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Ceramides Promote Apoptosis For Virus-Infected Lymphoma Cells Through Induction Of Ceramide Synthases And Viral Lytic Gene Expression, Lu Dai, Jimena Trillo-Tinoco, Aiping Bai, Yihan Chen, Jacek Bielawski, Luis Del Valle, Charles D. Smith, Augusto C. Ochoa, Zhiqiang Qin, Chris Parsons

School of Medicine Faculty Publications

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for several human cancers including primary effusion lymphoma (PEL), a rapidly progressive malignancy arising preferentially in immunocompromised patients. With conventional chemotherapy, PEL continues to portend high mortality, dictating the development of novel therapeutic strategies. Sphingosine kinase 2 (SphK2) represents a key gatekeeper for sphingolipid metabolism, responsible for conversion of ceramides to sphingosine-1-phosphate (S1P). We have previously demonstrated that targeting SphK2 using a novel selective inhibitor, ABC294640, leads to intracellular accumulation of ceramides and induces apoptosis for KSHV-infected PEL cells, while suppressing tumor progression in vivo. In the current study, we sought to …

Plastin 3 Expression Does Not Modify Spinal Muscular Atrophy Severity In The ∆7 Sma Mouse, Vicki L. Mcgovern, Aurelie Massoni-Laporte, Xueyong Wang, Thanh T. Le, Hao T. Le, Mark M. Rich, Arthur H. M. Burghes

Neuroscience, Cell Biology & Physiology Faculty Publications

Spinal muscular atrophy is caused by loss of the SMN1 gene and retention of SMN2. TheSMN2 copy number inversely correlates with phenotypic severity and is a modifier of disease outcome. The SMN2 gene essentially differs from SMN1 by a single nucleotide in exon 7 that modulates the incorporation of exon 7 into the final SMN transcript. The majority of the SMN2transcripts lack exon 7 and this leads to a SMN protein that does not effectively oligomerize and is rapidly degraded. However theSMN2 gene does produce some full-length SMN and theSMN2 copy number along with how …

Basal Cell Carcinoma—A Preventable Disease, Jamie Weaver

Nursing Student Class Projects (Formerly MSN)

Basal cell carcinoma (BCC) is a nonmelanoma skin cancer. According to the Skin Cancer Foundation, “BCC is the most frequently occurring form of all skin cancers. More than one out of every three new cancers is a skin cancer, and the vast majority are BCC’s” (www.skincancer.org). Exposure to ultraviolet (UV) rays is one of the main risk factors in developing a BCC. People with a lighter skin tone are at a higher risk of developing a BCC than those with a darker skin tone.

Neurological, Nutritional And Cognitive Effects Of Environmental Lead Exposure In Infants And Children, Melissa Bianchi

Nursing Student Class Projects (Formerly MSN)

Environmental lead exposure is a pertinent public health risk that affects our rural population in Wyandot County, Ohio. Children exposed to lead hazards through toys, home remodeling and contaminated soil and water are at a greater risk for developing neurological, cognitive and behavioral issues than are children not exposed to lead (Cecil et al., 2011). Wyandot County parents are not adequately educated on the risks and consequences of elevated blood lead levels in their children. As a child advocate and director of the Women, Infant and Children program for Wyandot County there is an obligation to educate and inform parents …

Exploring The Pathophysiological Concepts Of Ebola Virus, Andrew T. Wasson

Nursing Student Class Projects (Formerly MSN)

The Ebola virus is a member of the filoviridae family. Five distinctive species of ebolavirus have been identified, four of which are known to cause disease in humans (Martines, Ng, Greer, Rollin, and Zaki, 2014). The specific species known to cause disease in humans are Zaire, Sudan, Ivory Coast, and Bundibugyo (Bray & Chertow, 2014). Bah et al. (2015) report that the Zaire ebolavirus (EBOV) was the cause of the most recent West African outbreak and carries the highest human mortality rate among the five known species, with up to 90% of cases being fatal. Ebola is a filamentous, enveloped, …

Deep Venous Thrombosis In Surgical Orthopedic Patients, Kelly Marsh

Nursing Student Class Projects (Formerly MSN)

