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2021

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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

A Snapshot Investigation Into The Availability And Access To Codeine-Containing Medications Amongst The Irish Population., Katie O'Brien, Pádraig Mckeown, Joseph Phelan Dec 2021

A Snapshot Investigation Into The Availability And Access To Codeine-Containing Medications Amongst The Irish Population., Katie O'Brien, Pádraig Mckeown, Joseph Phelan

International Undergraduate Journal of Health Sciences

Codeine phosphate is a mild to moderate analgesic and has a weak cough suppressant activity that is available to purchase as an over the counter (OTC) painkiller in Ireland as a compound product. In recent years, countries such as Australia have introduced laws that prohibit the sale of the drug without a valid prescription. This move by Australia begs the question as to why this legislation was introduced and should Ireland follow suit.

The primary aims of the study were to determine knowledge among the general public of codeine-containing medications and their usage levels. The survey also investigated whether current …


Slo2.1 Channels: A New Molecular Mechanism To Regulate Uterine Excitability, Juan Jose Ferreira Dec 2021

Slo2.1 Channels: A New Molecular Mechanism To Regulate Uterine Excitability, Juan Jose Ferreira

Arts & Sciences Electronic Theses and Dissertations

At the end of pregnancy, the uterus transitions from a non-contractile state to a highly contractile state. Two processes primarily drive this transition. First, from the 28th week of pregnancy until labor, the resting membrane potential of uterine (myometrial) smooth muscle cells (MSMCs) gradually becomes more positive (depolarizes) (Parkington et al. 1999). Second, at the end of pregnancy, MSMCs express more oxytocin receptors and become more sensitive to oxytocin (Kimura et al. 1996). However, the detailed mechanisms by which these processes occur have not been determined. My central hypothesis was that the Na+-activated K+ channel SLO2.1 plays a key role …


Role Of Meibum And Tear Phospholipids In The Evaporative Water Loss Associated With Dry Eye., Samiyyah M. Sledge Dec 2021

Role Of Meibum And Tear Phospholipids In The Evaporative Water Loss Associated With Dry Eye., Samiyyah M. Sledge

Electronic Theses and Dissertations

It is generally believed that the tear film lipid surface film inhibits the rate of evaporation (Revap) of the underlying tear aqueous. It is also generally believed that changes in the composition of the tear film lipid layer is responsible for an increase in Revap in patients with dry eye. Both of these ideas have never been proven. The purpose of the current studies was to test these ideas. Revap was measured in vitro gravimetrically. Lipid spreading was measured using Raman spectroscopy and microscopy. The influence of the following surface films on the Revap of the sub phase of physiologically …


Differentiating The Mechanistic Role And Chemotherapeutic Potential Of Src And Podoplanin In Oncogenic Transformation, Edward P. Retzbach Dec 2021

Differentiating The Mechanistic Role And Chemotherapeutic Potential Of Src And Podoplanin In Oncogenic Transformation, Edward P. Retzbach

Graduate School of Biomedical Sciences Theses and Dissertations

There were an estimated 20 million new cancer cases worldwide in 2020, resulting in nearly 1000 deaths per hour [1]. Oral cancer exemplifies the difficulties of treating cancer patients. The first line for oral cancer treatment is surgery and radiation that can lead to patient disfigurement and decreased quality of life in cancer survivors [2-4]. Though there have been many developments in chemotherapy in the last 30 years, the 50% mortality rate associated with oral cancer has not changed [4, 5]. Longitudinal studies that track survival rates in oral cancer patients demonstrate a 3-fold reduction in patient deaths when patients …


Effects Of Localized Oxygen Production By Electrolysis On The First-Generation Glucose Sensor Response, Nandita Halder Dec 2021

Effects Of Localized Oxygen Production By Electrolysis On The First-Generation Glucose Sensor Response, Nandita Halder

Graduate Theses and Dissertations

Glucose sensors are very important for detecting blood glucose both in vitro and in vivo. First-generation glucose biosensors were based on the glucose oxidase (GOx) enzyme using molecular oxygen as the electron acceptor and therefore oxygen dependent. Unfortunately for in-vivo work, oxygen in the body is variable and limited. Alternative approaches to overcome the oxygen dependency came with their own limitations. The widely used and commercially available ex-vivo glucose test strip uses a mediator in place of oxygen to free it from oxygen dependency. The mediator-based technology, in most cases cannot be transferred to in vivo applications due to the …


