Biochemistry, Biophysics, and Structural Biology Commons^™

A High-Androgen Microenvironment Inhibits Granulosa Cell Proliferation And Alters Cell Identity, Renee M. Mcfee, Sarah M. Romereim, Alexandria P. Snider, Adam F. Summers, William E. Pohlmeier, Scott G. Kurz, Robert A. Cushman, John S. Davis, Jennifer R. Wood, Andrea S. Cupp

School of Veterinary and Biomedical Sciences: Faculty Publications

A naturally occurring bovine model with excess follicular fluid androstenedione (High A4), reduced fertility, and polycystic ovary syndrome (PCOS)-like characteristics has been identified. We hypothesized High A4 granulosa cells (GCs) would exhibit altered cell proliferation and/or steroidogenesis. Microarrays of Control and High A4 GCs combined with Ingenuity Pathway Analysis indicated that High A4 GCs had cell cycle inhibition and increased expression of microRNAs that inhibit cell cycle genes. Granulosa cell culture confirmed that A4 treatment decreased GC proliferation, increased anti-Müllerian hormone, and increased mRNA for CTNNBIP1. Increased CTNNBIP1 prevents CTNNB1 from interacting with members of the WNT signaling pathway thereby …

A High-Throughput Approach To Characterizing Arv1 On The Regulation Of Lipid Homeostasis Uncovers A Novel Interaction With Epidermal Growth Factor Receptor, Nicholas Anthony Wachowski

Graduate School of Biomedical Sciences Theses and Dissertations

Acyl-CoA cholesterol acyl transferase related enzyme-2 required for viability 1 (ARV1) was first recognized in Saccharomyces cerevisiae in a study done in 2000 by Tinkelenberg et al. In yeast, the deletion of ARV1 results in numerous defects including abnormal sterol trafficking [1], the reduction of sphingolipid metabolism [2], synthesis of glycosylphosphatidylinositol (GPI) anchor [3], ER stress [4], and hypersensitivity of fatty acids leading to lipoapoptosis [5]. Arv1 germline deletion in mice displayed a lean phenotype with increased energy [6]. In humans, ARV1 mutations lead to epileptic encephalopathy [7].

Non-alcoholic fatty liver disease (NAFLD) consists of simple steatosis to non-alcoholic steatohepatitis …

Mitochondrial Transfer From Mesenchymal Stem Cells Improves Neuronal Metabolism After Oxidant Injury In Vitro: The Role Of Miro1, Nancy Tseng, Scott C Lambie, Christopher Q Huynh, Bridget Sanford, Manisha Patel, Paco S Herson, D Ryan Ormond

Faculty, Staff and Students Publications

Stroke-induced cerebral ischemia is a major cause of death and disability. The disruption of blood flow results in neuronal and glial cell death leading to brain injury. Reperfusion restores oxygen to the affected tissue, but can also cause damage through an enhanced oxidative stress and inflammatory response. This study examines mitochondrial transfer from MSC to neurons and the role it plays in neuronal preservation after oxidant injury. We observed the transfer of mitochondria from MSC to mouse neurons in vitro following hydrogen peroxide exposure. The observed transfer was dependent on cell-to-cell contact and led to increased neuronal survival and improved …

Maldi-Tof Ms Biomarker Detection Models To Distinguish Rtx Toxin Phenotypes Of Moraxella Bovoculi Strains Are Enhanced Using Calcium Chloride Supplemented Agar, Matthew M. Hille, Michael L. Clawson, Aaron M. Dickey, Justin H. Lowery, John Dustin Loy

School of Veterinary and Biomedical Sciences: Faculty Publications

Moraxella bovoculi is the bacterium most often cultured from ocular lesions of cattle with infectious bovine keratoconjunctivitis, also known as bovine pinkeye. Some strains of M. bovoculi contain operons encoding for a repeats-in-toxin (RTX) toxin, which is a known virulence factor of multiple veterinary pathogens. We explored the utility of MALDI-TOF MS and biomarker detection models to classify the presence or absence of an RTX phenotype in M. bovoculi. Ninety strains that had undergone whole genome sequencing were classified by the presence or absence of complete RTX operons and confirmed with a visual assessment of hemolysis on blood agar. Strains …

A Biophysical Investigation Of Hiv-1 Envelope Cytoplasmic-Tail Mediated Retention In The Gag Lattice, Nicholas Scott Groves

