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The Combined Effects Of Proteasome Inhibitor Bortezomib With Topoisomerase I And Ii Inhibitors On Topoisomerase Enzymes, Emi̇ne Öksüzoğlu, Çi̇ydem Tirinoğlu, Bariş Keri̇moğlu

Turkish Journal of Medical Sciences

Background/aim: DNA topoisomerases are ubiquitous enzymes that regulate conformational changes in DNA topology during essential cellular processes, and, for this reason, have been characterized as the cellular targets of a number of anticancer drugs. Bortezomib is a powerful proteasome inhibitor used in the treatment of hematological malignancies. In this study, we investigated the inhibitory effects of bortezomib on human topoisomerase I and II enzymes both alone and in combination modes with camptothecin and etoposide. Materials and methods: The interactions of these drugs with topoisomerase enzymes were evaluated by relaxation assay in cell-free systems. IC50 values of the drugs on topoisomerase …

Virulence Factors, Biofilm-Forming Ability, And Antimicrobial Resistance Of Urinary Escherichia Coli Strains Isolated From Hospitalized Patients, Barbara Kot, Jolanta Wicha, Agata Gruzewska, Malgorzata Piechota, Katarzyna Wolska, Maria Obrebska

Turkish Journal of Medical Sciences

Background/aim: Escherichia coli is the most frequent cause of urinary tract infections. We investigated the possible associations between the origin of strains, antimicrobial resistance, the presence of urovirulence factors, and biofilm-forming ability. Materials and methods: Antibiotic susceptibility of E. coli strains was tested by disk diffusion method. Hemagglutination assays were performed for phenotypic characterization of the cell surface. Multiplex PCR was used for detection of virulence genes and for determination of phylogenetic relationships. Results: The resistance to ampicillin (55.5%) and tetracycline (39.3%) was significantly more frequent than to other antimicrobial agents. The fim gene was present in 92.5% of strains. …

Presence Of Pathogenic Escherichia Coli Is Correlated With Bacterial Community Diversity And Composition On Pre-Harvest Cattle Hides, Jessica Chopyk, Ryan M. Moore, Zachary Dispirito, Zachary R. Stromberg, Gentry L. Lewis, David G. Renter, Natalia Cernicchiaro, Rodney A. Moxley, K. Eric Wommack

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Since 1982, specific serotypes of Shiga toxin-producing Escherichia coli (STEC) have been recognized as significant foodborne pathogens acquired from contaminated beef and, more recently, other food products. Cattle are the major reservoir hosts of these organisms, and while there have been advancements in food safety practices and industry standards, STEC still remains prevalent within beef cattle operations with cattle hides implicated as major sources of carcass contamination. To investigate whether the composition of hide-specific microbial communities are associated with STEC prevalence, 16S ribosomal RNA (rRNA) bacterial community profiles were obtained from hide and fecal samples collected from a large …

Prevalence And Level Of Enterohemorrhagic Escherichia Coli In Culled Dairy Cows At Harvest, Zachary R. Stromberg, Gentry L. Lewis, Sharif S. Aly, Terry W. Lehenbauer, Joseph M. Bosilevac, Natalia Cernicchiaro, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

The primary objective of this study was to determine the prevalence and level of enterohemorrhagic Escherichia coli (EHEC) O26, O45, O103, O111, O121, and O145 (collectively EHEC-6) plus EHEC O157 in fecal, hide, and preintervention carcass surface samples from culled dairy cows. Matched samples (n=300) were collected from 100 cows at harvest and tested by a culture-based method and two molecular methods: NeoSEEK STEC (NS) and Atlas STEC EG2 Combo. Both the culture and NS methods can be used to discriminate among the seven EHEC types (EHEC-7), from which the cumulative prevalence was inferred, whereas the Atlas method can discriminate …

Recapitulating Cross-Species Transmission Of Sivcpz To Humans Using Humanized-Blt Mice, Zhe Yuan, Guobin Kang, Fangrui Ma, Wuxun Lu, Wenjin Fan, Christine M. Fennessey, Brandon F. Keele, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

The origins of HIV-1 have been widely accepted to be the consequence of simian immunodeficiency viruses from wild chimpanzees (SIVcpz) crossing over to humans. However, there has not been any in vivo study of SIVcpz infection of humans. Also, it remains largely unknown why only specific SIVcpz strains have achieved cross-species transmission and what transmission risk might exist for those SIVcpz strains that have not been found to infect humans. Closing this knowledge gap is essential for better understanding cross-species transmission and predicting the likelihood of additional cross-species transmissions of SIV into humans. Here we show hu-BLT mice are susceptible …

