Medical Immunology Commons^™

Transcriptional Profiling Of Immune Responses In Nhps After Low-Dose, Vsv-Based Vaccination Against Marburg Virus, Cecilia A. Prator, Brianna M. Doratt, Kyle L. O'Donnell, Justin Lack, Amanda N. Pinski, Stacy M. Ricklefs, Craig A. Martens, Ilhem Messaoudi, Andrea Marzi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Infection with Marburg virus (MARV), the causative agent of Marburg virus disease (MVD), results in haemorrhagic disease and high case fatality rates (>40%) in humans. Despite its public health relevance, there are no licensed vaccines or therapeutics to prevent or treat MVD. A vesicular stomatitis virus (VSV)-based vaccine expressing the MARV glycoprotein (VSV-MARV) is currently in clinical development. Previously, a single 10 million PFU dose of VSV-MARV administered 1–5 weeks before lethal MARV challenge conferred uniform protection in nonhuman primates (NHPs), demonstrating fast-acting potential. Additionally, our group recently demonstrated that even a low dose VSV-MARV (1000 PFU) protected NHPs …

Extracellular Vesicles Released After Cranial Radiation: An Insight Into An Early Mechanism Of Brain Injury., Suriyan Sukati, Jenni Ho, Luksana Chaiswing, Pradoldej Sompol, Harshul Pandit, Wendy Wei, Tadahide Izumi, Quan Chen, Heidi Weiss, Teresa Noel, Subbarao Bondada, D Allan Butterfield, Daret K St Clair

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Cranial radiation is important for treating both primary brain tumors and brain metastases. A potential delayed side effect of cranial radiation is neurocognitive function decline. Early detection of CNS injury might prevent further neuronal damage. Extracellular vesicles (EVs) have emerged as a potential diagnostic tool because of their unique membranous characteristics and cargos. We investigated whether EVs can be an early indicator of CNS injury by giving C57BJ/6 mice 10 Gy cranial IR. EVs were isolated from sera to quantify: 1) number of EVs using nanoparticle tracking analysis (NTA); 2) Glial fibrillary acidic protein (GFAP), an astrocyte marker; and 3) …

Similarly Efficacious Anti-Malarial Drugs Sj733 And Pyronaridine Differ In Their Ability To Remove Circulating Parasites In Mice, Arya Sheelanair, Aleksandra S. Romanczuk, Rosemary A. Aogo, Rohit Nemai Haldar, Lianne I. M. Lansink, Deborah Cromer, Yandira G. Salinas, R. Kiplin Guy, James S. Mccarthy, Miles P. Davenport, Ashraful Haque, David S. Khoury

Pharmaceutical Sciences Faculty Publications

BACKGROUND: Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the "parasite clearance curve", has been critical for assessing drug efficacy; yet underlying mechanisms remain partly unresolved. The clearance curve may be shaped both by the rate at which drugs kill parasites, and the rate at which drug-affected parasites are removed from circulation.

METHODS: In this context, two anti-malarials, SJ733, and an ACT partner drug, pyronaridine …

Establishment And Verification Of A Sars Cov2 Antibody Detection Assay Comparing Venous And Mitra Samples, Stephen C. Mayer

Theses and Dissertations--Medical Sciences

During the COVID-19 pandemic in 2020, the need for highly-specific, wide-spread, and rapid serological testing surged. In this study, we showed very strong positive correlation between venous blood collection and Mitra home sampling kits for the detection of anti- spike IgGs using an in-house ELISA protocol (based on a protocol from Mt. Sinai). This study demonstrates the utility of using at-home, patient-centric testing to enhance the sero-surveillance methods currently in place for viral tracking and monitoring.

Inhibition Of Bruton Tyrosine Kinase Reduces Neuroimmune Cascade And Promotes Recovery After Spinal Cord Injury, Chen Guang Yu, Vimala Bondada, Hina Iqbal, Kate L. Moore, John C. Gensel, Subbarao Bondada, James W. Geddes

