Medicine and Health Sciences Commons^™

Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast

Senior Honors Theses

This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms are partially …

Effectiveness Of Individual Nutrition Education Compared To Group Education, In Improving Anthropometric And Biochemical Indices Among Hypertensive Adults With Excessive Body Weight: A Randomized Controlled Trial, Danuta Gajewska, Alicja Kucharska, Marcin Kozak, Shahla M. Wunderlich, Joanna Niegowska

Department of Nutrition and Food Studies Scholarship and Creative Works

Objective: The study aims to compare the effectiveness of individual and group nutrition education methods in improving key anthropometric and biochemical markers in drug-treated, overweight-obese hypertensive adults. Methods: The randomized trial included 170 patients with pharmacologically well-controlled primary hypertension and body mass index (BMI) ≥ 25 kg/m². For six months, the patients received six sessions, either one-to-one individual nutrition education (IE, n = 89) or group education (GE, n= 81), developed by dietitians. Anthropometric measurements, body composition, and fasting measures of biochemical parameters were obtained at baseline and after six months of intervention. Results: 150 patients completed the …

Allele-Specific Rna Interference Prevents Neuropathy In Charcot-Marie-Tooth Disease Type 2d Mouse Models., Kathryn H Morelli, Laurie B Griffin, Nettie K Pyne, Lindsay M Wallace, Allison M Fowler, Stephanie N Oprescu, Ryuichi Takase, Na Wei, Rebecca Meyer-Schuman, Dattatreya Mellacheruvu, Jacob O Kitzman, Samuel G Kocen, Timothy J Hines, Emily L Spaulding, James R Lupski, Alexey Nesvizhskii, Pedro Mancias, Ian J Butler, Xiang-Lei Yang, Ya-Ming Hou, Anthony Antonellis, Scott Q Harper, Robert W Burgess

Department of Biochemistry and Molecular Biology Faculty Papers

Gene therapy approaches are being deployed to treat recessive genetic disorders by restoring the expression of mutated genes. However, the feasibility of these approaches for dominantly inherited diseases - where treatment may require reduction in the expression of a toxic mutant protein resulting from a gain-of-function allele - is unclear. Here we show the efficacy of allele-specific RNAi as a potential therapy for Charcot-Marie-Tooth disease type 2D (CMT2D), caused by dominant mutations in glycyl-tRNA synthetase (GARS). A de novo mutation in GARS was identified in a patient with a severe peripheral neuropathy, and a mouse model precisely recreating the mutation …

Influence Of Metabolic Capacity On The Consequences Of Spreading Depolarization, Katelyn M. Reinhart

Biomedical Sciences ETDs

In the United States, stroke is the fifth leading cause of death and stroke survivors often face long-term disability. After ischemic stroke, the ischemic territory can expand and recruit previously viable tissues into the lesioned area. During this critical period, there is an unsettling lack of interventions that prevent or treat secondary neuronal loss and cognitive decline. Clinical subdural recordings have revealed a close link between infarct progression and waves of spreading depolarizations (SD) in the acutely injured brain. SD is a slowly progressing wave of near-complete neuroglia depolarization that is extremely energetically demanding and this additional metabolic ‘hit’ …

Genetic Screening For Breast Cancer In The Primary Care Setting, Michael Nick Gomez

Doctor of Nursing Practice

The purpose of this project was to increase adherence to the U.S. Preventive Services Task Force and National Comprehensive Cancer Network guidelines for breast cancer screening and genetic testing.Screening for breast cancer risk factors including genetic testing helps reduce the incidence of breast cancer. A protocol was developed based on national clinical guidelines to increase screening and genetic testing for breast cancer. Provider responsibilities included screening all patients 18 years of age and older for risks factors of breast cancer, referring patients with a significant risk based on the screening for genetic testing and providing referrals for genetic counseling …