Electronic Theses and Dissertations

The infectivity of Human Immunodeficiency Virus is critically dependent on successful incorporation of the trimeric viral envelope glycoprotein, Envelope (Env), into Gag lattice assembly sites on the host-cell plasma membrane during virus biogenesis. The mechanistic nature of interaction between Gag, the structural protein, and Env, the viral spike, are dependent on the Gag matrix (MA) and Env cytoplasmic tail (CT) domains. Env laterally diffuses on the host cell plasma membrane until encountering a budding Gag lattice, where it is retained until particle scission and release. The mechanism of Env entry and retention in the lattice remains elusive and enigmatic. Here …

Optimized Microbial Recombinant Production Of Hiv-1 Anti-Envelope Antibody Fragments With Applications To Single Particle Tracking Of Virus Assembly, Merissa Michelle Bruns

Electronic Theses and Dissertations

In my findings, I have established a set series of protocols to recombinantly produce, purify and apply various fluorescent probes in vitro for the fluorescent labeling and study of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) protein during HIV viral assembly. There remains insufficient knowledge about the molecular dynamics and interactions of HIV-1 Env protein with its counterpart, Gag, on the inner host cell surface during assembly of a mature virus particle. There also remains an insufficient amount of data for the understanding and clarification of the mechanism of action of a known host cell HIV-1 restriction factor, …

Female And Male-Controlled Livestock Holdings Impact Pastoralist Food Security And Women’S Dietary Diversity, Henriette Gitungwa, Christopher Gustafson, E.Y. Jimenez, E. Wesley F. Peterson, M. Mwanzalila, Asha Makweta, E. Komba, R.R. Kazwala, J.A.K. Mazet, Elizabeth Vanwormer

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Food insecurity is a global problem that requires a One Health approach. As many households in low- and middle-income nations rely on crops and livestock that they produce to meet their household’s needs, food security and nutrition are closely linked to the health of animals and the environment. Resources controlled by women are more often allocated to uses that benefit the entire household, such as food, health, and educating children, than men’s resources. However, studies of gender control of resources among pastoralist societies are scant. We examined the effect of female and male control of livestock resources on food …

Sars-Cov-2: An Investigation On Mutagenicity And Its Effects On Infectivity And Mortality, Tyler Elliott Silverwood

Honors Theses and Capstones

SARS-CoV-2, the etiological agent of the COVID-19 pandemic, has rapidly become a worldwide public health concern. Classified as a betacoronavirus, it is the third human coronavirus (HCoV) to emerge in the 21st century that causes severe disease, alongside SARS-CoV and MERS-CoV. The genome consists of open reading frames encoding accessory proteins and four structural proteins, including the spike protein which is a key determinant of host cell tropism. Mutations within the genome, particularly the spike gene, have been linked in-vitro to increased binding affinity to the human receptor angiotensin-converting enzyme 2 (hACE2), increased fitness in human hosts, and immune evasion. …

Impact Of The Histidine‐Containing Phosphocarrier Protein Hpr On Carbon Metabolism And Virulence In Staphylococcus Aureus, Linda Pätzold, Anne-Christine Brausch, Evelyn-Laura Bielefeld, Lisa Zimmer, Greg A. Somerville, Markus Bischoff, Rosmarie Gaupp

School of Veterinary and Biomedical Sciences: Faculty Publications

Carbon catabolite repression (CCR) is a common mechanism pathogenic bacteria use to link central metabolism with virulence factor synthesis. In gram‐positive bacteria, catabolite control protein A (CcpA) and the histidine‐containing phosphocarrier protein HPr (encoded by ptsH) are the predominant mediators of CCR. In addition to modulating CcpA activity, HPr is essential for glucose import via the phosphotransferase system. While the regulatory functions of CcpA in Staphylococcus aureus are largely known, little is known about the function of HPr in CCR and infectivity. To address this knowledge gap, ptsH mutants were created in S. aureus that either lack the open reading …

An Evaluation Of The Anti-Carcinogenic Response Of Major Isothiocyanates In Non-Metastatic And Metastatic Melanoma Cells, Melina Mitsiogianni, Sotiris Kyriakou, Ioannis Anestopoulos, Dimitrios T. Trafalis, Maria V. Deligiorgi, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidi

