Digital Commons Network^™

Adiponectin Ameliorates The Apoptotic Effects Of Paraquat On Alveolar Type Ⅱ Cells Via Improvements In Mitochondrial Function., Yarong He, Liqun Zou, Yaxiong Zhou, Hai Hu, Rong Yao, Yaowen Jiang, Wayne Bond Lau, Tun Yuan, Wen Huang, Zhi Zeng, Yu Cao

Department of Emergency Medicine Faculty Papers

Previous studies have demonstrated that excessive reactive oxygen/nitrogen species (ROS/RNS)‑induced apoptosis is an important feature of the injury to the lung epithelium in paraquat (PQ) poisoning. However the precise mechanisms of PQ‑induced dysfunction of the mitochondria, where ROS/RNS are predominantly produced, remain to be fully elucidated. Whether globular adiponectin (gAd), a potent molecule protective to mitochondria, regulates the mitochondrial function of alveolar type II cells to reduce PQ‑induced ROS/RNS production remains to be investigated. The current study aimed to investigate the precise mechanisms of PQ poisoning in the mitochondria of alveolar type II cells, and to elucidate the role of …

Suppression Of Progranulin Expression Inhibits Bladder Cancer Growth And Sensitizes Cancer Cells To Cisplatin., Simone Buraschi, Shi-Qiong Xu, Manuela Stefanello, Igor Moskalev, Alaide Morcavallo, Marco Genua, Ryuta Tanimoto, Ruth Birbe, Stephen C. Peiper, Leonard G. Gomella, Antonino Belfiore, Peter C. Black, Renato V. Iozzo, Andrea Morrione

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

We have recently demonstrated a critical role for progranulin in bladder cancer. Progranulin contributes, as an autocrine growth factor, to the transformed phenotype by modulating Akt-and MAPK-driven motility, invasion and anchorage-independent growth. Progranulin also induces F-actin remodeling by interacting with the F-actin binding protein drebrin. In addition, progranulin is overexpressed in invasive bladder cancer compared to normal tissue controls, suggesting that progranulin might play a key role in driving the transition to the invasive phenotype of urothelial cancer. However, it is not established whether targeting progranulin could have therapeutic effects on bladder cancer. In this study, we stably depleted urothelial …

Changes In The Adult Glun2b Associated Proteome Following Adolescent Intermittent Ethanol Exposure, H. Scott Swartzwelder, Mary-Louise Risher, Kelsey M. Miller, Roger J. Colban, Danner G. Winder, Tiffany A. Wills

Biomedical Sciences

Adolescent alcohol use is the strongest predictor for alcohol use disorders. In rodents, adolescents have distinct responses to acute ethanol, and prolonged alcohol exposure during adolescence can maintain these phenotypes into adulthood. One brain region that is particularly sensitive to the effects of both acute and chronic ethanol exposure is the hippocampus. Adolescent intermittent ethanol exposure (AIE) produces long lasting changes in hippocampal synaptic plasticity and dendritic morphology, as well as in the susceptibility to acute ethanol-induced spatial memory impairment. Given the pattern of changes in hippocampal structure and function, one potential target for these effects is the ethanol sensitive …

Mathematical Analysis And Simulations Involving Chemotherapy And Surgery On Large Human Tumours Under A Suitable Cell-Kill Functional Response, Diego S. Rodrigues

Biology and Medicine Through Mathematics Conference

No abstract provided.

A Structured Telephonic Transition Program For Heart Failure Patients, Julia E. Robinson

Doctor of Nursing Practice Final Manuscripts

HF is a fatal condition affecting more than 5 million Americans leading to frequent hospitalizations, poor quality of life and death. The annual cost to the healthcare system is approximately $38 billion, ranking HF as one of the costliest conditions to manage. Significant evidence exists that HF self-care management programs improve patient self-care and decrease HF-related readmissions. Current guidelines recommend health professionals provide comprehensive HF education focused on knowledge, skills of management, and self-care behaviors.

