Digital Commons Network^™

Nucleotide Excision Repair: Impacts Of Environmental Carcinogens And Its Role In Cancer Susceptibility In Appalachian Kentucky, Nathaniel C. Holcomb

Theses and Dissertations--Toxicology and Cancer Biology

Lung cancer is a particularly devastating disease, accounting for the most deaths among all cancer types in the United States. Despite a reduction in the country’s smoking rates, cigarette smoking remains the number one risk factor for lung cancer. Additionally arsenic exposure, which occurs primarily through contaminated drinking water in the U.S., is associated with increased lung cancer incidence. The nucleotide excision repair (NER) pathway is critical for maintenance of genomic fidelity, removing DNA lesions that could otherwise promote DNA mutations and drive carcinogenesis. Tobacco smoking introduces significant amounts of DNA damage and produces characteristic DNA mutations found in lung …

Localization Of Fam171b Mrna Expression In Mouse Brain Using In-Situ Hybridization, Ashani Kumudika Sudasinghe

All Graduate Theses, Dissertations, and Other Capstone Projects

Proteins containing polyglutamine (polyQ) tracts within their primary amino acid sequence are particularly interesting because expansion mutation within them has been shown to underlie a growing list of severe neurodegenerative disorders including Huntington's Disease and several types of Spinocerebellar Ataxias. FAM171B is a novel polyQ protein that was originally identified via large scale sequencing efforts. However, to date, very little is known regarding its normal cellular function and expression pattern. In this study, in situ hybridization was utilized to assess whether FAM171B is expressed in developing (postnatal days 7, 21, 42) and adult mouse brains. The results of the experiments …

Validating Drug Targets Through Inhibition Of Protein-Protein Interactions In Mycobacterium Tuberculosis, Erin C. Driscoll

Honors Undergraduate Theses

Tuberculosis is the leading cause of death by single infectious disease worldwide; novel antibiotics are needed to continue to treat this disease. To goal of this project is to provide proof-of-principle support for the idea that targeting protein-protein interactions (PPI) is an appropriate course for the discovery of new drugs. This study optimized the M-PFC assay, which allows detection of PPI in Mycobacteria, through the use of stronger promoters and inducible expression of a peptide blocker by riboswitch. To accomplish this, promoter induction studies were used to find stronger promoters for the M-PFC, optimization of the riboswitch as a …

Activation And Expansion Of Natural Killer Cells For Cancer Immunotherapy With Ex21 Exosomes, Sara Khederzadeh

Honors Undergraduate Theses

In the field of cancer immunotherapy, NK cells are recognized for their ability to provide a form of innate immunity against tumor cells. However, the average abundance of NK cells in the blood can be as low as 5% of the total lymphocyte population. As a result, it has been a focus to find novel therapies to expand NK cells in vitro while subsequently enhancing the cytotoxicity of these cells. Previously-defined methods include the minimal expansion of NK cells with high levels of cytokines such as IL-2 and IL-15, as well as co-culturing NK cells with feeder cell populations that …

Analysis Of Meiotic Spindle And Zona Pellucida Birefringenceof Ivm Oocytes In Pcos Patients, Fereshteh Safian, Mohammad Ali Khalili, Sareh Ashourzadeh, Marjan Omidi

Turkish Journal of Medical Sciences

Background/aim: Polycystic ovarian syndrome (PCOS) is one of the most common causes of infertility. One of the best therapeutic options for PCOS patients is intracytoplasmic sperm injection (ICSI). In vitro maturation (IVM) can also be a useful technique for these women. The goal of this study was to evaluate both the zona pellucida (ZP) birefringence and meiotic spindle (MS) of in vivo- and in vitro-matured oocytes from PCOS patients using the PolScope system. Materials and methods: Immature oocytes undergoing IVM and MII oocytes were obtained from PCOS patients in an ICSI program. Using PolScope, the presence of MS and ZP …

Association Of The Cetp Gene Taqib And D442g Polymorphisms With Essentialhypertension In The Chinese Mongolian Population, Shudong Niu, Xiaoming Tao, Jingping Li, Yongyue Liu, Jian Wang, Mingyu Cong, Keyong Zhang, Wenyu Zhou, Changchun Qiu

