Medical Microbiology Commons^™

Wellness In The Face Of Frailty Among Older Adults In First Nations Communities, Morgan Slater, Gabrielle Bruser, Roseanne Sutherland, Melissa K Andrew, Wayne Warry, Kristen M Jacklin, Jennifer D Walker

Faculty, Staff and Student Publications

OBJECTIVES: First Nations people report high levels of wellness despite high rates of chronic illness. Our goal was to understand the factors associated with wellness among First Nations adults in Ontario who were considered frail.

METHODS: Using the First Nations Regional Health Survey, we created a profile of First Nations adults (aged 45+) who were categorized as "frail" (weighted sample size = 8121). We used multivariate logistic regression to determine associations between wellness (as measured by self-reported physical, emotional, mental, and spiritual balance) and determinants of health.

RESULTS: Rates of reported wellness were high among those who were frail, ranging …

Discovery Of An Orally Active Benzoxaborole Prodrug Effective In The Treatment Of Chagas Disease In Non-Human Primates, Angel M Padilla, Wei Wang, Tsutomu Akama, David S Carter, Eric Easom, Yvonne Freund, Jason S Halladay, Yang Liu, Sarah A Hamer, Carolyn L Hodo, Gregory K Wilkerson, Dylan Orr, Brooke White, Arlene George, Huifeng Shen, Yiru Jin, Michael Zhuo Wang, Susanna Tse, Robert T Jacobs, Rick L Tarleton

Faculty, Staff and Student Publications

Trypanosoma cruzi, the agent of Chagas disease, probably infects tens of millions of people, primarily in Latin America, causing morbidity and mortality. The options for treatment and prevention of Chagas disease are limited and underutilized. Here we describe the discovery of a series of benzoxaborole compounds with nanomolar activity against extra- and intracellular stages of T. cruzi. Leveraging both ongoing drug discovery efforts in related kinetoplastids, and the exceptional models for rapid drug screening and optimization in T. cruzi, we have identified the prodrug AN15368 that is activated by parasite carboxypeptidases to yield a compound that targets the messenger RNA …

Characteristics Of Community-Acquired Carbapenem-Resistant Enterobacterales, Rima Shrestha, Courtney L Luterbach, Weixiao Dai, Lauren Komarow, Michelle Earley, Gregory Weston, Erica Herc, Jesse T Jacob, Robert Salata, Darren Wong, Deverick Anderson, Kirsten B Rydell, Cesar A Arias, Liang Chen, David Van Duin, Mdro Investigators

Faculty, Staff and Student Publications

BACKGROUND: Community-acquired carbapenem-resistant Enterobacterales (CA-CRE) are an important threat.

METHODS: In CRACKLE-2, we defined patients with CA-CRE as admitted from home, without pre-existing conditions, and a positive culture within 48 h of admission. Healthcare-associated CRE (HA-CRE) were those with the lowest likelihood of community acquisition, not admitted from home and cultured >48 h after admission. Specific genetic markers in carbapenemase-producing Klebsiella pneumoniae were evaluated through random forest modelling.

RESULTS: CA-CRE and HA-CRE were detected in 83 (10%) and 208 (26%) of 807 patients. No significant differences were observed in bacterial species or strain type distribution. K. pneumoniae (204/291, 70%) was …

Overlapping And Distinct Functions Of The Paralogous Pagr Regulators Of Bacillus Anthracis, Ileana D Corsi, Theresa M Koehler

Faculty, Staff and Student Publications

The Bacillus anthracis pagA gene, encoding the protective antigen component of anthrax toxin, is part of a bicistronic operon on pXO1 that codes for its own repressor, PagR1. In addition to the pagAR1 operon, PagR1 regulates sap and eag, two chromosome genes encoding components of the surface layer, a mounting structure for surface proteins involved in virulence. Genomic studies have revealed a PagR1 paralog, PagR2, encoded by a gene on pXO2. The amino acid sequences of the paralogues are 71% identical and show similarity to the ArsR family of transcription regulators. We determined that the expression of either rPagR1 …

