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Tellurite Resistance In Shiga Toxin-Producing Escherichia Coli , Gentry L. Lewis, Quentin R. Jorgensen, John Dustin Loy, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

Potassium tellurite ( K₂TeO₃) is an effective selective agent for O157:H7 Shiga toxin-producing Escherichia coli (STEC), whereas tellurite resistance in non-O157 STEC is variable with information on O45 minimal. High-level K₂TeO₃ resistance in STEC is attributable to the ter gene cluster with terD an indicator of the cluster’s presence. Polymerase chain reactions for terD and K₂TeO₃ minimum inhibitory concentration (MIC) determinations in broth cultures were conducted on 70 STEC and 40 non-STEC control organisms. Sixty-six STEC strains (94.3%) were terD+ compared to 28 control organisms (70.0%; P < 0.001). The prevalence of terD in …

Epitope Mapping Of Serca2a Identifies An Antigenic Determinant That Induces Mainly Atrial Myocarditis In A/J Mice, Bharathi Krishnan, Chandirasegara Massilamany, Rakesh H. Basavalingappa, Arunakumar Gangaplara, Rajkumar Rajasekaran, Muhammad Z. Afzal, Vahid Khalilzad-Sharghi, You Zhou, Jean-Jack Riethoven, Shyam S. Nandi, Paras K. Mishra, Raymond A. Sobel, Jennifer L. Strande, David Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Sarcoplasmic/endoplasmic reticulum Ca²⁺ adenosine triphosphatase (SERCA)2a, a critical regulator of calcium homeostasis, is known to be decreased in heart failure. Patients with myocarditis or dilated cardiomyopathy develop autoantibodies to SERCA2a suggesting that they may have pathogenetic significance. In this report, we describe epitope mapping analysis of SERCA2a in A/J mice that leads us to make five observations: 1) SERCA2a contains multiple T cell epitopes that induce varying degrees of myocarditis. One epitope, SERCA2a 971–990, induces widespread atrial inflammation without affecting noncardiac tissues; the cardiac abnormalities could be noninvasively captured by echocardiography, electrocardiography, and magnetic resonance microscopy imaging. 2) SERCA2a …

Der P 1-Specific Treg And Breg Cells In Allergen Immunotherapy And Mechanism Of Immune Tolerance, Tadech Boonpiyathad

Chulalongkorn University Theses and Dissertations (Chula ETD)

Allergen-specific immunotherapy (AIT) involves the repeated administration of allergen products in order to induce clinical and immunologic tolerance to the offending allergen. The generation and maintenance of functional allergen-specific regulatory T (Treg) cells and regulatory B (Breg) cells are known in bee venom immunotherapy. However, in aeroallergen, house dust mite has not to be studied. The aim of the study is to identify the possible roles of Der p 1-specific active Treg (FOXP3+Helios+CD25+CD127-CD4+), ineffective Treg (ILT3-CD25+CD4+) and Breg (IL-10+IL-1RA+CD73-CD25+CD71+) cells changes during AIT and its correlation to treatment outcomes. We studied 25 allergic patients (20 responders and 5 non-responders) undergoing …

Comparison Of The Ocular Microbiome On Ocular Surface Between Chronic Stevens-Johnson Syndrome Patients And Healthy Subjects, Thanachaporn Kittipibul

Chulalongkorn University Theses and Dissertations (Chula ETD)

Background: Stevens-Johnson syndrome (SJS) usually causes ocular surface disease. 35% of these patients develop chronic ocular sequelae including symblepharon, limbal stem cell deficiency, etc. The sequelae from SJS may also affect the alteration of ocular microbiome. Subjects: 20 chronic SJS patients and 20 healthy subjects were enrolled for specimen collection from inferior conjunctiva for microbiome analysis by using conventional culture and next-generation sequencing(NGS) methods Methods: Prospective, age and sex matched analytical study Results: A significant higher proportion of culture-positive specimen was demonstrated in SJS group (SJS group 60%, healthy 10%, p-value=0.001). In SJS group, we found significantly higher severity score …

Systems Biology Of Human Cells Responded To Influenza B Virus Infection, Kritsada Sirivassanametha

Chulalongkorn University Theses and Dissertations (Chula ETD)