Physiology Faculty Publications

Microglia/astrocyte and B cell neuroimmune responses are major contributors to the neurological deficits after traumatic spinal cord injury (SCI). Bruton tyrosine kinase (BTK) activation mechanistically links these neuroimmune mechanisms. Our objective is to use Ibrutinib, an FDA-approved BTK inhibitor, to inhibit the neuroimmune cascade thereby improving locomotor recovery after SCI. Rat models of contusive SCI, Western blot, immunofluorescence staining imaging, flow cytometry analysis, histological staining, and behavioral assessment were used to evaluate BTK activity, neuroimmune cascades, and functional outcomes. Both BTK expression and phosphorylation were increased at the lesion site at 2, 7, 14, and 28 days after SCI. Ibrutinib …

Interleukin-10 Suppression Enhances T-Cell Antitumor Immunity And Responses To Checkpoint Blockade In Chronic Lymphocytic Leukemia., J R Rivas, Y Liu, S S Alhakeem, J M Eckenrode, F Marti, J P Collard, Y Zhang, K A Shaaban, N Muthusamy, G C Hildebrandt, L Chen, J S Thorson, M Leggas, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

T-cell dysfunction is a hallmark of B-cell Chronic Lymphocytic Leukemia (CLL), where CLL cells downregulate T-cell responses through regulatory molecules including programmed death ligand-1 (PD-L1) and Interleukin-10 (IL-10). Immune checkpoint blockade (ICB) aims to restore T-cell function by preventing the ligation of inhibitory receptors like PD-1. However, most CLL patients do not respond well to this therapy. Thus, we investigated whether IL-10 suppression could enhance antitumor T-cell activity and responses to ICB. Since CLL IL-10 expression depends on Sp1, we utilized a novel, better tolerated analogue of the Sp1 inhibitor mithramycin (MTM

Mitochondrial Phenotypes In Purified Human Immune Cell Subtypes And Cell Mixtures, Shannon Rausser, Caroline Trumpff, Marlon A. Mcgill, Alex Junker, Wei Wang, Siu-Hong Ho, Anika Mitchell, Kalpita R. Karan, Catherine Monk, Suzanne C. Segerstrom, Rebecca G. Reed, Martin Picard

Psychology Faculty Publications

Using a high-throughput mitochondrial phenotyping platform to quantify multiple mitochondrial features among molecularly defined immune cell subtypes, we quantify the natural variation in mitochondrial DNA copy number (mtDNAcn), citrate synthase, and respiratory chain enzymatic activities in human neutrophils, monocytes, B cells, and naïve and memory T lymphocyte subtypes. In mixed peripheral blood mononuclear cells (PBMCs) from the same individuals, we show to what extent mitochondrial measures are confounded by both cell type distributions and contaminating platelets. Cell subtype-specific measures among women and men spanning four decades of life indicate potential age- and sex-related differences, including an age-related elevation in mtDNAcn, …

Long-Term Survival Of Older Patients Hospitalized For Covid-19. Do Clinical Characteristics Upon Admission Matter?, Michał Chojnicki, Agnieszka Neumann-Podczaska, Mikołaj Seostianin, Zofia Tomczak, Hamza Tariq, Jerzy Chudek, Sławomir Tobis, Iwona Mozer-Lisewska, Aleksandra Suwalska, Andrzej Tykarski, Piotr Merks, Sylwia Kropińska, Małgorzata Sobieszczańska, Frank Romanelli, Katarzyna Wieczorowska-Tobis

Pharmacy Practice and Science Faculty Publications

Older adults are particularly susceptible to COVID-19 in terms of both disease severity and risk of death. To compare clinical differences between older COVID-19 hospitalized survivors and non-survivors, we investigated variables influencing mortality in all older adults with COVID-19 hospitalized in Poznań, Poland, through the end of June 2020 (n = 322). In-hospital, post-discharge, and overall 180-day mortality were analyzed. Functional capacity prior to COVID-19 diagnosis was also documented. The mean age of subjects was 77.5 ± 10.0 years; among them, 191 were females. Ninety-five (29.5%) died during their hospitalization and an additional 30 (9.3%) during the post-discharge period …

Bias Of The Immune Response To Pneumocystis Murina Does Not Alter The Ability Of Neonatal Mice To Clear The Infection, Cathryn J. Kurkjian, Melissa L. Hollifield, David J. Feola, Beth A. Garvy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Newborn mice are unable to clear Pneumocystis (PC) infection with the same efficiency as adults due, in part, to their inability to develop a robust immune response to infection until three weeks of age. It is known that infants tend develop a Th2 skewed response to antigen so we sought to determine whether a biased cytokine response altered the clearance of PC infection in neonatal mice. P. murina infection in neonatal mice resulted in increased IL-4 expression by CD4 T cells and myeloid cells, augmented IL-13 secretion within the airways and increased arginase activity in the airways, indicative of Th2-type …

