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In Vivo Structure-Function Analysis Of Drosophila Robo1, An Axon Guidance Receptor Critical For Midline Repulsive Signaling In The Embryonic Central Nervous System, Haley Brown

Graduate Theses and Dissertations

The repellant ligand Slit and its Roundabout (Robo) family receptors regulate many aspects of axon guidance in bilaterians, including midline crossing of axons during development of the embryonic CNS. Slit proteins are produced by midline cells and signal through Robo receptors expressed on the surface of axonal growth cones to repel axons from the midline. Disruption of Slit-Robo signaling causes ectopic midline crossing phenotypes in the CNS of a broad range of animals, including insects and vertebrates.

Drosophila Robo1 has a conserved ectodomain structure of five immunoglobulin-like (Ig) domains plus three fibronectin (FN) repeats. By utilizing a genomic rescue construct …

Neural Mechanisms Of The Rejection-Aggression Link, David S. Chester, Donald R. Lynam, Richard Milich, C. Nathan Dewall

Psychology Faculty Publications

Social rejection is a painful event that often increases aggression. However, the neural mechanisms of this rejection–aggression link remain unclear. A potential clue may be that rejected people often recruit the ventrolateral prefrontal cortex’s (VLPFC) self-regulatory processes to manage the pain of rejection. Using functional MRI, we replicated previous links between rejection and activity in the brain’s mentalizing network, social pain network and VLPFC. VLPFC recruitment during rejection was associated with greater activity in the brain’s reward network (i.e. the ventral striatum) when individuals were given an opportunity to retaliate. This retaliation-related striatal response was associated with greater levels of …

Therapeutic Potential Of A Plant-Made Cholera Toxin B Subunit Variant For The Treatment Of Ulcerative Colitis., Joshua Mark Royal

Electronic Theses and Dissertations

Cholera toxin B subunit (CTB) is a mucosal immunomodulatory protein that induces robust mucosal and systemic antibody responses. This well-known biological activity has been exploited in cholera prevention (as a component of Dukoral® vaccine) and vaccine development for decades. On the other hand, several studies have investigated CTB’s immunotherapeutic potential in the treatment of inflammatory diseases such as Crohn’s disease and asthma. Furthermore, we recently found that a plant-made variant of CTB (CTBp) could induce colon epithelial wound healing in mouse colitis models. In this thesis, it is revealed that the wound healing effects are unique to the plant-made variant, …

Inflammasome Independent Leukotriene-B4 Production Drives Crystalline Silica Induced Sterile Inflammation., Bindu Hegde

Electronic Theses and Dissertations

Silicosis is an irreversible lung inflammatory disease caused by chronic exposure to crystalline silica (CS) and is one of the most prevalent occupational diseases worldwide. Lipid chemoattractant Leukotriene B₄ (LTB₄) plays an important role in neutrophilic inflammation that drives silicosis and promotes lung cancer. Previous studies in our laboratory have demonstrated that CS-induced neutrophilic inflammation and lung tumor burden in K-ras^LA1 mice is abrogated in the LTB₄-receptor deficient mice. Another pathway whose importance is well studied in the progression of silicosis is the Nalp3 inflammasome pathway. Studies have shown inflammasome- dependent IL-1b to be …

Role Of Smarce1 And Bhlhe40 In Breast Cancer Metastasis, Aarti Sethuraman

Theses and Dissertations (ETD)

No abstract provided.

In-Vitro Simulation Of Acute Ischemic Stroke, Paolo Garcia

Biomedical Engineering Undergraduate Honors Theses

Acute ischemic stroke (AIS) is a condition that involves the occlusion of a blood vessel within the brain, effectively preventing the passage of oxygen and nutrients. AIS is highly prevalent in the United States, where nearly 795,000 strokes happen per year and 87% of those are ischemic. From a medical standpoint, the obstructing clot can be removed with the use of a stroke retrieval device. However, a need arises for testing the aforementioned devices on a patient’s specific vascular geometries in order to increase the likelihood of a successful procedure. Outlined is a process for developing a physical simulation of …

Enhanced Production Of Pro-Il-1Βeta Contributes To Immunopathology During The Coinfection Of Influenza A Virus And Streptococcus Pneumoniae, Angeline E. Rodriguez

