Biochemistry, Biophysics, and Structural Biology Commons^™

Determining The Effects Of Methanol, Ethanol, Isopropanol, And Glycerol On Both Thermal Stability And Catalytic Activity Of Rv0045c, An Enzyme From M. Tuberculosis, Katelyn Baumer

Undergraduate Honors Thesis Collection

Tuberculosis (TB) is a highly infectious respiratory disease contracted through the inhalation of Mycobacterium tuberculosis. Serine hydrolases are abundant in M. tuberculosis and serve as a model for studying the inhibition of TB. Rv0045c is an example of such with little known regarding its biological function. Rv0045c was exposed to methanol, ethanol, isopropanol, or glycerol and the effects of varying concentration of these alcohols on the catalytic efficiency and thermal stability of the enzyme was determined. The thermal stability of Rv0045c was found to decrease with concentration of methanol, ethanol, or isopropanol. The opposite was true of the thermal stability …

Nitrosative Stress Sensing In Porphyromonas Gingivalis: Structure And Function Of The Heme Binding Transcriptional Regulator Hcpr, Benjamin R. Belvin

Theses and Dissertations

Porphyromonas gingivalis, a Gram negative anaerobe implicated in the progression of periodontal disease, is capable of surviving and causing infection despite high levels of reactive nitrogen species found in the oral cavity due to its efficient nitrosative stress response. HcpR is an important sensor-regulator that plays a vital step in the initiation of the nitrosative stress response in many Gram negative anaerobic bacteria. We employ a combination of X-ray crystallography, SAXS, resonance Raman spectroscopy, UV-Vis spectroscopy, and molecular biology techniques to better understand this key regulator. Knockout of the hcpR gene in W83 P. gingivalis results in the inability of …

Exosomes Serve As Novel Modes Of Tick-Borne Flavivirus Transmission From Arthropod To Human Cells And Facilitates Dissemination Of Viral Rna And Proteins To The Vertebrate Neuronal Cells, Wenshuo Zhou, Michael Woodson, Biswas Neupane, Fengwei Bai, Michael B. Sherman, Kyung H. Choi, Girish Neelakanta, Hameeda Sultana

Biological Sciences Faculty Publications

Molecular determinants and mechanisms of arthropod-borne flavivirus transmission to the vertebrate host are poorly understood. In this study, we show for the first time that a cell line from medically important arthropods, such as ticks, secretes extracellular vesicles (EVs) including exosomes that mediate transmission of flavivirus RNA and proteins to the human cells. Our study shows that tick-borne Langat virus (LGTV), a model pathogen closely related to tick-borne encephalitis virus (TBEV), profusely uses arthropod exosomes for transmission of viral RNA and proteins to the human- skin keratinocytes and blood endothelial cells. Cryo-electron microscopy showed the presence of purified arthropod/neuronal exosomes …

Portulaca Oleracea Extract Can Inhibit Nodule Formation Of Colon Cancer Stem Cells By Regulating Gene Expression Of Notch Signal Transduction Pathway, Li Chen

Dissertations, Master's Theses and Master's Reports

The main aim of this study was to investigate the effects of Portulaca oleracea extract on tumor formation in colon cancer stem cells and chemotherapy sensitivity. In addition, this study analyzed the genetic changes within the Notch signal transduction pathway associated with the effects of the extracts. Serum-free cultures of colon cancer cells (HT-29) and HT-29 stem cells were treated with the chemotherapeutic drug 5-FU to assess sensitivity. Injections of the stem cells were also given to BALB/c mice to confirm tumor growth and characteristics. In addition, the effect of different concentrations of P. oleracea extract was tested on the …

Characterization Of Staphylococcal Nuclease And Tudor Domain Containing Protein 1 (Snd1) As A Molecular Target In Hepatocellular Carcinoma And Non-Alcoholic Steatohepatitis, Nidhi H. Jariwala

Theses and Dissertations

CHARACTERIZATION OF STAPHYLOCOCCAL NUCLEASE AND TUDOR DOMAIN CONTAINING PROTEIN 1 (SND1) AS A MOLECULAR TARGET IN HEPATOCELLULAR CARCINOMA AND NON-ALCOHOLIC STEATOHEPATITIS

Nidhi Jariwala, PhD

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Integrative Life Sciences

Virginia Commonwealth University, 2017

Devanand Sarkar, M.B.B.S., PhD.

