Medicine and Health Sciences Commons^™

Influence Of Maternal Breast Milk Ingestion On Acquisition Of The Intestinal Microbiome In Preterm Infants., Katherine E Gregory, Buck S Samuel, Pearl Houghteling, Guru Shan, Frederick M Ausubel, Ruslan I Sadreyev, W Allan Walker

Faculty Publications

BACKGROUND: The initial acquisition and early development of the intestinal microbiome during infancy are important to human health across the lifespan. Mode of birth, antibiotic administration, environment of care, and nutrition have all been shown to play a role in the assembly of the intestinal microbiome during early life. For preterm infants, who are disproportionately at risk of inflammatory intestinal disease (i.e., necrotizing enterocolitis), a unique set of clinical factors influence the establishment of the microbiome. The purpose of this study was to establish the influence of nutritional exposures on the intestinal microbiome in a cohort of preterm infants early …

Comparative Genomic Analysis Of Two Serotype 1/2b Listeria Monocytogenes Isolates From Analogous Environmental Niches Demonstrates The Influence Of Hypervariable Hotspots In Defining Pathogenesis, Aidan Casey, Kieran Jordan, Aidan Coffey, Edward M. Fox, Olivia Mcauliffe

Department of Biological Sciences Publications

The vast majority of clinical human listeriosis cases are caused by serotype 1/2a, 1/2b, 1/2c, and 4b isolates of Listeria monocytogenes. The ability of L. monocytogenes to establish a systemic listeriosis infection within a host organism relies on a combination of genes that are involved in cell recognition, internalization, evasion of host defenses, and in vitro survival and growth. Recently, whole genome sequencing and comparative genomic analysis have proven to be powerful tools for the identification of these virulence-associated genes in L. monocytogenes. In this study, two serotype 1/2b strains of L. monocytogenes with analogous isolation sources, but …

The Vibrio Cholerae Minor Pilin Tcpb Initiates Assembly And Retraction Of The Toxin-Coregulated Pilus, Dixon Ng, Tony Harn, Tuba Altindal, Subramania Kolappan, Jarrad Marles, Rajan Lala, Ingrid Spielman, Yang Gao, Caitlyn Hauke, Gabriela Kovacikova

Dartmouth Scholarship

Type IV pilus (T4P) systems are complex molecular machines that polymerize major pilin proteins into thin filaments displayed on bacterial surfaces. Pilus functions require rapid extension and depolymerization of the pilus, powered by the assembly and retraction ATPases, respectively. A set of low abundance minor pilins influences pilus dynamics by unknown mechanisms. The Vibrio cholerae toxin-coregulated pilus (TCP) is among the simplest of the T4P systems, having a single minor pilin TcpB and lacking a retraction ATPase. Here we show that TcpB, like its homolog CofB, initiates pilus assembly. TcpB co-localizes with the pili but at extremely low levels, equivalent …

Erratum To: Neonatal Hyperbilirubinemia In Infants With G6pd C.563c>T Variant, Bushra Moiz, Amna Nasir, Sarosh Ahmed Khan, Saleema Amin Kherani, Maqbool Qadir

Department of Pathology and Laboratory Medicine

No abstract provided.

Regulatory Mechanisms In Borrelia Burgdorferi-Induced Arthritis, Emily Siebers Hansen

Theses and Dissertations

Lyme arthritis is a common symptom of Lyme borreliosis that involves inflammation of the synovial joints. Elucidating the immune events involved in Lyme arthritis is complicated by the fact that not all individuals infected with B. burgdorferi develop arthritis. Additionally, Lyme arthritis manifests in different severities between affected individuals. It is known that an inflammatory response is initiated by B. burgdorferi infection and that inflammatory T cells contribute to the development of arthritis. However, the anti-inflammatory mechanisms that regulate the pathogenic T cells’ response are not entirely understood. Here, the hypothesis that a dysregulated immune response results in an excessive …

Xpert Mtb/Rif Assay Shows Faster Clearance Of Mycobacterium Tuberculosis Dna With Higher Levels Of Rifapentine Exposure., A Jayakumar, R M Savic, C K Everett, Debra Benator, D Alland, C M Heilig, M Weiner, S O Friedrich, N A Martinson, A Kerrigan, C Zamudio, S V Goldberg, W C Whitworth, J L Davis, P Nahid

