Digital Commons Network^™

Focused Transcranial Ultrasound For Treatment Of Neurodegenerative Dementia., Natalie Eleanor Nicodemus, Sergio Becerra, Taylor P Kuhn, Hannah R Packham, John Duncan, Kennedy Mahdavi, Jessica Iovine, Santosh Kesari, Scott Pereles, Mike Whitney, Michael Mamoun, Daniel Franc, Alexander Bystritsky, Sheldon Jordan

Articles, Abstracts, and Reports

Introduction: Preclinical studies support investigation of focused ultrasound for breakdown of cerebral pathologies in neurodegenerative conditions including Alzheimer's disease (AD) and Parkinson's disease (PD).

Methods: A focused transcranial Doppler device with probes (2 MHz, 520 mW/cm

Results: Of all, 62.5% of patients had one or more improved cognitive scores without data incongruence, 87% had stable or improved fine motor scores, and 87.5% had stable or improved gross motor scores. No adverse events were reported.

Discussion: The safety of focused transcranial Doppler and possible enhancement in patient functioning were suggested by outcome data.

A Developmental Study Of Apoptotic Markers And Histamine In Cephalopod Statocysts, Samantha Nicole Leef

Honors Theses and Capstones

Cephalopods can participate in complex navigation using landmarks that show context due to their statocysts. Statocysts are analogous to the vertebrate vestibular and auditory system encased in cartilage rather than bone making them more easily accessible. Age and anatomical dysfunctions are the reasons for many human vestibular malfunctions. Two of these sources are endolymph hydrops and aging. In the past, endolymph pressure changes were attributed to the ineffectual ion transport. Recent studies have illuminated the possibility of histamine receptors in the semicircular canal could be responsible for patients’ endolymph pressure changes rather than the previous belief that the pressure changes …

Long-Term Use Of Beta-Blocker Medication In Pediatric Long Qt Syndrome Patients: Neuropsychological Profiles, Kara J. Rudisill

PCOM Psychology Dissertations

Long QT syndrome (LQTS) is a heart rhythm disorder characterized by a disruption of the heart’s electrical activity that may cause accelerated and uncontrolled heartbeats referred to as ventricular fibrillation. LQTS is primarily treated with beta-blocker medications, which reduce the risk of experiencing an arrhythmia through regulating the heart rate. However, the potential neuropsychological side-effects associated with the use of beta-blocker medication may impact the executive functioning skills, mental health, and behavior of the affected pediatric population at home. As a result, a child’s academic performance and emotional regulation etiology may be misunderstood by his or her parents, caregivers, and …

Improving Access To Clean Water In Rural Ecuador: The Connection Between Willingness To Pay And Population Health, Micalea Leaska

Capstone Collection

Climate change is affecting social and environmental determinants of health through access to safe drinking water, safely managed sanitation systems, and access to health care services and the ability for individuals to break free from unsuitable circumstances. Ecological disturbances such as those caused by climate change can cause a shift in host vectors or a change in habitat that results in a greater likelihood of the pathogen coming in contact with humans. Water, sanitation, and hygiene (WASH) services and their accessibility to populations can directly impact a community’s vulnerability to diseases and limiting factors to increase economic growth. If rural …

Calibrated Short Tr Recovery Mri For Rapid Measurement Of Brain-Blood Partition Coefficient And Correction Of Quantitative Cerebral Blood Flow, Scott William Thalman

Theses and Dissertations--Biomedical Engineering

The high prevalence and mortality of cerebrovascular disease has led to the development of several methods to measure cerebral blood flow (CBF) in vivo. One of these, arterial spin labeling (ASL), is a quantitative magnetic resonance imaging (MRI) technique with the advantage that it is completely non-invasive. The quantification of CBF using ASL requires correction for a tissue specific parameter called the brain-blood partition coefficient (BBPC). Despite regional and inter-subject variability in BBPC, the current recommended implementation of ASL uses a constant assumed value of 0.9 mL/g for all regions of the brain, all subjects, and even all species.