Influenza B virus is a member of Orthomyxoviridae family which can cause influenza in human and affect to worldwide health problem. Systems biology is the computational modeling of molecular systems which is useful to predict how these biological systems change over time and under different conditions. In this study the multiomics was used to study human cellular response to influenza B virus infection. The transcriptome including mRNAs, lncRNAs and miRNAs and proteome were investigated by high-throughput technologies such as next-generation sequencing and mass spectrometry. The results showed that in human cells infected with influenza B virus, transcriptome including mRNAs, lncRNAs …

ความหลากหลายทางพันธุกรรมของหนอนพยาธิหัวใจและแบคทีเรีย Wolbachia Spp. ที่อาศัยอยู่ในหนอนพยาธิในเลือดของสุนัขที่เก็บจากกรุงเทพและปริมณฑล, หทัยทิพย์ สัจจาวงศ์วาณิชย์

Chulalongkorn University Theses and Dissertations (Chula ETD)

โรคหนอนพยาธิหัวใจสุนัข (Canine filariasis) มีสาเหตุจากหนอนพยาธิตัวกลมในกลุ่มฟิลาเรีย เช่น Dirofilaria immitis, D. repens, Brugia pahangi, B. malayi และ Acanthocheilonema reconditum เป็นต้น ซึ่งหนอนพยาธิสามารถก่อโรคได้ทั้งในสุนัข แมวและสามารถติดต่อสู่คนได้ นอกจากนี้มีรายงานการพบแบคทีเรีย Wolbachia อาศัยอยู่ร่วมกันแบบ endosymbiosis ภายในหนอนพยาธิ ซึ่งมีบทบาทสำคัญในการเจริญและการก่อโรคของหนอนพยาธิได้ อย่างไรก็ตามยังขาดข้อมูลเบื้องต้นเกี่ยวกับหนอนพยาธิในสุนัขและแบคทีเรีย Wolbachia ในประเทศไทย ดังนั้นงานวิจัยนี้จึงได้ทำการตรวจหาหนอนพยาธิกลุ่มฟิลาเรียและแบคทีเรีย Wolbachia ที่อาศัยในหนอนพยาธิจากตัวอย่างเลือดสุนัขที่สงสัยว่าเป็นโรคหนอนพยาธิหัวใจที่เก็บจากกรุงเทพมหานครและปริมณฑล จำนวน 57 ตัวอย่าง โดยอาศัยการตรวจทั้งทางจุลทรรศน์วิทยาและทางอณูชีววิทยา การตรวจหาตัวอ่อนหนอนพยาธิระยะไมโครฟิลาเรียด้วยวิธีทางอณูชีววิทยาอาศัยเทคนิค PCR ที่ตำแหน่งยีน COI และบริเวณ ITS1 และตรวจหาแบคทีเรีย Wolbachia ที่ตำแหน่งยีน FtsZ ด้วยวิธี nested PCR โดยพบตัวอ่อนระยะไมโครฟิลาเรียที่ให้ผลบวกภายใต้กล้องจุลทรรศน์จำนวน 16 ตัวอย่าง (28.07%) และจากการตรวจด้วย COI-PCR พบตัวอย่างที่ให้ผลบวกจำนวน 50 ตัวอย่าง (87.72%) โดยสามารถระบุสายพันธุ์ D. immitis 33 ตัวอย่าง (57.89%), B. pahangi 13 ตัวอย่าง (22.81%) และ B. malayi 4 ตัวอย่าง (7.02%) การตรวจด้วย ITS1-PCR พบตัวอย่างให้ผลบวกจำนวน 41 ตัวอย่าง (71.93%) สามารถระบุสายพันธุ์ D. immitis 30 ตัวอย่าง (52.63%) และ B. pahangi 11 ตัวอย่าง (19.30%) แต่ไม่สามารถตรวจพบ B. malayi และสามารถตรวจพบแบคทีเรีย Wolbachia จำนวน 47 …

การศึกษาแบบสุ่มแบ่งครึ่งข้างเพื่อเปรียบเทียบประสิทธิภาพการฉีดโบทูลินัมทอกซินชนิดเอกับ 0.9% โซเดียมคลอไรด์ในผื่นสะเก็ดเงินบนศีรษะ, เกศกนิษฐ์ ธรรมคำภีร์