Comparative Analysis Of Co-Cultured Amniotic Cell-Conditioned Media With Cell-Free Amniotic Fluid Reveals Differential Effects On Epithelial-Mesenchymal Transition And Myofibroblast Activation, Naiyou Liu, Charles M Bowen, Mohammadali M Shoja, Karen Larissa Castro De Pereira, Laxmi Priya Dongur, Antonio Saad, William K Russell, Thomas Christopher Broderick, Jeffrey H Fair, William Samuel Fagg

Faculty, Staff and Student Publications

Myofibroblast activation is a cellular response elicited by a variety of physiological or pathological insults whereby cells initiate a coordinated response intended to eradicate the insult and then revert back to a basal state. However, an underlying theme in various disease states is persistent myofibroblast activation that fails to resolve. Based on multiple observations, we hypothesized that the secreted factors harvested from co-culturing amniotic stem cells might mimic the anti-inflammatory state that cell-free amniotic fluid (AF) elicits. We optimized an amnion epithelial and amniotic fluid cell co-culture system, and tested this hypothesis in the context of myofibroblast activation. However, we …

Distinguishing Intrathyroid Parathyroid Adenoma From Colloid Nodules And Papillary Thyroid Carcinomas Using Multiphasic Multidetector Computed Tomography, J Matthew Debnam, T Linda Chi, Michael Kwon, Jia Sun, Dawid Schellingerhout, Brandon T Golant, Salmaan Ahmed, Nancy D Perrier, Thinh Vu

Faculty, Staff and Student Publications

OBJECTIVE: The aim of the study is to determine whether multiphase multidetector computed tomography (4D-MDCT) can differentiate between intrathyroid parathyroid adenomas (ITPAs), colloid nodules, and papillary thyroid carcinoma (PTC).

METHODS: We studied 22 ITPAs, 22 colloid nodules, and 11 PTCs in 55 patients. Hounsfield unit (HU) values of the nodules were measured on 4D-MDCT in the precontrast, arterial, venous, and delayed phases. Raw HU values, phase with peak enhancement, and washout percentages between the phases were evaluated.

RESULTS: Regardless of size, all ITPAs (22/22) showed peak enhancement in the arterial phase, which was significantly greater than both colloid nodules (15/22) …

Hepatic Circadian And Differentiation Factors Control Liver Susceptibility For Fatty Liver Disease And Tumorigenesis, Baharan Fekry, Aleix Ribas-Latre, Rachel Van Drunen, Rafael Bravo Santos, Samay Shivshankar, Yulin Dai, Zhongming Zhao, Seung-Hee Yoo, Zheng Chen, Kai Sun, Frances M Sladek, Mamoun Younes, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths, and the most common primary liver malignancy to present in the clinic. With the exception of liver transplant, treatment options for advanced HCC are limited, but improved tumor stratification could open the door to new treatment options. Previously, we demonstrated that the circadian regulator Aryl Hydrocarbon-Like Receptor Like 1 (ARNTL, or Bmal1) and the liver-enriched nuclear factor 4 alpha (HNF4α) are robustly co-expressed in healthy liver but incompatible in the context of HCC. Faulty circadian expression of HNF4α- either by isoform switching, or loss of expression- results in an increased …

Amphotericin B Resistance In Leishmania Mexicana: Alterations To Sterol Metabolism And Oxidative Stress Response, Edubiel A Alpizar-Sosa, Nur Raihana Binti Ithnin, Wenbin Wei, Andrew W Pountain, Stefan K Weidt, Anne M Donachie, Ryan Ritchie, Emily A Dickie, Richard J S Burchmore, Paul W Denny, Michael P Barrett

Faculty, Staff and Student Publications

Amphotericin B is increasingly used in treatment of leishmaniasis. Here, fourteen independent lines of Leishmania mexicana and one L. infantum line were selected for resistance to either amphotericin B or the related polyene antimicrobial, nystatin. Sterol profiling revealed that, in each resistant line, the predominant wild-type sterol, ergosta-5,7,24-trienol, was replaced by other sterol intermediates. Broadly, two different profiles emerged among the resistant lines. Whole genome sequencing then showed that these distinct profiles were due either to mutations in the sterol methyl transferase (C24SMT) gene locus or the sterol C5 desaturase (C5DS) gene. In three lines an additional deletion of …