Chemotherapy-Induced Cognitive Impairment: Focus On The Intersection Of Oxidative Stress And Tnfα., Nicole G Rummel, Luksana Chaiswing, Subbarao Bondada, Daret K St Clair, D Allan Butterfield

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Chemotherapy-induced cognitive impairment (CICI) has been observed in a large fraction of cancer survivors. Although many of the chemotherapeutic drugs do not cross the blood-brain barrier, following treatment, the structure and function of the brain are altered and cognitive dysfunction occurs in a significant number of cancer survivors. The means by which CICI occurs is becoming better understood, but there still remain unsolved questions of the mechanisms involved. The hypotheses to explain CICI are numerous. More than 50% of FDA-approved cancer chemotherapy agents are associated with reactive oxygen species (ROS) that lead to oxidative stress and activate a myriad of …

Apobec Mutagenesis Is Concordant Between Tumor And Viral Genomes In Hpv-Positive Head And Neck Squamous Cell Carcinoma, Daniel L. Faden, Krystle A. Lang Kuhs, Maoxuan Lin, Adam Langenbucher, Maisa Pinheiro, Meredith Yeager, Michael Cullen, Joseph F. Boland, Mia Steinberg, Sara Bass, James S. Lewis, Michael S. Lawrence, Robert L. Ferris, Lisa Mirabello

Epidemiology and Environmental Health Faculty Publications

APOBEC is a mutagenic source in human papillomavirus (HPV)-mediated malignancies, including HPV+ oropharyngeal squamous cell carcinoma (HPV + OPSCC), and in HPV genomes. It is unknown why APOBEC mutations predominate in HPV + OPSCC, or if the APOBEC-induced mutations observed in both human cancers and HPV genomes are directly linked. We performed sequencing of host somatic exomes, transcriptomes, and HPV16 genomes from 79 HPV + OPSCC samples, quantifying APOBEC mutational burden and activity in both host and virus. APOBEC was the dominant mutational signature in somatic exomes. In viral genomes, there was a mean of five (range 0–29) mutations per …

Targeted Oral Delivery Of Paclitaxel Using Colostrum-Derived Exosomes, Raghuram Kandimalla, Farrukh Aqil, Sara S. Alhakeem, Jeyaprakash Jeyabalan, Neha Tyagi, Ashish Agrawal, Jun Yan, Wendy Spencer, Subbarao Bondada, Ramesh C. Gupta

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) is the most common type accounting for 84% of all lung cancers. Paclitaxel (PAC) is a widely used drug in the treatment of a broad spectrum of human cancers, including lung. While efficacious, PAC generally is not well tolerated and its limitations include low aqueous solubility, and significant toxicity. To overcome the dose-related toxicity of solvent-based PAC, we utilized bovine colostrum-derived exosomes as a delivery vehicle for PAC for the treatment of lung cancer. Colostrum provided higher yield of exosomes and could be loaded with higher …

Report Of The Pathogenesis And Pathophysiology Of Lyme Disease Subcommittee Of The Hhs Tick Borne Disease Working Group, Sam T. Donta, Leith J. States, Wendy A. Adams, Troy Bankhead, Nicole Baumgarth, Monica E. Embers, Robert B. Lochhead, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

An understanding of the pathogenesis and pathophysiology of Lyme disease is key to the ultimate care of patients with Lyme disease. To better understand the various mechanisms underlying the infection caused by Borrelia burgdorferi, the Pathogenesis and Pathophysiology of Lyme Disease Subcommittee was formed to review what is currently known about the pathogenesis and pathophysiology of Lyme disease, from its inception, but also especially about its ability to persist in the host. To that end, the authors of this report were assembled to update our knowledge about the infectious process, identify the gaps that exist in our understanding of …

The Effects Of Myelin On Macrophage Activation Are Phenotypic Specific Via Cpla2 In The Context Of Spinal Cord Injury Inflammation, Timothy J. Kopper, Bei Zhang, William M. Bailey, Kara E. Bethel, John C. Gensel

