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Cytokeratin 18 And H-Fabp Levels In Intestinal Ischemia–Reperfusion Injury: Role Of Coenzyme Q10, Muaz Belvi̇ranli, Ni̇lsel Okudan, Hakki Gökbel, Aysel Kiyici, Mehmet Öz, Ayşe Kumak

Turkish Journal of Medical Sciences

The objective of this study was to investigate whether coenzyme Q10 (CoQ10) supplementation affects M30 and heart-type fatty acid binding protein (h-FABP) levels in intestinal ischemia-reperfusion injury-induced rats. Materials and methods: Thirty-two male Wistar rats were randomly divided into 4 groups. 1) Sham: Animals exposed to laparotomy without clamping the superior mesenteric artery (SMA); 2) ischemia-reperfusion (IR): rats exposed to laparotomy with occlusion of the SMA for 45 min, followed by 120 min of reperfusion period; 3) CoQ10 plus sham: 10 mg kg body weight^{-1} CoQ10 was administrated via intraperitoneal injection for 20 days, and thereafter animals were exposed to …

Assessment Of Hearing Ability With Pure-Tone Audiometry And Otoacoustic Emission Methods In Patients Undergoing Spinal Anesthesia, Zi̇ya Kaya, Levent Gürbüzler, Mustafa Süren, Semi̇h Arici, Serkan Karaman

Turkish Journal of Medical Sciences

To investigate the frequency of hearing loss after spinal anesthesia in patients undergoing spinal anesthesia using pure-tone audiometry and otoacoustic emission methods. Materials and methods: A total of 80 patients (40 females, 40 males, aged 18-65 years) were included in the study. For spinal anesthesia, a 27-gauge Quincke spinal needle was entered at the first attempt into the subarachnoidal space through the L4-L5 interval with the patient in the lateral decubitus position. The first day before spinal anesthesia, pure-tone audiometry, transient evoked otoacoustic emission, distortion product otoacoustic emission, and tympanometry were performed on all patients, and the same procedures were …

A Comparison Of Tramadol, Sufentanil, Meperidine, And Lidocaine In Prevention Of Pain Due To Rocuronium Injection, Mehtap Honca, Belkiz Berna Külah, Tarik Purtuloğlu, Tevfi̇k Honca, Nuray Camgöz Eryilmaz, Uğur Özkan, Eyüp Horasanli

Turkish Journal of Medical Sciences

Alleviation of the pain resulting from injection of rocuronium during anesthesia is still an unsolved problem. We aimed to compare the analgesic effects of sufentanil, tramadol, meperidine, and lidocaine on the pain from injection of rocuronium. Materials and methods: This prospective randomized double-blind study included 200 patients with ASA I-II. After a tourniquet was applied to the forearm, patients received 50 mg of tramadol (group T), 10 µg of sufentanil (group S), 40 mg of meperidine (group M), or 30 mg of lidocaine (group L). The tourniquet was released after 20 s and rocuronium was injected over 10 to 15 …

Phosphorylated Iκbα Predicts Poor Prognosis In Activated B-Cell Lymphoma And Its Inhibition With Thymoquinone Induces Apoptosis Via Ros Release, Azhar Hussain, Shahab Uddin, Maqbool Ahmed, Fouad Al-Dayel, Prashant P. Bavi, Khawla S. Al-Kuraya

Centre for Regenerative Medicine & Stem Cell Research

Activated B-cell lymphoma (ABC), one of the three subtypes of Diffuse Large B-cell Lymphoma (DLBCL) has the worst survival rate after upfront chemotherapy and is characterized by constitutively activated NFκB. We therefore studied the role of NFκB In a cohort of clinical DLBCL samples and ABC cell lines. In our clinical tissue microarray cohort of DLBCL samples, p-IκBα was detected in 38.3% of ABC DLBCL and was an independent prognostic marker for poor survival. In vitro, we found that Thymoquinone (TQ), a natural compound isolated from Nigella sativa caused release of ROS in ABC cells. TQ-mediated release of ROS …

Offspring And Maternal Health Benefits Of Exercise During Pregnancy, Lindsay G. Carter

Theses and Dissertations--Nutritional Sciences

Maternal lifestyle and nutrient intake during pregnancy can have long-lasting effects on the health of offspring as well as the mother. This dissertation focuses on the impact of maternal exercise during pregnancy on offspring insulin sensitivity and glucose uptake and the maternal effects of exercise during pregnancy.