Short Signature Rpob Gene Sequence To Differentiate Species In Mycobacterium Abscessus Group, Jian R Bao, Kileen L Shier, Ronald N Master, Robert S Jones, Richard B Clark

Faculty, Staff and Student Publications

Mycobacterium abscessus group (MAG) are rapidly growing acid-fast bacteria that consist of three closely related species: M. abscessus (Ma), M. bolletii (Mb), and M. massiliense (Mm). Differentiation of these species can be difficult but is increasingly requested owing to recent infectious outbreaks and their differential drug resistance. We developed a novel and rapid pyrosequencing method using short signature sequences (35 to 45 bp) at a hypervariable site in the rpoB gene to differentiate the three MAG species, along with M. chelonae (Mc), and M. immunogenum (Mi). This method was evaluated …

Gray And White Matter Abnormality In Patients With T2dm-Related Cognitive Dysfunction: A Systemic Review And Meta-Analysis, Teng Ma, Ze-Yang Li, Ying Yu, Bo Hu, Yu Han, Min-Hua Ni, Yu-Xiang Huang, Hao-Han Chen, Wen Wang, Lin-Feng Yan, Guang-Bin Cui

Faculty, Staff and Student Publications

Aims/hypothesis

Brain structure abnormality in patients with type 2 diabetes mellitus (T2DM)-related cognitive dysfunction (T2DM-CD) has been reported for decades in magnetic resonance imaging (MRI) studies. However, the reliable results were still unclear. This study aimed to make a systemic review and meta-analysis to find the significant and consistent gray matter (GM) and white matter (WM) alterations in patients with T2DM-CD by comparing with the healthy controls (HCs).

Methods

Published studies were systemically searched from PubMed, MEDLINE, Cochrane Library and Web of Science databases updated to November 14, 2021. Studies reporting abnormal GM or WM between patients with T2DM-CD and …

Changes Of Brain Function In Patients With Type 2 Diabetes Mellitus Measured By Different Analysis Methods: A New Coordinate-Based Meta-Analysis Of Neuroimaging, Ze-Yang Li, Teng Ma, Ying Yu, Bo Hu, Yu Han, Hao Xie, Min-Hua Ni, Zhu-Hong Chen, Yang-Ming Zhang, Yu-Xiang Huang, Wen-Hua Li, Wen Wang, Lin-Feng Yan, Guang-Bin Cui

Faculty, Staff and Student Publications

OBJECTIVE: Neuroimaging meta-analysis identified abnormal neural activity alterations in patients with type 2 diabetes mellitus (T2DM), but there was no consistency or heterogeneity analysis between different brain imaging processing strategies. The aim of this meta-analysis was to determine consistent changes of regional brain functions in T2DM

METHODS: Since the indicators obtained using varied post-processing methods reflect different neurophysiological and pathological characteristics, we further conducted a coordinate-based meta-analysis (CBMA) of the two categories of neuroimaging literature, which were grouped according to similar data processing methods: one group included regional homogeneity (ReHo), independent component analysis (ICA), and degree centrality (DC) studies, while …

Comparison Of Flash-Free And Conventional Bonding Systems: A Systematic Review And Meta-Analysis, He Wang, Ge Feng, Bo Hu, Haonan Tian, Yunchun Kuang, Tingwei Zhang, Jinlin Song

Faculty, Staff and Student Publications

OBJECTIVES: To review the literature systematically to compare the performance of adhesive precoated flash-free bonding systems with conventional adhesive precoated (APC) and operator-coated (OPC) bonding systems.

MATERIALS AND METHODS: PubMed, Cochrane Library, Web of Science, and Embase were searched for potential eligible studies. Study selection and data collection were conducted independently. Statistical analysis was performed by Review Manager 5.3. The Cochran Q test was used to test heterogeneity in the included studies. Risk of bias was evaluated using Cochrane RoB 2.0 tool for randomized controlled trials.