•The term venous thromboembolism (VTE) is defined as a syndrome that collectively comprises both deep vein thrombosis (DVT) and pulmonary embolism (PE). Each year approximately 350,000-900,000 people in the United States develop VTE and approximately 100,000 people die according to this cause (Streiff et al., 2014). Unfortunately, the reoccurrence rate for VTE remains very high, with an estimated risk of 10%-30% of VTE patients will develop another VTE within five years of the first incident (Streiff et al., 2014). •Deep vein thrombosis (DVT) is blood clot that forms in a large vein, usually in areas of slow blood flow such …

Multiple Myeloma, Matthew Crowley

Nursing Student Class Projects (Formerly MSN)

Multiple myeloma a rare and largely incurable malignant disease the affects the plasma cells. (Bilotti, Gleason, McNeill, and the International Myeloma Foundation Nurse Leadership Board, 2011). Understanding the pathophysiology of Multiple Myeloma (MM) and treatment options in Oncology and Hematology nursing can be difficult. It is the goal of this poster to outline the pathophysiology, prognosis, treatment options available to multiple myeloma patients. Multiple myeloma accounts for about 10% of hematologic malignancies in the U.S. (Kuo, Fenves, Mehta, 2011). MM is the second most common hematologic malignancy with twenty-four thousand new MM cases each year (Bianchi, and Anderson, 2014 )

Chikungunya Virus: A Case Study Of The Emerging Vector-Borne Disease, Lindsay D. Sullivan

Nursing Student Class Projects (Formerly MSN)

The Chikungunya virus (CHIKV) has spread like a wildfire in the Americas. Since its emergence in Sub-Saharan Africa as early at the 18th century, CHIKV has caused many isolated outbreaks in Africa, Southeast Asia, and Australia. Over the last decade, the vector-borne disease has inflicted millions of people on islands in the Indian Ocean, India, and now the Americas with the aid of viral mutations and international travel (Weaver and Lecuit, 2015). The first case of local CHIKV transmission in the Western Hemisphere was fairly recent. On the island of St. Martin in October 2013, an individual carrying an Asian …

Sepsis & Emergency Management, Sharon Herndon

Nursing Student Class Projects (Formerly MSN)

Sepsis is a potentially life-threatening complication of an infection and a leading cause of death in the United States (Cawcutt & Peters, 2014). Sepsis is a systemic inflammatory response syndrome (SIRS) to invading microorganisms. Sagy, Al-Qaquu, and Kim (2013) define sepsis in three categories. “Sepsis” would be defined as the presence of infection along with other general systemic signs and symptoms. “Severe Sepsis” would be defined as sepsis complicated by at least one organ dysfunction, and “Septic Shock” would be defined as severe sepsis with acute circulatory failure that may be characterized by persistent arterial hypotension unexplained by other causes. …

Understanding Bipolar Disorder, Tisha Perreira

Nursing Student Class Projects (Formerly MSN)

According to McCance, Huether, and Brashers (2014), bipolar disorder is classified as bipolar I and bipolar II mood disorder. Bipolar I disorder, causes extreme mood swings of mania or hypomania (emotional highs) or emotional lows (depression). Manic disorder symptoms include: excessive risky activities, irritable mood, elevated mood, distractibility, excessive talking, inflated self-esteem, racing/crowded thoughts, decreased need for sleep, and increase in goal-directed activity. Symptoms of depression include: loss of interest/pleasure, weight gain or loss, fatigue/loss of energy, feeling of worthlessness or excessive guilt, depressed/irritable mood, recent thoughts of death/suicide, insomnia/or hypersomnia, poor concentration/indecisiveness, and psychomotor agitation. Bipolar II disorder has …

Implications Of Underlying Pathophysiology Of Osteomyelitis In Diabetics For Nursing Care, Danielle Spencer

Nursing Student Class Projects (Formerly MSN)

Osteomyelitis is an infection of the bone caused by either bacteria, fungi, parasites, viruses or mycobacteria (McCance, et. al., 2014). The infection can enter bone either through an outside source or through the blood from a blood borne infection (McCance, et. al., 2014). The most common bacteria involved with osteomyelitis is Staphylococcus aureus (Hatzenbuehler & Pulling, 2011, p. 1027). Recently, at Dublin Methodist Hospital there has been an increase in the number of osteomyelitis cases in chronic uncontrolled diabetic patients requiring below the knee amputations. Two of the cases specifically were linked to chronic diabetic foot ulcers. Each of these …