Chulalongkorn University Theses and Dissertations (Chula ETD)

ปัจจุบันมีการรายงานผลการทดลองในสัตว์และรายงานผู้ป่วยเกี่ยวกับการรักษาผื่นสะเก็ดเงินบนผิวหนังที่ดื้อต่อการรักษาโดยการใช้โบทูลินัมทอกซินในชั้นหนังแท้ของผื่นสะเก็ดเงินและได้ผลดี จึงเป็นที่มาของการใช้โบทูลินัมทอกซินในผื่นสะเก็ดเงินบนหนังศีรษะ วัตถุประสงค์: เพื่อประเมินประสิทธิภาพของการฉีดโบทูลินัมทอกซินเอในผื่นสะเก็ดเงินบนหนังศีรษะโดยการวัดความรุนแรงของผื่นสะเก็ดเงินด้วย modified Psoriasis Severity Index (mPSI) วิธีการศึกษา: ผู้ป่วยสะเก็ดเงินที่มีผื่นบนศีรษะซึ่งไม่ตอบสนองต่อการรักษาด้วยยาทา 14 ราย แบ่งครึ่งศีรษะเป็นฝั่งซ้ายและฝั่งขวา จากนั้นฉีดโบทูลินัมทอกซินชนิดเอ (Dysport®) 62.5 units และ 0.9% โซเดียมคลอไรด์ในแต่ละฝั่งบนพื้นที่ 16 ตารางเซนติเมตร วัดการเปลี่ยนแปลงของผื่นสะเก็ดเงินโดยใช้ mPSI และหาร้อยละของผู้ป่วยที่มีค่า mPSI ลดลงเกิน 50% (mPSI50) ผลการศึกษา: จำนวนผู้ป่วยที่มีค่า mPSI ลดลงเกิน 50% (mPSI50) หลังฉีดโบทูลินัมทอกซินเทียบกับยาหลอกที่ระยะเวลาต่างๆดังนี้ 3/14 (21%) vs 0/14 (0%)/ 7/14 (50%) vs 1/14 (7%)/ 8/14 (57%) vs 4/14 (29%) และ 6/14 (43%) vs 2/14 (14%) ที่ 2, 4, 8 และ 12 สัปดาห์ตามลำดับและไม่พบผลข้างเคียงที่ร้ายแรงทั้งสองกลุ่ม สรุปผล: การฉีดโบทูลินัมทอกซินชนิดเอสามารถลดความรุนแรงของผื่นสะเก็ดเงินบนหนังศีรษะได้ และสามารถใช้รักษาผื่นสะเก็ดเงินบนหนังศีรษะที่ดื้อต่อการรักษาได้

Wnt Secretion Proteins Modulate Rankl-Induced Expression Of Aire In Thymic Epithelial Cells, Daniel Pollack

Dissertations and Theses

Thymic epithelial cells (TEC) are essential for a proper adaptive immune response by regulating thymocyte development and establishing central tolerance. In the thymus, TECs differentially express Wnt proteins, which activate canonical and non-canonical Wnt signaling pathways. Wnt signaling is thought to regulate cell survival, proliferation, and development although the direct molecular mechanisms in TECs have yet to be elucidated. The inducible inhibition of canonical Wnt signaling with Dkk1 leads to a rapid loss of TEC progenitors as well as a decline in mature Aire-expressing mTECs. Therefore, we explore the role of Wnt ligands potentially responsible for stimulating and/or regulating Wnt …

Sedentary Time And The Cumulative Risk Of Preserved And Reduced Ejection Fraction Heart Failure: From The Multi-Ethnic Study Of Atherosclerosis, Brandi Scot Rariden

UNF Graduate Theses and Dissertations

ABSTRACT

Purpose: The purpose of this study was to examine the relationship between self-reported sedentary time (ST) and the cumulative risk of preserved ejection fraction heart failure (HFpEF) and reduced ejection fraction heart failure (HFrEF) using a diverse cohort of U.S. adults 45-84 years of age.