Associate Professor, Department of Human and Molecular Genetics

Virginia Commonwealth University

Richmond, Virginia

SND1, a subunit of the miRNA regulatory complex RISC, has been implicated as an oncogene in hepatocellular carcinoma (HCC). Oncoprotein SND1 regulates gene expression at a post-transcriptional level in multiple cancers including hepatocellular carcinoma (HCC). …

Inflammatory Gene Expression In Women Diagnosed With Polycystic Ovarian Syndrome, Myles K. Taylor

Electronic Theses & Dissertations

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The pathophysiology of PCOS has conventionally thought to originate from androgen excess. However, recent evidence suggests that androgen excess is a downstream consequence to inflammatory dysregulation and subsequent metabolic abnormalities. Inflammatory mRNA gene expression of TNFa and IL-1ß in mononuclear cells isolated from women diagnosed with PCOS was explored using qPCR. Additionally, the correlations between body mass index (BMI) and fasting glucose on mRNA expression of TNFa and IL-1ß were explored. mRNA expression of both TNFa and IL-1ß were found to be significantly higher in PCOS …

The Rodent Parvovirus H-1 And Its Potential In Combination With Tien Hsien Liquid As A Treatment For Breast Cancer, Hayley I. Spires

Selected Honors Theses

Breast cancer is responsible for 12% of cancer diagnoses each year, and it is the leading cause of cancer-related mortality in women worldwide. Current treatments have provided some success in combatting the disease but are not considered a final solution. The framework for how researchers approach cancer has continued to change, and this includes the introduction of oncolytic viruses as novel therapeutics for cancer. The rodent parvovirus H-1 has shown strong potential in clinical and subclinical trials, but its S phase dependency limits its usefulness against cancer stem cell populations. Tien Hsien Liquid is commerically available, nontoxic, and has shown …

Presence Of A Prophage Determines Temperature-Dependent Capsule Production In Streptococcus Pyogenes., Leslie Brown, Jeong-Ho Kim, Kyu Hong Cho

Biochemistry and Molecular Medicine Faculty Publications

A hyaluronic acid capsule is a major virulence factor in the pathogenesis of Streptococcus pyogenes. It acts as an anti-phagocytic agent and adhesin to keratinocytes. The expression of the capsule is primarily regulated at the transcriptional level by the two-component regulatory system CovRS, in which CovR acts as a transcriptional repressor. The covRS genes are frequently mutated in many invasive strains, and a subset of the invasive CovRS mutants does not produce a detectable level of the capsule at 37 °C, but produces a significant amount of the capsule at sub-body temperatures. Here, we report that a prophage has a …

Insights Into The Molecular Roles Of Heparan Sulfate Proteoglycans (Hspgs-Syndecans) In Autocrine And Paracrine Growth Factor Signaling In The Pathogenesis Of Hodgkin's Lymphoma, Rajendra Ghardbaran

Publications and Research

Syndecans (SDC, SYND) comprise a group of four structurally related type 1 transmembrane heparan sulfate proteoglycans (HSPGs) that play important roles in tumorigenic processes. SDCs exert signaling via their protein cores and their conserved transmembrane and cytoplasmic domains or by forming complexes with growth factors (GFs). In classical Hodgkin's lymphoma (cHL), a lymphoid neoplasm of predominantly B cell origin, SDC1 and SDC4 are the active SDCs, and a number of GF (vascular endothelial growth factor, fibroblast growth factor, etc.) signaling pathways have been studied. However, despite extensive pre-clinical and clinical research on SDC-mediated GF signaling in many cancer types, there …

Blood-Tissue Barriers And Autoantibodies In Neurodegenerative Disease Pathogenesis: An Approach To Diagnostics And Disease Mechanism, Eric Luria Goldwaser

