Medical Sciences Commons^™

Notch Signaling Regulates Mitochondrial Metabolism And Nf-Κb Activity In Triple-Negative Breast Cancer Cells Via Ikkα-Dependent Non-Canonical Pathways, Fokhrul Hossain, Claudia Sorrentino, Deniz A. Ucar, Yin Peng, Margarite Matossian, Dorota Wyczechowska, Judy Crabtree, Jovanny Zabaleta, Silvana Morello, Luis Del Valle, Matthew Burow, Bridgette Collins-Burow, Antonio Pannuti, Lisa M. Minter, Todd E. Golde, Barbara A. Osborne, Lucio Miele

School of Medicine Faculty Publications

Triple negative breast cancer (TNBC) patients have high risk of recurrence and metastasis, and current treatment options remain limited. Cancer stem-like cells (CSCs) have been linked to cancer initiation, progression and chemotherapy resistance. Notch signaling is a key pathway regulating TNBC CSC survival. Treatment of TNBC with PI3K or mTORC1/2 inhibitors results in drug-resistant, Notch-dependent CSC. However, downstream mechanisms and potentially druggable Notch effectors in TNBC CSCs are largely unknown. We studied the role of the AKT pathway and mitochondrial metabolism downstream of Notch signaling in TNBC CSC from cell lines representative of different TNBC molecular subtypes as well as …

Autoimmune Hyperphosphatemic Tumoral Calcinosis In A Patient With Fgf23 Autoantibodies., Mary Scott Roberts, Peter D. Burbelo, Daniela Egli-Spichtig, Farzana Perwad, Christopher J. Romero, Shoji Ichikawa, Emily G. Farrow, Michael J. Econs, Lori C. Guthrie, Michael T. Collins, Rachel I. Gafni

Manuscripts, Articles, Book Chapters and Other Papers

Hyperphosphatemic familial tumoral calcinosis (HFTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is an autosomal recessive disorder of ectopic calcification due to deficiency of or resistance to intact fibroblast growth factor 23 (iFGF23). Inactivating mutations in FGF23, N-acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO (KL) have been reported as causing HFTC/HHS. We present what we believe is the first identified case of autoimmune hyperphosphatemic tumoral calcinosis in an 8-year-old boy. In addition to the classical clinical and biochemical features of hyperphosphatemic tumoral calcinosis, the patient exhibited markedly elevated intact and C-terminal FGF23 levels, suggestive of FGF23 resistance. However, no mutations in FGF23, KL, or FGF receptor 1 …

Week Of December 3, 2018, New York Medical College

InTouch

• SHSP Hosts Special Dean's Lecture
• SOM Office of Diversity and Inclusion Celebrates Native American Heritage Month
• D.P.T. Class of 2020 Present Community Service Projects
• Guests Celebrate at Touro College of Dental Medicine Gala
• Med Students Observe Movember for a Good Cause

Early Oral Feeding After Bowel Resection, Jennifer Strang

Theses & Dissertations

Research Focus: The primary purpose of this project was to determine if there was an association of factors with time to first solid meal in gastrointestinal (GI) surgery patients and the impact solid diet has on length of stay (LOS) in the hospital, GI symptoms, and incidence of post-operative ileus (POI). A secondary purpose was to observe and describe when an oral diet was started and the progression of diet after GI surgery.

Research Methods: This study was a cross-sectional, retrospective chart review of a convenience sample in a multi-centered hospital system conducted in 84 GI resection patients …

Assessment Of Interprofessional Team Collaboration Scale (Aitcs): Further Testing And Instrument Revision., Carole Orchard, Linda L Pederson, Emily Read, Cornelia Mahler, Heather Laschinger

Nursing Publications

INTRODUCTION: The need to be able to assess collaborative practice in health care teams has been recognized in response to the direction for team-based care in a number of policy documents. The purpose of this study is to report on further refinement of such a measurement instrument, the Assessment of Interprofessional Team Collaboration Scale (AITCS) first published in 2012. To support this refinement, two objectives were set: Objective 1: to determine whether the items from the data collected in 2016 load on the same factors as found for the 2012 version of the 37-item AITCS. Objective 2: to determine whether …