The first aim of this dissertation was to investigate if exercise prior to and during pregnancy and nursing would improve glucose uptake and insulin sensitivity in mice and rats. In both mice and rats, it was concluded that maternal exercise could enhance whole-body insulin sensitivity and increase glucose uptake into skeletal muscle and …

An Investigation Of Perinatal Polychlorinated Biphenyl Exposure On Body Composition And Glucose Homeostasis, Cetewayo S. Rashid

Theses and Dissertations--Nutritional Sciences

Recent advancements have uncovered environmental contributions to obesity and diabetes etiology. In fact, perinatal malnutrition resulting in low birth weight (LBW) has been shown to correlate with later life obesity and impaired glucose tolerance in aged offspring. LBW can result from a myriad of developmental perturbations including macronutrient restriction, hypoxia, maternal stress and toxin exposure.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants that bioaccumulate in the food chain resulting in dietary exposure in humans. Maternal and cord blood PCB levels are inversely associated with birth weight, and recent studies indicate that perinatal exposures to PCBs contribute to gender-specific obesity development …

Molecular Architecture Of The Uncleaved Hiv-1 Envelope Glycoprotein Trimer, Youdong Mao, Luis Castillo-Menendez, Liping Wang, Christopher Gu, Alon Herschhorn, Anik Désormeaux, Andrés Finzi, Shi-Hua Xiang, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

The human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer, a membrane-fusing machine, mediates virus entry into host cells and is the sole virusspecific target for neutralizing antibodies. Binding the receptors, CD4 and CCR5/CXCR4, triggers Env conformational changes from the metastable unliganded state to the fusion-active state. We used cryo-electron microscopy to obtain a 6-Å structure of the membranebound, heavily glycosylated HIV-1 Env trimer in its uncleaved and unliganded state. The spatial organization of secondary structure elements reveals that the unliganded conformations of both gp120 and gp41 subunits differ from those induced by receptor binding. The gp120 trimer association domains, which …

Variations In The Biological Functions Of Hiv-1 Clade C Envelope In A Shiv-Infected Rhesus Macaque During Disease Progression, For Yue Tso, Levon Abrahamyan, Shiu-Lok Hu, Ruth M. Ruprecht, Charles Wood

Nebraska Center for Virology: Faculty Publications

A better understanding of how the biological functions of the HIV-1 envelope (Env) changes during disease progression may aid the design of an efficacious anti-HIV-1 vaccine. Although studies from patient had provided some insights on this issue, the differences in the study cohorts and methodology had make it difficult to reach a consensus of the variations in the HIV-1 Env functions during disease progression. To this end, an animal model that can be infected under controlled environment and reflect the disease course of HIV-1 infection in human will be beneficial. Such an animal model was previously demonstrated by the infection …

Kaposi’S Sarcoma-Associated Herpesvirus Transactivator Rta Induces Cell Cycle Arrest In G0/G1 Phase By Stabilizing And Promoting Nuclear Localization Of P27Kip, Pankaj Kumar, Charles Wood

Nebraska Center for Virology: Faculty Publications

The Kaposi’s sarcoma-associated herpesvirus (KSHV) immediate-early gene, replication, and transcription activator (KRta) is a key viral protein that serves as the master regulator for viral lytic replication. In this study, we investigated the role of K-Rta in cell cycle regulation and found that the expression of K-Rta in doxycycline (Dox)-inducible BJAB cells induced cell cycle arrest in G₀/G₁ phase. Western blot analysis of key cell cycle regulators revealed that K-Rta-mediated cell cycle arrest was associated with a decrease in cyclin A and phosphorylated Rb (pS807/pS811) protein levels, both markers of S phase progression, and an increase in …

