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Catabolic Degradation Of Endothelial Vegfa Via Autophagy, Thomas Neill, Carolyn Chen, Simone Buraschi, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Extracellular matrix-evoked angiostasis and autophagy within the tumor microenvironment represent two critical, but unconnected, functions of the small leucine-rich proteoglycan, decorin. Acting as a partial agonist of vascular endothelial growth factor 2 (VEGFR2), soluble decorin signals via the energy sensing protein, AMP-activated protein kinase (AMPK), in the autophagic degradation of intracellular vascular endothelial growth factor A (VEGFA). Here, we discovered that soluble decorin evokes intracellular catabolism of endothelial VEGFA that is mechanistically independent of mTOR, but requires an autophagic regulator, paternally expressed gene 3 (PEG3). We found that administration of autophagic inhibitors such as chloroquine or bafilomycin A1, or depletion …

Hdr Brachytherapy For Skin Cancer Using H.A.M. Applicator, Timothy Richard Thatcher

UNLV Theses, Dissertations, Professional Papers, and Capstones

Skin cancer is the most common type of malignancy affecting both men and women in the United States. A majority of these cases are nonmelanoma skin cancers (NMSC) such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The goal of any skin cancer treatment is to cure the lesion itself while also preserving function and optimizing superficial cosmesis. High dose rate (HDR) brachytherapy provides an alternative to superficial x-ray or electron beam for skin cancer treatment. Utilizing an Iridium 192 source soldered to the end of a wire, surface dose can be administered at predetermined positions with sharper …

Transient Display Of Chimeric Proteins On Biological Surfaces As An Effective Strategy For Modulations Of Innate And Adaptive Immune Responses., Pradeep Shrestha

Electronic Theses and Dissertations

The major premise of this dissertation was to transiently display novel immunological ligands on biological membranes as a localized means of modulating innate and adaptive immune responses with applications to bone marrow and pancreatic islet transplantation. In Chapter two, we engineered donor allogeneic bone marrow cells to transiently display a novel form of FasL, SA-FasL, to efficiently purge out alloreactive donor T cells to prevent acute GVHD. In Chapter three, we engineered pancreatic islets with a novel form of CD47, SA-CD47, to modulate instant blood mediated inflammatory reaction (IBMIR) to prevent immediate islet graft loss following intraportal transplantation. GVHD is …

Effects Of Alternative Chemotherapeutic Agents On Thyroid Cancer Cell Line Ml-1, Husref Rizvanovic

Graduate Theses/Dissertations

Though differentiated thyroid carcinomas have decent prognosis when detected early, radioactive iodine (RAI) resistant and advanced thyroid cancers are still difficult to treat with existing therapies. Better therapeutic agents are needed. Studies have shown that aggressive thyroid cancers (ML-1) express the extracellular matrix protein, matrix metalloproteinase (MMP-2). MMP-2 has been linked to metastasis and aggressiveness of several cancers and has been shown to play a crucial role in tumor invasion. Chlorotoxin is a selective MMP-2 receptor agonist, and Saporin is a well-known ribosome-inactivating protein used for anti-cancer treatment; however, these two agents have never been studied when conjugated together. I …

Association Of Aβ With Ceramide-Enriched Astrosomes Mediates Aβ Neurotoxicity, Ahmed Elsherbini, Alexander S. Kirov, Michael B. Dinkins, Guanghu Wang, Haiyan Qin, Zhihui Zhu, Priyanka Tripathi, Simone M. Crivelli, Erhard Bieberich

Physiology Faculty Publications

Amyloid-β (Aβ) associates with extracellular vesicles termed exosomes. It is not clear whether and how exosomes modulate Aβ neurotoxicity in Alzheimer's disease (AD). We show here that brain tissue and serum from the transgenic mouse model of familial AD (5xFAD) and serum from AD patients contains ceramide-enriched and astrocyte-derived exosomes (termed astrosomes) that are associated with Aβ. In Neuro-2a cells, primary cultured neurons, and human induced pluripotent stem cell-derived neurons, Aβ-associated astrosomes from 5xFAD mice and AD patient serum were specifically transported to mitochondria, induced mitochondrial clustering, and upregulated the fission protein Drp-1 at a concentration corresponding to 5 femtomoles …

Week Of April 27, 2020, New York Medical College

InTouch

• NYMC Observes Yom Hashoah Virtually
• NYMC Experts Leading the Way in Coronavirus Updates