Medicine Faculty Publications

The Xpert MTB/RIF assay is both sensitive and specific as a diagnostic test. Xpert also reports quantitative output in cycle threshold (CT) values, which may provide a dynamic measure of sputum bacillary burden when used longitudinally. We evaluated the relationship between Xpert CT trajectory and drug exposure during tuberculosis (TB) treatment to assess the potential utility of Xpert CT for treatment monitoring. We obtained serial sputum samples from patients with smear-positive pulmonary TB who were consecutively enrolled at 10 international clinical trial sites participating in study 29X, a CDC-sponsored Tuberculosis Trials Consortium study evaluating the tolerability, safety, and antimicrobial activity …

The Role Of Streptococcus Gallolyticus Subspecies Gallolyticus In Colon Cancer Development, Jennifer L. Herold

Dissertations & Theses (Open Access)

Colorectal cancer (CRC) is the third most common cancer in men and women and is also the third most common cause of cancer death. A large body of evidence points towards the possibility that bacteria can have a significant impact on the development of cancer. It has been suggested that Streptococcus gallolyticus subsp. gallolyticus, a group D streptococci, may play a role in the development of CRC. Sg, formerly S. bovis biotype I, has been shown to be highly associated with CRC. In observing patients with either Sg bacteremia or endocarditis it was found that 25-80% of …

Whole Genome Sequencing As A Tool For Identifying Phenotypic Properties And Underlying Genetic Mechanisms In Staphylococcus Pseudintermedius, Matthew C. Riley

Doctoral Dissertations

Staphylococcus pseudintermedius is a Gram-positive bacterial opportunistic pathogen commonly associated with dermal infections in canines, but capable of causing serious disease in other species. Reports of human infections caused by S. pseudintermedius along with an increase in resistance to multiple antibiotics highlights the importance of this organism. Whole genome sequencing can allow large scale investigation of genetic mechanisms underlying phenotypic properties that contribute to the expansion of successful S. pseudintermedius clonal lineages.

The increase in multidrug and methicillin-resistant S. pseudintermedius (MRSP) may result from horizontal transfer of genetic material between bacterial isolates, yet is thought to be rare in Staphylococci …

Consensus Paper: Cerebellar Development., K Leto, M Arancillo, Ebe Becker, A Chiang, Et Al.

Faculty Publications

The development of the mammalian cerebellum is orchestrated by both cell-autonomous programs and inductive environmental influences. Here, we describe the main processes of cerebellar ontogenesis, highlighting the neurogenic strategies used by developing progenitors, the genetic programs involved in cell fate specification, the progressive changes of structural organization, and some of the better-known abnormalities associated with developmental disorders of the cerebellum.

A Novel Codon-Optimized Siv Gag-Pol Immunogen For Gene-Based Vaccination, Catherine M. Crosby, Eric A. Weaver, Reeti Khare, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Simian immunodeficiency virus (SIV) is a robust pathogen used in non-human primates to model HIV vaccines. SIV encodes a number of potential vaccine targets. By far the largest and most conserved protein target in SIV is its gag-pol protein that bears many epitopes to drive multivalent immune T cell responses. While gag-pol is an attractive antigen, it is only translated after a frame shift between gag and pol with the effect that gag and pol are expressed at an approximate 10/1 ratio. The codon bias of native lentiviral genes are also mismatched with the abundance of tRNAs in mammalian cells …

Alternate Efflux Pump Mechanism May Contribute To Drug Resistance In Extensively Drug-Resistant Isolates Of Mycobacterium Tuberculosis, Akbar Kanji, Rumina Hasan, Ambreen Zaver, Asho Ali, Kehkashan Imtiaz, Mussarat Ashraf, Taane G. Clark, Ruth Mc Nerney, Samreen Shafiq, Zahra Hasan

Department of Pathology and Laboratory Medicine

No abstract provided.