Low-Abundance Resistant Mutations In Hiv-1 Subtype C Antiretroviral Therapy-Naïve Individuals As Revealed By Pyrosequencing, Sandra Gonzalez, Damien C. Tully, Clement Gondwe, Charles Wood

Nebraska Center for Virology: Faculty Publications

Given the recent scale-up of antiretroviral therapy (ART) in sub-Saharan Africa, we sought to determine how often and at what levels do drug-resistant mutant variants exist in ART-naïve HIV subtype C infected individuals. Samples from 10 ART-naïve Zambian individuals were subjected to ultra-deep pyrosequencing (UDPS) to characterize the frequency of low-abundance drug resistance mutations in the pol gene. Low-abundance clinically relevant variants were detected for nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) in eight of the ten subjects. Intermediate to high-level resistance was predicted for the majority of NRTIs. Mutations conferring resistance to …

Clade C Hiv-1 Isolates Circulating In Southern Africa Exhibit A Greater Frequency Of Dicysteine Motif-Containing Tat Variants Than Those In Southeast Asia And Cause Increased Neurovirulence, Vasudev R. Rao, Ujjwal Neogi, Joshua S, Talboom, Ligia Padilla, Mustafizur Rahman, Cari Fritz-French, Sandra Gonzalez-Ramirez, Anjali Verma, Charles Wood, Ruth M. Ruprecht, Udaykumar Ranga, Tasnim Azim, Vinayaka R. Prasad

Nebraska Center for Virology: Faculty Publications

Background: HIV-1 Clade C (Subtype C; HIV-1C) is responsible for greater than 50% of infections worldwide. Unlike clade B HIV-1 (Subtype B; HIV-1B), which is known to cause HIV associated dementia (HAD) in approximately 15% to 30% of the infected individuals, HIV-1C has been linked with lower prevalence of HAD (0 to 6%) in India and Ethiopia. However, recent studies report a higher prevalence of HAD in South Africa, Zambia and Botswana, where HIV-1C infections predominate. Therefore, we examined whether Southern African HIV-1C is genetically distinct and investigated its neurovirulence. HIV-1 Tat protein is a viral determinant of neurocognitive dysfunction. …

Global Neuroaids Roundtable, Jeymohan Joseph, Cristian L. Achim, Michael J. Boivin, Bruce J. Brew, David B. Clifford, Deborah A. Colosi, Ronald J. Ellis, Robert K. Heaton, Amadou Gallo-Diop, Igor Grant, Georgette D. Kanmogne, Mahendra Kumar, Scott Letendre, Thomas D. Marcotte, Avindra Nath, Carlos A. Pardo, Robert H. Paul, Lynn Pulliam, Kevin Robertson, Walter Royal Iii, Ned Sacktor, Pasiri Sithinamsuwan, Davey M. Smith, Victor Valcour, Brian Wigdahl, Charles Wood

Nebraska Center for Virology: Faculty Publications

In May 2012, the Division of AIDS Research at the National Institute of Mental Health (NIMH) organized the “Global NeuroAIDS Roundtable” in conjunction with the 11th International Symposium on Neurovirology and the 2012 Conference on HIV in the Nervous System. The meeting was held in New York, NY, USA and brought together NIMH-funded investigators who are currently working on projects related to the neurological complications of AIDS (NeuroAIDS) in Africa, Asia, Eastern Europe, and Latin America in order to provide an opportunity to share their recent findings and discuss the challenges encountered within each country. The major goals of the …

Heterogeneity In Platelet Exocytosis, Deepa Jonnalagadda

Theses and Dissertations--Molecular and Cellular Biochemistry

Platelet exocytosis is essential for hemostasis and for many of its sequelae. Platelets release numerous bioactive molecules stored in their granules enabling them to exert a wide range of effects on the vascular microenvironment. Are these granule cargo released thematically in a context-specific pattern or via a stochastic, kinetically-controlled process? My work describes platelet exocytosis using a systematic examination of platelet secretion kinetics. Platelets were stimulated for increasing times with different agonists (i.e. thrombin, PAR1-agonist, PAR4-agonist, and convulxin) and micro-ELISA arrays were used to quantify the release of 28 distinct α-granule cargo molecules. Agonist potency directly correlated with the speed …

