Cell and Developmental Biology Commons^™

Mycoplasma Co-Infection Is Associated With Cervical Cancer Risk, Cameron Klein, Kandali Samwel, Crispin Kahesa, Julius Mwaiselage, John T. West, Charles Wood, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Tanzania faces one of the highest cervical cancer burdens in the world. Recent work has suggested that the bacterial family Mycoplasmataceae is associated with higher levels of human papillomavirus (HPV), human immunodeficiency virus (HIV), and pre-cancerous cervical lesions. Mycoplasmataceae infection in Tanzania is not well understood, especially when considering the differences between sexually transmitted species of Mycoplasmataceae. To establish the prevalence of common Mycoplasmataceae cervical infections and evaluate their relationship with risk factors for cervical cancer, 1160 Tanzanian women responded to an epidemiological questionnaire and were tested for HIV, HPV, cervical lesions, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma spp., and Lactobacillus …

Epstein Barr Virus-Immortalizedｂlymphocytes Exacerbate Experimental Autoimmune Encephalomyelitis In Xenograft Mice, Pascal Polepole, Alison Bartenslager, Yutong Liu, Thomas M. Petro, Samodha C. Fernando, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Multiple sclerosis (MS) is the most common autoimmune disorder affecting the central nervous system. Epstein-Barr virus (EBV) is a causative agent for infectious mononucleosis (IM) that is associated with MS pathogenesis. However, the exact mechanism by which EBV, specifically in IM, increases the risk for MS remains unknown. EBV immortalizes primary B lymphocytes in vitro and causes excessive B lymphocyte proliferation in IM in vivo. In asymptomatic carriers, EBV-infected B lymphocytes still proliferate to certain degrees, the process of which is tightly controlled by the host immune systems. Experimental autoimmune encephalomyelitis (EAE) mimics key features of MS in humans and …

A Decade In Review: A Systematic Review Of Universal Influenza Vaccines In Clinical Trials During The 2010 Decade, Brigette N. Corder, Brianna L. Bullard, Gregory Poland, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

On average, there are 3–5 million severe cases of influenza virus infections globally each year. Seasonal influenza vaccines provide limited protection against divergent influenza strains. Therefore, the development of a universal influenza vaccine is a top priority for the NIH. Here, we report a comprehensive summary of all universal influenza vaccines that were tested in clinical trials during the 2010–2019 decade. Of the 1597 studies found, 69 eligible clinical trials, which investigated 27 vaccines, were included in this review. Information from each trial was compiled for vaccine target, vaccine platform, adjuvant inclusion, clinical trial phase, and results. As we look …

Species D Adenoviruses As Oncolytic Viral Vectors, Brianna L. Bullard, Brigette N. Corder, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Oncolytic adenoviruses (Ad) have shown promising results in the therapeutic treatment of cancer. Ad type 5 (Ad5) is the most extensively utilized Ad type. However, several limitations exist to using Ad5 as an oncolytic virus, including high levels of anti-Ad5 neutralizing antibodies in the population, binding of the Ad5 hexon to blood coagulation factor X leading to liver sequestration and toxicity, and reduced expression of the primary receptor CAR on many tumors. Here, we use in vitro methods to explore the oncolytic potential of four alternative Ad types (Ad26, 28, 45, and 48) belonging to the species D Ad subgroup …

Recommendations For Measuring Hiv Reservoir Size In Cure- Directed Clinical Trials., Luis J. Montaner, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

Therapeutic strategies are being clinically tested either to eradicate the latent HIV reservoir or to achieve virologic control in the absence of antiretroviral therapy (ART). Attaining this goal will require a consensus on how best to measure the levels of persistently-infected cells with the potential to cause viral rebound upon ART cessation to assess the results of cure-directed strategies in vivo. Current measurements assess different aspects of the HIV provirus and its functionality, and produce divergent results. Here, we provide the collective insight and position from the BEAT-HIV Martin Delaney Collaboratory on which viral measurements to prioritize in HIV cure-directed …

Uterine Torsion Dystocia Complicated By Perosomus Elumbis In An Angus Calf Associated With A Consanguineous Mating, Alyssa B. Helms, Riley E. Thompson, Sam Lawton, Jessica L. Petersen, Allison Watson, Mee-Ja Sula, David J. Steffen, Brian K. Whitlock