Physiology Faculty Publications

Spinal cord injury (SCI) produces chronic, pro-inflammatory macrophage activation that impairs recovery. The mechanisms driving this chronic inflammation are not well understood. Here, we detail the effects of myelin debris on macrophage physiology and demonstrate a novel, activation state-dependent role for cytosolic phospholipase-A2 (cPLA₂) in myelin-mediated potentiation of pro-inflammatory macrophage activation. We hypothesized that cPLA₂ and myelin debris are key mediators of persistent pro-inflammatory macrophage responses after SCI. To test this, we examined spinal cord tissue 28-days after thoracic contusion SCI in 3-month-old female mice and observed both cPLA₂ activation and intracellular accumulation of lipid-rich myelin …

Laboratory Markers Predictive Of Fulminant Clostridioides Difficile Infection Refractory To Fluid Resuscitation, Omar Ahmad, Timothy N. Crawford, Vaneet Arora, Mitu Karki Maskey

Internal Medicine Faculty Publications

Background

Old age, leucocytosis, hypoalbuminemia, and elevated creatinine have been identified as risk factors for fulminant Clostridioides difficile infection (CDI). High ATLAS scores have also been linked to fatal disease. The affiliated studies, however, involved patients prescribed metronidazole - a regimen no longer standard of care. The variables were thus reassessed in patients prescribed optimal therapy.

Methods

Adults hospitalized with CDI at University of Kentucky Medical Center were retrospectively reviewed. Enrolled subjects were separated according to disease classification i.e. non-severe/severe versus fulminant CDI. Fulminant patients were further subdivided into hypotensive persons responsive to fluid resuscitation, and those with sequent shock, …

Immunomodulatory Effects Of Azithromycin Revisited: Potential Applications To Covid-19, Vincent J. Venditto, Dalia Haydar, Ahmed K. Abdel-Latif, John C. Gensel, Michael I. Anstead, Michelle G. Pitts, Jarrod W. Creameans, Timothy J. Kopper, Chi Peng, David J. Feola

Pharmaceutical Sciences Faculty Publications

The rapid advancement of the COVID-19 pandemic has prompted an accelerated pursuit to identify effective therapeutics. Stages of the disease course have been defined by viral burden, lung pathology, and progression through phases of the immune response. Immunological factors including inflammatory cell infiltration and cytokine storm have been associated with severe disease and death. Many immunomodulatory therapies for COVID-19 are currently being investigated, and preliminary results support the premise of targeting the immune response. However, because suppressing immune mechanisms could also impact the clearance of the virus in the early stages of infection, therapeutic success is likely to depend on …

S. Gordonii-Produced Hydrogen Peroxide Modulates Mir-663a And Ccl20 Expression In Oral Epithelial Cells, Marshall Houston Maynard

Theses and Dissertations--Medical Sciences

The mechanisms through which a persistent recognition of commensal bacteria by oral epithelial cells (OECs) mitigates an uncontrolled inflammatory response of the oral mucosa remain unknown. CCL20 secretion by OECs in response to pathogenic bacteria is regulated by S. gordonii (Sg)-induced miR-663a; nevertheless, the mechanisms involved in these Sg-modulated responses remain to be elucidated. Since Sg is a hydrogen peroxide (H₂O₂) producer, and H₂O₂ has been shown to stimulate miRNA expression, we hypothesized that H₂O₂ could be involved in Sg-induced miR663a and CCL20 responses. Expression of miR663a …

Immunostimulatory Membrane Proteins Potentiate H. Pylori-Induced Carcinogenesis By Enabling Caga Translocation, Matthew G. Varga, Cecily R. Wood, Julia Butt, Mackenzie E. Ryan, Wei-Cheng You, Kaifeng Pan, Tim Waterboer, Meira Epplein, Carrie L. Shaffer

Veterinary Science Faculty Publications

Infection with Helicobacter pylori is the single greatest risk factor for developing gastric adenocarcinoma. In prospective, population-based studies, seropositivity to the uncharacterized H. pylori proteins Hp0305 and Hp1564 was significantly associated with cancer risk in East Asia. However, the mechanism underlying this observation has not been elucidated. Here, we show that Hp0305 and Hp1564 act in concert with previously ascribed H. pylori virulence mechanisms to orchestrate cellular alterations that promote gastric carcinogenesis. In samples from 546 patients exhibiting premalignant gastric lesions, seropositivity to Hp0305 and Hp1564 was significantly associated with increased gastric atrophy across all stomach conditions. In vitro, …