Turkish Journal of Medical Sciences

Background/aim: This study aimed to explore the associations of the cholesteryl ester transfer protein (CETP) gene TaqIB and D442G polymorphisms with essential hypertension (EH). Materials and methods: In this case-control study, 883 hypertensive patients and 1044 normal controls were randomly selected from the Mongolian population of China. Polymerase chain reaction (PCR) and direct sequencing of PCR products were used to identify the genotypes. Haplotype analysis was performed by estimating the haplotype frequencies using the online SHEsis package. Results: The distribution frequency of the B2-G haplotype was significantly lower in the EH group than in the control group (0.7% vs. 1.9%, …

Modifications Of Mice Gut Microflora Following Oral Consumption Oflactobacillus Acidophilus And Bifidobacterium Bifidum Probiotics, Hossein Khavari-Daneshvar, Maryam Mosavi, Hamid Khodayari, Ebrahim Rahimi, Peyman Ranji, Amir Hossein Mohseni, Reyhaneh Mahmudian, Farzad Shidfar, Shahram Agah, Ali Mohammad Alizadeh

Turkish Journal of Medical Sciences

Background/aim: Thirty male BALB/c mice were equally divided into three groups: control, L. acidophilus, and B. bifidum for the assessment of the probiotics' stability in the gut microflora. Materials and methods: First, the gut microflora of the mice was checked every 3 days (days 3, 6, 9, and 12) without probiotic consumption, and then the mice were daily given orally 1.5 g of probiotics in 30 cc of drinking water. The consumption of probiotics was then stopped for recovery and then the consumption continued for 5 months. Results: On day 9 after the consumption of the probiotics, L. acidophilus and …

Telomerase Reverse Transcriptase In Atherosclerosis, Hua Qing

Theses and Dissertations--Pharmacology and Nutritional Sciences

Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase and the limiting factor for the enzyme activity. The expression of TERT and telomerase activity is increased in atherosclerotic plaques. However, the role of TERT dysregulation during atherosclerosis formation remains unknown.

The work herein first identified a multi-tiered regulation of TERT expression in smooth muscle cells (SMC) through histone deacetylase (HDAC) inhibition. HDAC inhibition induces TERT transcription and promoter activation. At the protein level in contrast, HDAC inhibition decreases TERT protein abundance through enhanced degradation, which decreases telomerase activity and induces senescence. Furthermore, during vascular remodeling in vivo, TERT protein …

From Dose To Response: In Vivo Nanoparticle Processing And Potential Toxicity, Uschi M. Graham, Gary Jacobs, Robert A. Yokel, Burtron H. Davis, Alan K. Dozier, M. Eileen Birch, Michael T. Tseng, Günter Oberdörster, Alison Elder, Lisa Delouise

Pharmaceutical Sciences Faculty Publications

Adverse human health impacts due to occupational and environmental exposures to manufactured nanoparticles are of concern and pose a potential threat to the continued industrial use and integration of nanomaterials into commercial products. This chapter addresses the inter-relationship between dose and response and will elucidate on how the dynamic chemical and physical transformation and breakdown of the nanoparticles at the cellular and subcellular levels can lead to the in vivo formation of new reaction products. The dose-response relationship is complicated by the continuous physicochemical transformations in the nanoparticles induced by the dynamics of the biological system, where dose, bio-processing, and …

Cardiac Chemical Exchange Saturation Transfer Mr Imaging Tracking Of Cell Survival Or Rejection In Mouse Models Of Cell Therapy, Ashley L. Pumphrey, Shaojing Ye, Zhengshi Yang, Jennifer Simkin, John C. Gensel, Ahmed Abdel-Latif, Moriel H. Vandsburger

Saha Cardiovascular Research Center Faculty Publications

Purpose:

To examine whether cardiac chemical exchange saturation transfer (CEST) imaging can be serially and noninvasively used to probe cell survival or rejection after intramyocardial implantation in mice.