Investigating Therapeutic Options For Lafora Disease Using Structural Biology And Translational Methods, Amanda R. Sherwood

Theses and Dissertations--Molecular and Cellular Biochemistry

Lafora disease (LD) is a rare yet invariably fatal form of epilepsy characterized by progressive degeneration of the central nervous and motor systems and accumulation of insoluble glucans within cells. LD results from mutation of either the phosphatase laforin, an enzyme that dephosphorylates cellular glycogen, or the E3 ubiquitin ligase malin, the binding partner of laforin. Currently, there are no therapeutic options for LD, or reported methods by which the specific activity of glucan phosphatases such as laforin can be easily measured. To facilitate our translational studies, we developed an assay with which the glucan phosphatase activity of laforin as …

Food Limitation As A Potentially Emerging Contributor To The Asian Vulture Crisis, Fakhar -I- Abbas, Thomas P. Rooney, Jibran Haider, Afsar Mian

Biological Sciences Faculty Publications

It was believed that the reason for decline in Asian vulture population is the drug, Diclofenac sodium (DFS), used in livestock. Even after declaring the DFS use banned by the government, apparent decrease in the population of vultures was reported. Alternate hypothesis was suggested that food limitation may be a cause of Asian vulture crisis in Pakistan. Very recent shifts in livestock utilization observed in Pakistan may present a significant barrier to vulture recovery. Increased livestock utilization is translated to fewer carcasses. Since 2005, no livestock carcasses were found in 1650 km transect in the habitat of vultures. Carcasses recorded …

Game-Based Curricula In Biology Classes: Multi-Level Assessment Of Science Learning, Troy D. Sadler, William L. Romine, Parker E. Stuart

Biological Sciences Faculty Publications

Video games played on computers, game consoles, tablets and smart phones have become a very popular medium in our society. A growing body of scholarship suggests that video games can support substantial learning (for reviews see Gee, 2007; Honey & Hilton, 2011; Squire, 2011). Research has documented ways in which games engage students deeply in thinking, learning, and collaboration (Gee, 2005). Evidence suggests that games can support development of critical thinking (Squire, 2006), creativity (Annetta, Cheng, & Holmes, 2010), and mastery and application of target concepts (Squire, 2011).

Hydrodynamic Modeling Of Ns-Laser Ablation, David Autrique, Vasilios Alexiades, Harihar Khanal

Publications

Laser ablation is a versatile and widespread technique, applied in an increasing number of medical, industrial and analytical applications. A hydrodynamic multiphase model describing nanosecond-laser ablation (ns- LA) is outlined. The model accounts for target heating and mass removal mechanisms as well as plume expansion and plasma formation. A copper target is placed in an ambient environment consisting of helium and irradiated by a nanosecond-laser pulse. The effect of variable laser settings on the ablation process is explored in 1-D numerical simulations.

The Role Of Complement In Experimental Cerebral Malaria, Theresa N. Ramos

All ETDs from UAB

Cerebral malaria (CM) is one of the most severe clinical complications of P. falciparum malaria with a fatality rate of 15-30%, and 10% of CM survivors have permanent neurological sequelae. Since inflammation is a central pathophysiological tenet of CM, we began examining the role of the complement system in pathogenesis of experimental cerebral malaria (ECM) using Plasmodium berghei ANKA (PbA) model. Previous studies using this model indicated that mice naturally deficient in complement component C5 were protected from cerebral complications, and wild type mice treated with anti-C5aR antibody were also protected. To determine the protective mechanism of naturally-C5 deficient mice, …

Commensal Microbiota And Its Impact On Health And Autoimmune Diabetets, Kyle James Wolf

All ETDs from UAB

Environmental exposures such as diet, use of antibiotics, and lifestyle have significant impact on the health of an individual. One mechanism that acts as a major pathway in these environmental exposures is the role intestinal commensal microbiota play in both metabolic and immunological responses. Metabolic pathways are altered through changes in metabolites provided by commensal microbiota; alterations in microbial make-up can have drastic impacts on metabolic function. Similarly, the development and maturation of the immune system is dependent on the intestinal microbes to induce tolerance and act as both an immune modulator as well as a barrier against pathogens. We …