Neutrophil: A New Player In Metastatic Cancers, Mengyue Wu, Mutian Ma, Zhenya Tan, Hong Zheng, Xia Liu

Toxicology and Cancer Biology Faculty Publications

The interaction between cancer cells and immune cells is important for the cancer development. However, much attention has been given to T cells and macrophages. Being the most abundant leukocytes in the blood, the functions of neutrophils in cancer have been underdetermined. They have long been considered an “audience” in the development of cancer. However, emerging evidence indicate that neutrophils are a heterogeneous population with plasticity, and subpopulation of neutrophils (such as low density neutrophils, polymorphonuclear-myeloid-derived suppressor cells) are actively involved in cancer growth and metastasis. Here, we review the current understanding of the role of neutrophils in cancer development, …

Hdac6 Mediates Macrophage Inos Expression And Excessive Nitric Oxide Production In The Blood During Endotoxemia, Yan Wang, Ke Wang, Jian Fu

Toxicology and Cancer Biology Faculty Publications

Excessive nitric oxide (NO) production and NO-mediated nitrative stress contribute to vascular dysfunction, inflammation, and tissue injury in septic shock. New therapeutic targets are urgently needed to provide better control of NO level during septic shock. In the present study, we investigated the role of HDAC6 in the regulation of NO production and nitrative stress in a mouse model of endotoxin-induced septic shock. HDAC6 deficient mice and a specific HDAC6 inhibitor were utilized in our studies. Our data clearly indicate that HDAC6 is an important mediator of NO production in macrophages. HDAC6 mediates NO production through the regulation of iNOS …

Cell Cycle Regulation In Macrophages And Susceptibility To Hiv-1, Isabella A. T. M. Ferreira, James Zachary Porterfield, Ravindra K. Gupta, Petra Mlcochova

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Macrophages are the first line of defence against invading pathogens. They play a crucial role in immunity but also in regeneration and homeostasis. Their remarkable plasticity in their phenotypes and function provides them with the ability to quickly respond to environmental changes and infection. Recent work shows that macrophages undergo cell cycle transition from a G0/terminally differentiated state to a G1 state. This G0-to-G1 transition presents a window of opportunity for HIV-1 infection. Macrophages are an important target for HIV-1 but express high levels of the deoxynucleotide-triphosphate hydrolase SAMHD1, which restricts viral DNA synthesis by decreasing levels of dNTPs. While …

Aging Induces B Cell Defects And Decreased Antibody Responses To Influenza Infection And Vaccination, Daniela Frasca, Bonnie B. Blomberg

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background: Aging is characterized by a progressive decline in the capacity of the immune system to fight influenza virus infection and to respond to vaccination. Among the several factors involved, in addition to increased frailty and high-risk conditions, the age-associated decrease in cellular and humoral immune responses plays a relevant role. This is in large part due to inflammaging, the chronic low-grade inflammatory status of the elderly, associated with intrinsic inflammation of the immune cells and decreased immune function.

Results: Aging is usually associated with reduced influenza virus-specific and influenza vaccine-specific antibody responses but some elderly individuals with higher pre-exposure …

The Promise Of Anti-Idiotype Revisited, Heinz Köhler, Anastas Pashov, Thomas Kieber-Emmons

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The promise of idiotype-based therapeutics has been disappointing forcing a new look at the concept and its potential to generate an effective approach for immunotherapy. Here, the idiotype network theory is revisited with regard to the development of efficacious anti-idiotype vaccines. The experience of polyclonal anti-Idiotype reagents in animal models as well as an understanding of the immune response in humans lends to the proposition that polyclonal anti-Idiotype vaccines will be more effective compared to monoclonal-based anti-Idiotype vaccines. This novel strategy can be adapted in Biotech-standard production of therapeutic antibodies.