Graduate School of Biomedical Sciences Theses and Dissertations

Brain homeostasis can be affected in a number of ways that lead to gross anatomical, cellular, and molecular disturbances giving rise to diseases like Alzheimer’s disease (AD) and related dementias. Unfortunately, the mechanistic pathoetiology of AD’s hallmark features of cerebral amyloid plaque buildup and neuronal death are still disputed. Using human brain AD sections, immunohistochemistry experiments revealed internalized surface proteins, co-localized to an expanded lysosomal compartment. Other stains for amyloid-β1-42 (Aβ42) and various immunoglobulin (Ig) species displayed them leaking out of the cerebrovasculature through a dysfunctional blood-brain barrier (BBB), binding to neurons in the vicinity, and localizing to intracellular vesicles …

Loss Of Exogenous Androgen Dependence By Prostate Tumor Cells Is Associated With Elevated Glucuronidation Potential, Brenna M. Zimmer, Michelle E. Howell, Qin Wei, Linlin Ma, Trevor Romsdahl, Eileen G. Loughman, Jennifer E. Markham, Javier Seravalli, Joseph J. Barycki, Melanie A. Simpson

Department of Biochemistry: Faculty Publications

Prostate epithelial cells control the potency and availability of androgen hormones in part by inactivation and elimination. UDP-glucose dehydrogenase (UGDH) catalyzes the NAD⁺-dependent oxidation of UDP-glucose to UDP-glucuronate, an essential precursor for androgen inactivation by the prostate glucuronidation enzymes UGT2B15 and UGT2B17. UGDH expression is androgen stimulated, which increases the production of UDP-glucuronate, and fuels UGT-catalyzed glucuronidation. In this study, we compared the glucuronidation potential and its impact on androgen-mediated gene expression in an isogenic LNCaP model for androgen dependent versus castration resistant prostate cancer. Despite significantly lower androgen-glucuronide output, LNCaP 81 castration resistant tumor cells expressed higher …

4,4’-Dichlorodiphenyltrichloroethane (Ddt) And 4,4’-Dichlorodiphenyldichloroethylene (Dde) Promote Adipogenesis In 3tl1 Adipocyte Cell Culture, J Kim, Q Sun, Y Yue, Kyong-Sup Yoon, K -Y Whang, J M. Clark, Y Park

SIUE Faculty Research, Scholarship, and Creative Activity

4,4’-Dichlorodiphenyltrichloroethane (DDT), a chlorinated hydrocarbon insecticide, was extensively used in the 1940s and 1950s. DDT is mainly metabolically converted into 4,4’- dichlorodiphenyldichloroethylene (DDE). Even though most countries banned DDT in the 1970s, due to the highly lipophilic nature and very stable characteristics, DDT and its metabolites are present ubiquitously in the environment, including food. Recently, there are publications on relationships between exposure to insecticides, including DDT and DDE, and weight gain and altered glucose homeostasis. However, there are limited reports regarding DDT or DDE and adipogenesis, thus we investigated effects of DDT and DDE on adipogenesis using 3T3-L1 preadipocytes. Treatment …

Proteomic Profiling Of Serum Derived Exosomes From Prostate Cancer Patients, David Turay

Loma Linda University Electronic Theses, Dissertations & Projects

Touted among the major achievements in the diagnosis and management of Prostate cancer (PCa) in the past few decades has been, the dramatic decline of men with advanced/metastatic PCa at diagnosis coupled with a significant improvement ( >90%) in the five and ten year survival rates of the disease. Non-palpable PCa (potentially clinically treatable disease) now accounts for 70-80% of all newly diagnosed cases of PCa. Preceding these changes by about a decade was the introduction of Prostatic Specific Antigen (PSA) into clinical practice; first as biomarker for monitoring response to therapy and subsequently as a complementary screening tool. It …

The Effects Of Pulmonary Hypertension In Diabetic Zucker Rats On Pulmonary Vascular Contraction And Right Ventricular Size, Michael Franzetti

Biological Sciences Undergraduate Honors Theses

Pulmonary hypertension is a life-threatening disease that is identified by a resting mean pulmonary arterial pressure over 25 mmHg and established by right heart catheterization (Saglam et al., 2015). The symptoms commonly associated with pulmonary hypertension include fatigue, dyspnea, syncope, and chest pain, which severely limit quality of life in diagnosed patients (Saglam et al., 2015). According to recent studies in patients with pulmonary hypertension, the one, three and five year mortality rates are 8%, 25%, and 34%, respectively (Burudpakdee, Shah, Joish, Divers, & Yaldo, 2014). Although some advances have been made in therapies for pulmonary hypertension, the prognosis is …