The …

Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford

Theses and Dissertations--Neuroscience

Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that …

Gay Men And Satisfaction With Health Care Interactions, Michael Huggins

Theses and Dissertations--Nursing

The purpose of this research was to determine relationships among depression, anxiety, self-rated physical and mental health, self-advocacy, internalized homophobia, and quality of patient-provider communication to satisfaction with health care interactions. These were measured while controlling for select demographic variables: age; ethnicity; urban or rural domicile; relationship status; household income; highest educational attainment; health insurance; disclosure to health care provider as a gay man; reason for last healthcare visit; and, general health self-rating. The specific aims of this study were to: 1) identify general characteristics of gay men in this sample; 2) examine how levels of satisfaction with health care …

The Effect Of Dorsal Rhizotomy On Renal Sodium Excretion Following Dorsal Spinal Stimulation, Tanko Tijani Ahmed

All Graduate Theses, Dissertations, and Other Capstone Projects

Hypertension is one of the most common risk factors in the development of heart disease, stroke and end stage renal failure. Sympathetic overactivity is believed to be one of the main mechanism behind resistant hypertension. Renal denervation has been used to treat resistant hypertension, although this procedure is an invasive one. Spinal cord stimulation (SCS) is a known modality to treat ischemic pain, angina pectoris, and peripheral vascular diseases. In previous studies in this laboratory, unilateral spinal cord stimulation in spontaneously hypertensive rat (SHR) at 67% of the motor threshold increased urinary sodium and water excretion significantly, without affecting mean …

Analysis Of Gene Transcription Changes Following Chlamydia Pneumoniae Infection Of Thpl Monocytes May Have Relevance To Alzheimer's Disease, Desiré Guthier

PCOM Biomedical Studies Student Scholarship

There is increasing evidence that neuroinflammation caused by infectious agents is an important etiologic factor in neurodegenerative diseases including Alzheimer's disease (AD). One infectious agent that has been associated with AD is Chlamydia pneumoniae (Cpn). Cpn DNA can be detected within peripherally circulating mononuclear cells and there is evidence that infected mononuclear cells could be involved in chronic infection and contribute to inflammation at numerous anatomical sites, including the brain. Understanding Cpn genetic changes progressing from an acute to a chronic infection within monocytes may help to further elucidate. the role of Cpn infected monocytes with regard to …

Mold, Allergic Diseases And Asthma: Assessing The Validity And Usefulness Of Indoor Air Sampling As A Tool In Providing Health Protective Advice To Occupants, William M. Sothern

Dissertations and Theses

Background: Asthma is a major health problem throughout the world, disproportionately affecting occupants of low-income housing, and exposure to damp and moldy living conditions is recognized as a significant risk factor for asthma and other respiratory diseases. However, there are no authoritative health guidance values (HGV's) for airborne mold, and current scientific thought holds that the establishment of such guidelines is not practicable. Nonetheless, environmental practitioners take air samples for mold as a routine component of their indoor environmental investigations and use the laboratory results as a tool together with other findings to guide recommendations for health protective actions. The …