Materials and Methods:

Experiments were compliant with the National Institutes of Health Guidelines on the Use of Laboratory Animals and approved by the Institutional Animal Care and Use Committee. One million C2C12 cells labeled with either europium (Eu) 10-(2-hydroxypropyl)-1,4,7-tetraazacyclododecane-1,4,7-triacetic acid (HP-DO3A) or saline via the hypotonic swelling technique were implanted into the anterior-lateral left ventricular wall in C57BL/6J (allogeneic model, n = 17) and C3H (syngeneic model, n = 13) mice. Imaging …

The Comparison Of Various Disinfectants? Efficacy On Staphylococcus Aureus And Pseudomonas Aeruginosa Biofilm Layers, Hati̇ce Köse, Nur Yapar

Turkish Journal of Medical Sciences

Background/aim: Because biofilms are resistant to antibiotics and biocides, they usually cause chronic persistent infections, which are arduous to cure and have high mortality and morbidity. Our study aimed to investigate the efficiency of orthophthalaldehyde, peracetic acid, hydrogen peroxide, and sodium hypochlorite on Pseudomonas aeruginosa and Staphylococcus aureus biofilm layers and live microbial cells. Materials and methods: Biofilm layers were determined by crystal violet assay and live microbial cells were determined using a resazurin assay. Results: For Pseudomonas aeruginosa, sodium hypochlorite showed the most influential disinfection because it diminished 83.6% of the biofilm layer and decreased 99.7% of live microbial …

Reactive Oxygen Species-Induced Global Dna Hypomethylation In Bladder Cancer Is Mediated Via Increased Formation Of 8-Hydroxy-2'-Deoxyguanosine, Patcharawalai Whongsiri

Chulalongkorn University Theses and Dissertations (Chula ETD)

Oxidative stress, as a consequence of the elevated reactive oxygen species (ROS), has been implicated in various chronic diseases including cancers by, for examples, causing oxidative DNA damage and altering epigenetic regulation. Long interspersed element-1 (LINE-1) is an only active retrotransposable elements in human DNA, comprising up to 17% of the whole genome. LINE-1 hypomethylation is reported in bladder cancer and evidently it is a consequence of oxidative stress. In this study, we investigated the expression of 5-methylcytosine (5-mC), 8-hydroxydeoxyguanosine (8-OHdG), LINE-1-endoced protein (ORF1p), histone H3K9me3 and HP1 alpha in bladder cancer tissues. Mechanistic insight into how oxidative stress affected …

Surface Proteomics Of Leptospira Interrogans Serovar Pomona, Praparat Thaibankluay

Chulalongkorn University Theses and Dissertations (Chula ETD)

Leptospirosis is a re-emerging zoonosis of global distribution including Thailand. It caused by pathogenic Leptospira. The pathogenesis is not clear. Surface-exposed proteins (PSEs) are first part for interactions with host cells, immune system and should be potential targets for vaccine development. To date, many researches study only individual PSEs but the studies of surface proteomic is less. The study of surface proteomic will be important information for pathogenesis studies and search for vaccine candidate. This study aimed to identify surface proteomics of pathogenic Leptospira by surface biotinylation and surface shaving using proteinase K that has been used to identify surface …

Visualizing Morphogenesis With The Processing Programming Language, Avik Patel, Amar Bains, Richard Millet, Tamira Elul

Faculty Publications & Research of the TUC College of Osteopathic Medicine

We used Processing, a visual artists’ programming language developed at MIT Media Lab, to simulate cellular mechanisms of morphogenesis – the generation of form and shape in embryonic tissues. Based on observations of in vivo time-lapse image sequences, we created animations of neural cell motility responsible for elongating the spinal cord, and of optic axon branching dynamics that establish primary visual connectivity. These visual models underscore the significance of the computational decomposition of cellular dynamics underlying morphogenesis.