School of Veterinary and Biomedical Sciences: Faculty Publications

Malignant melanoma is one of the most deadly types of solid cancers, a property mainly attributed to its highly aggressive metastatic form. On the other hand, different classes of isothiocy- anates, a class of phytochemicals, present in cruciferous vegetables have been characterized by considerable anti-cancer activity in both in vitro and in vivo experimental models. In the current study, we investigated the anti-cancer response of five isothiocyanates in an in vitro model of melanoma consisting of non-metastatic (A375, B16F-10) and metastatic (VMM1, Hs294T) malignant melanoma as well as non-melanoma epidermoid carcinoma (A431) and non-tumorigenic melanocyte-neighboring keratinocyte (HaCaT) cells. Our aim …

Il-10 As A Th2 Cytokine: Differences Between Mice And Humans, Mahima T. Rasquinha, Meghna Sur, Ninaad Lasrado, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

The discovery of interleukin (IL)-10 more than 30 years ago marked the beginning of our understanding of how cytokines regulate immune responses, based on cross-regulation between T helper (Th)1 and Th2 cytokines. Although multiple cell types were shown to produce IL-10, its identity as a Th2 cytokine remained strong since it was rigidly associated with Th2 clones in mice, whereas both Th1 and Th2 clones could secrete IL-10 in humans. However, as new Th1/Th2 cell functionalities emerged, anti-inflammatory action of IL-10 gained more attention than its inhibitory effect on Th1 cells, which may occur as an indirect consequence of suppression …

Of Pigs And Men: The Best-Laid Plans For Prevention And Control Of Swine Fevers, Jishu Shi, Lihua Wang, David Scott Mcvey

School of Veterinary and Biomedical Sciences: Faculty Publications

John Steinbeck drew the title of his novel “Of Mice and Men” from a line in a Robert Burns poem “To a mouse”: “The best-laid plans of mice and men/Go often awry.” Unlike John Steinbeck who used the title to mirror the characters who were struggling during the Great Depression to the mouse whose nest was accidentally destroyed by the poet (Burns 1785), we chose this line to emphasize that the best-laid plan can go wrong in infectious disease control and prevention. Here, we will discuss the contributing factors behind the global successes and failures in the prevention and control …

Special Issue: Shiga Toxin-Producing Escherichia Coli, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

Globally, Shiga toxin-producing Escherichia coli (STEC) is an important cause of diarrheal disease, most notably hemorrhagic colitis, and post-diarrheal sequela, such as hemolytic-uremic syndrome (HUS) [1]. Cattle are a major reservoir of STEC, with approx- imately half of the cases in humans attributable to foodborne exposure [2]. Prevention of human illness has mainly been through food safety measures [2]. Despite extensive research, no other generally accepted and effective preventive measures or therapies for STEC infections in human patients are available [3]. Many questions remain about STEC virulence factors, pathogenesis, detection, and other aspects that necessitate a continua- tion of basic …

Inhibition Of Zika Virus Replication By G-Quadruplex-Binding Ligands, Prativa Majee, Aryamav Pattnaik, Bikash R. Sahoo, Uma Shankar, Asit K. Pattnaik, Amit Kumar, Debasis Nayak

School of Veterinary and Biomedical Sciences: Faculty Publications

Zika virus (ZIKV), a mosquito-transmitted Flavivirus, emerged in the last decade causing serious diseases and affecting human health globally. Currently, no licensed vaccines or antivirals are available to combat ZIKV, although several vaccine candidates are in the pipeline. In recent years, the presence of non-canon- ical G-quadruplex (GQ) secondary structures in viral genomes has ignited significant attention as potential targets for anti- viral strategy. In this study, we identified several novel conserved potential GQ structures by analyzing published ZIKV genome sequences using an in-house algorithm. Bio- physical and biochemical analysis of the RNA sequences con- taining these potential GQ sequences …

Molecular And Genetic Studies On A Sipd/Ipad-Related Virulence Spike Protein From Immune-Suppressive Particles Of A Drosophila Parasitoid, Carlo Miguel A. Sevilla

Dissertations and Theses

Parasitoid wasps are effective biological control agents that have evolved intricate host immune suppression strategies to overcome host immune defenses. The most important anti-parasite defense mechanism is encapsulation, where the host’s blood cells surround the wasp egg. In the Drosophila/Leptopilina host-parasitoid system, extracellular vesicles (EVs) are oviposited along with the wasp egg. The EVs possess spikes and contain hundreds of proteins, some of which enable wasp eggs to escape encapsulation by changing the morphology and function of hemocytes, or killing them. Previous studies have identified an abundant surface/spike protein (SSp40) from Leptopilina heterotoma EVs. While p40, a predicted …