High Glucose Induces Reactivation Of Latent Kaposi’S Sarcoma-Associated Herpesvirus, Fengchun Ye, Yan Zeng, Jingfeng Sha, Tiffany Jones, Kurt Kuhne, Charles Wood, Shou-Jiang Gao

Nebraska Center for Virology: Faculty Publications

High prevalence of Kaposi’s sarcoma (KS) is seen in diabetic patients. It is unknown if the physiological condition of diabetes contributes to KS development. We found elevated levels of viral lytic gene expression when Kaposi’s sarcoma-associated herpesvirus (KSHV) infected cells were cultured in high glucose medium. To demonstrate the association between high glucose and KSHV replication, we xeno29

grafted telomerase-immortalized human umbilical vein endothelial cells that are infected with KSHV (TIVE-KSHV) into hyperglycemic and normal nude mice. The injected cells expressed significantly higher levels of KSHV lytic genes in hyperglycemic mice than in normal mice. We further demonstrated that high …

Persistent Low-Level Replication Of Sivδnef Drives Maturation Of Antibody And Cd8 T Cell Responses To Induce Protective Immunity Against Vaginal Siv Infection, Sama Adnan, R. Keith Reeves, Jacqueline Gillis, Fay E. Wong, Yi Yu, Jeremy V. Camp, Qingsheng Li, Michelle Connole, Yuan Li, Michael Piatak Jr., Jeffrey D. Lifson, Wenjun Li, Brandon F. Keele, Pamela A. Kozlowski, Ronald C. Desrosiers, Ashley T. Haase, R. Paul Johnson

Nebraska Center for Virology: Faculty Publications

Defining the correlates of immune protection conferred by SIVΔnef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that protect against SIV infection through detailed analyses of cellular and humoral immune responses in the blood and tissues of rhesus macaques vaccinated with SIVΔnef and then vaginally challenged with wild-type SIV. Despite the presence of robust cellular immune responses, animals at 5 weeks after vaccination displayed only transient viral suppression of challenge virus, whereas all macaques challenged at weeks 20 and 40 post-SIVΔnef …

Regulation Of Chronic And Acute Inflammatory Disease By Microrna And Microbiota, Pegah Mehrpouya-Bahrami

Theses and Dissertations

Inflammation is implicated in cancer development, degenerative diseases, allergies as well as artherosecelorsis. Dysregulated immune responses lead to chronic inflammation and tissue damage. Finding the ways to terminate inflammatory responses when no longer needed, demands further investigation. Herein, we investigated the modulation of acute and chronic inflammatory disease models by inducing antiinflammatory state. Acute inflammatory model was induced with SEB, an enterotoxin produced by a ubiquitous Gram-positive coccus, Staphylococcus aureus (S. aureus), which exerts profound toxic effects on the immune system, which leads to the cytokine storm and adverse immune response. SEB is the main cause of nosocomial infections, acute …

Distribution Of Hepatitis C Virus Genotypes Among Intravenous Drug Users In The Çukurova Region Of Turkey, Enver Üçbi̇lek, Bahri̇ Abayli, Mahmut Bakir Koyuncu, Durdane Midikli, Süveyda Gözüküçük, Alper Akdağ, Osman Özdoğan, Engi̇n Altintaş, Orhan Sezgi̇n

Turkish Journal of Medical Sciences

Background/aim: The most common hepatitis C virus (HCV) genotype in Turkey is genotype 1. However, there has not been a study about the distribution of HCV genotypes among intravenous drug users (IVDUs) in the Çukurova region of Turkey. This study was planned to understand if there is a difference between IVDUs and the normal population. Materials and methods: Between May 2010 and May 2014, anti-HCV positive IVDUs who applied to the 6 hospitals in the Çukurova region of Turkey were included in this study. Their HCV genotypes were studied. Results: Ninety-seven anti-HCV positive IVDUs were screened in terms of HCV …

Analgesia Followed By Long-Term Hyperalgesia Generated By Disinhibition Of The Basolateral Amygdala, Derek Atchley

Wayne State University Theses

Stress produces bimodal effects on pain peception. During exposure to a stressor pain responses are inibited (i.e. stress-induced analgesia). However, following long-term exposure to a stressor increases in responsiveness to painful stimuli may develop (i.e. stress-induced hyperalgesia). Here I evaluated how a key component of the subcortical defense circuit and target of stress hormones contributes to the development of both stress-induced analgesia and hyperalgesia. Bicuculline methiodide, a GABAA antagonist, injected into the basolateral amygdala was used to mimic the neural effects of a stressor or threat exposure. Immediately following injection pain responsiveness was decreased as measured by vocalizations after discharge …

