Life Sciences Commons^™

Genomic Epidemiology Of Clostridium Difficile Colonization And Transmission In An Intensive Care Unit Cohort, Brianne Ciferri

Dissertations and Theses

Abstract

Genomic epidemiology of Clostridium difficile colonization and transmission in an intensive care unit cohort

by Brianne Ciferri, MPH

Advisor: C. Mary Schooling, PhD

Introduction: Clostridiodes difficile (C. difficile) is a leading cause of healthcare associated infections (HAI) in the United States and responsible for an estimated incidence of 223,900 cases and 12,800 deaths per year^1,2. C. difficile can cause gastrointestinal illness with symptoms ranging from mild diarrheal illness to a life-threatening condition. C. difficile is an opportunistic pathogen in which spores can live in an undisturbed dormant state within the intestinal tract and become …

Insights Into Using Plants In Management Of Viral Diseases., Vyacheslav Dushenkov, Anna Dushenkov

Publications and Research

Botanical therapeutics possess a unique potential in the treatment of viral diseases. The pharmacological base and clinical use of botanical therapeutics have been extensively reviewed. The mode of action(s) may be built either on the direct interference with the virus's ability to enter human cells, virus replication, or exerting immune-modulatory and anti-inflammatory effects. The adjuvant treatment with botanical therapeutics has the potential to result in advances in symptom resolution, decrease in disease burden and shortening its duration.

Type Vi Secretion System Mutations Reduced Competitive Fitness Of Classical Vibrio Cholerae Biotype, Benjamin Kostiuk, Francis J. Santoriello, Laura Diaz-Satizabal, Fabiana Bisaro, Kyung-Jo Lee, Anna N. Dhody, Daniele Provenzano, Daniel Unterweger, Stefan Pukatzki

Publications and Research

The gram-negative bacterium Vibrio cholerae is the causative agent of the diarrhoeal disease cholera and is responsible for seven recorded pandemics. Several factors are postulated to have led to the decline of 6th pandemic classical strains and the rise of El Tor biotype V. cholerae, establishing the current 7th pandemic. We investigated the ability of classical V. cholerae of the 2nd and 6th pandemics to engage their type six secretion system (T6SS) in microbial competition against non-pandemic and 7th pandemic strains. We report that classical V. cholerae underwent sequential mutations in T6SS genetic determinants that initially exposed 2nd pandemic strains …

The Temperature-Dependent Conformational Ensemble Of Sars-Cov-2 Main Protease (Mpro), Ali Ebrahim, Blake T. Riley, Desigan Kumaran, Babak Andi, Martin R. Fuchs, Sean Mcsweeney, Daniel A. Keedy

Publications and Research

The COVID-19 pandemic, instigated by the SARS-CoV-2 coronavirus, continues to plague the globe. The SARS-CoV-2 main protease, or M^pro, is a promising target for development of novel antiviral therapeutics. Previous X-ray crystal structures of M^pro were obtained at cryogenic temperature or room temperature only. Here we report a series of high-resolution crystal structures of unliganded M^pro across multiple temperatures from cryogenic to physiological, and another at high humidity. We interrogate these datasets with parsimonious multiconformer models, multi-copy ensemble models, and isomorphous difference density maps. Our analysis reveals a temperature-dependent conformational landscape for M^pro, including …

Intangible Cultural Heritage: A Benefit To Climate-Displaced And Host Communities, Gül Aktürk, Martha B. Lerski

Publications and Research

Climate change is borderless, and its impacts are not shared equally by all communities. It causes an imbalance between people by creating a more desirable living environment for some societies while erasing settlements and shelters of some others. Due to floods, sea level rise, destructive storms, drought, and slow-onset factors such as salinization of water and soil, people lose their lands, homes, and natural resources. Catastrophic events force people to move voluntarily or involuntarily. The relocation of communities is a debatable climate adaptation measure which requires utmost care with human rights, ethics, and psychological well-being of individuals upon the issues …

Mitochondrial Distribution Of Glycine Receptors In Motor Neuron Cell Lines, Katsiaryna Milashevich

Student Theses and Dissertations

Although non-essential, glycine plays an important role in major metabolic reactions and is most known for its anti-inflammatory effects. An accumulation of contemporary research has shown that glycine is able to stabilize membrane potential using glycine receptors at the cellular level and to protect mitochondrial function directly, whether it is from inflammation, heavy metal poisoning, or ischemia-induced neuroinflammation. In this research, the existence of a hypothetical mitochondrial glycine receptor is examined. Immunofluorescence imaging was used to examine the presence of the glycine receptor subunits alpha 1 and alpha 2 in both non- differentiated and differentiated neuroblastoma cell lines. The preliminary …

When The Pandemic Opts For The Lockdown: Secretion System Evolution In The Cholera Bacterium, Francis J. Santoriello, Stefan Pukatzki

Publications and Research

Vibrio cholerae, the causative agent of the diarrheal disease cholera, is a microbe capable of inhabiting two different ecosystems: chitinous surfaces in brackish, estuarine waters and the epithelial lining of the human gastrointestinal tract. V. cholerae defends against competitive microorganisms with a contact-dependent, contractile killing machine called the type VI secretion system (T6SS) in each of these niches. The T6SS resembles an inverted T4 bacteriophage tail and is used to deliver toxic effector proteins into neighboring cells. Pandemic strains of V. cholerae encode a unique set of T6SS effector proteins, which may play a role in pathogenesis or pandemic …

Extracellular Vesicles Released By Human Retinal Pigment Epithelium Mediate Increased Polarised Secretion Of Drusen Proteins In Response To Amd Stressors, Miguel Flores-Bellver, Jason Mighty, Silvia Aparicio-Domingo, Kang V. Li, Cui Shi, Jing Zhou, Hannah Cobb, Patrick Mcgrath, German Michelis, Patricia Lenhart, Ganna Bilousova, Søren Heissel, Michael J. Rudy, Christina Coughlan, Andrew E. Goodspeed, S. Patricia Becerra, Stephen Redenti, M. Valeria Canto-Soler

Publications and Research

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Drusen are key contributors to the etiology of AMD and the ability to modulate drusen biogenesis could lead to therapeutic strategies to slow or halt AMD progression. The mechanisms underlying drusen biogenesis, however, remain mostly unknown. Here we demonstrate that under homeostatic conditions extracellular vesicles (EVs) secreted by retinal pigment epithelium (RPE) cells are enriched in proteins associated with mechanisms involved in AMD pathophysiology, including oxidative stress, immune response, inflammation, complement system and drusen composition. Furthermore, we provide first evidence that drusen-associated proteins are released as cargo of extracellular …

Development Of Light Actuated Chemical Delivery Platform On A 2-D Array Of Micropore Structure, Hojjat Rostami Azmand, Hojjat Rostami Azmand

Dissertations and Theses

Localized chemical delivery plays an essential role in the fundamental information transfers within biological systems. Thus, the ability to mimic the natural chemical signal modulation would provide significant contributions to understand the functional signaling pathway of biological cells and develop new prosthetic devices for neurological disorders. In this paper, we demonstrate a light-controlled hydrogel platform that can be used for localized chemical delivery in a high spatial resolution. By utilizing the photothermal behavior of graphene-hydrogel composites confined within micron-sized fluidic channels, patterned light illumination creates the parallel and independent actuation of chemical release in a group of fluidic ports. The …