Chemical And Biological Characterization Of The Anticancer Potency Of Salvia Fruticosa In A Model Of Human Malignant Melanoma, Sotiris Kyriakou, Venetia Tragkola, Michael Plioukas, Ioannis Anestopoulos, Paschalina S. Chatzopoulou, Eirini Sarrou, Dimitrios T. Trafalis, Maria V. Deligiorgi, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidi Nov 2021

Chemical And Biological Characterization Of The Anticancer Potency Of Salvia Fruticosa In A Model Of Human Malignant Melanoma, Sotiris Kyriakou, Venetia Tragkola, Michael Plioukas, Ioannis Anestopoulos, Paschalina S. Chatzopoulou, Eirini Sarrou, 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 aggressive types of skin cancer with an increasing incidence worldwide. Thus, the development of innovative therapeutic approaches is of great importance. Salvia fruticosa (SF) is known for its anticancer properties and in this context, we aimed to investigate its potential anti-melanoma activity in an in vitro model of human malignant melanoma. Cytotoxicity was assessed through a colorimetric-based sulforhodamine-B (SRB) assay in primary malignant melanoma (A375), non-malignant melanoma epidermoid carcinoma (A431) and non-tumorigenic melanocyte neighbouring keratinocyte (HaCaT) cells. Among eight (8) different fractions of S. fruticosa extracts (SF1-SF8) tested, SF3 was found to possess …


Mt10-Cvb3 Vaccine Virus Protects Against Cvb4 Infection By Inducing Cross-Reactive, Antigen-Specific Immune Responses, Ninaad Lasrado, Rajkumar Arumugam, Mahima T. Rasquinha, Meghna Sur, David Steffen, Jay Reddy Nov 2021

Mt10-Cvb3 Vaccine Virus Protects Against Cvb4 Infection By Inducing Cross-Reactive, Antigen-Specific Immune Responses, Ninaad Lasrado, Rajkumar Arumugam, Mahima T. Rasquinha, Meghna Sur, David Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Group B coxsackieviruses (CVB) containing six serotypes, B1–B6, affect various organs, and multiple serotypes can induce similar diseases such as myocarditis and pancreatitis. Yet, no vaccines are currently available to prevent these infections. Translationally, the derivation of vaccines that offer protection against multiple serotypes is highly desired. In that direction, we recently reported the generation of an attenuated strain of CVB3, termed Mt10, which completely protects against both myocarditis and pancreatitis induced by the homologous wild-type CVB3 strain. Here, we report that the Mt10 vaccine can induce cross-protection against multiple CVB serotypes as demonstrated with CVB4. We note that the …


Untargeted Lipidomics Of Non-Small Cell Lung Carcinoma Demonstrates Differentially Abundant Lipid Classes In Cancer Vs. Non-Cancer Tissue, Joshua M. Mitchell, Robert M. Flight, Hunter N. B. Moseley Oct 2021

Untargeted Lipidomics Of Non-Small Cell Lung Carcinoma Demonstrates Differentially Abundant Lipid Classes In Cancer Vs. Non-Cancer Tissue, Joshua M. Mitchell, Robert M. Flight, Hunter N. B. Moseley

Molecular and Cellular Biochemistry Faculty Publications

Lung cancer remains the leading cause of cancer death worldwide and non-small cell lung carcinoma (NSCLC) represents 85% of newly diagnosed lung cancers. In this study, we utilized our untargeted assignment tool Small Molecule Isotope Resolved Formula Enumerator (SMIRFE) and ultra-high-resolution Fourier transform mass spectrometry to examine lipid profile differences between paired cancerous and non-cancerous lung tissue samples from 86 patients with suspected stage I or IIA primary NSCLC. Correlation and co-occurrence analysis revealed significant lipid profile differences between cancer and non-cancer samples. Further analysis of machine-learned lipid categories for the differentially abundant molecular formulas identified a high abundance sterol, …


Physiological Roles Of Mammalian Transmembrane Adenylyl Cyclase Isoforms, Katrina F. Ostrom, Justin E. Lavigne, Tarsis F. Brust, Roland Seifert, Carmen Dessauer, Val J. Watts, Rennolds S. Ostrom Oct 2021