The Pathology Of Heart Failure, Kevin Ahman

Nursing Student Class Projects (Formerly MSN)

The topic I have chosen to research is heart failure. I have chosen this topic because I have treated many patients in the ICU with this condition, and find it an interesting pathology. Heart failure affects a significant portion of the patient population, and the rates are increasing. 5.1 million Americans ≥20 years of age have heart failure, projections show that by 2030, the prevalence of HF will increase 25% from 2013 estimates. At 40 years of age, the lifetime risk of developing HF for both men and women is 1 in 5. At 80 years of age, remaining lifetime …

Levels Of 8-Oxodg Predict Hepatobiliary Pathology In Opisthorchis Viverrini Endemic Settings In Thailand., Prasert Saichua, Anna Yakovleva, Christine Kamamia, Amar R. Jariwala, Paul J. Brindley, Jeffrey M. Bethony, + 8 More

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Opisthorchis viverrini is distinct among helminth infections as it drives a chronic inflammatory response in the intrahepatic bile duct that progresses from advanced periductal fibrosis (APF) to cholangiocarcinoma (CCA). Extensive research shows that oxidative stress (OS) plays a critical role in the transition from chronic O. viverrini infection to CCA. OS also results in the excision of a modified DNA lesion (8-oxodG) into urine, the levels of which can be detected by immunoassay. Herein, we measured concentrations of urine 8-oxodG by immunoassay from the following four groups in the Khon Kaen Cancer Cohort study: (1) O. viverrini negative individuals, (2) …

Abdominal Aortic Aneurysm: A Silent Killer, Kristen Springer

Nursing Student Class Projects (Formerly MSN)

Rupture of an abdominal aortic aneurysm (AAA) is a significant cause of mortality in the United States. “Often asymptomatic, AAA is considered a silent killer because it frequently remains undiagnosed until the time of rupture or the patient’s death” (Gordon & Toursarkinssian, p. 242). As healthcare professionals, being aware of the pathophysiology, risk factors and symptoms influencing this disease is important in aiding early diagnosis and treatment, helping to reduce complications and mortality rates of those affected.

Dualism And Doctrine, Dov Fox, Alex Stein

Indiana Law Journal

What kinds of harm among those that tortfeasors inflict are worthy of compensation? Which forms of self-incriminating evidence are privileged against government compulsion? What sorts of facts constitute a criminal defendant’s intent? Existing doctrine pins the answer to all of these questions on whether the injury, facts, or evidence at stake are “mental” or “physical.” The assumption that operations of the mind are meaningfully distinct from those of the body animates fundamental rules in our law.

A tort victim cannot recover for mental harm on its own because the law presumes that he is able to unfeel any suffering arising …

A Genetic Porcine Model Of Cancer, Lawrence B. Schook, Tiago V. Collares, Wenping Hu, Ying Liang, Fernanda M. Rodrigues, Laurie A. Rund, Kyle M. Schachtschneider, Fabiana K. Seixas, Kuldeep Singh, Kevin D. Wells, Eric M. Walters, Randall S. Prather, Christopher M. Counter

Toxicology and Cancer Biology Faculty Publications

The large size of the pig and its similarity in anatomy, physiology, metabolism, and genetics to humans make it an ideal platform to develop a genetically defined, large animal model of cancer. To this end, we created a transgenic "oncopig" line encoding Cre recombinase inducible porcine transgenes encoding KRAS^G12D and TP^53R167H, which represent a commonly mutated oncogene and tumor suppressor in human cancers, respectively. Treatment of cells derived from these oncopigs with the adenovirus encoding Cre (AdCre) led to KRAS^G12D and TP^53R167H expression, which rendered the cells transformed in culture and tumorigenic when engrafted into …

Numerical Simulation Of Terahertz Wave Interaction With Breast Cancer Tumor Tissue Sections, Abayomi Omotola Omolewu