Methods: Using data from the Multi-Ethnic Study of Atherosclerosis (MESA), we identified 6,814 subjects (52.9% female). All were free of baseline cardiovascular disease. Cox regression was used to calculate the hazard ratios (HR) associated with baseline ST and risk of overall heart failure (HF), HFpEF, and HFrEF. Weekly self-reported ST was dichotomized …

A Scale Space Local Binary Pattern (Sslbp) – Based Feature Extraction Framework To Detect Bones From Knee Mri Scans, Jinyeong Mun

Electronic Theses and Dissertations

The medical industry is currently working on a fully autonomous surgical system, which is considered a novel modality to go beyond technical limitations of conventional surgery. In order to apply an autonomous surgical system to knees, one of the primarily responsible areas for supporting the total weight of human body, accurate segmentation of bones from knee Magnetic Resonance Imaging (MRI) scans plays a crucial role. In this paper, we propose employing the Scale Space Local Binary Pattern (SSLBP) feature extraction, a variant of local binary pattern extractions, for detecting bones from knee images. The proposed methods consist of two phases. …

Proof-Of-Concept Testing Of A Real-Time Mhealth Measure To Estimate Postural Control During Walking: A Potential Application For Mild Traumatic Brain Injuries, Hyunhwa Lee, Sunchul Lee, Laura Salado, Jonica Estrada, Jacob White, Venkatesan Muthukumar, Szu-Ping Lee, Sambit Mohapatra

Nursing Faculty Research

Background: Most individuals with mild traumatic brain injury (mTBI) experience post-injury deficits in postural control. Currently available measures of postural control are lab-based or supervised, which may hinder timely symptom assessment for individuals with mTBI, including Asian populations, who do not seek initial screening post-injury. In this proof-of-concept testing study, we introduce a real-time mobile health (mHealth) system to measure postural control during walking. The proposed mHealth system can be used for home-based symptom assessment and management of mTBI. Methods: In our proposed mHealth system, a smartwatch, a smartphone, and a cloud server communicate to measure, collect, and store body …

Neuroendocrine Tumors Detected In Appendectomy Specimens: Ten-Year Single-Center Experience, Fatma Şenel, Hati̇ce Karaman, Hacer Demi̇r

Turkish Journal of Medical Sciences

Background/aim: The aim of this study was to investigate neuroendocrine tumors (NETs) detected in appendectomy specimens and the incidence and clinicopathologic characteristics of these tumors in our center. Materials and methods: A total of 13,863 patients were evaluated retrospectively. All underwent appendectomy operation in the Kayseri Training and Research Hospital and had a histopathological examination at the Pathology Clinic between January 2007 and March 2017. Age, sex, preoperative clinical findings, operation procedure, and histopathological examination results of the cases reported to be NET are presented. Results: NET was detected in 29 cases (0.2%) in the histopathological examination of 13,863 appendectomy …

Relationship Of Serum Hla-B Alleles And Tnf-? With Rheumatic Heart Disease, Mustafa Azmi̇ Eyi̇ol, Çağri Yayla, Serkan Ünlü, Abdurrahman Tufan, Mustafa Cemri̇, Mehmet Ridvan Yalçin, Nuri̇ Bülent Boyaci

Turkish Journal of Medical Sciences

Background/aim: Acute rheumatic fever and rheumatic heart disease are major causes of morbidity and mortality in developing countries. Genetic studies have determined that the immune response in rheumatic heart disease is genetically controlled and that there is a close relationship between the gene of concern and the class II human leukocyte antigen (HLA) gene. The aim of this study was to evaluate the relationship of serum HLA-B alleles and tumor necrosis factor alpha (TNF-∝) with rheumatic heart disease. Materials and methods: A total of 50 consecutive patients with rheumatic heart disease and 50 controls were enrolled in the study. HLA …

Effect Of Intravitreal Bevacizumab On Macular Thickness: Exploring Serum And Vitreousproangiogenic Biomarkers In Patients With Diabetic Macular Edema, Tayyaba Gul Malik, Syed Shoaib Ahmed, Roquyya Gul, Muhammad Khalil, Abrar Ahmed Malik, Masoom Khan