Mechanisms By Which Mnte-2-Pyp Suppresses Prostate Cancer Cell Growth, Yuxiang Zhu

Theses & Dissertations

Prostate cancer patients are often treated with radiotherapy. MnTE-2-PyP, is a superoxide dismutase (SOD) mimic and a known radioprotector of normal tissues. Our recent work demonstrates that MnTE-2-PyP also inhibits prostate cancer progression with radiotherapy; however, the mechanisms remain unclear. In this thesis, we identified that MnTE-2-PyP-induced intracellular H2O2 levels are critical in inhibiting growth of prostate cancer cells. We found that MnTE-2-PyP induced protein oxidations in PC3 cells and one major group of oxidized protein targets were involved in energy metabolism. The oxidative phosphorylation rates were significantly enhanced in both PC3 and LNCaP cells with MnTE-2-PyP treatment, but mitochondrial …

Correction: Moxley, R.A., Et Al. Intimate Attachment Of Escherichia Coli O157:H7 To Urinary Bladder Epithelium In The Gnotobiotic Piglet Model. Microorganisms 2020, 8, 263, Rodney A. Moxley, Tom W. Bargar, Stephen D. Kachman, Diane R. Baker, David Francis

School of Veterinary and Biomedical Sciences: Faculty Publications

The authors wish to make the following corrections to this paper [1]: On page 2, the sentence that reads, “Hence, EHEC is a rare but established cause of HUS in children and adults.” should read, “Hence, EHEC is a rare but established cause of UTI-associated HUS in children and adults.” On page 4, the sentence that reads, “As noted previously, 14 of 126 (13.3%) piglets orally inoculated with EHEC O157:H7 strains developed mild to moderate purulent cystitis within 8 d PI [25] (Table 1).” should read, “As noted previously, 14 of 105 (13.3%) piglets orally inoculated with EHEC O157:H7 strains …

Comprehensive Survey Of The Litter Bacterial Communities In Commercial Turkey Farms, Bishnu Adhikari, Guillermo Tellez-Isaias, Tieshan Jiang, Brian Wooming, Young Min Kwon

Poultry Science Faculty Publications and Presentations

The importance of microbiota in the health and diseases of farm animals has been well-documented for diverse animal species. However, studies on microbiotas in turkey and turkey farms are relatively limited as compared to other farm animal species. In this study, we performed a comprehensive survey of the litter microbiotas in 5 commercial turkey farms in the Northwest Arkansas (H, M, V, K, and R farms) including one farm with positive incidence of cellulitis (R farm). Altogether 246 boot swabs were used for 16S rRNA gene profiling of bacterial communities. At phylum level, 11 major bacterial phyla (≥0.01%) were recovered. …

Role Of Β-Glucan Structure In Dectin-1 Homo- And Hetero-Oligomerization In Innate Anti-Fungal Immunity, Eduardo U. Anaya

Biomedical Sciences ETDs

Dectin-1A is a C-type Lectin innate immunoreceptor that recognizes β-(1,3)-glucan, a structural component of Candida species cell walls. Dectin-1 has eight alternative splice isoforms including, A and B. Innate immunocytes can express one or both isoforms, but neither their relative responsiveness to β-glucan nor the potential for inter-isoform signaling cross-talk is well understood. In this study, we determine how the different structures of soluble β-glucans affect both isoforms and unravel how differences in glucan structure impact the earliest events in Dectin-1 signaling. Using quantitative microscopy techniques, we explored the role of glucan structure on Dectin-1A oligomerization, which is thought to …

Regulation Of In Vitro And In Vivo Hepatic Stellate Cell Activation By The Ayrl Hydrocarbon Receptor, Shivakumar Rayavara Veerabhadraiah

Boise State University Theses and Dissertations

Liver fibrosis is a pathological condition characterized by the excessive deposition of extracellular matrix material by activated hepatic stellate cells (HSCs). We recently reported that activation of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases HSC activation in vitro and in mouse models of experimental liver fibrosis. The goal of this project was to determine the mechanism by which AhR activation impacts HSC activation and the subsequent development of liver fibrosis. It is possible that HSCs are direct cellular targets for TCDD. Alternatively, TCDD could increase HSC activation indirectly by exacerbating hepatocyte damage …

