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Effects Of Eicosapentaenoic Acid (Epa) On Mouse Endothelial Cell Health, Spencer C. Pageau 2018 Grand Valley State University

Effects Of Eicosapentaenoic Acid (Epa) On Mouse Endothelial Cell Health, Spencer C. Pageau

Masters Theses

Cardiovascular disease is the number one killer of adults in the US (~800,000 lives every year:1 in 3 deaths). Evidence suggests omega-3 fatty acids like eicosapentaenoic acid (EPA), found in fish oils, reduce the risk of developing cardiovascular diseases. Many of these diseases are caused by atherosclerotic plaque development in vessels due to endothelial cell damage initiating inflammatory responses. Recent work argues omega-3 fatty acids stimulate anti-inflammatory responses by binding to Free Fatty Acid (FFA) receptors. Inflammatory responses in endothelial cells alter the expression of many proteins that affect the function of those cells. In particular, gap junction ...


An Interface Of The Taste And Reward Systems In The Brainstem And Its Role In Feeding, Louis Saites 2018 University of Tennessee Health Science Center

An Interface Of The Taste And Reward Systems In The Brainstem And Its Role In Feeding, Louis Saites

Theses and Dissertations (ETD)

We eat what tastes good. We also eat because it is necessary for our health. In fact, some of the most nutritious foods (e.g., vegetables) are often less appetizing, and the tastiest (e.g., fast food, ice cream) may be the least healthy. Despite the former, we may also have a lower limit of what we accept at which point nutrition becomes irrelevant (e.g., “spinach is just too yucky”). Further, we may eat unhealthily because of overwhelming urges. We investigated the complex interactions of taste and feeding at the neurobiological level using the experiments described.

In one sense ...


Coupling Of Smoothened To Inhibitory G Proteins Reduces Voltage-Gated K, Lan Cheng, Moza Al-Owais, Manuel Covarrubias, Walter J. Koch, David R. Manning, Chris Peers, Natalia A Riobo-Del Galdo 2018 Thomas Jefferson University

Coupling Of Smoothened To Inhibitory G Proteins Reduces Voltage-Gated K, Lan Cheng, Moza Al-Owais, Manuel Covarrubias, Walter J. Koch, David R. Manning, Chris Peers, Natalia A Riobo-Del Galdo

Department of Biochemistry and Molecular Biology Faculty Papers

SMO (Smoothened), the central transducer of Hedgehog signaling, is coupled to heterotrimeric Gi proteins in many cell types, including cardiomyocytes. In this study, we report that activation of SMO with SHH (Sonic Hedgehog) or a small agonist, purmorphamine, rapidly causes a prolongation of the action potential duration that is sensitive to a SMO inhibitor. In contrast, neither of the SMO agonists prolonged the action potential in cardiomyocytes from transgenic GiCT/TTA mice, in which Gi signaling is impaired, suggesting that the effect of SMO is mediated by Gi proteins. Investigation of the mechanism underlying the ...


Design, Synthesis, And Evaluation Of Homochiral Peptides Containing Arginine And Histidine As Molecular Transporters, Naglaa Salem El-Sayed, Taryn Miyake, Amir Nasrolahi Shirazi, Shang Eun Park, Jimmy Clark, Stephani Buchholz, Keykavous Parang, Rakesh Tiwari 2018 Chapman University

Design, Synthesis, And Evaluation Of Homochiral Peptides Containing Arginine And Histidine As Molecular Transporters, Naglaa Salem El-Sayed, Taryn Miyake, Amir Nasrolahi Shirazi, Shang Eun Park, Jimmy Clark, Stephani Buchholz, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Linear (HR)n and cyclic [HR]n peptides (n = 4,5) containing alternate arginine and histidine residues were synthesized. The peptides showed 0–15% cytotoxicity at 5–100 μM in human ovarian adenocarcinoma (SK-OV-3) cells while they exhibited 0–12% toxicity in human leukemia cancer cell line (CCRF-CEM). Among all peptides, cyclic [HR]4 peptide was able to improve the delivery of a cell impermeable fluorescence-labeled phosphopeptide by two-fold. Fatty acids of different alkyl chain length were attached at the N-terminal of the linear peptide (HR)4 to improve the molecular transporter property. Addition of fatty acyl chains was expected ...