The Copy Number Variation Landscape Of Congenital Anomalies Of The Kidney And Urinary Tract., Miguel Verbitsky, Rik Westland, Alejandra Perez, Krzysztof Kiryluk, Qingxue Liu, Priya Krithivasan, Adele Mitrotti, David A. Fasel, Ekaterina Batourina, Matthew G. Sampson, Monica Bodria, Max Werth, Charlly Kao, Jeremiah Martino, Valentina P. Capone, Asaf Vivante, Shirlee Shril, Byum Hee Kil, Maddalena Marasà, Jun Y. Zhang, Young-Ji Na, Tze Y. Lim, Dina Ahram, Patricia L. Weng, Erin L. Heinzen, Alba Carrea, Giorgio Piaggio, Loreto Gesualdo, Valeria Manca, Giuseppe Masnata, Maddalena Gigante, Daniele Cusi, Claudia Izzi, Francesco Scolari, Joanna A E Van Wijk, Marijan Saraga, Domenico Santoro, Giovanni Conti, Pasquale Zamboli, Hope White, Dorota Drozdz, Katarzyna Zachwieja, Monika Miklaszewska, Marcin Tkaczyk, Daria Tomczyk, Anna Krakowska, Przemyslaw Sikora, Tomasz Jarmoliński, Maria K. Borszewska-Kornacka, Robert Pawluch, Maria Szczepanska, Piotr Adamczyk, Malgorzata Mizerska-Wasiak, Grazyna Krzemien, Agnieszka Szmigielska, Marcin Zaniew, Mark G. Dobson, John M. Darlow, Prem Puri, David E. Barton, Susan L. Furth, Bradley A. Warady, Zoran Gucev, Vladimir J. Lozanovski, Velibor Tasic, Isabella Pisani, Landino Allegri, Lida M. Rodas, Josep M. Campistol, Cécile Jeanpierre, Shumyle Alam, Pasquale Casale, Craig S. Wong, Fangming Lin, Débora M. Miranda, Eduardo A. Oliveira, Ana Cristina Simões-E-Silva, Jonathan M. Barasch, Brynn Levy, Nan Wu, Friedhelm Hildebrandt, Gian Marco Ghiggeri, Anna Latos-Bielenska, Anna Materna-Kiryluk, Feng Zhang, Hakon Hakonarson, Virginia E. Papaioannou, Cathy L. Mendelsohn, Ali G. Gharavi, Simone Sanna-Cherchi

Manuscripts, Articles, Book Chapters and Other Papers

Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (that is, affecting coding regions) CNVs and were enriched for known genomic disorders (GD). Kidney anomaly (KA) cases were most enriched for exonic CNVs, encompassing GD-CNVs and novel deletions; obstructive uropathy (OU) had a lower CNV burden and an intermediate prevalence of GD-CNVs; and vesicoureteral reflux (VUR) had the fewest GD-CNVs but was enriched for novel exonic CNVs, …

Monocytes And Monocyte-Derived Antigen-Presenting Cells Have Distinct Gene Signatures In Experimental Model Of Multiple Sclerosis, Kelly L. Monaghan, Wen Zheng, Gangqing Hu, Edwin C. K. Wan

Faculty & Staff Scholarship

Multiple sclerosis (MS) is a chronic inflammatory disease mediated by a complex interaction between the autoreactive lymphocytes and the effector myeloid cells within the central nervous system (CNS). In a murine model of MS, experimental autoimmune encephalomyelitis (EAE), Ly6Chi monocytes migrate into the CNS and further differentiate into antigen-presenting cells (APCs) during disease progression. Currently, there is no information about gene signatures that can distinguish between monocytes and the monocyte-derived APCs. We developed a surface marker-based strategy to distinguish between these two cell types during the stage of EAE when the clinical symptoms were most severe, and performed transcriptome analysis …

Multi-Antigen Vaccination With Simultaneous Engagement Of The Ox40 Receptor Delays Malignant Mesothelioma Growth And Increases Survival In Animal Models., Peter R Hoffmann, Fukun W Hoffmann, Thomas A Premeaux, Tsuyoshi Fujita, Elisa Soprana, Maddalena Panigada, Glen M Chew, Guilhem Richard, Pooja Hindocha, Mark Menor, Vedbar S Khadka, Youping Deng, Lenny Moise, Lishomwa C Ndhlovu, Antonio Siccardi, Andrew D Weinberg, Anne S De Groot, Pietro Bertino

Articles, Abstracts, and Reports

Malignant Mesothelioma (MM) is a rare and highly aggressive cancer that develops from mesothelial cells lining the pleura and other internal cavities, and is often associated with asbestos exposure. To date, no effective treatments have been made available for this pathology. Herein, we propose a novel immunotherapeutic approach based on a unique vaccine targeting a series of antigens that we found expressed in different MM tumors, but largely undetectable in normal tissues. This vaccine, that we term p-Tvax, is comprised of a series of immunogenic peptides presented by both MHC-I and -II to generate robust immune responses. The peptides were …