RESULTS: Six studies were included and the overall risk-of-bias judgment was low risk of …

Kalium Channelrhodopsins Are Natural Light-Gated Potassium Channels That Mediate Optogenetic Inhibition, Elena G Govorunova, Yueyang Gou, Oleg A Sineshchekov, Hai Li, Xiaoyu Lu, Yumei Wang, Leonid S Brown, François St-Pierre, Mingshan Xue, John L Spudich

Faculty, Staff and Student Publications

Channelrhodopsins are used widely for optical control of neurons, in which they generate photoinduced proton, sodium or chloride influx. Potassium (K+) is central to neuron electrophysiology, yet no natural K+-selective light-gated channel has been identified. Here, we report kalium channelrhodopsins (KCRs) from Hyphochytrium catenoides. Previously known gated potassium channels are mainly ligand- or voltage-gated and share a conserved K+-selectivity filter. KCRs differ in that they are light-gated and have independently evolved an alternative K+ selectivity mechanism. The KCRs are potent, highly selective of K+ over Na+, and open in less than 1 ms following photoactivation. The permeability ratio PK/PNa of …

Blood–Brain Barrier Disruption Mediated By Ffa1 Receptor—Evidence Using Miniscope, Kristen L Lindenau, Jeffrey L Barr, Christopher R Higgins, Kevin T Sporici, Eugen Brailoiu, Gabriela C Brailoiu

Faculty, Staff and Student Publications

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), obtained from diet and dietary supplements, have been tested in clinical trials for the prevention or treatment of several diseases. n-3 PUFAs exert their effects by activation of free fatty acid (FFA) receptors. FFA1 receptor, expressed in the pancreas and brain, is activated by medium- to long-chain fatty acids. Despite some beneficial effects on cognition, the effects of n-3 PUFAs on the blood-brain barrier (BBB) are not clearly understood. We examined the effects of FFA1 activation on BBB permeability in vitro, using rat brain microvascular endothelial cells (RBMVEC), and in vivo, by assessing Evans …

Predicting Cancer Immunotherapy Response From Gut Microbiomes Using Machine Learning Models, Hai Liang, Jay-Hyun Jo, Zhiwei Zhang, Margaret A Macgibeny, Jungmin Han, Diana M Proctor, Monica E Taylor, You Che, Paul Juneau, Andrea B Apolo, John A Mcculloch, Diwakar Davar, Hassane M Zarour, Amiran K Dzutsev, Isaac Brownell, Giorgio Trinchieri, James L Gulley, Heidi H Kong

Faculty, Staff and Student Publications

Cancer immunotherapy has significantly improved patient survival. Yet, half of patients do not respond to immunotherapy. Gut microbiomes have been linked to clinical responsiveness of melanoma patients on immunotherapies; however, different taxa have been associated with response status with implicated taxa inconsistent between studies. We used a tumor-agnostic approach to find common gut microbiome features of response among immunotherapy patients with different advanced stage cancers. A combined meta-analysis of 16S rRNA gene sequencing data from our mixed tumor cohort and three published immunotherapy gut microbiome datasets from different melanoma patient cohorts found certain gut bacterial taxa correlated with immunotherapy response …

Regenerative Medicine Technologies Applied To Transplant Medicine An Update, Astgik Petrosyan, Filippo Montali, Andrea Peloso, Antonio Citro, Lori N Byers, Catherine La Pointe, Mara Suleiman, Alice Marchetti, Eoin P Mcneill, Allison L Speer, Wai Hoe Ng, Xi Ren, Benedetta Bussolati, Laura Perin, Paolo Di Nardo, Vincenzo Cardinale, Jerome Duisit, Alexandra Rose Monetti, John Richard Savino, Amish Asthana, Giuseppe Orlando

Faculty, Staff and Student Publications

Regenerative medicine (RM) is changing how we think and practice transplant medicine. In regenerative medicine, the aim is to develop and employ methods to regenerate, restore or replace damaged/diseased tissues or organs. Regenerative medicine investigates using tools such as novel technologies or techniques, extracellular vesicles, cell-based therapies, and tissue-engineered constructs to design effective patient-specific treatments. This review illustrates current advancements in regenerative medicine that may pertain to transplant medicine. We highlight progress made and various tools designed and employed specifically for each tissue or organ, such as the kidney, heart, liver, lung, vasculature, gastrointestinal tract, and pancreas. By combing both …