The Roles Of Malt1 In Nf-Κb Activation And Solid Tumor Progression, Deng Pan

Dissertations and Theses (Open Access)

The transcription factor NF-κB plays a central role in many aspects of biological processes and diseases, such as inflammation and cancer. Although it has been suggested thatNF-κB is critical in tumorigenesis and tumor progression, the molecular mechanism by which NF-κB is activated in solid tumor remains largely unknown. In the current work, we focus on growth factor receptor-induced NF-κB activation and tumor progression, including epidermal growth factor receptor (EGFR)-induced NF-κB in lung cancer and heregulin receptor (HER2)-induced NF-κB in breast cancer. We found that Mucosa-associated lymphoma translocation protein 1 (MALT1), also known as paracaspase, is required for EGFR-induced NF-κB activation …

Cll Metabolism Is Regulated By Prognostic Factors, Modulated By Stroma And Abrogated By Pi3k Inhibition, Hima Vangapandu

Dissertations and Theses (Open Access)

Metabolism of chronic lymphocytic leukemia (CLL), a disease characterized by the relentless accumulation of mature B cells has been little explored. Bone marrow stromal cells provide a survival benefit to CLL cells, in part through PI3K/AKT pathway. Compared with proliferative B-cell lines, metabolic fluxes of oxygen and lactate were low in quiescent malignant B lymphocytes from CLL patients. Glycolysis (extracellular acidification rate, ECAR) was consistently low in CLL samples, but oxygen consumption (OCR) varied considerably. Higher OCR was associated with poor prognostic factors such as ZAP 70 positivity, unmutated IgVH, high β2M levels, and higher Rai stage. Co-culture with the …

The Emergence Of The Zika, Chikungunya, And Dengue Viruses In Brazil, The Dominican Republic, And Puerto Rico, Nelson Xavier Del Pilar

Honors Scholar Theses

The Zika, Chikungunya, and Dengue viruses are three emerging viral infections of the 21st century. Outbreaks have occurred in twenty countries, including areas of South America, and territories in the Caribbean. These viral diseases are mosquito-borne infections transmitted primarily by Aedes aegypti and Aedes albopictus mosquitoes. The origins of the diseases, viral morphology, and vector transmission will be described in this review as well as symptoms that humans experience, medical testing procedures, and preventative measures. This study will focus on three locations: Brazil, the Dominican Republic, and Puerto Rico. There are many similarities between the three viruses to emphasize, but …

A Mir-200c/141-Bmi1 Autoregulatory Loop Regulates Oncogenic Activity Of Bmi1 In Cancer Cells., Mingu Kang, Manjari Dimri, Goberdhan P. Dimri

Biochemistry and Molecular Medicine Faculty Publications

MicroRNAs (miRNAs) are known to function as oncomiRs or tumor suppressors and are important noncoding RNA regulators of oncogenesis. The miR-200c/141 locus on chromosome 12 encodes miR-200c and miR-141, two members of the miR-200 family, which have been shown to function as tumor suppressive miRNAs by targeting multiple oncogenic factors such as polycomb group protein BMI1. Here, we show that BMI1 reciprocally functions as a transcriptional repressor of the miR-200c/141 cluster and that BMI1 inhibitors upregulate expression of miR-200c and miR-141. Our data suggest that BMI1 binds to the miR-200c/141 promoter and regulates it through transcription factor binding motifs E-box …

Metabolomics Reveals New Mechanisms For Pathogenesis In Barth Syndrome And Introduces Novel Roles For Cardiolipin In Cellular Function, Yana Sandlers, Kelly Mercier, Wimal Pathmasiri, Jim Carlson, Susan Mcritchie, Susan Sumner, Hilary J. Vernon