Dna Aptamer‑Based Rolling Circle Amplification Product As A Novel Immunological Adjuvant, Adil Sabr Al-Ogaili, Rohana Liyanage, Jack O. Lay Jr., Tieshan Jiang, Christine N. Vuong, Shilpi Agrawal, Thallapuranam Krishnaswamy Suresh Kumar, Luc R. Berghman, Billy M. Hargis, Young Min Kwon

Chemistry & Biochemistry Faculty Publications and Presentations

Several agonists to CD40 have shown to induce acquired immune responses. Here, we developed and evaluated the rolling circle amplification (RCA) products that are based on anti-CD40 DNA aptamers as a novel vaccine adjuvant. First, we developed DNA aptamers with specific binding affinity to chicken CD40 extra domain (chCD40ED). Next, we prepared the RCA products that consist of these aptamers to increase the spanning space and overall binding affinity to chCD40ED. Using 8 DNA aptamer candidates, 4 aptamer-based RCA products (aptamer RCAs) were generated, each consisting of two distinct aptamers. We demonstrated that all 4 aptamer RCAs significantly induced the …

Copper And Cobalt Metal Conjugation Enhances Flaviviral Replication, And Denv/Zikv Caused Thrombocytopenia Suppresses Integrin Signaling, Shovan Dutta

Biomedical Sciences Theses & Dissertations

Vector control is a global concern, and effective strategies have been on the way. Among the many different strategies, insect repellents to protect us from blood-feeding arthropods are very common. Food processing or preservatives in food expose us to several chemicals associated with insect repellents, insecticides, and pesticides. Using metallic conjugation with plant extracts or essential oils has become a widespread strategy to increase their efficacy. But it is worth it to be aware that some of those metallic compounds like Cobalt or Copper upon conjugation with thiosemicarbazone ligands derived from Citral and 2-acetylethiazole at the center coordination enhance both …

Microbiota Analysis Of Chickens Raised Under Stressed Conditions, Rabindra Kumar Mandal, Tieshan Jiang, Robert Wideman Jr, Troy Lohrmann, Young Min Kwon

Poultry Science Faculty Publications and Presentations

A substantial progress has been made toward understanding stress-associated gut and extraintestinal microbiota. However, a comprehensive understanding of the extraintestinal microbiota of chickens raised under stressed conditions is lacking. In this study, chickens were raised on a wire-floor model to induce stress, and the microbiota in the gut (ceca) and extraintestinal sites (blood, femur, and tibia) were characterized at different ages (1, 17, and 56 days) using 16S rRNA gene microbiota profiling. Open reference OTU picking showed extraintestinal sites had a significantly higher number of unassigned OTUs compared to ceca across all ages of chickens. Extraintestinal sites of all ages, …

Mesenchymal Stem Cells And Their Extracellular Vesicles: A Potential Game Changer For The Covid-19 Crisis, Dina H. Kassem, Mohamed M. Kamal

Pharmacy

Corona virus disease 2019 (COVID-19) is a global public health crisis. The high infectivity of the disease even from non-symptomatic infected patients, together with the lack of a definitive cure or preventive measures are all responsible for disease outbreak. The severity of COVID-19 seems to be mostly dependent on the patients’ own immune response. The over-activation of the immune system in an attempt to kill the virus, can cause a “cytokine storm” which in turn can induce acute respiratory distress syndrome (ARDS), as well as multi-organ damage, and ultimately may lead to death. Thus, harnessing the immunomodulatory properties of mesenchymal …

The Investigation Of Surface Structures On Various Pathogens And Their Interactions With The Human Immune System, Carmen M. Villalobos

Biomedical Engineering ETDs

The cell surface is the first interface the host immune system encounters and

its investigation has led to a better understanding of cellular biology and types of

pathways that pathogens target in a host cell. The cell surface has evolved to include

many functions such as manipulation of the cytoskeleton, cell signaling, membrane

trafficking, adhesion, and integration into host tissue. The pathogens of interest are

the pathogenic fungus, Candida albicans, and the parasite, Giardia lamblia and we

investigate the consequences of drug treatments on the cell surface, leading to

promising new targets.