Impaired Object-Location Learning And Recognition Memory But Enhanced Sustained Attention In M2 Muscarinic Receptor-Deficient Mice, Carola Romberg, Susan Bartko, Jürgen Wess, Lisa M. Saksida, Timothy J. Bussey

Brain and Mind Institute Researchers' Publications

© 2018, The Author(s). Rationale: Muscarinic acetylcholine receptors are known to play key roles in mediating cognitive processes, and impaired muscarinic cholinergic neurotransmission is associated with normal ageing processes and Alzheimer’s disease. However, the specific contributions of the individual muscarinic receptor subtypes (M1–M5) to cognition are presently not well understood. Objectives: The aim of this study was to investigate the contribution of M2-type muscarinic receptor signalling to sustained attention, executive control and learning and memory. Methods: M2 receptor-deficient (M2−/−) mice were tested on a touchscreen-operated task battery testing visual discrimination, behavioural flexibility, object-location associative learning, attention and response control. Spontaneous …

The Psychological Science Accelerator: Advancing Psychology Through A Distributed Collaborative Network, Hannah Moshontz, Lorne Campbell, Charles R. Ebersole, Hans Ijzerman, Heather L. Urry, Patrick S. Forscher, Jon E. Grahe, Randy J. Mccarthy, Erica D. Musser, Jan Antfolk, Christopher M. Castille, Thomas Rhys Evans, Susann Fiedler, Jessica Kay Flake, Diego A. Forero, Steve M. Janssen, Justin Robert Keene, John Protzko, Balazs Aczel, Sara Álvarez Solas, Daniel Ansari, Dana Awlia, Ernest Baskin, Carlota Batres, Martha Lucia Borras-Guevara, Cameron Brick, Priyanka Chandel, Armand Chatard, William J. Chopik, David Clarance, Nicholas A. Coles, Katherine S. Corker

Brain and Mind Institute Researchers' Publications

Concerns have been growing about the veracity of psychological research. Many findings in psychological science are based on studies with insufficient statistical power and nonrepresentative samples, or may otherwise be limited to specific, ungeneralizable settings or populations. Crowdsourced research, a type of large-scale collaboration in which one or more research projects are conducted across multiple lab sites, offers a pragmatic solution to these and other current methodological challenges. The Psychological Science Accelerator (PSA) is a distributed network of laboratories designed to enable and support crowdsourced research projects. These projects can focus on novel research questions, or attempt to replicate prior …

Dna Methylation-Based Age Prediction And Telomere Length In White Blood Cells And Cumulus Cells Of Infertile Women With Normal Or Poor Response To Ovarian Stimulation., Scott J. Morin, Xin Tao, Diego Marin, Yiping Zhan, Jessica Landis, Jenna Bedard, Richard T. Scott, Emre Seli

Department of Biochemistry and Molecular Biology Faculty Papers

An algorithm assessing the methylation levels of 353 informative CpG sites in the human genome permits accurate prediction of the chronologic age of a subject. Interestingly, when there is discrepancy between the predicted age and chronologic age (age acceleration or "AgeAccel"), patients are at risk for morbidity and mortality. Identification of infertile patients at risk for accelerated reproductive senescence may permit preventative action. This study aimed to assess the accuracy of the "epigenetic clock" concept in reproductive age women undergoing fertility treatment by applying the age prediction algorithm in peripheral (white blood cells [WBCs]) and follicular somatic cells (cumulus cells …