Increased Heme-Oxygenase 1 Expression In Mesenchymal Stem Cell-Derived Adipocytes Decreases Differentiation And Lipid Accumulation Via Upregulation Of The Canonical Wnt Signaling Cascade, Luca Vanella, Komal Sodhi, Dong Hyun Kim, Nitin Puri, Mani Maheshwari, Terry D . Hinds, Lars Bellner, Dov Goldstein, Stephen J . Peterson, Joseph I. Shapiro M.D., Nader G. Abraham 2018 Marshall University

Increased Heme-Oxygenase 1 Expression In Mesenchymal Stem Cell-Derived Adipocytes Decreases Differentiation And Lipid Accumulation Via Upregulation Of The Canonical Wnt Signaling Cascade, Luca Vanella, Komal Sodhi, Dong Hyun Kim, Nitin Puri, Mani Maheshwari, Terry D . Hinds, Lars Bellner, Dov Goldstein, Stephen J . Peterson, Joseph I. Shapiro M.D., Nader G. Abraham

Mani Maheshwari

Introduction:

Heme oxygenase (HO), a major cytoprotective enzyme, attenuates oxidative stress and obesity. The canonical Wnt signaling cascade plays a pivotal role in the regulation of adipogenesis. The present study examined the interplay between HO-1and the Wnt canonical pathway in the modulation of adipogenesis in mesenchymal stem cell (MSC)-derived adipocytes.

Methods:

To verify the role of HO-1 in generating small healthy adipocytes, cobalt protoporphyrin (CoPP), inducer of HO-1, was used during adipocyte differentiation. Lipid accumulation was measured by Oil red O staining and lipid droplet size was measured by BODIPY staining.

Results:

During adipogenesis in vitro, differentiating pre-adipocytes display ...


Cerium Oxide Nanoparticles Inhibit Lipopolysaccharide Inducedmap Kinase/Nf-Kb Mediated Severe Sepsis, Mani Maheshwari, Nandini Manne PhD, Shinichi Asano, Eric Blough, Kevin M. Rice, Niraj Nepa,, Erin Fankhanel 2018 Marshall University

Cerium Oxide Nanoparticles Inhibit Lipopolysaccharide Inducedmap Kinase/Nf-Kb Mediated Severe Sepsis, Mani Maheshwari, Nandini Manne Phd, Shinichi Asano, Eric Blough, Kevin M. Rice, Niraj Nepa,, Erin Fankhanel

Mani Maheshwari

The life threatening disease of sepsis is associated with high mortality. Septic patient survivability with currently available treatments has failed to improve. The purpose of this study was to evaluate whether lipopolysaccharide (LPS) induced sepsis mortality and associated hepatic dysfunction can be prevented by cerium oxide nanoparticles (CeO2NPs) treatment in male Sprague Dawley rats. Here we provide the information about the methods processing of raw data related to our study published in Biomaterials (Selvaraj et al., Biomaterials, 2015, In press) and Data in Brief (Selvaraj et al., Data in Brief, 2015, In Press). The data present here provides confirmation of ...


Extracellular Release Of Virulence Factor Major Surface Protease Via Exosomes In Leishmania Infantum Promastigotes, Skye Marshall, Patrick H Kelly, Brajesh K Singh, R Marshall Pope, Peter Kim, Bayan Zhanbolat, Mary E Wilson, Chaoqun Yao 2018 University of Iowa

Extracellular Release Of Virulence Factor Major Surface Protease Via Exosomes In Leishmania Infantum Promastigotes, Skye Marshall, Patrick H Kelly, Brajesh K Singh, R Marshall Pope, Peter Kim, Bayan Zhanbolat, Mary E Wilson, Chaoqun Yao

Stead Family Department of Pediatrics Publications

BACKGROUND: The Leishmania spp. protozoa are introduced into humans through a sand fly blood meal, depositing the infectious metacyclic promastigote form of the parasite into human skin. Parasites enter a variety of host cells, although a majority are found in macrophages where they replicate intracellularly during chronic leishmaniasis. Symptomatic leishmaniasis causes considerable human morbidity in endemic regions. The Leishmania spp. evade host microbicidal mechanisms partially through virulence-associated proteins such as the major surface protease (MSP or GP63), to inactivate immune factors in the host environment. MSP is a metalloprotease encoded by a tandem array of genes belonging to three msp ...


