Diseases Commons^™

Dichotomous Scoring Of Tdp-43 Proteinopathy From Specific Brain Regions In 27 Academic Research Centers: Associations With Alzheimer's Disease And Cerebrovascular Disease Pathologies, Yuriko Katsumata, David W. Fardo, Walter A. Kukull, Peter T. Nelson

Biostatistics Faculty Publications

TAR-DNA binding protein 43 (TDP-43) proteinopathy is a common brain pathology in elderly persons, but much remains to be learned about this high-morbidity condition. Published stage-based systems for operationalizing disease severity rely on the involvement (presence/absence) of pathology in specific anatomic regions. To examine the comorbidities associated with TDP-43 pathology in aged individuals, we studied data from the National Alzheimer’s Coordinating Center (NACC) Neuropathology Data Set. Data were analyzed from 929 included subjects with available TDP-43 pathology information, sourced from 27 different American Alzheimer’s Disease Centers (ADCs). Cases with relatively unusual diseases including autopsy-proven frontotemporal lobar degeneration (FTLD-TDP or FTLD-tau) …

Als Mutations Of Fus Suppress Protein Translation And Disrupt The Regulation Of Nonsense-Mediated Decay, Marisa Kamelgarn, Jing Chen, Lisha Kuang, Huan Jin, Edward J. Kasarskis, Haining Zhu

Toxicology and Cancer Biology Faculty Publications

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by preferential motor neuron death. Approximately 15% of ALS cases are familial, and mutations in the fused in sarcoma (FUS) gene contribute to a subset of familial ALS cases. FUS is a multifunctional protein participating in many RNA metabolism pathways. ALS-linked mutations cause a liquid–liquid phase separation of FUS protein in vitro, inducing the formation of cytoplasmic granules and inclusions. However, it remains elusive what other proteins are sequestered into the inclusions and how such a process leads to neuronal dysfunction and degeneration. In this study, we developed …

Manganese-Enhanced Magnetic Resonance Imaging: Overview And Central Nervous System Applications With A Focus On Neurodegeneration, Ryan A. Cloyd, Shon A. Koren, Jose F. Abisambra

Physiology Faculty Publications

Manganese-enhanced magnetic resonance imaging (MEMRI) rose to prominence in the 1990s as a sensitive approach to high contrast imaging. Following the discovery of manganese conductance through calcium-permeable channels, MEMRI applications expanded to include functional imaging in the central nervous system (CNS) and other body systems. MEMRI has since been employed in the investigation of physiology in many animal models and in humans. Here, we review historical perspectives that follow the evolution of applied MRI research into MEMRI with particular focus on its potential toxicity. Furthermore, we discuss the more current in vivo investigative uses of MEMRI in CNS investigations and …

Dna Methylation By Restriction Modification Systems Affects The Global Transcriptome Profile In Borrelia Burgdorferi, Timothey Casselli, Yvonne Tourand, Adam Scheidegger, William K. Arnold, Anna Proulx, Brian Stevenson, Catherine A. Brissette

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Prokaryote restriction modification (RM) systems serve to protect bacteria from potentially detrimental foreign DNA. Recent evidence suggests that DNA methylation by the methyltransferase (MTase) components of RM systems can also have effects on transcriptome profiles. The type strain of the causative agent of Lyme disease, Borrelia burgdorferi B31, possesses two RM systems with N6-methyladenosine (m6A) MTase activity, which are encoded by the bbe02 gene located on linear plasmid lp25 and bbq67 on lp56. The specific recognition and/or methylation sequences had not been identified for either of these B. burgdorferi MTases, and it was not previously known whether these RM …

Hdl In Endocrine Carcinomas: Biomarker, Drug Carrier, And Potential Therapeutic, Emily E. Morin, Xiang-An Li, Anna Schwendeman