Graduate Theses and Dissertations

This thesis presents numerical simulation of terahertz (THz) wave interaction with breast cancer tumor tissue sections. The obtained results are expressed in THz images of heterogeneous material that mimics the excised breast cancer tissue sections. The finite-element software package ANSYS High Frequency Structural Simulator (HFSS) was used in this work. HFSS is a full wave frequency domain three-dimensional (3D) electromagnetic simulation package. In this work, four breast cancer tissue models based on pathology images were simulated and images of the models were obtained at 1 THz. An incident Gaussian beam was raster scanned over tissue model configurations and the reflected …

Effect Of Sirna Pre-Exposure On Subsequent Response To Sirna Therapy, Hamidreza Montazeri Aliabadi, Parvin Mahdipoor, Cezary Kucharski, Nicole Chan, Hasan Uludag

Pharmacy Faculty Articles and Research

PURPOSE. An alternative cancer therapy based on RNA interference (RNAi) has shown considerable promise but the possibility of resistance development is not known. This study explored the possibility of therapeutic resistance against siRNA nanoparticles in human cancer cells. METHODS. Two approaches to siRNA treatment were undertaken using lipid-modified polyethylenimines, a single high concentration (shock) and repeated increasing concentrations (gradual). The targets were Mcl-1, RPS6KA5 and KSP in MDA-MB-435 cells. RESULTS. There was no evidence of resistance development in shock-treated cells, while the decrease in mRNA levels of targeted proteins was not as robust in naïve cells in gradual treatment. However, …

Embracing Multiple Definitions Of Learning, Andrew B. Barron, Eileen A. Hebets, Thomas A. Cleland, Courtney L. Fitzpatrick, Mark E. Hauber, Jeffrey R. Stevens

Eileen Hebets Publications

Definitions of learning vary widely across disciplines, driven largely by different approaches used to assess its occurrence. These definitions can be better reconciled with each other if each is recognized as coherent with a common conceptualization of learning, while appreciating the practical utility of different learning definitions in different contexts.

Learning is a major focus of research in psychology, neuro- science, behavioral ecology, evolutionary theory, and computer science, as well as in many other disciplines. Despite its conceptual prevalence, definitions of learning differ enormously both within and between these disciplines, and new definitions continue to be proposed [1]. Ongoing disputes …

Neural Plasticity In Response To Intervention In Adolescents With Autism Spectrum Disorders, Sheryl Jayne Stevens

Dissertations (1934 -)

Current theories of Autism Spectrum Disorders (ASD) suggest that they may develop from the transactional interaction between biological risk factors and environmental processes (Dawson et al., 2009). Due to the brain’s experience-expectant nature, one’s degree of social exposure may have a significant impact on their brain development and behavioral presentation. In addition to the primary critical neurodevelopmental period identified in early childhood, recent research has demonstrated a second period of substantial neurodevelopment during the adolescent period (Sisk & Foster, 2004). This study investigated the neural and behavioral impact of participation in an empirically validated behavioral intervention (The Program for the …

Effects Of Cocaine Sensitization On Drug Self-Administration, Mesocorticolimbic Sapap Levels, And Prefrontal Ionotropic Glutamate Receptors, Kyle Christopher Summers

Theses and Dissertations (ETD)

Towards the goal of improving the knowledge base of how drugs of abuse function to create addicts and using currently uninvestigated areas of this knowledge base, we focused our research studies the male albino rat, and strived to explain how cocaine sensitization alters particular molecular mechanisms in the mesocorticolimbic system related to glutamate receptors, SAPAPs, and affects drug self-administration. Taking all the previously discussed research studies into consideration, we hypothesized that low-dose cocaine self-administration would yield a significant elevation in drug seeking behavior for psychostimulant sensitized animals. For specific changes at the PSD, we hypothesized that acute cocaine exposure and/or …

A Structural And Functional Comparison Between Infectious And Non-Infectious Autocatalytic Recombinant Prp Conformers, Geoffrey P. Noble, Daphne W. Wang, Daniel J. Walsh, Justin R. Barone, Michael B. Miller, Koren A. Nishina, Sheng Li, Surachai Supattapone