Blockade Of Fibroblast Activation Protein In Combination With Radiation Treatment In Murine Models Of Pancreatic Adenocarcinoma., Andrew J Gunderson, Tomoko Yamazaki, Kayla Mccarty, Michaela Phillips, Alejandro F Alice, Shelly Bambina, Lauren Zebertavage, David Friedman, Benjamin Cottam, Pippa Newell, Michael J. Gough, Marka R Crittenden, Pieter Van Der Veken, Kristina H Young

Articles, Abstracts, and Reports

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a fibrotic stroma with a poor lymphocyte infiltrate, in part driven by cancer-associated fibroblasts (CAFs). CAFs, which express fibroblast activation protein (FAP), contribute to immune escape via exclusion of anti-tumor CD8+ T cells from cancer cells, upregulation of immune checkpoint ligand expression, immunosuppressive cytokine production, and polarization of tumor infiltrating inflammatory cells. FAP is a post-proline peptidase selectively expressed during tissue remodeling and repair, such as with wound healing, and in the tumor microenvironment by cancer-associated fibroblasts. We targeted FAP function using a novel small molecule inhibitor, UAMC-1110, and mice with germline knockout …

A Microbial-Based Cancer Vaccine For Induction Of Egfrviii-Specific Cd8+ T Cells And Anti-Tumor Immunity., Lauren Zebertavage, Shelly Bambina, Jessica Shugart, Alejandro Alice, Kyra D Zens, Peter Lauer, Bill Hanson, Michael J. Gough, Marka R Crittenden, Keith S Bahjat

Articles, Abstracts, and Reports

Dysregulated signaling via the epidermal growth factor receptor (EGFR)-family is believed to contribute to the progression of a diverse array of cancers. The most common variant of EGFR is EGFRvIII, which results from a consistent and tumor-specific in-frame deletion of exons 2-7 of the EGFR gene. This deletion generates a novel glycine at the junction and leads to constitutive ligand-independent activity. This junction forms a novel shared tumor neo-antigen with demonstrated immunogenicity in both mice and humans. A 21-amino acid peptide spanning the junctional region was selected, and then one or five copies of this 21-AA neo-peptide were incorporated into …

Is Honey, As Adjunctive Therapy, Effective In Alleviating Nasal Allergy Symptoms?, Arielle N. Ditzel

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether honey used as adjunctive therapy is effective in alleviating nasal allergy symptoms.

STUDY DESIGN: This is a systematic review of three randomized controlled trials published between 2010-2013, all in the English language.

DATA SOURCES: Three randomized controlled trials, which studied the effects of honey used as adjunctive therapy for the relief of nasal allergy symptoms, these were obtained using PubMed.

OUTCOMES MEASURED: The outcome of each study was a patient reported decrease in the number of days and the severity of nasal allergy symptoms including: sneezing, itching, nasal …

Are Plasma Rich Platelets More Effective In Decreasing Chronic Lower Back Pain As Compared To Epidural Injections In Young Adults?, Linda M. Leones

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this selective EBM review is to determine whether or not PRP injections are more effective in decreasing chronic lower back pain as compared to epidural injections in young adults.

Study Design: Systematic review of three English language randomized controlled trials (RCTs), all published after 2012.

Data Sources: Two double-blind RCTs and one randomized open blinded end point (PROBE), which analyzed the effectiveness of PRP and epidural injections in young adults with chronic lower back pain. All studies were found using PubMed.