Physiology Faculty Publications

High-density lipoprotein (HDL) have long been studied for their protective role against cardiovascular diseases, however recently relationship between HDL and cancer came into focus. Several epidemiological studies have shown an inverse correlation between HDL-cholesterol (HDL-C) and cancer risk, and some have even implied that HDL-C can be used as a predictive measure for survival prognosis in for specific sub-population of certain types of cancer. HDL itself is an endogenous nanoparticle capable of removing excess cholesterol from the periphery and returning it to the liver for excretion. One of the main receptors for HDL, scavenger receptor type B-I (SR-BI), is highly …

The Roles Of Primary Cilia In Cardiovascular Diseases, Rajasekharreddy Pala, Maha Jamal, Qamar Alshammari, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are microtubule-based organelles found in most mammalian cell types. Cilia act as sensory organelles that transmit extracellular clues into intracellular signals for molecular and cellular responses. Biochemical and molecular defects in primary cilia are associated with a wide range of diseases, termed ciliopathies, with phenotypes ranging from polycystic kidney disease, liver disorders, mental retardation, and obesity to cardiovascular diseases. Primary cilia in vascular endothelia protrude into the lumen of blood vessels and function as molecular switches for calcium (Ca2+) and nitric oxide (NO) signaling. As mechanosensory organelles, endothelial cilia are involved in blood flow sensing. Dysfunction in endothelial …

Quantitative Gadolinium-Free Cardiac Fibrosis Imaging In End Stage Renal Disease Patients Reveals A Longitudinal Correlation With Structural And Functional Decline, Tori A. Stromp, Tyler J. Spear, Rebecca M. Holtkamp, Kristin N. Andres, Joshua C. Kaine, Wissam H. Alghuraibawi, Steve W. Leung, Brandon K. Fornwalt, Moriel H. Vandsburger

Physiology Faculty Publications

Patients with end stage renal disease (ESRD) suffer high mortality from arrhythmias linked to fibrosis, but are contraindicated to late gadolinium enhancement magnetic resonance imaging (MRI). We present a quantitative method for gadolinium-free cardiac fibrosis imaging using magnetization transfer (MT) weighted MRI, and probe correlations with widely used surrogate markers including cardiac structure and contractile function in patients with ESRD. In a sub-group of patients who returned for follow-up imaging after one year, we examine the correlation between changes in fibrosis and ventricular structure/function. Quantification of changes in MT revealed significantly greater fibrotic burden in patients with ESRD compared to …

Development Of A Diagnostic Marker For Phlebotomus Papatasi To Initiate A Potential Vector Surveillance Program In North America, Austin Merchant, Tian Yu, Jizhe Shi, Xuguo Zhou

Entomology Faculty Publications

Phlebotomus papatasi, an Old World sand fly species, is primarily responsible for the transmission of leishmaniasis, a highly infectious and potentially lethal disease. International travel, especially military rotations, between domestic locations and P. papatasi-prevalent regions in the Middle East poses an imminent threat to the public health of US citizens. Because of its small size and cryptic morphology, identification of P. papatasi is challenging and labor-intensive. Here, we developed a ribosomal DNA-polymerase chain reaction (PCR)-based diagnostic assay that is capable of detecting P. papatasi genomic DNA from mixed samples containing multiple sand flies native to the Americas. Serial …

Hiv Tat And Morphine-Induced Neurodegeneration In A Beclin 1 Hemizygous Mouse Model, Jessica A. Lapierre

FIU Electronic Theses and Dissertations

Early in infection, HIV crosses the blood-brain barrier and induces neuropathology. Viral presence in the CNS coupled with secretion of neurotoxic proteins causes neuroinflammation, glial dysfunction, excitotoxicity, and neuronal death. Despite advances in combined antiretroviral therapy, HIV-infected patients present with a spectrum of cognitive and psychomotor deficits collectively referred to as HIV-associated neurological disorders (HAND). A subset of HAND patients abuses drugs such as opiates like heroin and morphine show an exacerbation and rapid progression of HIV neuropathology; however, the mechanisms of this synergy are not well understood. Autophagy is a lysosomal degradative process which eliminates and recycles cytosolic components …