School of Veterinary and Biomedical Sciences: Faculty Publications

A six-year-old multiparous Angus cow was presented for dystocia. Vaginal and rectal examinations revealed an approximately 360° counterclockwise uterine torsion. The torsion was corrected by rolling the cow counterclockwise (three episodes) with the aid of a plank coupled with manual detorsion via the vagina. The placement of obstetric chains followed by manual traction ultimately delivered a stillborn male calf with evidence of vertebral aplasia, arthrogryposis, and abdominal organ herniation. Patient history and subsequent parentage verification revealed that the calf was the result of a consanguineous (mother to son) mating. Tissue samples from the affected calf and blood samples from the …

Identification Of Immunogenic Epitopes That Permit The Detection Of Antigen-Specific T Cell Responses In Multiple Serotypes Of Group B Coxsackievirus Infections, Ninaad Lasrado, Arunakumar Gangaplara, Rajkumar Arumugam, Chandirasegara Massilamany, Sayli Pokal, Yuzhen Zhou, Shi-Hua Xiang, David Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Coxsackievirus group B (CVB) contains six serotypes that can affect various organs. Some of these organ-specific diseases such as myocarditis and pancreatitis can be caused by more than one serotype. Thus, development of immunological tools common to multiple serotypes is desired. This is especially critical for analyzing antigen-specific T cell responses at a single cell level. To this end, we made efforts to identify the immunogenic epitopes of CVB3 leading us to localize three T cell epitopes within the viral protein 1 (VP1) namely, VP1 681–700, VP1 721–740 and VP1 771–790. First, we confirmed their immunogenicity in the immunization settings. …

First Records Of Established Populations Of Ixodes Scapularis (Acari: Ixodidae) Collected From Three Nebraska Counties, Lindsey E. Nielsen, Roberto Cortinas, Paul D. Fey, Peter C. Iwen, David H. Nielsen

School of Veterinary and Biomedical Sciences: Faculty Publications

Reported cases of Lyme disease in Nebraska have been assumed to be imported from other endemic areas. Previous surveillance efforts provided no evidence of established populations as only individual specimens of Ixodes scapularis (Say) had been collected. In the winter of 2018, adult I. scapularis were found on a dog at Two Rivers State Recreation Area, Douglas County, prompting tick collection at the site and nearby natural areas. In May 2019, all life stages of host-seeking I. scapularis were collected using dragging and flagging techniques in sites located near the Platte River in Douglas, Sarpy, and Saunders counties. This is …

Methods Of Treating Or Preventing Zika Virus Infection, Shi-Hua Xiang, Nicholas Palermo, Asit K. Pattnaik, Aryamay Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

This document relates to methods and materials for treating a mammal having a Zika virus (ZIKV) infection. For example, a composition including one or more non-nucleoside RNA polymerase inhibitors can be administered to a mammal having, or at risk of developing, a ZIKV infection to treat the mammal.

Recent Advances In The Diagnosis Of Classical Swine Fever And Future Perspectives, Lihua Wang, Rachel Madera, Yuzhen Li, D. Scott Mcvey, Jishu Shi

School of Veterinary and Biomedical Sciences: Faculty Publications

Classical swine fever (CSF) is a highly contagious viral disease of pigs, including wild boar. It is regarded as one of the major problems in the pig industry as it is still endemic in many regions of the world and has the potential to cause devastating epidemics, particularly in countries free of the disease. Rapid and reliable diagnosis is of utmost importance in the control of CSF. Since clinical presentations of CSF are highly variable and may be confused with other viral diseases in pigs, laboratory diagnosis is indispensable for an unambiguous diagnosis. On an international level, well-established diagnostic tests …

Evaluation Of A Baculovirus-Expressed Vp2 Subunit Vaccine For The Protection Of White-Tailed Deer (Odocoileus Virginianus) From Epizootic Hemorrhagic Disease, Sun Young Sunwoo, Leela E. Noronha, Igor Morozov, Jessie D. Trujilo, In Joong Kim, Erin E. Schirtzinger, Bonto Faburary, Barbara S. Drolet, Kinga Urbaniak, D. Scott Mcvey, David A. Meekins, Mitchell V. Palmer, Velmurugan Balaraman, William C. Wilson, Juergen A. Richt