Graduate Theses/Dissertations

Viral bacterial coinfections are known to cause severe pneumonia, especially in the elderly and in pediatric patients. Antibiotics like β-Lactams kill the bacteria but fail to improve symptoms suggesting a faulty immune system may play an important role in the disease. Interleukin-1β (IL-1β) is an important immune signaling cytokine responsible for inflammation. It exists as an inactive precursor that can be activated by caspase-1 containing inflammasomes (multi-protein complex). Influenza A virus (IAV) and Streptococcus pneumoniae (S. pneumoniae) activate the inflammasome through the NOD-like receptor protein NLRP3 and/or AIM2. Previous reports in mice indicate that IL-1β levels are dramatically …

Tissue Engineered Micro And Macrovasculature Utilizing Stromal Vascular Fraction., Joseph Samir Zakhari

Electronic Theses and Dissertations

This dissertation describes the use of stromal vascular fraction to tissue engineer 3D microvasculature and macrovasculature. Stromal vascular fraction is an easily isolatable cell source from adipose tissue depots. It has demonstrated remarkable potential both in vitro and in vivo for forming microcirculation capable of perfusion upon implantation. SVF is clinically utilized as a therapeutic cell source for anti-inflammation for osteoarthritis and is being studied for ischemic tissue application to stimulate revascularization. The work described herein is divided within four chapters. Chapter I provides an introductory overview and lists the aims and hypothesis for the dissertation. Chapter II describes experiments …

Intestinal Permeability And Microbial Dysbiosis In Acute Coronary Syndrome (Miacs Study), Tarik Z. Alhmoud

Biomedical Sciences ETDs

Background: Acute Coronary Syndrome (ACS) is a leading cause of morbidity and mortality. Metabolic syndrome and obesity are major risk factors for atherosclerosis and ACS. Dysbiosis plays an important role in metabolic syndrome and obesity. Studies show a markedly increased risk of heart attacks in patients with high levels of the pro-atherogenic metabolite trimethylamine-N-Oxide (TMAO). TMAO is produced by the intestinal microbial flora through metabolism of dietary phospholipids; Gram-negative bacteria (Phylum Proteobacteria) is the major source of TMAO metabolism. Patients with obesity and metabolic syndrome have a defective intestinal tight-junctional (TJ) barrier, which allows paracellular permeation of luminal antigens such …

Three Speeds Of Yoga And The Effects On Salivary Cortisol Levels In Female Nursing Students, Meagan Hennekens

All NMU Master's Theses

Purpose: Nursing students are prone to stress-related diseases, such as depression and anxiety, which are associated with chronically elevated cortisol levels due to the excessive firing of the Hypothalamic Pituitary Adrenal (HPA) axis. This study assessed three speeds of yoga and how they acutely affected salivary cortisol levels within female nursing students. Methods: Students participated in three yoga sessions cadenced at different speeds in a non-randomized order: (i) standard-speed yoga (SSY), (ii) high-speed yoga (HSY), and (iii) slow-speed yoga (SLSY). Each class integrated sequencing concepts from the brahmana/langhana strategy (BLS) and the Para Yoga Blueprint (PYB). Cortisol samples were …

Protein Trafficking Of Bk Channel Β1 Subunits In Cerebral Artery Myocytes, Xue Zhai

Theses and Dissertations (ETD)

Rationale: Large-conductance calcium (Ca²⁺)-activated potassium channels (BK) are expressed in arterial myocytes to control arterial contractility. It is composed of pore- forming BKα and auxiliary β1 subunits. Auxiliary β1 subunits associate with BKα which modulate Ca²⁺ sensitivity of BK channel. Previous data showed that BKα locates at cell membrane, whereas β1 subunits are primarily intracellular which regulated by Rab11A- positive recycling endosomes. Endothelin-1 (ET-1), a vasoconstrictor, induces contraction of myocytes. ET-1 inhibits BK channel but mechanisms are not fully understood. It is unclear that vasoconstrictors regulate the cellular distribution of BK channels. Furthermore, BK channels are involved …

Somatic Mutation Detection In Leukemia-Derived Circulating Dna: Utility In Monitoring Clonal Dynamics And Disease Response In Pediatric Acute Lymphoblastic Leukemia, Sarah Hisham Abdelaziz Youssef

Theses and Dissertations (ETD)