Parp-1 Regulates Dna Repair Factor Availability., M J Schiewer, Amy C. Mandigo, Nicolas Gordon, Fangjin Huang, Sanchaika Gaur, Renée De Leeuw, Shuang G Zhao, Joseph Evans, Sumin Han, Theodore Parsons, Ruth Birbe, Peter Mccue, Christopher Mcnair, Saswati N. Chand, Ylenia Cendon-Florez, Peter Gallagher, Jennifer J Mccann, Neermala Poudel Neupane, Ayesha A Shafi, Emanuela Dylgjeri, Lucas J Brand, Tapio Visakorpi, Ganesh V Raj, Costas D. Lallas, Edouard J Trabulsi, Leonard G Gomella, Adam Dicker Md, Phd, William Kevin Kelly, Benjamin E Leiby, Beatrice Knudsen, Felix Y Feng, Karen E Knudsen

Department of Cancer Biology Faculty Papers

PARP-1 holds major functions on chromatin, DNA damage repair and transcriptional regulation, both of which are relevant in the context of cancer. Here, unbiased transcriptional profiling revealed the downstream transcriptional profile of PARP-1 enzymatic activity. Further investigation of the PARP-1-regulated transcriptome and secondary strategies for assessing PARP-1 activity in patient tissues revealed that PARP-1 activity was unexpectedly enriched as a function of disease progression and was associated with poor outcome independent of DNA double-strand breaks, suggesting that enhanced PARP-1 activity may promote aggressive phenotypes. Mechanistic investigation revealed that active PARP-1 served to enhance E2F1 transcription factor activity, and specifically promoted …

The Cardiovascular Demands Of Division I Sideline Cheerleaders During Training And Football Games, Mckenna Cornett

Theses and Dissertations

The purpose of this study was to evaluate the autonomic balance and cardiovascular demands of collegiate sideline cheerleaders between practice and game settings, and throughout four quarters of a football game; and to evaluate the physical fitness of collegiate Division I cheerleaders. Eleven cheerleaders volunteered to participate (age; 18.9+0.8y, height; 163.2+4.3cm, and body mass; 64.9+8.7kg). Basic physical fitness was assessed by evaluating blood pressure, resting heart rate, grip strength, and body composition. Physiological data (maximal heart rate [HR], average HR, physiological intensity, physiological load, maximal activity, and average activity) were collected at four practices and four games using a Zephyr …

The Single Mitochondrion Of The Kinetoplastid Parasite Crithidia Fasciculata Is A Dynamic Network., John Dimaio, Gordon Ruthel, Joshua J. Cannon, Madeline F. Malfara, Megan L. Povelones

Department of Medical Laboratory Sciences & Biotechnology Faculty Papers

Mitochondria are central organelles in cellular metabolism. Their structure is highly dynamic, allowing them to adapt to different energy requirements, to be partitioned during cell division, and to maintain functionality. Mitochondrial dynamics, including membrane fusion and fission reactions, are well studied in yeast and mammals but it is not known if these processes are conserved throughout eukaryotic evolution. Kinetoplastid parasites are some of the earliest-diverging eukaryotes to retain a mitochondrion. Each cell has only a single mitochondrial organelle, making them an interesting model for the role of dynamics in controlling mitochondrial architecture. We have investigated the mitochondrial division cycle in …

Virulence Regulation In Pseudomonas Aeruginosa Via The Alginate Regulators, Algu And Algr, The Posttranscriptional Regulator, Rsma, And The Two-Component System, Algz/R, Sean Stacey

Electronic Theses and Dissertations

Pseudomonas aeruginosa is a Gram-negative bacillus able to colonize a wide variety of environments. In the human host, P. aeruginosa can establish an acute infection or persist and create a chronic infection. P. aeruginosa is able to establish a niche and persist in human hosts by using a wide array of virulence factors used for: movement, killing host cells, and evading immune cells and antibiotics. Understanding virulence factors and their regulation has proved to be an important means of combating the morbidity and mortality of P. aeruginosa as well as the ever-increasing threat of drug resistance. By targeting virulence factors …

Lakeshore Modification Reduces Secondary Production Of Macroinvertebrates In Littoral But Not Deeper Zones, Marlene Pätzig, Yvonne Vadeboncoeur, Mario Brauns

