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Exploring The Design Space Of Antifungal Peptides, Miryam Kikhwa

Seton Hall University Dissertations and Theses (ETDs)

The synthesis, characterization, and evaluation of antifungal activity of peptides FQ15 and FG10 will be conducted to address the hypothesis. The hypothesis of this thesis is that a peptide with similar properties to AS15 would have similar activity against Cryptococcus neoformans. This study addresses the challenge of drug- resistant microbes by developing inhibitors targeting lipid flippase and exploring their potential as antimicrobial agents against Cryptococcus neoformans. Chapter 1 provides a historical context of the background on the development of antimicrobials and common antifungal treatments, as well as an introduction about C. neoformans and its resistance mechanism. Chapter 2 introduces the …

Synthesis, Characterization And Biological Evaluation Of Polyarginine Derived Bone-Targeting Peptides, Gina L. Antuono

Seton Hall University Dissertations and Theses (ETDs)

Osteoblast-targeting peptides in the treatment of bone disease is a new and novel approach to offering effective treatment of various cancers and can be used in bio-medical, medicinal chemistry and biotechnology applications. By targeting adhesion proteins produced by osteoblast cells, certain cancers which migrate and metastasize to the bone may be more effectively treated. An osteoblast-targeting peptide composed of Ser-Asp-Ser-Ser-Asp (SDSSD) which selectively binds to osteoblast cells via periostin has recently been identified. This peptide was functionalized with polyurethane, generating nanomicelles which encapsulated RNA for the therapeutic treatment of osteoporosis. This study has served as the basis for the research …

Rational Design, Synthesis And Biology Of Immunostimulatory Peptides, Nelson Casanova

Seton Hall University Dissertations and Theses (ETDs)

This dissertation reports the design, synthesis, characterization, and biological studies of three uniquely structured peptides, derived from ubiquitinated multiple myeloma proteins and ubiquitinated B7H6 ligand. The peptides were made into linear or branched shapes, with the branched peptides containing both major histocompatibility complex (MHC) class two and NKp30 binding motifs properties in one peptide. This results in an immunocytotoxic response (via cytokines and chemokines) of both natural killer cells and cytotoxic T lymphocytes (CTLs). These shapes were determined for data comparison but also to increase cytokine proliferation, the shapes help with healthy cell aviation. Thus, the linear monomer (contains a …

The Role Of Dha In The Impact Of Trem2 On Microglia Activation And Alzheimer’S Disease, Michael A. Palmieri Iii

Seton Hall University Dissertations and Theses (ETDs)

Alzheimer’s disease (AD) is a neurological disease that is associated with microglia activation. An important receptor involved in microglia activation is Triggering receptor expressed on myeloid cells 2 (TREM2). Recent studies suggest that docosahexaenoic acid (DHA) could reduce the neuroinflammation that is associated with microglia activation. We hypothesized that when DHA concentration was increased, TREM2 expression would decrease, microglia activity would be inhibited, and a resulting decrease in neuroinflammation would be observed. We examined peer-reviewed journal articles from 2017-2022 that investigated the relationship between TREM2 activation and severity of AD symptoms, the protective properties of DHA against AD, and the …

Manganese Chloride Effects Chondrogenesis Of Atdc5 Cells, Isabella Somera

Seton Hall University Dissertations and Theses (ETDs)

Manganese is an essential trace element found in humans, which aids in several processes including brain and nerve function, glucose metabolism, calcium absorption, and bone formation and homeostasis. Specifically, bone homeostasis utilizes osteoblasts and osteoclasts, cells which function to build and reabsorb bone respectively, as well as chondrocytes, cells which aid in endochondral ossification. Chondrocytes deposit extracellular matrix components, such as aggrecan, collagen, and proteoglycans, that provide the necessary scaffold for osteoblasts to synthesize and mineralize bone. Activation of the rapamycin (mTOR) pathway influences the regulation of several cellular processes, such as skeletal development and bone homeostasis. In this study, …