The Stimulation Of Dendritic Cells By Cationic Lipids, John Peyton Bush

Theses and Dissertations--Medical Sciences

The discovery that cationic lipids can independently stimulate the immune system has generated interest in their potential as vaccine adjuvants. Here, we show that the cationic lipid R-DOTAP can independently stimulate type 1 interferon production in dendritic cells in both primary culture and immortalized cell culture. Levels of type 1 interferon production are cell line-dependent and limited in vitro by lipid-induced cell death. We show that cationic lipids can independently activate TLR-7 and TLR-9, suggesting a mechanism for type 1 interferon induction. This TLR-stimulatory activity is not restricted to R-DOTAP and can be extended to other similar cationic lipids in …

The Role Of Cd8 T Cell Immunodominance And Regulatory T Cells In Neonatal Immunity To Influenza Virus, Luke Heil

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Neonates are more susceptible to influenza virus infection than adults, resulting in increased morbidity and mortality as well as delayed clearance of the virus. Efforts to improve influenza infection outcomes in neonates typically center on prevention, although current vaccines fall short of complete protection and can only be administered in humans after 6 months of life. We propose that as the neonatal immune system responds differently than the adult immune system, interventions that are efficacious or tolerable in adults cannot be guaranteed to perform the same in neonates. T cell vaccines that target conserved influenza virus epitopes have been proposed …

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

Microbiology, Immunology, and Molecular Genetics Faculty Publications

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

Floxed-Cassette Allelic Exchange Mutagenesis Enables Markerless Gene Deletion In Chlamydia Trachomatis And Can Reverse Cassette-Induced Polar Effects, Gabrielle Keb, Robert Hayman, Kenneth A. Fields

Microbiology, Immunology, and Molecular Genetics Faculty Publications

As obligate intracellular bacteria, Chlamydia spp. have evolved numerous, likely intricate, mechanisms to create and maintain a privileged intracellular niche. Recent progress in elucidating and characterizing these processes has been bolstered by the development of techniques enabling basic genetic tractability. Florescence-reported allelic exchange mutagenesis (FRAEM) couples chromosomal gene deletion with the insertion of a selection cassette encoding antibiotic resistance and green fluorescent protein (GFP). Similar to other bacteria, many chlamydial genes exist within polycistronic operons, raising the possibility of polar effects mediated by insertion cassettes. Indeed, FRAEM-mediated deletion of Chlamydia trachomatis tmeA negatively impacts the expression of tmeB. We …

Antibody Epitope Specificity For Dsdna Phosphate Backbone Is An Intrinsic Property Of The Heavy Chain Variable Germline Gene Segment Used, Tatjana Srdic-Rajic, Heinz Kohler, Vladimir Jurisic, Radmila Metlas

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Analysis of protein sequences by the informational spectrum method (ISM) enables characterization of their specificity according to encoded information represented with defined frequency (F). Our previous data showed that F(0.367) is characteristic for variable heavy chain (VH) domains (a combination of variable (V), diversity (D) and joining (J) gene segments) of the anti-phosphocholine (PC) T15 antibodies and mostly dependent on the CDR2 region, a site for PC phosphate group binding. Because the T15 dsDNA-reactive U4 mutant also encodes F(0.367), we hypothesized that the same frequency may also be characteristic for anti-DNA antibodies. Data obtained from an analysis of 60 spontaneously …

The Conquest Of Pus -- A History Of Bitumen, Creosote And Carbolic Acid, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

In the Western world from antiquity on, open wounds were treated topically with petroleum-derived substances, such as bitumen, asphalt, pitch, and tar. The immediate aim was to stifle bleeding and ease pain but a potential benefit was preventing local corruption with pus formation. In the early 19th century, creosote was recovered from bitumen and found to reduce suppuration. Carbolic acid was later isolated from creosote and recognized as an underlying active agent. In the 1860s, carbolic acid was first employed by Jules Lemaire to treat local skin infections and later by Joseph Lister to prevent the suppuration in compound fractures. …

Transcriptomic Insights On The Virulence-Controlling Csra, Badr, Rpon, And Rpos Regulatory Networks In The Lyme Disease Spirochete, William K. Arnold, Christina R. Savage, Kathryn G. Lethbridge, Trever C. Smith, Catherine A. Brisette, Janakiram Seshu, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Borrelia burgdorferi, the causative agent of Lyme disease, survives in nature through a cycle that alternates between ticks and vertebrates. To facilitate this defined lifestyle, B. burgdorferi has evolved a gene regulatory network that ensures transmission between those hosts, along with specific adaptations to niches within each host. Several regulatory proteins are known to be essential for the bacterium to complete these critical tasks, but interactions between regulators had not previously been investigated in detail, due to experimental uses of different strain backgrounds and growth conditions. To address that deficit in knowledge, the transcriptomic impacts of four critical …