Turkish Journal of Medical Sciences

Background/aim: This study evaluates diabetic macular-edema (DME) patients for the effect of intravitreal bevacizumab (IVB) injection on macular thickness and proangiogenic biomarkers in serum and vitreous. Materials and methods: Forty DME patients were analyzed for macular thickness (MT). Twelve proangiogenic biomarkers in serum and vitreous were analyzed before and after IVB. Results: Significant decrease in MT with vitreal vascular endothelial growth factor-A (VEGF-A) was observed as expected after IVB, while serum VEGF-A did not follow a decreasing trend in contrast to VEGF-C, which decreased both in serum and vitreous. Other vitreal factors like bone morphogenetic protein-9 (BMP9) and fibroblast growth …

Parvovirus B19 Seroprevalence In Turkish Blood Donors, Şeni̇z Göral, İdi̇l Yeni̇cesu, Gülendam Bozdayi, Aysu Duyan Çamurdan, Ayli̇n Altay Koçak

Turkish Journal of Medical Sciences

Background/aim: Parvovirus risk in blood transfusion has become a popular research topic since there are limited data on parvovirus seroprevalence in blood donors in Turkey. The aim of this study was to investigate parvovirus seroprevalence in blood donors in Turkey. Materials and methods: Blood samples of 988 blood donors admitted to a university blood bank were obtained for parvovirus B19 IgM and IgG detection. The samples were analyzed using the ELISA method. Results: IgM positivity of 3.92% and IgG positivity of 58.9% was detected in the blood samples. Parvovirus IgM positivity was found to be the highest in the age …

The Role Of Melatonin In Preventing Ovarian Tissue Damage In Rats Exposed To Magnetic Fields, Zahi̇de Küçük, Uğurkan Erkayiran, Muzaffer Çaydere, Damla Kayalp, Deni̇z Karçaaltincaba

Turkish Journal of Medical Sciences

Objectives: We observed the efficacy of melatonin in preventing ovarian tissue damage in rats exposed to magnetic fields. Materials and methods: Forty rats were divided into four treatment groups: Group 1, control group (n = 10); Group 2, melatonin administration only (n = 10); Group 3, magnetic field exposure only (n = 10); Group 4, magnetic field exposure with melatonin administration (n = 10). The magnetic field was applied at a dose of 20 μT for 30 min/day for 10 days. Melatonin was orally administered at a dose of 10 mg/kg. We evaluated follicle count, degree of fibrosis, amount of …

The Histopathological Effects Of Calcium Triglyceride Bone Cement Andchitosan On The Healing Of Experimental Bone Defects, Levent Uslucan, Berkem Atalay, Cüneyt Korhan Oral, Mustafa Sami̇ Yildirim, Abdulkadi̇r Burak Çankaya

Turkish Journal of Medical Sciences

Background/aim: This study evaluated the histopathological effects of two different bone grafts, calcium triglyceride bone cement (CTBC) and chitosan, on the healing of experimental bone defects. Materials and methods: Ninety-two Sprague Dawley male rats, with a weight of 240 ± 20 g, were used. Two experimental groups that consisted of 64 rats were divided into four subgroups due to the sacrification days, which were 7, 14, 30, and 60. After creating an 8-mm- long and 1-mm-wide cortico-cancellous bone defect in the right tibia of each rat, CTBC and chitosan were applied to the bone defects. In the main group, after …

Neuropeptide Y Cells Regulate Anxiety Behavior, Katelynn Corder

All ETDs from UAB

Dysregulation of the GABAergic system has long been implicated in anxiety disorders. Classic anxiolytic drugs, such as benzodiazepines, increase GABAergic transmission by modulating GABA¬A receptors, relieving anxiety symptoms. However, these treatments are not always effective and are often accompanied by negative side effects. Glutamate decarboxylase (GAD) is the enzyme responsible for producing GABA. Recent studies have shown that when the isoform GAD67 is reduced in specific brain regions or GABAergic subtypes, differential anxiety effects were found. These studies suggest that targeting specific GABAergic cell subtypes may provide a more effective treatment for anxiety disorders. Neuropeptide Y (NPY) is an abundant …