Investigation Of The Effect Of Trace Element, Copper Chloride, On Chondrogenic Cell Line, Atdc5 Function, Alexandra Bambrick

Seton Hall University Dissertations and Theses (ETDs)

Copper chloride (CuCl₂) is an essential trace element found in humans, which helps to aid in brain and nerve function, glucose metabolism, calcium absorption, and bone formation. Bone formation utilizes a variety of cell types, including, osteoblasts, osteoclasts, and chondrocytes. Chondrocytes deposit cartilage components like collagen and proteoglycans that provide the necessary scaffold for osteoblasts to synthesize and mineralize bone. Copper chloride is known to aid in osteogenesis, maintain bone metabolism, and regulate bone mineral density, but its role in chondrogenesis is still unclear (15).

In this study, it is hypothesized that CuCl₂ treatments would enhance chondrogenic …

Bis-Indolyl Compounds And The Induction Of Apoptosis In T98g Glioblastoma Multiforme Cells, Margot C. Brown

Seton Hall University Dissertations and Theses (ETDs)

1,1-bis(3’idolyl)-1(aryl)methane compounds (BIM compounds) have been shown to have anti-cancer properties in colon cancer, bladder cancer, and leukemia cells. The purpose of this work was to determine if BIM compounds could be an effective treatment of glioblastoma multiforme. Sulforhodamine B (SRB) assays showed that 20µM of the BIM compounds could inhibit cellular proliferation of the T98G glioblastoma multiforme cell line over 72 hours. Then immunoblotting was used to analyze the molecular pathway induced by BIM compounds. An increase in the expression of both BAX and cleaved caspase 3 suggest BIM compounds activate programmed cell death, or apoptosis in glioblastoma cells. …

Drosophila Melanogaster As A Model For Male Reproductive System Ethanol Toxicity, Gbemisola Ilelaboye

Seton Hall University Dissertations and Theses (ETDs)

Drosophila melanogaster has been extensively used in different types of research as a model organism due to its high reproductivity, short life span, and easy maintenance. In this paper, we examined drosophila as a model for ethanol toxicity in the male reproductive system. We developed three assays: The DAPI assay, sperm viability assay, and tubulin staining assay. The DAPI assay is a nuclear staining assay that assesses the effects of various ethanol concentrations in late spermiogenesis in which increased detrimental effects to the sperm bundles were observed. The second assay consisted of the sperm viability assay which showed an increase …

Flippase Inhibitors As Antimicrobial Agents, Robert Tancer

Seton Hall University Dissertations and Theses (ETDs)

Drug resistant microbes are a considerable challenge for modern medicine to overcome. The research described in this dissertation involved development of lipid flippase inhibitors and investigating their potential as antimicrobial agents against various drug resistant microbes. The microbes primarily investigated were methicillin resistant Staphylococcus aureus (MRSA) & Cryptococcus neoformans. Chapter 1 reviews the historical perspective and summarizes the current state of the field of research. In Chapter 2, the design space of an antimicrobial peptide known as humimycin was explored and the effects of modifications on its structure were observed against MRSA. Several key observations resulted. Most notably, the …

Effects Of Sodium Orthovanadate On Lps-Induced Senescent Raw 264.7 Cells, Andrew Pugliese

Seton Hall University Dissertations and Theses (ETDs)

Cellular senescence is considered a signal transduction process where damaged or stressed cells arrest proliferation. Exogenous stressors including bacterial infection, chemotherapy, and irradiation can drive normal cells to senescence. Sodium orthovanadate (Na₃VO₄) is a phosphatase inhibitor known to mediate the release of the proinflammatory cytokine, TNF-a. We hypothesized that NaVO₄ treatment will reduce proinflammatory expression from senescent cells. In our study we illustrate that prolonged exposure to LPS caused RAW 264.7 cells induced morphological changes indicative of senescent cells including the formation of giant multinucleated cells (GMCs). Furthermore, we found that RAW 264.7 GMC cells …