Physiological Roles Of Mammalian Transmembrane Adenylyl Cyclase Isoforms, Katrina F. Ostrom, Justin E. Lavigne, Tarsis F. Brust, Roland Seifert, Carmen Dessauer, Val J. Watts, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Adenylyl cyclases (ACs) catalyze the conversion of ATP to the ubiquitous second messenger cAMP. Mammals possess nine isoforms of transmembrane ACs, dubbed AC1-9, that serve as major effector enzymes of G protein-coupled receptors. The transmembrane ACs display varying expression patterns across tissues, giving potential for them having a wide array of physiologic roles. Cells express multiple AC isoforms, implying that ACs have redundant functions. Furthermore, all transmembrane ACs are activated by Gαs so it was long assumed that all ACs are activated by Gαs-coupled GPCRs. AC isoforms partition to different microdomains of the plasma membrane and form …


Inheritance Of A Mutation Causing Neuropathy With Splayed Forelimbs In Jersey Cattle, A. Al-Khudhair, D. J. Null, J. B. Cole, C. W. Wolfe, David J. Steffen, P. M. Vanraden Oct 2021

Inheritance Of A Mutation Causing Neuropathy With Splayed Forelimbs In Jersey Cattle, A. Al-Khudhair, D. J. Null, J. B. Cole, C. W. Wolfe, David J. Steffen, P. M. Vanraden

School of Veterinary and Biomedical Sciences: Faculty Publications

A new undesirable genetic factor, neuropathy with splayed forelimbs (JNS), has been identified recently in the Jersey breed. Calves affected with JNS are unable to stand on splayed forelimbs that exhibit significant extensor rigidity and excessive lateral abduction at birth. Affected calves generally are alert at birth but exhibit neurologic symptoms, including spasticity of head and neck and convulsive behavior. Other symptoms reported include dislocated shoulders, congenital craniofacial anomalies, and degenerative myelopathy. Inheritance of an undesirable genetic factor was determined from a study of 16 affected calves reported by Jersey breeders across the United States. All of their pedigrees traced …


Validation Of Arterial Spin Labeling For Longitudinal Monitoring And Differential Diagnosis Of Frontotemporal Dementia, Tracy Ssali Oct 2021

Validation Of Arterial Spin Labeling For Longitudinal Monitoring And Differential Diagnosis Of Frontotemporal Dementia, Tracy Ssali

Electronic Thesis and Dissertation Repository

Frontotemporal dementia (FTD) is a devastating neurodegenerative disease characterized by a rapid decline in behavioural, language, and motor abilities. Advances in the understanding of FTD genetics and pathophysiology, and the subsequent development of novel disease modifying treatments have highlighted the need for tools to assess their efficacy. While structural magnetic resonance imaging (MRI) and functional imaging with 18F-flurodeoxyglucose (FDG) positron emission tomography (PET) are used for clinical diagnosis, structural changes are subtle at the early stages and PET imaging is expensive and access limited. Given the coupling of cerebral blood flow (CBF) to energy metabolism, an attractive alternative is …


The Novel Orfv Protein Orfv113 Activates Lpa-P38 Signaling, Sushil Khatiwad, Gustavo Delho, Sabal Chaulagai, Daniel L. Rock Oct 2021

The Novel Orfv Protein Orfv113 Activates Lpa-P38 Signaling, Sushil Khatiwad, Gustavo Delho, Sabal Chaulagai, Daniel L. Rock

School of Veterinary and Biomedical Sciences: Faculty Publications

Viruses have evolved mechanisms to subvert critical cellular signaling pathways that regulate a wide range of cellular functions, including cell differentiation, proliferation and chemotaxis, and innate immune responses. Here, we describe a novel ORFV protein, ORFV113, that interacts with the G protein-coupled receptor Lysophosphatidic acid receptor 1 (LPA1). Consistent with its interaction with LPA1, ORFV113 enhances p38 kinase phosphorylation in ORFV infected cells in vitro and in vivo, and in cells transiently expressing ORFV113 or treated with soluble ORFV113. Infection of cells with virus lacking ORFV113 (OVIA82Δ113) significantly decreased p38 phosphorylation and viral plaque size. …


Exogenous Surfactant As A Delivery Vehicle For Intrapulmonary Therapeutics, Brandon J. Baer Oct 2021