Chemistry Faculty Publications

Barth Syndrome is the only known Mendelian disorder of cardiolipin remodeling, with characteristic clinical features of cardiomyopathy, skeletal myopathy, and neutropenia. While the primary biochemical defects of reduced mature cardiolipin and increased monolysocardiolipin are well-described, much of the downstream biochemical dysregulation has not been uncovered, and biomarkers are limited. In order to further expand upon the knowledge of the biochemical abnormalities in Barth Syndrome, we analyzed metabolite profiles in plasma from a cohort of individuals with Barth Syndrome compared to age-matched controls via ¹H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. A clear distinction between metabolite profiles of …

Targeting An Essential Gtpase Obg For The Development Of Broad-Spectrum Antibiotics, Josephine A. Bonventre, Ryszard A. Zielke, Konstantin V. Korotkov, Aleksandra E. Sikora

Molecular and Cellular Biochemistry Faculty Publications

A promising new drug target for the development of novel broad-spectrum antibiotics is the highly conserved small GTPase Obg (YhbZ, CgtA), a protein essential for the survival of all bacteria including Neisseria gonorrhoeae (GC). GC is the agent of gonorrhea, a prevalent sexually transmitted disease resulting in serious consequences on reproductive and neonatal health. A preventive anti-gonorrhea vaccine does not exist, and options for effective antibiotic treatments are increasingly limited. To address the dire need for alternative antimicrobial strategies, we have designed and optimized a 384-well GTPase assay to identify inhibitors of Obg using as a model Obg protein from …

Utility And Origin Of Blood-Based Autoantibodies For Early Detection And Diagnosis Of Neurodegenerative Diseases, Cassandra Demarshall

Graduate School of Biomedical Sciences Theses and Dissertations

Autoantibodies are self-reactive antibodies that have been widely implicated as causal agents of autoimmune diseases. They are found in the blood of all human sera, regardless of age, gender, or the presence or absence of disease. While the underlying reason for their ubiquity remains unknown, it has been hypothesized that they participate in the clearance of blood-borne cell and tissue debris generated in both healthy and diseased individuals on a daily basis. Although much evidence supports this debris clearance role, recent studies also suggest a causal role for autoantibodies in disease. My thesis work has focused on this "cause and/or …

Molecular Basis Of Sex Differences In Cardiac Hypertrophy And Heart Failure, Maya James

Online Theses and Dissertations

Transforming growth factor beta ligands and receptors are known to be pro-hypertrophic and pro-fibrotic factors in the heart, and are known to contribute to the development of cardiac hypertrophy and heart failure. It is well established that premenopausal females possess a lower incidence of these pathologies. We and others have observed a greater level of fibrosis in male hearts compared to female hearts in rodent models of cardiac hypertrophy. It is well established that estrogen is cardioprotective in that it can prevent the development of cardiac hypertrophy, as well as abrogate the development of heart failure following sustained cardiac hypertrophy. …

A Mechanistic Study Of An Ipsc Model For Leigh’S Disease Caused By Mtdna Mutataion (8993 T>G), John P. Galdun

Theses and Dissertations

Mitochondrial diseases encompass a broad range of devastating disorders that typically affect tissues with high-energy requirements. These disorders have been difficult to diagnose and research because of the complexity of mitochondrial genetics, and the large variability seen among patient populations. We have devised and carried out a mechanistic study to generate a cell based model for Leigh’s disease caused by mitochondrial DNA mutation 8993 T>G. Leigh’s disease is a multi-organ system disorder that depends heavily on the mutation burden seen within various tissues. Using new reprogramming and sequencing technologies, we were able to show that Leigh’s disease patient fibroblasts …

Investigation Of Anaplasma Phagocytophilum And Anaplasma Marginale Adhesin-Host Cell Interactions, Kathryn S. Hebert

Theses and Dissertations

Anaplasma phagocytophilum and A. marginale are the etiologic agents of bovine anaplasmosis and human granulocytic anaplasmosis, respectively. As obligate intracellular pathogens, binding and entry of host cells is a prerequisite for survival. The molecular events associated with these processes are poorly understood. Identifying the adhesins mediating binding, delineating their key functional domains, and determining the molecular determinants to which they bind not only benefits better understanding of Anaplasma spp. pathobiology, but could also benefit the development of novel approaches for protecting against infection. We previously demonstrated that A. phagocytophilum outer membrane protein A (ApOmpA) is critical for bacterial binding and …

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …

The Role Of Oxidative Stress In The Mechanisms Of Ammonia-Induced Brain Swelling And Tolerance In The Goldfish (Carassius Auratus), David F. Jones Lisser Mr.