The Effects Of Chronic Ethanol Exposure On Caenorhabditis Elegans Germline, Andrea Zegarra

Seton Hall University Dissertations and Theses (ETDs)

Ethanol is the most commonly abused drug in the world. Alcohol consumption increases a number of health risks, morbidity and mortality, and chronic and acute diseases. Some health risks include high blood pressure, stroke, liver disease, cancer, and can include mental health and social problems. Chronic alcohol consumption can lead to learning and memory problems, along with alcohol dependence. Additionally, alcohol consumption has an impact on ovarian reserve, steroid hormone production, sperm quality, fecundity, and fertility treatments. The purpose of this study was to analyze the effects of ethanol exposure on fertility of the N2 wild type as measured by …

Clinically Relevant Dosage Of Vancomycin Does Not Negatively Impact Periosteum Derived Osteoblast Precursor Cellular Functions, Alexis Hernandez

Seton Hall University Dissertations and Theses (ETDs)

Surgical site infections (SSI) can develop post-operatively and carry significant clinical and financial implications. SSI can carry a cost of up to $30,000 per case, as well as an estimated 6 day longer hospitalization. Patients with Type II Diabetes (DM) have an increased susceptibility to infection and suffer from poor bone healing overall. Therefore, diabetic patients who have undergone orthopedic surgery risk both an increased chance of developing an SSI as well as suboptimal bone healing. Vancomycin and other antibiotics have traditionally been used prophylactically to prevent infection, however the effect of vancomycin on bone healing in a diabetic population …

Effects Of Palmitate On The Expression Of Inflammatory Cytokines In Microglial Cells, Shiyu Ma

Seton Hall University Dissertations and Theses (ETDs)

Obesity has become a pandemic health issue for the development of more serious illnesses such as insulin resistance, cardiovascular diseases, and hypertension. Among those pathological conditions, low grade chronic inflammation triggered by saturated fatty acids (SFA) such as palmitate (PA) has been suggested to be the culprit of crimes and various signaling modulators ranging from cellular surface receptors such as toll like receptors (TLRs) and G- protein – coupled receptor 40 (GPR40) to intracellular kinases like mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) have been postulated. In this study, mouse BV2 cells were treated with different concentrations of …

Plasma Agriculture: Characterization Of Dbd Plasma Jet And Analysis Of Effects When Treated On Sweet Basil (Ocimum Basilicum), William Davis

Seton Hall University Dissertations and Theses (ETDs)

Plasma agriculture is an increasingly diverse field, where effects of nonthermal or cold plasma are measured by their influence on plant physiology and growth rate. Effects range from sterilization, germination, increased growth rate, cell metabolism, and so forth. This study aims to investigate the understanding of the generation of specific reactive oxygen and nitrogen species (RONS) from a nonthermal atmospheric DBD helium-based plasma jet and identify quantifiable effects that can directly translate to different applications related to plasma agriculture. Basil plants were separated into treated and control groups and grown hydroponically. The treated plants received a 30 second exposure treatment …

A Functional Three-Dimensional Microphysiological Model Of Myeloma Bone Disease, Richard Visconti

Seton Hall University Dissertations and Theses (ETDs)

Multiple myeloma (MM) is a hematologic cancer caused by a mature B cell neoplasm, or plasmacytoma, that infiltrates the skeleton at several sites. The disease is characterized by uninhibited transformed plasma cell proliferation that disrupts skeletal homeostasis leading to decreased bone modeling and increased bone resorption. Osteolytic lesions (OL) or voids left in the bone, remain long after the treatment of the cancer and indicate disease progression to myeloma bone disease (MBD). Current combinatorial MM therapies inhibit malignant plasma cell proliferation, slow the progression towards MBD, and increase the mean five-year survival rate, but do little to improve osteoblastic function …

Isotype-Specific Outcomes In Fc Gamma Receptor Targeting Of Pspa Using Fusion Proteins As A Vaccination Strategy Against Streptococcus Pneumoniae Infection, Kari Wiedinger