Pulmonary Infections After Tuberculosis, Kauser Jabeen

Department of Pathology and Laboratory Medicine

Aims and Objective: Despite effective treatment of pulmonary tuberculosis (TB) patients, destruction of lung parenchyma may lead to complications including repeated infections. These infections are often misdiagnosed or wrongly identified as TB recurrence, and hence are not treated effectively. The frequency and severity of these infections vary with the extent of damage, and are much more prominent in patients with post-TB bronchiectasis and fibrocavitary diseases. This presentation will focus on the epidemiology, treatment, and management of post-TB infections and challenges, and the impact of these infections on public health in high-TB-burden countries.
Methods: Published literature and review articles were evaluated …

Tuberculosis In Vulnerable Populations In Eastern Mediterranean Region-Implications For Control, Sadia Shakoor, Rumina Hasan

Department of Pathology and Laboratory Medicine

Objectives: Socially and economically disadvantaged or "vulnerable" people are at high risk of tuberculosis (TB) and also contribute to active chains of TB transmission. Included in such vulnerable populations are children, women, prisoners, people living with human immunodeficiency virus, the homeless, and displaced people. The ongoing active transmission of TB among such populations is made more difficult to assess and control by difficult access, health inequities, poverty, and other chronic and debilitating health conditions at individual, domestic, and community levels.
Methods: The 22 Eastern Mediterranean Region member states encompass diverse sociopolitical and socioeconomic situations with far-reaching effects on vulnerable populations …

Massive Pulmonary Embolism Presenting As Seizures, Shahrukh Hashmani, Fateh Ali Tipoo Sultan, Murtaza Kazmi, Amammarah Yasmeen

Department of Pathology and Laboratory Medicine

Pulmonary embolism can present in various ways, though seizure activity has been rarely reported. We report a 38 years old male who had met a road traffic accident, underwent surgery, presented a month later with seizures, chest pain, shortness of breath and low blood pressure. Massive pulmonary embolism was diagnosed on CTPA, with classical features on ECG and echocardiogram and the patient was successfully managed with thrombolysis. Massive pulmonary embolism (MPE) should be kept in mind in patients who present with seizures, chest pain and haemodynamic instability.

Epidemiology Of White Spot Syndrome Virus In The Daggerblade Grass Shrimp (Palaemonetes Pugio) And The Gulf Sand Fiddler Crab (Uca Panacea), Muhammad

Dissertations

Ever since the first outbreaks of White spot syndrome virus (WSSV), which causes White Spot Disease (WSD), in Asia in the early 1990s, the pathogen has been a major constraint to the profitability of the shrimp aquaculture industry across the globe. WSSV has a broad host range and is routinely detected in wild decapod crustaceans. In the present study, two common species in the tidal salt marsh along the northern coast of the Gulf of Mexico, the daggerblade grass shrimp (Palaemonetes pugio) and the Gulf sand fiddler crab (Uca panacea), were investigated for their role as …

A Microbiomic Approach To The Characterization Of The Impacts And Influences Of Viral, Bacterial, And Harmful Algal Bloom Toxins On The Bottlenose Dolphin, Corey David Russo

Dissertations

As apex predators that display high site fidelity Tursiops truncatus (bottlenose dolphin) are indicators of marine ecosystem health. Bottlenose dolphins, additionally, display pathogenesis and immune response similar to that of humans. Humans and coastal bottlenose dolphins, in particular, are constantly exposed to the same industrial, agricultural and domestic toxins and pathogens, contaminants and pollutants. Thus, studies on the bottlenose dolphin are also valuable in bridging the gap between ocean and human health. Bottlenose dolphins are susceptible to viral bacterial and toxin infection. Infection in the bottlenose dolphin manifests itself in the form of mass stranding events, unusual mortality events, chronic …

Effect Of Time Duration Of Digestion/Decontamination Technique On Yield Of Mycobacteria And Contamination Rates From Sterile Body Fluids (Pleural And Ascitic Fluid) And Pus Specimens, Samreen Shafiq, Faryal Saleem, Kauser Jabeen, Joveria Farooqi, Warda Alam, Sadia Hanif, Shazia Ali, Sadia Shakoor, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background:
Duration of digestion/decontamination has a considerable impact on yield of mycobacteria especially from sterile body fluids and pus specimens. Additionally, duration of digestion/decontamination affects the contamination rates. This study evaluates the effect of digestion/decontamination protocol for 15 and 20min versus inoculation of media directly from the sample on contamination rates as well as the yield of mycobacteria from pus and sterile fluids other than cerebrospinal fluids.
Methods:
Pleural fluid (n=60), pus (n=48) and ascitic fluid (n=12) specimens were cultured for mycobacteria and evaluated for contamination and mycobacterial yield using three different processing methodologies: without digestion/decontamination with 5% NaOH-NALC (D/D), …