Challenges Of Pediatric Disease In Adulthood, Dennis J. Baumgardner, Brian Chicoine

Journal of Patient-Centered Research and Reviews

Some chronic diseases — such as the rare bone disease X-linked hypophosphatemia, the impetus for a study reported within Volume 7, Issue 2 of the Journal of Patient-Centered Research and Reviews — are diagnosed in childhood but become more symptomatic in adulthood. In this editorial, the challenges, pitfalls, and opportunities regarding the care of adults with childhood-onset chronic diseases are examined using Down syndrome, cystic fibrosis, congenital heart disease, and Hirschsprung disease as examples.

Giving Credence To The Experience Of X-Linked Hypophosphatemia In Adulthood: An Interprofessional Mixed-Methods Study, Melissa Hughes, Carolyn Macica, Catherine Meriano, Maya Doyle

Journal of Patient-Centered Research and Reviews

Purpose: X-linked hypophosphatemia (XLH) is a rare X-linked dominant metabolic bone disease, often diagnosed in childhood but causing increasing physical debilitation and pain in adulthood. Physical comorbidities of XLH in adulthood include pervasive and early-onset degenerative arthritis, mineralizing enthesophytes and osteophytes, osteomalacia and pseudofracture, dental abscesses, and hearing loss.

Methods: This mixed-methods analysis included physical findings, diagnostic imaging, occupational and physical therapy assessments, and semi-structured interviews by social work to understand the functional outcomes and lived experience of XLH in adulthood, through connections between qualitative data obtained by social work and occupational therapy with the quantitative findings from other disciplines. …

Dancing During Labor: Social Media Trend Or Future Practice?, Caroline P. Toberna, Drew Horter, Kayla Heslin, Marie M. Forgie, Emily Malloy, Jessica J. F. Kram

Journal of Patient-Centered Research and Reviews

Over the past 30 years, medical interventions in pregnancy and childbirth have increased. Some pregnant women seek less invasive and nonpharmacological options to manage discomforts during labor. While exercise during pregnancy is recommended, less is known about exercise, specifically dancing, during labor. While anecdotal evidence is supportive, little is known about the implications of exercise and dance during the first stage of labor for pain reduction and labor progression. Some movements common in dance, such as expanding hip circles that loosen and relax muscles of the pelvic floor, may be beneficial to women during labor. Available evidence suggests that dancing …

Introduction To Covid-19 Research, Amanda Scull

Dartmouth Library Workshops and Presentations

No abstract provided.

Vaccines In Current Culture: The Hpv Vaccine Controversy, Alyssa Johnston

Senior Honors Theses

The use of vaccinations has drastically decreased mortality and morbidity rates related to infectious disease and has become an intrinsic part of modern health care. However, the fear of risks related to vaccines has been partially responsible for the decisions of many parents to delay or avoid vaccinating their children. The human papilloma virus (HPV) vaccine specifically is one of the most controversial vaccines in current culture due to reports of new onset or exacerbation of autoimmune diseases, infertility, and even death following its administration. This review synthesizes information regarding the relevance and safety of the HPV vaccine, as well …

Week Of April 20, 2020, New York Medical College

InTouch

• Members of the SOM Class of 2020 Graduate Early and Enter the Fight Against COVID-19
• GSBMS Student Lillian Huang Makes an Impact During COVID-19 Crisis
• AOA Virtual Visiting Professor's Lecture Set for April 27

Insights From Immuno-Oncology: The Society For Immunotherapy Of Cancer Statement On Access To Il-6-Targeting Therapies For Covid-19., Paolo Antonio Ascierto, Bernard Fox, Walter Urba, Ana Carrizosa Anderson, Michael B Atkins, Ernest C Borden, Julie Brahmer, Lisa H Butterfield, Alessandra Cesano, Daniel Chen, Tanja De Gruijl, Robert O Dillman, Charles G Drake, Leisha A Emens, Thomas F Gajewski, James L Gulley, F Stephen Hodi, Patrick Hwu, David Kaufman, Howard Kaufman, Michael Lotze, Douglas G Mcneel, Kim Margolin, Francesco Marincola, Michael J Mastrangelo, Marcela V Maus, David R Parkinson, Pedro J Romero, Paul M Sondel, Stefani Spranger, Mario Sznol, George J Weiner, Jon M Wiggington, Jeffrey S Weber

Department of Microbiology and Immunology Faculty Papers

No abstract provided.

