological Analyses Of The Role Of The Vrk1 Protein Kinase In Mammary Epithelial Cells, Aye M. Mon

MUSC Theses and Dissertations

Vaccinia-related kinase 1 (VRK1) is a pro-proliferative nuclear serine/threonine kinase. Mice engrafted with VRK1-depleted MDA-MB-231 cells develop fewer distal metastases than mice engrafted with control cells, suggesting a potential role for VRK1 in cell migration, invasion, and/or colonization. In work described herein, we investigated the impact of VRK1 overexpression on human mammary epithelial cells. We demonstrated that VRK1 overexpression in MCF10A cells (normal mammary epithelial cells) diminishes cell invasion and impairs both single-cell and sheet migration, as well as the migration-associated processes of cell spreading and cytoskeletal rearrangement. Interestingly, VRK1-overexpressing cells show reduced accumulation of the mesenchymal marker vimentin and …

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The Role Of Soluble Guanylyl Cyclase Signaling In Mitochondrial Biogenesis And Renal Injury, Pallavi Bhargava Jan 2018

The Role Of Soluble Guanylyl Cyclase Signaling In Mitochondrial Biogenesis And Renal Injury, Pallavi Bhargava

MUSC Theses and Dissertations

Soluble Guanylyl Cyclase (sGC) is responsible for converting GTP to cyclic GMP (cGMP). sGC function and regulation is complex and cell-type dependent. An increase in cGMP production can target phosphodiesterases (PDEs), cGMP gated ion channels, and protein kinase G (PKG). Increasing sGC activity and inhibiting the degradation of cGMP by targeting PDEs are two approaches to maintaining cGMP levels in a given system. Interestingly, cGMP can also regulate mitochondrial biogenesis (MB), the generation of new and functional mitochondria. Previously in our laboratory, we have shown that MB is suppressed after ischemia and reperfusion (I/R) injury and certain mitochondrial biogenic compounds …

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Investigating The Pubertal Effects Of High Advanced Glycation End Product (Age) Consumption On Mammary Gland Development, Jamie F. Randise Jan 2018

Investigating The Pubertal Effects Of High Advanced Glycation End Product (Age) Consumption On Mammary Gland Development, Jamie F. Randise

MUSC Theses and Dissertations

The mammary gland continues to develop postnatally through puberty, pregnancy, lactation and involution. Evidence supports the notion that critical events in mammary development permanently alter developmentally regulated programs which influence the breast microenvironment to increase breast cancer risk. Advanced glycation end-products (AGEs) are highly reactive metabolites that irreversibly accumulate in tissues as we grow older. The pathogenic effects of AGEs include tissue degeneration, protein dysfunction, aberrant cell signaling and reduced genetic fidelity. AGE accumulation can contribute to pro-inflammatory and -oxidant phenotypes when signaling through the receptor for advanced glycation end-products. AGEs form during normal metabolism but critically, lifestyle factors such …

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Sleep And Thermoregulation: A Study Of The Effect Of Ambient Temperature Manipulation On Mouse Sleep Architecture, Asma'a A. Ajwad Jan 2018

Sleep And Thermoregulation: A Study Of The Effect Of Ambient Temperature Manipulation On Mouse Sleep Architecture, Asma'a A. Ajwad

Theses and Dissertations--Biomedical Engineering

Good quality sleep is essential for mental and physical health. Inadequate sleep impacts memory consolidation, learning and cognition, immune function, autonomic regulation, physical performance, and other vital functions. In many neurological disorders that are associated with sleep problems such as epilepsy and Alzheimer’s disease, changes in brain circuitry affect sleep-wake regulation mechanisms; this is reflected in anomalous sleep-wake architecture and usually accompanied by poor sleep depth. Thus, over many years, many approaches have been tried in humans and animal models with the goal of improving sleep quality. Unfortunately, each of those approaches comes with limitations or side effects. Thus, there …

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Metformin Suppresses Retinal Angiogenesis And Inflammation In Vitro And In Vivo, Jing Han, Yue Li, Xiuli Liu, Tongrong Zhou, Haijing Sun, Paul Edwards, Hua Gao, Fu-Shin Yu, Xiaoxi Qiao Jan 2018

Metformin Suppresses Retinal Angiogenesis And Inflammation In Vitro And In Vivo, Jing Han, Yue Li, Xiuli Liu, Tongrong Zhou, Haijing Sun, Paul Edwards, Hua Gao, Fu-Shin Yu, Xiaoxi Qiao

Ophthalmology Articles

The oral anti-diabetic drug metformin has been found to reduce cardiovascular complications independent of glycemic control in diabetic patients. However, its role in diabetic retinal microvascular complications is not clear. This study is to investigate the effects of metformin on retinal vascular endothelium and its possible mechanisms, regarding two major pathogenic features of diabetic retinopathy: angiogenesis and inflammation. In human retinal vascular endothelial cell culture, metformin inhibited various steps of angiogenesis including endothelial cell proliferation, migration, and tube formation in a dose-dependent manner. Its anti-angiogenic activity was confirmed in vivo that metformin significantly reduced spontaneous intraretinal neovascularization in a very-low-density …