Despite the improved outcome associated with current treatment strategies ofpediatric acute lymphoblastic leukemia (ALL), relapse still represents a major challenge. Pediatric ALL demonstrates branched evolution in response to selective pressure exerted by therapy; relapse founder clones emerge from pre-leukemic clones or minor subclones present at diagnosis. It is hence crucial to develop biomarkers capable of tracking subclones throughout therapy. Current practices for monitoring disease response in leukemia rely on the analysis of BM biopsy sample at specific time points throughout therapy. Not only the invasiveness of the BM biopsy hinders the sequential sampling, but also, the currently implied techniques are …

The Systemic Quantification Of Immune Cell Populations In Various Murine Models: How Age, Tumor Burden, And Immunotherapy Affect The Immune Response, Kavita Sinha

Honors Scholar Theses

Immunotherapy as a form of cancer treatment has become increasingly popular in the past few decades. Researchers have worked to figure out how to best use the body’s natural defense mechanism, the immune system, to fight off and destroy cancer cells. In particular, the goal has been to manipulate checkpoint blockades such as CTLA-4 and PD-1 in order to take the breaks off of the immune system, allowing for a prolonged immune response to the cancer. This work has led to the development of human versions of anti-CTLA4 antibodies (ipilimumab, tremelimumab) and anti-PD1 antibodies (pembrolizumab and Nivolumab) that are currently …

Characterization Of The Hepatotoxicity Of Rifampicin And Isoniazid, Christopher T. Brewer

Theses and Dissertations (ETD)

In a mouse model, rifampicin and isoniazid combination treatment results in cholestatic liver injury that is associated with an increase of protoporphyrin ix (PPIX), the penultimate heme precursor. Excess PPIX is believed to bind to bile acids, precipitate in bile canaliculi, and form bile plugs leading to cholestasis fol owed by liver injury. Both ferrochelatase (FECH/Fech) and aminolevulinic acid synthase 1 (ALAS1/Alas1) are crucial enzymes in regulating heme biosynthesis. Isoniazid has recently been reported to up-regulate Alas1 but down-regulate Fech protein levels in mice; however the mechanism of isoniazid mediated heme synthesis …

Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin

Senior Honors Theses

The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research is …

Outcomes Of Genetic Testing In A Genitourinary Genetics Clinic, Annelise Pace

Dissertations and Theses (Open Access)

Several known hereditary cancer syndromes confer an increased risk for genitourinary (GU)related malignancies. Various guidelines indicate when to refer patients to genetic counseling for GU-related hereditary cancer syndromes but there is limited research on the clinical picture of these patients, including their cancerous and non-cancerous features, the genetic testing strategy for this population, and the probability of having a positive germline mutation if testing is performed. The purpose of this study is to determine the most common indications for ordering genetic testing in a GU Genetics Clinic and evaluate whether there is a relationship between the indication for genetic testing …

Pre-Season Vitamin D And Iron Levels As A Predictor Of Musculoskeletal Injury In Division I Athletes, Mariellen Katherine Veach

Graduate Theses and Dissertations

Context: Pre-season testing that includes the analysis of micronutrient serum levels in the blood has become a routine part of pre-participation examinations in collegiate football. Objective: Assess the predictability of vitamin D and iron serum levels as indicators of future injury during a subsequent competitive season for lower extremity sprains, strains, and fractures. Additionally, determine the effectiveness of vitamin D supplementation on increasing serum 25(OH)D levels and preventing injury. Design: Cohort Study. Setting: National Collegiate Athletic Association Division I football program. Participants: Football athletes (n=349) who underwent pre-participation examinations and participated in at least one of three competitive football seasons. …

Finding Small-Bowel Lesions: Challenges In Endoscopy-Image-Based Learning Systems, Jungmo Ahn, Loc Nguyen Huynh, Rajesh Krishna Balan, Youngki Lee, Jeonggil Ko

Research Collection School Of Computing and Information Systems

Capsule endoscopy identifies damaged areas in a patient's small intestine but often outputs poor-quality images or misses lesions, leading to either misdiagnosis or repetition of the lengthy procedure. The authors propose applying deep-learning models to automatically process the captured images and identify lesions in real time, enabling the capsule to take additional images of a specific location, adjust its focus level, or improve image quality. The authors also describe the technical challenges in realizing a viable automated capsule-endoscopy system.