Oscillations Of The Circadian Clock Protein, Bmal-1, Align To Daily Cycles Of Mechanical Stimuli: A Novel Means To Integrate Biological Time Within Predictive In Vitro Model Systems, Hannah K Heywood, Laurence Gardner, Martin M Knight, David A Lee

Faculty, Staff and Student Publications

PURPOSE: In vivo, the circadian clock drives 24-h rhythms in human physiology. Isolated cells in vitro retain a functional clockwork but lack necessary timing cues resulting in the rapid loss of tissue-level circadian rhythms. This study tests the hypothesis that repeated daily mechanical stimulation acts as a timing cue for the circadian clockwork. The delineation and integration of circadian timing cues into predictive in vitro model systems, including organ-on-a-chip (OOAC) devices, represent a novel concept that introduces a key component of in vivo physiology into predictive in vitro model systems.

METHODS: Quiescent bovine chondrocytes were entrained for 3 days by …

Critical Analysis Of Laboratory Requisition Forms Received In A Cytopathology Laboratory Of A Tertiary Care Centre: An Audit And Review Of Literature, Shivali Sehgal, Sujata Jetley, Zeeba S Jairajpuri, Sabina Khan

Faculty, Staff and Student Publications

BACKGROUND: A laboratory requisition form (LRF) is the main communication link between the laboratories and the clinicians. In a cytopathology laboratory, incomplete forms with inadequate information significantly impact the quality of the results and waste precious time of the lab.

AIMS: The aim of this study was to audit the LRFs for adequacy of demographic and clinical data and to analyze the reasons for the same.

SETTINGS AND DESIGN: A retrospective study was conducted in the cytopathology laboratory of a tertiary care center.

MATERIALS AND METHODS: All the original LRFs received for Pap smears and FNACs of 1-month duration were …

Radiofrequency Ablation In Combination With Cd73 Inhibitor Ab680 Reduces Tumor Growth And Enhances Anti-Tumor Immunity In A Syngeneic Model Of Pancreatic Ductal Adenocarcinoma, Erika Y Faraoni, Lincoln N Strickland, Baylee J O'Brien, Joseph F Barraza, Nirav C Thosani, Curtis J Wray, Tingting W Mills, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma presents a 5-year overall survival rate of 11%, placing an imperative need for the discovery and application of innovative treatments. Radiofrequency ablation represents a promising therapy for PDA, as studies show it induces coagulative necrosis and a host adaptive immune response. In this work we evaluated the effects of RFA treatment in vivo by establishing a syngeneic mouse model of PDA and performing tumor ablation in one flank. Our studies revealed RFA acutely impaired PDA tumor growth; however, such effects were not sustained one week after treatment. Adenosine (ADO) pathway represents a strong immunosuppressive mechanism that was …

Single-Cell Rna Sequencing Reveals Intratumoral Heterogeneity And Potential Mechanisms Of Malignant Progression In Prostate Cancer With Perineural Invasion, Bao Zhang, Shenghan Wang, Zhichao Fu, Qiang Gao, Lin Yang, Zhentao Lei, Yuqiang Shi, Kai Le, Jie Xiong, Siyao Liu, Jiali Zhang, Junyan Su, Jing Chen, Mengyuan Liu, Beifang Niu

Faculty, Staff and Student Publications

Background: Prostate cancer (PCa) is the second most common cancer among men worldwide. Perineural invasion (PNI) was a prominent characteristic of PCa, which was recognized as a key factor in promoting PCa progression. As a complex and heterogeneous disease, its true condition is difficult to explain thoroughly with conventional bulk RNA sequencing. Thus, an improved understanding of PNI-PCa progression at the single-cell level is needed.

