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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 …

Investigation Into The Role Of Platelet Derived Growth Factor (Pdgf) In Type I Collagen Glomerulopathy, Isaac C. Springer

Graduate Theses/Dissertations

Progressive accumulation of collagen and extracellular matrix (ECM) proteins within renal glomeruli have implications for or result in renal fibrosis and glomerulosclerosis, with both events culminating in renal failure. To model this accumulation the Col1a2-deficient mouse model was used. The Col1a2-deficientmouse model is characterized by a mutation in the a2(I) chain, preventing incorporation into the type I collagen molecule. As a result, an α1(I) collagen chain incorporates into the collagen triple helix forming homotrimeric type I collagen, as opposed to heterotrimeric type I collagen. This change is due to the secondary wound healing response in response to ECM accumulation, …

Pituitary Adenylate Cyclase-Activating Polypeptide (Pacap) Signaling In The Prefrontal Cortex Modulates Cued Fear Learning, But Not Spatial Working Memory, In Female Rats, Adam J. Kirry, Matthew R. Herbst, Sarah E. Poirier, Michelle M. Maskeri, Amy C. Rothwell, Robert C. Twining, Marieke R. Gilmartin

Biomedical Sciences Faculty Research and Publications

A genetic polymorphism within the gene encoding the pituitary adenylate cyclase- activating polypeptide (PACAP) receptor type I (PAC1R) has recently been associated with hyper-reactivity to threat-related cues in women, but not men, with post-traumatic stress disorder (PTSD). PACAP is a highly conserved peptide, whose role in mediating adaptive physiological stress responses is well established. Far less is understood about the contribution of PACAP signaling in emotional learning and memory, particularly the encoding of fear to discrete cues. Moreover, a neurobiological substrate that may account for the observed link between PAC1R and PTSD in women, but not men, has yet to …

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 …

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 …

Tumor Immunotherapy: Mechanisms Of Acquired Resistance And Characterization Of Immune Related To Xicities, Ashvin Jaiswal

Dissertations and Theses (Open Access)

Tumor immunotherapy has shown very promising clinical benefit across an array of cancers; however, two major challenges remain unresolved in the field. First, many patients do not respond to therapy at all or relapse after a period of remission. Second, there are often dose-limiting immune related adverse effects associated with immunomodulation.

In order to understand the mechanisms employed by tumors to evade immunotherapeutic responses, we established a murine model of melanoma designed to elucidate the molecular mechanisms underlying immunotherapy resistance. Through multiple in vivo passages, we selected a B16 melanoma tumor line that evolved complete resistance to combination blockade of …

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

Theses and Dissertations (ETD)

No abstract provided.

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 …

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 …

Loss Of The Na+/H+ Exchange Regulatory Factor 1 Results In Increased Susceptibility To Cisplatin-Induced Acute Kidney Injury., Adrienne M. Bushau-Sprinkle

Electronic Theses and Dissertations

Background. Acute kidney injury (AKI), an abrupt loss of kidney function which carries a high mortality and confers an increased risk of chronic kidney disease, develops in 30% of patients who receive cisplatin, a widely used chemotherapeutic agent [1], [2], [3]. The sodium hydrogen exchange regulatory factor isoform 1 (NHERF1) is a scaffolding protein that anchors multiple membrane proteins, in renal proximal tubules [4]. NHERF-1 deficient mice have aberrant localization of BBM proteins in intracellular compartments [5]. The investigators have recently demonstrated NHERF1 deficient proximal tubule cells have an underlying …

Behavior Coding Strategies: Population Coupling And The Functional Role Of Excitatory/Inhibitory Balance In Primary Motor Cortex, Patrick Aaron Kells

Graduate Theses and Dissertations

The complexities of an organism’s experience of- and interaction with the world are emergent phenomena produced by large populations of neurons within the cerebral cortex and other brain regions. The network dynamics of these populations have been shown to be sometimes synchronous, with many neurons firing together, and sometimes asynchronous, with neurons firing more independently, leading to a decades-old debate within the neuroscience community. This discrepancy comes from viewing the system at two different scales; at the single cell level, the spiking activity of two neurons within cortex tend to be rather independent, but when the average activity of a …