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The Intersection Of Garp And B Cells For Maintaining Immunological Tolerance Via Surface Tgf-Β Modulation, Caroline Hathaway Wallace Jan 2018

The Intersection Of Garp And B Cells For Maintaining Immunological Tolerance Via Surface Tgf-Β Modulation, Caroline Hathaway Wallace

MUSC Theses and Dissertations

Glycoprotein-A repetitions predominant (GARP, encoded by Lrrc32) is a cell surface docking receptor for latent TGFβ, with no known direct signaling mechanism. GARP is highly expressed by megakaryocytes, platelets, and activated regulatory T cells and is implicated in immune evasion by cancer. While the pleotropic roles of active TGF-β on immune cell functions have been largely elucidated, the function of the membrane latent TGF-β – GARP axis has only been investigated in regulatory T cells and platelets. We discovered that GARP is expressed on the surface of highly activated human and mouse B cells by ligands for multiple Toll-like receptors. …

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Characterization Of Early Acute Inflammation In A Mouse Calvarial Critical-Sized Defect: Augmentation Via Rhbmp-2 And Pglcnac Administration, Zachary James Grey Jan 2018

Characterization Of Early Acute Inflammation In A Mouse Calvarial Critical-Sized Defect: Augmentation Via Rhbmp-2 And Pglcnac Administration, Zachary James Grey

MUSC Theses and Dissertations

Background: Currently, the gold standard intervention for substantially large bone wounds is autologous bone grafting. While effective, this therapy is complicated by creation of an invasive second surgical site and limited material available for harvest. INFUSE® Bone Graft (rhBMP-2 delivered via an absorbable collagen sponge or ACS) has been widely used as a graft substitute, resulting in robust bone formation, but at the cost of increased inflammation and often poor healing outcomes. A better understanding of the mechanisms by which rhBMP-2 influences inflammatory processes and how these processes can be modulated through other therapies will inform future novel pharmacological avenues …

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The Roles Of Macrophages And Alternative Complement Signaling In Auditory Nerve Development And Function, Lashardai Neniara Brown Jan 2018

The Roles Of Macrophages And Alternative Complement Signaling In Auditory Nerve Development And Function, Lashardai Neniara Brown

MUSC Theses and Dissertations

Hearing relies on the transmission of auditory information from sensory hair cells to the brain through the auditory nerve. This relay of information requires hair cells to be innervated by spiral ganglion neurons (SGNs) in an exclusive manner and for SGNs and their axons to be ensheathed by myelinating and non-myelinating glial cells. In the developing auditory nerve, mistargeted SGN axons undergo retraction or pruning, and excessive neural cells are eliminated to obtain the characteristic innervation pattern seen in the mature cochlea. The mechanisms governing auditory nerve maturation remain unclear. However, in peripheral nerves, key contributors to the establishment of …

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Nanoparticle Orientation To Control Rna Loading And Ligand Display On Extracellular Vesicles For Cancer Regression, Fengmei Pi, Daniel W. Binzel, Tae Jin Lee, Zhefeng Li, Meiyan Sun, Piotr G. Rychahou, Hui Li, Farzin Haque, Shaoying Wang, Carlo M. Croce, Bin Guo, B. Mark Evers, Peixuan Guo Jan 2018

Nanoparticle Orientation To Control Rna Loading And Ligand Display On Extracellular Vesicles For Cancer Regression, Fengmei Pi, Daniel W. Binzel, Tae Jin Lee, Zhefeng Li, Meiyan Sun, Piotr G. Rychahou, Hui Li, Farzin Haque, Shaoying Wang, Carlo M. Croce, Bin Guo, B. Mark Evers, Peixuan Guo

Markey Cancer Center Faculty Publications

Nanotechnology offers many benefits, and here we report an advantage of applying RNA nanotechnology for directional control. The orientation of arrow-shaped RNA was altered to control ligand display on extracellular vesicle membranes for specific cell targeting, or to regulate intracellular trafficking of small interfering RNA (siRNA) or microRNA (miRNA). Placing membrane-anchoring cholesterol at the tail of the arrow results in display of RNA aptamer or folate on the outer surface of the extracellular vesicle. In contrast, placing the cholesterol at the arrowhead results in partial loading of RNA nanoparticles into the extracellular vesicles. Taking advantage of the RNA ligand for …

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Mechanisms And Treatment Of Halogen Inhalation-Induced Pulmonary And Systemic Injuries In Pregnant Mice, James Lambert Jan 2018

Mechanisms And Treatment Of Halogen Inhalation-Induced Pulmonary And Systemic Injuries In Pregnant Mice, James Lambert

All ETDs from UAB

Toxic chemicals may pose an increased threat to vulnerable populations such as pregnant women and their unborn fetuses. The halogen bromine has numerous industrial utilities that include flame retardant, pharmaceutical, insecticide, and bleaching additive production. At room temperature, bromine is a volatile liquid. When the gas is inhaled, bromine causes exposure-dependent acute and chronic pulmonary and systemic injuries that range from mild eye and airway irritation to severe damage to the cardiopulmonary system and other organs, which can lead to death. If exposure is survived, patients still may develop reactive airway disease syndrome and pulmonary fibrosis as well as restrictive …