Modeling In The Physiology Classroom, Sowmya Anjur

Faculty Publications & Research

Physiology and Disease is a Biology elective at IMSA that has been developed to be mostly student-centered. Some examples of student projects include modeling heart structure to reflect function and creating LED arduino monitors to measure heart rate. Students also measure their lung capacity and blood pressure to demonstrate correlation of these values with heart rate, and trace the correlation back to neuronal controls. Projects such as these integrate other disciplines such as engineering and conform to NGSS Science and Engineering standards and NGSS Cross cutting Concepts standards. Students take responsibility for their own learning and articulate better on tests.

Epigenetic Mechanisms Regulating The Functional Effects Of Chronic Alcohol Exposure Of Human Monocyte-Derived Dendritic Cells, Tiyash Parira

FIU Electronic Theses and Dissertations

The effects of alcohol abuse are multi-dimensional since alcohol is widely known to affect both the innate and adaptive immune systems. Recently, epigenetics has come into focus and has been implicated in many diseases as well as substance abuse disorders. Therefore, research efforts of understanding the epigenetic mechanisms underlying substance abuse effects including alcohol abuse have become more predominant.

In our laboratory, we have studied different epigenetic changes induced by alcohol exposure including regulation of histone deacetylases (HDACs), histone quantity, and histone modifications such as acetylation and deacetylation. We have observed differential effects of acute and chronic alcohol exposure in …

Intranasal Rapamycin Ameliorates Alzheimer-Like Cognitive Decline In A Mouse Model Of Down Syndrome, Antonella Tramutola, Chiara Lanzillotta, Eugenio Barone, Andrea Arena, Ilaria Zuliani, Luciana Mosca, Carla Blarzino, D. Allan Butterfield, Marzia Perluigi, Fabio Di Domenico

Chemistry Faculty Publications

Background: Down syndrome (DS) individuals, by the age of 40s, are at increased risk to develop Alzheimer-like dementia, with deposition in brain of senile plaques and neurofibrillary tangles. Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain, prior and after the development of Alzheimer Disease (AD). The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways, including insulin signaling and autophagy, involved in pathology onset and progression. Within this context, the therapeutic use of mTOR-inhibitors may prevent/attenuate the neurodegenerative phenomena. By our work we aimed to rescue mTOR signalling …

Mycobacterium Tuberculosis Inhibitors: Action And Resistance, Pamela K. Garcia-Moreno

FIU Electronic Theses and Dissertations

Tuberculosis, an infectious disease caused by Mycobacterium tuberculosis, has been a global health problem for years. The emergence of drug resistance in this organism generates the necessity of exploring novel targets and developing new drugs. Topoisomerases are enzymes found in all kingdoms of life responsible for overcoming the topological barriers encountered during essential cellular processes. The genomes of mycobacteria encode only one type IA topoisomerase (MtopI), which has been validated as a novel TB drug target. The goal of this study is to obtain new information on the mechanism and resistance of endogenous and synthetic inhibitors of MtopI.

Rv1495 is …

Cell Specific Control Of The Pallidostriatal Pathway, Shubha Verma '19

Student Publications & Research

Parkinson’s Disease is a neurodegenerative disorder of the basal ganglia. The main cause for Parkinson’s Disease is the depletion of dopamine, a neurotransmitter. The basal ganglia contains four major nuclei: the substantia nigra, the subthalamic nucleus, the external globus pallidus, and the striatum. These nuclei communicate with each other by the use of neurons.

Stem Cell Generated Β-Cells: A Possible Solution To The Growing Problem Of Type 1 Diabetes, Danielle Rae Steffen

Biology: Student Scholarship & Creative Works

Type 1 diabetes is a growing problem throughout the world. At this time, there is no functional cure, only various treatment options. However, in recent years there has been a significant increase in both the quantity and quality of research into potential cures for type 1 diabetes. This has led to a variety of new possibilities, the most promising of which are β-cells generated from the patient’s own stem cells.