Post-Traumatic Stress Disorder: Review Of Dsm Criteria And Functional Neuroanatomy, Cornelius W. Thomas

Marshall Journal of Medicine

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for post-traumatic stress disorder (PTSD) consist of over twenty possible symptoms that can be divided into six broad categories. These categories correlate with specific brain networks that regulate emotions, behaviors, and autonomic function. Normal functioning of these networks depends on two key regions; the prefrontal cortex and the amygdala. The prefrontal cortex provides top-down executive control over amygdala, whereas the amygdala is critical for threat detection and activation of the ‘fight or flight’ response. Events that trigger extreme and/or prolonged fear can cause persisting dysregulation within the prefrontal-amygdala circuit; resulting …

Bioprospecting Deep-Sea Actinobacteria For Novel Anti-Infective Natural Products, Dongbo Xu, Linna Han, Chunhui Li, Qi Cao, Duolong Zhu, Nolan H. Barrett, Dedra Harmody, Jing Chen, Haining Zhu, Peter J. Mccarthy, Xingmin Sun, Guojun Wang

Molecular and Cellular Biochemistry Faculty Publications

The global prevalence of drug resistance has created an urgent need for the discovery of novel anti-infective drugs. The major source of antibiotics in current clinical practice is terrestrial actinobacteria; the less-exploited deep-sea actinobacteria may serve as an unprecedented source of novel natural products. In this study, we evaluated 50 actinobacteria strains derived from diverse deep water sponges and environmental niches for their anti-microbial activities against a panel of pathogens including Candida albicans, Clostridium difficile, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA), and Pseudomonas aeruginosa. More than half of the tested strains (27) were identified as …

Linear Ubiquitin Chain-Binding Domains, Lilian Fennell, Simin Rahighi, Fumiyo Ikeda

Pharmacy Faculty Articles and Research

Ubiquitin modification (ubiquitination) of target proteins can vary with respect to chain lengths, linkage type, and chain forms, such as homologous, mixed, and branched ubiquitin chains. Thus, ubiquitination can generate multiple unique surfaces on a target protein substrate. Ubiquitin‐binding domains (UBDs) recognize ubiquitinated substrates, by specifically binding to these unique surfaces, modulate the formation of cellular signaling complexes and regulate downstream signaling cascades. Among the eight different homotypic chain types, Met1‐linked (also termed linear) chains are the only chains in which linkage occurs on a non‐Lys residue of ubiquitin. Linear ubiquitin chains have been implicated in immune responses, cell death …

Week Of April 30, 2018, New York Medical College

InTouch

• Kelly A. Hutcheson, M.D., M.B.A., Is Appointed Chair of the Department of Ophthalmology
• NYMC Celebrates Public Health Week
• Department of Physical Therapy Hosts Fourteenth Annual Doctoral Project Presentation Day
• NYMC on the Move
• NYMC Faculty Participate in " Pediatric Advances for the Primary Care Clinician: Cutting Edge Expertise"

Herpes Zoster Patient Education: A Coloring Book Approach, Sophia Charuhas

Senior Honors Theses

Shingles, the disease caused by the herpes zoster virus, is a widespread and widely misunderstood illness in the United States. It is preventable, but many at-risk patients do not know what measures they may take to prevent it. Clear communication from physician to patient is crucial for patient understanding of diseases. Many patient education materials on herpes zoster currently available are often unused. It is therefore beneficial to public health to disseminate new mediums of medical communication, and one way of accomplishing this is through adult coloring books. The pathophysiology of herpes zoster virus is here explored and the idea …

Common Ribs Of Inhibitory Synaptic Dysfunction In The Umbrella Of Neurodevelopmental Disorders, Rachel Ali Rodriguez, Christina Joya, Rochelle M. Hines

Psychology Faculty Research

The term neurodevelopmental disorder (NDD) is an umbrella term used to group together a heterogeneous class of disorders characterized by disruption in cognition, emotion, and behavior, early in the developmental timescale. These disorders are heterogeneous, yet they share common behavioral symptomatology as well as overlapping genetic contributors, including proteins involved in the formation, specialization, and function of synaptic connections. Advances may arise from bridging the current knowledge on synapse related factors indicated from both human studies in NDD populations, and in animal models. Mounting evidence has shown a link to inhibitory synapse formation, specialization, and function among Autism, Angelman, Rett …

Factors Involved In Suppression Of Human Vγ9vδ2 T-Lymphocytes And Impact Of Checkpoint Blockades On The Effector Functions Of Vγ9vδ2 T-Lymphocytes, Minji Choi, Andrew Wiemer, Andrea Hubbard, Brian Aneskievich