A Macaque Connectome For Large-Scale Network Simulations In Thevirtualbrain, Kelly Shen, Gleb Bezgin, Michael Schirner, Petra Ritter, Stefan Everling, Anthony R. Mcintosh

Brain and Mind Institute Researchers' Publications

© 2019, The Author(s). Models of large-scale brain networks that are informed by the underlying anatomical connectivity contribute to our understanding of the mapping between the structure of the brain and its dynamical function. Connectome-based modelling is a promising approach to a more comprehensive understanding of brain function across spatial and temporal scales, but it must be constrained by multi-scale empirical data from animal models. Here we describe the construction of a macaque (Macaca mulatta and Macaca fascicularis) connectome for whole-cortex simulations in TheVirtualBrain, an open-source simulation platform. We take advantage of available axonal tract-tracing datasets and enhance the existing …

Predator-Induced Fear Causes Ptsd-Like Changes In The Brains And Behaviour Of Wild Animals, Liana Y. Zanette, Emma C. Hobbs, Lauren E. Witterick, Scott A. Macdougall-Shackleton, Michael Clinchy

Brain and Mind Institute Researchers' Publications

© 2019, The Author(s). Predator-induced fear is both, one of the most common stressors employed in animal model studies of post-traumatic stress disorder (PTSD), and a major focus of research in ecology. There has been a growing discourse between these disciplines but no direct empirical linkage. We endeavoured to provide this empirical linkage by conducting experiments drawing upon the strengths of both disciplines. Exposure to a natural cue of predator danger (predator vocalizations), had enduring effects of at least 7 days duration involving both, a heightened sensitivity to predator danger (indicative of an enduring memory of fear), and elevated neuronal …

Consciousness-Specific Dynamic Interactions Of Brain Integration And Functional Diversity, Andrea I. Luppi, Michael M. Craig, Ioannis Pappas, Paola Finoia, Guy B. Williams, Judith Allanson, John D. Pickard, Adrian M. Owen, Lorina Naci, David K. Menon, Emmanuel A. Stamatakis

Brain and Mind Institute Researchers' Publications

Prominent theories of consciousness emphasise different aspects of neurobiology, such as the integration and diversity of information processing within the brain. Here, we combine graph theory and dynamic functional connectivity to compare resting-state functional MRI data from awake volunteers, propofol-anaesthetised volunteers, and patients with disorders of consciousness, in order to identify consciousness-specific patterns of brain function. We demonstrate that cortical networks are especially affected by loss of consciousness during temporal states of high integration, exhibiting reduced functional diversity and compromised informational capacity, whereas thalamo-cortical functional disconnections emerge during states of higher segregation. Spatially, posterior regions of the brain’s default mode …

Sighting Acute Myocardial Infarction Through Platelet Gene Expression., Giuliana Gobbi, Cecilia Carubbi, Guidantonio Malagoli Tagliazucchi, Elena Masselli, Prisco Mirandola, Filippo Pigazzani, Antonio Crocamo, Maria Francesca Notarangelo, Sergio Suma, Elvezia Paraboschi, Giuseppe Maglietta, Srikanth Nagalla, Giulia Pozzi, Daniela Galli, Mauro Vaccarezza, Paolo Fortina, Sankar Addya, Adam Ertel, Paul Bray, Stefano Duga, Carlo Berzuini, Marco Vitale, Diego Ardissino

Department of Cancer Biology Faculty Papers

Acute myocardial infarction is primarily due to coronary atherosclerotic plaque rupture and subsequent thrombus formation. Platelets play a key role in the genesis and progression of both atherosclerosis and thrombosis. Since platelets are anuclear cells that inherit their mRNA from megakaryocyte precursors and maintain it unchanged during their life span, gene expression profiling at the time of an acute myocardial infarction provides information concerning the platelet gene expression preceding the coronary event. In ST-segment elevation myocardial infarction (STEMI), a gene-by-gene analysis of the platelet gene expression identified five differentially expressed genes: FKBP5, S100P, SAMSN1, CLEC4E and S100A12. The logistic regression …