การวิเคราะห์อาการความผิดปกติช่วงกลางคืน ทั้งอาการการเคลื่อนไหวผิดปกติ และอาการที่ไม่เกี่ยวกับการเคลื่อนไหวในผู้ป่วยโรคพาร์กินสัน โดยการพัฒนาเครื่องมือที่ใช้ติดกับผู้ป่วยเพื่อประเมินอาการที่บ้านของผู้ป่วย, จิรดา ศรีเงิน

Chulalongkorn University Theses and Dissertations (Chula ETD)

อาการเคลื่อนไหวลำบากตอนนอน (nocturnal hypokinesia) เป็นอาการที่ทำให้เกิดผลแทรกซ้อนตามมา ได้ หลากหลาย ตั้งแต่ความรุนแรงของอาการน้อย เช่นอาการ หรือเสียชีวิตฉับพลันขณะนอน ซึ่งอาการเคลื่อนไหวลำบากขณะนอน เป็นปัญหาที่ไม่ค่อยได้รับความสนใจจากแพทย์โดยทั่วไป และตรวจพบได้ยากในการตรวจที่ห้องตรวจผู้ป่วยนอกปกติ จุดประสงค์ของการศึกษานี้ เพื่อการพัฒนาอุปกรณ์ในการวัดการเคลื่อนไหวตอนนอน ชนิดที่ใช้ติดกับตัวผู้ป่วย เพื่อใช้ประเมินอาการที่บ้าน และเปรียบเทียบการเคลื่อนไหวตอนนอน ของผู้ป่วยพาร์กินสัน กับคู่สามีหรือภรรยาของผู้ป่วยที่ไม่ได้เป็นโรคพาร์กินสัน ร่วมกับการหาปัจจัยที่ส่งผลต่อการเกิดอาการเคลื่อนไหวลำบากตอนนอน (nocturnal hypokinesia) ในผู้ป่วยพาร์กินสัน การดำเนินการศึกษาวิจัย เริ่มจากการพัฒนาชุดวัดการเคลื่อนไหวตอนนอน ชนิดติดกับตัวผู้ป่วย ซึ่งประกอบด้วย accelerometer และ gyroscope 3 แนวแกน ที่มีขนาดเล็ก เพื่อติดที่บริเวณลำตัวและแขนขาของผู้ป่วย ผลการศึกษา พบว่าในผู้ป่วยพาร์กินสัน 27 ราย และคู่สามีภรรยาที่ไม่ได้เป็นโรคพาร์กินสัน มีอายุเฉลี่ย น้ำหนัก ไม่แตกต่างกัน และผู้ป่วยมีการดำเนินโรค ส่วนใหญ่อยู่ในช่วงระดับกลาง มีอาการทั้งอาการเคลื่อนไหวผิดปกติ และอาการที่ไม่เกี่ยวกับการเคลื่อนไหว และมีการตอบสนองต่อการรักษาโดยยาทดแทนโดปามีน ไม่สม่ำเสมอ จากผลการประเมินด้วยชุดวัดการเคลื่อนไหวตอนนอน พบว่า ผู้ป่วยพลิกตัว ความเร็วและความเร่งเฉลี่ยในการพลิกตัว น้อยกว่าคู่สามีหรือภรรยา (P < 0.001) และมุมที่เฉลี่ยในการพลิกตัว น้อยกว่าคู่สามีหรือภรรยา (P= 0.003) และพบความสัมพันธ์ระหว่าง อาการละเมอผิดปกติ (RBD) กับจำนวนการพลิกตัวในช่วงครึ่งหลังของการนอน การศึกษานี้ได้แสดงให้เห็นถึงประสิทธิภาพของชุดวัดการเคลื่อนไหวตอนนอน ที่พัฒนาขึ้นร่วมกับ แสดงให้เห็นการประเมินอาการตอนกลางคืน เป็นค่าที่วัด เปรียบเทียบได้ และพบอาการเคลื่อนไหวลำบากในผู้ป่วยพาร์กินสัน เพื่อประโยชน์ในการปรับยาเพื่อครอบคลุมอาการตอนกลางคืนต่อไป

Microbiota, Diet And Medication In Human Gut Disorders, Adam Clooney

Theses

The microbiota, a community of micro-organisms in a particular environment, have been intensely researched in the past decade and interest appears to continue to increase. The human body is richly populated with bacterial cells (3.8x10'^) and alterations in these communities are associated with disease. The work presented in this thesis explores aspects of microbiota research methodologies with regard to optimisation and concerns over a lack of reproducibility. Additionally, we investigated the effects of medication, in particular Proton Pump Inhibitors, on the human gut microbiota, along with comparisons between the microbiota of patients with active and inactive Inflammatory Bowel Disease.