Post-Transcriptional Regulation Of Myeloid Cell Leukemia 1 In Cancers, Jia Cui

All ETDs from UAB

Apoptosis, a highly regulated process of programmed cell death, is essential for maintaining normal tissue homeostasis. Myeloid cell leukemia 1 (MCL1), an anti-apoptotic BCL-2 family protein, lies at the center of apoptosis regulation. Overexpression of MCL1 has been identified as a key contributor to tumorigenesis and further enables resistance to anti-cancer chemotherapies and radiation. Due to the critical roles of MCL1 in cancer, it is essential to understand the regulatory mechanisms of MCL1 expression in cells. Previous studies have detailed how MCL1 expression is controlled by multiple mechanisms. However, characterization of the post-transcriptional regulation of MCL1 mRNA has been poorly …

Novel Insights Into Neurofibromin Function And Human Neurofibromatosis Type 1 Mutations Using Genetically Engineered Mouse Models, Ashley Nicole Turner

All ETDs from UAB

Loss of NF1 in different developmental and cellular contexts leads to unique physiological outcomes due to loss of neurofibromin function, including embryonic lethality, sporadic cancers, and the genetic disorder NF1. Neurofibromin acts as a tumor suppressor by modulation of RAS signaling, with other functions of this multi-domain protein being less clear. Even within the monogenic disorder of NF1, the clinical heterogeneity and mutational spectrum are immense, revealing the complexity underlying this disorder. There is a huge urgency and need for NF1 therapeutic treatments, and the same urgency to develop in vivo models to better understand NF1 that can be utilized …

Nf-Κb And Methyl-Lysine Signaling In The Epigenetic Regulation Of Memory, William Mitchell Webb

All ETDs from UAB

Epigenetic mechanisms such as DNA methylation and histone methylation are critical regulators of gene transcription during memory consolidation and retrieval. However, the means by which these mechanisms are themselves initiated and directed to specific gene regions, and the extent to which these marks coordinate control of gene expression, remain poorly understood. In this dissertation, we explore the role of methyl-lysine signaling in the epigenetic regulation of gene expression in two contexts. First, we investigated the role of histone H3 lysine 4 tri-methylation (H3K4me3) and DNA 5-hydroxymethylation (5hmC) during memory retrieval, finding that these marks increased globally and at CpG-enriched coding …

Identification Of Molecular Regulators Of Morphogenesis During Early Development Of Xenopus, Ivan Popov

All ETDs from UAB

During embryonic development of all animal species, dramatic changes in morphology occur to transform a single-celled zygote into a well-organized adult body that contains different organs positioned in stereotypical ways for the species. The processes that shape tissues and organs are called morphogenesis, and gastrulation is the first morphogenetic process in embryogenesis. During gastrulation, three germ layers are specified and a set of regionally specific cell movements act in concert to position these germ layers for proper establishment of future body plan of the developing animal. Although factors regulating cell lineage specification have been studied extensively, the molecular machinery controlling …

Molecular Characterization Of The Rare Cftr Mutation P67l As A Model For Genotype-Specific Drug Development And Personalized Medicine In Cystic Fibrosis, Carleen Mae Pomperada Sabusap

All ETDs from UAB

The traditional CFTR functional defect subcategories (i.e. protein misfolding, gating, conductance, etc.) are sometimes inadequate for determining patients most likely to benefit from emerging modulator treatment. We employ the P67L variant as emblematic of ways a thorough biochemical analysis of a rare CF defect can guide new therapeutic approaches, help predict drug response, and facilitate clinical precision. Historically, P67L has been designated a class IV conductance abnormality (i.e., malformed ion pore). In contrast, our studies demonstrate P67L disrupts CFTR protein maturation, prompts misfolding, causes gating defects, and exhibits wild-type like conductance. We show that P67L CFTR is robustly rescued by …

Endothelin-1 And The Diurnal Regulation Of Sodium Excretion, Jermaine Gajrae Johnston

All ETDs from UAB

Healthy individuals typically have a diurnal rhythm in sodium (Na+) excretion, with levels higher during the daytime and lower at nighttime. While the mechanism behind this rhythm is not yet fully understood, molecular clock genes such as Bmal1 may contribute to the diurnal variation in urinary Na+ excretion (UNaV). Endothelin-1 (ET-1) is a peptide that aids in the regulation of Na+ balance through activation of the endothelin B (ETB) receptor. Although the ETB receptor has been shown to play an important role in promoting natriuresis, whether this varies according to time of day is unknown. This dissertation examines the role …