Altered Motor, Anxiety-Related And Attentional Task Performance At Baseline Associate With Multiple Gene Copies Of The Vesicular Acetylcholine Transporter And Related Protein Overexpression In Chat::Cre+ Rats, Craig P. Mantanona, Johan Alsiö, Joanna L. Elson, Beth M. Fisher, Jeffrey W. Dalley, Timothy Bussey, Ilse S. Pienaar

Brain and Mind Institute Researchers' Publications

© 2019, The Author(s). Transgenic rodents expressing Cre recombinase cell specifically are used for exploring mechanisms regulating behavior, including those mediated by cholinergic signaling. However, it was recently reported that transgenic mice overexpressing a bacterial artificial chromosome containing choline acetyltransferase (ChAT) gene, for synthesizing the neurotransmitter acetylcholine, present with multiple vesicular acetylcholine transporter (VAChT) gene copies, resulting in altered cholinergic tone and accompanying behavioral abnormalities. Since ChAT::Cre+ rats, used increasingly for understanding the biological basis of CNS disorders, utilize the mouse ChAT promotor to control Cre recombinase expression, we assessed for similar genotypical and phenotypical differences in such rats compared …

Are Specific Learning Disorders Truly Specific, And Are They Disorders?, Lien Peters, Daniel Ansari

Brain and Mind Institute Researchers' Publications

© 2019 The Authors Specific learning disorders, such as dyslexia and dyscalculia, are frequently studied to inform our understanding of cognitive development, genetic mechanisms and brain function. In this Opinion Paper, we discuss limitations of this research approach, including the use of arbitrary criteria to select groups of children, heterogeneity within groups and overlap between domains of learning. By drawing on evidence from cognitive science, neuroscience and genetics, we propose an alternative, dimensional framework. We argue that we need to overcome the problems associated with a categorical approach by taking into account interacting factors at multiple levels of analysis that …

Coordination Of Airway Protective Behaviors And Swallow: Effects Of Afferent Feedback And Sex., Alyssa D. Huff

Electronic Theses and Dissertations

This dissertation represents a series of studies describing mechanisms related to breathing, upper airway behaviors and their coordination in man and animal. Chapter two transformed the cough swallow aspiration protocol from the cat (previous work) to the human introducing a new strategy, volume targeting, in swallow breathing coordination. Chapter three evaluated swallow breathing coordination at increasing altitudes. As respiratory drive altered due to hypoxia and hypocapnia, swallow breathing coordination shifted toward inspiration occurring during the transition from inspiration and expiration. The collection of the two previous studies led to development of an animal model to evaluate volume targeting and …

The Acute Effect Of Water Intake On Glucose Regulation In Low Drinkers, Adam David Seal

Graduate Theses and Dissertations

Previous evidence suggests the hormone arginine vasopressin (AVP) may be a modifiable factor contributing to hyperglycemia. Significant differences in urine concentration and copeptin, a marker for AVP, have been observed between low and high water drinkers. Purpose: The purpose was to investigate the acute effect of adequate water intake on glucose regulation in low drinkers. Methods: 7 healthy (5 males, 2 female) low drinkers were recruited using a water frequency questionnaire (WFQ), spot and 24-h urine sample (age 43±6 y, BMI 30.9±3, WFQ volume 823±403 mL∙d-1, 24 h Uosm 961±105 mmol∙kg-1, copeptin 8.17±3.05 pmol∙L-1). During two experimental protocols, participants remained …

Quantitative Study Of The Antimicrobial Effects Of Silver On The Motility Of Escherichia Coli, Benjamin Russell

Graduate Theses and Dissertations

In recent decades, the number of antibiotic-resistant bacterial infections has grown to become a serious global threat. This rise can be attributed to the widespread misuse of antibiotics and the lack of newly developed drugs to fight resistant organisms. Novel bactericidal substances have, therefore, garnered significant research interest. Silver, due to its powerful antimicrobial effects, is one such substance. Silver is typically most effective in cationic form; however, advancements in nanotechnology have paved the way for the controlled fabrication of nano-silver. Silver nanoparticles have been shown to have increased antibacterial potency for a variety of reasons, including the release of …

Investigating The Effects Of Excitotoxic Stimuli On The Suprachiasmatic Nucleus, Rachel A. Brandes

Chancellor’s Honors Program Projects

No abstract provided.