School of Veterinary and Biomedical Sciences: Faculty Publications

Epizootic hemorrhagic disease virus (EHDV) is an arthropod-transmitted RNA virus and the causative agent of epizootic hemorrhagic disease (EHD) in wild and domestic ruminants. In North America, white-tailed deer (WTD) experience the highest EHD-related morbidity and mortality, although clinical disease is reported in cattle during severe epizootics. No commercially licensed EHDV vaccine is available in North America. The objective of this study was to develop and evaluate a subunit vaccine candidate to control EHD in WTD. Recombinant VP2 (rVP2) outer capsid proteins of EHDV serotypes 2 (EHDV-2) and 6 (EHDV-6) were produced in a baculovirus-expression system. Mice and cattle vaccinated …

Amphiphilic Cyclobutenes And Cylobutanes, Wantanee Sittiwong, Patrick H. Dussault, Raul G. Barletta, Robert Powers

School of Veterinary and Biomedical Sciences: Faculty Publications

This disclosure relates to amphiphilic compounds containing a cyclobutene or cyclobutane moiety. In some embodiments, the compounds are useful for treating infection by Mycobacterium such as Mycobacterium tuberculosis. Cyclobutene containing compounds are also useful as monomers in the preparation of amphiphilic polymers.

Non-Neuroinvasivevirusesand Uses Thereof, Gregory A. Smith, Patricia J. Sollars, Gary E. Pickard, Ekaterina E. Heldwein

School of Veterinary and Biomedical Sciences: Faculty Publications

Provided herein are compositions and methods for vaccination and research applications. In particular, provided herein are non-neuroinvasive herpesviruses and alpha herpesviruses and uses thereof.

Mitochondrial Metabolism In Astrocytes Regulates Brain Bioenergetics, Neurotransmission And Redox Balance, Jordan Rose, Christian Brian, Aglaia Pappa, Mihalis I. Panayiotidi, Rodrigo Franco

School of Veterinary and Biomedical Sciences: Faculty Publications

In the brain, mitochondrial metabolism has been largely associated with energy production, and its dysfunction is linked to neuronal cell loss. However, the functional role of mitochondria in glial cells has been poorly studied. Recent reports have demonstrated unequivocally that astrocytes do not require mitochondria to meet their bioenergetics demands. Then, the question remaining is, what is the functional role of mitochondria in astrocytes? In this work, we review current evidence demonstrating that mitochondrial central carbon metabolism in astrocytes regulates overall brain bioenergetics, neurotransmitter homeostasis and redox balance. Emphasis is placed in detailing carbon source utilization (glucose and fatty acids), …

Mechanisms Of Sex Hormones In Autoimmunity: Focus On Eae, Ninaad Lasrado, Ting Jia, Chandirasegaran Massilamany, Rodrigo Franco, Zsolt Illes, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Sex-related differences in the occurrence of autoimmune diseases is well documented, with females showing a greater propensity to develop these diseases than their male counterparts. Sex hormones, namely dihydrotestosterone and estrogens, have been shown to ameliorate the severity of inflammatory diseases. Immunologically, the beneficial effects of sex hormones have been ascribed to the suppression of effector lymphocyte responses accompanied by immune deviation from pro-inflammatory to anti-inflammatory cytokine production. In this review, we present our view of the mechanisms of sex hormones that contribute to their ability to suppress autoimmune responses with an emphasis on the pathogenesis of experimental autoimmune encephalomyelitis.