Triatomines: Trypanosomatids, Bacteria, And Viruses Potential Vectors?, Caroline Barreto Viera, Yanna Reis Praça, Kaio Luis Da Silva Bentes, Paula Beatriz Santiago, Sofia Marcelino Martins Silva, Gabriel Dos Santos Silva, Flávia Nader Motta, Izabela Marques Dourado Bastos, Jaime Martins De Santana, Carla Nunes De Araújo

Harold W. Manter Laboratory: Library Materials

Triatominae bugs are the vectors of Chagas disease, a major concern to public health especially in Latin America, where vector-borne Chagas disease has undergone resurgence due mainly to diminished triatomine control in many endemic municipalities. Although the majority of Triatominae species occurs in the Americas, species belonging to the genus Linshcosteus occur in India, and species belonging to the Triatoma rubrofasciata complex have been also identified in Africa, the Middle East, South-East Asia, and in the Western Pacific. Not all of Triatominae species have been found to be infected with Trypanosoma cruzi, but the possibility of establishing vector transmission …

Triatomines: Trypanosomatids, Bacteria, And Viruses Potential Vectors? [Review], Caroline Barreto Vieira, Yanna Reis Praça, Kaio Luís Da Silva Bentes, Paula Beatriz Santiago, Sofia Marcelino Martins Silva, Gabriel Dos Santos Silva, Flávia Nader Motta, Izabela Marques Dorado Bastos, Jaime Martins De Santana, Carla Nunes De Araújo

Harold W. Manter Laboratory: Library Materials

Triatominae bugs are the vectors of Chagas disease, a major concern to public health especially in Latin America, where vector-borne Chagas disease has undergone resurgence due mainly to diminished triatomine control in many endemic municipalities. Although the majority of Triatominae species occurs in the Americas, species belonging to the genus Linshcosteus occur in India, and species belonging to the Triatoma rubrofasciata complex have been also identified in Africa, the Middle East, South-East Asia, and in the Western Pacific. Not all of Triatominae species have been found to be infected with Trypanosoma cruzi, but the possibility of establishing vector transmission …

Hyperhomocysteinemia As A Risk Factor For Vascular Contributions To Cognitive Impairment And Dementia, Brittani R. Price, Donna M. Wilcock, Erica M. Weekman

Physiology Faculty Publications

Behind only Alzheimer’s disease, vascular contributions to cognitive impairment and dementia (VCID) is the second most common cause of dementia, affecting roughly 10–40% of dementia patients. While there is no cure for VCID, several risk factors for VCID, such as diabetes, hypertension, and stroke, have been identified. Elevated plasma levels of homocysteine, termed hyperhomocysteinemia (HHcy), are a major, yet underrecognized, risk factor for VCID. B vitamin deficiency, which is the most common cause of HHcy, is common in the elderly. With B vitamin supplementation being a relatively safe and inexpensive therapeutic, the treatment of HHcy-induced VCID would seem straightforward; however, …

Hidden Cost Of Disease In A Free-Ranging Ungulate: Brucellosis Reduces Mid-Winter Pregnancy In Elk, Gavin C. Cotterill, Paul C. Cross, Arthur D. Middleton, Jared D. Rogerson, Brandon M. Scurlock, Johan T. Du Toit

Wildland Resources Faculty Publications

Demonstrating disease impacts on the vital rates of free‐ranging mammalian hosts typically requires intensive, long‐term study. Evidence for chronic pathogens affecting reproduction but not survival is rare, but has the potential for wide‐ranging effects. Accurately quantifying disease‐associated reductions in fecundity is important for advancing theory, generating accurate predictive models, and achieving effective management. We investigated the impacts of brucellosis (Brucella abortus) on elk (Cervus canadensis) productivity using serological data from over 6,000 captures since 1990 in the Greater Yellowstone Ecosystem, USA. Over 1,000 of these records included known age and pregnancy status. Using Bayesian multilevel models, …