Emergence Of Carbapenem Resistant Enterobacteriaceae In Abu Dhabi, 2009-2015, Aqdas Bilal Butt

Theses

The rapid emergence of carbapenem resistant Enterobacteriaceae (CRE) is a global phenomenon that has not spared the United Arab Emirates. However, unlike in most Western countries with similarly developed health care system, very little data have been available locally on the rate and dynamics of antimicrobial resistance in general, and that of CRE, in particular. Our laboratory has been collecting CRE isolates from Abu Dhabi hospitals since 2009. In the current study we subjected 394 such independent strains, representing 34.0% of the total CRE encountered, to a detailed analysis that included the determination of their antibiotic susceptibility profile, of the …

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 …

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 …

Can Alcaligenes Be A New Treatment For Staphylococcus Species?, Devin Narwani

Undergraduate Honors Theses

Members of the Staphylococcus genus are known to cause serious human infections in the clinical environment. Many species of this genus are typically found among the normal flora of the skin, nasal cavities, and the linings of the throat; however, the bacterium becomes an opportunistic infection when there is a break in the physical barriers or when a contaminated medical device is implanted in the human body. As more resistant strains are beginning to appear it is becoming drastically harder to treat patients infected with this bacterium. One such strain is Methicillin Resistant Staphylococcus aureus (MRSA). MRSA is a major …

Otologic Blast Injuries, Michelle Singer

Dissertations, Theses, and Capstone Projects

The otologic system functions as a highly sensitive pressure transducer. Because of this, the ear is the most commonly affected organ in primary blast injury. Frequently encountered symptoms include hearing loss, tinnitus, and tympanic membrane perforations. The ear is repeatedly overlooked during triage and easily forgotten in subjects with multiple injuries after major catastrophic events such as explosions. This systematic review provides an overview of the most common otologic injuries observed after blast exposure in a variety of settings and populations. An analysis of 35 studies and an additional 23 reviews was performed in attempt to uncover patterns of otologic …

Synaptic Nanomodules Underlie The Organization And Plasticity Of Spine Synapses., Martin Hruska, Nathan T. Henderson, Sylvain J. Le Marchand, Haani Jafri, Matthew B. Dalva

Department of Neuroscience Faculty Papers

Experience results in long-lasting changes in dendritic spine size, yet how the molecular architecture of the synapse responds to plasticity remains poorly understood. Here a combined approach of multicolor stimulated emission depletion microscopy (STED) and confocal imaging in rat and mouse demonstrates that structural plasticity is linked to the addition of unitary synaptic nanomodules to spines. Spine synapses in vivo and in vitro contain discrete and aligned subdiffraction modules of pre- and postsynaptic proteins whose number scales linearly with spine size. Live-cell time-lapse super-resolution imaging reveals that NMDA receptor-dependent increases in spine size are accompanied both by enhanced mobility of …

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 …

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"

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 …

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 …

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.

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 Nutrition Intake Of Football Players, Heba S. Abdelhaliem, Hoda M. El Gezrey

Journal of Medicine in Scientific Research

Introduction Despite football being the most popular sport in Egypt, most players do not know their needed nutritional requirements. The metabolic rate and energy consumption increased dramatically in football players. Thus, nutrition plays a significant role in improving the performance and the quality of life for these players. Objective This study aimed to assess the nutritional status of 50 football players aged between 15 and 19 years in Gomhorya Club – Menoufia. Participants and methods Dietary intake was evaluated for 7 days by using dietary assessment tools (24-h recall). This data was used to determine energy, macronutrients, micronutrients, and fiber. …

Human Cancer And Platelet Interaction, A Potential Therapeutic Target, Shike Wang, Zhenyu Li, Ren Xu