Exogenous Surfactant As A Delivery Vehicle For Intrapulmonary Therapeutics, Brandon J. Baer

Electronic Thesis and Dissertation Repository

As an organ system, the lung has unique advantages and disadvantages for direct drug delivery. Its contact with the external environment allows for the airways to be easily accessible to intrapulmonary delivery. However, its complex structure, which divides into more narrow airways with each branch, can make direct delivery to the remote alveoli challenging. The objective of this thesis was to overcome this issue by using exogenous surfactant, a lipoprotein complex used to treat neonatal respiratory distress syndrome, as a carrier for pulmonary therapeutics. It was hypothesized that therapeutics administered with a surfactant vehicle would display enhanced delivery to the …


Alterations To The Brain Following Traumatic Brain Injury, Jacqueline Mader Oct 2021

Alterations To The Brain Following Traumatic Brain Injury, Jacqueline Mader

Honors Projects

Traumatic brain injuries (TBIs) have been labeled as a modern-day epidemic, increasing exponentially with the advancement of technology and society. Gaining a better understanding of the cognitive paths, including the chemical and electrical signals of the brain, neural correlates, and possible interventions for TBI patients allows for the best possible outcome for every patient, and allows for the further advancement of care. By revising and reassessing the ways in which TBIs are categorized and described the prognosis for recovery paints a more realistic view for each individual patient case. The symptoms and impairments that may occur post-injury can be monitored …


Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude C. Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson Sep 2021

Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude C. Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson

Physiology Faculty Publications

BACKGROUND: Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer's disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field.

METHODS: Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4.

RESULTS: Single-cell …


Targeting The Cdk6 Dependence Of Ph+ Acute Lymphoblastic Leukemia, Patrizia Porazzi, Marco De Dominici, Joseph Salvino, Bruno Calabretta Sep 2021

Targeting The Cdk6 Dependence Of Ph+ Acute Lymphoblastic Leukemia, Patrizia Porazzi, Marco De Dominici, Joseph Salvino, Bruno Calabretta

Department of Cancer Biology Faculty Papers

Ph+ ALL is a poor-prognosis leukemia subtype driven by the BCR-ABL1 oncogene, either the p190-or the p210-BCR/ABL isoform in a 70:30 ratio. Tyrosine Kinase inhibitors (TKIs) are the drugs of choice in the therapy of Ph+ ALL. In combination with standard chemotherapy, TKIs have markedly improved the outcome of Ph+ ALL, in particular if this treatment is followed by bone marrow transplantation. However, resistance to TKIs develops with high frequency, causing leukemia relapse that results in


Effect Of Carbon Monoxide Releasing Molecule 3 (Corm - 3) On Platelet Adhesion To Human Brain Microvascular Endothelial Cells, Najat S. El-Farra Aug 2021

Effect Of Carbon Monoxide Releasing Molecule 3 (Corm - 3) On Platelet Adhesion To Human Brain Microvascular Endothelial Cells, Najat S. El-Farra

Undergraduate Student Research Internships Conference

Sepsis is characterized by the widespread inflammation of the body. Systemic inflammation activates and recruits inflammatory cells (e.g., leukocytes) and platelets to the affected organs.

During these inflammatory conditions, human brain microvascular endothelial cells (hBMEC) and platelets both upregulate adhesive molecules rendering platelets to adhere to hBMEC.

Although carbon monoxide is thought of as a toxic molecule to many, previous work shows its anti-inflammatory properties. Evidence has shown carbon monoxide-releasing molecules (e.g., CORM-3; that release small, non-toxic amounts of CO) can combat the effects of severe inflammation in several in vivo animal model.