Triad3a Induces The Degradation Of Early Necrosome To Limit Ripk1-Dependent Cytokine Production And Necroptosis., Norah A. Alturki, Scott McComb, Ardeshir Ariana, Dikchha Rijal, Robert G. Korneluk, Shao-Cong Sun, Emad S Alnemri, Subash Sad 2018 University of Ottawa; King Saud University

Triad3a Induces The Degradation Of Early Necrosome To Limit Ripk1-Dependent Cytokine Production And Necroptosis., Norah A. Alturki, Scott Mccomb, Ardeshir Ariana, Dikchha Rijal, Robert G. Korneluk, Shao-Cong Sun, Emad S Alnemri, Subash Sad

Department of Biochemistry and Molecular Biology Faculty Papers

Understanding the molecular signaling in programmed cell death is vital to a practical understanding of inflammation and immune cell function. Here we identify a previously unrecognized mechanism that functions to downregulate the necrosome, a central signaling complex involved in inflammation and necroptosis. We show that RipK1 associates with RipK3 in an early necrosome, independent of RipK3 phosphorylation and MLKL-induced necroptotic death. We find that formation of the early necrosome activates K48-ubiquitin-dependent proteasomal degradation of RipK1, Caspase-8, and other necrosomal proteins. Our results reveal that the E3-ubiquitin ligase Triad3a promotes this negative feedback loop independently of typical RipK1 ubiquitin editing enzymes ...


The Role Of Wnt3a In Ischemic Stroke, Nathanael Matei 2018 Loma Linda University

The Role Of Wnt3a In Ischemic Stroke, Nathanael Matei

Loma Linda University Electronic Theses, Dissertations & Projects

After ischemic stroke, apoptosis of neurons is a primary factor in determining outcome. Wnt3a is a naturally occurring protein that has been shown to have protective effects in the brain for traumatic brain injury. Although wnt3a has been investigated in the phenomena of neurogenesis, anti-apoptosis, and anti-inflammation, it has never been investigated as a therapy for stroke. We hypothesized that the potential neuroprotective agent wnt3a would reduce infarction and improve behavior following ischemic stroke by attenuating neuronal apoptosis and promoting cell survival through the Frizzled-1/PIWI1a/FOXM1 pathway in MCAO rats. 229 Sprague-Dawley rats were assigned to male, female, and ...


The Mitochondrial Protease Htra2 Restricts The Nlrp3 And Aim2 Inflammasomes., Ian Gaël Rodrigue-Gervais, Karine Doiron, Claudia Champagne, Lindsey Mayes, Gabriel André Leiva-Torres, Paulin Vanié, Todd Douglas, Silvia M. Vidal, Emad S. Alnemri, Maya Saleh 2018 McGill University; INRS-Institut Armand Frappier

The Mitochondrial Protease Htra2 Restricts The Nlrp3 And Aim2 Inflammasomes., Ian Gaël Rodrigue-Gervais, Karine Doiron, Claudia Champagne, Lindsey Mayes, Gabriel André Leiva-Torres, Paulin Vanié, Todd Douglas, Silvia M. Vidal, Emad S. Alnemri, Maya Saleh

Department of Biochemistry and Molecular Biology Faculty Papers

Activation of the inflammasome pathway is crucial for effective intracellular host defense. The mitochondrial network plays an important role in inflammasome regulation but the mechanisms linking mitochondrial homeostasis to attenuation of inflammasome activation are not fully understood. Here, we report that the Parkinson's disease-associated mitochondrial serine protease HtrA2 restricts the activation of ASC-dependent NLRP3 and AIM2 inflammasomes, in a protease activity-dependent manner. Consistently, disruption of the protease activity of HtrA2 results in exacerbated NLRP3 and AIM2 inflammasome responses in macrophages ex vivo and systemically in vivo. Mechanistically, we show that the HtrA2 protease activity regulates autophagy and controls the ...


The Association Of Kangaroo Mother Care, Energy Conservation, And Bonding In Preterm Neonates, Dorothy Forde 2018 University of San Diego

The Association Of Kangaroo Mother Care, Energy Conservation, And Bonding In Preterm Neonates, Dorothy Forde

Dissertations

Purpose:To examine the association of kangaroo mother care (KMC) on energy utilization and bonding as evidenced by reduced biochemical markers of adenosine triphosphate (ATP) degradation, hypoxanthine (Hx), xanthine (Xa), and uric acid (UA), and (allantoin), a measure of oxidative stress in preterm infants 24-36 weeks gestation. A secondary objective was to compare specific physiological parameters using bedside monitoring and perfusion and oxygenation of the gut using near-infrared spectroscopy (NIRS) during 1 hour of KMC compared to incubator care.

Study design: A randomized controlled trial (RCT) examining the effects of 1-hour of KMC or 1-hour incubator care on urinary markers ...