Outcome(s) Measured: Each of the articles analyzed the pain relief and function ability stated by …

Optimization Of Primary Cilia Detection In Musculoskeletal Tissue, Ragen Engel

Williams Honors College, Honors Research Projects

The objective of this research project was to optimize a laboratory technique for visualizing primary cilia in musculoskeletal tissue of young swine, specifically the growth plate of long bones. This was accomplished through varying fixation procedures, antigen retrieval methods, antibody concentrations, and incubation times. By varying these parameters, a reproducible procedure was developed to examine the primary cilia in multiple tissues including ligament, fascia, and growth plate. This experiment introduced variances in fixation methods, with methanol or formalin. Paraffin and frozen embedding techniques were also varied for comparison with regards to cilia visualization. Results from the acetylated alpha tubulin (aTUB) …

Strategies To Enhance The Anti-Leukemic Activity Of Venetoclax (Abt-199) In Aml Through Targeting Of Mcl-1, Daniel Luedtke

Wayne State University Dissertations

Acute Myeloid Leukemia (AML) is a frustratingly difficult to treat disease (67% 5 year survival for children and 24% for adults). The standard of care, similar to outcomes, has seen few improvements over the last several decades. The Bcl-2 family, which controls cell survival and apoptosis, is dysregulated in AML. Bcl-2, which is overexpressed in AML and associated with chemoresistance, is a promising therapeutic target. The now FDA approved venetoclax (ABT-199) is a BH3 mimetic that is able to bind to anti-apoptotic Bcl-2 and prevent it from sequestering pro-apoptotic Bim. While overall response rates are promising, our lab and others …

Investigation Of The Role For Methyl-Cpg Binding Protein 2 Variant Mbd2_V2 In Cancer Stem Cells And Obesity-Associated Cancers, Emily A. Teslow

Wayne State University Dissertations

Obesity is a risk factor for both TNBC and PCa, and pro-inflammatory features associated with obesity, including upregulated production of ROS, promote CSCs. Previously published work from the Bollig-Fischer laboratory established that TNBC CSCs could be inhibited by neutralizing ROS in culture with H2O2 targeted antioxidants. In this report, antioxidant treatment resulted in the downregulation of mRNA splicing variant MBD2_v2. MBD2_v2 was highly expressed in CSCs versus bulk TNBC cells and supported self-renewal in vitro. As obesity is coupled with increased ROS, we hypothesized that obesity could drive CSCs via MBD2_v2 expression. The work presented in this thesis addressed this …

Novel Insights Into The Use Of Ercc1 As A Biomarker For Response To Platinum-Based Chemotherapy In Lung Cancer, Joshua Ryan Heyza

Wayne State University Dissertations

ERCC1/XPF is a DNA endonuclease with variable expression in primary tumor specimens, and has been investigated as a predictive biomarker for efficacy of platinum-based chemotherapy in non-small cell lung cancers where up to 30-60% of tumors harbor low to undetectable ERCC1 expression. The failure of an international, randomized Phase III clinical trial utilizing ERCC1 expression to predict response to platinum-based chemotherapy suggests additional mechanisms underlying the basic biology of ERCC1 in the response to platinum-DNA damage remain unknown. In this work, we aimed to characterize a panel of ERCC1 knockout cell lines generated via CRISPR-Cas9 where we identified a synthetic …

Effects Of Alpha-Gpc And Huperzine-A On Short Term Memory, Anaerobic Power Output, Post Exhaustion Compared To Caffeine And Placebo In Healthy College Age Students, John P. Isaacs

Online Theses and Dissertations

Introduction: The use of multi-ingredient pre-workout supplements has been steadily on the rise in the fitness industries. Companies make claims about improvements in performance both physically and cognitively for users but seldom provide research to back up the claims made about the ingredients or dosages. Purpose: To examine the effects of Huperzine-A and Alpha-GPC on short term memory and anaerobic power output, post exhaustion compared to caffeine and placebo in healthy college age students. Methods: The study was conducted as a double blind, placebo controlled, randomized design on 62 healthy adults (N=62 height 68.4 ± 3.5 in., weight 78.5 ± …

Mitochondrial Superoxide Disrupts The Metabolic And Epigenetic Landscape Of Cd4, Cassandra M. Moshfegh, Christopher W. Collins, Venugopal Gunda, A. Vasanthakumar, J. Z. Cao, Pankaj K. Singh, L. A. Godley, Adam J. Case