Biological Evaluation Of Fda-Approved Drugs As Mirna-31 Inhibitors Using Real Time Qrt-Pcr And A Luciferase Assay, Nicholas Sienkiewicz

Honors Theses

MicroRNAs (miRNAs) are a group of post-transcriptional, negative regulators of gene expression, consisting of ~19-24 nucleotides. Since their discovery in 1993, miRNAs have been found to be involved in a diverse amount of cellular and disease pathways, including certain types of cancer. Overexpression of certain oncogenic miRNAs, including miRNA-31, have been shown to play a role in cancer cell development. Recent findings have suggested that miRNAs play a significant role in every stage of colorectal cancer (CRC) initiation, progression, and development, as well as induce resistance to chemotherapy drugs like 5-FU. In particular, research has shown that increased levels of …

Biochemical And Structural Characterization Of The Atg8/Lc3 Lipidation Pathway, Yumei Zheng

Theses and Dissertations (ETD)

Atg8 and its eukaryotic orthologues LC3 and GARBARAP family proteins (referred here to Atg8 family proteins) play crucial roles in autophagy through their covalent ligation to lipids, typically phosphatidylethanolamine (PE), in a process known as lipidation. Lipidation of Atg8 family proteins regulates numerous facets of the autophagy process, including regulating expansion of the phagophore membrane, recruiting selected cargoes for degradation, and providing an autophagosome membrane-bound platform mediating dynamic interactions with other regulatory proteins. Atg8 family proteins are ubiquitin-like proteins (UBLs), and their lipidation involves a divergent UBL conjugation cascade including Atg7, Atg3, and Atg12–Atg5-Atg16 acting as E1, E2, and E3 …

Week Of April 13, 2020, New York Medical College

InTouch

• NYMC Community Set to Commemorate Holocaust Remembrance Day on April 20
• Med Student's Novel Research May Improve Ability to Predict Outcomes for Older Neurosurgery Patients

Covid 19 What You Need To Know, Dawn P. Wooley, Giancarlo Mariani, Craig Woolley, Laura M. Luehrmann

Neuroscience, Cell Biology & Physiology Faculty Publications

This is the first presentation in the new Shelter-in-Place lecture series. This first lecture is two-fold. First, it covers the basics of the COVID-19 virus including: how it spreads, possible origin, and other pertinent information. This portion of the presentation was followed by an overview of the international recruitment efforts in response to the virus, including: student perspectives, recruitment methods, and other important information.

Biological Sex Influences Susceptibility To Acinetobacter Baumannii Pneumonia In Mice, Sílvia Pires, Adeline Peignier, Jeremy Seto, Davida S. Smyth, Dane Parker

Publications and Research

Acinetobacter baumannii (A. baumannii) is an extremely versatile multidrug-resistant pathogen with a very high mortality rate; therefore, it has become crucial to understand the host response during its infection. Given the importance of mice for modeling infection and their role in preclinical drug development, equal emphasis should be placed on the use of both sexes. Through our studies using a murine model of acute pneumonia with A. baumannii, we observed that female mice were more susceptible to infection. Likewise, treatment of male mice with estradiol increased their susceptibility to infection. Analysis of the airway compartment revealed enhanced inflammation and reduced …

Apple Cider Vinegar Weight Loss Drinks On Pinterest, Sydney Chamberlain, Jana Mitchell, Davis Major, Lena Elimam, Cassandra Cleland

Showcase of Osprey Advancements in Research and Scholarship (SOARS)

Background: More than a third of adults in the U.S. are currently trying to lose weight. Social media, specifically Pinterest with more than 322 million users, has changed the way people seek health information specifically weight loss. Apple cider vinegar has shown great promise for weight loss in controlled lab settings, yet these claims are widely shared on social media and may not yield the same benefits.