In this current study, we are looking …


Investigations In The Cellular And Molecular Biology Of Human Airway Mucociliary Tissue, Vincent Manna Aug 2021

Investigations In The Cellular And Molecular Biology Of Human Airway Mucociliary Tissue, Vincent Manna

Graduate School of Biomedical Sciences Theses and Dissertations

Our laboratory has integrated the use of a human-derived, in vitro model of airway mucociliary tissue. We isolate human nasal epithelial cells (HNECs) from the nasal mucociliary tissue of donors with a small brush and expand the airway progenitor cells in culture. The HNECs are then seeded onto semi-permeable transwell inserts. The inserts are in contact with the media in the lower chamber but don’t contain media in the upper chamber therefore the cells are exposed to the air while drawing nutrients from the media below, this is called the Air-Liquid Interface (ALI). HNECs cultured at the ALI initiate a …


Nucleotide P2y₂ Receptor-Dependent Leukocyte-Endothelial Interaction, Spencer E. Thomas Aug 2021

Nucleotide P2y₂ Receptor-Dependent Leukocyte-Endothelial Interaction, Spencer E. Thomas

MSU Graduate Theses

Extracellular nucleotides (ATP, UTP) released from cells act on nucleotide receptors to promote vascular inflammation. Increased leukocyte-endothelial interaction is a hallmark of vascular inflammation. The nucleotide P2Y₂ receptor (P2Y₂R), activated by extracellular ATP≈UTP, plays a role in cardiovascular homeostasis and immune regulation. Moreover, accumulating evidence from studies in vitro and in vivo models have implicated the P2Y₂R in the inflammatory response significantly contributing to the progression and pathogenesis of asthma, atherosclerosis, sepsis, and ischemia. I hypothesized that P2Y₂R activation by UTP, an agonist of the receptor, increased leukocyte rolling and adhesion in the microvasculature from baseline. To test the hypothesis, …


Modulation Of Glucose Homeostasis By Nucleotide P2y2 Receptor And Biological Sex, Hailee Anne Marino Aug 2021

Modulation Of Glucose Homeostasis By Nucleotide P2y2 Receptor And Biological Sex, Hailee Anne Marino

MSU Graduate Theses

Recent insights into the pathological role of Nucleotide P2Y2 receptor suggest P2Y2R involvement in high fat diet-induced obesity and potentiates insulin resistance. However, these recent insights do not demonstrate how P2Y2R modulates glucose homeostasis under physiological conditions. Further, it remains unknown how sex biological factors influence P2Y2R receptor signaling in the regulation of glucose homeostasis. The research objective for the present study is to elucidate the novel roles of P2Y2 in fasting blood glucose and glucose tolerance (basal insulin sensitivity) under resting conditions in males and females. We expected that under physiological …


African Swine Fever Virus Cd2v Protein Induces Β-Interferon Expression And Apoptosis In Swine Peripheral Blood Mononuclear Cells, Sabal Chaulangain, Gustavo A. Delhon, Sushil Khatiwada, Daniel L. Rock Jul 2021

African Swine Fever Virus Cd2v Protein Induces Β-Interferon Expression And Apoptosis In Swine Peripheral Blood Mononuclear Cells, Sabal Chaulangain, Gustavo A. Delhon, Sushil Khatiwada, Daniel L. Rock

School of Veterinary and Biomedical Sciences: Faculty Publications

African swine fever (ASF) is a hemorrhagic disease of swine characterized by massive lymphocyte depletion in lymphoid tissues due to the apoptosis of B and T cells, a process likely triggered by factors released or secreted by infected macrophages. ASFV CD2v (EP402R) has been implicated in viral virulence and immunomodulation in vitro; however, its actual function(s) remains unknown. We found that CD2v expression in swine PK15 cells induces NF-κB-dependent IFN-β and ISGs transcription and an antiviral state. Similar results were observed for CD2v protein treated swine PBMCs and macrophages, the major ASFV target cell. Notably, treatment of swine PBMCs and …


Medical Schools Ignore The Nature Of Consciousness At Great Cost, Anoop Kumar Jul 2021

Medical Schools Ignore The Nature Of Consciousness At Great Cost, Anoop Kumar

Journal of Wellness

The essential question of the relationship between consciousness and matter is ignored in medical school curricula, leading to a machine-like view of the human being that contributes to physician burnout and intellectual dissatisfaction. The evidence suggesting that the brain may not be the seat of consciousness is generally ignored to preserve the worldview of the primacy of matter. By investigating new frameworks detailing the nature of consciousness at different levels of hierarchy, we can bring intellectual rigor to a once opaque subject that supports a fundamental reality about our experience: We are human beings, not only human bodies.