Seton Hall University Dissertations and Theses (ETDs)

Streptococcus pneumoniae (Spn) remains a considerable threat to public health despite the availability of antibiotics and polysaccharide conjugate vaccines. The lack of mucosal immunity in addition to capsular polysaccharide diversity, has proved to be problematic in developing a universal vaccine against Spn. Targeting antigen to Fc receptors is an attractive way to augment both innate and adaptive immunity against mucosal pathogens, by promoting interactions with activating Fcγ receptors (FcγR) that mediate diverse immunomodulatory functions. The effect of targeting FcγR is highly influenced by the IgG subclass, which bares differential affinities for activating and inhibitory FcγR. In the current study we …

Effects Of Aurora Kinase C Expression On Retina Pigmented Epithelial Cell Migration, Proliferation, And Anchorage Independent Growth, Justin Bejar

Seton Hall University Dissertations and Theses (ETDs)

Cancer is a common and deadly disease in the United States with 1,806,590 new cancer cases in 2019 and 606,520 cancer deaths projected in 2020. These deaths are primarily due to the uncontrolled cell proliferation and migratory nature of the disease. Many cancer cells express genes normally restricted to meiotic cells. For example, Aurora Kinase C (AURKC) is known to regulate chromosome segregation in meiotic cells yet it is expressed in many different types of cancer, such as breast, prostate, colorectal, liver, cervical, thyroid, and testicular cancers. As a means to study the function of AURKC, an …

Chemical Tools For Residue-Specific And Secondary Amine Selective Petasis (Sasp) Bioconjugation Of Peptides And Proteins, Yonnette Sim

Seton Hall University Dissertations and Theses (ETDs)

Chemical protein synthesis is an invaluable tool that enables the construction of novel protein design, incorporation of non-native functionalities, elucidation of structure-function relationships and enable a wide diversity of modifications (such as Post Translation Modification) to study protein functions. Native Chemical Ligation (NCL) in conjunction with Fmoc Solid Phase Peptide Synthesis (SPPS) is the most used method for synthesis of functional peptides and proteins. The synthesis relies on the reaction of a C-terminal peptide thioester and a N-terminal cysteine peptide. Fmoc SPPS of peptide thioester for chemical protein synthesis via NCL is a challenge. Methods that exist for the synthesis …

Chromatographic Behavior Of Therapeutic Monoclonal Antibodies In Hybrid Hydrophobic Interaction Chromatography (Hhic), Madhaviprasanna Srikoti

Seton Hall University Dissertations and Theses (ETDs)

Chromatographic Behavior of Therapeutic Monoclonal Antibodies in Hybrid Hydrophobic Interaction Chromatography (HHIC) using Poly (alkyl aspartamide) Silica Columns

A hybrid mode of hydrophobic interaction chromatography (HHIC) is an emerging chromatographic technique for the separation of biomolecules under non-denaturing conditions. This technique separates biomolecules in their native form where the difference in surface hydrophobicity is maximized. Hybrid mode of HIC (HHIC) methodology uses HIC stationary phases made with poly (alkyl aspartamide) silica columns, which function as a hybrid form of conventional HIC and reversed-phase chromatography (RPLC). This research provided fundamental knowledge about the impact of chromatographic parameters on the separation of …

Cd11b+ Depletion Of Bone Marrow Derived Macrophages Negatively Affects Bone Fracture Healing, Sarah Hozain

Seton Hall University Dissertations and Theses (ETDs)

Hematoma formation and inflammation occurs during the beginning stages of fracture repair, which require the presence of innate cells such as macrophages. Macrophages are subdivided into proinflammatory, M1, or anti-inflammatory, M2, phenotypes with different functions, cytokine profiles, and surface markers. In this study, in vitro and in vivo models were used to deplete M1 macrophages, using Mac-1 Sap conjugated antibody (Mac1SAP), to determine the effects on fracture healing. In vitro study, primary macrophages isolated from mice femoral bone marrow were harvested and differentiated into M1 macrophages (+LPS), M2 macrophages (+IL-4), or undifferentiated then treated with either vehicle or 10pM Mac1SAP. …