Myocardial Ischemia Reperfusion Injury: Apoptotic, Inflammatory And Oxidative Stress Role Of Galectin-3, Suhail Al-Salam, Satwat Hashmi

Department of Biological & Biomedical Sciences

Background/aims: Myocardial reperfusion has the potential to salvage the ischemic myocardium after a period of coronary occlusion. Reperfusion, however, can cause a wide spectrum of deleterious effects. Galectin-3 (GAL-3), a beta galactoside binding lectin, is closely associated with myocardial infarction (MI), myocardial fibrosis and heart failure. In our study, we investigated its role in ischemia-reperfusion injuries (IR) as this phenomenon is extremely relevant to the early intervention after acute MI.
Methods: C57B6/J wild type (WT) mice and GAL-3 knockout (KO) mice were used for murine model of IR injury in the heart where a period of 30 minutes ischemia was …

Vancomycin Delays Clindamycin-Induced Fatality In The Hamster Model Of Clostridioides [Clostridium] Difficile Infection, Amelia E. Fox-King, Chrisabelle Mefferd, Jacqueline R. Phan, Nancy O. Nou, Ernesto Abel-Santos, Brian P. Hedlund

LSAMP Poster Presentations

Antibiotics can leave the host gut microbiome susceptible to Clostridioides [Clostridium] difficile colonization and lethal toxin production. For instance, clindamycin-induced susceptibility to C. difficile infection (CDI) results in rapid fatality in hamster models, yet vancomycin has been shown to offer increased survival in hamsters challenged with C. difficile. We aim to develop an antibiotic treatment that will facilitate CDI susceptibility without prompt fatality in hamster models. An antibiotic regimen starting with a continuous vancomycin treatment along with a single clindamycin dosage is thought to reduce the major disruption in the indigenous gut microbiome and prevent clindamycin-induced death. …

In Vitro And Ex-Vivo Evaluation Of Topical Formulations Designed To Minimize Transdermal Absorption Of Vitamin K1, Ramina Nabiee, Barent Dubois, Laura Green, Ajay Sharma, Siu Fun Wong, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Topical application of Vitamin K1 has been demonstrated to effectively treat papulopustular skin rash, a serious and frequently encountered side effect of Epidermal Growth Factor Inhibitors (EGFRIs). Systemic absorption of vitamin K1 from skin and the resultant consequence of antagonizing EGFRIs anticancer effects jeopardizes the clinical acceptability of this rather effective treatment. The purpose of the present study was to rationally formulate and evaluate the release rate and transdermal absorption of a wide range of Vitamin K1 dermal preparations with a variety of physiochemical properties. A library of 33 formulations with were compounded and tested for Vitamin K1 permeation using …

8th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association

Annual Postdoctoral Science Symposium Abstracts

The mission of the Annual Postdoctoral Science Symposium (APSS) is to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience. The MD Anderson Postdoctoral Association convened its inaugural Annual Postdoctoral Science Symposium (APSS) on August 4, 2011.

The APSS provides a professional venue for postdoctoral scientists to develop, clarify, and refine their research as a result of formal reviews and critiques of faculty and other postdoctoral scientists. Additionally, attendees discuss current research on a broad range of subjects while promoting academic interactions and enrichment and developing new collaborations.

Eye Tissue Regeneration: Seam As A Cure For Prevalent Eye Disease, Molly Bute

Biology: Student Scholarship & Creative Works

SEAM (Self-formed ectodermal autonomous multizone) is a form of eye tissue regeneration discovered by Japanese scientists in 2016. This tissue regeneration encompasses tissues from all areas of the human eye. The SEAM forms tissues using stem cells, induced pluripotent stem cells were used in the first study, and produces four concentric zones. The SEAM that has been created was shown to cure corneal blindness in animal models, and has the potential to cure a multitude of human eye diseases in the future.