Dartmouth Scholarship

Infectious prions contain a self-propagating, misfolded conformer of the prion protein termed PrPSc. A critical prediction of the protein-only hypothesis is that autocatalytic PrPSc molecules should be infectious. However, some autocatalytic recombinant PrPSc molecules have low or undetectable levels of specific infectivity in bioassays, and the essential determinants of recombinant prion infectivity remain obscure. To identify structural and functional features specifically associated with infectivity, we compared the properties of two autocatalytic recombinant PrP conformers derived from the same original template, which differ by >105-fold in specific infectivity for wild-type mice. Structurally, hydrogen/deuterium exchange mass spectrometry (DXMS) studies revealed that solvent …

Exogenous 17-Β Estradiol Administration Blunts Progression Of Established Angiotensin Ii-Induced Abdominal Aortic Aneurysms In Female Ovariectomized Mice, Sean E. Thatcher, Xuan Zhang, Shannon Woody, Yu Wang, Yasir Alsiraj, Richard Charnigo, Alan Daugherty, Lisa A. Cassis

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Abdominal aortic aneurysms (AAAs) occur predominately in males. However, AAAs in females have rapid growth rates and rupture at smaller sizes. Mechanisms contributing to AAA progression in females are undefined. We defined effects of ovariectomy, with and without 17-β estradiol (E2), on progression of established angiotensin II (AngII)-induced AAAs in female mice.

METHODS: We used neonatal testosterone exposures at 1 day of age to promote susceptibility to AngII-induced AAAs in adult female Ldlr^-/- mice. Females were infused with AngII for 28 days to induce AAAs, and then stratified into groups that were sham, ovariectomized (Ovx, vehicle), or Ovx …

Week Of June 29, 2015, New York Medical College

InTouch

• New Campus Walkway is Now Open
• NYMC School of Medicine Pilots "The Healer's Art" Program
• Dr. Halperin Hosts Chancellor's Circle Reception
• Dr. Miller Hosts Special Dean's Lecture
• Department of Family and Community Medicine Hosts Annual Faculty Development and Appreciation Dinner
• Office of Medical Education Hosts Preceptor Appreciation Banquet
• NYMC Welcomes Class of 2018 D.P.T. Students
• Students Take a Study Break with Leonard

Novel Imidazopyridine Derivatives Possess Anti-Tumor Effect On Human Castration-Resistant Prostate Cancer Cells., Matthew A. Ingersoll, Anastesia S. Lyons, Sakthivel Muniyan, Napoleon D'Cunha, Tashika Robinson, Kyle Hoelting, Jennifer G. Dwyer, Xiu R. Bu, Surinder K. Batra, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

Prostate cancer (PCa) is the second leading cause of cancer-related death afflicting United States males. Most treatments to-date for metastatic PCa include androgen-deprivation therapy and second-generation anti-androgens such as abiraterone acetate and enzalutamide. However, a majority of patients eventually develop resistance to these therapies and relapse into the lethal, castration-resistant form of PCa to which no adequate treatment option remains. Hence, there is an immediate need to develop effective therapeutic agents toward this patient population. Imidazopyridines have recently been shown to possess Akt kinase inhibitory activity; thus in this study, we investigated the inhibitory effect of novel imidazopyridine derivatives HIMP, …

Taranis Functions With Cyclin A And Cdk1 In A Novel Arousal Center To Control Sleep In Drosophila., Dinis J.S. Afonso, Die Liu, Daniel R. Machado, Huihui Pan, James E.C. Jepson, Dragana Rogulja, Kyunghee Koh

Department of Neuroscience Faculty Papers

Sleep is an essential and conserved behavior whose regulation at the molecular and anatomical level remains to be elucidated. Here, we identify TARANIS (TARA), a Drosophila homolog of the Trip-Br (SERTAD) family of transcriptional coregulators, as a molecule that is required for normal sleep patterns. Through a forward-genetic screen, we isolated tara as a novel sleep gene associated with a marked reduction in sleep amount. Targeted knockdown of tara suggests that it functions in cholinergic neurons to promote sleep. tara encodes a conserved cell-cycle protein that contains a Cyclin A (CycA)-binding homology domain. TARA regulates CycA protein levels and genetically …

Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors, Bruno Ramos-Molina, Adam N. Lick, Amir Nasrolahi Shirazi, Donghoon Oh, Rakesh Tiwari, Naglaa Salem El-Sayed, Keykavous Parang, Iris Lindberg