Students' Performance, Satisfaction And Retention In A Hybrid And Traditional Face-To-Face Science Course, Principles Of Biology I, In A Community College, Abdallah Mohammad Matari

Seton Hall University Dissertations and Theses (ETDs)

Hybrid teaching, comprised of both in-class and online teaching, is rapidly becoming a favorite mode of teaching and learning. Online and hybrid courses on have become more and more appealing to both higher education institutions and the students they serve. In particular, hybrid teaching has an increase appeal to community colleges as they serve a diverse student population with varied academic levels, cultural background, and personal responsibilities. Hybrid courses promotes flexibility in course scheduling options for students and enables institutions to accept more students without worrying about physical classroom space concerns. This study explored and compared students’ learning outcomes, satisfaction, …

Understanding The Biopsychological Effects Of Trauma On Learning: An Investigation Of Interventions To Support Faculty, Joan Buzick

Seton Hall University Dissertations and Theses (ETDs)

The current era in higher education has brought changes to the academic profession. Faculty have an increasing number of responsibilities in addition to their traditional role as an instructor. At the same time, faculty are engaging with a changing and diverse student population. The population has more challenges, with increased stressors, than have been historically observed in higher education students. For many, the stressors are trauma-related and are a growing concern. Trauma has been shown to impact cognitive, social, emotional, and physical well-being. What has been learned about trauma is, to a great extent, a result of the relatively recently …

5 Lipoxygenase's Role In Chondrogenesis Of The Atdc5 Cell Line, Tien My Tran

Seton Hall University Dissertations and Theses (ETDs)

5-Lipoxygenase metabolizes arachidonic acid (AA) to generate leukotrienes (LTs). Leukotrienes are very potent inflammatory mediators that can have negative effects on bone healing and cartilage tissue generation. Recent studies have shown that decreasing 5-lipoxygenase (5-LO) activity during fracture healing accelerates endochondral ossification and decreases healing time in animal fracture models, however, the roles of 5-LO in chondrogenesis is not fully investigated. In this study, we tested the hypothesis that 5-LO inhibition will increase the process of chondrogenesis. The ABT-761 is an N-hydroxyurea analog structurally similar to zileuton, which is a 5-LO enzyme inhibitor, The ATDC5 cell line which is derived …

Analysis Of Post-Translational Modifications And Expression Of Stat3 Under Desferrioxamine Induced Hypoxia In Human Neuroblastoma Cells, Veronica Harrison

Seton Hall University Dissertations and Theses (ETDs)

ABSTRACT:

Oxygen homeostasis is critical for optimal energy production in eukaryotic organisms. The signal transduction pathways involved with detection and mitigation of hypoxia have been carefully scrutinized in an effort to elucidate how metabolism and survival is maintained. Characterization of these pathways and their involvement in physiological processes such as blood cell production in the bone marrow and microvessel formation in developing embryos provides a model of how these functions are executed. Less well-characterized mechanisms in disease states such as solid tumors still confound researchers whose efforts to find effective treatments are falling short. Cancer cells exploit the activities …

Vanadium Compounds Modulate Osteoblast Proliferation And Function, Bryan Sosa

Seton Hall University Dissertations and Theses (ETDs)

Osteoblastogenesis is an essential part of the bone healing process. Insulin has been shown to improve bone healing in both normal and diabetic bone healing models. In addition, insulin mimetic compounds such as Zinc chloride (ZnCl₂) and Vanadyl acetylacetonate (VAC) have also been shown to improve bone healing in these models as well. The purpose of this study was to determine the effects of vanadium compounds VAC and Vanadium (II) sulfate (VSO₄) in osteoblast proliferation and function. In addition the mechanisms by which growth and function are facilitated by these Vanadium compounds were also evaluated. In …

Comparison Of Nickel And Cobalt Induced Hypoxic Cell Models Using Cell Proliferation Assay, Melissa Delcasale