Microbiota …

In Vitro Three-Dimensional Skin Tissue Constructs, Tinashe Dereck Gombedza

Theses

Human skin provides fortification against peripheral threats which may compromise the integrity and health of the human body. Its presence as the largest human organ forms a protective barrier making it an effective first line of defence against pathogenic, chemical and physical damage. Tissue engineering technology has enabled the development of in vitro three-dimensional (3D) organotypic skin cultures in order to understand the skin's physiology and architecture. This advancement has enabled the use of 3D skin model platforms to study skin diseases and conditions as well as facilitate drug discovery, clinical research and cosmetic product development.

In this study, an …

The Histopathological And Stereological Assessment Of The Effect Of Topically Administered Leptin On Cerebral Vasospasm In An Experimental Subarachnoid Hemorrhage Model, Cem Demi̇rel, Cengi̇z Çokluk, Abdurrahman Aksoy, Kerameddi̇n Aydin, Mehmet Emi̇n Önger, Eni̇s Kuruoğlu, Abdullah Hi̇lmi̇ Marangoz, Ömür Gülsüm Deni̇z, Süleyman Kaplan

Turkish Journal of Medical Sciences

Background/aim: Cerebral vasospasm is a term that refers to prolonged, slowly progressing but reversible pathological narrowing of cerebral arteries occurring several days after subarachnoid hemorrhage (SAH), usually accompanied by a decrease in perfusion distal to the affected artery. Leptin is an endogenous polypeptide hormone that can be carried freely and bound to protein in the blood. Materials and methods: We investigated the superiority of topical application of leptin that may make a contribution to the development of new treatment modalities for unconscious patients in brain injury intensive care units and its preventive effect, which is considered to have multifactorial pathogenesis …

The Effects Of Mesenchymal Stem Cells On The Structure And Contractile Force Of The Carotid Artery In A Rat Aneurysm Model, Özbeyen Atalay, Handan Sevi̇m, Seçi̇l Karahi̇sar Turan, Mehmet Ali̇ Onur, Özer Ayli̇n Gürpinar

Turkish Journal of Medical Sciences

Background/aim: An aneurysm is a pathological enlargement of an artery characterized by the thinning of the elastic fiber layer in the tunica media. Because the aneuritic artery wall is weakened, these vessels can rupture and cause serious bleeding. Surgical methods are often used for the treatment of aneurysms. However, cell-based therapies are less invasive and potentially safer alternatives. In this study, the therapeutic efficacy of rat adipose tissue-derived mesenchymal stem cells (MSCs) was investigated in a new carotid artery aneurysm model.Materials and methods: Arteries were pretreated with elastase to create aneurysms. Gelatin matrices containing MSCs were applied to the outer …

Effects Of Valproic Acid On Sympathetic Activity And Left Ventricularmyocardial Remodelling In Rats During Pressure Overload, Yang Liu, Siyu Li, Zhigang Zhang, Zhanjun Lv, Huijie Jiang, Xiao Tan, Fengquan Liu

Turkish Journal of Medical Sciences

Background/aim: Pressure overload induces cardiac remodelling and results in heart failure. Enhanced sympathetic outflow participates in the development of cardiac remodelling for the duration of pressure overload as an independent factor. Valproic acid has recently been shown to reduce neuronal injury and have antiinflammatory and antiapoptotic effects as a histone deacetylase inhibitor. We speculate that the drug plays a specific role in alleviating cardiac remodelling by inhibiting sympathetic activity. Materials and methods: Surgery of partial abdominal aortic constriction was performed on male Sprague-Dawley rats. After 4 weeks, animal models of pressure overload were validated and then valproic acid (300 mg/kg) …

Evaluation Of The Effects Of Montelukast, Mometasone Furoate, And Combined Therapyon Adenoid Size: A Randomized, Prospective, Clinical Trial With Objective Data, Bi̇rgül Tuhani̇oğlu, Sanem Okşan Erkan