Mycobacterial Contamination Of Bronchoscopes: Challenges And Possible Solutions In Low Resource Settings, Dania Khalid Saeed, Sadia Shakoor, Seema Irfan, Rumina Hasan

Department of Pathology and Laboratory Medicine

The use of bronchoscopes has increased in tuberculosis (TB) diagnostics to circumvent the diagnostic challenges that are associated with low sputum volume and smear-negative TB. In healthcare facilities situated in low income countries that have a high burden of TB, adequate decontamination of bronchoscopes is a challenge and often overlooked to save on time and costs. This amplifies the risk of outbreaks and pseudo-outbreaks due to Mycobacterium tuberculosis and nontuberculosis mycobacteria. In this minireview, we review published literature of contaminated bronchoscopes causing pseudo-outbreaks of M. tuberculosis and nontuberculosis mycobacteria in an effort to determine common sources, and possible mitigation strategies …

Oral Microbial Burden Of Periodontal Pathogens Among Orthodontic Patients, David Jolley

UNLV Theses, Dissertations, Professional Papers, and Capstones

Objectives

Many research studies involving orthodontic patients have a natural inclination to focus on changes in levels of cariogenic pathogens after bracket placement, and very few studies examine the role of changes of periodontal pathogens – particularly among adult patients. Interestingly, recent evidence suggests that increased levels of a specific periodontal pathogen, Fusobacterium nucleatum, may elevate risk for development of colon cancer in adults through direct pathways. Based upon this new evidence, the objective of the current study was to screen saliva samples taken from orthodontic patients to determine the prevalence of periodontal pathogens, including F. Nucleatum, T. denticola, and …

Current Antibiotics And Future Herbal Extract Methods To Treat Methicillin-Resistant Staphylococcus Aureus (Mrsa): Focusing On Inhibition Of Penicillin-Binding Protein 2a (Pbp2a), Mgayya R. Makullah

Senior Honors Theses

Methicillin-Resistant Staphylococcus aureus (MRSA) has developed resistance towards a number of antibiotics. This resistance creates a challenge when trying to treat MRSA with a number of antibiotics. This is mainly caused by the penicillin-binding proteins 2a (PBP2a). PBP2a have significantly less affinity for beta-lactam antibiotics compared to the other penicillin-binding proteins (PBPs) expressed by non-resistant strains. New treatments involving a combination of antibiotics and herbal extracts are being developed and used to inactivate PBP2a, allowing the previous ineffective antibiotics to be more effective.

Ebola Vp40 In Exosomes Can Cause Immune Cell Dysfunction, Michelle Pleet, Allison Mathiesen, Catherine Demarino, Yao Akpamagbo, Robert Barclay, Sergey N. Iordanskiy, +6 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Ebola virus (EBOV) is an enveloped, ssRNA virus from the family Filoviridae capable of causing severe hemorrhagic fever with up to 80–90% mortality rates. The most recent outbreak of EBOV in West Africa starting in 2014 resulted in over 11,300 deaths; however, long-lasting persistence and recurrence in survivors has been documented, potentially leading to further transmission of the virus. We have previously shown that exosomes from cells infected with HIV-1, HTLV-1 and Rift Valley Fever virus are able to transfer viral proteins and non-coding RNAs to naïve recipient cells, resulting in an altered cellular activity. In the current manuscript, we …

Transcriptomic Analysis Implicates The P53 Signaling Pathway In The Establishment Of Hiv-1 Latency In Central Memory Cd4 T Cells In An In Vitro Model, Cory White, Bastiaan Moesker, Nadejda Beliakova-Bethell, Laura Martins, Celsa Spina, Alberto Bosque, +4 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The search for an HIV-1 cure has been greatly hindered by the presence of a viral reservoir that persists despite antiretroviral therapy (ART). Studies of HIV-1 latency in vivo are also complicated by the low proportion of latently infected cells in HIV-1 infected individuals. A number of models of HIV-1 latency have been developed to examine the signaling pathways and viral determinants of latency and reactivation. A primary cell model of HIV-1 latency, which incorporates the generation of primary central memory CD4 T cells (TCM), full-length virus infection (HIVNL4-3) and ART to suppress virus replication, was used to investigate the …