30-Day Oral Acetaminophen Tolerance In Adult Horses, Sarah E. Foreman 2018 Augustana College, Rock Island Illinois

30-Day Oral Acetaminophen Tolerance In Adult Horses, Sarah E. Foreman

Celebration of Learning

There are no controlled studies of acetaminophen toxicity in horses. The objective was to test the hypotheses that oral acetaminophen administered at a dosage 25% higher than that sometimes used in horses would result in measurable hepatic toxicity as seen in humans and other species. Six healthy adult horses were administered 25 mg/kg acetaminophen powder in corn syrup twice daily for 30 days. Three other horses served as negative controls receiving only corn syrup. Jugular venous blood samples were obtained on days 7 and 1 before treatment; on treatment days 1, 2, 5, 8, 12, 15, 19, 22, 26 ...


Engineered Exosomes For Delivery Of Therapeutic Sirnas To Neurons, Reka A. Haraszti 2018 University of Massachusetts Medical School

Engineered Exosomes For Delivery Of Therapeutic Sirnas To Neurons, Reka A. Haraszti

GSBS Dissertations and Theses

Extracellular vesicles (EVs), exosomes and microvesicles, transfer endogenous RNAs between neurons over short and long distances. We have explored EVs for siRNA delivery to brain. (1) We optimized siRNA chemical modifications and siRNA conjugation to lipids for EV-mediated delivery. (2) We developed a GMP-compatible, scalable method to manufacture active EVs in bulk. (3) We characterized lipid and protein content of EVs in detail. (4) We established how protein and lipid composition relates to siRNA delivering activity of EVs, and we reverse engineered natural exosomes (small EVs) into artificial exosomes based on these data.

We established that cholesterol-conjugated siRNAs passively associate ...


The State Of The Translational Chaperone Icd-1 During Apoptosis In Caenorhabditis Elegans, Kyle Cicalese 2018 James Madison University

The State Of The Translational Chaperone Icd-1 During Apoptosis In Caenorhabditis Elegans, Kyle Cicalese

Senior Honors Projects, 2010-2019

The unfolded protein response (UPR) is a signal transduction cascade that mitigates low levels of misfolded protein stress in the endoplasmic reticulum (ER) in an effort to save the affected cell, while prolonged and/or acute ER stress leads to UPR-initiated apoptosis (programmed cell death). One putative step driving apoptosis is the cleavage of chaperones, proteins tasked to help misfolded proteins refold, by caspases, proteases essential to the execution of apoptosis. We are studying the nascent polypeptide-associated complex (NAC), a heterodimeric chaperone complex essential for viability, to determine if its beta subunit is cleaved by caspases during apoptosis to prevent ...


Tumor Immunotherapy: Mechanisms Of Acquired Resistance And Characterization Of Immune Related Toxicities, Ashvin Jaiswal 2018 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Tumor Immunotherapy: Mechanisms Of Acquired Resistance And Characterization Of Immune Related Toxicities, Ashvin Jaiswal

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Tumor immunotherapy has shown very promising clinical benefit across an array of cancers; however, two major challenges remain unresolved in the field. First, many patients do not respond to therapy at all or relapse after a period of remission. Second, there are often dose-limiting immune related adverse effects associated with immunomodulation.

In order to understand the mechanisms employed by tumors to evade immunotherapeutic responses, we established a murine model of melanoma designed to elucidate the molecular mechanisms underlying immunotherapy resistance. Through multiple in vivo passages, we selected a B16 melanoma tumor line that evolved complete resistance to combination blockade of ...


Novel Determinants That Influence Azole Susceptibility In Candida Glabrata And Candida Albicans, Sarah Garland Whaley 2018 University of Tennessee Health Science Center

Novel Determinants That Influence Azole Susceptibility In Candida Glabrata And Candida Albicans, Sarah Garland Whaley

Theses and Dissertations (ETD)

Despite the scientific and medical communities’ best efforts, the incidence of fungal infections in susceptible populations continues to rise. The most common cause of these opportunistic fungal infections is Candida. In fact, Candida is the fourth most common pathogen associated with nosocomial blood stream infections. Reported mortality rates for patients with candidemia vary, but have not decreased in the past fifteen years and are reported to be as high as 50%. Candida glabrata, second only to Candida albicans among Candida infections, expresses high rates of resistance to treatment with arguably the best class of currently available antifungals - the azoles.

Other ...