The Iowa Model of Evidence Based Practice provided the foundation for the practice change. Structured telephonic support (STS) was based on Bandura’s Self- Efficacy behavior …

Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez

Biology: Student Scholarship & Creative Works

ABSTRACT: The HIV-1 pandemic continues to thrive due to ineffective HIV-1 vaccines. Historically, the world’s most infectious diseases, such as polio and smallpox, have been eradicated or have come close to eradication due to the advent of effective vaccines. Highly active antiretroviral therapy is able to delay the onset of AIDS but can neither rid the body of HIV-1 proviral DNA nor prevent further transmission. A prophylactic vaccine that prevents the various mechanisms HIV-1 has to evade and attack our immune system is needed to end the HIV-1 pandemic. Recent advances in engineered nuclease systems, like the CRISPR/Cas9 system, have …

How Diet Intervention Via Modulation Of Dna Damage Response Through Micrornas May Have An Effect On Cancer Prevention And Aging, An In Silico Study, Felicia Carotenuto, Maria C. Albertini, Dario Coletti, Alessandra Vilmercati, Luigi Campanella, Zbigniew Darzynkiewicz, Laura Teodori

NYMC Faculty Publications

The DNA damage response (DDR) is a molecular mechanism that cells have evolved to sense DNA damage (DD) to promote DNA repair, or to lead to apoptosis, or cellular senescence if the damage is too extensive. Recent evidence indicates that microRNAs (miRs) play a critical role in the regulation of DDR. Dietary bioactive compounds through miRs may affect activity of numerous genes. Among the most studied bioactive compounds modulating expression of miRs are epi-gallocatechin-3-gallate, curcumin, resveratrol and n3-polyunsaturated fatty acids. To compare the impact of these dietary compounds on DD/DDR network modulation, we performed a literature search and an in …

Radiation-Enhanced Therapeutic Targeting Of Galectin-1 Enriched Malignant Stroma In Triple Negative Breast Cancer, Meenakshi Upreti, Amar Jyoti, Sara E. Johnson, Elden P. Swindell, Dana L. Napier, Pallavi Sethi, Ryan Chan, Jonathan M. Feddock, Heidi L. Weiss, Thomas V. O'Halloran, B. Mark Evers

Pharmaceutical Sciences Faculty Publications

Currently there are no FDA approved targeted therapies for Triple Negative Breast Cancer (TNBC). Ongoing clinical trials for TNBC have focused primarily on targeting the epithelial cancer cells. However, targeted delivery of cytotoxic payloads to the non-transformed tumor associated-endothelium can prove to be an alternate approach that is currently unexplored. The present study is supported by recent findings on elevated expression of stromal galectin-1 in clinical samples of TNBC and our ongoing findings on stromal targeting of radiation induced galectin-1 by the anginex-conjugated arsenic-cisplatin loaded liposomes using a novel murine tumor model. We demonstrate inhibition of tumor growth and metastasis …

Ubr3, A Novel Modulator Of Hh Signaling Affects The Degradation Of Costal-2 And Kif7 Through Poly-Ubiquitination, Tongchao Li, Junkai Fan, Bernardo Blanco-Sánchez, Nikolaos Giagtzoglou, Guang Lin, Shinya Yamamoto, Manish Jaiswal, Kuchuan Chen, Jie Zhang, Wei Wei, Michael T. Lewis, Andrew K. Groves, Monte Westerfield, Jianhang Jia, Hugo J. Bellen

Markey Cancer Center Faculty Publications

Hedgehog (Hh) signaling regulates multiple aspects of metazoan development and tissue homeostasis, and is constitutively active in numerous cancers. We identified Ubr3, an E3 ubiquitin ligase, as a novel, positive regulator of Hh signaling in Drosophila and vertebrates. Hh signaling regulates the Ubr3-mediated poly-ubiquitination and degradation of Cos2, a central component of Hh signaling. In developing Drosophila eye discs, loss of ubr3 leads to a delayed differentiation of photoreceptors and a reduction in Hh signaling. In zebrafish, loss of Ubr3 causes a decrease in Shh signaling in the developing eyes, somites, and sensory neurons. However, not all tissues that require …

The Retinal Determination Gene Network: From Developmental Regulator To Cancer Therapeutic Target., Deguang Kong, Yu Liu, Qian Liu, Na Han, Cuntai Zhang, Richard G. Pestell, Kongming Wu, Gaosong Wu