University Scholar Projects

Chronic antigenic stimulation leads to T cell exhaustion, which drastically dampens T cell effector functions. Upon exhaustion, T cells progressively lose their proliferative capacity, cytokine production, and cytotoxic effector functions against tumors. T cell exhaustion involves programmed cell death-1 (PD-1), which is an inhibitory co-stimulation receptor. Limited scope of studies has been done regarding impact of PD-1 expression on the effector functions of γδ T cells. In this study, we investigated expression of PD-1 and its impact on effector functions of human γδ T cells. When γδ T cells were stimulated with phosphoantigens (HMBPP and POM₂-C-HMBP) and analyzed …

Cd8+ T-Cell Responses In Vaccination: Reconsidering Targets And Function In The Context Of Chronic Antigen Stimulation, Gabriela L. Cosma, Laurence Eisenlohr

Department of Microbiology and Immunology Faculty Papers

Cytotoxic CD8 T cells play important roles in eliminating infected and transformed cells. Owing to their potential for therapeutic applications, significant efforts are dedicated toward developing CD8 T cell-based vaccines. Thus far, CD8 T-cell vaccination strategies have had limited success therapeutically in contrast to those targeting antibody-based immunity. However, if the current challenges and gaps in the understanding of T-cell biology are overcome, the full potential of rational CD8 T-cell vaccine design might be realized. Here, we review recent progress in this direction, focusing on target selection and maintenance of function in the settings of chronic infections and cancers.

A Cytotoxic Evaluation Of A Chalcone Derivative Library On A549 Cells, Mary Elaine Kuo

Undergraduate Theses

Chalcones, a precursor to flavonoids, are chemical compounds found naturally in plants. The chalcones’ structure consists of a ketone bridge attached to two aromatic rings. Varying substituents on the aromatic rings allow for different affects, including anti-cancer properties. As a Michael acceptor, chalcones interact with pathways that cause inhibition of the initiation, promotion, and progression of cancer tumors. We have screened 32 compounds for growth inhibition in lung cells that vary the flexibility and confirmation of the 3 carbon bridge between the two aromatic rings as well as the effects of electronic modifications to the aromatic ring. We have found …

Thalamocortical Processing Of Temporal Cues In Sounds, Kasey Smith

Honors Scholar Theses

The ability of the brain to extract meaningful information from complex sounds is what allows mammals to understand species-specific communication as well as important environmental cues such as the sound of water or of potential predators or prey. The auditory cortex of humans and other mammals contains multiple cortical regions that unique sensitivities to both spectral and temporal sound cues. This discourse will explore three main factors proposed to determine these distinct processing capabilities in regard to temporal sound cues; the distribution of glutamate transporters in the thalamus, the architecture of afferent pathways between the thalamus and auditory cortex, and …

Evaluation Of Oxytocin And Serotonin Levels In Autism Spectrum Disorder, Amal El-Ramly, Azza Samy, Eman Soliman, Golnar Oteify

Journal of Medicine in Scientific Research

Objective Autism spectrum disorder (ASD) is a complex neurological and developmental disorder that affects how a person acts and interacts, communicates with others, and learns. Endocrine and neuropeptide factors are some among the list of possible etiologic or predisposing contenders. Abnormalities in the brain serotonin system are reported in ASD, including evidence of altered serotonin synthesis and receptor binding, as well as dystrophic serotonergic axons. Blood oxytocin levels are also a focus of ASD research. This work aimed to assess oxytocin and serotonin levels as biomarkers in individuals with ASD. Participants and methods Serotonin and oxytocin levels, as biochemical parameters …

Outcome Of Cochlear Implantation In Children With Enlarged Vestibular Aqueduct (Eva) And Mondini Dysplasia (Incomplete Partition Type Ii), Abir Omara, Amr Younes, Azza Sami, Ihab Sefein, Iman Elrouby, Soha Hamada

Journal of Medicine in Scientific Research

Background Congenital inner ear abnormality is a major cause of sensorineural hearing loss in children, about 20% of children with congenital sensorineural hearing loss (SNHL) have associated malformations of the temporal bone, and increased experience in cochlear implantation has led to more children with abnormal cochleo-vestibular anatomy submitted to this procedure. Aim To evaluate the outcome of cochlear implantation in cases with enlarged vestibular aqueduct (EVA) and Mondini deformity (incomplete partition type II) following cochlear implantation and comparing the results with cochlear implant cases without inner ear anomalies. Patients and methods 69 children all less than 6 years of age, …