Seton Hall University Dissertations and Theses (ETDs)

Hypoxia is an imbalance in oxygen delivery and oxygen consumption, ultimately affecting cell survival. Low levels of oxygen diminish adenosine triphosphate synthesis resulting from a decline in oxidative phosphorylation in the mitochondria, therefore inducing apoptosis and cell death. To create a hypoxia mimicked environment, we used hypoxia mimetic compounds cobalt and nickel to treat human neuroblastoma (NMB) cells. Using hypoxic mimic human neuronal cell models, we examined and compared the effects of compound-induced hypoxia on NMB cell proliferation. The cells were treated with 100mM and 300mM concentrations of each compound at 24- and 48-hour intervals. To investigate cell proliferation, the …

Zinc Chloride Enhanced Chondrogenesis Is Vegf Dependent, Gilbert M. Sharp Iv

Seton Hall University Dissertations and Theses (ETDs)

Researchers have begun investigating whether insulin mimetics such as ZnCl2 could promote bone healing in both non-diabetic and diabetic fracture healing similarly to insulin. Our research focused on understanding the mechanism by which ZnCl2 affects chondrogenesis, an important component of bone fracture healing. The increases in proteoglycan deposition and cell proliferation seen in our data may be a result of ZnCl2 induction of the IGF-1 pathway. When the VEGF pathway was inhibited in ZnCl2- or insulin-treated cells significant decreases in proteoglycan deposition occurred on day 7 and 14 (P=0.007 for ZnCl2, P=0.028 for insulin) when compared to controls. This data …

Applications Of Sirna For Cancer Gene Therapy, Christopher Nicholas Cultrara

Seton Hall University Dissertations and Theses (ETDs)

Gene therapy is a potent and versatile nano-medicine strategy in the treatment of cancer. Of the many tools currently used in this application, short-interfering RNA (siRNA) are among the most commonly employed due to their ability to silence oncogenic mRNA with high precision through the RNA interference (RNAi) pathway potentially leading to cancer cell death. Our work revolves around silencing the Glucose-Regulated Proteins (GRPs) whose expressions are upregulated in cancerous tissues and are implicated in the proliferative, pro-survival, and anti-apoptotic pathways that govern tumor biology. Here we present a variety of applications to improve the potency and functionality of GRP-targeting …

Expanding The Toolbox With Site-Specific Methods Of Bioconjugation, Tiauna S. Howard

Seton Hall University Dissertations and Theses (ETDs)

Bioconjugation is an important tool for studying complex biological systems, with site-specificity being the major challenge. Reactions based on amino acid derived organocatalysts have been widely used in organic synthesis, particularly for the asymmetric synthesis of small molecules but this concept has not been vastly explored on biomolecules. To combat these limitations, two chemical strategies are developed to effectively attach synthetic molecules site specifically to proteins. First, a protein modification technique based on conjugation at a non-native functional handle, an aldehyde or ketone, is developed. This functional handle is chemically introduced onto the biomolecules before undergoing the organocatalyzed aldol reaction, …

Analysis Of Sublethal Toxicity In Developing Zebrafish Embryos Exposed To A Range Of Petroleum Substances Using Be-Spme And Whole Transcriptome Microarray, Bryan Matthew Hedgpeth

Seton Hall University Dissertations and Theses (ETDs)

The OECD 236 Fish Embryo Acute Toxicity Test guideline relies on four endpoints to describe exposure related effects (coagulation, lack of somite formation, tail-bud detachment from yolk-sac, and presence of heartbeat). Danio rerio (zebrafish) embryos were used to investigate these endpoints along with a number of additional sublethal effects (i.e. cardiac dysfunction, pericardial edema, yolk sac edema, tail curvature, hatch success, pericardial edema area, craniofacial malformation, swim bladder development, fin development, and heart rate) following five day exposures to one of seven petroleum substances. The substances investigated included two crude oils, three gas oils, a diluted bitumen, and a petrochemical …