Msto1 Mutations Cause Mtdna Depletion, Manifesting As Muscular Dystrophy With Cerebellar Involvement., S Donkervoort, R Sabouny, P Yun, L Gauquelin, K R Chao, Y Hu, I Al Khatib, A Töpf, P Mohassel, B B Cummings, R Kaur, D Saade, S A Moore, L B Waddell, M A Farrar, J K Goodrich, P Uapinyoying, S H S Chan, A Javed, M E Leach, P Karachunski, J Dalton, L Medne, A Harper, C Thompson, Isabelle Thiffault, S Specht, R E Lamont, Carol J. Saunders, H Racher, F P Bernier, D Mowat, N Witting, J Vissing, R Hanson, Keith A. Coffman, Meagan K. Hainlen, J S Parboosingh, A Carnevale, G Yoon, R E Schnur, Care4rare Canada Consortium, K M Boycott, J K Mah, V Straub, A Reghan Foley, A M Innes, C G Bönnemann, T E Shutt

Manuscripts, Articles, Book Chapters and Other Papers

MSTO1 encodes a cytosolic mitochondrial fusion protein, misato homolog 1 or MSTO1. While the full genotype-phenotype spectrum remains to be explored, pathogenic variants in MSTO1 have recently been reported in a small number of patients presenting with a phenotype of cerebellar ataxia, congenital muscle involvement with histologic findings ranging from myopathic to dystrophic and pigmentary retinopathy. The proposed underlying pathogenic mechanism of MSTO1-related disease is suggestive of impaired mitochondrial fusion secondary to a loss of function of MSTO1. Disorders of mitochondrial fusion and fission have been shown to also lead to mitochondrial DNA (mtDNA) depletion, linking them to the mtDNA …

Identification And Molecular Analysis Of Dna In Exosomes, Jena Tavormina

Dissertations & Theses (Open Access)

Exosomes are heterogeneous nanoparticles 50-150nm in diameter. Exosomes contain many functional cargo components, such as protein, DNA, and RNA. While protein and RNA exosome content has been extensively studied, very little work has been done to characterize exosomal DNA. Here, we demonstrate that exosomal DNA is heterogeneous and its packaging into exosomes is dependent on the cell of origin. Furthermore, through a rigorous assessment of various isolation methods, we identify Size Exclusion Chromatography (SEC) as the best method for the isolation of exosomal DNA for downstream applications. Additionally, we evaluate the methylation status of exosomal DNA and demonstrate that exosomal …

The Dynamic Impacts Of Online Healthcare Community On Physician Altruism: A Hidden Markov Model, Kai Luo, Qiu-Hong Wang, Hock Hai Teo

Research Collection School Of Computing and Information Systems

Physician altruism is not only a key foundation of modern medical professionalism, but also a critical component in the theoretical health economics study. There is considerable interest in understanding the impacts of contemporary healthcare technology on physician altruism. In this paper, we investigate the dynamic influence of multiple incentive mechanisms developed by an online healthcare community (OHC) on physician altruism. We model physician altruism as the degree of tendency to benefit the patients at the cost of oneself and focus on the incentive mechanisms that give physicians social and economic returns. The dynamics of physician altruism is characterized via a …