Journal Articles: Eppley Institute

While the role of mitochondrial metabolism in controlling T-lymphocyte activation and function is becoming more clear, the specifics of how mitochondrial redox signaling contributes to T-lymphocyte regulation remains elusive. Here, we examined the global effects of elevated mitochondrial superoxide (O₂^-) on T-lymphocyte activation using a novel model of inducible manganese superoxide dismutase (MnSOD) knock-out. Loss of MnSOD led to specific increases in mitochondrial O₂^- with no evident changes in hydrogen peroxide (H₂O₂), peroxynitrite (ONOO^-), or copper/zinc superoxide dismutase (CuZnSOD) levels. Unexpectedly, both mitochondrial and glycolytic metabolism showed significant reductions …

Fascin Controls Metastatic Colonization And Mitochondrial Oxidative Phosphorylation By Remodeling Mitochondrial Actin Filaments, Shengchen Lin, Chongbiao Huang, Venugopal Gunda, Jianwei Sun, Srikumar P. Chellappan, Zengxun Li, Victoria Izumi, Bin Fang, John Koomen, Pankaj K. Singh, Jihui Hao, Shengyu Yang

Journal Articles: Eppley Institute

The deregulation of the actin cytoskeleton has been extensively studied in metastatic dissemination. However, the post-dissemination role of the actin cytoskeleton dysregulation is poorly understood. Here, we report that fascin, an actin-bundling protein, promotes lung cancer metastatic colonization by augmenting metabolic stress resistance and mitochondrial oxidative phosphorylation (OXPHOS). Fascin is directly recruited to mitochondria under metabolic stress to stabilize mitochondrial actin filaments (mtF-actin). Using unbiased metabolomics and proteomics approaches, we discovered that fascin-mediated mtF-actin remodeling promotes mitochondrial OXPHOS by increasing the biogenesis of respiratory Complex I. Mechanistically, fascin and mtF-actin control the homeostasis of mtDNA to promote mitochondrial OXPHOS. The …

Metabolic Alterations In Pancreatic Cancer Progression, Enza Vernucci, Jaime Abrego, Venugopal Gunda, Surendra K. Shukla, Aneesha Dasgupta, Vikrant Rai, Nina V. Chaika, Kyla Buettner, Alysha Illies, Fang Yu, Audrey J. Lazenby, Benjamin J. Swanson, Pankaj K. Singh

Journal Articles: Eppley Institute

Pancreatic cancer is the third leading cause of cancer-related deaths in the USA. Pancreatic tumors are characterized by enhanced glycolytic metabolism promoted by a hypoxic tumor microenvironment and a resultant acidic milieu. The metabolic reprogramming allows cancer cells to survive hostile microenvironments. Through the analysis of the principal metabolic pathways, we identified the specific metabolites that are altered during pancreatic cancer progression in the spontaneous progression (KPC) mouse model. Genetically engineered mice exhibited metabolic alterations during PanINs formation, even before the tumor development. To account for other cells in the tumor microenvironment and to focus on metabolic adaptations concerning tumorigenic …

The Mitochondrial Deoxyguanosine Kinase Is Required For Cancer Cell Stemness In Lung Adenocarcinoma, Shengchen Lin, Chongbiao Huang, Jianwei Sun, Oana Bollt, Xiuchao Wang, Eric Martine, Jiaxin Kang, Matthew D. Taylor, Bin Fang, Pankaj K. Singh, John Koomen, Jihui Hao, Shengyu Yang