Pharmacy Faculty Articles and Research

Cationic cell-penetrating peptides have been widely used to enhance the intracellular delivery of various types of cargoes, such as drugs and proteins. These reagents are chemically similar to the multi-basic peptides that are known to be potent proprotein convertase inhibitors. Here, we report that both HIV-1 TAT47-57 peptide and the Chariot reagent are micromolar inhibitors of furin activity in vitro. In agreement, HIV-1 TAT47-57 reduced HT1080 cell migration, thought to be mediated by proprotein convertases, by 25%. In addition, cyclic polyarginine peptides containing hydrophobic moieties which have been previously used as transfection reagents also exhibited potent furin inhibition in vitro …

Caspase-8 Scaffolding Function And Mlkl Regulate Nlrp3 Inflammasome Activation Downstream Of Tlr3., Seokwon Kang, Teresa Fernandes-Alnemri, Corey Rogers, Lindsey Mayes, Ying Wang, Christopher Dillon, Linda Roback, William Kaiser, Andrew Oberst, Junji Sagara, Katherine A Fitzgerald, Douglas R Green, Jianke Zhang, Edward S Mocarski, Emad S Alnemri

Department of Biochemistry and Molecular Biology Faculty Papers

TLR2 promotes NLRP3 inflammasome activation via an early MyD88-IRAK1-dependent pathway that provides a priming signal (signal 1) necessary for activation of the inflammasome by a second potassium-depleting signal (signal 2). Here we show that TLR3 binding to dsRNA promotes post-translational inflammasome activation through intermediate and late TRIF/RIPK1/FADD-dependent pathways. Both pathways require the scaffolding but not the catalytic function of caspase-8 or RIPK1. Only the late pathway requires kinase competent RIPK3 and MLKL function. Mechanistically, FADD/caspase-8 scaffolding function provides a post-translational signal 1 in the intermediate pathway, whereas in the late pathway it helps the oligomerization of RIPK3, which together with …

Ganoderma Lucidum Reduces Obesity In Mice By Modulating The Composition Of The Gut Microbiota, Chih-Jung Chang, Chuan-Sheng Lin, Chia-Chen Lu, Jan Martel, Yun-Fei Ko, David M. Ojcius, Shun-Fu Tseng, Tsung-Ru Wu, Yi-Yuan Margaret Chen, John Ding-E. Young, Hsin-Chih Lai

All Dugoni School of Dentistry Faculty Articles

Obesity is associated with low-grade chronic inflammation and intestinal dysbiosis. Ganoderma lucidum is a medicinal mushroom used in traditional Chinese medicine with putative anti-diabetic effects. Here, we show that a water extract of Ganoderma lucidum mycelium (WEGL) reduces body weight, inflammation and insulin resistance in mice fed a high-fat diet (HFD). Our data indicate that WEGL not only reverses HFD-induced gut dysbiosis—as indicated by the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin-bearing Proteobacteria levels—but also maintains intestinal barrier integrity and reduces metabolic endotoxemia. The anti-obesity and microbiota-modulating effects are transmissible via horizontal faeces transfer from WEGL-treated mice to HFD-fed mice. We further …

Gonad: Genome-Editing Via Oviductal Nucleic Acids Delivery System: A Novel Microinjection Independent Genome Engineering Method In Mice., Gou Takahashi, Channabasavaiah B. Gurumurthy, Kenta Wada, Hiromi Miura, Masahiro Sato, Masato Ohtsuka

Journal Articles: Genetics, Cell Biology & Anatomy

Microinjection is considered the gold standard technique for delivery of nucleic acids (NAs; transgenes or genome editing tools such as CRISPR/Cas9 systems) into embryos, for creating genetically modified organisms. It requires sophisticated equipment as well as well-trained and highly skilled personnel to perform the micro-injection technique. Here, we describe a novel and simple microinjection-independent technique, called Genome-editing via Oviductal Nucleic Acids Delivery (GONAD). Using GONAD, we show that NAs (e.g., eGFP mRNA or Cas9 mRNA/sgRNAs) can be effectively delivered to pre-implantation embryos within the intact mouse oviduct by a simple electroporation method, and result in the desired genetic modification in …