Evidence For Anti-Viral Effects Of Complete Freund’S Adjuvant In The Mouse Model Of Enterovirus Infection, Arunakumar Gangaplara, Chandirasegaran Massilamany, Ninaad Lasrado, David J. Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Group B coxsackieviruses (CVBs) belonging to the genus, Enterovirus and contain six serotypes that induce various diseases, whose occurrence may involve the mediation of more than one serotype. We recently identified immunogenic epitopes within coxsackieviruses B3 (CVB3) viral protein 1 that induce anti-viral T cell responses in mouse models of CVB infections. In our investigations to determine the protective responses of the viral epitopes, we unexpectedly noted that animals immunized with complete Freund’s adjuvant (CFA) alone and later challenged with CVB3 were completely protected against myocarditis. Similarly, the pancreatitis-inducing ability of CVB3 was remarkably reduced to only 10% in the …

Porcine Reproductive And Respiratory Syndrome Virus Reverse Genetics And The Major Applications, Jayeshbhai Chaudhari, Hiep Vu

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive sense, single-stranded RNA virus that is known to infect only pigs. The virus emerged in the late 1980s and became endemic in most swine producing countries, causing substantial economic losses to the swine industry. The first reverse genetics system for PRRSV was reported in 1998. Since then, several infectious cDNA clones for PRRSV have been constructed. The availability of these infectious cDNA clones has facilitated the genetic modifications of the viral genome at precise locations. Common approaches to manipulate the viral genome include site-directed mutagenesis, deletion of viral genes or …

An Evidence For Surface Expression Of An Immunogenic Epitope Of Sarcoplasmic/Endoplasmic Reticulum Calcium-Atpase2a On Antigen-Presenting Cells From Naive Mice In The Mediation Of Autoimmune Myocarditis, Rajkumar Arumugam, Bharathi Yalaka, Chandirasegara Massilamany, Ms Shihabudeen Haider Ali, Ninaad Lasrado, Sabarirajan Jayaraja, Jean-Jack Riethoven, Xinghui Sun, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

We recently reported identification of sarcoplasmic/endoplasmic reticulum calcium-ATPase2a (SERCA2a) 971–990, which induces atrial myocarditis by generating autoreactive T cells in A/J mice. However, it was unknown how antigen-sensitized T cells could recognize SERCA2a 971–990, since SERCA2a-expression is confined to an intracellular compartment. In this report, we present evidence that antigen-presenting cells (APCs) from lymphoid and non-lymphoid organs in naïve animals present SERCA2a 971–990 and stimulate antigen-specific T cells. Using major histocompatibility complex (MHC) class II dextramers for SERCA2a 971–990, we created a panel of T cell hybridomas and demonstrated that splenocytes from naïve A/J mice stimulated the hybridoma cells without …

Viral Myocarditis Involves The Generation Of Autoreactive T Cells With Multiple Antigen Specificities That Localize In Lymphoid And Non-Lymphoid Organs In The Mouse Model Of Cvb3 Infection, Rakesh H. Basavalingappa, Rajkumar Arumugam, Ninaad Lasrado, Bharathi Yalaka, Chandirasegara Massilamany, Arunakumar Gangaplara, Jean-Jack Riethoven, Shi-Hua Xiang, David Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Autoreactive T cells may contribute to post-viral myocarditis induced with Coxsackievirus B3 (CVB3), but the underlying mechanisms of their generation are unclear. Here, we have comprehensively analyzed the generation of antigen-specific, autoreactive T cells in the mouse model of CVB3 infection for antigens implicated in patients with myocarditis/dilated cardiomyopathy. First, comparative analysis of CVB3 proteome with five autoantigens led us to identify three mimicry epitopes, one each from adenine nucleotide translocator 1 (ANT), sarcoplasmic/ endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) and cardiac troponin I. None of these induced cross-reactive T cell responses. Next, we generated major histocompatibility complex (MHC) class …

Lps, A Tlr-4 Agonist And Viper A Tlr-4 Inhibitor Upregulate Phagocytosis Of Zymosan In Bv2 Cells, Sherouk Alzeory

Dissertations and Theses

Microglia cells are the first line of innate immunity defense in the central nervous system (CNS). They play a critical role in maintaining CNS homeostasis by having an active but yet balanced phagocytic activity. However, in various CNS related diseases, microglia cells have been shown to malfunction. In Alzheimer's Disease (AD), hyperactive microglia with impaired phagocytic activity is the main hallmark of this disease, along with the accumulation of amyloid-beta aggregates. Additionally, emerging new studies have suggested a fungal infection etiology to AD, specifically in relation to Candida albicans (C.albicans). Thus, understanding the mechanism of fungal clearance in the …