Journal Articles: Eppley Institute

The mitochondrial deoxynucleotide triphosphate (dNTP) is maintained by the mitochondrial deoxynucleoside salvage pathway and dedicated for the mtDNA homeostasis, and the mitochondrial deoxyguanosine kinase (DGUOK) is a rate-limiting enzyme in this pathway. Here, we investigated the role of the DGUOK in the self-renewal of lung cancer stem-like cells (CSC). Our data support that DGUOK overexpression strongly correlates with cancer progression and patient survival. The depletion of DGUOK robustly inhibited lung adenocarcinoma tumor growth, metastasis, and CSC self-renewal. Mechanistically, DGUOK is required for the biogenesis of respiratory complex I and mitochondrial OXPHOS, which in turn regulates CSC self-renewal through AMPK-YAP1 signaling. …

Inhibition Of Geranylgeranyl Diphosphate Synthase Is A Novel Therapeutic Strategy For Pancreatic Ductal Adenocarcinoma, Staci L. Haney, Michelle L. Varney, Yashpal S. Chhonker, Simon Shin, Kamiya Mehla, Ayrianne J. Crawford, Heather Jensen Smith, Lynette M. Smith, Daryl J. Murry, Michael A. Hollingsworth, Sarah A. Holstein

Journal Articles: Eppley Institute

Rab proteins play an essential role in regulating intracellular membrane trafficking processes. Rab activity is dependent upon geranylgeranylation, a post-translational modification that involves the addition of 20-carbon isoprenoid chains via the enzyme geranylgeranyl transferase (GGTase) II. We have focused on the development of inhibitors against geranylgeranyl diphosphate synthase (GGDPS), which generates the isoprenoid donor (GGPP), as anti-Rab agents. Pancreatic ductal adenocarcinoma (PDAC) is characterized by abnormal mucin production and these mucins play important roles in tumor development, metastasis and chemo-resistance. We hypothesized that GGDPS inhibitor (GGDPSi) treatment would induce PDAC cell death by disrupting mucin trafficking, thereby inducing the unfolded …

Protease-Mediated Growth Of Staphylococcus Aureus On Host Proteins Is Opp3 Dependent, Mckenzie K. Lehman, Austin S. Nuxoll, Kelsey J. Yamada, Tammy Kielian, Steven D. Carson, Paul D. Fey

Journal Articles: Pathology and Microbiology

Staphylococcus aureus has the ability to cause infections in multiple organ systems, suggesting an ability to rapidly adapt to changing carbon and nitrogen sources. Although there is little information about the nutrients available at specific sites of infection, a mature skin abscess has been characterized as glucose depleted, indicating that peptides and free amino acids are an important source of nutrients for the bacteria. Our studies have found that mutations in enzymes necessary for growth on amino acids, including pyruvate carboxykinase (ΔpckA) and glutamate dehydrogenase (ΔgudB), reduced the ability of the bacteria to proliferate within a …

Csf Inflammatory Markers Differ In Gram-Positive Versus Gram-Negative Shunt Infections., Gwenn Skar, David Synhorst, Matthew K. Beaver, Jessica N. Snowden

Journal Articles: Pediatrics

BACKGROUND: Cerebrospinal fluid (CSF) shunt placement is frequently complicated by bacterial infection. Shunt infection diagnosis relies on bacterial culture of CSF which can often produce false-negative results. Negative cultures present a conundrum for physicians as they are left to rely on other CSF indices, which can be unremarkable. New methods are needed to swiftly and accurately diagnose shunt infections. CSF chemokines and cytokines may prove useful as diagnostic biomarkers. The objective of this study was to evaluate the potential of systemic and CSF biomarkers for identification of CSF shunt infection.

METHODS: We conducted a retrospective chart review of children with …

Search Strategy For "The Benefits, Burdens, And Risks Of Participation In Pediatric Palliative Care And End Of Life Research: A Systematic Review", Pamela S. Hinds, Vanessa N. Madrigal, Cynthia J. Bell, Cynthia M. Schmidt, Amy R. Newman, Kim Mooney-Doyle, Jessica L. Spruit, Tessie October, Christine A. Fortney, Melissa Kurtz Uveges, Kitty Montgomery, Katherine Patterson Kelly, Meaghann S. Weaver

Search Strategies: Leon S. McGoogan Health Sciences Library

No abstract provided.