Purpose: This study used directed content analysis to examine how apple cider vinegar weight loss drinks were portrayed on Pinterest, a social media website used to bookmark online content. Methods: Using the search …

Integrating Mouse And Human Genetic Data To Move Beyond Gwas And Identify Causal Genes In Cholesterol Metabolism, Jenny N Nguyen, Fernanda B Leyva Jaimes, Sophia M Ly, Jacqueline A Brinkman, Marco De Giorgi, Sushma Kaul, Cara L Green, Samantha L St Clair, Sabrina L Belisle, Julia M Rios, David W Nelson, Mary G Sorci-Thomas, William R Lagor, Dudley W Lamming, Chi-Liang Eric Yen, Brian W Parks

Faculty, Staff and Students Publications

Identifying the causal gene(s) that connects genetic variation to a phenotype is a challenging problem in genome-wide association studies (GWASs). Here, we develop a systematic approach that integrates mouse liver co-expression networks with human lipid GWAS data to identify regulators of cholesterol and lipid metabolism. Through our approach, we identified 48 genes showing replication in mice and associated with plasma lipid traits in humans and six genes on the X chromosome. Among these 54 genes, 25 have no previously identified role in lipid metabolism. Based on functional studies and integration with additional human lipid GWAS datasets, we pinpoint Sestrin1 as …

Acetylation Of Histone H3k27 Signals The Transcriptional Elongation For Estrogen Receptor Alpha, Fangrui Wu, Wen-Si Yang, Zheng Zhang, Tong Huo, Yingmin Zhu, Chengtai Yu, Hong Kim, Mark Lee, Zhen Tang, Kevin Phillips, Bin He, Sung Yun Jung, Yongcheng Song, Bokai Zhu, Rui-Ming Xu, Qin Feng

Faculty, Staff and Students Publications

As approximately 70% of human breast tumors are estrogen receptor α (ERα)-positive, estrogen and ERα play essential roles in breast cancer development. By interrupting the ERα signaling pathway, endocrine therapy has been proven to be an effective therapeutic strategy. In this study, we identified a mechanism by which Transcription Start Site (TSS)-associated histone H3K27 acetylation signals the Super Elongation Complex (SEC) to regulate transcriptional elongation of the ESR1 (ERα) gene. SEC interacts with H3K27ac on ESR1 TSS through its scaffold protein AFF4. Depletion of AFF4 by siRNA or CRISPR/Cas9 dramatically reduces expression of ESR1 and its target genes, consequently inhibiting …

Week Of April 6, 2020, New York Medical College

InTouch

• New York Medical College and Touro College and University System Host Second COVID-19 Symposium
• GHHS Supports Student Volunteer Efforts Amidst Pandemic
• Clinical Skills and Simulation Center Pilots Virtual Standardized Patient Assessments
• Faculty Expert, Patricia L. Gerbarg, M.D., Provides Tips on Breathing Techniques for Coping During Unprecedented Times

Visualizing Metabolic Network Dynamics Through Time-Series Metabolomic Data., Lea F Buchweitz, James T Yurkovich, Christoph Blessing, Veronika Kohler, Fabian Schwarzkopf, Zachary A King, Laurence Yang, Freyr Jóhannsson, Ólafur E Sigurjónsson, Óttar Rolfsson, Julian Heinrich, Andreas Dräger

Articles, Abstracts, and Reports

BACKGROUND: New technologies have given rise to an abundance of -omics data, particularly metabolomic data. The scale of these data introduces new challenges for the interpretation and extraction of knowledge, requiring the development of innovative computational visualization methodologies. Here, we present GEM-Vis, an original method for the visualization of time-course metabolomic data within the context of metabolic network maps. We demonstrate the utility of the GEM-Vis method by examining previously published data for two cellular systems-the human platelet and erythrocyte under cold storage for use in transfusion medicine.

RESULTS: The results comprise two animated videos that allow for new insights …

Early Cell-Cell Coupling Impairs Stem Cell Retention When Co-Cultured With Hypoxic Cardiomyocytes, Jack Tietema

Student Scholars Day Posters

Rationale: Bone marrow-derived mesenchymal stem cells (BM-MSC) induce beneficial effects in the heart following hypoxia but loss of these cells would diminish their effect. We hypothesized that coupling between BM-MSC and cardiomyocytes (CM) through gap junctions (GJ) during hypoxia may play an important role in stem cell retention. Methods and Results: Both human and murine BM-MSC express connexin43 (Cx43), a critical protein in the formation of GJ. FACS analysis revealed that BM-MSC exhibited a significant reduction in apoptosis (3-5 fold; p

Testing The Ancestral Function Of Divergent Candida Albicans Virulence-Associated Proteins Via Expression In Saccharomyces Cerevisiae Mutants, Curtis Mack

