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Molecular Mechanisms In Cftr-F508del Degradation And The Functional Defect Of Cftr Absence In Rabbits, Carthic Rajagopalan

Wayne State University Dissertations

Cystic Fibrosis (CF) is the most common, lethal autosomal recessive disorder, and is caused by mutations in the cystic fibrosis transmembrane conductance regulator protein (CFTR), an anion channel that is found in most epithelial cells lining the airway and gut. The most common mutation of CFTR is deletion of phenylalanine at position 508 (CFTR-F508del), which produces a misfolded protein. Through the ubiquitin proteasome system (UPS), this misfolded protein is ubiquitinated and signaled for degradation via the cytosolic proteasome. Previous studies demonstrating experimental restoration of F508DEL-CFTR trafficking to the plasma membrane showed partial function of the chloride channel, raising therapeutic speculations. …

Front Cover, North American Bird Bander

North American Bird Bander

No abstract provided.

A Comparative Study Of Equine Gut Microbiomes Using 16s And 18s Rrna Sequencing, Jillian Jorgenson

Undergraduate Honors Thesis Projects

The gut microbiome of domestic horses (Equus ferus caballus) can be broken down into two primary divisions of interest: (1) prokaryotic composition, consisting of bacteria and archaea and (2) fungal composition. Within the gut, there are also eukaryotic parasite communities that may interact with the microbiome. While each has been the subject of various scientific explorations, in this study we analyze the potential interconnectedness of these categories. To determine the extent to which each component of the gut microbiome/parasitic communities influences the other, DNA was extracted and amplified from the fecal samples of eight horses. A combination of …

His Friend Judas: Why Didn't He Betray His Messiah?, Trevan Hatch

Faculty Publications

A question that Christians might ask is, if Jesus was so entrenched within and embracive of Judaism, then why did he condemn Jewish leaders and why was he ultimately rejected and killed by his fellow Jews? In this and the next four chapters (chapters 6–10) we will challenge the assumptions of that very question and illustrate that “the Jews” did not reject and kill Jesus, and that Jesus did not reject and condemn “the Jews.” We will explore the relationship between Jesus and his peers. We start in this chapter by looking at Judas, whose story is perhaps Exhibit A …

Differential Oviposition And Offspring Success Of Gray Treefrogs In The Presence Of An Invasive Fish, Geoffrey R. Smith, Johanna J. Harmon

Faculty Publications

No abstract provided.

Parkinson's Disease And The Gastrointestinal Microbiome, Michal Lubomski, Ai Huey Tan, Shen-Yang Lim, Andrew J. Holmes, Ryan L. Davis, Carolyn M. Sue

Medical Papers and Journal Articles

Recently, there has been a surge in awareness of the gastrointestinal microbiome (GM) and its role in health and disease. Of particular note is an association between the GM and Parkinson’s disease (PD) and the realisation that the GM can act via a complex bidirectional communication between the gut and the brain. Compelling evidence suggests that a shift in GM composition may play an important role in the pathogenesis of PD by facilitating the characteristic ascending neurodegenerative spread of α-synuclein aggregates from the enteric nervous system to the brain. Here, we review evidence linking GM changes with PD, highlighting mechanisms …

Advances In Screening For Undiagnosed Atrial Fibrillation For Stroke Prevention And Implications For Patients With Obstructive Sleep Apnoea: A Literature Review And Research Agenda, Nestor Gahungu, Christopher Judkins, Eli Gabbay, David Playford

Medical Papers and Journal Articles

Atrial fibrillation (AF) is the most common type of sustained cardiac arrhythmia encountered in clinical practice, and its burden is expected to increase in most developed countries over the next few decades. Because AF can be silent, it is often not diagnosed until an AF-related complication occurs, such as stroke. AF is also associated with increased risk of heart failure, lower quality of life, and death. Anticoagulation has been shown to dramatically decrease embolic risk in the setting of atrial fibrillation, resulting in growing interest in early detection of previously undiagnosed AF. Newly developed monitoring devices have improved the detection …

Developing A Practice-Based Research Agenda For Grief And Bereavement Care, Ashton Hay, Christopher W. Hall, Margaret Sealey, Elizabeth Lobb, Lauren J. Breen

Medical Papers and Journal Articles

We aimed to identify practitioners’ perspectives on current research priorities in grief and bereavement care. Grief and bereavement care providers were invited to participate in a three-phase Delphi study to create expert consensus on the top priorities for grief and bereavement research. A total of 140 participants completed Phase 1, 84 completed Phase 2, and 70 completed Phase 3. These top 10 research priorities form the basis of a practice-based research agenda for grief and bereavement care to enable researchers to respond to key issues in grief and bereavement care that will ultimately improve the lives of bereaved people.