Prostate Cancer Resistance To Cabazitaxel Chemotherapy, Diane Begemann

Theses and Dissertations--Toxicology and Cancer Biology

The plasticity of prostate tumors contributes to the heterogeneity in response and acquisition of therapeutic resistance in advanced prostate cancer. Disruption of the phenotypic landscape via epithelial-mesenchymal transition (EMT) enables prostate tumors to invade and metastasize. Our previous studies demonstrated that cabazitaxel (a 2^nd generation FDA-approved taxane chemotherapy) that is used for treatment of castration-resistant prostate cancer (CRPC), causes reversal of EMT to mesenchymal-epithelial transition (MET). The present study examined the effect of sequencing cabazitaxel chemotherapy mediated MET on prostate tumor re-differentiation and its impact on overcoming resistance in models of advanced prostate cancer.

The presence of DHT (1nM) …

Dispelling The Mirage Of C4-Driven Drought Tolerance In Poaceae: A Phylogenomic Study, Matthew P. Nissenbaum

Graduate Research Theses & Dissertations

Climate change has been considered a key driver for adaptations in water usage efficiency (WUE) in plants. Perceptions persist that C4 photosynthesis is indicative of some level of WUE. Here, we examined the interaction and evolution of WUE within the grass family, Poaceae, as it pertains to photosynthetic pathway. Unique to this study is the magnitude of taxa sampled, presence of intrageneric sampling, and use of complete plastid genomes (plastomes) for phylogenomic analyses.

310 species were sampled, including 26 with newly sequenced plastomes, which were assembled de novo from next-generation sequencing data. Additional plastomes were downloaded from the National Center …

The Exploration Of Nanotoxicological Copper And Interspecific Saccharomyces Hybrids, Matthew Joseph Winans Phd

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nanotechnology takes advantage of cellular biology’s natural nanoscale operations by interacting with biomolecules differently than soluble or bulk materials, often altering normal cellular processes such as metabolism or growth. To gain a better understanding of how copper nanoparticles hybridized on cellulose fibers called carboxymethyl cellulose (CMC) affected growth of Saccharomyces cerevisiae, the mechanisms of toxicity were explored. Multiple methodologies covering genetics, proteomics, metallomics, and metabolomics were used during this investigation. The work that lead to this dissertation discovered that these cellulosic copper nanoparticles had a unique toxicity compared to copper. Further investigation suggested a possible ionic or molecular mimicry …

Novel Roles Of Tobacco-Associated Genes Underlying Disparate Survival In Appalachian Head And Neck Squamous Cell Carcinoma, Brenen William Papenberg

Graduate Theses, Dissertations, and Problem Reports (ETD)

Head and neck squamous cell carcinoma (HNSCC) is an aggressive neoplasm primarily caused by tobacco consumption or human papillomavirus (HPV) infection. Incidence and mortality rates for HNSCC vary geographically. Appalachian residents consume tobacco products to a greater extent than national averages, a risk factor known to promote HPV-negative HNSCC through increased genomic instability. Male Appalachian patients display significantly worse relative survival than Appalachian females or non-Appalachian residents of either sex. Secondary analysis of available cancer registry outcome data from 2007-2013 indicates that white males with stage IV oral cavity/pharyngeal (OC/P) HNSCC are responsible for the decreased male survival observed within …

Role Of Ciliary Proteins Adp Ribosylation Factor Like Gtpase 13b (Arl13b) And Bardet-Biedl Syndrome-8 (Bbs8) In Photoreceptor Outer Segment Morphogenesis, Maintenance, And Viability, Tanya L. Dilan

Graduate Theses, Dissertations, and Problem Reports (ETD)

Photoreceptor neurons are modified primary cilia with an extended ciliary compartment known as the outer segment (OS). The mechanisms behind the elaboration of photoreceptor cilia, OS morphogenesis, and maintenance remain poorly understood. In this work, we focused on dissecting the role of two ciliary proteins, the small GTPase ADP-ribosylation factor-like GTPase 13B (ARL13B) and Bardet-Biedl Syndrome-8 (BBS8) in the context of photoreceptor biology. Both BBS8 and ARL13B are linked to defects in ciliogenesis (cilia development) and Retinitis Pigmentosa (vision loss). ARL13B is implicated in regulating ciliary length, and BBS8 is part of the Bardet-Biedl Syndrome complex (BBSome); the BBSome is …