Attenuated Strain Of Cvb3 With A Mutation In The Car‑Interacting Region Protects Against Both Myocarditis And Pancreatitis, Ninaad Lasrado, Arunakumar Gangaplara, Chandirasegaran Massilamany, Rajkumar Arumugam, Allison Shelbourn, Mahima T. Rasquinha, Rakesh H. Basavalingappa, Gustavo Delhon, Shi-Hua Xiang, Asit K. Pattnaik, David Steffen, Jay Reddy Jun 2021

Attenuated Strain Of Cvb3 With A Mutation In The Car‑Interacting Region Protects Against Both Myocarditis And Pancreatitis, Ninaad Lasrado, Arunakumar Gangaplara, Chandirasegaran Massilamany, Rajkumar Arumugam, Allison Shelbourn, Mahima T. Rasquinha, Rakesh H. Basavalingappa, Gustavo Delhon, Shi-Hua Xiang, Asit K. Pattnaik, David Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Coxsackievirus B3 (CVB3), is commonly implicated in myocarditis, which can lead to dilated cardiomyopathy, in addition to causing acute pancreatitis and meningitis. Yet, no vaccines are currently available to prevent this infection. Here, we describe the derivation of a live attenuated vaccine virus, termed mutant (Mt) 10, encoding a single amino acid substitution H790A within the viral protein 1, that prevents CVB3 infection in mice and protects from both myocarditis and pancreatitis in challenge studies. We noted that animals vaccinated with Mt 10 developed virus neutralizing antibodies, predominantly containing IgG2a and IgG2b, and to a lesser extent IgG3 and IgG1. …


Synphilin-1 And Its Effects On Pathogenesis Of Parkinson’S Disease, Mirghani Mohamed Jun 2021

Synphilin-1 And Its Effects On Pathogenesis Of Parkinson’S Disease, Mirghani Mohamed

Honors Scholar Theses

Parkinson's Disease (PD) is a progressive neurodegenerative and movement disorder primarily caused by the degradation of dopaminergic neurons. Known markers of neurodegeneration in PD are Lewy Bodies, which are fibrillar aggregates that are found in the brains of PD patients. Lewy Bodies can accumulate from specific mutations in the SNCA gene that codes for alpha-synuclein, a protein enriched in presynaptic neurons. A mutated SNCA gene can cause conformational aggregates of alpha-synuclein to form toxic species mediating neuronal death. Research into alpha-synuclein has led to the discovery of a binding partner known as synphilin-1 that is also found in protein aggregates …


Lipocalin-2 Ameliorates The Signs And Outcomes Of Diabetes Mellitus In An Animal Model, Saeeda Mohammed Al Jaberi Jun 2021

Lipocalin-2 Ameliorates The Signs And Outcomes Of Diabetes Mellitus In An Animal Model, Saeeda Mohammed Al Jaberi

Theses

Lipocalin-2 (LCN2) is a new adipocytokine consisting of 198 amino acids. It is also referred to as neutrophil gelatinase-associated lipocalin, siderocalin, uterocalin, α1-microglobulin related protein, or 24p3. LCN2 belongs to a large group of transport proteins that are capable of carrying small and lipid-soluble molecules in blood circulation. It has two membrane receptors, megalin/glycoprotein GP330, which binds human LCN2 and SLC22A17 or 24p3R, which forms complexes with mouse Lcn2 protein. LCN2 is encoded by a gene located at chromosome locus 9q34.11. LCN2 was initially isolated from neutrophil granules released at the site of infection and inflammation in humans and from …


Component Causes Of Infectious Bovine Keratoconjunctivitis—Non-Moraxella Organisms In The Epidemiology Of Infectious Bovine Keratoconjunctivitis, John Dustin Loy, Kristin A. Clothier, Gabriele Maier May 2021

Component Causes Of Infectious Bovine Keratoconjunctivitis—Non-Moraxella Organisms In The Epidemiology Of Infectious Bovine Keratoconjunctivitis, John Dustin Loy, Kristin A. Clothier, Gabriele Maier

School of Veterinary and Biomedical Sciences: Faculty Publications

• Non-Moraxella organisms are associated with infectious bovine keratoconjunctivitis (IBK).

Mycoplasma bovoculi can cause conjunctivitis and has a potential role in IBK pathogenesis.

• Other Non-Mycoplasma agents can cause disease that resembles IBK but is clinically different.

• Genomics and molecular technology are advancing research in this area.

• Classification and determination of pathogenesis potential of these organisms may be better understood through metagenomics and whole genome sequencing.