Sulindac Sulfide Amide As A Novel Agent For The Prevention And Treatment Of Lung Cancer, Evrim Gurpinar

All ETDs from UAB

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac sulfide (SS) have shown promising antineoplastic activity in multiple tumor types, but toxicities resulting from cyclooxygenase (COX) inhibition limit their use in cancer prevention. We recently described a N,N-dimethylethyl amine derivative of SS, sulindac sulfide amide (SSA), that does not inhibit COX-1 or -2, yet displays potent tumor cell growth inhibitory activity. Here, we studied the basis for the growth inhibitory effects of SSA on human lung adenocarcinoma cell lines and evaluated its preclinical pharmacology. SSA potently inhibited the growth of lung tumor cells with IC50 values of 2-5 μ compared with 44-52 …

Clinical Consequences Of Micrornas In Colorectal Cancer, Liselle C. Bovell

All ETDs from UAB

Colorectal cancer (CRC) is a heterogeneous disease, and factors such as tumor location, the environment, genetics, and ethnic differences, can influence its development and progression. Over the last few decades, overall CRC mortality rates have declined; however, racial disparities in mortality rates have increased. The discovery of biomarkers that focus on identifying individual differences based on confounders such as tumor stage and patient race/ethnicity is needed, for such biomarkers can lead to development of personalized therapeutic approaches to target these molecules. MicroRNAs (miRNAs) are a class of small molecules that regulate genes at the post-transcriptional level. Altered miRNA expression levels …

Regulation Of Glioma Cell Migration And Proliferation By A Non-Selective Cation Channel., Arun Kumar Rooj

All ETDs from UAB

Two of the most striking features of brain tumors are their unusual ability to robustly proliferate and migrate in the brain. Previous results from our laboratory suggest that glioma cells express a non-selective cation channel that is composed of Epithelial Sodium Channel (ENaC) and Acid Sensing Ion Channel (ASIC) subunits. We hypothesize that this glioma specific current regulates glioma cell migration and proliferation by modulating an intracellular signaling pathway. To test our hypothesis, we have attenuated this cationic conductance by either pharmacological blockers (psalmotoxin-1 and benzamil), or by knocking down expression of a particular subunit of this cross-clade ion channel …

The Duty To Rescue In Genomic Research, Michael Ulrich

Student Articles and Papers

No abstract provided.

Development And Validation Of A Predictive Model Of Acute Glucose Response To Exercise In Individuals With Type 2 Diabetes, Bryan S. Gibson, Sheri R. Colberg, Paul Poirier, Denise Maria Martins Vancea, Jason Jones, Robin Marcus

Human Movement Studies & Special Education Faculty Publications

Background: Our purpose was to develop and test a predictive model of the acute glucose response to exercise in individuals with type 2 diabetes.

Design and methods: Data from three previous exercise studies (56 subjects, 488 exercise sessions) were combined and used as a development dataset. A mixed-effects Least Absolute Shrinkage Selection Operator (LASSO) was used to select predictors among 12 potential predictors. Tests of the relative importance of each predictor were conducted using the Lindemann Merenda and Gold (LMG) algorithm. Model structure was tested using likelihood ratio tests. Model accuracy in the development dataset was assessed by leave-one-out cross-validation. …

Bmp7 Gene Transfer Via Gold Nanoparticles Into Stroma Inhibits Corneal Fibrosis In Vivo, Ashish Tandon, Ajay Sharma, Jason T. Rodier, Alexander M. Klibanov, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

This study examined the effects of BMP7 gene transfer on corneal wound healing and fibrosis inhibition in vivo using a rabbit model. Corneal haze in rabbits was produced with the excimer laser performing -9 diopters photorefractive keratectomy. BMP7 gene was introduced into rabbit keratocytes by polyethylimine-conjugated gold nanoparticles (PEI2- GNPs) transfection solution single 5-minute topical application on the eye. Corneal haze and ocular health in live animals was gauged with stereo- and slit-lamp biomicroscopy. The levels of fibrosis [a-smooth muscle actin (aSMA), F-actin and fibronectin], immune reaction (CD11b and F4/80), keratocyte apoptosis (TUNEL), calcification (alizarin red, vonKossa and osteocalcin), and …