Biological Sciences Faculty Publications

Littoral macroinvertebrates are an integral component of lake food webs, but their productivity may be affected by shoreline alteration. We hypothesized that human modification of lake shores simplifies habitat diversity, which, in turn, affects littoral macroinvertebrate production and patterns of depth–production relationships. Furthermore, we expected that lakeshore modification would favor nonnative species, potentially compensating for negative effects of lakeshore modification on production of native taxa. To test these ideas, we estimated benthic macroinvertebrate production in the upper littoral, middle littoral, and profundal zones of a large lowland lake (Lake Scharmützelsee) in Northeast Germany. We collected samples between April and November …

Using The Engagedmd Multimedia Platform To Improve Informed Consent For Ovulation Induction, Intrauterine Insemination, And In Vitro Fertilization, Jody L. Madeira, Jennifer Rehbein, Mindy S. Christianson, Miryoung Lee, J. Preston Parry, Guido Pennings, Steven R. Lindheim Md

Articles by Maurer Faculty

Objective: To study patient and provider feedback on how a multimedia platform (EngagedMD) helps patients to understand the risks and consequences of in vitro fertilization (IVF), ovulation induction (OI), and intrauterine insemination (IUI) treatments and the impact of the informed consent process.

Design: Prospective survey study.

Setting: IVF units in the United States.

Patient(s): Six-thousand three-hundred and thirty-three patients who viewed the multimedia platform before IVF or OI-IUI treatment at 13 U.S. IVF centers and 128 providers.

Intervention(s): Quantitative survey with 17 questions.

Main Outcome Measure(s): Assessment of the impact of a multimedia platform on patient anxiety, comprehension, and satisfaction …

The First In Vivo Human Methionine Sulfide Proteome And The Impact Of Smoking, Abdullah Qassab

Graduate Theses and Dissertations

Reactive oxygen species are naturally generated within the human body and they are known to modulate signaling pathway and mediate other physiological activities. However, excessive generation of ROS and the inability of body defense system in detoxifying them results in the so called “oxidative stress”. Methionine has powerful antioxidant properties due to the presence of electronegative sulfur in its structure. Therefore, Met is readily oxidized, and methionine sulfoxide has been linked to several pathological conditions.

The urinary proteome is an attractive candidate for the discovery of biomarkers to diagnose and classify health conditions because of the non-invasive collection procedure. However, …

Dna Methylation By Restriction Modification Systems Affects The Global Transcriptome Profile In Borrelia Burgdorferi, Timothey Casselli, Yvonne Tourand, Adam Scheidegger, William K. Arnold, Anna Proulx, Brian Stevenson, Catherine A. Brissette

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Prokaryote restriction modification (RM) systems serve to protect bacteria from potentially detrimental foreign DNA. Recent evidence suggests that DNA methylation by the methyltransferase (MTase) components of RM systems can also have effects on transcriptome profiles. The type strain of the causative agent of Lyme disease, Borrelia burgdorferi B31, possesses two RM systems with N6-methyladenosine (m6A) MTase activity, which are encoded by the bbe02 gene located on linear plasmid lp25 and bbq67 on lp56. The specific recognition and/or methylation sequences had not been identified for either of these B. burgdorferi MTases, and it was not previously known whether these RM …

Levels Of Par-1 Kinase Determine The Localization Of Bruchpilot At The Drosophila Neuromuscular Junction Synapses., Kara R. Barber, Martin Hruska, Keegan M. Bush, Jade A. Martinez, Hong Fei, Irwin B. Levitan, Matthew B. Dalva, Yogesh P. Wairkar