Non-Nad-Like Poly(Adp-Ribose) Polymerase-1 Inhibitors Effectively Eliminate Cancer In Vivo, Colin Thomas, Yingbiao Ji, Niraj Lodhi, Elena Kotova, Aaron Dan Pinnola, Konstantin Golovine, Peter Makhov, Kate Pechenkina, Vladimir Kolenko, Alexei V. Tulin

Publications and Research

The clinical potential of PARP-1 inhibitors has been recognized N10 years ago, prompting intensive research on their pharmacological application in several branches of medicine, particularly in oncology. However, natural or acquired resistance of tumors to known PARP-1 inhibitors poses a serious problemfor their clinical implementation. Present study aims to reignite clinical interest to PARP-1 inhibitors by introducing a new method of identifying highly potent inhibitors and presenting the largest known collection of structurally diverse inhibitors. The majority of PARP-1 inhibitors known to date have been developed as NAD competitors. NAD is utilized by many enzymes other than PARP-1, resulting in …

Epigenetics And Shared Molecular Processes In The Regeneration Of Complex Structures, Labib Rouhana, Junichi Tasaki

Biological Sciences Faculty Publications

The ability to regenerate complex structures is broadly represented in both plant and animal kingdoms. Although regenerative abilities vary significantly amongst metazoans, cumulative studies have identified cellular events that are broadly observed during regenerative events. For example, structural damage is recognized and wound healing initiated upon injury, which is followed by programmed cell death in the vicinity of damaged tissue and a burst in proliferation of progenitor cells. Sustained proliferation and localization of progenitor cells to site of injury give rise to an assembly of differentiating cells known as the regeneration blastema, which fosters the development of new tissue. Finally, …

The Nobel Prize In Chemistry 2015: Exciting Discoveries In Dna Repair By Aziz Sancar, David K. Orren

Toxicology and Cancer Biology Faculty Publications

On October 7, 2015, the Nobel Prize in Chemistry for 2015 was awarded to three deserving scientists for their pioneering research on DNA repair. Tomas Lindahl was recognized for studies that uncovered the inherent instability of DNA as well as the mechanism of the base excision repair pathway, Paul Modrich for characterization of the mismatch repair pathway, and Aziz Sancar for mechanistic elucidation of the nucleotide excision repair (NER) pathway. For me, the announcement of these awards in my area of research was extremely gratifying, particularly so because Aziz was my mentor during my Ph.D. studies that examined the steps …

Characterization Of Inhibitor Of Differentiation (Id) Proteins In Human Cornea, Rajiv R. Mohan, Brandie R. Morgan, Govinduraj Anumanthan, Ajay Sharma, Shyam S. Chaurasia, Frank G. Rieger

Pharmacy Faculty Articles and Research

Inhibitor of differentiation (Id) proteins are DNA-binding transcription factors involved in cellular proliferation, migration, inflammation, angiogenesis and fibrosis. However, their expression and role in the cornea is unknown. The present study was undertaken to characterize the expression of Id proteins and their interactions with the pro-fibrotic cytokine Transforming Growth Factor β1 (TGFβ1) and anti-fibrotic cytokine, bone morphogenic protein 7 (BMP7) in human cornea. Human donor corneas procured from Eye Bank were used. Id proteins were localized in human corneal sections using immunofluorescence. Primary cultures of human corneal fibroblasts (HCF) were established and treated with either TGFβ1 (5 ng/ml) or BMP7 …

The Role Of Sod1 Acetylation In Neurodegeneration, Michael Kaliszewski

Electronic Theses and Dissertations

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting motor neurons. Cu, Zn superoxide dismutase (SOD1), a cytoplasmic free radical scavenging enzyme, is mutated in familial ALS (fALS) and post-translational modification of the wild-type protein has been associated with sporadic ALS (sALS). Proteomic studies indicate that SOD1 is acetylated at Lys123; however, the role of this modification remains unknown. To investigate its function, we generated antibodies for Lys123-acetylated SOD1 (Ac-K123 SOD1). Sod1 deletion in Sod1-/- mice, K123 mutation, or preabsorption with Ac-K123 peptide suppressed immunoreactivity, confirming antibody specificity. In the normal central nervous system, Ac-K123 SOD1 maps to glutamatergic …