Department of Medical Oncology Faculty Papers

Although originally identified for its function in Drosophila melanogaster eye specification, the Retinal Determination Gene Network (RDGN) is essential for the development of multiple organs in mammals. The RDGN regulates proliferation, differentiation and autocrine signaling, and interacts with other key signaling pathways. Aberrant expression of RDGN members such as DACH, EYA and SIX contributes to tumor initiation and progression; indeed, the levels of RDGN members are clinically prognostic factors in various cancer types. Stimulation or suppression of the activities of these crucial components can block cancer cell proliferation, prevent cancer stem cell expansion and even reverse the EMT process, thereby …

The Transcription Factor Runx2 Regulates Receptor Tyrosine Kinase Expression In Melanoma., Rajeev K Boregowda, Daniel J Medina, Elke Markert, Michael A Bryan, Wenjin Chen, Suzie Chen, Anna Rabkin, Michael J Vido, Samuel I Gunderson, Marina Chekmareva, David J Foran, Ahmed Lasfar, James S Goydos, Karine A Cohen-Solal

Department of Cancer Biology Faculty Papers

Receptor tyrosine kinases-based autocrine loops largely contribute to activate the MAPK and PI3K/AKT pathways in melanoma. However, the molecular mechanisms involved in generating these autocrine loops are still largely unknown. In the present study, we examine the role of the transcription factor RUNX2 in the regulation of receptor tyrosine kinase (RTK) expression in melanoma. We have demonstrated that RUNX2-deficient melanoma cells display a significant decrease in three receptor tyrosine kinases, EGFR, IGF-1R and PDGFRβ. In addition, we found co-expression of RUNX2 and another RTK, AXL, in both melanoma cells and melanoma patient samples. We observed a decrease in phosphoAKT2 (S474) …

Interaction Of Tau With The Rna-Binding Protein Tia1 Regulates Tau Pathophysiology And Toxicity, Tara Vanderweyde, Daniel J. Apicco, Katherine Youmans-Kidder, Peter E. A. Ash, Casey Cook, Edroaldo Lummertz Da Rocha, Karen Jansen-West, Alissa A. Frame, Allison Citro, John D. Leszyk, Pavel Ivanov, Jose F. Abisambra, Martin Steffen, Hu Li, Leonard Petrucelli, Benjamin Wolozin

Sanders-Brown Center on Aging Faculty Publications

Dendritic mislocalization of microtubule associated protein tau is a hallmark of tauopathies, but the role of dendritic tau is unknown. We now report that tau interacts with the RNA-binding protein (RBP) TIA1 in brain tissue, and we present the brain-protein interactome network for TIA1. Analysis of the TIA1 interactome in brain tissue from wild-type (WT) and tau knockout mice demonstrates that tau is required for normal interactions of TIA1 with proteins linked to RNA metabolism, including ribosomal proteins and RBPs. Expression studies show that tau regulates the distribution of TIA1, and tau accelerates stress granule (SG) formation. Conversely, TIA1 knockdown …

World Allergy Organization-Mcmaster University Guidelines For Allergic Disease Prevention (Glad-P): Vitamin D, Juan José Yepes-Nuñez, Alessandro Fiocchi, Ruby Pawankar, Carlos A. Cuello-Garcia, Yuan Zhang, Gian Paolo Morgano, Kangmo Ahn, Suleiman Al-Hammadi, Arnav Agarwal, Shreyas Gandhi, Kirsten Beyer, Wesley Burks, Giorgio W. Canonica, Motohiro Ebisawa, Rose Kamenwa, Bee Wah Lee, Haiqi Li, Susan Prescott, John J. Riva, Lanny Rosenwasser, Hugh Sampson, Michael Spigler, Luigi Terracciano, Andrea Vereda, Susan Waserman, Holger J. Schünemann, Jan L. Brożek

Paediatrics and Child Health, East Africa

Background: The prevalence of allergic diseases is approximately 10 % in infants whose parents and siblings do not have allergic diseases and 20–30 % in those with an allergic first-degree relative. Vitamin D is involved in the regulation of the immune system and it may play a role in the development, severity and course of asthma and other allergic diseases.