Genetic Influence On Scar Height And Pliability After Burn Injury In Individuals Of European Ancestry: A Prospective Cohort Study, Hilary J. Wallace, Gemma Cadby, Phillip E. Melton, Fiona M. Wood, Sian Falder, Margaret M. Crowe, Lisa J. Martin, Karen Marlow, Sarah V. Ward, Mark W. Fear

Medical Papers and Journal Articles

After similar extent of injury there is considerable variability in scarring between individuals, in part due to genetic factors. This study aimed to identify genetic variants associated with scar height and pliability after burn injury. An exome-wide array association study and gene pathway analysis were performed on a prospective cohort of 665 patients treated for burn injury. Outcomes were scar height (SH) and scar pliability (SP) sub-scores of the modified Vancouver Scar Scale (mVSS). DNA was genotyped using the Infinium^® HumanCoreExome-24 BeadChip. Associations between genetic variants (single nucleotide polymorphisms) and SH and SP were estimated using an additive genetic …

Impulse Control Disorders In Dopamine Agonist-Treated Hyperprolactinemia: Prevalence And Risk Factors, Sunita M.C De Sousa, John Baranoff, R Louise Rushworth, Jessica Butler, Jane Sorbello, Juanita Vorster, Tanya Thompson, Ann I. Mccormack, Warrick J. Inder, David J. Torpy

Medical Papers and Journal Articles

Context: There are growing reports of dopamine agonist (DA)-induced impulse control disorders (ICDs) in hyperprolactinemic patients. However, the magnitude of this risk and predictive factors remain uncertain.

Objective: To determine ICD prevalence and risk factors in DA-treated hyperprolactinemic patients compared to community controls.

Design, Setting and Participants: Multicenter cross-sectional analysis of 113 patients and 99 healthy controls.

Main Outcome Measures: Participants completed a neuropsychological questionnaire consisting of the Depression Anxiety Stress Scale (DASS21), Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s disease (QUIP-S), Hypersexual Behavior Inventory (HBI), Hypersexual Behavior Consequences Scale and Social Desirability Response Set Scale. Demographic and clinical data were …

Exposure To Second Hand Smoke And 10-Year (2002–2012) Incidence Of Cardiovascular Disease In Never Smokers: The Attica Cohort Study, Elena Critselis, Demosthenes B. Panagiotakos, Ekavi N. Georgousopoulou, Paraskevi Katsaounou, Christina Chrysohoou, Christos Pitsavos

Medical Papers and Journal Articles

Background: Despite WHO Framework Convention of Tobacco Control (FCTC) adoption, effective implementation of national smoking bans remains pending in several countries. This study quantified the association of second hand smoke (SHS) exposure and 10-year cardiovascular disease (CVD) among never smokers in such settings.

Methods: In 2001–2002, a sample of 1514 males and 1528 females (range: 18–89 years old) were randomly selected in Greece. Frequency and duration of SHS exposure (i.e. exposure extending >30 min/day) within the home and/or workplace were assessed by interview. Following a 10-year follow-up period (2002–2012), incidence of non-fatal and fatal CVD (ICD-10) was evaluated among n …

Lipoprotein (A) And 10-Year Cardiovascular Disease Incidence In Apparently Healthy Individuals: A Sex-Based Sensitivity Analysis From Attica Cohort Study, Matina Kouvari, Demosthenes B. Panagiotakos, Christina Chrysohoou, Ekavi N. Georgousopoulou, Mary Yannakoulia, Dimitrios Tousoulis, Christos Pitsavos

Medical Papers and Journal Articles

The association between lipoprotein (a) (Lp(a)) and 10-year first fatal/nonfatal cardiovascular disease (CVD) risk in apparently healthy men and women was evaluated. The ATTICA prospective study was conducted during 2001-2012 and included n = 1514 men and n = 1528 women (age >18 years) from the greater Athens area, Greece. Follow-up CVD assessment (2011-2012) was achieved in n = 2020 participants (n = 317 cases); baseline Lp(a) was measured in n = 1890 participants. The recommended threshold of 50 mg/dL was used to define abnormal Lp(a) status. Ten-year CVD-event rate was 14% and 24% in participants with Lp(a)Lp(a) ≥50 mg/dL, …