Farber Institute for Neuroscience Faculty Papers

Functional synaptic networks are compromised in many neurodevelopmental and neurodegenerative diseases. While the mechanisms of axonal transport and localization of synaptic vesicles and mitochondria are relatively well studied, little is known about the mechanisms that regulate the localization of proteins that localize to active zones. Recent finding suggests that mechanisms involved in transporting proteins destined to active zones are distinct from those that transport synaptic vesicles or mitochondria. Here we report that localization of BRP-an essential active zone scaffolding protein in Drosophila, depends on the precise balance of neuronal Par-1 kinase. Disruption of Par-1 levels leads to excess accumulation of …

The Effects Of Habitual Protein Consumption On Vasodilation In Young Adults, Natalie O'Neal, Jordan Rezac

Health, Human Performance and Recreation Undergraduate Honors Theses

Introduction: Blood pressure is a critical indicator for a number of health risks and conditions, such as hypertension (high blood pressure), heart failure, and stroke. Decreasing blood pressure occurs by vasodilation (relaxation) of blood vessels. The consumption of high amounts of protein is hypothesized to have a correlation with the vasodilation of vessels, thus creating a decrease in blood pressure. Purpose: The purpose of this study was to relate blood vessel diameter to habitual protein consumption. Our findings have the power to make individuals more aware of the effect their habitual protein intake can have on cardiovascular health. Methods: This …

Floxed-Cassette Allelic Exchange Mutagenesis Enables Markerless Gene Deletion In Chlamydia Trachomatis And Can Reverse Cassette-Induced Polar Effects, Gabrielle Keb, Robert Hayman, Kenneth A. Fields

Microbiology, Immunology, and Molecular Genetics Faculty Publications

As obligate intracellular bacteria, Chlamydia spp. have evolved numerous, likely intricate, mechanisms to create and maintain a privileged intracellular niche. Recent progress in elucidating and characterizing these processes has been bolstered by the development of techniques enabling basic genetic tractability. Florescence-reported allelic exchange mutagenesis (FRAEM) couples chromosomal gene deletion with the insertion of a selection cassette encoding antibiotic resistance and green fluorescent protein (GFP). Similar to other bacteria, many chlamydial genes exist within polycistronic operons, raising the possibility of polar effects mediated by insertion cassettes. Indeed, FRAEM-mediated deletion of Chlamydia trachomatis tmeA negatively impacts the expression of tmeB. We …

Sumo-Mediated Regulation Of Nlrp3 Modulates Inflammasome Activity., Rachael Barry, Sidonie Wicky John, Gianmaria Liccardi, Tencho Tenev, Isabel Jaco, Chih-Hong Chen, Justin Choi, Paulina Kasperkiewicz, Teresa Fernandes-Alnemri, Emad S Alnemri, Marcin Drag, Yuan Chen, Pascal Meier

Department of Biochemistry and Molecular Biology Faculty Papers

The NLRP3 inflammasome responds to infection and tissue damage, and rapidly escalates the intensity of inflammation by activating interleukin (IL)-1β, IL-18 and cell death by pyroptosis. How the NLRP3 inflammasome is negatively regulated is poorly understood. Here we show that NLRP3 inflammasome activation is suppressed by sumoylation. NLRP3 is sumoylated by the SUMO E3-ligase MAPL, and stimulation-dependent NLRP3 desumoylation by the SUMO-specific proteases SENP6 and SENP7 promotes NLRP3 activation. Defective NLRP3 sumoylation, either by NLRP3 mutation of SUMO acceptor lysines or depletion of MAPL, results in enhanced caspase-1 activation and IL-1β release. Conversely, depletion of SENP7 suppresses NLRP3-dependent ASC oligomerisation, …

Adolescent Sexual And Reproductive Health In The Gambia., Sandhya Lohani

Electronic Theses and Dissertations

Adolescence is a crucial period in human development. Knowledge and awareness about when to have children, when to have sex, and use of contraceptives impacts the chances of teenage pregnancy and risk of sexually transmitted diseases. The objective of this study is to determine the prevalence and associated risk factors related to age of sexual debut, teenage pregnancy, and use of contraceptives in the Gambia. This study also compares the data with 2014 survey research conducted in the Gambia. The total study population were 50 adolescents aged 13-21 years from Bafuluto and surrounding communities in the Gambia. Among 50 respondents, …