Management Of Acute Postoperative Hypertension For Reducing Cardiovascular Complications In Cancer Patients: When And How Aggressively?, Ning Lou, Daofeng Wang, Zhi Wang, Wenfeng Ye, Xiao Liu

Turkish Journal of Medical Sciences

Background/aim: We sought to determine what factors cardiovascular complications (CVCs) correlate with in cancer patients with acute postoperative hypertension (APH) and to define when and how aggressively to treat this disorder in the present study. Materials and methods: A retrospective observational study of cancer patients with postoperative hypertension at a single intensive care unit between July 2007 and June 2013 was conducted. The outcome of interest was the incidence of a CVC. Results: There were 1162 patients enrolled, of which 92 (7.9%) experienced one or more CVCs. Preexisting hypertension (OR 38.3, 95% CI 3.2-457.4, P = 0.004) and choice of …

Exhaled Carbon Monoxide Is A Marker Of Heavy Nicotine Dependence, Eli̇f Babaoğlu, Ayşegül Karalezli̇, Mükremi̇n Er, Hati̇ce Canan Hasanoğlu, Derya Öztuna

Turkish Journal of Medical Sciences

Background/aim: Exhaled CO level provides an objective measure of a patient's smoking status. The relationship between CO levels and nicotine dependence is controversial. The aim of this study is to evaluate the relationship between exhaled CO levels and nicotine dependence as well as to demonstrate that exhaled CO levels may be used as a marker of nicotine dependence. Materials and methods: Two hundred eighty-nine patients (132 females, 157 males) were included in the study. Smoking duration, the age of smoking initiation, exhaled CO levels, and Fagerström Test for Nicotine Dependence (FTND) scores were recorded. The relationship between FTND scores and …

Simulation Of Cryolipolysis As A Novel Method For Noninvasive Fat Layer Reduction, Abbas Majdabadi, Mohammad Abazari

Turkish Journal of Medical Sciences

Background/aim: Regarding previous problems in conventional liposuction methods, the need for development of new fat removal operations was appreciated. In this study we are going to simulate one of the novel methods, cryolipolysis, aimed to tackle those drawbacks. Materials and methods: We think that simulation of clinical procedures contributes considerably in efficacious performance of the operations. To do this we have attempted to simulate temperature distribution in a sample fat of the human body. Using Abaqus software we have presented the graphical display of temperature-time variations within the medium. Results: Findings of our simulation indicate that tissue temperature decreases after …

Surgical Management Of Large-Cell Neuroendocrinelung Carcinoma: An Analysis Of 25 Cases, Funda İncekara, Koray Aydoğdu, Ebru Sayilir, Seli̇m Şaki̇r Erkmen Gülhan, Funda Demi̇rağ, Sadi̇ Kaya, Göktürk Findik

Turkish Journal of Medical Sciences

Background/aim: Large-cell neuroendocrine carcinoma (LCNEC) of the lung is a relatively uncommon and aggressive subset of pulmonary neuroendocrine tumors, which include typical and atypical carcinoid, and small-cell lung cancer. LCNEC of the lung accounts for no more than 1% of all lung cancers. LCNECs show features of high-grade neuroendocrine tumors and patients with LCNEC have a very poor prognosis. Materials and methods: Twenty-five patients (22 males and 3 females; mean years 60.7; range 48 to 77 years) who underwent pulmonary resection for large-cell neuroendocrine carcinoma between January 2004 and December 2014 were investigated retrospectively. Results: Type of surgery, pathologic TNM …

New Immunohistochemical Markers In The Differential Diagnosisof Nonsmall Cell Lung Carcinoma, Ferda Bi̇r, Duygu Çeli̇ker, Bi̇nnaz Fatma Evyapan, Arzu Yaren, Tamer Edi̇rne

Turkish Journal of Medical Sciences

Background/aim: The aim of this study was to investigate Napsin-A, NTRK-1, NTRK-2, Desmoglein-3, and Desmocollin-3 in the differential diagnosis and prognosis of nonsmall cell lung cancer. Materials and methods: The expression of Napsin-A, NTRK-1, NTRK-2, and Desmoglein-3 was examined by immunohistochemistry in 50 squamous cell carcinomas and 50 adenocarcinomas. Desmocollin-3 was investigated in 29 squamous cell carcinoma and 29 adenocarcinoma cases. Associations between expression profiles of Napsin-A, NTRK-1, NTRK-2, Desmoglein-3, and Desmocollin-3 in lung cancers and clinicopathological variables were analyzed. Results: Napsin-A staining was statistically significant in detecting adenocarcinomas versus squamous cell carcinomas. The sensitivity of Napsin-A for adenocarcinomas was …