Methods: In this study, we performed scRNAseq on tumor tissues of three PNI-PCa patients. Principal component analysis (PCA) and Uniform manifold approximation and projection (UMAP) were used to reduce dimensionality and visualize the cellular composition …

Incfv Plasmid Ped208: Sequence Analysis And Evidence For Translocation Of Maintenance/Leading Region Proteins Through Diverse Type Iv Secretion Systems, Abu Amar M Al Mamun, Kimberly Kissoon, Kouhei Kishida, William C Shropshire, Blake Hanson, Peter J Christie

Faculty, Staff and Student Publications

Two phylogenetically distantly-related IncF plasmids, F and pED208, serve as important models for mechanistic and structural studies of F-like type IV secretion systems (T4SSFs) and F pili. Here, we present the pED208 sequence and compare it to F and pUMNF18, the closest match to pED208 in the NCBI database. As expected, gene content of the three cargo regions varies extensively, although the maintenance/leading regions (MLRs) and transfer (Tra) regions also carry novel genes or motifs with predicted modulatory effects on plasmid stability, dissemination and host range. By use of a Cre recombinase assay for translocation (CRAfT), we recently reported that …

The Immunoregulatory Landscape Of Human Tuberculosis Granulomas, Evan Li, Antony Rodriguez, Amber U Luong, David Allen, John Morgan Knight, Farrah Kheradmand, David B Corry

Faculty, Staff and Student Publications

The allergic airway diseases chronic rhinosinusitis (CRS), allergic fungal rhinosinusitis (AFRS), asthma, allergic bronchopulmonary mycosis/aspergillosis (ABPM/A), and cystic fibrosis (CF) share a common immunological signature marked by T H 2 and TH 17 cell predominant immune responses, the production of IgE antibody, and atypical inflammatory cell infiltrate that includes eosinophils and other innate immune effector cells. Severe forms of these disorders have long been recognized as being related to hypersensitivity reactions to environmental fungi. Increasingly however,environmental fungi are assuming a more primary role in the etiology of these disorders, with airway mycosis, a type of non-invasive airway fungal infection,recognized as …

In Vivo Transplantation Of Human Intestinal Organoids Enhances Select Tight Junction Gene Expression, Mariaelena A Boyle, David J Sequeira, Eoin P Mcneill, Zachary K Criss, Noah F Shroyer, Allison L Speer

Faculty, Staff and Student Publications

BACKGROUND: Short bowel syndrome is a potentially fatal condition with inadequate management options. Tissue-engineered small intestine (TESI) is a promising solution, but confirmation of TESI function will be crucial before human application. We sought to define intestinal epithelial barrier function in human intestinal organoid (HIO)-derived TESI.

MATERIALS AND METHODS: HIOs were generated in vitro from human embryonic stem cells. After 1 mo, HIOs were collected for analysis or transplanted into the kidney capsule of immunocompromised mice. Transplanted HIOs (tHIOs) were harvested for analysis at 4 or 8 wk. Reverse transcription quantitative polymerase chain reaction and immunofluorescent staining were performed for …

Conservation Of Epithelial-To-Mesenchymal Transition Process In Neural Crest Cells And Metastatic Cancer, April Zhang, Hira Aslam, Neha Sharma, Aryeh Warmflash, Walid D Fakhouri

Faculty, Staff and Student Publications

Epithelial to mesenchymal transition (EMT) is a highly conserved cellular process in several species, from worms to humans. EMT plays a fundamental role in early embryogenesis, wound healing, and cancer metastasis. For neural crest cell (NCC) development, EMT typically results in forming a migratory and potent cell population that generates a wide variety of cell and tissue, including cartilage, bone, connective tissue, endocrine cells, neurons, and glia amongst many others. The degree of conservation between the signaling pathways that regulate EMT during development and metastatic cancer (MC) has not been fully established, despite ample studies. This systematic review and meta-analysis …

The Cardiac Neural Crest Cells In Heart Development And Congenital Heart Defects, Eileen M Burd, Ahmed Babiker, Jessica K Fairley, Divya Bhamidipati, Laila E Woc-Colburn, Blaine A Mathison

Faculty, Staff and Student Publications

No abstract provided.