Managing Anxiety Disorders In Adults, Gregory Wilkins, Gavin Andrews, Caroline Bell, Philip Boyce, Christopher Gale, Ronald Rapee, Lisa Lampe

Medical Papers and Journal Articles

The GP has a key role in identifying patients presenting with anxiety symptoms and ensuring appropriate acute and long-term management. There are two key messages for GPs to follow: once you have made a diagnosis of an anxiety disorder, tell the patient you have a treatment for it. Second, do not let your anxiety lead you to prescribe inappropriately or overinvestigate for all possible differential diagnoses.

The Potential Therapeutic Effects Of Creatine Supplementation On Body Composition And Muscle Function In Cancer, C M. Fairman, K L. Kendall, Nicolas H. Hart, D R. Taaffe, D A. Galvao, R U. Newton

Health Sciences Papers and Journal Articles

Low muscle mass in individuals with cancer has a profound impact on quality of life and independence and is associated with greater treatment toxicity and poorer prognosis. Exercise interventions are regularly being investigated as a means to ameliorate treatment-related adverse effects, and nutritional/supplementation strategies to augment adaptations to exercise are highly valuable. Creatine (Cr) is a naturally-occurring substance in the human body that plays a critical role in energy provision during muscle contraction. Given the beneficial effects of Cr supplementation on lean body mass, strength, and physical function in a variety of clinical populations, there is therapeutic potential in individuals …

Treatment, Prevention And Public Health Management Of Impetigo, Scabies, Crusted Scabies And Fungal Skin Infections In Endemic Populations: A Systematic Review, Philippa J. May, Steven Y.C Tong, Andrew C. Steer, Bart J. Currie, Ross M. Andrews, Jonathan R. Carapetis, Asha C. Bowen

Health Sciences Papers and Journal Articles

We conducted a systematic review of the treatment, prevention and public health control of skin infections including impetigo, scabies, crusted scabies and tinea in resource-limited settings where skin infections are endemic. The aim is to inform strategies, guidelines and research to improve skin health in populations that are inequitably affected by infections of the skin and the downstream consequences of these. The systematic review is reported according to the PRISMA statement. From

1759 titles identified, 81 full text studies were reviewed and key findings outlined for impetigo, scabies, crusted scabies and tinea. Improvements in primary care and public health management …

Increased Risk Of Blood Transfusion In Patients With Diabetes Mellitus Sustaining Non-Major Burn Injury, Linda Mai, Katrina Spilsbury, Dale W. Edgar, Aaron Berghuber, Fiona M. Wood

Health Sciences Papers and Journal Articles

Background: Due to the increased mortality and morbidity associated with blood transfusion, identifying modifiable predictors of transfusion are vital to prevent or minimise blood use. We hypothesised that burn patients with diabetes mellitus were more likely to be prescribed a transfusion. These patients tend to have increased age, number of comorbidities, infection risk and need for surgery which are all factors reported previously to be associated with blood use.

Objective: To determine whether patients with diabetes mellitus who have sustained a burn ≤20% total body surface area (TBSA) are at higher risk of receiving red blood cell transfusion compared to …

Proteomic Analysis Of Cortical Neuronal Cultures Treated With Poly-Arginine Peptide-18 (R18) And Exposed To Glutamic Acid Excitotoxicity, Gabriella Macdougall, Ryan S. Anderton, Frank L. Mastaglia, Neville W. Knuckey, Bruno P. Meloni

Health Sciences Papers and Journal Articles

Poly-arginine peptide-18 (R18) has recently emerged as a highly effective neuroprotective agent in experimental stroke models, and is particularly efficacious in protecting cortical neurons against glutamic acid excitotoxicity. While we have previously demonstrated that R18 can reduce excitotoxicity-induced neuronal calcium influx, other molecular events associated with R18 neuroprotection are yet to investigated. Therefore, in this study we were particularly interested in protein expression changes in R18 treated neurons subjected to excitotoxicity. Proteomic analysis was used to compare protein expression patterns in primary cortical neuronal cultures subjected to: (i) R18-treatment alone (R18); (ii) glutamic acid excitotoxic injury (Glut); (iii) R18-treatment and …