Peripheral Flt-3 Ligand Levels As A Pathobiological Parameter Duringthe Clinical Course Of Acute Myeloid Leukemia, Memduh Şahi̇n, İbrahi̇m Celaletti̇n Haznedaroğlu, Demi̇rcan Özbalci

Turkish Journal of Medical Sciences

Background/aim: FLT-3 ligand is a growth factor affecting the hematopoietic lineage. The aim of this study was to evaluate the variability of peripheral FLT-3 ligand during the clinical course of acute myeloid leukemia (AML) patients. Materials and methods: Twenty-four patients were enrolled in this study in order to assess alterations in the circulating levels of FLT-3 ligand during the clinical course of AML. Results: We studied the association in the diagnostic period between the FLT-3 ligand and peripheral blood cells together with serum electrolytes. FLT-3 ligand levels (pg/mL) during the aplastic period due to remission induction and consolidation were higher …

Chrysin Prevents Brain Damage Caused By Global Cerebralischemia/Reperfusion In A C57bl/J6 Mouse Model, Mehmet Aki̇f Durak, Mustafa Namik Öztanir, Neşe Başak Türkmen, Osman Çi̇ftçi̇, Asli Taşlidere, Mehmet Tecelli̇oğlu, Ari̇f Önder

Turkish Journal of Medical Sciences

Background/aim: The present study investigated the neuroprotective effects of chrysin (CRS) following global cerebral ischemia and reperfusion (I/R) in a C57BL/J6 mouse model. Materials and methods: A total of 40 mice were equally divided into four groups: (1) sham-operated (SH = control), (2) global cerebral I/R (I/R), (3) CRS, and (4) CRS + I/R. In the I/R group, the bilateral carotid arteries were clipped for 15 min and the mice were treated with vehicle (corn oil) for 10 days. In the CRS group, CRS (50 mg/kg) was given for 10 days without carotid occlusion. In the CRS + I/R group …

Proliferation And Differentiation Markers Of Colorectal Adenocarcinomaand Their Correlation With Clinicopathological Factors, Olivera Mitrovic Ajtic, Slobodan Todorovic, Milos Diklic, Tijana Suboticki, Bojana Beleslin-Cokic, Gordana Jovcic, Vladan Cokic

Turkish Journal of Medical Sciences

Background/aim: The purpose of this study was to investigate proliferation and differentiation markers in colorectal adenocarcinoma and their correlation with clinicopathological factors. Materials and methods: Samples were collected from 38 patients with colorectal adenocarcinoma and 10 healthy controls. E-cadherin, carcinoembryonic antigen (mCEA), cyclin B1, vascular endothelial growth factor (VEGF), and erythropoietin (EPO) receptor (EPOR) were examined by immunohistochemistry; VEGF and EPO were examined by real-time PCR. Results: The tumor samples were mostly characterized by large dimension (pT3), moderate level of differentiation (G2), negative lymph node status (N0), and no metastasis. Cyclin B1 and VEGF gene and protein expressions were significantly …

Expression Of Maspin In Testis Tumors With Germ Cells Andits Relation With Angiogenesis Factors, Hüseyi̇n Çeli̇k, Tahsi̇n Turunç, Nebi̇l Bal, Eray Hasirci, Alaaddi̇n Akay, Çeti̇n Levent Peşki̇rci̇oğlu

Turkish Journal of Medical Sciences

Background/aim: We aimed to evaluate the importance of maspin expression in testicular tumors with germ cells, its effect on prognosis, and the relation with angiogenesis factors. Materials and methods: The paraffin blocks of the orchiectomy materials of 32 patients who had undergone orchiectomy due to testicular tumors were taken within the scope of the study. The specimens of the cases included in the study group were reexamined under light microscope. Results: While just one maspin-positive sample was found in the seminoma cases, maspin stained positively in 6 of the nonseminoma germ cell tumors (NSGCTs). No statistical difference was found between …

Effects Of Naloxone And Yohimbine In Polycystic Ovary Syndrome: A Rabbit Model Study, Sumera Sajjad, Sadia Tobassum, Umer Farooq, Husna Malik, Musadiq Idris