Theses and Dissertations (Comprehensive)

Toxic build-ups of ammonia can cause potentially fatal brain swelling in mammals, but such swelling is reversible in the anoxia- and ammonia-tolerant goldfish (Carassius auratus). The mechanisms of ammonia-induced brain swelling and tolerance remain elusive, but several studies have suggested a role for reactive oxygen species (ROS), which may damage proteins and lipids in the plasma membrane of astrocytes in the brain. As a result, osmotic gradients across cell membranes may be altered leading to water uptake by astrocytes and swelling. While a role for ROS has been proposed in mammals, no studies have addressed this question in …

Phylogenetic Investigation Of Enteric Bovine Coronavirus In Ireland Reveals Partitioning Between European And Global Strains, Lynda Gunn, P. J. Collins, M. J. O'Connell, Helen O'Shea

Department of Biological Sciences Publications

Background

Bovine coronavirus is a primary cause of neonatal calf diarrhea worldwide, and is also associated with acute diarrhea in adult cattle during the winter season. There are no reports on molecular characterization of bovine coronavirus in Ireland, and little data exists apart from serological studies.

Findings

In this study, 11 neonatal (mean age 9 days) calf BCoV strains from the south of Ireland were collected over a one year period and characterized using molecular methods. The spike gene which encodes a protein involved in viral entry, infectivity and immune response shows the most variability amongst the isolates and was …

Effect Of Genetic Background On The Dystrophic Phenotype In Mdx Mice., William D Coley, Laurent Bogdanik, Maria Candida Vila, Qing Yu, Terence A Partridge, Kanneboyina Nagaraju, +12 Additional Authors

Genomics and Precision Medicine Faculty Publications

Genetic background significantly affects phenotype in multiple mouse models of human diseases, including muscular dystrophy. This phenotypic variability is partly attributed to genetic modifiers that regulate the disease process. Studies have demonstrated that introduction of the γ-sarcoglycan null allele onto the DBA/2J background confers a more severe muscular dystrophy phenotype than the original strain, demonstrating the presence of genetic modifier loci in the DBA/2J background. To characterize the phenotype of dystrophin deficiency on the DBA/2J background, we created and phenotyped DBA/2J-congenic Dmdmdx mice (D2-mdx) and compared them to the original, C57BL/10ScSn-Dmdmdx (B10-mdx) model. These strains were compared to their respective …

Structural And Functional Interactions Between Bro1 Domain Of Human Alix Protein And Nucleocapsid Packaging Rna Complex From Hiv, Scott Gross

Graduate School of Biomedical Sciences Theses and Dissertations

A virus is only as powerful as its ability to spread. Enveloped retroviruses, namely HIV-1, use exocytosis pathways that normal host cells use to release particles from the plasma membrane. The main pathways of interest in this study are the Endosomal Sorting Complex Required for Transport (ESCRT) and adjacent ALIX pathways. The ESCRT pathway is especially important for degradation of receptor/cargo complexes that form Multi-Vesicular Bodies (MVBs). Currently, there is no known therapy that targets this endosomal pathway, which would prevent the spread of the virus to other cells. The virus has adapted to jump from pathway to pathway when …

Age-Dependent Breakdown Of The Blood Brain Barrier And Associated Changes In S100b Ko Mice, Eric V. Brown

Graduate School of Biomedical Sciences Theses and Dissertations

Autoantibodies play an important role in many autoimmune diseases. Recent research has shown that breakdown of the blood brain barrier (BBB) occurs concomitant to generation of brain reactive autoantibodies in many neurodegenerative diseases, which serve as biomarkers and drivers of pathology. SI00B, a calcium binding protein found most highly expressed in astrocytes which ensheathe the BBB, has many functions in neural development and signaling. Currently literature indicates that S100B KO mice develop normally, with no phenotypic abnormalities. Here, it is demonstrated that S100B KO mice seem to develop a chronic BBB breakdown similar to that seen in human neurodegenerative diseases. …