Intratumoral Sting Activation Sensitizes Poorly Immunogenic Cancers To Checkpoint Blockade Immunotherapy, Casey Ager

Dissertations and Theses (Open Access)

Unprecedented durable tumor regression can be achieved in patients with checkpoint blockade immunotherapy, yet these responses are rare and are not observed in all tumor types. Castration resistant prostate cancer (CRPC) and pancreatic adenocarcinoma (PDAC) are two common lethal cancers that remain refractory to checkpoint blockade, requiring development of new therapeutic approaches to promote responsivity in patients with these diseases. Both CRPC and PDAC are characterized by an immunosuppressive tumor milieu rich in cells of the myeloid lineage, which regulate T cell activity in many ways independent of the coinhibitory receptor axis. We investigated whether activation of acute inflammatory signaling …

Cholesterol Metabolism And Statin Effects On An Fh Class Ii Ldl-Receptor Mutation., Linda Omer

Electronic Theses and Dissertations

Familial hypercholesterolemia (FH) is a common genetic disease and has been studied with the aim of finding a curative measure for decades. FH is caused by mutations in the low-density lipoprotein receptor (LDLR) resulting in defects in LDL-cholesterol (LDL-C)-receptor mediated endocytosis and development of premature cardiovascular disease (CVD). Here I describe the use of a corrected and non-corrected LDLR FH cell model to investigate receptor-mediated endocytosis and statin effects. For these studies, we reprogrammed FH fibroblast cells to induced pluripotent stem cells (iPSC) and confirmed their pluripotency and ability to differentiate to hepatocyte-like cells (HLC). A clustered regularly interspaced short …

Non-Neutralizing Antibodies Elicited By Recombinant Lassa-Rabies Vaccine Are Critical For Protection Against Lassa Fever., Tiago Abreu-Mota, Katie R. Hagen, Kurt Cooper, Peter B. Jahrling, Gene Tan, Christoph Wirblich, Reed F. Johnson, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Lassa fever (LF), caused by Lassa virus (LASV), is a viral hemorrhagic fever for which no approved vaccine or potent antiviral treatment is available. LF is a WHO priority disease and, together with rabies, a major health burden in West Africa. Here we present the development and characterization of an inactivated recombinant LASV and rabies vaccine candidate (LASSARAB) that expresses a codon-optimized LASV glycoprotein (coGPC) and is adjuvanted by a TLR-4 agonist (GLA-SE). LASSARAB elicits lasting humoral response against LASV and RABV in both mouse and guinea pig models, and it protects both guinea pigs and mice against LF. We …

A Virus-Encoded Type I Interferon Decoy Receptor Enables Evasion Of Host Immunity Through Cell-Surface Binding., Bruno Hernáez, Juan Manuel Alonso-Lobo, Imma Montanuy, Cornelius Fischer, Sascha Sauer, Luis J. Sigal, Noemí Sevilla, Antonio Alcamí

Department of Microbiology and Immunology Faculty Papers

Soluble cytokine decoy receptors are potent immune modulatory reagents with therapeutic applications. Some virus-encoded secreted cytokine receptors interact with glycosaminoglycans expressed at the cell surface, but the biological significance of this activity in vivo is poorly understood. Here, we show the type I interferon binding protein (IFNα/βBP) encoded by vaccinia and ectromelia viruses requires of this cell binding activity to confer full virulence to these viruses and to retain immunomodulatory activity. Expression of a variant form of the IFNα/βBP that inhibits IFN activity, but does not interact with cell surface glycosaminoglycans, results in highly attenuated viruses with a virulence similar …

Development Of Onchocerca Volvulus In Humanized Nsg Mice And Detection Of Parasite Biomarkers In Urine And Serum., John B. Patton, Sasisekhar Bennuru, Mark L. Eberhard, Jessica A. Hess Ligas, April R. Torigian, Sara Lustigman, Thomas B. Nutman, David Abraham

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: The study of Onchocerca volvulus has been limited by its host range, with only humans and non-human primates shown to be susceptible to the full life cycle infection. Small animal models that support the development of adult parasites have not been identified.