Altered Gut Microbiome In Parkinson's Disease And The Influence Of Lipopolysaccharide In A Human Α-Synuclein Over-Expressing Mouse Model, Anastazja M. Gorecki, Leah Preskey, Megan C. Bakeberg, Jade E. Kenna, Christi Gildenhuys, Gabriella Macdougall, Sarah A. Dunlop, Frank L. Mastaglia, P Anthony Akkari, Frank Koengten, Ryan S. Anderton

Health Sciences Papers and Journal Articles

The interaction between the gut microbiota and alpha-synuclein (αSyn) aggregation in Parkinson’s disease (PD) is receiving increasing attention. The objective of this study was to investigate gut microbiota, and effects of an inflammatory lipopolysaccharide (LPS) trigger in a human αSyn over-expressing mouse model of PD (Thy1-αSyn). Stool samples from patients with confirmed PD and Thy1-αSyn mice were analyzed using 16S ribosomal RNA sequencing. Compared to healthy controls, the relative abundance of mucin-degrading Verrucomicrobiae and LPS-producing Gammaproteobacteria were greater in PD patients. In mice, the abundance of Gammaproteobacteria was negligible in both Thy1-αSyn and wild-type (WT) animals, while Verrucomicrobiae were reduced …

Entomological Assessment Of Dengue Virus Transmission Risk In Three Urban Areas Of Kenya, Sheila B. Agha, David P. Tchouassi, Michael J. Turell, Armanda D.S. Bastos, Rosemary Sang

All Peer-Reviewed Publications

Urbanization is one of the major drivers of dengue epidemics globally. In Kenya, an intriguing pattern of urban dengue virus epidemics has been documented in which recurrent epidemics are reported from the coastal city of Mombasa, whereas no outbreaks occur in the two major inland cities of Kisumu and Nairobi. In an attempt to understand the entomological risk factors underlying the observed urban dengue epidemic pattern in Kenya, we evaluated vector density, human feeding patterns, vector genetics, and prevailing environmental temperature to establish how these may interact with one another to shape the disease transmission pattern. We determined that (i) …

Ordered Steps, Or, The Wards Of India : A Biograpy Of The Lives Of Ernest Fremont Ward And Phebe Elizabeth Cox Ward, Missionaries To India, 1880-1927, Ethel Ellen Ward

Heritage Material

No abstract provided.

Lives Of Early Methodist Preachers, A. Stephens, Thomas Jackson

Heritage Material

No abstract provided.

Diuretic, Natriuretic, And Vasodepressor Activity Of A Lipid Fraction Enhanced In Medium Of Cultured Mouse Medullary Interstitial Cells By A Selective Faah Inhibitor, Zdravka P. Daneva

Theses and Dissertations

The relationship between the endocannabinoid system in the renal medulla and the long-term regulation of blood pressure is not well understood. To investigate the possible role of the endocannabinoid system in renomedullary interstitial cells, mouse medullary interstitial cells (MMICs) were obtained, cultured and characterized for their responses to treatment with a selective inhibitor of fatty acid amide hydrolase (FAAH), PF-3845. Treatment of MMICs with PF-3845 increased cytoplasmic lipid granules detected by Sudan Black B staining and multilamellar bodies identified by transmission electron microscopy. HPLC analyses of lipid extracts of MMIC culture medium revealed a 205nm-absorbing peak that showed responsiveness to …

Characterization Of The Novel Interaction Between Neisseria Gonorrhoeae Tdfj And Its Human Ligand S100a7, Stavros Maurakis

Theses and Dissertations

Neisseria gonorrhoeae is an obligate human pathogen that causes the common STI gonorrhea, which presents a growing threat to global health. The WHO estimated 78 million new cases of gonorrhea worldwide in 2017, with estimates of 820,000 new cases in the United States alone according to the CDC. High-frequency phase and antigenic variation inherent in N. gonorrhoeae, coupled with its natural ability to rapidly acquire and stably integrate antimicrobial resistance factors into its genome, have culminated in an infection against which there is no effective vaccine, and for which the list of viable therapeutic options is quickly shrinking. Moreover, no …

Estimating Causal Effects In The Presence Of Spatial Interference, Keith W. Zirkle

Theses and Dissertations

Environmental epidemiologists are increasingly interested in establishing causality between exposures and health outcomes. A popular model for causal inference is the Rubin Causal Model (RCM), which typically seeks to estimate the average difference in study units' potential outcomes. If the exposure Z is binary, then we may express this as E[Y(Z=1)-Y(Z=0)]. An important assumption under RCM is no interference; that is, the potential outcomes of one unit are not affected by the exposure status of other units. The no interference assumption is violated if we expect spillover or diffusion of exposure effects based on units' proximity to other units and …