Turkish Journal of Medical Sciences

Background/aim: The incidence of adenoid hypertrophy is 2%-3% in children. Adenoidectomy is a commonly performed procedure in children that may cause complications such as early or late bleeding (4%-5%), recurrence of adenoid tissue (10%-20%), and postoperative respiratory problems (27%). Therefore, medical therapy alternatives to adenoidectomy are important and must be tried before surgery. In this study, we investigated the efficacy of mometasone furoate, montelukast, and a combination of these drugs in pediatric patients with adenoid hypertrophy who were scheduled for reduction with medical therapy after not being recommended for surgery.Materials and methods: The study included 120 children with adenoid hypertrophy …

The Relationship Between Nonsuicidal Self-Injurious Behavior And Manners Of Death: A Multicenter Autopsy Study, Sai̇t Özsoy, Hacer Yaşar Teke, Hüseyi̇n Çeti̇n Ketenci̇, Ertuğrul Gök, Kenan Karbeyaz, Taner Akar, Hani̇fe Alkurt-Alkan, Mesut Akyol, Mehmet Ayhan Cöngöloğlu, Sermet Sezi̇gen, Ahmet Zahi̇t Dursun, Alper Özkök, Serhat Sari

Turkish Journal of Medical Sciences

Background/aim: This study aimed to determine the relationship between nonsuicidal self-injurious behavior (NSSIB) and manners of death.Materials and methods: This study retrospectively evaluated 6604 autopsy cases evaluated at forensic medicine institutes of six major cities of Turkey. The study group consisted of all cases with NSSIB findings. The control group was created from cases without signs of NSSIB. Results: We found that the numbers of possible suicide and homicide cases in the NSSIB (+) group were significantly higher than in the NSSIB (-) group. The possibility of death due to suicide was 3.213 times and homicide was 2.004 times higher …

Molecular Analysis And Prevalence Of Huntington Disease In Northwestern Iran, Mahmoud Shekari Khaniani, Parisa Aob, Mohammadreza Ranjouri, Sima Mansoori Derakhshan

Turkish Journal of Medical Sciences

Background/aim: Huntington disease (HD) is a progressive adult-onset neurodegenerative disorder presenting an autosomal dominant inheritance. Since there is no information on the prevalence of HD in northwestern Iran, the aim of the present study was to determine the prevalence of HD and the number of CAG trinucleotide repeats in the population of northwestern Iran.Materials and methods: Genomic DNA was extracted from whole blood by the salting-out method. DNA samples were analyzed to determine the number of CAG trinucleotide repeats of the HD gene. An abnormally large number of CAG repeats, which is a diagnostic factor for the disease, was detected …

Isolation And Culture Of Adult Mouse Vestibular Nucleus Neurons, Aydin Hi̇m, Serap Altuntaş, Gürkan Öztürk, Ender Erdoğan, Nureddi̇n Cengi̇z

Turkish Journal of Medical Sciences

Background/aim: Isolated cell cultures are widely used to study neuronal properties due to their advantages. Although embryonic animals are preferred for culturing, their morphological or electrophysiological properties may not reflect adult neurons, which may be important in neurodegenerative diseases. This paper aims to develop a method for preparing isolated cell cultures of medial vestibular nucleus (MVN) from adult mice and describe its morphological and electrophysiological properties.Materials and methods: Vestibular nucleus neurons were mechanically and enzymatically isolated and cultured using a defined medium with known growth factors. Cell survival was measured with propidium iodide, and electrophysiological properties were investigated with current-clamp …

The International Scientific Association For Probiotics And Prebiotics (Isapp) Consensus Statement On The Definition And Scope Of Prebiotics, Glenn R. Gibson, Robert W. Hutkins, Mary Ellen Sanders, Susan L. Prescott, Raylene A. Reimer, Seppo J. Salminen, Karen Scott, Catherine Stanton, Kelly S. Swanson, Patrice D. Cani, Kristin Verbeke, Gregor Reid

Department of Food Science and Technology: Faculty Publications

In December 2016, a panel of experts in microbiology, nutrition and clinical research was convened by the International Scientific Association for Probiotics and Prebiotics to review the definition and scope of prebiotics. Consistent with the original embodiment of prebiotics, but aware of the latest scientific and clinical developments, the panel updated the definition of a prebiotic: a substrate that is selectively utilized by host microorganisms conferring a health benefit. This definition expands the concept of prebiotics to possibly include non-carbohydrate substances, applications to body sites other than the gastrointestinal tract, and diverse categories other than food. The requirement for selective …