METHODOLOGY/PRINCIPAL FINDINGS: We hypothesized that highly immunodeficient NSG mice would support the survival and maturation of O. volvulus and alteration of the host microenvironment through the addition of various human cells and tissues would further enhance the level of parasite maturation. NSG mice were humanized with: (1) umbilical cord derived CD34+ stem cells, (2) fetal derived liver, …

The Study Of Alcoholic Liver Diseases, Seun Emmanuel Owoseni

Electronic Theses and Dissertations

Excessive alcohol consumption is the primary contributing factor in the development of alcoholic liver diseases (ALD). Nicotine contained in tobacco is a major addictive alkaloid, which enhances the effects of ALDs. The major enzyme involved in nicotine metabolism is cytochrome P450 2A5 (CYP2A5) which is produced in the liver. Alcohol can stimulate the CYP2A5 enzyme. We utilized cyp2a5-/- knockout mice in this research to examine the effects of CYP2A5.

The cyp2a5-/- mice and wild-type (WT) mice were fed liquid ethanol diet with or without nicotine to induce ALD. Nicotine enhancing effects on ALD were observed in WT mice but not …

Epidermal Growth Factor Receptor (Egfr) Inhibition By Polychlorinated Biphenyls Contributes To Non-Alcoholic Fatty Liver Disease (Nafld)., Josiah Hardesty

Electronic Theses and Dissertations

This dissertation describes how poly-chlorinated biphenyls (PCBs) exacerbate the pathogenesis of non-alcoholic fatty liver disease (NAFLD). While PCBs were banned in 1979, they still persist in contaminated biota, including food, and are detected in human plasma and adipose. The body burden of PCBs is associated with elevation of liver enzymes and necrosis markers in humans, characteristic of NAFLD. PCB exposure in high-fat diet fed mice leads to steatohepatitis that recapitulate the findings seen in exposed humans. The global estimate of people diagnosed with NAFLD is up to 1 in 4 people, unrelated to dietary or genetic factors. The hepatic mechanisms …

The Tumor Microenvironment Regulates Retinoblastoma Cell Survival, Zachary K. Goldsmith

Theses and Dissertations (ETD)

Retinoblastoma (Rb) is the most common intraocular malignancy in children comprising 4% of all pediatric tumors. Early intervention increases survival rates up to 95% in developed countries; being survival rates associated to socio-economic status. Despite the high survival rates in developed countries, preservation of the eye and vision are continuing challenges in the management of Rb. Vitreous seeds constitute the greatest challenge in treatment of Rb. The unique location of these seeds within the vitreous makes them difficult to treat. Viable seeds showed reduced proliferative capacity and metabolism. making the majority refractory to current chemotherapeutics. This prompted the development of …

The Role Of Bip Co-Chaperone Sil1 In Marinesco-Sjögren Syndrome Pathogenesis, Viraj Paresh Ichhaporia

Theses and Dissertations (ETD)

Marinesco-Sjögren syndrome (MSS) is a rare, autosomal recessive, multisystem disorder, which is characterized by cerebellar ataxia, early-onset bilateral cataracts, and progressive myopathy amongst other symptoms. MSS has been attributed to mutations in the SIL1 gene, which encodes a nucleotide exchange factor for the endoplasmicreticulum- resident Hsp70 chaperone, BiP. To date, there are 46 MSS-associated mutations that have been reported in SIL1, which occur throughout this gene and are predicted to result in a loss of SIL1’s function. The large majority of these mutations cause deletions of large fractions of the SIL1 protein. Nine MSS-associated mutations are particularly interesting because they …