Objective: The World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations addressing the use of vitamin D in primary prevention of allergic diseases.

Methods: Our WAO guideline panel identified the most relevant clinical questions and performed a …

Quality Improvement: An Update For Outpatient Oncology Education, Nicole R. Gee

Master's Projects and Capstones

This project is focused on quality improvement in patient satisfaction with regard to side effect management after oncology patient education. The global aim of this project is to improve oncology-specific patient education through the development of an evidenced-based educational binder to be given to patients in a hospital outpatient infusion center and used as an educational guide for nursing staff. Effective standardized patient education has been seen to improve: satisfaction, quality of life, adherence, self-management, outcomes, and reduce unnecessary emergency room visits (Dalby, 2013; Mann, 2011; Smith et al., 2013). A rise in patient confidence for nausea and vomiting self-care, …

Revealing The Quality Of Movement: A Meta-Analysis Review To Quantify The Thresholds To Pathological Variability During Standing And Walking, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

Neuromotor processes are inherently noisy, which results in variability during movement and fluctu-ations in motor control. Although controversial, low levels of variability are traditionally considered healthy, while increased levels are thought to be pathological. This systematic review and meta-analysisof the literature investigates the thresholds between healthy and pathological task variability.

After examining 13,195 publications, 109 studies were included. Results from over 3000 healthy sub-jects and 2775 patients revealed an overall positive effect size of pathology on variability of 0.59 forwalking and 0.80 for sway. For the coefficient of variation of stride time (ST) and sway area (SA), upperthresholds of 2.6% …

The Mysteries Of Your Blood, Alexandra J. Mauer

BU Well

Did you know that your blood type can be useful for determining disease susceptibility and even creating a diet that works best for your personal metabolism? The Mysteries of your Blood is an article that delves into the science behind the ABO blood types and explains why your body can handle certain foods, stress, and illness differently than someone with a different blood type. It proposes a new, perplexing way to determine how to avoid certain health problems while at the same time offering suggestions of what to eat or, rather, what to avoid eating.

Effect Of Using Culturally Sensitive Education In Increasing Mammogram Use And Breast Cancer Awareness: African Female Immigrants, Gertrude Mumba-Kaunda

Evidence-Based Practice Project Reports

Despite the advances in medical technology, breast cancer is the most common cancer among women and is the second leading cause of death in African-American and Caucasian women in the United States. Mammography has shown to be one of the best methods to reduce late detection of breast cancer. The American Cancer Society recommends monthly self-breast examination (SBE), clinical breast examinations every 3 years, and yearly mammography starting at the age of 40. Despite the recommendations, there is still significant disparity among different racial groups, when it comes to death rates, which can be attributed to low screening rates. The …

Estrogen Regulates Mirna Expression: Implication Of Estrogen Receptor And Mir-124/Akt2 In Tumor Growth And Angiogenesis., Cheng-Fei Jiang, Dong-Mei Li, Zhu-Mei Shi, Lin Wang, Min-Min Liu, Xin Ge, Xue Liu, Ying-Chen Qian, Yi-Yang Wen, Lin-Lin Zhen, Jie Lin, Ling-Zhi Liu, Bing-Hua Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

It is currently known that estrogen plays an important role in breast cancer (BC) development, but the underlying molecular mechanism remains to be elucidated. Accumulating evidence has revealed important roles of microRNAs in various kinds of human cancers, including BC. In this study, we found that among the microRNAs regulated by estrogen, miR-124 was the most prominent downregulated miRNA. miR-124 was downregulated by estradiol (E2) treatment in estrogen receptor (ER) positive BC cells, miR-124 overexpression suppressed cell proliferation, migration and invasion in BC cells; while the suppression of miR-124 using Anti-miR-124 inhibitor had opposite cellular functions. Under the E2 treatment, …

Investigating The Use Of Chloroquine As Antineoplastic Therapy, Catherine E. Herron, Alexandra E. Mason