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Mechanotransduction Signaling In Podocytes From Fluid Flow Shear Stress., Tarak Srivastava, Hongying Dai, Daniel P. Heruth, Uri S. Alon, Robert E. Garola, Jianping Zhou, R Scott Duncan, Ashraf El-Meanawy, Ellen T. Mccarthy, Ram Sharma, Mark L. Johnson, Virginia J. Savin, Mukut Sharma Jan 2018

Mechanotransduction Signaling In Podocytes From Fluid Flow Shear Stress., Tarak Srivastava, Hongying Dai, Daniel P. Heruth, Uri S. Alon, Robert E. Garola, Jianping Zhou, R Scott Duncan, Ashraf El-Meanawy, Ellen T. Mccarthy, Ram Sharma, Mark L. Johnson, Virginia J. Savin, Mukut Sharma

Manuscripts, Articles, Book Chapters and Other Papers

Recently, we and others have found that hyperfiltration-associated increase in biomechanical forces, namely, tensile stress and fluid flow shear stress (FFSS), can directly and distinctly alter podocyte structure and function. The ultrafiltrate flow over the major processes and cell body generates FFSS to podocytes. Our previous work suggests that the cyclooxygenase-2 (COX-2)-PGE2-PGE2 receptor 2 (EP2) axis plays an important role in mechanoperception of FFSS in podocytes. To address mechanotransduction of the perceived stimulus through EP2, cultured podocytes were exposed to FFSS (2 dyn/cm2) for 2 h. Total RNA from cells at the end of FFSS treatment, 2-h post-FFSS, and 24-h …

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Selective Inhibition Of The P38Α Mapk-Mk2 Axis Inhibits Inflammatory Cues Including Inflammasome Priming Signals, Chun Wang, Yael Alippe, Yousef Abu-Amer, Gabriel Mbalaviele, Et Al Jan 2018

Selective Inhibition Of The P38Α Mapk-Mk2 Axis Inhibits Inflammatory Cues Including Inflammasome Priming Signals, Chun Wang, Yael Alippe, Yousef Abu-Amer, Gabriel Mbalaviele, Et Al

Open Access Publications

p38α activation of multiple effectors may underlie the failure of global p38α inhibitors in clinical trials. A unique inhibitor (CDD-450) was developed that selectively blocked p38α activation of the proinflammatory kinase MK2 while sparing p38α activation of PRAK and ATF2. Next, the hypothesis that the p38α-MK2 complex mediates inflammasome priming cues was tested. CDD-450 had no effect on NLRP3 expression, but it decreased IL-1β expression by promoting IL-1β mRNA degradation. Thus, IL-1β is regulated not only transcriptionally by NF-κB and posttranslationally by the inflammasomes but also posttranscriptionally by p38α-MK2. CDD-450 also accelerated TNF-α and IL-6 mRNA decay, inhibited inflammation in …

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Possible Effects Of Long-Term Weather Changes And Extreme Weather Events On Mice Population Abundances In Monteverde, Costa Rica, December 2017, Emily S. Parker Dec 2017

Possible Effects Of Long-Term Weather Changes And Extreme Weather Events On Mice Population Abundances In Monteverde, Costa Rica, December 2017, Emily S. Parker

Monteverde Institute: Tropical Ecology and Conservation

Mice and rat abundance is determined by a multitude of factors, including, but not limited to: climate change, predation, and food availability. In this study, I analyzed the effects of daily and long-term weather on rodent populations to understand a possible decrease in abundance from 2016 to 2017 in Monteverde, Puntarenas, Costa Rica. I took observations of individuals from four different sites: Santa Elena, Bajo del Tigre, Dwight and Rachel Crandell Memorial Reserve, and the Estación Biológica Monteverde. While a considerable number of specimens were captured in Bajo del Tigre, I observed the total abundance of rodents to be significantly …

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Fluorescence-Reported Allelic Exchange Mutagenesis Reveals A Role For Chlamydia Trachomatis Tmea In Invasion That Is Independent Of Host Ahnak, M. J. Mckuen, Konrad E. Mueller, Y. S. Bae, Kenneth A. Fields Dec 2017

Fluorescence-Reported Allelic Exchange Mutagenesis Reveals A Role For Chlamydia Trachomatis Tmea In Invasion That Is Independent Of Host Ahnak, M. J. Mckuen, Konrad E. Mueller, Y. S. Bae, Kenneth A. Fields

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Development of approaches to genetically manipulate Chlamydia is fostering important advances in understanding pathogenesis. Fluorescence-reported allelic exchange mutagenesis (FRAEM) now enables the complete deletion of specific genes in C. trachomatis L2. We have leveraged this technology to delete the coding sequences for a known type III effector. The evidence provided here indicates that CT694/CTL0063 is a virulence protein involved in chlamydial invasion. Based on our findings, we designate the gene product corresponding to ct694-ctl0063 translocated membrane-associated effector A (TmeA). Deletion of tmeA did not impact development of intracellular chlamydiae. However, the absence of TmeA manifested as a decrease in infectivity …

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