Pediatric Cancers: Development And Treatment Methods, Makayla M. Walker

Student Publications

Pediatric cancers are cancers that develop in kids and adolescents ages 0-19. Pediatric cancers usually develop in three ways: through inherited gene mutations, parental exposure to toxins, and acquired gene mutations. While cancer can affect children and adults alike, treatment becomes more difficult for children due to their physical predevelopment stages. Therefore, it is important to discuss all methods of treatment when dealing with a particular pediatric cancer in order to choose the most effective method.

Editorial: Ion Channel Trafficking And Cardiac Arrhythmias, Marcel A. G. Van Der Heyden, Brian P. Delisle, Hugues Abriel

Physiology Faculty Publications

No abstract provided.

Astrocyte Activation And The Calcineurin/Nfat Pathway In Cerebrovascular Disease, Susan D. Kraner, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Calcineurin (CN) is a Ca²⁺/calmodulin-dependent protein phosphatase with high abundance in nervous tissue. Though enriched in neurons, CN can become strongly induced in subsets of activated astrocytes under different pathological conditions where it interacts extensively with the nuclear factor of activated T cells (NFATs). Recent work has shown that regions of small vessel damage are associated with the upregulation of a proteolized, highly active form of CN in nearby astrocytes, suggesting a link between the CN/NFAT pathway and chronic cerebrovascular disease. In this Mini Review article, we discuss CN/NFAT signaling properties in the context of vascular disease and …

Justice Served Fresh: Associations Between Food Insecurity, Community Gardening, And Property Value, Micajah Daniels, Courtney Coughenour Ph.D

McNair Poster Presentations

Numerous stakeholders in Nevada have used a variety of efforts to combat the growth of food insecurity facing Nevadans. The purpose of this research project is to understand the association between food insecurity, community gardens, and property value. Following the wealth of scholarship on these topics and data collected from community garden agencies in Southern Nevada, the research questions for this project include: (1) Where are community gardens located in SNV? (2) What efforts community gardens agencies are doing to address food insecurity (most interested in their efforts using community gardens)? (3) What are the perceptions of supports and barriers …

Myocyte [Na+]I Dysregulation In Heart Failure And Diabetic Cardiomyopathy, Sanda Despa

Pharmacology and Nutritional Sciences Faculty Publications

By controlling the function of various sarcolemmal and mitochondrial ion transporters, intracellular Na⁺ concentration ([Na⁺]_i) regulates Ca²⁺ cycling, electrical activity, the matching of energy supply and demand, and oxidative stress in cardiac myocytes. Thus, maintenance of myocyte Na⁺ homeostasis is vital for preserving the electrical and contractile activity of the heart. [Na⁺]_i is set by the balance between the passive Na⁺ entry through numerous pathways and the pumping of Na⁺ out of the cell by the Na⁺/K⁺-ATPase. This equilibrium is perturbed in heart failure, …

Brain Endothelial Erythrophagocytosis And Hemoglobin Transmigration Across Brain Endothelium: Implications For Pathogenesis Of Cerebral Microbleeds, Rudy Chang, Juan Castillo, Alexander C. Zambon, Tatiana B. Krasieva, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Peripheral endothelial cells are capable of erythrophagocytosis, but data on brain endothelial erythrophagocytosis are limited. We studied the relationship between brain endothelial erythrophagocytosis and cerebral microhemorrhage, the pathological substrate of MRI-demonstrable cerebral microbleeds. To demonstrate the erythrophagocytic capability of the brain endothelium, we studied the interactions between brain endothelial cells and red blood cells exposed to oxidative stress in vitro, and developed a new in vitro cerebral microbleeds model to study the subsequent passage of hemoglobin across the brain endothelial monolayer. Using multiple approaches, our results show marked brain endothelial erythrophagocytosis of red blood cells exposed to oxidative stress compared …