Senior Honors Projects, 2010-2019

Chloroquine (CQ) is an oral lysosomotropic agent routinely used as an anti-malarial drug (Espina & Liotta, 2013). In recent years, it has been discovered that CQ also possesses anticancer effects, potentially due to the drug’s inhibition of autophagy (Kimura, Takabatake, Takahashi, & Isaka, 2012). Autophagy is a normal cellular pathway that allows for the degradation of cytoplasmic contents. In cancer cells autophagy can also serve as a pro-survival pathway under stressful metabolic conditions, ultimately promoting the survival of malignant cells (Sui et al., 2013). Therefore, in recent years CQ has been speculated as a potential antineoplastic therapy. When administered in …

Recurrent Mutations Of T-Cell Receptor And Co-Stimulatory Signaling Proteins In Peripheral T-Cell Lymphomas, Joseph Rohr

Theses & Dissertations

Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T-cell neoplasms with a poor prognosis. Recently, mutations in TET2 and other epigenetic modifiers as well as RHOA have been identified in these diseases, particularly in angioimmunoblastic T-cell lymphoma (AITL). CD28 is the major co-stimulatory receptor in T-cells which, upon binding ligand, induces sustained T-cell proliferation and cytokine production when combined with T-cell receptor stimulation, through many signaling molecules including VAV1. This thesis identifies recurrent mutations in CD28 in PTCLs, as well as mutations in VAV1. Two residues of CD28 – D124 and T195 – were recurrently mutated in 11.3% …

Fbxo30 Regulates Mammopoiesis By Targeting The Bipolar Mitotic Kinesin Eg5., Yan Liu, Yin Wang, Zhanwen Du, Xiaoli Yan, Pan Zheng, Yang Liu

Pediatrics Faculty Publications

Fbxo30 is an orphan member of the F-box protein family with no known substrate or function. Here we report that, while Fbxo30^−/− mice exhibit normal development, growth, lifespan, and fertility, the females fail to nurture their offspring as a result of defective mammopoiesis. Mass spectrometry analysis of Fbxo30-associated proteins revealed that Fbxo30 specifically interacts with the bipolar spindle kinesin EG5 (encoded byKif11). As a result, Fbxo30 targets Eg5 for ubiquitinylation and controls its oscillation during the cell cycle. Correlated with EG5 dysregulation, Fbxo30^−/− mammary epithelial cells exhibit multiple defects in centrosome homeostasis, mitotic spindle …

Compositions And Methods For Treating Retinal Degradation, Jayakrishna Ambati, Benjamin J. Fowler

Ophthalmology and Visual Science Faculty Patents

The present disclosure relates to compositions and methods for treating retinal damage and/or retinal degradation. More specifically, this disclosure relates to methods for treating degradation of the retinal pigment epithelium by administering compositions comprising a nucleoside and/or a nucleoside or nucleotide reverse transcriptase inhibitor.

Thyroid Cancer And Tumor Collaborative Registry (Tccr)., Oleg Shats, Whitney Goldner, Jianmin Feng, Alexander Sherman, Russell B. Smith, Simon Sherman

Journal Articles: Eppley Institute

A multicenter, web-based Thyroid Cancer and Tumor Collaborative Registry (TCCR, http://tccr.unmc.edu) allows for the collection and management of various data on thyroid cancer (TC) and thyroid nodule (TN) patients. The TCCR is coupled with OpenSpecimen, an open-source biobank management system, to annotate biospecimens obtained from the TCCR subjects. The demographic, lifestyle, physical activity, dietary habits, family history, medical history, and quality of life data are provided and may be entered into the registry by subjects. Information on diagnosis, treatment, and outcome is entered by the clinical personnel. The TCCR uses advanced technical and organizational practices, such as (i) metadata-driven software …

Acth Prevents Deficits In Fear Extinction Associated With Early Life Seizures, Andrew T. Massey, David K. Lerner, Gregory L. Holmes, Rod C. Scott, Amanda Hernan

Dartmouth Scholarship

Objective: Early life seizures (ELS) are often associated with cognitive and psychiatric comorbidities that are detrimental to quality of life. In a rat model of ELS, we explored long-term cognitive outcomes in adult rats. Using ACTH, an endogeneous HPA-axis hormone given to children with severe epilepsy, we sought to prevent cognitive deficits. Through comparisons with dexamethasone, we sought to dissociate the corticosteroid effects of ACTH from other potential mechanisms of action.