Pathogenesis, Molecular Genetics, And Genomics Of Mycobacterium Avium Subsp. Paratuberculosis, The Etiologic Agent Of Johne’S Disease, Govardhan Rathnaiah, Denise K. Zinniel, John P. Bannantine, Judith R. Stabel, Yrjo T. Grohn, Michael T. Collins, Raul G. Barletta

School of Veterinary and Biomedical Sciences: Faculty Publications

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiologic agent of Johne’s disease in ruminants causing chronic diarrhea, malnutrition, and muscular wasting. Neonates and young animals are infected primarily by the fecal–oral route. MAP attaches to, translocates via the intestinal mucosa, and is phagocytosed by macrophages. The ensuing host cellular immune response leads to granulomatous enteritis characterized by a thick and corrugated intestinal wall. We review various tissue culture systems, ileal loops, and mice, goats, and cattle used to study MAP pathogenesis. MAP can be detected in clinical samples by microscopy, culturing, PCR, and an enzyme-linked immunosorbent assay. There are commercial …

A Systems Biology Approach For Predicting Essential Genes And Deciphering Their Dynamics Under Stress In Streptococcus Sanguinis, Fadi El-Rami

Theses and Dissertations

Infectious diseases are the top leading cause of death worldwide. Identifying essential genes, genes indispensable for survival, has been proven indispensable in defining new therapeutic targets against pathogens, major elements of the minimal set genome to be harnessed in synthetic biology, and determinants of evolutionary relationships of phylogenetically distant species. Thus, essentiality studies promise valuable revenues that can decipher much of biological complexities.

Taking advantage of the available microbial sequences and the essentiality studies conducted in various microbial models, we proposed a framework for the prediction of essential genes based on our experimentally verified knowledge of the pathways involved in …

Characterization Of The Role Of Insulin-Like Growth Factor Binding Protein 7 (Igfbp7) Using A Genetic Knockout Mouse Model, Maaged A. Akiel

Theses and Dissertations

In the US, the incidence and mortality rates of hepatocellular carcinoma (HCC) are alarmingly increasing since no effective therapy is available for the advanced disease. Activation of IGF signaling is a major oncogenic event in diverse cancers, including HCC. Insulin-like growth factor binding protein-7 (IGFBP7) inhibits IGF signaling by binding to IGF-1 receptor (IGF-1R) and functions as a potential tumor suppressor for hepatocellular carcinoma (HCC). IGFBP7 abrogates tumors by inducing cancer-specific senescence and apoptosis and inhibiting angiogenesis. We now document that Igfbp7 knockout (Igfbp7-/- ) mouse shows constitutive activation of IGF signaling, presents with pro-inflammatory and immunosuppressive microenvironment, and develops …

Role Of Translation Initiation In Regulation Of Epithelial Junctions And Cell Motility, Fahda Fawaz Alsharief

Theses and Dissertations

The integrity and barrier properties of intestinal epithelium are determined by specialized adhesive structures known as intercellular junctions; composed of adherens junctions (AJs), tight junctions (TJs) and focal adhesions that mediate cell-cell and cell matrix interactions, respectively. These two types of epithelial cell adhesions regulate each other during disruption and restitution of the epithelial barrier. Inflammatory cytokines such as interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) are elevated during intestinal inflammation. The most notable effects of IFNγ and TNFα on intestinal epithelial homeostasis involve disruption of apical junctions and attenuation of cell migration. Although molecular mechanisms underlying these …

Tissue Factor Expression, Regulation, And Signaling In Human Airway Cells, Michael D. Davis

Theses and Dissertations

Rationale: Tissue Factor (TF) is a transmembrane glycoprotein that canonically functions as the initiator of the coagulation cascade. Increased levels of TF have been associated with inflammatory airway diseases. Since lipopolysaccharide (LPS) is known to elicit and inflammatory response in airway epithelium, we hypothesized that airway epithelial cells release TF when exposed to LPS. Since TF aids in local wound healing, we also hypothesized that inhibition of TF would decrease NHBE growth. The specific aim of this work was to evaluate the effects of LPS exposure on TF production and release from airway epithelia and determine the signaling pathways involved. …