P16ink4a Expression And Immunologic Aging In Chronic Hiv Infection, Susan Ribeiro, Jeffrey Milush, Edecio Cunha-Neto, Esper Kallas, Jorge Kalil, Luiz Felipe D. Passero, Peter W. Hunt, Steven Deeks, Douglas F. Nixon, Devi Sengupta

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Chronic HIV infection is characterized by increased immune activation and immunosenescence. p16 INK4a (p16) is a member of the cyclin-dependent kinase antagonist family that inhibits cellular proliferation, and its protein expression increases during normal chronological aging. However, some infectious diseases can increase the expression of this anti-proliferative protein, potentially accelerating immunological aging and dysfunction. In order to investigate the immunological aging in HIV patients, p16 protein expression was evaluated by flow cytometry, in T cell subsets in a cohort of chronically HIV-infected patients on and off ART as well as age-matched healthy controls. Results showed that untreated HIV-infected subjects exhibited …

Chemokine Levels In The Penile Coronal Sulcus Correlate With Hiv-1 Acquisition And Are Reduced By Male Circumcision In Rakai, Uganda., Jessica L Prodger, Ronald H Gray, Brett Shannon, Kamnoosh Shahabi, Xiangrong Kong, Kate Grabowski, Godfrey Kigozi, Fred Nalugoda, David Serwadda, Maria J Wawer, Steven J Reynolds, Cindy M. Liu, Aaron A R Tobian, Rupert Kaul

Environmental and Occupational Health Faculty Publications

Individual susceptibility to HIV is heterogeneous, but the biological mechanisms explaining differences are incompletely understood. We hypothesized that penile inflammation may increase HIV susceptibility in men by recruiting permissive CD4 T cells, and that male circumcision may decrease HIV susceptibility in part by reducing genital inflammation. We used multi-array technology to measure levels of seven cytokines in coronal sulcus (penile) swabs collected longitudinally from initially uncircumcised men enrolled in a randomized trial of circumcision in Rakai, Uganda. Coronal sulcus cytokine levels were compared between men who acquired HIV and controls who remained seronegative. Cytokines were also compared within men before …

Interleukin-17a Promotes Cd8 T Cell Cytotoxicity To Facilitate West Nile Virus Clearance, Amber M. Paul, Dhiraj Acharya, Penghua Wang, Jianfeng Dai, David Gate

Publications

CD8 T cells are crucial components of immunity and play a vital role in recovery from West Nile virus (WNV) infection. Here, we identify a previously unrecognized function of interleukin-17A (IL-17A) in inducing cytotoxic-mediator gene expression and promoting CD8 T cell cytotoxicity against WNV infection in mice. We find that IL-17A-deficient (Il17a/) mice are more susceptible to WNV infection and develop a higher viral burden than wild-type (WT) mice. Interestingly, the CD8 T cells isolated from Il17a/ mice are less cytotoxic and express lower levels of cytotoxic-mediator genes, which can be restored by supplying recombinant IL-17A in vitro and in …

Antiviral Cd8(+) T Cells Restricted By Human Leukocyte Antigen Class Ii Exist During Natural Hiv Infection And Exhibit Clonal Expansion., Srinika Ranasinghe, Pedro A Lamothe, Damien Z Soghoian, Samuel W Kazer, Michael B Cole, Alex K Shalek, Nir Yosef, R. Brad Jones, Faith Donaghey, Chioma Nwonu, Priya Jani, Gina M Clayton, Frances Crawford, Janice White, Alana Montoya, Karen Power, Todd M Allen, Hendrik Streeck, Daniel E Kaufmann, Louis J Picker, John W Kappler, Bruce D Walker