Systems Biology Of The Functional And Dysfunctional Endothelium, Jennifer Frueh, Nataly Maimari, Takayuki Homma, Sandra M. Bovens, Ryan M. Pedrigi, Leila Towhidi, Rob Krams

Department of Mechanical and Materials Engineering: Faculty Publications

This review provides an overview of the effect of blood flow on endothelial cell (EC) signalling pathways, applying microarray technologies to cultured cells, and in vivo studies of normal and atherosclerotic animals. It is found that in cultured ECs, 5–10% of genes are up- or down-regulated in response to fluid flow, whereas only 3–6% of genes are regulated by varying levels of fluid flow. Of all genes, 90%are regulated by the steady part of fluid flow and 10% by pulsatile components. The associated gene profiles show high variability from experiment to experiment depending on experimental conditions, and importantly, the bioinformatical …

Multifactorial Modulation Of The Blood-Brain Barrier: Relationship To Stroke, Bei Zhang

Theses and Dissertations--Nutritional Sciences

The blood-brain barrier (BBB) is a dynamic interface, mainly consisting of highly specialized brain microvascular endothelial cells (BMECs) that segregate the central nervous system (CNS) from the peripheral circulation. Impairment of the BBB, due to disruption of tight junction (TJ) proteins and inflammatory responses, may initiate and/or contribute to the progress of CNS disorders, including stroke. Stroke is the second leading cause of death worldwide. It has been shown that aging and environmental pollutants can induce brain endothelium dysfunction, and are considered as risk factors for stroke.

Deficiency of telomerase is highly linked with aging-associated vascular diseases. Evidence indicates that …

Coplanar Pcb-Induced Inflammation And Dietary Interventions, Katryn Elizabeth Eske

Theses and Dissertations--Nutritional Sciences

Diseases, such as cardiovascular disease (CVD), are linked to chronic low levels of inflammation. This inflamed state is the product of risk factors including exposure to environmental pollutants, such as polychlorinated biphenyls (PCBs), which are correlated with increased risk for CVD and diabetes. In response to this health risk, our research addresses the mechanisms by which coplanar PCBs elicit an inflammatory response and the mitigation of PCB-induced inflammation through dietary intervention using docosahexaenoic acid (DHA), an omega-3 lipid. Investigators from the University of Kentucky Engineering Department are developing remediation technologies that detoxify PCBs through dechlorination. We studied the cellular toxicity …

Novel Insights Into The Function And Regulation Of Group X Secretory Phospholipase A2, Joseph D. Layne Jr

Theses and Dissertations--Nutritional Sciences

Group X secretory phospholipase A₂ (GX sPLA₂) hydrolyzes membrane phospholipids producing free fatty acids and lysophospholipids. Previous studies from our lab suggest that mice with targeted deletion of GX sPLA₂ (GX KO) have increased age-related weight gain due to an increase in overall adiposity. Paradoxically, this increased adiposity is associated with improved age-related glucose intolerance. GX KO mice also demonstrate a reduced inflammatory response to lipopolysaccharide injection. In vitro studies indicate this phenotype may be attributable to blunted macrophage mediated inflammatory responses. Given the role of macrophages in promoting adipose tissue (AT) inflammation and metabolic dysfunction …

Pax3 Expression, Protein Modifications And Downstream Target Gene Profiling In Melanocytes And Melanoma Cells, Danielle Bartlett

Theses: Doctorates and Masters

PAX3 is a transcription factor. It plays a major role in the development of melanocytes in the embryo. As a result of alternative splicing, the gene gives rise to eight different transcripts which encode proteins that have differing structures and are therefore likely to activate different downstream target genes. The presence of post-translational modifications has also been shown to alter the functions of the proteins.

PAX3 regulates the maintenance of undifferentiated melanoblasts and mediates pathways involved in proliferation, migration and survival. It has been shown to be expressed in melanoblasts, adult melanocytes, naevi and in most melanoma cells. This implies …