Student Scholars Day Posters

Candida albicans is an opportunistic fungal pathogen and a member of the normal human microbiota. It is closely related to the harmless fungus, Saccharomyces cerevisiae. Some genes associated with the virulent nature of C. albicans are similar to genes in S. cerevisiae. Three of these genes, PHO13, NRG1, and TUP1 are known to repress the change from yeast to filamentous growth in C. albicans, an important virulence trait. However, similar genes in S. cerevisiae are known to have functional differences. Our goal was to see if the ancestral function of these genes have drifted apart by examining …

A Comparison Of Power Variables For Two Loading Methods In Weighted Vertical Jumps 2020, Jonathan Tanguay

Master's Theses

Training exercises to develop muscular strength and power, such as the weighted jump squat, commonly utilize barbells and dumbbells to increase resistance. Strength coaches often measure improvements in peak force, peak power, and rate of force development to determine effectiveness of a training program. The purpose of this study was to determine if equipment selection (barbells vs. dumbbells) affects peak force, peak power, and/or rate of force development in weighted jump squats. Thirteen physically active, college-aged males (age: 21.6 ± 2.0 years, height: 182.8 ± 9.7 cm, body mass: 87.2 ± 9.0 kg, lean mass: 72.3 ± 8.1 kg) performed …

Assay Development For Isolation And Characterization Of Anticancer Properties Of Marine Fungi, Kyra Ricci

Honors Theses

Metabolites from fungi have potential use in the drug discovery process and have been used in the past to develop therapeutic agents for human use. Initial characterization of potential therapeutic properties of fungi is thus an important first step in identifying novel therapeutic compounds. In the present study, marine fungi were isolated from Myrtle Beach and assayed for anticancer properties using the soft agar colony formation assay in a 3D in vitro cellular environment. Many species were isolated from environmental samples, displaying unique morphologies and growth patterns. To optimize the soft agar assay in a six-well cell culture plate for …

Las Perspectivas Y Experiencias De Los Profesionales Del Campo De La Reproducción Asistida En La Ciudad Autónoma De Buenos Aires Y Bahía Blanca En El Año 2020. / The Perspectives And Experiences Of The Professionals In The Field Of Assisted Reproduction In The Autonomous City Of Buenos Aires And Bahía Blanca In 2020., Calder Hollond

Independent Study Project (ISP) Collection

En este informe se realiza una exploración del campo de la reproducción asistida en Argentina en 2020 a través de entrevistas personales con seis profesionales en el campo. Estos profesionales vienen de Capital Federal y Bahía Blanca y ofrecen perspectivas diversas en el estado del campo en este momento, los cambios que han pasado en los últimos años, y una mirada hacia el futuro. Este informe utiliza una metodología cualitativa y exploratoria, y un diseño observacional transversal. Además, emplea una muestra no probabilística y un diseño descriptivo para introducir el tema de reproducción asistida en Argentina y después analizarlo a …

Perceived Effectiveness Of Stem Cell Injections In Adults With Joint Injuries, Delaney Marie Merrill

Senior Theses

Introduction: Osteoarthritis plagues around 27 million Americans. Stem cell injections are a new method of treatment that could potentially cure this by regenerating cartilage in joints. Purpose: The purpose of this study is to examine the perceived effectiveness of stem cells at regenerating cartilage in joints, specifically the knees, hips, and shoulders. Methods: Participants were recruited via social media, forums, and from healthcare clinics that offer stem cell treatments. They were asked to complete a survey focusing primarily on the treatment protocol and how the injured joint felt post-stem cell injection. Frequencies were calculated to describe problematic joints, treatment history, …

Quality Of Life Of Children With Spinal Muscular Atrophy: Parents’ Perspectives In Light Of New Treatments, Analyssa R. Tallas

Theses and Dissertations

Purpose: To directly compare parents’ perspectives of the quality of life of their children with Spinal Muscular Atrophy (SMA) who received supportive care, nusinersen (Spinraza®), onasemnogene abeparvovec-xioi (Zolgensma®), or both nusinersen and onasemnogene abeparvovec-xioi. Methods: The parents of children with SMA were recruited to complete anonymous online surveys. All surveys included qualitative questions about quality of life. Surveys regarding children in the 1-12-month and 13-24-month age groups included the Pediatric Quality of Life Infant Scales assessment. Surveys regarding children in the 2-4-year age group included the Pediatric Quality of Life Inventory 4.0 Generic Core Scales and the Pediatric Quality of …