Molecular Mechanisms Of Antimicrobial Resistance In Multi-Drug Resistant Enterococci, Ayesha Khan

Dissertations and Theses (Open Access)

Antibiotic resistance is a major global public health threat. Enterococci are recalcitrant, nosocomial pathogens that can be intrinsically resistant to valuable antibiotics, like beta-lactams, or evolve resistance to all existing antimicrobials. The LiaFSR system regulates resistance to cell membrane (CM) stressors like daptomycin (DAP), a front-line drug for multi-drug resistant infections. DAP resistance (DAP-R) in E. faecalis is mediated by CM phospholipid alterations. Emergence of DAP-R often leads to b-lactam resensitization, a phenomenon called the seesaw effect. The molecular mechanism of DAP-R and the seesaw effect are unknown. Here we show that LiaX is a surface exposed protein whose C-terminal …

Microbiotyping The Sinonasal Microbiome, Ahmed Bassiouni, Sathish Paramasivan, Arron Shiffer, Matthew R Dillon, Emily K Cope, Clare Cooksley, Mahnaz Ramezanpour, Sophia Moraitis, Mohammad Javed Ali, Benjamin S Bleier, Claudio Callejas, Marjolein E Cornet, Richard G Douglas, Daniel Dutra, Christos Georgalas, Richard J Harvey, Peter H Hwang, Amber U Luong, Rodney J Schlosser, Pongsakorn Tantilipikorn, Marc A Tewfik, Sarah Vreugde, Peter-John Wormald, J Gregory Caporaso, Alkis J Psaltis

Faculty, Staff and Student Publications

This study offers a novel description of the sinonasal microbiome, through an unsupervised machine learning approach combining dimensionality reduction and clustering. We apply our method to the International Sinonasal Microbiome Study (ISMS) dataset of 410 sinus swab samples. We propose three main sinonasal “microbiotypes” or “states”: the first is Corynebacterium-dominated, the second is Staphylococcus-dominated, and the third dominated by the other core genera of the sinonasal microbiome (Streptococcus, Haemophilus, Moraxella, and Pseudomonas). The prevalence of the three microbiotypes studied did not differ between healthy and diseased sinuses, but differences in their distribution were evident based …

Autoimmune Responses To Atherosclerotic Lipids: A Study In Murine Models Of Atherosclerosis And Obesity, Hanjing Wu

Dissertations and Theses (Open Access)

Atherosclerosis is a chronic, complex arterial disease characterized by intimal lipid accumulation and inflammation. A unique lipid-binding molecule, namely cluster of differentiation 1d (CD1d), may impact atherosclerosis. Structurally, CD1d acts as a nonpolymorphic cell-surface receptor, resembling the major histocompatibility complex-I (MHC-I). While MHC-I restricts peptide antigen presentation to T cells, CD1d presents lipid antigens to T cells named CD1d-restrictedd T cells. Although increased expression of CD1d has been found in human plaques, the exact nature of CD1d-recognized lipids in atherosclerosis remains to be determined. Three groups of lipids may undergo oxidation in atherosclerosis producing atherogenic lipids: phospholipids, fatty acids, and …

Identification Of The Causative Bacteria In Musculoskeletal Infections Using 16s Rdna - Denaturing Gradient Gel Electrophoresis Analysis, Karen Gomez

Dissertations and Theses (Open Access)

Musculoskeletal infections are infections of the bone and surrounding tissues. They are currently diagnosed based on culture analysis, which is the gold standard for pathogen identification. However, these clinical laboratory methods are frequently inadequate for the identification of the causative agents, because a large percentage (25-50%) of confirmed musculoskeletal infections are false negatives in which no pathogen is identified in culture. My data supports these results. The goal of this project was to use PCR amplification of a portion of the 16S rRNA gene to test an alternative approach for the identification of these pathogens and to assess the diversity …

Subacute Neural Stem Cell Therapy For Traumatic Brain Injury, Mikhail Bogdanov, Philip N Heacock, William Dowhan

Faculty, Staff and Student Publications

A protocol is described using lipid mutants and thiol-specific chemical reagents to study lipid-dependent and host-specific membrane protein topogenesis by the substituted-cysteine accessibility method as applied to transmembrane domains (SCAM). SCAM is adapted to follow changes in membrane protein topology as a function of changes in membrane lipid composition. The strategy described can be adapted to any membrane system.