Markey Cancer Center Faculty Publications

Cancer patients experience a four-fold increase in thrombosis risk, indicating that cancer development and progression are associated with platelet activation. Xenograft experiments and transgenic mouse models further demonstrate that platelet activation and platelet-cancer cell interaction are crucial for cancer metastasis. Direct or indirect interaction of platelets induces cancer cell plasticity and enhances survival and extravasation of circulating cancer cells during dissemination. In vivo and in vitro experiments also demonstrate that cancer cells induce platelet aggregation, suggesting that platelet-cancer interaction is bidirectional. Therefore, understanding how platelets crosstalk with cancer cells may identify potential strategies to inhibit cancer metastasis and to reduce …

Out Of The Shell: Exploring The Phagocytic Capabilities Of The B Cell And Isolated Lymphoid Follicle-Lie Structures In The Red-Eared Slider, Trachemys Scripta, Marc A. Ashford Jr.

Theses and Dissertations

Management of immunity is crucial for survival in all living organisms. While there is a large amount of research for established model organisms, such as the mouse model, much less is known about reptiles. When compared to immunity in mammals, we discover many differences such as susceptibility to certain pathogens, alteration of immune processes due to environmental temperature, the total absence of certain lymphoid organs contained in mammals, among many others. Despite this, the reptile has shown in many studies that they are worthy systems to study immunity in an evolutionary perspective and recent studies may show that they may …

Modified Origins Of Cortical Projections To The Superior Colliculus In The Deaf: Dispersion Of Auditory Efferents., Blake E Butler, Julia K Sunstrum, Stephen G Lomber

Brain and Mind Institute Researchers' Publications

Following the loss of a sensory modality, such as deafness or blindness, crossmodal plasticity is commonly identified in regions of the cerebrum that normally process the deprived modality. It has been hypothesized that significant changes in the patterns of cortical afferent and efferent projections may underlie these functional crossmodal changes. However, studies of thalamocortical and corticocortical connections have refuted this hypothesis, instead revealing a profound resilience of cortical afferent projections following deafness and blindness. This report is the first study of cortical outputs following sensory deprivation, characterizing cortical projections to the superior colliculus in mature cats (

Effects Of Aging & Exercise On Production Of Glial Cell Line-Derived Neurotrophic Factor Protein By Fast & Slow Skeletal Muscle, Maria Jaramillo

Honors Theses

Exercise is a positive form of reinforcing positive lifestyle choices. There are many benefits to exercising such as decreased risk of cardiovascular disease and improved mental condition (Centers for Disease Control and Prevention). In addition, exercise can serve a protecting role for the nervous system. One form in which exercise can protect the nervous system is by increasing the production of neurotrophic factors, specifically glial cell line-derived neurotrophic factor. Another way by which exercise can protect the nervous system is by preserving muscle tissue due to actively recruiting it. The goal of this study was to explore the effects of …

Effects Of Muscle Activation On Gdnf Protein Content In Skeletal Muscle, Ramsey Potter

Honors Theses

Impairment of neuromuscular function as a result of aging is primarily associated with degeneration of the peripheral nervous system and loss of type II muscle fibers (Lexell et al, 1988). Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor found in skeletal muscle that has been shown to rescue motor neurons from axotomy-induced cell death (Oppenheim et al., 1995) and to induce NMJ plasticity (Keller-Peck et al., 2001). The aim of this study was to examine GDNF protein content following muscle activation in vitro and in vivo models. GDNF protein content was measured in rat gastrocnemius muscles following differing …

Credibility, Replicability, And Reproducibility In Simulation For Biomedicine And Clinical Applications In Neuroscience., Lealem Mulugeta, Andrew Drach, Ahmet Erdemir, C A Hunt, Marc Horner, Joy P. Ku, Jerry G Myers, Rajanikanth Vadigepalli, William W. Lytton

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Modeling and simulation in computational neuroscience is currently a research enterprise to better understand neural systems. It is not yet directly applicable to the problems of patients with brain disease. To be used for clinical applications, there must not only be considerable progress in the field but also a concerted effort to use best practices in order to demonstrate model credibility to regulatory bodies, to clinics and hospitals, to doctors, and to patients. In doing this for neuroscience, we can learn lessons from long-standing practices in other areas of simulation (aircraft, computer chips), from software engineering, and from other biomedical …