Linear Ubiquitin Chain-Binding Domains, Lilian Fennell, Simin Rahighi, Fumiyo Ikeda 2018 Vienna BioCenter

Linear Ubiquitin Chain-Binding Domains, Lilian Fennell, Simin Rahighi, Fumiyo Ikeda

Pharmacy Faculty Articles and Research

Ubiquitin modification (ubiquitination) of target proteins can vary with respect to chain lengths, linkage type, and chain forms, such as homologous, mixed, and branched ubiquitin chains. Thus, ubiquitination can generate multiple unique surfaces on a target protein substrate. Ubiquitin‐binding domains (UBDs) recognize ubiquitinated substrates, by specifically binding to these unique surfaces, modulate the formation of cellular signaling complexes and regulate downstream signaling cascades. Among the eight different homotypic chain types, Met1‐linked (also termed linear) chains are the only chains in which linkage occurs on a non‐Lys residue of ubiquitin. Linear ubiquitin chains have been implicated in immune ...


Effects Of Aging & Exercise On Production Of Glial Cell Line-Derived Neurotrophic Factor Protein By Fast & Slow Skeletal Muscle, Maria Jaramillo 2018 Western Michigan University

Effects Of Aging & Exercise On Production Of Glial Cell Line-Derived Neurotrophic Factor Protein By Fast & Slow Skeletal Muscle, Maria Jaramillo

Honors Theses

Exercise is a positive form of reinforcing positive lifestyle choices. There are many benefits to exercising such as decreased risk of cardiovascular disease and improved mental condition (Centers for Disease Control and Prevention). In addition, exercise can serve a protecting role for the nervous system. One form in which exercise can protect the nervous system is by increasing the production of neurotrophic factors, specifically glial cell line-derived neurotrophic factor. Another way by which exercise can protect the nervous system is by preserving muscle tissue due to actively recruiting it. The goal of this study was to explore the effects of ...


Increasing Autophagy And Blocking Nrf2 Suppress Laminopathy-Induced Age-Dependent Cardiac Dysfunction And Shortened Lifespan, Shruti Bhide, Adriana S Trujillo, Maureen T O'Connor, Grant H Young, Diane E Cryderman, Sahaana Chandran, Mastaneh Nikravesh, Lori L Wallrath, Girish C Melkani 2018 San Diego State University

Increasing Autophagy And Blocking Nrf2 Suppress Laminopathy-Induced Age-Dependent Cardiac Dysfunction And Shortened Lifespan, Shruti Bhide, Adriana S Trujillo, Maureen T O'Connor, Grant H Young, Diane E Cryderman, Sahaana Chandran, Mastaneh Nikravesh, Lori L Wallrath, Girish C Melkani

Department of Biochemistry Publications

Mutations in the human LMNA gene cause a collection of diseases known as laminopathies. These include myocardial diseases that exhibit age-dependent penetrance of dysrhythmias and heart failure. The LMNA gene encodes A-type lamins, intermediate filaments that support nuclear structure and organize the genome. Mechanisms by which mutant lamins cause age-dependent heart defects are not well understood. To address this issue, we modeled human disease-causing mutations in the Drosophila melanogaster Lamin C gene and expressed mutant Lamin C exclusively in the heart. This resulted in progressive cardiac dysfunction, loss of adipose tissue homeostasis, and a shortened adult lifespan. Within cardiac cells ...


Ferrocenylchalcone-Uracil Conjugates: Synthesis And Cytotoxic Evaluation, Amandeep Singh, Vishu Mehra, Neda Sadeghiani, Saghar Mozaffari, Keykavous Parang, Vipan Kumar 2018 Guru Nanak Dev University

Ferrocenylchalcone-Uracil Conjugates: Synthesis And Cytotoxic Evaluation, Amandeep Singh, Vishu Mehra, Neda Sadeghiani, Saghar Mozaffari, Keykavous Parang, Vipan Kumar

Pharmacy Faculty Articles and Research

Huisgen’s azide-alkyne cycloaddition reaction was employed to synthesize a series of 1H-1,2,3-triazole-tethered uracil-ferrocenyl chalcone conjugates with the aim of evaluating their in vitro anti-proliferative efficacy on human leukemia (CCRF-CEM) and human breast adenocarcinoma (MDA-MB-468) cell lines. Cytotoxic evaluation studies identified a number of synthesized conjugates that inhibited the proliferation of leukemia cancer cells by ~70% after 72 h. The selected synthesized conjugates were found to be significantly less cytotoxic against normal kidney cell line (LLC-PK1) when compared with CCRF-CEM cancer cells.


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