It's A Hard Nacht Life: Understanding How Nlrp12 Ticks, Abbigale Julia Brown

MSU Graduate Theses

The protein NOD- like receptor pyrin domain containing 12 (NLRP12) comes from a family of protein receptors with a wide range of functions including fertility as well as anti-inflammatory properties. The biological role of NLRP12 is poorly understood: research on the mechanisms behind its function and/or activation remains contradictory between different cell models. Current research suggests its involvement in a multi-protein complex named the inflammasome. The alternative hypothesis that has also been proposed is that NLRP12 is not a part of the inflammasome, rather it negatively regulates a transcription factor known as NF-��B down stream of Toll-like receptors. NLRP12 is …

Examining The Theoretical Mechanisms Underlying Health Information Exchange Impact On Healthcare Outcomes: A Physician Agency Perspective, Fang Zhou, Qiu-Hong Wang, Hock Hai Teo

Research Collection School Of Computing and Information Systems

Health information exchange (HIE) is presumed to reduce medical costs by facilitating information sharing across healthcare providers. Existing studies focused on different medical costs or one set of costs, and resulted in mixed findings. We examine the effects of patient access to HIE on two of the most important medical costs of a hospitalization episode - test costs and medication costs - through a natural experiment and the discharge data of a hospital. Besides the negative direct effect of access to HIT on tests costs, we also find its positive spillover effect on medication costs, such that more patients having …

Genome-Wide Association Analysis Of Hippocampal Volume Identifies Enrichment Of Neurogenesis-Related Pathways, Emrin Horgusluoglu-Moloch, Shannon L. Risacher, Paul K. Crane, Derrek Hibar, Paul M. Thompson, Andrew J. Saykin, Kwangsik Nho, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, John Morris, Leslie M. Shaw, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher

Medical Biophysics Publications

© 2019, The Author(s). Adult neurogenesis occurs in the dentate gyrus of the hippocampus during adulthood and contributes to sustaining the hippocampal formation. To investigate whether neurogenesis-related pathways are associated with hippocampal volume, we performed gene-set enrichment analysis using summary statistics from a large-scale genome-wide association study (N = 13,163) of hippocampal volume from the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium and two year hippocampal volume changes from baseline in cognitively normal individuals from Alzheimer’s Disease Neuroimaging Initiative Cohort (ADNI). Gene-set enrichment analysis of hippocampal volume identified 44 significantly enriched biological pathways (FDR corrected p-value < 0.05), of which 38 pathways were related to neurogenesis-related processes including neurogenesis, generation of new neurons, neuronal development, and neuronal migration and differentiation. For genes highly represented in the significantly enriched neurogenesis-related pathways, gene-based association analysis identified TESC, ACVR1, MSRB3, and DPP4 as significantly associated with hippocampal volume. Furthermore, co-expression network-based functional analysis of gene expression data in the hippocampal subfields, CA1 and CA3, from 32 normal controls showed that distinct co-expression modules were mostly enriched in neurogenesis related pathways. Our results suggest that neurogenesis-related pathways may be enriched for hippocampal volume and that hippocampal volume may serve as a potential phenotype for the investigation of human adult neurogenesis.

Multimodal Hippocampal Subfield Grading For Alzheimer’S Disease Classification, Kilian Hett, Vinh Thong Ta, Gwenaëlle Catheline, Thomas Tourdias, José V. Manjón, Pierrick Coupé, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, Davie Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Tom Montine

Medical Biophysics Publications

© 2019, The Author(s). Numerous studies have proposed biomarkers based on magnetic resonance imaging (MRI) to detect and predict the risk of evolution toward Alzheimer’s disease (AD). Most of these methods have focused on the hippocampus, which is known to be one of the earliest structures impacted by the disease. To date, patch-based grading approaches provide among the best biomarkers based on the hippocampus. However, this structure is complex and is divided into different subfields, not equally impacted by AD. Former in-vivo imaging studies mainly investigated structural alterations of these subfields using volumetric measurements and microstructural modifications with mean diffusivity …