Risk Factors Associated With Multiple Myeloma, Stephen Gragg

All ETDs from UAB

Multiple myeloma (MM) is a hematologic malignancy in which clonal plasma cells accumulate in the bone marrow, leading to the formation of lytic bone lesions, hypercalcemia, anemia, renal insufficiency, and immunosuppression. It develops from a pre-malignant condition known as monoclonal gammopathy of undetermined significance (MGUS), which is prevalent in up to 3% of White populations over the age of 50 years, and twice that in Black populations. Although much progress has been made toward understanding the large scale genomic aberrations that facilitate the formation of MGUS clones and the various copy-number variations and mutations that trigger the development of MM, …

Mechanisms Of Leucine-Rich Repeat Kinase 2 And Alphα-Synuclein In Pathogenesis Of Parkinson Disease, Hisham Abdelmotilib

All ETDs from UAB

Two pathological hallmarks define Parkinson disease (PD) including dopaminergic neurodegeneration in substantia nigra pars compacta (SNpc) and accumulation of α-synuclein insoluble inclusions, called Lewy pathology, in surviving neurons. LRRK2 (encoding Leucine-rich repeat kinase 2) and SNCA (encoding α-synuclein (α-syn)) are two major genes linked to PD. Pathogenic mutations in these two genes cause autosomal dominant (AD) PD. Additionally, genetic variations in LRRK2 and SNCA are associated with increased risk of sporadic PD. Cellular and animal studies using preformed α-syn fibrils (PFF) demonstrate that the fibrils can be internalized by neurons and act as seeds that can recruit and corrupt endogenously …

Effects Of Novel Inhibitors Against Wnt/Β-Catenin Signaling In Ovarian And Triple-Negative Breast Cancers, Abhishek Gangrade

All ETDs from UAB

Ovarian and triple-negative breast cancers (TNBC) are aggressive due to their dependence on Wnt/β-catenin signaling. Niclosamide, a strong inhibitor of Wnt/β-catenin signaling, is an efficacious cytotoxic agent for various cancers in vitro, including ovarian and breast cancers. However, it has cross-reactivity with mTOR, STAT3, and Notch pathways. A limitation of using the agent in animal studies involves its poor water solubility and bioavailability. This study investigates novel compounds based on the structure of niclosamide to improve specificity for the Wnt/β-catenin signaling pathway. The investigation evaluates three questions: 1) whether WNT974 inhibits Wnt/β-catenin signaling in ovarian cancer; 2) whether novel analogs …

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

All ETDs from UAB

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

Mitochondria-To-Nucleus Retrograde Signaling And Its Role In Cancer, Trevor Carden

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Mitochondrial dysfunction is considered a hallmark of cancer. Mitochondria are essential, cellular organelles that participate in processes including energy production, calcium homeostasis and steroid metabolism. Mitochondria have been more recently appreciated for their role in cellular signaling, bringing about a greater understanding of their role in many diseases including cancer. Retrograde signaling is a mechanism by which the nucleus responds to mitochondrial dysfunction by modulating its own transcriptional programs to maintain metabolic and cellular processes. Many genes have already been identified as participants in or mediators of this signaling mechanism; these include cell signaling, metabolic and structural genes as well …

The Mechanism Of Tgf-Β Function In Development Of The Axial Skeleton, Ga I Ban

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THE MECHANISM OF TGF-β FUNCTION IN DEVELOPMENT OF THE AXIAL SKELETON GA I BAN CELL, MOLECULAR DEVELOPMENTAL BIOLOGY ABSTRACT Back pain is caused by degeneration of intervertebral discs (IVD). IVD consists of two compartments: the annulus fibrosus (AF) and the nucleus pulposus (NP). One strategy for treatment of IVD degeneration is stem cell therapy, which would require an in-depth knowledge of how the IVD develops. Currently, the molecular mechanism of IVD development are not well defined. AF and vertebral bodies (VB) are derived from the same embryonic progenitor, sclerotome. Specification of sclerotome is determined by complex interactions among various growth …