Turkish Journal of Medical Sciences

Background/aim: To assess the therapeutic effects of naloxone and yohimbine on polycystic ovary syndrome (PCOS) in a rabbit model in terms of body weight and endocrinological parameters (luteinizing hormone, insulin, and estradiol). Materials and methods: A total of 50 adult, reproductively mature female rabbits (Oryctolagus cuniculus) were divided into five groups (n = 10/group). In the control group PCOS was not induced (negative control group), whereas in the remaining four groups (n = 40) PCOS was induced with a single i.m. injection of testosterone daily and were designated as follows: positive control, naloxone-treated (NalT), yohimbine-treated (YohT), and naloxone+yohimbine-treated (NalYT) groups. …

Novel Targets For Mitochondrial Dysfunction Following Traumatic Brain Injury, Heather M. Yonutas

Theses and Dissertations--Neuroscience

Mitochondrial dysfunction is a phenomenon observed in models of Traumatic Brain Injury (TBI). Loss of mitochondrial bioenergetics can result in diminished cellular homeostasis leading to cellular dysfunction and possible cellular death. Consequently, the resultant tissue damage can manifest as functional deficits and/or disease states. Therapeutic strategies to target this mitochondrial dysfunction have been investigated for models TBI and have shown promising effects.

For this project, we tested the hypothesis that mitoNEET, a novel mitochondrial membrane protein, is a target for pioglitazone mediated neuroprotection. To test this, we used a severe Controlled Cortical Impact (CCI) injury model in mitoNEET null and …

The Role Of Pxr And Ikkβ Signaling In Cardiometabolic Disease, Robert N. Helsley

Theses and Dissertations--Pharmacology and Nutritional Sciences

Cardiovascular disease (CVD) is the leading cause of death worldwide and is partially attributed to perturbations in lipid metabolism. Xenobiotics, such as pharmaceutical drugs and environmental chemicals, have been associated with increased risk of CVD in multiple large-scale human population studies, but the underlying mechanisms remain poorly defined. We and others have identified several xenobiotics as potent agonists for the pregnane X receptor (PXR), a nuclear receptor that can be activated by numerous drugs as well as environmental and dietary chemicals. However, the role of PXR in mediating the pathophysiological effects of xenobiotic exposure in humans and animals remains elusive. …

Effects Of Mammalian Target Of Rapamycin Inhibition On Circuitry Changes In The Dentate Gyrus Of Mice After Focal Brain Injury, Corwin R. Butler

Theses and Dissertations--Physiology

Post-traumatic epilepsy is a common outcome of severe traumatic brain injury (TBI). The development of spontaneous seizures after traumatic brain injury generally follows a latent period of little to no symptoms. The series of events occurring in this latent period are not well understood. Additionally, there is no current treatment to prevent the development of epilepsy after TBI (i.e. antiepileptogenics). One cell signaling pathway activated in models of TBI and in models of epilepsy is the mammalian target of rapamycin (mTOR). mTOR activity is sustained for weeks after the initial insult in models of TBI, and the inhibition of mTOR …

Protein Kinase A And Epac Mediate Chronic Pain After Injury: Prolonged Inhibition By Endogenous Y1 Receptors In Dorsal Horn, Weisi Fu

Theses and Dissertations--Physiology

Inflammation or nerve injury sensitizes several populations of nociceptive neurons in the dorsal horn of the spinal cord, including those that express the neuropeptide Y (NPY) Y1 receptor (Y1R). Our overall hypothesis is that after tissue or nerve injury, these Y1R-expressing neurons enter a state of latent sensitization (LS) that contributes to vulnerability to the development of chronic pain; furthermore, LS is under the tonic inhibitory control of endogenous Y1R signaling. First, we evaluated the intracellular signaling pathways that become activated in Y1R-expressing neurons and participate in LS. To do this, we established behavioral models of inflammatory or neuropathic pain, …

Regulation Of Uv-Protective Pathways Downstream Of The Melanocortin 1 Receptor In Melanocytes, Erin M. Wolf Horrell

Theses and Dissertations--Physiology

Malignant cutaneous melanoma is the deadliest form of skin cancer, and a majority of melanoma diagnoses are a result of exposure to ultraviolet (UV) radiation. UV radiation causes DNA damage, which if not repaired correctly via nucleotide excision repair (NER) can result in mutations and melanomagenesis. The melanocortin 1 receptor (MC1R) is a G_s protein coupled receptor located on melanocyte plasma membranes and is involved in protecting the skin from UV induced damage. MC1R signaling results in the activation of two protective pathways: 1) induction of eumelanin synthesis downstream of micropthalmia-associated transcription factor (MITF) and 2) acceleration of NER …