Microbiology, Immunology, and Tropical Medicine Faculty Publications

CD8(+) T cell recognition of virus-infected cells is characteristically restricted by major histocompatibility complex (MHC) class I, although rare examples of MHC class II restriction have been reported in Cd4-deficient mice and a macaque SIV vaccine trial using a recombinant cytomegalovirus vector. Here, we demonstrate the presence of human leukocyte antigen (HLA) class II-restricted CD8(+) T cell responses with antiviral properties in a small subset of HIV-infected individuals. In these individuals, T cell receptor β (TCRβ) analysis revealed that class II-restricted CD8(+) T cells underwent clonal expansion and mediated killing of HIV-infected cells. In one case, these cells comprised 12% …

Spyb, A Small Heme-Binding Protein, Affects The Composition Of The Cell Wall In Streptococcus Pyogenes, Rebecca J. Edgar, Jing Chen, Sashi Kant, Elena Rechkina, Jeffrey S. Rush, Lennart S. Forsberg, Bernhard Jaehrig, Parastoo Azadi, Veronika Tchesnokova, Evgeni V. Sokurenko, Haining Zhu, Konstantin V. Korotkov, Vijay Pancholi, Natalia Korotkova

Molecular and Cellular Biochemistry Faculty Publications

Streptococcus pyogenes (Group A Streptococcus or GAS) is a hemolytic human pathogen associated with a wide variety of infections ranging from minor skin and throat infections to life-threatening invasive diseases. The cell wall of GAS consists of peptidoglycan sacculus decorated with a carbohydrate comprising a polyrhamnose backbone with immunodominant N-acetylglucosamine side-chains. All GAS genomes contain the spyBA operon, which encodes a 35-amino-acid membrane protein SpyB, and a membrane-bound C3-like ADP-ribosyltransferase SpyA. In this study, we addressed the function of SpyB in GAS. Phenotypic analysis of a spyB deletion mutant revealed increased bacterial aggregation, and reduced sensitivity to β-lactams of the …

Laboratory Exercises In Microbiology: Discovering The Unseen World Through Hands-On Investigation, Joan Petersen, Susan Mclaughlin

Open Educational Resources

The exercises in this laboratory manual are designed to engage students in hand-on activities that reinforce their understanding of the microbial world. Topics covered include: staining and microscopy, metabolic testing, physical and chemical control of microorganisms, and immunology. The target audience is primarily students preparing for a career in the health sciences, however many of the topics would be appropriate for a general microbiology course as well.

Replication-Transciption Switch In Human Mitochondria, Karen Agaronyan

Graduate School of Biomedical Sciences Theses and Dissertations

Coordinated replication and expression of mitochondrial genome is critical for metabolically active cells during various stages of development. However, it is not known whether replication and transcription can occur simultaneously without interfering with each other and whether mtDNA copy number can be regulated by the transcription machinery. Human mitochondrial RNA polymerase (mtRNAP) is a central enzyme involved in gene expression in mitochondria. It generates genome-size polycistronic transcripts and also makes replication primers at two origins of replication. MtRNAP is distantly related to phage T7 RNAP. While T7 RNAP is optimized to produce large amounts of transcripts to overcompete the bacterial …

Type I Interferon Induction By Neisseria Gonorrhoeae: Dual Requirement Of Cyclic Gmp-Amp Synthase And Toll-Like Receptor 4, Warrison A. Andrade, Sarika Agarwal, Shunyan Mo, Scott A. Shaffer, Joseph P. Dillard, Tobias Schmidt, Veit Hornung, Katherine A. Fitzgerald, Evelyn A. Kurt-Jones, Douglas T. Golenbock

Katherine A. Fitzgerald

The innate immune system is the first line of defense against Neisseria gonorrhoeae (GC). Exposure of cells to GC lipooligosaccharides induces a strong immune response, leading to type I interferon (IFN) production via TLR4/MD-2. In addition to living freely in the extracellular space, GC can invade the cytoplasm to evade detection and elimination. Double-stranded DNA introduced into the cytosol binds and activates the enzyme cyclic-GMP-AMP synthase (cGAS), which produces 2'3'-cGAMP and triggers STING/TBK-1/IRF3 activation, resulting in type I IFN expression. Here, we reveal a cytosolic response to GC DNA that also contributes to type I IFN induction. We demonstrate that …