Etv2/Myct1 Axis In The Regulation Of Tumor Angiogenesis And Anti-Tumor Immunity, Ashraf Ul Kabir May 2021

Etv2/Myct1 Axis In The Regulation Of Tumor Angiogenesis And Anti-Tumor Immunity, Ashraf Ul Kabir

Arts & Sciences Electronic Theses and Dissertations

Angiogenesis is a critical determinant of neoplastic growth and metastatic spread. As such, anti-angiogenic approaches have long been tried to throttle down tumor progression. However, current anti-angiogenic treatments so far have produced modest clinical benefits. Further in-depth research has provided rationales behind these disappointing and apparent perplexing clinical outcomes. It is now established that VEGF (vascular endothelial growth factor) and other prominent current angiogenic targets are neither specific to the vascular system nor the pathological conditions explaining the sub-optimal angiogenic control following the existing treatments. This suggests that anti-angiogenesis could still be a viable strategy for cancer patients should there …


Mechanisms Of Natural Killer Cell Anti-Tumor Function And Homeostasis, Julia Alexandra Wagner May 2021

Mechanisms Of Natural Killer Cell Anti-Tumor Function And Homeostasis, Julia Alexandra Wagner

Arts & Sciences Electronic Theses and Dissertations

Natural killer (NK) cells are innate lymphoid cells (ILCs) that mediate anti-tumor and anti-viral immune responses. They do so via two primary effector functions: cytokine production and direct cytotoxicity. Unlike adaptive T and B lymphocytes, NK cells do not rearrange their DNA to express a predominant antigen-specific receptor, and instead express a variety of stochastically-expressed, germline DNA-encoded activating and inhibitory receptors whose signals integrate to govern their functional responses. What results is a diverse repertoire of NK cells capable of recognizing a variety of malignantly-transformed or virally-infected cells. Studies from several groups have established the anti-tumor potential of NK cells, …


A Screen Of Fda-Approved Drugs Identifies Inhibitors Of Protein Tyrosine Phosphatase 4a3 (Ptp4a3 Or Prl-3), Dylan R. Rivas, Mark Vincent C. Dela Cerna, Caroline N. Smith, Shilpa Sampathi, Blaine G. Patty, Donghan Lee, Jessica S. Blackburn May 2021

A Screen Of Fda-Approved Drugs Identifies Inhibitors Of Protein Tyrosine Phosphatase 4a3 (Ptp4a3 Or Prl-3), Dylan R. Rivas, Mark Vincent C. Dela Cerna, Caroline N. Smith, Shilpa Sampathi, Blaine G. Patty, Donghan Lee, Jessica S. Blackburn

Molecular and Cellular Biochemistry Faculty Publications

Protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3) is highly expressed in a variety of cancers, where it promotes tumor cell migration and metastasis leading to poor prognosis. Despite its clinical significance, small molecule inhibitors of PRL-3 are lacking. Here, we screened 1443 FDA-approved drugs for their ability to inhibit the activity of the PRL phosphatase family. We identified five specific inhibitors for PRL-3 as well as one selective inhibitor of PRL-2. Additionally, we found nine drugs that broadly and significantly suppressed PRL activity. Two of these broad-spectrum PRL inhibitors, Salirasib and Candesartan, blocked PRL-3-induced migration in human embryonic kidney cells …


Search For Palladin, An Actin-Associated Protein, In Pig Retinal Pigmented Epithelium And Its Role In Epithelial-Mesenchymal Transition, Katrina Powell May 2021

Search For Palladin, An Actin-Associated Protein, In Pig Retinal Pigmented Epithelium And Its Role In Epithelial-Mesenchymal Transition, Katrina Powell

Undergraduate Theses

This study investigates the expression of Palladin, a phosphoprotein product of the PALLD gene, in the retinal pigmented epithelium (RPE). Palladin is an actin cross-linking protein and plays a role in cell adhesion and motility. Published reports have demonstrated that a down regulation of Palladin in colon cancer cells results in a reorganization of the actin cytoskeleton, causing the cells to lose their typical shape, become proliferative and migratory. This process is otherwise known as epithelial-mesenchymal transition (EMT). A similar EMT phenomenon is observed when the RPE is exposed to the vitreous humor in patients with proliferative vitreoretinopathy (PVR). In …