Results: Although rats with a history of ELS were able to acquire a conditioned fear learning paradigm and controls, these rats had significant deficits in their ability to extinguish …

Lasers In Tattoo And Pigmentation Control: Role Of The Picosure(®) Laser System., Richard Torbeck, Richard Bankowski, Sarah Henize, Nazanin Saedi

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND AND OBJECTIVES: The use of picosecond lasers to remove tattoos has greatly improved due to the long-standing outcomes of nanosecond lasers, both clinically and histologically. The first aesthetic picosecond laser available for this use was the PicoSure(®) laser system (755/532 nm). Now that a vast amount of research on its use has been conducted, we performed a comprehensive review of the literature to validate the continued application of the PicoSure(®) laser system for tattoo removal.

STUDY DESIGN AND METHODS: A PubMed search was conducted using the term "picosecond" combined with "laser", "dermatology", and "laser tattoo removal".

RESULTS: A total …

Calpain-5 Expression In The Retina Localizes To Photoreceptor Synapses, Kellie A. Schaefer, Marcus A. Toral, Gabriel Velez, Allison J. Cox, Sheila A. Baker, Nicholas C. Borcherding, Diana F. Colgan, Vimala Bondada, Charles B. Mashburn, Chen Guang Yu, James W. Geddes, Stephen H. Tsang, Alexander G. Bassuk, Vinit B. Mahajan

Spinal Cord and Brain Injury Research Center Faculty Publications

Purpose: We characterize calpain-5 (CAPN5) expression in retinal and neuronal subcellular compartments.

Methods: CAPN5 gene variants were classified using the exome variant server, and RNA-sequencing was used to compare expression of CAPN5 mRNA in the mouse and human retina and in retinoblastoma cells. Expression of CAPN5 protein was ascertained in humans and mice in silico, in mouse retina by immunohistochemistry, and in neuronal cancer cell lines and fractionated central nervous system tissue extracts by Western analysis with eight antibodies targeting different CAPN5 regions.

Results: Most CAPN5 genetic variation occurs outside its protease core; and searches …

Providing Pediatric Patients With A Voice : Understanding How Children Want To Live Before They Die, Nina Friedman

Graduate Student Independent Studies

This paper explores what quality of life is for pediatric patients and how health care professionals, a certified child life specialist in particular, can help the patient, family, and medical team to navigate treatment options and decisions regarding end-of-life.

Medical Education Digest, Vol. 18 No. 3 (May-June 2016) Final Issue, Nova Southeastern University

Medical Education Digest

No abstract provided.

A Conserved Dna Repeat Promotes Selection Of A Diverse Repertoire Of Trypanosoma Brucei Surface Antigens From The Genomic Archive., Galadriel Hovel-Miner, Monica R Mugnier, Benjamin Goldwater, George A M Cross, F Nina Papavasiliou

Microbiology, Immunology, and Tropical Medicine Faculty Publications

African trypanosomes are mammalian pathogens that must regularly change their protein coat to survive in the host bloodstream. Chronic trypanosome infections are potentiated by their ability to access a deep genomic repertoire of Variant Surface Glycoprotein (VSG) genes and switch from the expression of one VSG to another. Switching VSG expression is largely based in DNA recombination events that result in chromosome translocations between an acceptor site, which houses the actively transcribed VSG, and a donor gene, drawn from an archive of more than 2,000 silent VSGs. One element implicated in these duplicative gene conversion events is a DNA repeat …

Characterization Of Bacterial Pathogens Involved In Aerobic Vaginitis: Prevalence, Strain Characterization And Sequelae, Leslie A. Lafferty

Graduate School of Biomedical Sciences Theses and Dissertations

Aerobic vaginitis (AV) is a more recently defined infection that involves aerobic pathogenic bacteria that replace the normal flora of the vaginal tract. It is commonly mistaken for other vaginal infections, such as bacterial vaginosis (BV), because they share many common symptoms. AV leads to complications during pregnancy, such as premature delivery and amnion infection, and is diagnosed by indications that range from vaginal discharge to inflammation. Because this infection is difficult to diagnose differentially from other vaginal infections, it is important to determine what pathogens are involved in AV so that we may have the ability to detect them. …