Mousebytes, An Open-Access High-Throughput Pipeline And Database For Rodent Touchscreen-Based Cognitive Assessment, Flavio H. Beraldo, Daniel Palmer, Sara Memar, David I. Wasserman, Wai Jane V. Lee, Shuai Liang, Samantha D. Creighton, Benjamin Kolisnyk, Matthew F. Cowan, Justin Mels, Talal S. Masood, Chris Fodor, Mohammed A. Al-Onaizi, Robert Bartha, Tom Gee, Lisa M. Saksida, Timothy J. Bussey, Stephen S. Strother, Vania F. Prado, Boyer D. Winters, Marco A.M. Prado

Medical Biophysics Publications

© 2019, eLife Sciences Publications Ltd. All rights reserved. Open Science has changed research by making data accessible and shareable, contributing to replicability to accelerate and disseminate knowledge. However, for rodent cognitive studies the availability of tools to share and disseminate data is scarce. Automated touchscreen-based tests enable systematic cognitive assessment with easily standardised outputs that can facilitate data dissemination. Here we present an integration of touchscreen cognitive testing with an open-access database public repository (mousebytes.ca), as well as a Web platform for knowledge dissemination (https://touchscreencognition.org). We complement these resources with the largest dataset of age-dependent high-level cognitive assessment of …

3d Vessel-Wall Virtual Histology Of Whole-Body Perfused Mice Using A Novel Heavy Element Stain, P. Joy Dunmore-Buyze, Charmainne Cruje, Zengxuan Nong, Jason J. Lee, John A. Kiernan, J. Geoffrey Pickering, Maria Drangova

Medical Biophysics Publications

Virtual histology – utilizing high-resolution three-dimensional imaging – is becoming readily available. Micro-computed tomography (micro-CT) is widely available and is often coupled with x-ray attenuating histological stains that mark specific tissue components for 3D virtual histology. In this study we describe a new tri-element x-ray attenuating stain and perfusion protocol that provides micro-CT contrast of the entire vasculature of an intact mouse. The stain – derived from an established histology stain (Verhoeff’s) – is modified to enable perfusion through the vasculature; the attenuating elements of the stain are iodine, aluminum, and iron. After a 30-minute perfusion through the vasculature (10-minute …

Comparison Of Quality Control Methods For Automated Diffusion Tensor Imaging Analysis Pipelines, Seyyed M.H. Haddad, Christopher J.M. Scott, Miracle Ozzoude, Melissa F. Holmes, Stephen R. Arnott, Nuwan D. Nanayakkara, Joel Ramirez, Sandra E. Black, Dar Dowlatshahi, Stephen C. Strother, Richard H. Swartz, Sean Symons, Manuel Montero-Odasso, Robert Bartha

Medical Biophysics Publications

© 2019 Haddad et al. The processing of brain diffusion tensor imaging (DTI) data for large cohort studies requires fully automatic pipelines to perform quality control (QC) and artifact/outlier removal procedures on the raw DTI data prior to calculation of diffusion parameters. In this study, three automatic DTI processing pipelines, each complying with the general ENIGMA framework, were designed by uniquely combining multiple image processing software tools. Different QC procedures based on the RESTORE algorithm, the DTIPrep protocol, and a combination of both methods were compared using simulated ground truth and artifact containing DTI datasets modeling eddy current induced distortions, …

The Bin1 Rs744373 Snp Is Associated With Increased Tau-Pet Levels And Impaired Memory, Nicolai Franzmeier, Anna Rubinski, Julia Neitzel, Michael Ewers, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowski, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Lew Kuller, Marcus Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, Marek M. Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue

Medical Biophysics Publications

© 2019, The Author(s). The single nucleotide polymorphism (SNP) rs744373 in the bridging integrator-1 gene (BIN1) is a risk factor for Alzheimer’s disease (AD). In the brain, BIN1 is involved in endocytosis and sustaining cytoskeleton integrity. Post-mortem and in vitro studies suggest that BIN1-associated AD risk is mediated by increased tau pathology but whether rs744373 is associated with increased tau pathology in vivo is unknown. Here we find in 89 older individuals without dementia, that BIN1 rs744373 risk-allele carriers show higher AV1451 tau-PET across brain regions corresponding to Braak stages II–VI. In contrast, the BIN1 rs744373 SNP was not associated …

The Identification Of Long Non-Coding Rna Zfas1 Through An Exploratory Rna-Sequencing Analysis And Its Association With Epithelial-To-Mesenchymal Transition In Colon Cancer Adenocarcinoma., Stephen J. O'Brien

Electronic Theses and Dissertations

Colorectal adenocarcinoma is the fourth most common cancer diagnosed worldwide and is a significant cause of morbidity and mortality. This dissertation performed an exploratory RNA-sequencing analysis comparing gene expression between colon adenocarcinoma tissue and paired normal colon epithelium. After identification of a number of lncRNAs that were increased in expression in colon adenocarcinoma compared to normal colon epithelium, we aimed to validate the expression and investigate their function in vitro. Specifically, we focused on the lncRNA ZFAS1 and its association with epithelial-to-mesenchymal transition. These studies found the following: 1. Seven candidate lncRNAs were identified from the exploratory RNA-sequencing analysis to …

The Effects Of Nicotine And Cigarette Smoking On Cardiac Electrophysiology., Affan B. Irfan

Electronic Theses and Dissertations

Cigarette smoking is a leading cause of preventable disease and premature death worldwide. The adverse effects of cigarette smoking, including proarrhythmia, are related to the mixture of chemicals, including nicotine (which sustains tobacco addiction). However, it remains unclear which individual tobacco smoke constituents and biological pathways mediate this increased risk. The purpose of this research was to explore the chronic effects of cigarette smoking, as well as compare the acute effects of nicotine and cigarette smoking, and the possible role of β-adrenoreceptors, on human cardiac electrophysiology. Chapter 1 is a comprehensive literature review of (a) the ex vivo and in …

A Rewiring Model Of Intratumoral Interaction Networks., Mengmeng Sang, Shawn Rice, Libo Jiang, Xin Liu, Claudia Gragnoli, Chandra P. Belani, Rongling Wu

Division of Endocrinology, Diabetes and Metabolic Diseases Faculty Papers

Intratumoral heterogeneity (ITH) has been regarded as a key cause of the failure and resistance of cancer therapy, but how it behaves and functions remains unclear. Advances in single-cell analysis have facilitated the collection of a massive amount of data about genetic and molecular states of individual cancer cells, providing a fuel to dissect the mechanistic organization of ITH at the molecular, metabolic and positional level. Taking advantage of these data, we propose a computational model to rewire up a topological network of cell-cell interdependences and interactions that operate within a tumor mass. The model is grounded on the premise …

Tamoxifen Activity Against Plasmodium In Vitro And In Mice, Ada Weinstock, Julio Gallego-Delgado, Cláudia Gomes, Julian Sherman, Cyrus Nikain, Sandra Gonzalez, Edward Fisher, Ana Rodriguez

Publications and Research

Background: Tamoxifen is an oestrogen receptor modulator that is widely used for the treatment of early stage breast cancer and reduction of recurrences. Tamoxifen is also used as a powerful research tool for controlling gene expression in the context of the Cre/loxP site-specific recombination system in conditional mutant mice.

Methods: To determine whether the administration of tamoxifen affects Plasmodium growth and/or disease outcome in malaria, in vitro studies assessing the effect of tamoxifen and its active metabolite 4-hydroxytamoxifen on Plasmodium falciparum blood stages were performed. Tamoxifen effects were also evaluated in vivo treating C57/B6 mice infected with Plasmodium berghei (ANKA …