Grainyhead-Like 2 Sensitizes Cells To Natural Killer Cell Cytotoxicity And Promotes The Interferon Response, Ian Philip Macfawn

Graduate Theses, Dissertations, and Problem Reports (ETD)

Our research determined that the epithelial master transcription factor Grainyhead-like 2 (GRHL2) promotes sensitivity to Natural Killer (NK) cell-mediated killing, and modulates the interferon I (IFN-I) response of epithelial cells. Immune surveillance by NK cells constitutes a major selective pressure for circulating tumor cells. Epithelial (GRHL2-expressing) cells exhibited significantly higher rates of NK conjugation, a crucial step in direct cell-mediated cytotoxicity. Mechanistically, GRHL2 upregulates expression of intercellular adhesion molecule 1 (ICAM-1), a cell surface molecule critical for NK to target cell synaptogenesis. GRHL2 epigenetically regulates gene expression, and we found that GRHL2 mutant proteins unable to interact with the epigenetic …

Evidence Of Y Chromosome Long Non-Coding Rnas Involved In The Radiation Response Of Male Non-Small Cell Lung Cancer Cells, Tayvia Brownmiller

Graduate Theses, Dissertations, and Problem Reports (ETD)

Non-small cell lung cancer (NSCLC) is the number one cause of cancer related mortality in the United States and worldwide. Advanced and therapeutically resistant lung tumors contribute to the high rate of mortality from NSCLC, therefore there is a need for new methods of diagnosing and treating this disease. Long non-coding RNAs (lncRNAs) have been shown to be a crucial component of human molecular biology, regulating nearly every cellular pathway from chromatin condensation to transcription and translation. Furthermore, many lncRNAs have been classified as oncogenes or tumor suppressors, highlighting the various molecular mechanisms they are involved in regarding the formation …

Breast Cancer Associated Muscle Fatigue: Novel Targets To Improve Survival And Quality Of Life, Hannah Elizabeth Wilson

Graduate Theses, Dissertations, and Problem Reports (ETD)

Women diagnosed with breast cancer (BC) currently represent the largest group of cancer survivors in the United States, accounting for over 20% of those living after a cancer diagnosis. Most BC survivors report an unusual degree of fatigue, which can present prior to diagnosis and continue for many years after treatment cessation. Recent studies show that deficits in muscle function predict shorter survival in cancer, perhaps due to the fact that fatigue is known to reduce a patient’s tolerance to anti-cancer therapies. Therefore, improving muscle function in BC patients has the potential to improve both quality of life and survival …

The Effects Of Internal Physiology On Polyphenic Horn Development In The Dung Beetle Onthophagus Taurus, Naomi Garrett Williamson

Graduate Theses, Dissertations, and Problem Reports (ETD)

An organism’s phenotype can be affected in development by alterations to gene expression based on environmental inputs. Nutrition is one such environmental input and the central regulator of development of large horn or small horn phenotypes in the dung beetle species, Onthophagus taurus. However, little is known about the nature of chemical compounds that are critical to this plastic horn development. To better understand these compounds, we are utilizing an untargeted metabolomic approach as well as a targeted gene approach. Through the metabolomic approach, it was uncovered that environmental conditions tend to have a greater impact on metabolomic composition …

Investigation Of Glutamate Carboxypeptidase Ii Roles In The Folate Cycle Dependent Reproduction And Development Of Caenorhabditis Elegans, Jessica M. Derham

Masters Theses

Glutamate Carboxypeptidase II (GCPII) is a transmembrane, zinc metallopeptidase that is expressed in a wide range of organisms, including roundworms, mice, and humans. In humans, GCPII is primarily expressed in the prostate, kidneys, small intestine, and central nervous system. Within the small intestine, the expected function of GCPII is to aid in the absorption of dietary folate from the intestinal lumen. GCPII cleaves excess glutamates from folate to yield monoglutamated folate which is then readily transported into the enterocyte. Folate can then be used through the one carbon metabolic cycle for the synthesis of nucleotides, conversion of homocysteine to methionine, …