Regulation Of Cancer-Specific Mirnas By Mda-7/Il-24, Danielle Scheunemann

Theses and Dissertations

Melanoma differentiation associated gene 7/Interleukin-24 (MDA-7/IL-24) is a secreted cytokine which acts as a tumor suppressor. It is capable of selectively killing cancer cells, regardless of anatomic origin, while sparing normal cells. miRNAs are master regulators of gene expression that can play two roles in cancer: tumor-suppression and oncogenesis. We identified a number of miRNAs that are regulated by MDA-7/IL-24 using a PCR plate array containing probes for miRNAs known to play a role in prostate cancer. We independently validated the array with qRT-PCR to identify three miRNAs which are downregulated by MDA-7/IL-24 treatment in DU145, PC3, and PC3ML prostate …

Translational Insights Into The Genetic Etiology Of Mental Health Disorders: Examining Risk Factor Models, Neuroimaging, And Current Dissemination Practices, Jessica L. Bourdon

Theses and Dissertations

Psychiatric genetics is a basic science field that has potential for practical application and effective translation. To date, translational frameworks utilized by this field have been linear (e.g., sequential) in nature, focusing on molecular genetic information. It is proposed that non-linear (e.g., socio-ecological) frameworks are a better way to immediately translate non-molecular genetic information. This dissertation explored the translation of psychiatric genetic information in two ways. First, a survey was sent to academic stakeholders to assess the state of the science regarding the translation of genetic information to the clinical care of mental health disorders. Findings from this indicate a …

Social Jetlag, Depressive Symptoms, And Longitudinal Outcomes In College Students, Morgan P. Reid

Theses and Dissertations

Social jetlag refers to the chronic shift in sleep timing between work and free days and has been associated with a variety of negative physical and psychological outcomes. Existing research on social jetlag has relied heavily on cross-sectional studies, preventing researchers and practitioners from assessing the effects of social jetlag over time. The current study used longitudinal data to explore the directionality of the association between social jetlag and depressive symptoms as well as the longitudinal associations between social jetlag, academic performance, and wellbeing in college students. Gender and race were also assessed as potential moderators of these associations. Cross-lagged …

Role Of Sarm1 In Chronic Immune-Mediated Central Nervous System Inflammation, Kenneth E. Viar Ii

Theses and Dissertations

SARM1 is an injury-induced nicotinamide adenine dinucleotide nucleosidase (NADase) that was previously shown to promote axonal degeneration in response to traumatic, toxic, and excitotoxic stressors. This raises the question of whether a SARM1-dependent program of axonal degeneration is central to a common pathway contributing to disease burden in neurological disorders. The degree to and mechanism by which SARM1 inactivation decreases the pathophysiology of such disorders is of interest to establish the rationale to pursue SARM1 as a therapeutic target. In this study, we compare the course and pathology of experimental autoimmune encephalomyelitis (EAE) in Sarm1-knockout (KO) mice and wild-type …

The Role Of Sphingosine Kinase 2 In Alcoholic Liver Disease, Eric K. Kwong

Theses and Dissertations

Alcoholic liver disease (ALD) is one of the most common liver diseases worldwide characterized by the accumulation of lipids within the liver, inflammation and the possibility of progressing to cirrhosis and liver failure. More importantly, there are currently no effective treatments for ALD and liver transplantation remains the only therapeutic option for end-stage liver disease. Previous studies have shown that ALD is a result of a combination of endoplasmic reticulum (ER) stress, lipid metabolism dysregulation and inflammation. It has been previously reported that alcohol disrupts gut microbiota homeostasis and causes increased endotoxins that contribute to the pathology of ALD. However, …

Behavioral And Immune Implications Of Chronic Predator Exposure In Adolescent Mice, Kimaya R. Council

Theses and Dissertations

Evidence suggests that toxic stressors introduced early in development have prolonged effects on neuronal function due, in part, to the maturation of the hypothalamic- pituitary- adrenal (HPA) axis during adolescence. Early life stress has been implicated as a driver of mood and anxiety disorders, like depression and post-traumatic stress disorder - the extent to which appears to be sex dependent. While it is known that early life stress results in several consequences in adulthood, the mechanisms by which these changes manifest are unclear. Stress-induced changes in mood and behavior are often associated with alterations in inflammatory reactivity in both the …