Investigating The Role Of Quaking In Antigen Uptake And Cross-Presentation By Dendritic Cells, Yating Li

Dissertations and Theses (Open Access)

Dendritic cells (DCs) are considered the most potent antigen presenting cells (APC) due to their superior capability of cross-presenting exogenous antigens to CD8⁺ T cell for strong adaptive immune responses. They internalize foreign antigens by phagocytosis, endocytosis or macropinocytosis, which are then processed in endosomal compartments and loaded onto MHC Class I molecules. However, the molecular mechanisms regulating exogenous antigen uptake and cross-presentation by DCs are not fully understood.

In this study, we discovered that an RNA-binding protein, Quaking (QKI) plays a pivotal role in antigen uptake by DCs. Our previous studies in neural stem cells and microglia have …

In Ovo Administration Of Defined Lactic Acid Bacteria Previously Isolated From Adult Hens Induced Variations In The Cecae Microbiota Structure And Enterobacteriaceae Colonization On A Virulent Escherichia Coli Horizontal Infection Model In Broiler Chickens, Margarita A. Arreguin-Nava, Brittany D. Graham, Bishnu Adhikari, Melissa Agnello, Callie M. Selby, Xochitl Hernandez-Velasco, Christine N. Vuong, Bruno Solis-Cruz, Daniel Hernandez-Patlan, Juan David Latorre, Guillermo Tellez Jr., Billy M. Hargis, Guillermo Tellez-Isaias

Poultry Science Faculty Publications and Presentations

The effects of in ovo administration of a defined lactic acid microbiota (LAM), previously isolated from adult hens, in the cecae microbiota structure and Enterobacteriaceae colonization after exposure to virulent Escherichia coli during the hatching phase of broiler chickens were evaluated. Embryos inoculated with LAM showed a significant (P < 0.05) reduction of Enterobacteriaceae colonization at day-of-hatch (DOH) and day (d) 7. Furthermore, there was a significant increase in total lactic acid bacteria on DOH, body weight (BW) DOH, BW d7, and d0–d7 BW gain and reduced mortality d0–d7 was observed in the LAM group compared with that in phosphate-buffered saline (PBS) control. …

Establishment Of Mucuna Bracteata As A Platform For The Production Of Anti-Toxoplasma Immunoglobulin, Abd Aziz Nazrin

Student Works (2020-2029)

Production of recombinant proteins using plant system has gained a continuous momentum in the past decade. Traditionally, recombinant proteins are commercially produced through mammalian cell lines and microbial fermentation. These conventional platforms have intricate scalability, safety issues and costly. On the other hand, plants are easily scalable, economically competitive and do not harbor animal or human pathogens. As eukaryote, plants are capable to carry out complex post-translational modifications that are necessary for functional biological activities such as disulphide bridging and glycosylation. The aim of this study is to establish a new platform for the production of recombinant pharmaceutical protein in …

Modulating Matrix Metalloproteases And Inflammation In Huntington’S Disease, Alejandro Lopez Ramirez

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Huntington’s disease (HD) is a rare and incurable autosomal neurodegenerative disease affecting 1-10 in every 100,000 people in the world. There is no cure for HD and treatments available alleviate certain symptoms for short periods of time. Evidence suggests that neuropathology of HD begins with the proteolysis of the mutated Huntingtin (mHTT) protein. A variety of proteases, like the matrix metalloproteases, cleave mHTT creating proteinaceous fragments that are thought to be neurotoxic. As these fragments increase in the brain, the damage to neurons also increases, leading to chronic inflammation due to hyper reactive microglia and astrocytes attempting to minimize and …

The Autoimmune System: The Effect Of Physiological Stressors On Autoantibody Glycosylation And Fidelity Of Autoantibody Profiles, Rahil Kheirkhah

Graduate School of Biomedical Sciences Theses and Dissertations

The presence of thousands of autoantibodies (aABs) in the human sera is typical, and therefore it is possible to identify an aAB profile for each individual. In the first part of this thesis, we will show the cerebrospinal fluid also exhibits an extraordinarily complex immunoglobulin G aAB profile that is composed of thousands of aABs. We show that the pattern of expression of individual aABs in CSF closely mimics that in the blood, indicative of a blood-based origin for CSF aABs. In addition, using longitudinal serum samples obtained over a span of nine years, we show remarkable stability in aAB …